Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization.

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Th1-type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

Antiviral immune response in patients with multiple sclerosis and healthy siblings.

The objective of this study was to determine the immune responses to candidate viral triggers of multiple sclerosis in patients and healthy siblings raised in the same family household. Virus antigen-specific IgG responses to Epstein-Barr virus-derived gene products as well as to human herpersvirus-6, human cytomegalovirus, and measles virus were evaluated in 25 multiple sclerosis patients and compared with 49 healthy full-siblings. IgG responses to the latent Epstein-Barr virus-encoded nuclear antigen-1 (EBNA1) were selectively increased in individuals with multiple sclerosis compared with their unaffected siblings. We conclude that elevated IgG responses towards EBNA1 are associated with the development of multiple sclerosis.

Left anterior descending coronary artery: long-term angiographic results of CABG with endarterectomy.

AIM: The procedure of coronary bypass grafting (CABG) with coronary endarterectomy (CE) is controversial. However, in the setting of severely calcified coronary arteries CE may enable complete revascularization. Complete revascularization, especially of the left anterior descending artery (LAD), is important for long-term outcome. In this study we assessed long-term LAD graft patency and anterior wall function after CABG with CE of the LAD. METHODS: Between 1984 and 1992, 283 patients underwent CABG with CE of the LAD. In 50 patients (47 men), aged 59+/-7.6 (40-77), clinical reassessment and surveillance angiography were performed. In all patients complete revascularization had been achieved with 3.5+/-1 (1-5) grafts/patient with 1-3 CE/patient. The LAD was grafted either with a saphenous vein segment (N=38) or with left intern thoracic artery (N=12). A graft obstructed less than 50% in diameter was defined as patent. RESULTS: At follow-up 39 patients (78%) were in CCS class I/II and had improved significantly (P<0.000). Control angiography after 7.6+/-2.5 (3.5-11.7) years after CABG revealed a patent LAD graft in 30/50 patients (60%). Actuarial graft patency was 100%, 96%, and 56% after 2, 5, and 10 years and was lower in patients with diabetes (P=0.001). Deterioration of anterior wall motion was observed in 17 patients (34%) and was more frequent if anterior wall motion was preoperatively normal (P=0.002), irrespective of LAD graft patency. CONCLUSION: Clinical status and long-term graft patency of grafts on endarterectomized LAD is considerable. However, patients with preoperatively normal anterior wall function are at increased risk for myocardial damage in the long-term.

Long-term behavior and quality of life after corrective cardiac surgery in infancy for tetralogy of Fallot or ventricular septal defect.

The objective of this study was to evaluate behavior and quality of life in children after corrective cardiac surgery in infancy. Twenty cyanotic (tetralogy of Fallot) and 20 acyanotic children (ventricular septal defect), operated at a mean age of 0.7 years with deep hypothermic circulatory arrest (DHCA) and low-flow cardiopulmonary bypass (CPB), were assessed at a mean age of 7.4 years by the Child Behavior Checklist (CBCL) and the German KINDL. Test results were related to perioperative and neurodevelopmental outcome. Compared to healthy children and not significantly different between the groups, internalizing and externalizing problems were elevated, school performance and total competence were reduced, and self- and parent-reported quality of life was not reduced. Parent-reported problems and reduced physical status were correlated with longer durations of DHCA and CPB. Internalizing and externalizing problems, reduced school competence, and reduced self-esteem were associated with reduced endurance capacity. Externalizing problems were related to reduced gross motor function. Poor school competence was related to reduced intelligence and academic achievement. Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are not at significantly higher risk for behavioral problems and reduced quality of life than those with acyanotic heart defects. The risk of long-term psychosocial maladjustment after corrective surgery in infancy is increased compared to that for normal children and related to the presence of neurodevelopmental dysfunction.

Mechanical aortic and mitral valve replacement in infants and children.

BACKGROUND: The aim of this study was to evaluate early and late outcomes after mechanical systemic heart valve replacement in pediatric patients. METHODS: Between October 1981 and December 2003, 32 children (mean age 7.2 +/- 5.4 years; 4 months - 15.9 years) underwent mechanical mitral (MVR, n = 17), aortic (AVR, n = 13) or double valve replacement (DVR, n = 2) with St. Jude Medical valves. Twenty-two patients (69 %) had undergone previous cardiac surgery. Anticoagulation self-management was used since 1995. RESULTS: The operative mortality was 3.1 %. Perioperative complications were complete heart block (n = 5), ventricular fibrillation (n = 1) and myocardial infarction (n = 1) and were exclusively related to patients with MVR. Mean calculated valve size ratio (geometric prosthesis orifice area/normal valve size area) was 1.72 (1.07 - 2.85) for AVR and 1.4 (0.88 - 3.12) for MVR. Mean follow-up was 9.1 +/- 6.6 years (range 0.4 - 23.2 years, cumulative 283 patient-years). There were two late deaths in patients with MVR. Actuarial survival after 10 years was 93.8 %. Late complications were endocarditis (n = 2), minor hemorrhagic event (n = 1), and stroke (n = 1). Anticoagulation self-management is well accepted by all patients/parents. Overall 10-year freedom from any anticoagulation-related adverse event with phenprocoumon was 89.1 % (1.2 %/patient year). Nine patients required reoperations: redo-MVR (outgrowth of prostheses (n = 3), pannus overgrowth (n = 2), closure of paravalvular leak after AVR (n = 2), partial aortic valve thrombosis (n = 1) and redo-DVR (n = 1 for endocarditis). Freedom from reoperation after 10 years was 80.9 %. CONCLUSIONS: Mechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients. Perioperative morbidity was exclusively related to patients with MVR. Oversizing was often possible to avoid early reoperation for outgrowth. The operative mortality and long-term morbidity are acceptable. Anticoagulation self-management is safe and well accepted.

Systemic mechanical heart valve replacement in children under 16 years of age.

UNLABELLED: We report the early and late outcome following left-sided mechanical heart valve replacement in children. Between 10/1981 and 02/2001, 27 children (13 male, mean age 7.2 +/- 5.2 years, range 0.53-15.7 years) underwent mechanical mitral (MVR 16), aortic (AVR 9) or double valve replacement (DVR 2) with St. Jude Medical valves. Eighteen children (66.7%) had undergone previous cardiac surgery. Valve disease was congenital in 23, due to endocarditis in 2 and rheumatic in 2 patients. Concomitant cardiac surgery was performed in 12 patients (44.4%). Operative mortality was 3.7% (1/27). Perioperative complications were complete heart block (5) and myocardial infarction (1). Mean follow-up was 6.5+/-5.9 years (range 0.4-19 years, total 169.9 patient-years). There was one valve-related late death due to mitral valve thrombosis without phenprocoumon. Actuarial survival after 1, 5 and 10 years was 93, 93 and 93%. Late complications included endocarditis (2), minor hemorrhagic event (1) and stroke (1). Overall 10-year freedom from any anticoagulation-related adverse event under phenprocoumon was 91% (1.3%/patient year). Eight patients required reoperations: re-MVR (5; outgrowth of the prostheses (3), pannus overgrowth (2)), closure of paravalvular leak after AVR (2), and re- DVR (1; endocarditis). Actuarial freedom from reoperation after 1, 5 and 10 years was 96, 88 and 76%. CONCLUSION: Mechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients with good results. Operative mortality and the incidence of any valve-related events as endocarditis, reoperation, thromboembolism or anticoagulation related bleeding is acceptable.

Procalcitonin is a valuable prognostic marker in cardiac surgery but not specific for infection.

BACKGROUND: The prognostic value of elevated serum levels of procalcitonin (PCT) in patients early after cardiac surgery on cardiopulmonary bypass (CPB) remains unclear. In a prospective study, we investigated whether PCT is useful as a prognostic marker in cardiac surgery with respect to mortality, complications and infections, and whether PCT is a specific marker for occurrence of infections. METHODS: Within 8 months, a subset of 80 high-risk patients (APACHE II-score: 25.1 +/- 4.7 (mean +/- SD)) out of a consecutive cohort of 776 patients was investigated. Demographic data, operative data and clinical endpoints (mortality, infection, severe complication) were documented. Serum levels of PCT were analyzed preoperatively and at postoperative day 1. RESULTS: Hospital mortality in this high-risk group was 21.3 %, infections occurred in 33.8 % and complications in 58.8 % of the patients. Preoperative PCT was normal in all patients. Postoperative PCT was increased in non-survivors compared to survivors (34.3 +/- 7.0 ng/ml vs. 15.9 +/- 4.9 ng/ml; p < 0.05), in patients with severe complications (30.3 +/- 6.7 ng/ml vs. 5.5 +/- 1.4 ng/ml; p < 0.05) and in patients with infections (38.4 +/- 11.3 ng/ml vs. 10.8 +/- 1.6 ng/ml; p < 0.05). Area under receiver operating characteristic curve for PCT as predictor of mortality, infections and complications was 0.772 (95 %-confidence-interval (CI): 0.651 - 0.894), 0.720 (95 %-CI: 0.603 - 0.837) and 0.861 (95 %-CI: 0.779 - 0.943), respectively. PCT was not different with infectious compared to non-infectious complications. CONCLUSIONS: High levels of PCT are associated with mortality, infections, and severe complications early after cardiac surgery using cardiopulmonary bypass and therefore provide a valuable prognostic marker. However, PCT does not discriminate between infectious and non-infectious complications.

Results of exercise testing at a mean age of 10 years after neonatal arterial switch operation.

AIM: This prospective follow-up study investigated long-term exercise capacity at a mean age of 10 y after neonatal arterial switch operation for transposition of the great arteries in a large group of homogeneous unselected children. METHODS: 56 asymptomatic children, aged 7.9-14.3 y (10.5 +/- 1.6, mean +/- SD), were examined with respect to exercise tolerance, electrocardiographic (ECG) response and activity of biochemical markers for myocardial injury. The protocol included standard electrocardiography, M-mode and two-dimensional echocardiography at rest, a Bruce walking treadmill test to voluntary exhaustion, and determination of cardiac troponin I and T, creatine kinase and myoglobin from venous blood samples at rest and 4 h after exercise. Heart rate, blood-pressure response to exercise stress and endurance time were compared with published results of age-matched normal children. RESULTS: 54 patients (96.4%) had normal exercise capacity; a reduction in 2 patients was not due to cardiac disease. Heart rate and systolic blood pressure rose significantly between rest and peak exercise and did not differ from normal controls, whereas diastolic blood pressure was lower. ECG remained normal at rest and on exercise in 54 children (96.4%). Serum values of cardiac troponin I and T, creatine kinase and myoglobin were normal at rest and after exercise in all patients. CONCLUSION: The study demonstrates excellent long-term exercise capacity after neonatal arterial switch operation. Exercise testing is a useful and non-invasive screening method to detect patients with clinically relevant exercise-induced myocardial ischaemia and should be routinely performed in growing patients.

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries.

AIMS: To evaluate behavioural outcome and quality of life in children aged 8-14 years after neonatal arterial switch operation for transposition of the great arteries. METHODS: Sixty children operated as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were evaluated at age 7.9-14.3 years by the Child Behaviour Checklist (CBCL) and the Inventory for the Assessment of the Quality of Life in Children and Adolescents (IQCL). RESULTS: Parent reported behavioural outcome on all CBCL problem and competence scores was worse, whereas quality of life on self reported IQCL scores was not reduced compared to the normal population. On multivariate analysis, severe preoperative hypoxia was related to parent reported social problems; peri- and postoperative cardiocirculatory insufficiency was associated with internalizing, externalizing, attention, and total behavioural problems. Reduced expressive language was associated with total behavioural problems, and poor academic achievement was related to parent reported deficits in school performance. Impaired neurological status and reduced endurance capacity both predicted self reported stress by illness. CONCLUSIONS: The neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with parent reported long term behavioural impairment, but not with self reported general reduction in quality of life. This discrepancy may be a result of different perception of illness. In our experience, increased risk of long term psychosocial maladjustment after neonatal corrective cardiac surgery is related to the presence of neurological impairment and reduced endurance capacity.

Tumor necrosis factor-alpha and troponin I release in porcine cardiac lymph and coronary sinus blood before and after cardiopulmonary bypass.

To assess the concentrations of cardiac troponin I (cTnI) and tumor necrosis factor-alpha (TNFalpha) in cardiac lymph compared with coronary sinus (CS) blood and to measure cardiac lymph flow before and after cardiopulmonary bypass (CPB). In 21 pigs, the main cardiac lymph trunk was cannulated before institution of standardized CPB. Lymph flow, cTnI and TNFa in cardiac lymph and CS blood were measured before and after CPB for 6 hours. Before CPB, cTnI concentration was 215 +/- 36 nglml in cardiac lymph and 0.5 +/- 0.1 nglml in CS blood, respectively. After aortic declamping a significant elevation of cTnI values was measured in cardiac lymph and CS blood. cTnl concentration in cardiac lymph and CS blood peaked 6 hrs after CPB (10,556 +/- 4,735 vs. 22.2 +/- 3.7 nglml, p < 0.01). TNFalpha concentration at baseline was 23.2 +/- 5.6 pg/ml in lymph and 18.7 +/- 9.5 pg/ml in CS blood, and there was no significant release of TNFalpha up to the end of the experiment. Baseline cardiac lymph flow was 3.07 +/- 0.35 ml/h and declined after aortic clamping (0.72 +/- 0.16 ml/h; p < 0.01) and peaked one hour after CPB (5.66 +/- 0.97 ml/h; p < 0.01). In conclusion, very high cTnI concentrations in cardiac lymph suggest serious perioperative myocardial damage after CPB with cardioplegia, which is underestimated by cTnI release into the bloodstream. In our study, the myocardium was not a major source of TNFalpha release.

Fate of intramural coronary arteries after arterial switch operation.

BACKGROUND: To evaluate the impact of intramural coronary arteries for the peri-, postoperative and long-term course after arterial switch operation (ASO). METHODS: ASO was performed in 351 patients between 1981 and 2000 with dextrotransposition of the great arteries (d-TGA). Five patients (1.4 %) had an intramural coronary artery. Coronary transfer was performed with a collar under dissection of the commissure without longitudinal splitting of the intramural section. RESULTS: None of these patients died; the intraoperative course was uneventful, and no myocardial ischemic changes were observed. In three patients, follow-up cardiac catheterization after 5, 16 and 53 months revealed an occlusion of the intramural coronary ostium. Exercise electrocardiography and myocardial scintiscan showed myocardial ischemia. Two of these patients underwent a successful internal mammary artery bypass. CONCLUSIONS: The intramural course of coronary arteries in patients with d-TGA is rare and does not cause increased mortality or myocardial infarction rates. However, the risk of coronary occlusion over time seems to be high. Therefore, patients with this condition require selective coronary angiography and frequent exercise investigations. Revascularization with an internal mammary artery bypass may be indicated.

Tissue engineering: complete autologous valve conduit--a new moulding technique.

OBJECTIVE: The use of fibrin gel, which can be produced from patients' blood, was investigated as an autologous, biodegradable scaffold. A new moulding technique was developed to create a complete aortic root. METHODS: A new moulding technique was generated for the creation of complete valve conduit. On the basis of biomechanical valve design studies, a tricuspid "ventricular" and "aortic" stamp were developed. A silicone-coated aluminum cylinder was used to circumferentially limit the mould. The cell/gel suspension was filled into the mould and polymerization was started. RESULTS: The creation of complex structures such as complete valve conduits is possible with the moulding technique described. With a layer thickness of up to 2 mm, histological investigations showed excellent tissue development with viable fibroblasts surrounded by collagen bundles. CONCLUSION: Fibrin gel unifies many properties of an ideal scaffold: The formation of complex structures is possible, the degradation and polymerization is controllable and the formation of the extracellular matrix is excellent.

Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell damage and myocardial cell death related to cardiac surgery.

OBJECTIVES: The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND: Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS: Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS: Synthesis of IL10 was significantly higher, while that of TNFalpha was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS: Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

The St. Jude "Silzone" valve: midterm results in treatment of active endocarditis.

BACKGROUND: The Silzone-coated St. Jude Medical valve (SJM "Silzone" valve), developed to reduce prosthetic valve endocarditis (PVE), was recalled by SJM due to a higher rate of paravalvular leaks. The aim of this study was to determine the efficacy of the SJM "Silzone" valve in avoiding PVE and to evaluate the frequency of paravalvular leaks, when the valve was used exclusively for active bacterial endocarditis. METHODS: From January 1998 to December 1999, the SJM "Silzone" valve was implanted in 40 consecutive patients with active endocarditis (20 aortic, 14 mitral, and 6 both valves). Late transesophageal echocardiography was performed in 87% of survivors, and transthoracic echocardiography in the remaining 13%. Follow-up was 100%. RESULTS: Hospital mortality was 17.5%. Early PVE occurred in 2 of 40 patients (5%). There were two late deaths without signs of recurrent PVE. A hemodynamic relevant paravalvular leak necessitating reoperation was seen in 2 patients within 6 months after operation. The rate of a minor paravalvular leak was 13% (4 of 31 patients). CONCLUSIONS: The SJM "Silzone" valve when implanted for active bacterial endocarditis does not give better results than other mechanical prostheses with regard to early recurrence of endocarditis. The rate of a hemodynamic relevant paravalvular leak requiring reoperation seems rather high during the early postoperative period, whereas the occurrence of minor paravalvular leaks is comparable with that of other mechanical prostheses. Routine observation, recommended for all patients with mechanical heart valves, is also sufficient for patients with the SJM "Silzone" valve.

Aortopexy reduces anastomosis stress after repair of coarctation.

Restenosis after repair of coarctation with hypoplastic distal aortic arch is an important complication. Complete removal of ductal tissue, resection of isthmus area, and side-to-side arterioplasty of the distal aortic arch leads to a wide distance between the aortic arch and descending aorta; therefore, the anastomosis may remain under tension, increasing risk of restenosis. To reduce the tension, aortopexy of the descending aorta was used. The operative technique and the results in 16 neonates and infants are presented.

Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic mitral valve disease.

OBJECTIVES: Mitral valve combined with coronary artery surgery is associated with a higher hospital mortality than each operation in particular. Controversy exists regarding the predictive value of ischemic mitral valve disease (MVD) on outcome. METHODS: Between 1984 and 1997, 262 patients underwent mitral valve operations (replacement, n = 198; repair, n = 64) in combination with coronary revascularization. The etiology of MVD was secondary to ischemic heart disease (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups were similar in age, cardiac risk factors and pulmonary artery pressure. Patients of group I had significantly more severe coronary artery disease, more often an impaired left ventricle and myocardial infarction, and were in a worse functional condition. The mean number of bypass grafts was significantly higher in group I. The follow-up was 98% (230/234 patients). RESULTS: With 19.5%, the hospital mortality was significantly increased in group I compared with 6.7% in group II (P = 0.002; overall, 10.7%). Mitral valve repair or replacement had no influence on early outcome, although mitral valve repair was performed more often in group I (37 versus 19%). The survival (valve-related event-free survival) after discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and 53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II, respectively. The long-term functional capacity was equally good in both groups (New York Heart Association mean, 1.86 versus 1.72). CONCLUSIONS: Patients with ischemic MVD are in a worse cardiac condition with significantly higher hospital mortality than patients with non-ischemic MVD and coronary artery bypass grafting. Once discharged from hospital, both groups have comparable long-term outcomes, with the best results in patients with degenerative MVD.

Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance, and post-operative organ damage.

This study examined the hypothesis that core temperature (T(o)) during cardiopulmonary bypass (CPB) influences the perioperative systemic inflammatory response and post-operative organ damage. Twenty-four pigs were assigned to a T(o) regimen during CPB: normothermia (T(o) 37 degrees C; n = 8), moderate hypothermia (T(o) 28 degrees C; n = 8), or deep hypothermia (T(o) 20 degrees C; n = 8). Perioperative leukocyte activation, endotoxin release, and production of tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL10) were examined with regard to post-operative organ damage, which was scored at histological examination of tissue probes of heart, lungs, liver, kidney, and ileum, taken 6 h after CPB. Total blood leukocyte count and TNFalpha plasma levels during CPB were significantly lower and IL10 levels were significantly higher in the moderate hypothermic group than in both other groups. Elastase activity, leukotriene B4-, and endotoxin levels were not affected by T(o) regimen. Moderate hypothermia was associated with the lowest histological organ damage score and normothermia with the highest. In all animals organ damage score for heart, lungs, and kidneys correlated significantly with TNFalpha levels at the end of CPB. Our data demonstrate a clear relationship between TNFalpha production during cardiac operations and post-operative multiple-organ damage. Moderate hypothermia, by stimulating IL10 synthesis and suppressing TNFalpha production during CPB, might provide organ protection.

[Direct evidence of cytomegalovirus in coronary atheromas of patients with advance coronary heart artery disease]. / Direkter Nachweis von Zytomegalievirus in koronaren Atheromen von Patienten mit fortgeschrittener koronarer Herzerkrankung.

BACKGROUND AND AIM: Experimental and clinical data support an infectious cause of atherosclerosis and thereby coronary artery disease. This study was intended to assess the prevalence and possible clinical associations of the presence of cytomegalovirus DNA within coronary samples from patients undergoing coronary artery bypass grafting. PATIENTS AND METHODS: A coronary thrombendatherectomy was performed in 53 patients with advanced coronary artery disease. Two samples of each atheroma were used for further analysis and pathogen detection. RESULT: In 30% of patients with advanced coronary artery disease cytomegalovirus DNA was detected in coronary samples as assessed by highly sensitive PCR methods. The occurrence of the virus within the vessels was characterized by an inhomogeneous distribution pattern. CONCLUSION: Due to an increased proportion of restenotic lesions and a higher degree of calcification in cytomegalovirus-positive lesions, a causative association between the virus presence and mechanisms of restenosis post angioplasty is further supported. Antiviral pharmacological interventions to prevent restenosis in high-risk patients, however, seem not to be justified by the data currently available.

Specific blocking to improve biopanning in biological samples such as serum and hybridoma supernatants.

Screening phage-displayed peptide libraries (biopanning) is an important technique for acquiring peptide ligands and for mapping peptide epitopes recognized by antibodies (Ab). In biological samples, other materials, not only contaminants but also natural constituents, often interfere with biopanning. Capture methods use anchoring Abs that reduce the need for purification of the intended panning target from a crude sample. This capture method is analogous to sandwich ELISA. However, when the target molecule concentration is low in the initial mixture, the panning of a captured target often yields epitopes that bind to the capture antibody rather than the target of interest. We have developed a methodology that utilizes specific blocking reagents of the capture Ab to extend the sensitivity and applicability of the capture approach to phage panning. A flowchart is presented to enable the worker to begin panning with the simplest approach and then to employ sandwich capture and specific blocking reagents as necessary.

Systemic right ventricular failure after atrial switch operation: midterm results of conversion into an arterial switch.

BACKGROUND: Failure of the systemic right ventricle after atrial switch operation can be treated by conversion into an arterial switch operation. METHODS: Four patients, age 38 to 59 months, presented with right ventricular failure after Senning operation and ventricular septal defect closure. One patient had elevated left ventricular pressure; in the other three patients the left ventricle was retrained to a left ventricular/right ventricular pressure ratio of 0.8 or greater by pulmonary artery banding in 12 to 24 months. RESULTS: Postoperative course after arterial switch operation was prolonged, but clinical condition was good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to-moderate aortic regurgitation was present; only 1 patient had preserved sinus rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left ventricular dysfunction. The survivors are in New York Heart Association functional class I to II. Fractional shortening has improved (29% to 37%); aortic regurgitation has not increased. No patient has undisturbed sinus rhythm. CONCLUSIONS: Conversion of an atrial into an arterial switch is an alternative to cardiac transplantation in childhood. However, the procedure is demanding. Long-term morbidity is caused by rhythm disturbances. Aortic valve performance and left ventricular function require close observation.