PubMed Health⌕ Search

Biomedical subjects

Hans-Reinhard Zerkowski

Publications and source records attributed to Hans-Reinhard Zerkowski.

At least 19 recordsLinked to original sources
PubMed2007

Cancer/testis antigen expression and specific cytotoxic T lymphocyte responses in non small cell lung cancer.

Non small cell lung cancers (NSCLC) express cancer/testis antigens (CTA) genes and MAGE-A expression correlates with poor prognosis in squamous cell carcinomas. We addressed cytotoxic T lymphocytes (CTL) responses to HLA class I restricted CTA epitopes in TIL from NSCLC in an unselected group of 33 patients consecutively undergoing surgery. Expression of MAGE-A1, -A2, -A3, -A4, -A10, -A12 and NY-ESO-1 CTA genes was tested by quantitative RT-PCR. Monoclonal antibodies (MAb) recognizing MAGE-A and NY-ESO-1 CTA were used to detect CTA by immunohistochemistry. CD8(+) TIL obtained from tumors upon culture with anti CD3 and anti CD28 mAb and IL-2 were stimulated with autologous mature DC (mDC) and HLA-A*0101 restricted MAGE-A1(161-169) or MAGE-A3(168-176) peptides or HLA-A*0201 restricted MAGE-A4(230-239), MAGE-A10(254-262), NY-ESO-1(157-165) or multi-MAGE-A (YLEYRQVPV) peptides or a recombinant vaccinia virus (rVV) encoding MAGE-A and NY-ESO-1 HLA-A*0201 restricted epitopes and CD80 co-stimulatory molecule. Specificity was assessed by (51)Cr release and multimer staining. At least one CTA gene was expressed in tumors from 15/33 patients. In 10 specimens, at least 4 CTA genes were concomitantly expressed. These data were largely confirmed by immunohistochemistry. TIL were expanded from 26/33 specimens and CTA-specific CTL activity was detectable in 7/26 TIL. In 6, however, specific cytotoxicity was weak, (<40% lysis at a 50:1 E:T ratio) and multimer staining was undetectable. In one case, high (>60% lysis at 50:1 E:T ratio) MAGE-A10(254-262) specific, HLA-A*0201 restricted response was observed. Supportive evidence was provided by corresponding multimer staining. Although CTA genes are frequently expressed in NSCLC, detection of CTL reactivity against CTA epitopes in TIL from nonimmunized NSCLC patients represents a rare event.

Aged↗
PubMed2007

Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy.

The patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel. Changes in tone were monitored isometrically on ring preparations from both arteries in organ baths with modified Krebs-Henseleit solution containing 1.25 mm calcium chloride at 1 g passive preload. In intraindividual comparisons maximal receptor-mediated contractile responses to noradrenaline and endothelin-1 and endothelium-dependent acetylcholine-induced relaxant responses revealed no differences between both arteries. By contrast, depolarization-induced contractions to potassium chloride (KCl) appeared to be significantly higher in RA than in ITA. Further analysis, however, revealed that this difference was due to preoperative calcium entry blocker (Ca(2+)eB) therapy. Compared with control tissues, maximal responses to KCl were significantly attenuated in the ITA but unchanged in RA when arteries were obtained from patients with preoperative Ca(2+)eB therapy. The present results suggested that functional responses to pharmacological stimuli of both RA and ITA were quite similar. Preoperative Ca(2+)eB therapy, however, attenuated markedly responses to KCl of the ITA leaving those of RA unchanged. These results, demonstrating a lower sensitivity to Ca(2+)eB of RA, therefore suggested that in addition to Ca(2+)eB other classes of drug may be more effective at reducing the propensity of RA conduits to vasospasm.

Adrenergic alpha-Antagonists↗
PubMed2006

Ischemia monitoring in off-pump coronary artery bypass surgery using intravascular near-infrared spectroscopy.

BACKGROUND: In off-pump coronary artery bypass surgery, manipulations on the beating heart can lead to transient interruptions of myocardial oxygen supply, which can generate an accumulation of oxygen-dependent metabolites in coronary venous blood. The objective of this study was to evaluate the reliability of intravascular near-infrared spectroscopy as a monitoring method to detect possible ischemic events in off-pump coronary artery bypass procedures. METHODS: In 15 elective patients undergoing off-pump myocardial revascularization, intravascular near-infrared spectroscopic analysis of coronary venous blood was performed. NIR signals were transferred through a fiberoptic catheter for signal emission and collection. For data analysis and processing, a miniature spectrophotometer with multivariate statistical package was used. Signal acquisition and analysis were performed before and after revascularization. Spectroscopic data were compared with hemodynamic parameters, electrocardiogram, transesophageal echocardiography and laboratory findings. RESULTS: A conversion to extracorporeal circulation was not necessary. The mean number of grafts per patient was 3.1 +/- 0.6. An intraoperative myocardial ischemia was not evident, as indicated by electrocardiogram and transesophageal echocardiography. Continuous spectroscopic analysis showed reproducible absorption spectra of coronary sinus blood. Due to uneventful intraoperative courses, clear ischemia-related changes could be detected in none of the patients. CONCLUSION: Our initial results show that intravascular near-infrared spectroscopy can reliably be used for an online intraoperative ischemia monitoring in off-pump coronary artery bypass surgery. However, the method has to be further evaluated and standardized to determine the role of spectroscopy in off-pump coronary artery bypass surgery.

Coronary Artery Bypass, Off-Pump↗
PubMed2006

Eleven-year single-center experience with the ATS Open Pivot Bileaflet heart valve.

BACKGROUND: The ATS Open Pivot Heart Valve was first introduced in 1992 and has been implanted routinely at our institution since 1993. Valve selection was based on surgeon preference. The objective of this study is to retrospectively analyze our 11-year clinical results with ATS prostheses. METHODS: Between January 1993 and December 2003, 601 ATS valves (393 aortic valve replacement [AVR], 168 mitral valve replacement [MVR], 20 aortic plus mitral valve replacement [DVR]) were implanted in 581 patients (377 male, 204 female; mean age, 63.7 years; range 18 to 89). Preoperatively, 47 (8%) were New York Heart Association class I, 212 (36.5%) were class II, 267 (46%) were class III, and 55 (9.5%) were class IV. Preoperative comorbidities were coronary artery disease, 167 (29%); diabetes mellitus, 72 (12%); cerebrovascular disease, 2 (0.3%); endocarditis, 53 (9%); and atrial fibrillation, 115 (20%). RESULTS: Follow-up is 99% complete. Data represent 2,500 cumulative patient-years. Mean follow-up is 4.3 +/- 2.6 years (range, 0.1 to 11.6). Overall hospital mortality is as follows: AVR, 3.8% (15 patients); MVR, 1.8% (3 patients); DVR, 10% (2 patients). Structural valve failure was not encountered. Overall survival at 10 years is AVR, 84.7% +/- 3.1%, AVR plus coronary artery bypass, 67.5% +/- 8.2%; MVR, 59.8% +/- 7.1%, MVR plus coronary artery bypass, 39% +/- 27.8%; and DVR, 74.3% +/- 10%. Freedom from valve-related death at 10 years is AVR, 99.2%; MVR, 94.6%; and DVR, 100%. Linearized rates for postoperative complications are paravalvular leak, 0.6% per patient-year; valve thrombosis, 0.04% per patient-year; thromboembolism, 1.1% per patient-year; major bleeding, 0.5% per patient-year; and de novo prosthesis endocarditis, 0.1% per patient-year. Postoperative mortality risk was significantly elevated by diabetes (p < 0.01), but not by other comorbidities. CONCLUSIONS: Our 11-year experience demonstrates low rates of adverse events and valve-related complications with the ATS Open Pivot heart valve.

Adolescent↗
PubMed2006

Effects of on-pump versus off-pump coronary artery bypass graft surgery on right ventricular function.

OBJECTIVES: Right ventricular dysfunction is a possible cause of cardiac failure after coronary surgery. The use of cardiopulmonary bypass is regarded as a major cause for its occurrence, and it has been postulated that performing coronary surgery without cardiopulmonary bypass might reduce ventricular dysfunction. Therefore, this prospective, randomized, controlled study tested the hypothesis that off-pump coronary surgery would better preserve right ventricular systolic and diastolic function than conventional bypass surgery. METHODS: Fifty patients scheduled for elective coronary artery bypass surgery were randomly assigned to conventional or off-pump surgery. Right ventricular function was assessed by intraoperative transesophageal echocardiography immediately before and after coronary surgery. Right ventricular ejection fraction was used as a marker of global systolic function and tricuspid early/late (atrial) ratio as a marker of the global diastolic function. Peak systolic and early diastolic velocities of the lateral tricuspid annulus were studied to assess systolic and diastolic function in the area of the right ventricular free wall. RESULTS: Surgery was completed according to randomization in 48 of 50 patients. Preoperative characteristics were similar in both groups. Intraoperative differences between the two groups included a higher volume of allogeneic blood transfusion in the conventional surgery group. At the end of surgery, global systolic right ventricular function was similarly maintained and diastolic function similarly impaired in both groups. There were no significant intergroup differences in any of the echocardiographic markers of right ventricular function. CONCLUSIONS: Off-pump surgery did not better preserve right ventricular systolic and diastolic function than did conventional coronary surgery.

Aged↗
PubMed2005

Freezing without surrounding cryomedium preserves the endothelium and its function in human internal mammary arteries.

PURPOSE: Cryopreserved human blood vessels may become important tools in bypass surgery. Optimal cryopreservation of an arterial graft should, therefore, preserve both histological and physiological characteristics of smooth muscle and endothelium comparable to the unfrozen artery. METHODS: Rings from human internal mammary arteries (IMA) were investigated in vitro either unfrozen or after immersion into a cryomedium (RPMI 1640 containing 1.8M Me2SO and 0.1M sucrose) and cryostorage with and without surrounding medium. RESULTS: In unfrozen IMA, neither contractile responses to noradrenaline (NA) nor endothelium-dependent relaxant responses to acetylcholine (ACH) was modified after exposure of the IMA to cryomedium or during activation of protein kinase C by phorbol-12,13-dibutyrate (PDBu). Exposure to cryomedium with gradually increasing Me2SO content before starting the cooling process did not improve the post-thaw functional activity of the artery. Optimal post-thaw recovery of contractile responses to NA and PGF(2alpha) was observed after freezing at a speed of -1.2 and -3 degrees C/min in arteries stored with and without surrounding cryomedium. Compared to unfrozen controls, the ACH-induced endothelium-dependent relaxation during active tone induced by 3 microM PGF(2alpha) reached 16 and 56% after freezing with and without surrounding medium. All functional data were reflected by electron microscopy images showing considerably better preservation of the endothelial layer after freezing without medium. CONCLUSION: Freezing of human arteries at a mean cooling rate of -3 degrees C/min and storage without surrounding medium offers the prospect of optimal preservation of both smooth muscle and endothelial function in cryopreserved human IMA.

Acetylcholine↗
PubMed2005

Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass.

OBJECTIVES: Cytokines contribute to the development of the systemic inflammatory response syndrome or multiple-organ failure frequently observed after cardiopulmonary bypass-supported cardiac surgery. To quantify the contribution of bypass-induced versus trauma-induced inflammatory response after coronary artery bypass grafting, we examined plasma cytokine levels in 120 patients with coronary artery disease who were treated with or without cardiopulmonary bypass-assisted procedures. METHODS: Patients were treated in accordance with one of the following protocols: (1) elective percutaneous coronary intervention without cardiopulmonary bypass (n = 69), (2) cardiopulmonary bypass-supported percutaneous coronary intervention (cardiopulmonary bypass-percutaneous coronary intervention; n = 10), and (3) cardiopulmonary bypass-supported coronary artery bypass grafting (cardiopulmonary bypass-coronary artery bypass grafting; n = 41). Cytokine levels (picograms/milliliter) were measured by enzyme-linked immunosorbent assay from plasma samples obtained at various time points. RESULTS: Interleukin-6 was measured in blood samples from all 3 patient populations. The maximum interleukin-6 level was 13.6 +/- 22.3 pg/mL in the percutaneous coronary intervention group, 170.4 +/- 165.4 pg/mL in the cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 +/- 285.7 pg/mL in the cardiopulmonary bypass-coronary artery bypass grafting group. Interleukin-6 levels were significantly different, and the 95% confidence intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary intervention group, bypass duration correlated well with interleukin-6 production ( r = 0.915; P < .001), whereas these parameters did not correlate in patients who underwent cardiopulmonary bypass-coronary artery bypass grafting ( r = 0.307; P = .054). CONCLUSIONS: These findings support the suggestion that surgical trauma and cardiopulmonary bypass contribute to the inflammatory response after cardiac surgery, although trauma may contribute to a higher degree.

Angioplasty, Balloon, Coronary↗
PubMed2004

Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina--on-treatment analysis of the TIME trial.

AIM: To assess treatment effects of optimised medical therapy and PCI or CABG surgery on one-year outcome in patients 75 years old with chronic angina. METHODS AND RESULTS: On-treatment analysis of the TIME data: all re-vascularised patients (REVASC n=174: 112 randomised to revascularisation and 62 to drugs with late revascularisation) were compared to all patients on continued drug therapy (MED n=127: 86 randomised to drugs and 41 to revascularisation only). Baseline characteristics of both groups were similar (age 80 +/- 4 years). Risk of death at one year (adjusted hazard ratio (HR)=1.31; 95%-CI: 0.58-2.99; P=0.52) and of death/infarction (adjusted hazard RATIO=1.77; 95%-CI 0.91-3.41; P=0.09) were comparable between REVASC and MED patients. Furthermore, the risk of death within 30 days was even slightly lower among REVASC patients (unadjusted hazard RATIO=0.73; 95%-CI: 0.21-2.53; P=0.98). Overall, REVASC patients had greater improvements in symptoms and well-being than MED patients (P<0.01). Surgical patients had similar mortality rates as angioplasty patients, but they also had greater symptomatic improvements (P<0.01). CONCLUSION: Treated medically, elderly patients with chronic angina have a similarly high 30-day and one-year mortality as patients of the same age being re-vascularised; however, they can expect lower improvements in symptoms and well being.

Aged↗
PubMed2004

Attenuation of lipopolysaccharide-induced hyperreactivity of human internal mammary arteries by melatonin.

Reactive oxygen species (ROS) are thought to be important mediators in ischaemia/reperfusion injury following coronary vasospasm. The most ubiquitous action of melatonin is that of a free radical scavenger. Therefore, we investigated the action of melatonin by monitoring changes in the tone on ring preparations from human internal mammary arteries (IMA). In quiescent IMA rings melatonin (0.1 nm-10 microm) never elicited any change in baseline tension but 1-100 nm melatonin enhanced significantly maximal responses to noradrenaline (NA) in arteries with endothelial function. In NA (1 microm) precontracted arteries inhibition of nitric oxide (NO(*)) formation by N(G)-monomethyl-L-arginine (l-NMMA, 100 and 400 microm) eliminated 43 +/- 7 and 61 +/- 7% of the acetylcholine (ACH) effect. Melatonin (100 and 400 nm) attenuated maximal endothelium-dependent relaxant responses to ACH slightly by 23 +/- 9 and 17 +/- 9% leaving responses to direct stimulation of soluble guanylate cyclase by sodium nitroprusside unchanged. Incubation of IMA for 20 hr at 37 degrees C with 1 microg/mL lipopolysaccharide (LPS) enhanced maximal NA effects to 147 +/- 18% (n = 22, P < 0.01) whereas 50 microg/mL LPS reduced the NA maxima to 68 +/- 9% (n = 10, P < 0.01) of the control effects. The LPS-induced potentiation was completely attenuated by coincubation with melatonin (400 nm) and significantly reduced by coincubation with the thromboxane synthase inhibitor dazoxiben (10 microm). It is suggested that the LPS-induced hyperreactivity of vascular smooth muscle is mediated through enhanced release of ROS and prostanoids and that melatonin inhibits the vascular hyperreactivity through selective scavenging of ROS.

Acetylcholine↗
PubMed2004

Doppler microembolic signals during cardiopulmonary bypass: comparison of two membrane oxygenators.

We undertook this study to evaluate the dependence of Doppler microembolic signal (MES) counts, detected during cardiopulmonary bypass, on the type of oxygenator used. A total of 90 patients, 71 men and 19 women, aged 60 +/- 10 years (mean +/- SD), undergoing elective cardiac surgery for coronary artery bypass grafting (one vessel, n = 6; two vessels, n = 24; three vessels, n = 33; four vessels, n = 9) or valve replacement (mitral valve, n = 2, aortic valve, n = 15, both valves, n = 1) were monitored with transcranial Doppler sonography during the complete surgical procedure. The surgical and anesthetic techniques were standardized in all patients, except for the type of membrane oxygenator used (COBE CML Duo, n = 55 or DIDECO D 703, n = 35). MES count was expressed as total number of MES detected in both middle cerebral arteries during cardiopulmonary bypass (CPB) and also as total MES number divided by the CPB duration in minutes (MES min(-1)). No significant differences in patients' age or sex and type and duration of operation were noted between the two groups. MES incidence while the patients were on cardiopulmonary bypass was 100%. MES counts during CPB were 309 (236-502) and 143 (86-233) for DIDECO and COBE oxygenators, respectively (p < 0.00001). MES min(-1) were also significantly higher in patients operated with DIDECO, as compared to COBE oxygenators (3.7 (2.4-5.6) versus 1.5 (1-2.4), respectively, p < 0.0001). Inter-observer variability was satisfactory (k = 0.72). Use of a DIDECO D 703 oxygenator resulted in significantly higher MES counts as compared to the COBE CML Duo oxygenator. The clinical relevance of this finding remains to be determined.

Age Factors↗
PubMed2004

Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia.

STUDY OBJECTIVES: To investigate the factors that predict survival after lung resection for invasive pulmonary aspergillosis (IPA) in patients with neutropenia, in order to assist the selection of patients who are most likely to have a successful outcome. DESIGN: Retrospective single-center study. SETTING: University hospital hemato-oncologic isolation unit and division of thoracic surgery. PATIENTS: Forty-one patients with hematologic disease and suspected IPA who underwent lung resection. INTERVENTIONS: Lobectomy (n = 23), wedge resection (n = 16), and enucleation (n = 2). RESULTS: Mortality within 30 days was 10% (4 of 41 patients). Major perioperative complications occurred in 10%. One death was possibly related to surgery (pleural aspergillosis). Of the patients with proven aspergillosis, 87.1% were cleared of infection, but fungal relapse occurred in 10%. Overall survival was 65% at 6 months, 58% at 12 months, and 40% at 5 years after surgery. Baseline characteristics and intraoperative data did not differ significantly between survivors and nonsurvivors at 6 months or 12 months after surgery. Perioperative complications did not significantly influence the outcome. Multivariate analysis of 12-month survival revealed that the variables, progression, or recurrence of the underlying hematologic disease (relative risk [RR], 4.64; 95% confidence interval [CI], 3.51 to 5.77; p < 0.0001), fungal relapse (RR, 5.06; 95% CI, 3.83 to 6.28; p < 0.0001), and to a minor extent the type of the underlying hematologic disease (p < 0.018) were the most important predictors of patient survival. CONCLUSIONS: Lung resection for IPA is feasible with an acceptable operative risk. While at 10%, the perioperative mortality is considerable; the nonsurgical mortality is reported to be between 30% and 90%. Fungal infection is cleared in > 80% of patients. Mid- to long-term survival can be achieved if the underlying hematologic disease is under control. It is not yet possible to define a group of patients with IPA who are most likely to benefit from lung resection.

Adolescent↗