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Biomedical subjects

Ernst Wolner

Publications and source records attributed to Ernst Wolner.

At least 73 records · Page 4Linked to original sources

Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance.

Sepsis causes lymphopenia which is inversely correlated with patient survival. The role of apoptosis-specific immune-activation and activation-induced cell-death in sepsis is incompletely understood. Fifteen septic patients and 20 healthy controls were included. T-cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNFR1, sCD95, interleukin-1beta converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T-cell proliferation were significantly decreased in septic patients. The percentages of CD3(+) and CD4(+) T cells and CD19(+) B cells were significantly reduced. Percent memory T-cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/annexin-V(+)) were significantly increased in sepsis. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Anti-CD3 antibody triggering induced a 56% increase of CD4 T-cell death in septic patients vs. 7.5% in controls relative to IgG. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in septic patients Th1 T-cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.

Adult↗

Aberrant T cell activation and heightened apoptotic turnover in end-stage renal failure patients: a comparative evaluation between non-dialysis, haemodialysis, and peritoneal dialysis.

Patients in end-stage renal disease (ESRD) have a high incidence of bacterial and viral infections. Fifteen non-dialysed (ND), 15 haemodialysed (HD), 15 patients with peritoneal dialysis (PD), and 15 healthy controls were included. T cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNF-R1, sCD95, interleukin-1beta-converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T cell proliferation were significantly decreased in ESRD patients. CD3(+), CD19(+) B cells, and percentage of CD4(+) T cells were significantly reduced. Percent memory T cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/Annexin V+) were significantly increased in ESRF. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in ESRD patients Th1 T cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.

Aged↗

Coronary reoperations: recurrence of angina and clinical outcome with and without cardiopulmonary bypass.

BACKGROUND: We compared our experience of minimal tissue dissection and target vessel revascularization without cardiopulmonary bypass (CPB) with the standard procedure of total dissection of the heart and complete revascularization with CPB in patients who had elective reoperative coronary artery bypass grafting (redo-CABG). METHODS: We analyzed recurrence of angina and clinical outcome in 118 patients who had elective redo-CABG between January 1995 and April 2002. Seventy-four patients had redo-CABG with CPB, and 44 patients had redo-CABG without CPB. RESULTS: Perioperative outcome was comparable with regard to morbidity and mortality rates. At follow-up, the mean Canadian Cardiovascular Society score was 1.3 +/- 0.6 in patients who had redo-CABG with CPB and 1.7 +/- 0.8 in patients who had redo-CABG without CPB (p = 0.02). At follow-up, patients who had redo-CABG without CPB had a higher rate of recurrence of angina (log rank = 0.001) and higher use of nitrates (p = 0.015). Target vessel revascularization was an independent predictor of recurrence of angina in younger patients (< 75 years; p = 0.012) but not in the elderly (> or = 75 years; p = 0.142). CONCLUSIONS: In elective redo-CABG patients, minimal tissue dissection and target vessel revascularization without cardiopulmonary bypass did not add significant benefit with regard to perioperative morbidity and mortality. The unsatisfactory relief of symptoms does not seem to justify target vessel revascularization by a less invasive approach. Therefore, this technique should be offered exclusively to patients at high risk with complete revascularization using CPB, such as the elderly.

Aged↗

Pleurovenous shunting in the treatment of nonmalignant pleural effusion.

BACKGROUND: The goals of treatment of chronic nonmalignant pleural effusion are relief of dyspnea and improved quality of life. Treatment options include needle thoracentesis, tube thoracostomy chemical pleurodesis, and pleurectomy. Pleurovenous shunting (PVS) represents an alternative, minimally invasive method. METHODS: Since 1999, 12 patients underwent pleurovenous shunting for right-sided pleural effusion in our center. Indications were hepatic hydrothorax (n = 6, one as bridging to liver transplantation), nephrotic syndrome (n = 4), and chylothorax (n = 2, one as bridging to lung transplantation). All patients received Denver shunt systems from the pleural cavity to either the subclavian or jugular vein. RESULTS: Shunt occlusion was observed in one case (chylothorax) 4 weeks after implantation. There was one early death, which was not related to the procedure (hepatic failure). No air embolism or infection was observed. All systems were patent throughout the observation period of 1 to 40 months (mean = 13.3 months), and none of the patients required further treatment for pleural effusion. CONCLUSION: Pleurovenous shunting offers an efficient, minimally invasive alternative to other surgical methods for treatment of recurrent nonmalignant pleural effusion.

Aged↗

A double patch sandwich technique for surgical repair of acute aortic dissection type A.

BACKGROUND: This study compares two groups of patients with acute aortic dissection type A in whom two different techniques of anastomotic reinforcement were used, and evaluates the impact of these two techniques on perioperative blood loss and surgical outcome. METHODS: One hundred eighty-five consecutive patients with acute aortic dissection type A between 1998 and 2002 were grouped according to the technique utilized for reinforcing the aortic anastomotic site. Group A consisted of 21 patients in whom a novel double patch sandwich technique was used, whereas in group B (164 patients) conventional Teflon felt strips served as reinforcement. RESULTS: Preoperative profiles were comparable for both groups. Deep hypothermia and circulatory arrest were used in 180 patients (97%). Retrograde cerebral perfusion and retrograde cardioplegia were used in 70 patients (38%). Hospital mortality for the two groups was 4.7% (1 of 21) and 18% (29 out of 164), p < 0.30, respectively. On average 2 versus 6 U of PRBC (p < 0.21), and 3 versus 5 U of FFP (p < 0.004) were given during operation in groups A and B, respectively, and indicates reduced suture line bleeding in group A. CONCLUSIONS: Modifications in the surgical technique for repair of acute aortic dissection type A, and in anastomotic reinforcement in particular, may lead to substantial reduction of suture line bleeding and diminished blood loss and transfusion requirements, and favorably affects patient outcome. Nevertheless, continued effort is mandatory to further enhance surgical outcome in this patient population.

Acute Disease↗

Special considerations on the implantation technique for the MicroMed-DeBakey ventricular assist device axial pump.

Implantable continuous flow axial pumps were introduced to clinical settings in November 1998 with the MicroMed-DeBakey ventricular assist device. Axial pumps continuously unload the failing left ventricle and accurate positioning of the inflow cannula prevents substantial reductions in pump flow. Considerations on the implantation technique are made to minimize surgical trauma, to prevent ventricular collapse, to optimize inflow conditions (flow increased from 4.3 +/- 0.6 to 6.7 +/- 0.3 L/min), and to facilitate the subsequent transplantation.

Adolescent↗

The incidence of transient neurologic dysfunction after ascending aortic replacement with circulatory arrest.

BACKGROUND: Transient neurologic dysfunction (TND) namely postoperative confusion, delirium, and agitation after aortic operation, particularly after deep hypothermic circulatory arrest (DHCA), remains an underestimated adverse event in the early outcome of these patients. Although no influence on long-term outcome has been reported so far, this entity markedly affects the early outcome and leads to prolonged intensive care unit and hospital stay. METHODS: Between January 1997 and January 2003, 160 consecutive patients (130 type A dissections [81%] and 30 elective atherosclerotic aneurysms [19%]) had surgical repair with DHCA for a thoracic aortic aneurysm limited to the ascending aorta. From those, 40 patients (25%) underwent DHCA alone, whereas in 13 patients (8%) antegrade cerebral perfusion and in 103 patients (64%) retrograde cerebral perfusion was used for further brain protection. RESULTS: The overall incidence of TND was 18% (28 of 160) with a significant association between duration of circulatory arrest and the incidence of TND (13.8% in DHCA < 30 minutes versus 37.9% in DHCA > 40 minutes; p < 0.05). Furthermore the severity of TND was directly associated with the duration of circulatory arrest and age. In contrast, however, the use of retrograde cerebral perfusion had no influence on the incidence of TND, (p < 0.05). Intensive care unit stay as well as hospital stay were prolonged in the patients with TND (intensive care unit 14.3 +/- 14.2 days versus 10.8 +/- 13.7 days, p < 0.05; hospital stay 15.6 +/- 10.1 days versus 11.4 +/- 7.9 days, p < 0.05). CONCLUSIONS: Duration of DHCA, regardless of whether retrograde cerebral perfusion was used, was the most important predictor of the incidence of transient neurologic dysfunction in patients who had replacement of the ascending thoracic aorta. The occurrence of TND leads to impaired functional recovery as well as prolonged intensive care unit and hospital stay.

Age Factors↗

Risk factors of mortality and permanent neurologic injury in patients undergoing ascending aortic and arch repair.

OBJECTIVES: To analyze outcome in elderly patients after surgical repair of the ascending aorta and the aortic arch as compared with their younger counterparts and to determine risk factors of mortality and permanent neurologic injury. Patients and methods Between January 1995 and February 2003, a total of 369 patients underwent ascending aortic and arch repair. Indications for surgical intervention were acute type A dissections in 174 (47%) patients (<75 years, n = 147; > or =75 years, n = 27) and chronic atherosclerotic aneurysms in 195 (53%) patients (<75 years, n = 168; > or =75 years, n = 27). Emergency surgery was performed in 167 (45%) patients; 202 patients (54.7%) underwent surgery requiring deep hypothermic circulatory arrest. Pre- and intraoperative factors were evaluated by means of stepwise logistic regression analysis to determine risk factors of mortality and permanent neurologic injury. RESULTS: Overall in-hospital mortality was 11.6%. In-hospital mortality with regard to indication for surgical intervention was comparable in both age groups (type A dissection: <75 years, 15.6%; > or =75 years, 18.5%; P =.731; chronic atherosclerotic aneurysm: <75 years, 7.7%; > or =75 years, 7.4%; P =.933). Permanent neurologic injury was observed in 5.0%. Permanent neurologic injury with regard to surgical intervention was comparable in both age groups (type A dissection: <75 years, 8.8%; > or =75 years, 3.7%; P =.359; chronic atherosclerotic aneurysm: <75 years, 3.0%; > or =75 years, 3.7%; P =.843). Stepwise logistic regression analysis revealed preoperative hemodynamic instability (odds ratio 4.3; P =.000), duration of cardiopulmonary bypass (odds ratio 2.1; P =.001), and permanent neurologic injury (odds ratio 1.7; P =.033) but not age as independent predictors affecting mortality. Utilization of but not duration of deep hypothermic circulatory arrest was the only independent predictor of permanent neurologic injury (odds ratio 2.8; P =.019). CONCLUSIONS: Age shows a trend toward a higher risk of mortality but does not predict a higher incidence of permanent neurologic injury after ascending aortic and arch repair. As utilization of deep hypothermic circulatory arrest remains the only independent predictor of permanent neurologic injury, alternative approaches to maintain cerebral perfusion during ascending aortic and arch repair are warranted.

Adult↗

Neurocognitive deficit following mitral valve surgery.

OBJECTIVE: Neurocognitive deficit is an important complication in patients undergoing open heart surgery. The aim of this prospective, contemporary study was to objectively measure neurocognitive brain function following mechanical mitral valve replacement and mitral valve repair. METHODS: Forty consecutive, unselected patients (mechanical valve replacement n=20, mean age 65+/-14; valve repair n=20, mean age 64+/-7, P=0.896) entered this prospective, contemporary study. Neurocognitive function was objectively measured by means of P300 auditory evoked potentials (peak latencies, ms) and two standard psychometric tests (Mini Mental State Examination, Trailmaking Test A (TTA)), preoperatively, 7 days and 4 months postoperatively. RESULTS: Before operation, neurocognitive brain function was comparable in both patients groups (mechanical valve replacement versus valve repair: P300 potentials 374+/-25 versus 378+/-46 ms; P=0.791 and TTA 57+/-15 versus 54+/-10 s; P=0.552). Following mechanical valve replacement, neurocognitive function continuously worsened (7 day-follow-up: P300 potentials 392+/-28, P=0.001 versus preop and TTA 65+/-17, P=0.0001; 4-month follow-up: P300 potentials 406+/-39, P=0.0004; TTA 69+/-17, P=0.0001). Interestingly, neurocognitive brain function was unaffected in patients undergoing valve repair (7-day follow-up: P300 potentials 386+/-40, P=0.890 versus preop and TTA: 53+/-10, P=0.644; 4-month follow-up: P300 potentials 374+/-36, P=0.166 and TTA 54+/-11, P=0.147). At 4-month follow-up, patients with mechanical prostheses performed worse as compared to valve repair (P300 potentials: P=0.024; TTA P=0.014). CONCLUSION: As shown by P300 auditory evoked potentials and Trailmaking Test A, there is marked neurocognitive damage related to mechanical valve replacement, whereas mitral valve repair does not affect neurocognitive function. This finding supports the beneficial effect of mitral valve repair over mechanical valve replacement in the decision-making tree of borderline cases, which are suitable for both types of procedure.

Adult↗

Neurocognitive deficit following aortic valve replacement with biological/mechanical prosthesis.

OBJECTIVE: The aim of this study was to objectively measure neurocognitive deficit following aortic valve replacement with a mechanical or biological prosthesis. MATERIALS AND METHODS: In this prospective, contemporary study we followed 82 consecutive patients undergoing isolated aortic valve replacement with either a mechanical (n=29, mean age=52+/-7 years) or a biological (n=53, mean age=68+/-10 years) valve prosthesis. Neurocognitive function was measured by means of objective P300 auditory evoked potentials (peak latencies, ms) and two standard psychometric tests (Trailmaking Test A, Mini Mental State Examination) before the operation, 7 days and 4 months after the operation, respectively. RESULTS: Since P300 peak latencies increase with age, preoperative P300 measures are lower in patients receiving mechanical valves (360+/-35 ms, mean 52 years) as compared to patients receiving biological valves (381+/-34 ms, 68 years, P=0.0001). Seven days after surgery, P300 peak latencies were prolonged (-worsened) in both groups as compared to preoperative values (mechanical valves: 384+/-36 ms; P=0.0001 and biological valves: 409+/-39 ms; P=0.0001). Although on a different level (-age-related), this development was comparable within both groups (P=0.800). Four months after surgery, P300 peak latencies normalized in the mechanical valve group (372+/-27 ms, P=0.857 versus preoperative), while in contrast in the biological valve group they remained prolonged (417+/-37 ms, P=0.0001). We found no difference within patients receiving different types of biological or mechanical aortic valves. CONCLUSION: Postoperative neurocognitive damage is not reversible in (-elderly) patients with biological aortic valve replacement, while in contrast postoperative neurocognitive damage is reversible in (-younger) patients with mechanical valve replacement. For this contrary development, age seems to be most important, whereas damage related to type of valve prosthesis may be overestimated.

Adult↗

Endovascular stent graft placement in patients with acute thoracic aortic syndromes.

OBJECTIVE: In the present study, the effectiveness of endovascular stent grafts (ESG) in the treatment of acute aortic complications, such as acute dissection type B, penetrating ulcer and traumatic aortic rupture is evaluated. PATIENTS AND METHODS: From June 1997 to February 2002, 66 patients were treated with ESG. Out of this cohort, 19 patients (28.8%) were subjected to stent grafting due to acute aortic syndromes. Acute dissection type B was present in 11 patients (16.6%), a penetrating ulcer was diagnosed in six patients (9%) and in 2 patients (3%) a traumatic aneurysm was the indication for operation. There were 16 male and three female patients with a mean age of 60 years (20-85 years). Excluder stent grafts (Gore) were used in 15 patients, the Talent device (Medtronic) was implanted in four patients. RESULTS: Stent graft placement was technically successful in all patients. Hospital mortality was 0%. Paraparesis occurred in one patient (5.2%), which could be managed successfully without remaining neurological deficit after installation of cerebrospinal fluid drainage for 72h. In another patient, overstenting of the left subclavian artery caused ischemia of the left arm and left subclavian to carotid artery bypass had to be performed. ICU-stay ranged from 1 to 6 days (mean 2.4 days) and the patients could be discharged after an average hospital stay of 8 days. In the follow-up period, one patient died due to myocardial infarction and one patient had to be re-operated due to contained rupture of the thoracic aorta caused by an endoleak. CONCLUSIONS: The study suggests that endovascular stent grafting is an excellent and effective treatment modality for the acute aortic accident, which can be recommended for high-risk patients too. However, close follow-up examination is indicated and long-term results have to be awaited to evaluate the real effectiveness of this method.

Adult↗

Long-term survival (>10 years) of patients >60 years with induction therapy after cardiac transplantation.

OBJECTIVE: Cardiac transplantation has become an established method for end-stage heart disease. Short- and mid-term outcome has been known to be similar between younger and older (>60 years) recipients. So far, nothing is known about long-term outcome of old patients and the potential long-term effects of antibody induction therapy in these patients. The purpose of this study was to analyse long-term outcome of old cardiac transplant recipients who underwent antibody induction therapy. METHODS: Since 1989, 203 patients (total n = 882) above 60 years have been transplanted at our center. On these patients n = 66 were above 65 years. Survival, incidences of rejection, infection, cancer, graft arteriosclerosis and the amount of renal insufficiency were compared with patients <60 years (n = 679), transplanted during the same period of time. Freedom from specific event was computed by Kaplan-Meier analysis and compared by log-rank test. RESULTS: Ten year survival was similar in all groups (<60 years: 53.7%; 60-64 years: 53.1% and >65 years: 60.2%; P = NS). Causes of death were similar in all patient groups. There were significant fewer rejection episodes in the older patient group (freedom from rejection: 74.9 vs. 83.5 vs. 90.6; P = 0.03). Yet significantly more number of patients >65 years were without steroid maintenance therapy (43.1%) compared to other patient groups (8.2 vs. 9.3%; P < 0.05). There was no difference in overall freedom from severe infection (74.1 vs. 67.7 vs. 85.3%; P = NS), whereas there was a trend towards more CMV disease in the oldest patient group (82.7 vs. 88.6 vs. 70.8%; P=0.06). The incidence of cancer was similar in all groups (freedom from cancer: 82.2 vs. 84.7 vs. 79.1%; P = NS), as well as there was no difference in severe graftsclerosis between all patients (79.2 vs. 93.7 vs. 93.3%; P = NS). There was no difference in development of chronic renal dysfunction (creatinine > 2.0 mg/dl) between the three groups (10 vs. 14 vs. 16%; P = NS). CONCLUSIONS: Old recipients of cardiac transplants have a similar long-term outcome than younger recipients. They were less prone to rejections, had a similar incidence of severe infections and showed a trend towards more CMV disease. All patients had a very low rate of graft arteriosclerosis that was similar amongst the groups. Age-related decline of the immune system further enhanced by immunomodulation of antibody induction therapy might be accounted for the results as well as steroid-free immunosuppression.

Age Factors↗

Long-term results of CMV hyperimmune globulin prophylaxis in 377 heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation. METHODS: We studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups. RESULTS: During the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034). CONCLUSIONS: Cytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.

Antiviral Agents↗

CD32-mediated platelet aggregation in vitro by anti-thymocyte globulin: implication of therapy-induced in vivo thrombocytopenia.

Induction therapy with polyclonal antithymocyte-globulin (ATG) is widely used in the prophylaxis and treatment of acute cardiac-allograft rejection. Thrombocytopenia, however, is a major side-effect of ATG therapy and its mechanisms are poorly understood. The influence of ATG on platelet aggregation was studied aggregometrically, expression of platelet surface activation antigens CD62P and CD63 was determined by flow cytometry analysis, and electron microscopy was utilized to determine thrombocyte morphology. Treatment of platelets with ATG markedly induced aggregation, whereas OKT3 or anti-IL-2R antibodies did not. Furthermore, platelets incubated with ATG featured an up-regulation of the surface activation markers CD62P and CD63, secretion of platelet-bound sCD40L (CD154) and increased signs of aggregation in electron microscopy analysis. The capacity of ATG to induce platelet aggregation was completely blocked by antibodies against the low-affinity Fc IgG receptor (CD32). Since blocking of CD32 abrogates platelet aggregation, we suggest that CD32 plays a crucial role in ATG-induced thrombocytopenia.

Flow Cytometry↗