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Biomedical subjects

E Wolner

Publications and source records attributed to E Wolner.

At least 91 records · Page 5Linked to original sources
PubMed2000

Adhesion molecule behavior during rejection and infection episodes after heart transplantation.

In cardiac transplant recipients the release of soluble cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune activation. It is uncertain whether there is a specific pattern of release during infection or cardiac allograft rejection. In a prospective study, 30 consecutive cardiac allograft recipients were followed for a median period of 11.4 months (range 1-34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E-Selectin (sE-Selectin) were measured in addition to acute phase proteins (C-reactive protein, alpha1-antitrypsin), complement factors (C3, C4) and beta2-microglobulin. The measured serum levels were correlated with the clinical status of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy subjects served as controls. Six days before biopsy-proven cardiac allograft rejection sICAM-1-release started to increase (p < 0.05) as compared to uneventful clinical status. The peak concentration of sICAM-1 was measured three days before rejection. On the day of rejection, serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were increased, whereas sE-Selectin was not markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were elevated at the day of diagnosis and both parameters reached peak levels three days after onset of chemotherapy. In multivariate analysis soluble adhesion molecules only weakly discriminated between rejection and infection (sensitivity: 13%, specificity: 95%). Although, in combination with routine blood parameters the discriminatory power could be improved (sensitivity: 85%, specificity: 85%) the clinical utility of these markers in non-invasive monitoring is limited.

Adult↗
PubMed2000

Different modes of degeneration in autologous and heterologous heart valve prostheses.

BACKGROUND AND AIM OF THE STUDY: This study was performed to elucidate the mechanism of primary tissue failure of bioprosthetic heart valves, which were fabricated from autologous pericardium (Autogenics). Results were compared with the degeneration pattern of heterologous pericardial bioprostheses. METHODS: Between March 1994 and December 1996, 87 Autogenics heart valves were implanted in the aortic position. Since then, 15 valves had to be explanted due to structural deterioration. The average implant period was 33+/-8 months. All explants were examined by gross morphological evaluation and X-ray analysis to identify the failure mode of these devices. In eight explanted autologous tissue valves and six explanted heterologous pericardial bioprostheses, exact morphological evaluation was performed by scanning electron microscopy, microscopic and immunohistochemical techniques. RESULTS: All autologous tissue valves failed due to cuspal tears localized at the commissures. Nocalcification could be detected by X-ray analysis and microscopic methods. Endothelial cell coverage was evident at the outflow surface of all autologous bioprostheses. Histological examination showed severe disintegration of the collagen fibers by insudated plasma proteins and erythrocytes, and the absence of the original fibroblasts. Collagen fibers were vigorously altered between the inner and outer stent of the Autogenics valve. In contrast, heterologous pericardial valves failed due to severe calcification of the cusps. Histological evaluation displayed invasion of macrophages and calcific deposits. The collagenous texture of the pericardial tissue was significantly better preserved compared with autologous tissue. CONCLUSION: High biocompatibility of autologous tissue valves is indicated by the absence of calcium deposits, macrophages and foreign body giant cells, and the presence of endothelial cell ingrowth. Severe disintegration of autologous tissue suggests that brief immersion in glutaraldehyde generates inadequate mechanical stability of bioprosthetic heart valve material. Heterologous valves exhibit low biocompatibility but superior preservation of the collagenous biomaterial.

Aged↗
PubMed2000

Does the Ross operation fulfil the objective performance criteria established for new prosthetic heart valves?

BACKGROUND AND AIM OF THE STUDY: Objective Performance Criteria (OPC) were established to compare a new heart valve prosthesis with fixed standards of linearized complication rates for morbid events: thromboembolism, thrombosis, hemorrhage, leakage and endocarditis. Although the pulmonary autograft operation provides optimal hemodynamic performances, the morbidity of both the autograft and homograft remain topics of controversy. METHODS: Valve-related morbid events and echocardiography in 109 patients who have undergone the Ross operation since 1991 were evaluated at annual follow up examination (mean 2.8 years; range: 1 month to 8 years). Linearized rates (number of events per 100 years patient exposure) were calculated to establish the safety and efficacy of this operation (288.7 years cumulative patient-years). RESULTS: Three patients died perioperatively (2.8%); two patients were reoperated due to autograft incompetence (1.8%, both valve repairs). No patient is currently on anticoagulation therapy, and no events of thromboembolism, valve thrombosis or bleeding were observed during follow up. Two patients had homograft endocarditis but were asymptomatic with moderate incompetence at the last follow up examination. There was no significant increase in aortic incompetence (AI) or pulmonary incompetence (PI) between discharge and follow up (AI, 0.4 +/- 0.5 versus 0.6 +/- 0.6; PI, 0.2 +/- 0.4 versus 0.4 +/- 0.6). In comparing the OPC (events per patient-year) for the Ross operation with those for tissue and mechanical valves, the results were: thromboembolism 0% (tissue 2.5%, mechanical 3%), valve thrombosis 0% (0.2% and 0.8%), all bleeding 0% (1.4% and 3.5%), major bleeding 0% (0.9% and 1.5%), all leakage 0.7% (1.2% and 1.2%), major leakage 0.7% (1.2% and 1.2%) and endocarditis 0.7% (1.2% and 1.2%). CONCLUSION: The pulmonary autograft procedure provides optimal hemodynamics and echocardiographic performance, and low valve-related complication rates; thus, the OPC for tissue and mechanical heart valve prostheses can be fulfilled by this technically demanding operation. These results confirm that the autograft is an ideal aortic valve replacement device.

Adolescent↗
PubMed2000

Mid-term follow up of mitral valve reconstruction due to active infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Mitral valve reconstruction in patients with acute endocarditis (AE) is a challenging operation which prompts the surgeon into immediate action. This report summarizes the mid-term results of 22 patients who required mitral valve reconstruction due to AE. METHODS: Mean patient age was 46 years (range: 20-79 years); mean follow up was 46 months (range: 1-90 months). Preoperatively, >70% of patients had severe mitral regurgitation and were in NYHA functional class III. Surgical techniques used were annuloplasty (n = 16; 10 with Carpentier ring, five Wooler-Kay and one Frater); suture closure of the perforation (n = 1), patch closure of the perforation (n = 5), leaflet resection with primary closure (n = 2), leaflet resection with patch closure (n = 8), and chordal transfer (n = 3). Additional surgery included CABG (n = 3) and De Vega plasty (n = 4). Aortic valve replacement or reconstruction (n = 9) included one mechanical valve, one bioprosthesis, one reconstruction and six homografts. Patients were followed up annually in our outpatient department and/or by questionnaires. RESULTS: Two patients died perioperatively due to either low output syndrome or uncontrolled sepsis. There were three reoperations; two of these were successful, and one patient subsequently died. In addition, one patient died six years after operation due to prostatic cancer, and one seven years later due to progressive heart failure. At the last follow up, 15 patients were in NYHA class I (68%) and five in class II (23%); no or only mild mitral insufficiency was seen on transthoracic echocardiography (91%). The estimated survival rate at 60 months was 87 +/- 12.7%, and 12 patients were followed up for >60 months. No incidence of recurrent valve infection occurred. CONCLUSION: Mitral valve reconstruction in patients with AE shows a low incidence of valve-related complications with promising postoperative functional results and mid-term survival. On this basis, mitral valve reconstruction for mitral insufficiency secondary to AE may be recommended as a valve salvage treatment, when it is technically possible.

Endocarditis, Bacterial↗
PubMed1999

[The DeBakey VAD axial flow pump: first clinical experience with a new generation of implantable, nonpulsatile blood pumps for long-term support prior to transplantation].

Because of the high frequency of acute hemodynamic deterioration in patients awaiting cardiac transplantation, mechanical techniques of circulatory support to bridge the period until transplantation have become a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives in terms of ventricular assistance and/or as a total cardiac substitute. A DeBakey VAD axial flow pump was implanted in two male patients (aged 44 and 65 years, respectively) suffering from end-stage left heart failure. In the initial postoperative period the mean flow rate of the pump was 3.9 +/- 0.5 l/min. In both patients, the early postoperative phase was characterised by a completely non-pulsatile flow profile. Two weeks after implantation and partial recovery of the natural left ventricle, increasing pulse pressures became evident and net flow increased to 4.5 +/- 0.6 l/min. Patients were mobilised and made to under-go regular physical training. Hemolysis produced by the pump was low while free haemoglobin stayed in physiological ranges, increasing only slightly from 2.1 +/- 0.8 mg/dl preoperatively to 3.0 +/- 1.5 mg/dl ten weeks after implantation. One patient was successfully transplanted on day 74 after implantation of the DeBakey VAD while the second patient is, after 110 days of pumping, still waiting for transplantation. This first experience concerning clinical implantation of the DeBakey VAD axial flow pump showed that the device is promising as a means of providing mechanical support to bridge the period until cardiac transplantation.

Adult↗
PubMed1999

Azathioprine and 6-mercaptopurine alter the nucleotide balance in endothelial cells.

Graft vascular disease after solid organ transplantation is a main complication that limits long-term survival of the graft. An injury of the endothelium and subsequent vascular response is considered to be responsible for smooth muscle cell hyperplasia with resulting luminal narrowing. What is less certain are the precise steps leading to endothelial injury and subsequent vessel disease. Since the immunosuppressive drug azathioprine is in clinical use due to its antiproliferative effect on lymphocytes, we were interested in how far it exerts effects on the vascular endothelium. Azathioprine and its metabolite 6-mercaptopurine, a potent inhibitor of purine salvage pathway enzymes, dose dependently led to decreased endothelial cell proliferation as well as to decreases in intracellular purine nucleotides adenosine-triphosphate and guanosine-triphosphate. By increasing the formation of the pyrimidine nucleotide uridine-triphosphate within 24 hours, azathioprine and its metabolite altered the endothelial nucleotide balance. Since not only the formation of toxic thio- and methylthiopurines (thio-guanosine-monophosphate, methyl-thio-inosine-monophosphate) was measured, the activity of the enzyme thiopurinemethyltransferase was induced (3.21+/-2.04 U per 10(9) cells, mean+/-SD). These findings indicate that the vascular endothelium plays an active role in the metabolization of the established immunosuppressant azathioprine that then exerts specific toxic effects on endothelial cells.

Azathioprine↗
PubMed1999

[Results of lung-volume reduction surgery in end-stage lung emphysema].

BACKGROUND: Surgical treatment of diffuse, nonbullous emphysema was first described by Brantigan et al. in 1957 and was reintroduced by Cooper et al. in 1995 as lung-volume reduction surgery (LVRS). Meanwhile it has become an internationally established procedure in the treatment of lung emphysema. We report our results after LVRS in 91 patients. METHODS: Between September 1994 and August 1998 LVRS was performed through median sternotomy (n = 15), videoendoscopy (n = 49), thoracotomy (n = 18) or combined video endoscopy on one side and thoracotomy on the other (n = 9) in 91 patients (aged 33-80 years; mean 56,4 years). All patients showed progression of severe dyspnea despite maximum medical and physical therapy. RESULTS: Perioperative mortality was 5.5 % (5 patients). Seventy-five percent of the patients showed significant functional improvement [postoperatively above 120 % of the preoperative forced expiratory volume in 1 s (FeV1)]. Mean FeV1 significantly increased by 28.6 % from 25.5 +/- 1.2 % predicted (% p) preoperatively to 32.8 +/- 1.9 % p during the first 6 months postoperatively (p < 0.005). Furthermore, the mean RV was reduced from 320.3 +/- 7.9 % p preoperatively to 248.4 +/- 7.5 % p 6 months postoperatively and mean TLC from 140.2 +/- 2.4 % p to 126.1 +/- 2.1 % p (p < 0.005). Intrinsic PEEP decreased significantly from 5.1 +/- 0.4 cm H(2)O preoperatively to 2.3 +/- 0.3 cm H(2)O postoperatively (p < 0.05). CONCLUSION: LVRS is an excellent therapeutic option for selected patients with severe emphysema and additional signs of severe hyperinflation. It results in significant postoperative functional improvement and marked increase in quality of life. The long-term benefit of LVRS remains to be defined.

Adult↗
PubMed1999

T4 lung tumors with infiltration of the thoracic aorta: is an operation reasonable?

BACKGROUND: Only anecdotal reports about the results of combined resection of T4 lung tumors infiltrating the thoracic aorta exist. METHODS: Seven patients (mean age, 57.5 years; range, 43 to 78 years) underwent a resection of the infiltrated segment of the thoracic aorta together with a left pneumonectomy (n = 6) or left upper lobectomy (n = 1). Five tumors were primary non-small cell lung carcinomas (T4N2 in 3 patients, T4N1 in 2), one was a metastasis of breast cancer, and one was rhabdomyosarcoma. RESULTS: No patient died perioperatively. The 2 patients with rhabdomyosarcoma and metastasis of breast cancer died 2 and 7 months postoperatively. Of the 5 patients with bronchial carcinoma, 3 died after 17, 26, and 27 months as a result of distant metastasis. Two patients are alive after 14 and 50 months without evidence of disease recurrence. One-year, 2-year, and 4-year survival rates for patients with bronchial carcinoma were 100%, 75%, and 25%, respectively. CONCLUSIONS: Combined resection of the lung and thoracic aorta can be performed with low morbidity and mortality when offered to highly selected patients. Adequate local control of tumor can be achieved for N1 and single-level N2 non-small cell lung carcinomas, but not for tumors with other histologies.

Adenocarcinoma↗
PubMed1999

Development of a totally implantable biventricular bypass centrifugal blood pump system.

BACKGROUND: During the past 2 years, the development of a totally implantable biventricular bypass rotary blood pump system has been made. METHODS: An extracorporeal gyro centrifugal pump, the CIE3, was miniaturized and developed into the PI601, a totally implantable plastic pump. Two-day anatomic and hemodynamic feasibility studies demonstrated that these two pump systems were easily implantable inside a calf's abdominal wall, directly under the diaphragm. The priming volume of the pump was 20 mL, with sufficient cardiac outputs at approximately 2,000 rpm and requiring less than 10 W of power. Two-week antithrombogenic screening tests also revealed these pump systems to be quite antithrombogenic. In addition, 1-month system reliability studies demonstrated fail-safe reliable performances. RESULTS AND CONCLUSIONS: Encouraged by these preliminary studies, the PI601 model was converted to the permanently implantable titanium gyro pump PI702 model. The long-term implantations were initiated approximately 3 months ago, and two such long-term LVAD studies are currently underway with no sign of difficulty (October 10, 1997). They were followed 283 days and 72 days, respectively. Both terminated due to functional inflow obstruction. There were no blood clots or emboli at autopsy.

Animals↗
PubMed1999

Cardiac transplantation and simultaneous surgical repair of an aortic aneurysm.

Simultaneous cardiac transplantation and surgical repair of an aortic aneurysm has not been reported previously. At our institution, a 59-year-old patient with an aneurysm of the ascending aorta and aortic arch required orthotopic cardiac transplantation for end-stage cardiomyopathy. He underwent successful surgical replacement of his ascending aorta and transverse arch (in circulatory arrest and deep hypothermia) at the time of heart transplantation.

Anastomosis, Surgical↗
PubMed1999

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair.

OBJECTIVE: Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS: Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS: Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION: Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.

Adult↗
PubMed1999

Independent prognostic role of p16 expression in lung cancer.

OBJECTIVES: The cyclin-dependent kinase p16 (also known as Ink4A, Mts1, Cdkn2, and Cdkn4i) has been proposed as a tumor suppressor gene mapped on chromosome segment 9p21. This study evaluated p16 protein expression in 135 lung cancer specimens and investigated potential genetic alterations occurring in this gene. RESULTS: We found altered p16 immunohistochemical expression to be a frequent event in lung cancer and to be independent of either the histologic type or any other clinical-pathologic feature. Western blot analyses performed on about one third of the specimens correlated highly with these results. In addition, we found p16 immunohistochemical expression to be a favorable prognostic factor in lung cancer in that its reduction or loss correlated with a worse outcome for the patients. Polymerase chain reaction amplification and direct sequencing of p16 exons 1 and 2 revealed no mutations, indicating that p16-altered expression in lung cancer is not necessarily linked to mutational events of these genes. CONCLUSIONS: We conclude that p16-altered expression is both an independent and frequent event in lung cancer and may have an important role in tumorigenesis and in malignant progression of a significant proportion of these cancers. However, the actual incidence and relevance of p16 mutations in this neoplasm continues to be debated, and its analysis seems inconclusive. Our results suggest a prognostic role for the immunodetection of this protein on formalin-fixed and paraffin-embedded specimens. They further suggest its routine use in the evaluation of the frequently unpredictable behavior of lung cancer.

Adenocarcinoma↗
PubMed1999

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS: Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS: A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS: In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Memantine for prevention of spinal cord injury in a rabbit model.

BACKGROUND: This study was conducted to investigate the effect of memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist, on the neurologic outcome of spinal cord ischemia after aortic occlusion. MATERIALS AND METHODS: New Zealand White rabbits were anesthetized and spinal cord ischemia was induced for 40 minutes by infrarenal aortic occlusion. Animals were randomly allocated to 3 groups. Group 1 (n = 8, control) received no pharmacologic intervention, group 2 (n = 8) received intra-aortic memantine infusion (20 mg/kg) after aortic crossclamping, and group 3 (n = 8) was treated with systemic memantine infusion (20 mg/kg) 45 minutes before aortic occlusion. Neurologic status was scored by the Tarlov system (in which 4 is normal and 0 is paraplegia) at 12, 24, 36, and 48 hours after the operation. Lumbar spinal root stimulation potentials and motor evoked potentials from lower limb muscles were monitored before, during, and after the operation. After the animals were killed, the spinal cords were studied histopathologically. RESULTS: All potentials disappeared shortly after aortic crossclamping. They returned earlier in both memantine-treated groups than in the placebo group. Histologic examination of spinal cords revealed a few abnormal motor neurons in memantine-treated rabbits but found extensive injury in the control group. At 12 hours the median Tarlov scores were 0 in the control group (group 1), 2 in the intra-aortic memantine group (group 2, P =.001 versus control), and 3 in the systemic group (group 3, P =.0002 versus control). At 24 hours median Tarlov scores were 0, 2.5 (P =.0002), and 4 (P =. 0002), respectively. Finally, at both 36 and 48 hours median Tarlov scores were 0, 3 (P =.0006), and 4 (P =.0002), respectively. CONCLUSION: Memantine significantly reduced neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion.

Animals↗