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Stephan Korom

Publications and source records attributed to Stephan Korom.

12 recordsLinked to original sources
PubMed2006

CD26/dipeptidylpeptidase IV-targeted therapy of acute lung rejection in rats.

BACKGROUND: CD26 is a T-cell co-stimulator, and interacts with adenosine deaminase, human immunodeficiency virus (HIV) Tat-1 protein and extracellular matrix. It possesses dipeptidylpeptidase IV (DPP IV) catalytic activity, which is linked to its co-stimulatory efficacy. We investigated the effect of specific DPP IV systemic activity inhibition on acute pulmonary rejection. METHODS: Rat single-lung transplantation (Tx) was performed (LBNF1/LEW donor/recipient) in two groups (n = 12). Group I (n = 6) received daily treatment with a Pro-Pro-diphenylphosphonate derivative (AB197), and Group II served as an untreated control. At Day 5 post-Tx, ventilatory parameters, cytotoxicity and mixed lymphocyte reaction were analyzed and staining for ISHLT rejection grade and proliferating cell nuclear antigen (PCNA) was performed. RESULTS: Treatment with AB192 abrogated acute rejection and preserved pulmonary function up to Day 5 post-Tx for PO2 (Group II: 24.9 +/- 6.9 mm Hg; Group I: 149.5 +/- 24.3 mm Hg; p < 0.001), PCO2 (Group II: 53.3 +/- 13.6 mm Hg; Group I: 39.0 +/- 9.8 mm Hg; p < 0.05) and peak airway pressure (Group II: 50.7 +/- 17.2 mm Hg; Group I: 20.2 +/- 10.0 mm Hg; p < 0.01). Controls showed moderate/severe rejection (ISHLT Grade A2 or 3), grafts from inhibited hosts revealed no/mild rejection (Grade A0 to 2: Group II: 2.8 +/- 0.3; Group I: 1.25 +/- 1.0; p < 0.005). Proliferating cell nuclear antigen (PCNA) staining of rejection-associated cellular infiltrates showed a significant reduction in positivity in perivascular infiltrates (34 +/- 11.5%; p < 0.05) and bronchial surface epithelium (31.7 +/- 10.6%; p < 0.05) in Group I vs Group II (55.9 +/- 8.4% and 57.2 +/- 4.5%). CONCLUSIONS: Irreversible enzymatic inhibition of DPP IV has been shown to abrogate acute pulmonary rejection, maintain pulmonary function, and preserve histomorphologic architecture. These results extend earlier findings and illustrate the role of CD26/DPP IV in alloantigen-mediated immune responses.

Animals↗
PubMed2006

Sildenafil extends survival and graft function in a large animal lung transplantation model.

OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. METHODS: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except for the sildenafil application, the control group (II) (n=4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5h, cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial pressure, pCO(2), pO(2)) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(-5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improved.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.

BACKGROUND: In this study, we prospectively analyzed the functional outcome and the survival after lung-volume reduction surgery (LVRS) in patients with end-stage emphysema who were initially potential candidates for lung transplantation (LTX), and investigated the impact of LVRS on posttransplant course in patients who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of video-assisted, bilateral stapled resection of target areas. During the same period, 31 patients underwent primary LTX for end-stage emphysema (LTX group). Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking distance, and dyspnea score were assessed preoperatively and at predetermined times after operation. Survival analysis was performed by use of the Kaplan-Meier method. RESULTS: All the functional variables significantly improved after LVRS and peaked within the first year. Subjective improvement was observed for up to 5 years after LVRS, and 53% (31 of 58) of the patients were still alive and had not undergone transplantation after a median follow-up of 44 months. Fourteen percent (8 of 58) of the patients underwent secondary LTX because of progressive worsening of the respiratory function after a median bridging time between LVRS and LTX of 33 months. Postoperative recovery after transplantation and median survival time were comparable between the 8 patients of the LVRS/LTX group and the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9). CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and lung function in selected patients who are initially potential candidates for LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4 to 5 years and does not impair the chances for a subsequent successful LTX.

Adult↗
PubMed2005

Extended donor lungs: eleven years experience in a consecutive series.

OBJECTIVE: The aim of this study was to delineate the profile of extended donor lungs in comparison to ideal donor lungs and to analyse their outcome. Particular attention was given to donor lungs with a low PaO(2) (<250mmHg) before harvesting or with multiple extended criteria. METHODS: Between 1993 and 2003, 148 patients (79 women, 69 men, mean age 39.9 years) underwent lung transplantation. Indications were cystic fibrosis in 35.8%, emphysema in 26.4%, pulmonary fibrosis in 12.2%, pulmonary hypertension in 9.5%, and others in 16.1%. Donor data and recipients medical files were reviewed. Criteria for donor lungs were considered extended if one or more of the following criteria were met: age >55 years, smoking >20 pack-years, PaO(2) before harvesting <300mmHg, pathologic chest X-ray, and purulent secretion at bronchoscopy. A comparison between recipients from ideal and from extended donor lungs was performed with respect to the median duration of mechanical ventilation, the median length of stay at the intensive care unit, postoperative complications, the 30-day and the 1-year survival, and the 6-month follow-up spirometry. RESULTS: Sixty-three (42.6%) donor lungs were considered extended and 20 (31.7%) met more than one criteria. Outcome comparison between recipients from ideal (I) and extended (II) donor lungs did not statistically differ in postoperative complications (18.8% (I) vs. 26.9% (II), P=0.32), mean duration of mechanical ventilation (d) (4.4+/-2.7 (I) vs. 2.6+/-2.1 (II), P=0.2), mean length of stay at the ICU (d) (11.5+/-8.8 (I) vs. 9.2+/-6.9 (II), P=0.4), 6-month pulmonary function (FEV1=83+/-23% of the predicted value (I) vs. 82+/-18% (II), P=0.81), 30-day survival (90.6% (I) vs. 93.7% (II), P=0.56), 1-year survival (83.5% (I) vs. 81% (II), P=0.83). Thirty-day survival was also comparable even in recipients from donor lungs with PaO(2)<250mmHg (n=8) (90.6% (I) vs. 87.5%, P=0.57). The number of extended criteria had no impact on the outcome. The combination of PaO(2)<300mmHg with purulent secretion at bronchoscopy seemed to influence the early outcome of recipients from extended donor lungs negatively. CONCLUSIONS: Our results suggest that the use of selected extended donor lungs does not compromise the outcome after transplantation. PaO(2) <250mmHg before harvesting of the lungs is not an absolute contra-indication for transplantation.

Adult↗
PubMed2004

Catamenial pneumothorax revisited: clinical approach and systematic review of the literature.

BACKGROUND: Catamenial pneumothorax is a rare entity of spontaneous, recurring pneumothorax in women. It has been associated with thoracic endometriosis, yet varying clinical courses and the lack of consistent intraoperative findings have led to conflicting etiologic theories. METHODS: We discuss etiology, clinical course, and surgical treatment of 3 women with catamenial pneumothorax. In addition, the world literature since the first description is reviewed. RESULTS: Three women (31, 32, and 39 years old) had recurrent, menses-associated, right-sided spontaneous pneumothoraces. They had undergone video-assisted thoracoscopic surgery previously, with various unsuccessful procedures. Finally, with video-assisted thoracoscopic surgery multiple small perforations in the tendinous part of the right diaphragm with adjacent endometrial implants were detected. After plication of the involved area, 2 patients have been free of recurrence for 22 and 13 months, respectively. Laparoscopic evaluation in 1 woman with a further recurrence revealed asymptomatic pelvic endometriosis. This patient has been free of recurrence since initiation of luteinizing hormone-releasing hormone analog therapy for 17 months. In a review of 229 cases of catamenial pneumothorax in the literature, adequate information was given for 195 patients (85.2%). One hundred fifty-four (79%) were treated surgically, with detailed findings reported for 140 (91%). Thoracic endometriosis was diagnosed in 73 patients (52.1%), and 54 (38.8%) showed diaphragmatic lesions. Pleurodesis, with or without diaphragmatic repair or wedge resection, was performed in 81.7% of the cases. CONCLUSIONS: Catamenial pneumothorax may be suspected in ovulating women with spontaneous pneumothorax, even in the absence of symptoms associated with pelvic endometriosis. During video-assisted thoracoscopic surgery, inspection of the diaphragmatic surface is paramount. Plication of the involved area alone can be successful. In complicated cases, hormonal suppression therapy is a helpful adjunct.

Adult↗
PubMed2004

Melatonin in vivo prolongs cardiac allograft survival in rats.

Melatonin, secreted by the pineal gland, is a multifunctional agent which (i) protects tissues from damage through free radical scavenging and attenuates ischemia/reperfusion injury in organ grafts; (ii) acts synergistically with cellular antioxidants; and (iii) displays complex, dose-dependent immunoenhancing and suppressing effects in vitro and in vivo. We analyzed the immunomodulatory effect of melatonin on acute allograft rejection. Cardiac grafts were transplanted from LBNF1 to LEW rats and anastomosed to the abdominal great vessels. The effect of low-dose (LD; 20 mg/kg/day) and high-dose (HD; 200 mg/kg/day) melatonin treatment in recipients compared with untreated controls was investigated. HD melatonin therapy abrogated acute rejection, significantly prolonging allograft survival (mean survival: 12.3 +/- 1 days S.D., n = 8, P < 0.0001) compared with untreated controls, which rapidly reject the transplant (6.3 +/- 1 days n = 12). LD therapy did not extend survival significantly (7.3 +/- 1.1 days, n = 12). Allospecific IgM showed a significant decrease in animals receiving HD therapy versus untreated recipients at days 10 and 14 post-transplantation (P < 0.01), whereas in the LD group at day 10, a significant increase in allospecific IgM (P < 0.01) over the HD cohort was demonstrated. HD treatment markedly reduced lymphocyte proliferative capacity compared with controls and the LD group. HD melatonin treatment abrogated acute allograft rejection and significantly prolonged graft survival. Our results suggest an involvement of melatonin in humoral and cellular immune pathways following perfused organ transplantation. These findings may indicate a novel therapeutic approach, based on modulation of the neuroendocrine/immune axis through melatonin as a possible future immunosuppressant in organ transplantation.

Animals↗
PubMed2003

Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.

BACKGROUND: We compared the diagnostic accuracy of integrated positron-emission tomography (PET) and computed tomography (CT) with that of CT alone, that of PET alone, and that of conventional visual correlation of PET and CT in determining the stage of disease in non-small-cell lung cancer. METHODS: In a prospective study, integrated PET-CT was performed in 50 patients with proven or suspected non-small-cell lung cancer. CT and PET alone, visually correlated PET and CT, and integrated PET-CT were evaluated separately, and a tumor-node-metastasis (TNM) stage was assigned on the basis of image analysis. Nodal stations were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathological assessment of tumor stage and node stage. Extrathoracic metastases were confirmed histopathologically or by at least one other imaging method. A paired sign test was used to compare integrated PET-CT with the other imaging methods. RESULTS: Integrated PET-CT provided additional information in 20 of 49 patients (41 percent), beyond that provided by conventional visual correlation of PET and CT. Integrated PET-CT had better diagnostic accuracy than the other imaging methods. Tumor staging was significantly more accurate with integrated PET-CT than with CT alone (P=0.001), PET alone (P<0.001), or visual correlation of PET and CT (P=0.013); node staging was also significantly more accurate with integrated PET-CT than with PET alone (P=0.013). In metastasis staging, integrated PET-CT increased the diagnostic certainty in two of eight patients. CONCLUSIONS: Integrated PET-CT improves the diagnostic accuracy of the staging of non-small-cell lung cancer.

Aged↗
PubMed2003

CD26/DPP IV in experimental and clinical organ transplantation.

UNLABELLED: The T-cell activation-Ag CD26 possesses dipeptidyl peptidase IV (DPP IV) enzymatic activity. Costimulatory efficacy and immunocompetence are associated with the enzymatic activity. GOALS: In models of experimental cardiac allograft transplantation (HTx), we analyzed the role of CD26/DPP IV during organ rejection. Also, we investigated CD26 enzymatic and cellular expression in human recipients of kidney transplants (Tx). MATERIAL AND METHODS: Heterotopic HTx in rats, models of acute and accelerated rejection. Monitoring of DPP IV serum levels and humoral immunity. Propro-diphenyl phosphonate was employed to inhibit DPP IV activity during rejection. In a prospective study, surface expression of CD26, 3, 4, 8, 45, 122 and ADA on PBL and DPP IV serum activity were measured in kidney recipients for 24 months post-transplantation. RESULTS: Acute rejection was . associated with increased serum DPP IV activity (p < 0.005). Specific inhibition abrogated acute (p < 0.0001) and accelerated (p < 0.01) rejection, impairing cytotoxicity and allospecific Ig-synthesis. Kidney recipients displayed a significant drop in CD26 expression on PBL for up to 18 months postoperatively (p < 0.001). CD4, 8, 45, 122 and ADA expression kinetics were only briefly affected. DPP IV enzymic activity stayed depressed for at least 12 months (p < 0.001). CONCLUSION: CD26/DPP IV is pivotal in T-cell mediated immune responses toward allo-Ag. In clinical transplantation, engraftment/immunosuppression are reflected by CD26 cellular and enzymatic expression posttransplantation and may serve as an indicator for immunomodulation.

Animals↗
PubMed2003

The influence of the rapamycin-derivate SDZ RAD on the healing of airway anastomoses.

OBJECTIVE: Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses. MATERIALS AND METHODS: The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n=4) were without, and study animals (group 2, n=6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured. RESULTS: All animals survived without complications. Serum levels of SDZ RAD were 30.9+/-8.7 ng/ml (recommended level 20-40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75+/-0.35 vs. 7.69+/-1.39 N, P=0.01). Histology did not show a significant change in histoarchitecture between the groups. CONCLUSIONS: Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients.

Anastomosis, Surgical↗
PubMed2003

Tissue engineered cartilage generated from human trachea using DegraPol scaffold.

OBJECTIVE: To date numerous attempts have been undertaken to conquer the challenging problem of reconstructing long segmental tracheal defects, as yet without lasting success. Recently, employing concepts of tissue engineering in animals, cartilage-like constructs were transplanted in vivo. However, both the feasibility of fabricating tracheal replacements and the use of human tracheal chondrocytes (HTC) for tissue engineering are still under investigation. In this study, we optimized isolation and cultivation techniques for human tracheal cartilage, assessing the feasibility of seeding these cells onto a novel, three-dimensional (3-D) polyester-urethane polymer (DegraPol). METHODS: Human tracheal cartilage was harvested from the trachea of lung donors, digested in 0.3% collagenase II, and the condrocytes serially passaged every 7-9 days. Cells were also cultivated over agar plate during the total 6-8 weeks expansion phase. Thereafter, chondrocytes were seeded onto DegraPol (pore sizes 150-200 microm) with a seeding density of 2.4 x 10(7)/ml, and chondrocyte-polymer constructs maintained during in vitro static culture. RESULTS: HTC displayed stable proliferation kinetics in monolayer culture with positive expression of collagen type II. Following polymer seeding, both cellular proliferation and extracellular matrix (ECM) production, as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and glycosaminoglycan assays, continued over extended culture. Active growth of HTC on DegraPol was further demonstrated by Alcian blue staining, with the histomorphological appearance of the construct resembling that of native cartilage. Scanning electron microscopy showed chondrocyte growth and ECM synthesis both on the surface and inside the porous scaffold, with a dense cell layer on the surface of the scaffold and a lower cell distribution in the scaffold's interior. CONCLUSIONS: The harvested chondrocytes from human trachea cartilage expand well in vitro and possess the ability to form new cartilage-like tissue when seeded onto DegraPol matrix. However, improved culture conditions are needed to permit cellular growth throughout cell-polymer constructs.

Absorbable Implants↗
PubMed2002

Prevention of recurrent empyema after pneumonectomy for chronic infection.

OBJECTIVES: Pneumonectomy in chronic pulmonary infection with empyema is associated with a high mortality rate and an increased risk of recurrent empyema. The surgical resection is technically demanding, and successful management continues to be a challenge. METHODS: We evaluated a concept which combines (pleuro-)pneumonectomy or completion pneumonectomy with surgical debridement of the pleural cavity and packing with povidine-iodine soaked dressings. The debridement and packing is repeated in the operating theater after 48 h until the chest cavity is macroscopically clean. Finally, the pleural space is obliterated with antibiotic solution. RESULTS: Between February 1997 and October 2000, 11 patients (average age of 59 years, ranging from 25 to 84) with destroyed lung caused by tuberculosis (six), aspergilloma (two), bronchiectasis (one), esophago-pleural fistula (one) or broncho-pleural fistula after lobectomy for bronchial carcinoma (one) and ongoing chronic infection with acute empyema (ten) (25-2500 days between first and definitive therapy) were treated. Pleural culture findings showed Aspergillus in four, Mycobacterium in two, Enterococcus in two, Candida in one and Staphylococcus in one, respectively. The mean number of interventions was 2.9 (2-4). The chest was definitively closed in all patients within 1 week. The mean hospitalization time was 19 days (9-31 days). In the follow-up (10-54 months), there was no recurrence of empyema. One patient (84 years) died at day 31, due to sepsis. CONCLUSIONS: Pneumonectomy combined with repeated surgical debridement and antimicrobial therapy enables the successful treatment of chronic pulmonary infection with empyema within a short time period.

Adult↗