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Biomedical subjects

M Stangl

Publications and source records attributed to M Stangl.

At least 19 recordsLinked to original sources

The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model.

BACKGROUND: The transplantation of live donor kidneys harvested laparoscopically is associated with a higher incidence of delayed graft function than the transplantation of grafts harvested via the open technique. The delay is believed to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy (LDN). The aim of this study was to evaluate whether renal function and blood perfusion can be enhanced by the periarterial application of papaverine during LDN. METHODS: Renal function and blood flow were studied in a porcine model that included a total of 24 pigs (20-30 kg). In 12 of the pigs, urine output and creatinine clearance were determined as measures of renal function. In the other 12 pigs, renal blood flow was determined using fluorescent-labeled microspheres. In each group, the pigs were randomized into two subgroups, one with and one without a perivascular injection of 50 mg papaverine. RESULTS: As compared to the controls, the animals receiving papaverine had a significantly higher urine output (3.1 +/- 1.6 vs 0.9 +/- 0.45 ml/h/kg; p = 0.02), superior creatinine clearance (2.22 +/- 0.5 vs 0.95 +/- 0.1 ml/min/kg; p = 0.038), and enhanced renal blood flow (4.9 +/- 2.2 vs 2.1 +/- 0.8 ml/min/g; p = 0.008). CONCLUSIONS: When applied to the tissue surrounding the renal artery, papaverine substantially improves renal function and blood flow during laparoscopic live kidney donation. Whether graft optimization during kidney procurement also translates into improved posttransplantation function remains to be established.

Animals↗

Contrast-enhanced MR angiography in patients after kidney transplantation.

The aim of this study was to investigate the value of a contrast-enhanced 3D MR angiography in detecting postoperative vascular complications after kidney transplantation in comparison with digital subtraction angiography (DSA). Forty-one patients who underwent a kidney transplantation were examined with MR angiography and DSA. Contrast-enhanced MR angiography was performed as a dynamic measurement with one precontrast and three postcontrast measurements. Maximum intensity projection reconstructions were performed for all postcontrast data sets after DSA. The results were evaluated by two independent observers who were unaware of the DSA results. Twenty-three hemodynamically significant arterial stenoses were identified with DSA in the iliac arteries ( n=7), the renal allograft arteries ( n=12), and in their first branches ( n=4). For a patient-based analysis the sensitivity and specificity, respectively, for observer 1 were 100 and 97%, and for observer 2, 100 and 93%. Respective data were 100 and 100% after a consensus evaluation by two observers. Complications involving the renal veins were detected in 2 cases and perfusion defects of the kidney parenchyma were detected in 4 cases. Contrast-enhanced MR angiography is a reliable method in identifying postoperative arterial stenoses after kidney transplantation. In addition, dynamic MR angiography can be helpful in detecting venous complications and perfusion defects in kidney allografts.

Adult↗

[Living donors in kidney transplantation. Renaissance by non-related donors?].

Renal Transplantation is hampered worldwide by the continuing lack of cadaveric organs. The discrepancy between the number of patients on the waiting list and the number of organs available is further compounded by the still unresolved problem of chronic transplant failure. Against this background, the arguments for increasing acceptance of the use of kidneys from living donors, both related and unrelated, are discussed. Initial reports on appreciably improved transplant survival rates of organs from unrelated living donors (85% survival after 3 years [19]) have since been confirmed by more recent studies. Our own results, in part obtained during a prospective study involving 103 patients (53 related, 50 unrelated) done between October 1994 and April 1999, with strict psychological care/evaluation prior to and after transplantation, revealed a four-year transplant survival rate of 98% in both groups. So far, the higher rejection rate of 34% in unrelated, vs. 13.2% in related, donors has not led to any earlier chronic dysfunction of the transplant. The expanded use of living kidney donors is not only ethically justifiable, but also improves the outcome.

Ethics, Medical↗

Chronic persistent knee pain after repeated diagnostic arthroscopy: osteoid osteoma, a primarily overlooked diagnosis in a young woman.

We report a case of osteoid osteoma of the distal femur in an adolescent female patient that was primarily overlooked and led to repeated diagnostic arthroscopy of the knee. A thorough history and physical examination of the joint as well as adequate roentgenographic studies could have spared this patient two unnecessary arthroscopies and indicated the correct therapy.

Adolescent↗

Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors.

Recombinant adeno-associated virus type 2 (rAAV) is a promising vector for in vivo gene therapy. Transduction by rAAV requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. Because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with rAAV transduction. Therefore, we examined the influence of different anticoagulants on rAAV transduction in vitro. rAAV transduction was inhibited by 40.5 +/- 7.9% at heparin concentrations of 0.1 U/ml, and by 81.7 +/- 3.6% at 1.0 U/ml. The low molecular weight (LMW) heparin tinzaparin inhibited rAAV transduction by 20.2 +/- 3.8% at 0.1 U/ml and 37.1 +/- 1.8% at 1.0 U/ml. The inhibitory effect was significantly weaker compared with heparin at 1.0 U/ml, (P < 0.01). The LMW heparinoid danaparoid inhibited rAAV transduction by 8.8 +/- 3.5% at 0.1 U/ml (P < 0.01 compared with heparin). In contrast, recombinant hirudin did not interfere at all with rAAV transduction. In summary, the results demonstrate that inhibition of rAAV transduction by heparin occurs rapidly and at therapeutically used concentrations. LMW heparinoids and above all recombinant hirudin might be alternatives for heparin when vascular gene transfer with rAAV requires transient anticoagulation.

Anticoagulants↗

Repeated endoscopic ovum pick-up in sheep.

Endoscopy is an effective and minimally invasive technique which offers the possibility of repeated ovum pick-up (OPU). In this study 4 different treatment programs (Groups A, B, C and D) for repeated endoscopic OPU in sheep were investigated. The number of follicles and oocytes, quality of cumulus-oocyte-complexes (COCs), and detectable effects on fertility of the donor ewes were compared. Each group consisted of 5 East Friesian Milksheep. In Group A, follicles were punctured twice a week, in Group B once a week, and in Group C once a week followed by administration of 1500 IU PMSG 48 h prior to OPU. In Group D follicles were punctured and the sheep stimulated with 1500 IU PMSG 48 h prior to OPU once every 2 weeks. The PMSG-stimulated sheep received anti-PMSG immediately after OPU. Over a period of 10 weeks 216 OPU-sessions were performed. A total of 1978 follicles was punctured, and 1098 oocytes were recovered, for a collection rate of 55.5%. In the Groups A, B, C and D an average of 6.8, 8.6, 12.2 and 14.9 follicles per animal and session was aspirated, and an average of 3.8, 4.9, 7.0 and 7.6 COCs per animal per session was recovered, respectively. No significant differences between groups were observed in the collection rates (51.1 to 57.1%) or in the quality of the COCs, and 65 to 70% of the COCs were suitable for in vitro production of ovine embryos. Seven sheep developed small adhesions between the ovary and infundibulum. After the study 15 ewes became pregnant following natural mating with the same fertile ram (5 from Group A, 1 from Group B, 4 from Group C and 5 from Group D). In conclusion, OPU once a week in PMSG/anti-PMSG treated ewes was found to be the most effective treatment program for oocyte collection.

Animals↗

Impact of immunoadsorption on xenogeneic extracorporeal pig liver perfusion: assessment of organ function during autologous reperfusion.

The shortage of liver grafts has resulted in an intensive search for alternative strategies of liver support in acute liver failure. Extracorporeal perfusion of pig livers (ECLP) is not a new concept, but recent improvements in cardiopulmonary bypass technology and new knowledge about xenogeneic immunologic mechanisms have made it a potential therapeutic modality. In previous suboptimal experimental and clinical models, no statements about the beneficial effect of long-lasting periods of ECLP were made. The aim of this study was to evaluate the capacity of pig liver for metabolic regeneration after xenogeneic ECLP under largely physiologic conditions. To delay hyperacute rejection (HAR), we utilized immunoadsorption (IA) of naturally preformed xenogeneic antibodies (XNAbs). This led to a stable xenogeneic ECLP for 45 min. However, IA was not able to prevent completely organ damage or loss of function resulting from insufficient autologous reperfusion. The inability to regenerate during autologous reperfusion provides a new measure of the function of a xenogeneic perfused pig liver. In addition, our results implicate that patients with fulminant liver failure will benefit from short perfusions with several fresh organs rather than from long perfusion with a single pig liver.

Animals↗

Procalcitonin, a new indicator for non-viral infections in heart, lung or liver transplant patients.

PCT is a highly specific analyse which shows significant diagnostic validities when non-viral infections are compared with rejection episodes. PCT discriminates inflammatory events such as rejection or viral infections and non-viral infections including bacterial, fungal and protozoal infections. The half-life of PCT is 24 h indicating a clearly competent antibiotic treatment. PCT provides vital information early to clinicians and allows them to improve the management of bacterial/fungal infection in immunocompromised transplant patients. PCT thus facilitates and improves the outcome of survival rate and the quality of life in the postoperative period of patients with heart, lung or liver grafts.

Bacterial Infections↗

Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8.

In order to take advantage of the biorecognition between lectins and specific carbohydrates for targeted drug delivery, fluorescein-labelled lectins of different carbohydrate specificities were screened for binding to human colorectal carcinoma cell lines by flow cytometry and confocal microscopy. The lectin-binding rate increased as follows: Dolichos biflorus agglutinin, DBA<peanut agglutinin, PNA<Lens culinaris agglutinin, LCA<Solanum tuberosum lectin, STL<Ulex europaeus isoagglutinin I, UEA-I<wheat germ agglutinin, WGA (Caco-2); PNA<UEA-I<WGA (HT-29); DBA<UEA-I<WGA (HCT-8), thus reflecting the glycosylation pattern of the cells. Compared to the BSA-binding capacity of the cells, the extent of nonspecific binding was strongly dependent on the type of cell line and lectin under investigation being lower than 2% in the case of WGA, STL and UEA-I/Caco-2 and HT-29 cells. Whereas 50% of DBA was bound nonspecifically to Caco-2 cells, the interactions DBA/HCT-8 and PNA/HT-29 were due to nonspecific binding. By competitive inhibition of lectin-adhesion to the cells upon addition of the complementary carbohydrate, specificity of lectin-binding was confirmed except for the interaction of DBA/HCT-8 and PNA/HT-29. Following on from this work, we consider WGA-, STL- and UEA-I-mediated drug delivery to be a promising approach for peroral bioadhesive formulations adhering to absorptive enterocytes.

Caco-2 Cells↗

Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression: first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients.

BACKGROUND: The currently used macrolide immunosuppressants, i.e., cyclosporine and tacrolimus, exert considerable nephrotoxicity. We aimed to avoid the nephrotoxic effects by applying a cyclosporine-free regimen for the induction as well as for the maintenance treatment of renal allograft recipients using mycophenolate mofetil (MMF) as the primary immunosuppressant. METHODS: Thirteen patients were converted from cyclosporine (CsA) to MMF monotherapy. For 4 weeks, MMF (2 g/day) was added to the CsA treatment, before CsA was tapered by weekly steps of 25 mg/day and without "safeguard treatment" with additional immunosuppressants. In a second approach, 12 patients older than 50 years, and receiving a renal graft from a donor older than 50 years, were treated primarily with MMF combined with steroids and an induction therapy using antithymocyte globulin, and without the addition of CsA. RESULTS: Thirteen long-term renal transplant patients could be converted from CsA to MMF monotherapy. Conversion resulted in an immediate and long-lasting improvement of their median creatinine values by 20%. No serious adverse events occurred. In the second cohort of 12 patients, MMF was used as the primary immunosuppressant. All patients are alive and no grafts were lost after 4 months (n= 12) and after 6 months (n=7). The median creatinine values achieved after 4 and 6 months were 1.16+/-0.25 and 1.30+/-0.21 mg/dl, respectively. One patient was converted to CsA because of a reversible rejection episode (8.3%), and another patient was converted because of cytomegalovirus disease. Major complications consisted of wound-healing disturbances (16.6%) and cytomegalovirus infections (41.6%). CONCLUSION: MMF monotherapy can be safely applied as long-term maintenance immunosuppression with improvement of renal function. Steroids are not required as an adjunct to MMF. MMF monotherapy, in the absence of drug-related nephrotoxicity, is particularly beneficial for grafts derived from marginal donors, such as donors of advanced age.

Acute Disease↗

Impact of immunoadsorption on complement activation, immunopathology, and hepatic perfusion during xenogeneic pig liver perfusion.

BACKGROUND: The impact of antibody adsorption by immunoapheresis on liver damage, complement activation, and hepatic perfusion was evaluated against the background of an application in extracorporeal pig liver perfusion for hepatic coma. METHODS: Eighteen pig livers were ex vivo perfused close to physiological conditions with fresh human blood for 4 hr. The influence of the perfusion circuit was investigated by perfusions of the circuit in the absence of livers (group 1 [G1]; n=5). Livers were xenoperfused without modifications in group 2 (G2; n=6). In group 3 (G3; n=6), pure Sepharose columns were used prior to liver perfusion. Immunoapheresis with Ig-Therasorb 100 columns was used in group 4 (G4; n=6). RESULTS: IgG was reduced by 95%, IgM by 72%, and IgA by 82% in G4, but only by about 30% in G3 (P<0.05). C4d, Bb fragment, and C3a levels were significantly lower in G4 than in G3 and G2 (P<0.05) after 180 min. Immunoadsorption diminished antibody and complement deposition as well as hepatocellular damage in G4. Portal angiographies demonstrated improved hepatic perfusion in G4. CONCLUSION: Immunoapheresis reduced organ damage as well as complement activation and improved hepatic perfusion during xenogeneic pig liver perfusion.

Acute Disease↗

Aggressive treatment of the first acute rejection episode using first-line anti-lymphocytic preparation reduces further acute rejection episodes after human kidney transplantation.

The detrimental effect of acute rejection episodes on long-term outcome of renal allografts in cyclosporin-treated patients is well established, although has not been seen by all investigators. To analyse the possibility that aggressive treatment of the first episode may ameliorate this detrimental effect, we performed an open label, randomised prospective trial in cyclosporin-based, immunosuppressed recipients of postmortem renal allografts in order to compare two different treatment protocols during primary acute rejection episodes: (1) group 1 of 25 patients received 3 x 250 mg methylprednisolone (MP) i.v.; (2) group 2 of 25 patients received 7 x anti-thymocyte globulin (ATG)-Fresenius i.v. (4 mg/kg body weight). During a period of 4 years, the following clinical observations were made: (1) The incidence of an acute re-rejection episode was significantly reduced in the ATG-treated study group (16%) compared to the MP-treated study group (72%); (2) The severity of the first acute rejection episode (intensity of renal dysfunction measured in terms of 10-day creatinine area under curve) showed no significant difference between the groups (37 mg x 10-d/dl to 58 mg x 10-d/dl); and (3) The half-lives of allografts in both groups have not shown any significant differences so far. In conclusion, aggressive treatment of the first rejection episode of renal allografts with the use of ATG reduced the incidence of re-rejection episodes which, however, are not reflected so far by improvement of the 4-year survival rate of these allografts. Since it could be observed that re-rejection is an even worse predictor for chronic transplant failure, a better long-term outcome of renal allografts in ATG-treated patients may be expected during a longer observation period. The incidence of a third episode was also reduced in the ATG-treated group (0%) compared to the MP-treated group (12%).

Adult↗