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Biomedical subjects

F Iberer

Publications and source records attributed to F Iberer.

At least 19 recordsLinked to original sources
PubMed2006

Cryopreservation of insulin-producing cells microencapsulated in sodium cellulose sulfate.

INTRODUCTION: Diabetes mellitus may be treated with pancreatic islet cell transplantation. The use of xenogenic islet cells may overcome the shortage of human donor organs. Microencapsulation seems to be a promising method for immunoprotection. Since isolation, purification, encapsulation, and transplantation of islet cells are labor-intensive, cryopreservation has emerged as an attractive system for islet banking. In this study sodium cellulose sulfate (NaCS), a novel method for microencapsulation of islet cells, was tested for its capability to protect cells during cryopreservation. METHODS: HIT-T15 cells were microencapsulated in NaCS. Cells were frozen and thawed using three different media containing varying amounts of dimethylsulfoxide (DMSO) and glycerol. Cell viability and cell growth were monitored using 3-(-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide before freezing and 1 week after thawing. RESULTS: NaCS did not show any negative impact on the growth rates of encapsulated HIT-T15 cells compared with nonencapsulated controls. Nonencapsulated cells were adequately cryopreserved by both DMSO- and glycerol-containing freezing media. DMSO was not suitable for cryopreservation of encapsulated HIT-T15 cells, whereas glycerol seemed to produce no considerable cell loss during freezing and thawing. DISCUSSION: Islet banking of cells encapsulated in NaCS was feasible. Microencapsulation did not harm islet cell recovery. As NaCS is less immunogenic and more biocompatible than other materials used for microencapsulation, it may be a promising method for immunoisolation of islet cells to replace the endocrine pancreas in a physiological way.

Animals↗
PubMed2006

Morphological and functional characterization of a pancreatic beta-cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride).

BACKGROUND: Late diabetic complications cannot be prevented totally by current antidiabetic strategies. Therefore, new therapeutic concepts of insulin replacement such as pancreas transplantation are evolving. Due to the shortage of human donor organs, transplantation of microencapsulated xenogeneic pancreatic islet cells has attracted considerable attention. Sodium cellulose sulfate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC) is a material with favorable biogenic properties that has been used for microencapsulation of various cell types. However, there are no data on the suitability of NaCS/PDADMAC for microencapsulation of pancreatic beta-cells. MATERIAL AND METHODS: Cell growth and viability of NaCS/PDADMAC-microencapsulated HIT-T15 cells, an immortalized hamster pancreatic beta-cell line, were assessed using a dimethylthiazol-diphenyltetrazoliumbromide (MTT)-based cell growth determination kit and apoptosis was detected by antibodies against activated caspase 3. Glucose-dependent insulin secretion was assessed with ELISA and the uptake of glucose was measured using fluorescence-labeled glucose. RESULTS: Statistical analysis revealed no differences in glucose-dependent cell proliferation, insulin secretion and glucose uptake between non-microencapsulated and microencapsulated HIT-T15 cells. Stimulation of HIT-T15 cells with glucose (100 mg/ml) resulted in a biphasic insulin secretion response. CONCLUSION: Microencapsulation of HIT-T15 cells in NaCS/PDADMAC does not influence cell proliferation, insulin secretion and glucose uptake. Our results indicate that NaCS/PDADMAC is well suited for microencapsulation of pancreatic beta-cells.

Animals↗
PubMed2005

Nonnephrotoxic immunosuppression in patients after liver transplantation.

INTRODUCTION: Calcineurin inhibitor (CI)-associated renal impairment and renal failure after liver transplantation has been recognized since the early days of its use. Various strategies have been used to prevent or slow down the progression of renal dysfunction in liver transplant recipients, but did not succeed. In this report, we describe the course of renal function of 58 stable liver transplant recipients and compared 2 groups with different immunosuppressive protocols. METHODS: In the study group, 22 patients at various intervals from liver transplantation were included. The immunosuppressive therapy consisted of Sirolimus (SRL). Additional all patients except 2 received Mycophenolate Mofetil (MMF) and 14 of them also received Tacrolimus. Patients of the control group (36 patients) had an immunosuppressive therapy with calcineurin inhibitors. Patients were monitored for creatinine monthly and creatinine clearance (CCr) every sixth month. Risk factors for renal dysfunction were evaluated. RESULTS: After introduction of SRL in patients with renal impairment and after a mean follow-up time of 12 (2-26) months, there was a decrease of 28.3% in mean creatinine and of 41.8% in mean urea. We observed an improvement of renal function in all patients initially after introduction of SRL. In the control group, in comparison to preoperative levels, there was an increase of 27.5% in mean creatinine and of 13.3% in mean urea after a mean follow-up time of 3.6 years with CI therapy. CONCLUSION: The results of our retrospective study showed that with SRL renal impairment could be stopped and renal function could be improved. We suggest administering immunosuppressive therapy with SRL in combination with low dose Tacrolimus and/or MMF for patients with renal impairment.

Adult↗
PubMed2005

Center experience in liver transplantation (LTX): management of dermal side effects caused by sirolimus.

INTRODUCTION: Sirolimus improves post transplant maintenance therapy in LTX. Dermal side effects causing pain and discomfort can limit patients' compliance. The package insert mentions such skin disorders as acne and rash. One case of sirolimus-induced leucocytoclastic vasculitis is reported in the literature. METHODS: From July 1998 to October 2003, Sirolimus was implemented in the immunosuppressive protocol in 23 out of 60 liver recipients. Sirolimus target levels are between 3 and <10 ng/dl. Combination with a calcineurinblocker and/or MMF (mycophenolate mofetil) depending on liver function and creatinine is standard. Weekly patient monitoring in the first month after discharge included physical examination, blood samples and immunosuppresant trough levels. Biopsies were taken from untypical efflorescences. RESULTS: Three patients with non-specific effloresces were reported: one with leucocytoclastic vasculitis and one with exfoliate forearm dermatitis required change of medication while one perivascular lymphocytic eosinophilic dermatitis subsided after dose reduction. In three cases of mouth ulcer, trough levels exceeded 10 ng/dl and in six patients acne diminished after dose reduction. Eighteen out of 23 patients are still receiving sirolimus. Reasons for removal from the study were incompliance and incompatibility. Two patients died. DISCUSSION: Immunosuppressants inevitably produce side effects in TX recipients. The positive management of troublesome side effects contributes importantly to compliance and patient survival.

Acne Vulgaris↗
PubMed2004

[Consensus-recommendations for sirolimus in liver transplantation].

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

Drug Therapy, Combination↗
PubMed2004

Dyslipidemia during sirolimus therapy in patients after liver transplantation.

INTRODUCTION: Sirolimus (SRL) is an immunosuppressive agent of potential benefit in clinical liver transplantation (LTX). One of the major side effects of SRL is hyperlipidemia, which is reported in up to 44% of patients. In this report, we describe the lipid profiles of 20 stable liver transplant recipients who received SRL for immunosuppression. METHODS: The study group received SRL in combination with tacrolimus and/or mycophenolate mofetil (MMF). The control group was administered calcineurin inhibitor (CI) and MMF. Fasting serum cholesterol level, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) were measured regularly. Furthermore, the total cholesterol/HDL ratio and the LDL/HDL ratio were evaluated. Diabetes and hypertension were monitored as well. RESULTS: In the SRL group, hypercholesterolemia was found in three patients (15%) and hypertriglyceridemia in two patients (10%). There was no marked difference from the control group, although a higher association of SRL with hyperlipidemia was described in the literature. Furthermore, HDL and LDL levels were similar in both groups, as well as total cholesterol/HDL ratio and LDL/HDL ratio. Diabetes and hypertension had a similar incidence in both the groups. Thus, there was no difference concerning the cardiovascular atherosclerosis risk between the immunosuppressive protocol with SRL or with CI. DISCUSSION: The results of our retrospective study demonstrated that the immunosuppressive regimen can potentially influence the incidence of hyperlipidemia in patients after LTX. SRL in combination with tacrolimus and/or MMF had no higher incidence of hyperlipidemia than CI and MMF. The combination of immunosuppressive therapy with low dose and low levels of each immunosuppressive agent could decrease the risk of atherosclerosis and its complications in long-term survivors after LTX.

Adult↗
PubMed2003

Occurance of apoptosis during ischemia in porcine pancreas islet cells.

PURPOSE: Pancreas islet transplantation is a potential treatment of diabetes mellitus and porcine organs provide an easily available source of cells. Unfortunately quality and quantity of isolated islets are still not satisfactory. Apoptosis occurs in freshly isolated islets and plays a significant role in early graft loss. We evaluated the influence of four storage solutions on porcine pancreas islets. METHOD: After warm ischemia of 15-20 minutes 12 organs were stored in 4 cold preservation solutions: Histidine-Tryptophan-Ketoglutarate solution (HTK), Hank's buffered saline solution (HBSS), University of Wisconsin (UW) solution and Ringer-Lactate (R). After cold ischemia for 100 minutes, organs were fixed in 3% formalin. Apoptotic cells were counted on hematocylin-eosin stainings. RESULTS: Most apoptotic cells were found in organs stored in R. Low numbers were found in the other groups. The difference between organs stored in R and organs stored in UW, HTK, or HBSS was highly significant. No significant difference could be found between UW, HTK and HBSS. CONCLUSION: Cold and warm ischemia of the pancreas seems to induce apoptosis in islet cells. Preservation solutions cause less apoptosis than electrolyte solution. No significant differences could be found among the preservation solutions.

Animals↗
PubMed2002

Correlation between changes in stroke volume and the paced intracardiac electrogram.

AIM: The aim of this study was to examine the relation between cardiac haemodynamics and parameters extracted from the intracardiac electrogram obtained during pacing, i.e. ventricular evoked response. METHODS AND RESULTS: In the course of routinely scheduled right heart catheterization, intracardiac electrograms and cardiac haemodynamics were monitored simultaneously in ten heart transplant patients (two females, aged 48 +/- 12 (18-59) years), using pacemaker telemetry and Swan-Ganz thermodilution techniques. Different haemodynamic states were induced by pacemaker programming (pacing rate changes) and table tilting (postural changes). Forty different haemodynamic states were assessed, with an average of three (2.4) haemodynamic variations in each patient. Linear regression analysis between relative stroke volume changes and relative changes in the R wave slew rate as extracted from the evoked responses revealed a strong, inverse, and highly significant correlation (r= - 0.93, P<0.0001) between those parameters. Similar results were obtained for pacing rate and postural variations alone, respectively. CONCLUSIONS: The strong correlation between changes in stroke volume and R slew rate indicates that paced intracardiac electrograms reflect changes in the size and geometry of the heart. Telemetrically recorded intracardiac electrograms may thus be used non-invasively to assess key aspects of cardiac haemodynamics.

Adolescent↗
PubMed2000

Non-invasive graft monitoring after heart transplantation: rationale to reduce the number of endomyocardial biopsies.

The endomyocardial biopsy is invasive, reduces quality of life and cannot be repeated daily. Initial studies on noninvasive cardiac graft monitoring have been presented recently. During the heart transplant procedure, we implanted wideband telemetric pacemakers and fractally coated, epimyocardial electrodes. On biopsy days and during each follow-up, intramyocardial electrogram sequences were obtained. The maximum T-slew rate from the ventricular evoked response (VER) was automatically calculated and compared to the biopsy results (n = 331, ISHLT grading). The VER T-slew rate was significantly lower during rejection grade 2 or higher. The negative predictive value to exclude rejection was 98%. Using a single threshold diagnosis model, 74% of the biopsies could have been avoided. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after heart transplantation.

Adolescent↗
PubMed2000

Non-invasive cardiac allograft monitoring: the graz experience.

Based on previous reports by our group, initial studies on non-invasive cardiac graft monitoring have been presented recently. In this study we define new parameters to monitor rejection and infection after heart transplantation (HTX) the ventricular evoked response (VER) T-slew rate parameter is defined as the maximum negative slope in the descending part of the repolarization phase of the VER. We calculated the VER duration parameter in milliseconds and defined it as the time between the pacemaker spike and the cross-over of the baseline, with the slope line used to calculate the VER T-slew rate. During the HTX procedure, we implant wide-band telemetric pacemakers and fractally coated, epimyocardial electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During each follow-up and on biopsy days, intramyocardial electrogram sequences were obtained and sent via the Internet to the central data-processing unit in Graz. We scored the infection status of the patients before data acquisition. The VER parameters were automatically calculated and send back within a few minutes. We prospectivly compared 1,613 follow-ups from 42 patients with biopsy (International Society of Heart and Lung Transplantation grading) and infection classification. The VER duration parameter did not change during rejection; however, we found an increase during clinically apparent infection. The VER T-slew rate parameter was lower during rejection grade 2 or higher, as well as during clinically apparent infection. The negative predictive value to rule out rejection was 99%. Our results indicate that rejection and infection cause different, reproducible effects on the electrical activity of the transplanted heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.

Action Potentials↗
PubMed1998

Mild chronic anemia following heart transplantation: a syndrome with prognostic relevance?

The clinical relevance of mild chronic anemia in patients after heart transplantation (HTX) has not yet been demonstrated. Forty-five outpatients who had undergone HTX 2-99 months prior to investigation and who had not received blood transfusions or erythropoietin (EPO) before data acquisition were observed over a period of 37 months. Anemia was found in 36 of the 45 patients and was normocytic, normochromic, and slightly anisocytotic (coefficient of variation = 16 +/- 2, normal 11.5-14.5). Anemic patients showed elevated EPO levels, whereas in nonanemic patients EPO levels were normal. Survival after HTX differed significantly in anemic and nonanemic patients (P < 0.02), with 100% survival in the nonanemic and 85% in the anemic group. Chronic anemia in patients after HTX shows a typical pattern. Even when mild, anemia in patients after HTX seems to be of prognostic value and thus might be an indicator of chronic disorders.

Adolescent↗