PubMed Health⌕ Search

Biomedical subjects

P Mohacsi

Publications and source records attributed to P Mohacsi.

At least 19 recordsLinked to original sources
PubMed2006

Diastolic dysfunction in human cardiac allografts is related with reduced SERCA2a gene expression.

Previous studies demonstrated that impaired left ventricular (LV) relaxation in cardiac allografts limits exercise tolerance post-transplant despite preserved systolic ejection fraction (EF). This study tested in human cardiac allografts whether the isovolumic relaxation time (IVRT), which provides the basis for most of diastolic LV filling, relates with gene expression of regulatory proteins of calcium homeostasis or cardiac matrix proteins. Gene expression was studied in 31 heart transplant recipients (25 male, 6 female) 13-83 months post-transplant with LVEF >50%, LV end-diastolic pressure <20 mmHg, normal LV mass index and without allograft rejection or significant cardiac pathology. IVRT related with the other diastolic parameters e-wave velocity (r = -0.46; p = 0.01), e/a-wave ratio (r = -0.5; p < 0.01) but not with heart frequency (r = -0.16; p = 0.4). No relation of IVRT was observed for immunosuppression, mean rejection grade or other medication. IVRT was not related with gene expression of desmin, collagen I, phospholamban, the Na+-Ca2+ exchanger, the ryanodine receptor or interstitial fibrosis but correlated inversely with SERCA2a (r = -0.48; p = 0.02). Prolonged IVRT is associated with decreased SERCA2a expression in cardiac allografts without significant other pathology. Similar observations in non-transplanted patients with diastolic failure suggest that decreased SERCA2a expression is an important common pathomechanism.

Adult↗
PubMed2005

[Indication, management and problems of cardiac transplantation].

Cardiac transplantation (HTx) remains one of the most important options for the management of end stage heart failure which is treated with optimal medical therapy. Evolving surgical techniques (implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT)) and mechanical device-therapie (ventricular assist devices (VAD)) and medical therapies have yielded incremental improvements in outcomes. These alternatives to HTx, however, usually only postpone the occurrence of the final end stage situation. This explains why HTx remains the last option for a substantial number of especially younger severe heart failure patients with upcoming renal failure. It is very recommendable to refer such kind of patients to university-based and specialized advanced heart failure and cardiac transplant centers, in time. This allows the introduction of optimal medical therapy, the careful medical and psychological evaluation and preparation of the considered HTx, as well as the full information procedure which has to be delivered to HTx candidates. HTx candidates should be aware about outcome numbers, medication toxicities, complications of immunosuppression, as well as the ever-present threat of cardiac allograft vasculopathy, infections and neoplasias after HTx.

Donor Selection↗
PubMed2004

Solid organ transplantation across the ABO histo-blood group barrier: a case report.

The ABO blood group system until recently constituted an insuperable barrier for solid organ transplantation, but cases of heart transplantation in infants and kidney transplantation in adults have been reported, wherein ABO-incompatible grafts have been successful. In 1990, the molecular genetic basis of three major alleles at the ABO locus was elucidated; A and B glycosyltransferases are specified by a variety of functional alleles at this locus. The antibody response to ABH antigens, namely, naturally occurring anti-A/B IgM and IgG isotype agglutinins, are controlled preoperatively by recipient conditioning using plasma exchange, immunoadsorption, and immunosuppressive regimens. We report an O-type patient who accidentally received a B-type cardiac allograft in 1997 who survived for 5 years, dying for an unrelated reason. Over a period of 45 months semiquantitatively we monitored the expression of ABO-type antigens in graft heart vessels using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies. We observed a progressive change in the antigenic profile of graft endothelial cells from B- to O-type, which was first detected at 1 year posttransplant and most prominent 3 years later, the end of the observation period. No temporal relationship was observed between the transition from B to O expression, the anti-B antibody levels or the immunosuppressive regimen.

ABO Blood-Group System↗
PubMed2002

New concepts in organ preservation.

Organ preservation between donor and recipient is an important link in a chain that ultimately should lead to long term survival of the recipient thanks to a well-preserved, functionally intact organ. The period of organ ischaemia outside the body is subject to a number of biochemical stress factors which become known in more detail as knowledge on biochemical and immunological mechanisms improves. Efficacy of preservation fluids hence reduction of ischaemia injury may become enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme oxygenase modulators, endothelin-l-inhibitors, quenchers of free radicals and anti-apoptotic agents. Many of these compounds, albeit of great theoretical interest, have not (yet?) made their way into clinical practice. This contribution is a survey of some promising agents, concentration and physicochemical interactions of which are analysed in some detail.

Acetylcysteine↗
PubMed2001

Successful management of a B-type cardiac allograft into an O-type man with 3(1/2)-year clinical follow-up.

BACKGROUND: In May 1997, a 19-year-old male patient of histo-blood group type O suffering from congenital end-stage heart failure accidentally received a cardiac allograft of type B and is still alive in fair condition. METHODS: In addition to conventional immunosuppressive therapy, plasma exchange (PEX), extracorporeal immunoabsorption (EIA), intravenous immunoglobulins (IVIG), and C1 inhibitor were used. RESULTS: Such treatment successfully reduced both IgM and IgG anti-B levels and complement hyperactivity and allowed to reach the state of accommodation without obvious signs of rejection. The patient has been surviving for 42 months; retransplantation with an O-type heart remained unnecessary. CONCLUSION: Humoral rejection has been avoided in this patient, with PEX, EIA, IVIG, and C1 inhibitor substantially contributing to this success. With future availability of such combined therapies, preferably before transplantation, vascular rejection events caused by preformed antibodies and complement (ABO mismatch or anti-HLA) could be prevented or treated.

ABO Blood-Group System↗
PubMed2001

Effect of carvedilol on survival in severe chronic heart failure.

BACKGROUND: Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure. METHODS: We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded. RESULTS: There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.00013, unadjusted; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol (95 percent confidence interval, 13 to 33 percent; P<0.001). The favorable effects on both end points were seen consistently in all the subgroups we examined, including patients with a history of recent or recurrent cardiac decompensation. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02). CONCLUSIONS: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.

Adrenergic beta-Antagonists↗
PubMed2001

AB0/O terminology.

Explore the source record for details and available documents.

ABO Blood-Group System↗
PubMed2001

Doppler tissue imaging for assessing left ventricular diastolic dysfunction in heart transplant rejection.

OBJECTIVE: To test the hypothesis that diastolic mitral annular motion velocity, as determined by Doppler tissue imaging and left ventricular diastolic flow propagation velocity, is related to the histological degree of heart transplant rejection according to the International Society of Heart and Lung Transplantation (ISHLT). METHODS: In 41 heart transplant recipients undergoing 151 myocardial biopsies, the following Doppler echocardiographic measurements were performed within one hour of biopsy: transmitral and pulmonary vein flow indices; mitral annular motion velocity indices; left ventricular diastolic flow propagation velocity. RESULTS: Late diastolic mitral annular motion velocity (A(DTI)) and mitral annular systolic contraction velocity (SC(DTI)) were higher in patients with ISHLT < IIIA than in those with ISHLT >/= IIIA (A(DTI), 8.8 cm/s v 7.7 cm/s (p = 0.03); SC(DTI), 19.3 cm/s v 9.3 cm/s (p < 0.05)). Sensitivity and specificity of A(DTI) < 8.7 cm/s (the best cut off value) in predicting significant heart transplant rejection were 82% and 53%, respectively. Early diastolic mitral annular motion velocity (E(DTI)) and flow propagation velocity were not related to the histological degree of heart transplant rejection. CONCLUSIONS: Doppler tissue imaging of the mitral annulus is useful in diagnosing heart transplant rejection because a high late diastolic mitral annular motion velocity can reliably exclude severe rejection. However, a reduced late diastolic mitral annular motion velocity cannot predict severe rejection reliably because it is not specific enough.

Blood Flow Velocity↗
PubMed2000

[Long-term management after heart transplantation--an assessment of current status].

Due to an improvement of results after heart transplantation, there is a continuously growing number of long-term surviving patients. Aimed at a characterization of established diagnostic and therapeutic protocols, the Working Group of Thoracic Organ Transplantation within the German Society of Cardiology performed a survey among all German heart transplantation centers. Based on the experience of 1,500 patients, the clinical relevance as well as approaches for prevention and treatment of rejection, infection, cardiac allograft vasculopathy, malignancy, hypertension, renal insufficiency, and quality of life were assessed by a questionnaire. As a result, a time dependency of expected complications could clearly be shown. While early after HTX acute rejection and infection episodes were judged as clinically important, later on cardiac allograft vasculopathy, malignancy, and renal insufficiency predominate as relevant complications. This spectrum was reflected by a differentiated diagnostic protocol (early after HTX more frequent diagnostic procedures for rejection and infection, later intensified examinations to identify cardiac allograft vascular disease and malignancy) as well as by different intensities of immunosuppression and concomittant medication. Regarding further improvement of survival rates and quality of life, future clinical and scientific activities should be focused on the prevention of late complications after heart transplantation.

Aftercare↗
PubMed2000

Anti-Galalpha1-3Gal IgM/IgG antibody levels in infants: do they have a clinical relevance in pediatric xenotransplantation?

BACKGROUND: Anti-Galalpha1-3Gal antibodies (anti-Gal) compose a major obstacle to xenotransplantation. As it is known, there is an immunological window during which infants are thought to have no xenoreactive antibodies. Therefore, we were interested in investigating the occurrence of these antibodies in newborns and infants up to 2 years of age. METHODS: IgM/IgG isotypes of anti-Gal from 74 serum samples of 16 mothers, with the respective cord bloods, and 42 infants of 4 age groups (Group I: day 1-6 months, II: 7-12 months, III: 13-18 months, and IV: 19-24 months) were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA). A synthetic Galalpha1-3Gal disaccharide-polyacrylamide glycoconjugate was used for coating and monoclonal antibodies were used for the detection of heavy chain isotypes. Antibody concentrations were referred to an internal standard and expressed as arbitrary ELISA units (U). Hemagglutination titers against rabbit erythrocytes (E(R)) were determined in addition. RESULTS: Maternal serum samples showed a wide interindividual variability (IgM: 87 +/- 33 U (mean +/- SD), IgG 59 +/- 39 U) whereas in cord blood no detectable IgM was seen in presence of IgG (52 +/- 34 U). From Group I to IV there was a gradual increase of anti-Gal IgM towards an average of 70% of the adult levels whereas IgG fell to an average of approximately 20% of cord blood levels. Hemagglutination titers followed an increasing tendency with cord blood starting from 1:16 and reaching 1:256 in Group IV. CONCLUSION: The humoral immune response to the Galalpha1-3Gal epitope (alpha-Gal) in infancy follows the generally known development of specific antibodies in humans.

Antibodies, Anti-Idiotypic↗
PubMed2000

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure.

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.

Adolescent↗
PubMed2000

Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists.

BACKGROUND: Erythropoietin (Epo), a growth factor produced by the kidney, is important in heart failure patients to promote oxygen delivery to tissues. Seventy-two chronic heart failure (CHF) patients at our outpatient clinic were subjected to morning serum Epo-level measurements and classified according to NYHA criteria. RESULTS: Forty-eight patients of classes III and IV had a significantly elevated serum Epo-level of 42.9+/-40.3 mIU/ml (mean+/-1 S.D.) when compared to the mean level of 24 patients of classes I and II who had a normal range mean value of 13.4+/-6.2 mIU/ml (P<0.05). Patients on angiotensin-converting enzyme (ACE) inhibitors showed a trend towards lower serum Epo-levels compared to patients treated with angiotensin-II type-1 receptor antagonists (AT(1) antagonists) (levels: 33.3+/-35.6 mIU/ml and 43.6+/-38.1 mIU/ml). This trend did not, however, reach statistical significance (P=0.36). CONCLUSION: We suggest that a desirable Epo increase in class III and IV CHF patients could be achieved by either recombinant human Epo administration or, possibly, by appropriate selection of the concomitant medical therapy. A large prospective study shall investigate the possible advantage of AT(1) antagonists over ACE-inhibitors with regard to Epo effect.

Angiotensin Receptor Antagonists↗
PubMed1998

[Conventional heart surgery with the fast-track-method: experiences from a pilot study].

Early release after cardiac surgery can be promoted by implementation of a standard protocol for accelerated perioperative and early postoperative care, with optimal education and support of the patient playing a key role. We report on our preliminary experience with 100 selected patients who underwent a "fast track" protocol following coronary artery bypass (n = 61), valve replacement or reconstruction (n = 34) or closure of an atrial septal defect (n = 5) between 1996 and 1998. Surgery was performed through a midline sternotomy using normothermic or mild hypothermic cardiopulmonary bypass. Patients undergoing cardiac surgery with less invasive techniques were excluded from this study. The following criteria had to be fulfilled for early hospital discharge: sinus rhythm, temperature below 37.5 degrees C, stable haematocrit around 0.30, uncomplicated wound healing and complete mobilisation including stair exercises. Mean duration of the operation was 137 +/- 24 minutes and mean intubation time was 4.5 +/- 3 hours. Mean duration of hospitalisation from the day of the operation was 4.9 +/- 2.1 days. There was no early or late mortality in this group of patients and only 2 patients had to be re-admitted on postoperative day 10 and 14 because of atrial fibrillation in one and a wound healing problem in the other. Accelerated recovery and early hospital discharge is highly attractive in selected patients; in helps to promote early cardiac rehabilitation and the costs of the procedure can be substantially reduced. According to our experience and the most recent literature, this approach does not expose patients to higher mortality or morbidity. In addition, fast-tracked patients have shown a higher level of satisfaction. Under optimal cooperation between surgery, anaesthesiology and intensive care unit, the fast-track protocol can be applied in approximately 30% of overall adult cardiac surgery patients.

Adult↗
PubMed1998

[Ethical aspects of heart transplantation].

Since the very beginning of organ transplantation, ethical considerations have been regularly discussed. However, all important religions support transplantation. On the donor side there is continuous argument on the definition of brain death. The legal approach in determining whether explantation of organs is allowed or not is country-specific. In Switzerland, moreover, rules still differ from one canton to another and a new transplantation law is at present under consideration. To avoid further shortage of organs, various models have been suggested (such as rewarded giftings) but rejected on ethical grounds. On the recipients' side the main discussion centres on who should be the first to receive an offered organ. Specific questions on xenotransplansplantation and transplantation in newborns are briefly addressed.

Brain Death↗