Validation of in silico prediction by in vitro immunoserological results of fine epitope mapping on citrate synthase specific autoantibodies.

In silico antibody-antigen binding predictions are generally employed in research to rationalize epitope development. These techniques are widely spread despite their technical limitations. To validate the results of these bioinformatic calculations evidence based comparative in vitro studies are necessary. We have used a well-conserved mitochondrial inner membrane antigen-citrate synthase to develop a model for comparative analysis of the predicted and the immunoserologically verified epitopes of circulating autoantibodies. Epitopes were predicted using accepted tools: the GCG Wisconsin package and TEPITOPE 2000. An overlapping multipin ELISA assay--covering 49% of the citrate synthase molecule--was developed to map autoantibody epitopes of individuals (healthy, systemic autoimmune, and heart transplanted) in different immunopathological conditions. From the 40 synthesized decapeptides 34 were predicted in silico and 27 were validated in vitro. Thirty-two percent of epitopes were recognized by majority of sera 47% by at least one sera. False positive predictions were 21%. There was major difference in the recognized epitope pattern under different immunopathological conditions. Our results suggest that special databases are needed for training and weighing prediction methods by clinically well-characterized samples, due to the differences in the immune response under different health status. The development of these special algorithms needs a new approach. A high number of samples under these special immunological conditions are to be mapped and then used for the "fine tuning" of different prediction algorithms.

[The state of heart transplantation in Hungary]. / A szívátültetés helyzete Magyarországon.

The first heart transplantation was performed in 1992 in Hungary. In the last nearly ten years 42 patients have got new heart. Among them 16 died. Authors discuss the changes of the surgical techniques and the postoperative treatment during this period, and what results were obtained with these new methods. They deal with problems, why so small number of the transplantations were performed. The causes of the death of the 16 patients were discussed.

[Surgical considerations in type-B aortic dissection]. / Sebészi megfontolások B típusú aorta disszekció esetében.

Inspite of remarkable progress in both diagnostic and therapeutic development in treating aortic dissections this continues to be one of the most severe vascular catastrophies complicated by high mortality. While aortic dissections Type A are to treat surgically in our days, in majority of patients with Type B dissections hypotensive treatment is the method of choice providing better chance for survival preventing effectively aneurysm formation and rupture at the site of intimal tear. However in certain cases Type B dissection produces either isthmic aneurysm formation, or with distal progression may afflict long segmental thoracic, thoracoabdominal or abdominal deterioration of the aorta and its side branches. The spinal, visceral, renal and lower limb ischemia threatens viability of these organs and hypotensive medication may enhance risk. Prompt evaluation and selection of these cases with proper surgical reconstruction help us to reduce mortality. At our department we have performed 33 thoracoabdominal endoaortectomies with meticulous reconstruction of renal and visceral orifices. The mortality rate in this subgroup of patients was 6%, meanwhile almost 70% in those, treated medically but had the severe distal branch involvement. Based on our experiences in selected patients with Type B aortic dissections we recommend this procedure in order to achieve improvement of results.

[New method for the intraoperative biochemical monitoring of cerebrospinal fluid in surgery of thoracoabdominal aortic aneurysms]. / Uj módszer a cerebrospinalis fluidum (CSF) intraoperatív biokémiai monitorozásában thoracoabdominalis aortaaneurysma-mútétek során.

Paraplegia remains to be one of the most dangerous complications following thoracoabdominal aortic surgery with an incidence of 0.5 to 40%. Therefore, intraoperative monitoring of spinal cord function is very important when choosing the appropriate surgical technique. Early detection of spinal cord injury continues to be a crucial problem, moreover, the currently applied electrophysiological methods appear to be inaccurate. The aim of the study was to detect prospective spinal cord injury intraoperatively by monitoring the biochemical parameters of the cerebrospinal fluid (CSF). The authors studied the reversible aerobic/anaerobic metabolic changes by monitoring CSF lactate levels, moreover S-100 protein and neuron-specific enolase (NSE) concentrations--specific for neuroglia and neuronal injury, respectively. One of the important methods to prevent paraplegia is the intraoperative CSF drainage, which may improve spinal cord perfusion. Between 1996-1998 51 patients underwent reconstructive thoracic or thoracoabdominal aortic aneurysm operation. The continuously drained CSF was collected in 10 ml fractions during the preparation, whereas during aortic cross-clamping and de-clamping 10 minute fractions were used. All CSF samples were immediately analysed intraoperatively for pH, pCO2, HCO3, potassium and lactate levels, S-100 protein and NSE were analysed by immunoluminescence. CSF lactate levels increased slightly during aortic clamping and a moderate, but non-significant increase was found in the hyperemic phase (reperfusion) in patients without spinal cord ischemia. Spinal cord injury was detected in 7 cases. These patients exhibited a significant CSF-lactate increase (control vs aortic cross-clamping: 1.9 vs 5.3 mmol/l), moreover CSF-lactate remained elevated throughout the whole operation. Paraplegia did not occur, Tarlov 2 paraparesis developed in four cases and three patients displayed cerebral damage. Intraoperative CSF--especially CSF-lactate--monitoring may help the operating team to detect early anaerobic changes of the metabolism the spinal cord.

[Cardiovascular autonomic regulation following orthoptic heart transplantation]. / A cardiovascularis autonóm reguláció vizsgálata orthotopicus szívátültetést követóen.

Numerous recent observations have indicated autonomic reinnervation of transplanted human hearts. In order to assess autonomic regulation 5 patients were studied 1 to 5 years following cardiac transplantation. A series of tests were performed, including blood pressure and ECG recordings on rest, during 15/min patterned breathing, isometric handgrip exercise, and Valsalva manoeuvre. The time domain indices (SDRR, pNN50, rMSSD) and the frequency domain indices of heart rate variability were also studied. Among the five patients under study only one exhibited features compatible with both sympathetic and parasympathetic reinnervation. Traditional autonomic reflex tests and the analysis of time and frequency domain indices of HRV serve as simple tool in primary assessment of cardiac reinnervation.

[Anesthesia for heart transplantation]. / A szívátültetés anaesthesiája.

Heart transplantation, as a therapeutic possibility, has been available since 1992 in Hungary. The authors present the anaesthetic aspects and clinical experiences of this worldwide used therapeutic method. The specialties of the narcosis, the importance of the aseptic techniques, and the treatment of the denervated heart are emphasised.