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Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tacrolimus is an important part of immunosuppressive therapy after solid organ transplantation. The therapeutic range of the drug from the calcineurin inhibitor group is narrow. Adjustment of the blood concentration can be very complicated but to be able to avoid the occurrence of side effects or ineffective immunosuppression it is inevitable. This article summarizes the properties of tacrolimus pharmacokinetics, pharmacogenetics and pharmacodynamics. We will focus on individual variations of cytochrome enzymes. In the following part, a new method for screening high risk patients will be introduced. We will present the publications of the determination of the concentration/dose (C/D) ratio. By determining the C/D ratio, researchers identify fast and slow metabolizing patient groups. Fast metabolizers require higher doses in general and the occurrence of complications is also more frequent in this group. Long-term results are lagging behind the slow metabolizing group. The long-term results of renal transplantation nowadays contribute to the postoperative period and the later years rather than the surgery itself. It includes the proper management of previous illnesses (e.g., hypertension, diabetes, endocrinological problems), detection of complications (e.g., infections, malignancies), and the precise regulation of immunosuppressive therapy. Orv Hetil. 2019; 160(30): 1178-1183.

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.

The incidence and number of species involved in the spectrum of sexually transmitted infections continue to increase. Laboratories have to be prepared for identification of unusual microbes. In our practice, a male patient had recurring urethritis and balanitis after having repeated unprotected insertive sexual intercourse with female piglets. He also had allergy to scents and some metals, otherwise he showed no general symptoms. Specimens were swabbed from the urethra, inflamed glans, rectum, mouth onto several culture media, subsequently isolates were tested for their morphology, biochemical activity. Kurthia gibsonii was isolated from urethra and glans. No concomitant infection with other microbes was detected, haemoculture was negative. Relying upon antibiotic sensitivity test, he was cured with 2 × 500 mg oral cefuroxime for 15 days, and topical gentamycin cream for 2 months. This is the first reported sexually transmitted, zoonotic infection without generalization by Kurthia spp. We report first the antibiogram of K. gibsonii. Slight differences in the antibiotic sensitivity suggest independent infection and sensitivity of urethral and mucous membrane tissues to distinct K. gibsonii strains. Allergy of the patient might predispose to opportunistic infection. Such aspects ought to be tested in details in further cases.

Biofilm-forming Staphylococcus epidermidis strains are common cause of the periprosthetic infection. The treatment of the periprosthetic infection is very problematic, so the prevention of these infections by an antibiotic containing prothesis could be an option for prevention.The purpose of the present study was to examine the in vitro effects of drug delivery systems (DDSs), namely Wax 1 and Wax 2 with different vancomycin content: 0.5, 1, 2 and 4 mg. In order to control the antibacterial activity of DDSs killing curve study was performed and in order to determine the antibiotic release and the antibiotic peak concentration from the DDSs biological assay was carried out.The time kill curve studies showed, that both DDSs with all vancomycin concentration decreased significantly the bacterial counts, however, Wax 2 with 4 mg vancomycin significantly decreased the bacterial count than all the other groups.The vancomycin release was the best with the highest peak concentration from DDSs with 4 mg vancomycin contain; it was significantly better than in the other groups, however, no significant difference was observed between Wax 1 and Wax 2 in this respect.These findings suggest that Wax 2 with 4 mg vancomycin content could be a potential agent for clinical use.

Adenoviruses have increasingly been recognized as significant viral pathogens causing high morbidity and mortality especially among immunocompromised individuals such as transplant recipients and AIDS patients. Through the infection process, after the adenovirus fiber and penton are bonded to cell surface receptors through special amino acid moieties, secondary messengers activate protein kinases, pro-inflammatory cytokines and chemokines. Serotype and species specific antibodies also are induced. Recombinant human adenoviruses have been pivotal in the development of gene therapy strategies and have shown a great promise for the treatment of genetic disorders and malignancies. Recent studies have enlightened their harmful immunological effects dependent on fiber and hexon polypeptide structure and receptor binding. Pre-existing antibodies or those elicited by vectors neutralize input recombinant adenovirus particles rendering them ineffective. Mediators induce serious even lethal side effects and cytotoxic reactions which extinguish transgene expression. To overcome these difficulties new strategies are required in the application of recombinant adenoviruses to redirect vector entry from the natural receptors to alternative binding sites or using rare human or animal adenovirus fiber molecules to modify the native fiber structure by altering amino acid structure and creating chimeric fibers. This requires searching for, isolating and characterizing new serotypes, mutants or variants for new generation vectors. Human adenovirus 1 feline isolate (feline adenovirus) might fulfil these criteria.

In the decade prior to the turn of the millennium, great interest was raised, and rightly so, by the STD (syphilis and HIV/AIDS) epidemic that developed in the Eastern-Central European Region. Its coincidence with the far-reaching political and economic changes that took place at that time suggested a link between the two events.Hungary, where these infections had had low incidence before the period investigated, also experienced an increase in STD incidence. The trend in syphilis infection during the 20 years between 1985-2004, that preceded the turn of the millennium and when finally Hungary joined the European Union, have been analyzed. Due to the nature of venereological epidemiological surveillance in Hungary, syphilis prevalence data are appropriate for further analysis from socio-demographic aspects. Behavioural changes underlying the specific features of the epidemics in Hungary had developed several years earlier and cannot be linked to the political and economic changes that started in the early 90s. The only exception is the phenomenon of growing migration that appeared simultaneously with the political changes and had a decisive impact on the spread and level of infection in some areas in the country. As shown by our data, trends seen in specific demographic groups (females, rural population) preceded the suddenly occurring political changes by about 15 years.

The life expectancy of patients with type 1 diabetes mellitus is inferior to that of patients with some malignancies. Simultaneous pancreas-kidney transplantation is the procedure providing the best survival results among all options of renal replacement therapy. The operative techniques and immunosuppresion have been standardized in the last decade. Although the number of transplantable organs falls behind the need, simultaneous pancreas-kidney transplantation is the method of choice for the eligible patients. The results of the two Hungarian simultaneous pancreas-kidney transplantation programs are in accordance with data published in the international literature.

The first Hungarian kidney transplantation was performed by András Németh in Szeged in 1962, approximately 50 years ago. A preliminary agreement with Eurotransplant was signed in 2011, and special patient groups gained benefit from this cooperation in 2012, wnich lead to a full membership to Eurotransplant. This event inspired the authors to review the history of Hungarian kidney transplantation of the past 50 years, from the first operation to recent via the specific cornerstones of the transplant program. The donor of the first Hungarian kidney transplantation was the brother of the recipient. The operation itself was technically successful, but the lack of immunosuppression caused graft rejection, and the patient died after 79 days. His brother, the donor, is still healthy, after 50 years, and he encourages everybody to donate organs. Organized kidney transplant program started more than 10 years later, such as 1973, in Budapest. The program was supported by the Ministry of Health. New centers joined the program later, Szeged in 1979, Debrecen in 1991 and Pécs in 1993. These four transplant centers work currently in Hungary, and 6611 kidney transplantation has been performed up to the end of year 2012.

In this study antibiotic combinations for multidrug-resistant Klebsiella pneumoniae strains were investigated. The study included a colistin-susceptible and a colistin-resistant KPC-2 producing K. pneumoniae ST258 strains isolated in 2008 and 2009 during an outbreak in Hungary. Antibiotic combinations were analyzed by checkerboard technique and fractional inhibitory concentration indices were calculated. The following antibiotics were tested: ceftazidime, cefotaxime, ceftriaxone, ampicillin, imipenem, ertapenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, polymyxin B and colistin. Combinations including 0.25 μg/ml colistin plus 1 μg/ml rifampicin, 0.25 μg/ml polymyxin B plus 1 μg/ml rifampicin, 1 μg/ml imipenem plus 2 μg/ml tobramycin, were found synergistic.These in vitro synergistic combinations suggest potential therapeutical options against infections caused by KPC-2 producing, multidrug-resistant K. pneumoniae ST258.

Human adenoviruses function as genetic models and vectors for gene therapy. Upper respiratory, gastrointestinal or ocular infections usually have mild course without any major complication in immunocompetent individuals. However, reactivation from latency in immunocompromised patients may lead to death. Depending on the underlying diseases, different adenovirus serotypes damage different organs. In children with severe combined immunodeficiency syndrome, serotypes of species A and C induce lung, liver or bladder inflammation. Paediatric hematopoietic stem cell transplantation is frequently followed by serotype 31-induced pneumonia, enteritis, cystitis. B serotypes can destroy transplanted organs. In AIDS patients, D and novel F serotypes cause enteritis. Recombinants of B serotypes induce urinary tract infections. Progression of lymphomas, tumours, and systemic lupus erythematosus might be facilitated by immunosuppressive effects of adenoviruses. As far as the diagnostic work-up of adenoviruses, detection of viral DNA and virus copy number is predictive, while serology testing is quite unreliable. For treatment, cidofovir derivates, ribavirin, ganciclovir, vidarabine and microRNA have been used.

Antiretroviral effect of thiolated nucleotide 4-thio-uridylate (S4UMP, designated as UD29) against human immunodeficiency virus type 1 (HIV-1) have been quantitatively determined in cell-based viral infectivity assays. In syntitium inhibition assay on MT-2 human T-cell line UD29 prevented cell fusion and formation of syntitia induced by HIV-1IIIB with IC50 values of 11.7 μg/ml. In a single-cycle viral infection assay (MAGI assay) UD29 proved to have a potent inhibitory effect against HIV-1IIIB on HeLaCD4-LTR/β-gal cells, which was dose dependent with IC50 values of 4.75 μg/ml and IC90 of 39.7 μg/ml. UD29 showed a most prominent antiviral effect when administered 30 min prior HIV-1 infection. As HIV entry requires thiol/disulfide exchange process, results suggest that reactive -SH group of enol-form of the thiolated nucleotide may interfere with the function of cell surface proteins. UD29 cannot penetrate into cells and may have an interactive role in redox processes active in viral entry.

Streptococcus pneumoniae is responsible for a high level of morbidity and mortality, especially among children. For a long time, only the polysaccharide vaccine was available against pneumococcal infections, but in the last decade special conjugate vaccines were developed for paediatric use. These vaccines have made a deep impact on serotype distribution all over the world, by suppressing those serotypes included in the vaccines, while new, previously rare types emerged. These changes have been monitored closely in numerous publications all over the world. Nevertheless, data on pneumococcal serotypes in Hungary were mostly published in Hungarian, therefore not available in the international literature. In this meta-analysis, our aim was to collect and summarise all available data, and try to follow the changes observed after the introduction of the conjugate vaccines.

Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide, especially among children <5 years. Healthy carriers are the most important sources of infections and the carriage also peaks in the first years of life, especially among children attending communities. In this study, for the first time in Hungary, we surveyed the nasal carriage of healthy children, just before the use of the conjugate vaccine started increasing.Nasal specimens of 358 children were cultured and pneumococci isolated. The strains were serotyped with antisera and PCR, genotyped by PFGE and their antibiotic sensitivity determined by agar dilution method.The carriage rate was 37.71%. The isolates were sensitive to most tested antibiotics, except for macrolides. In this cohort of specimens still the widespread, so-called "pediatric serotypes" dominated (14, 19F, 23F, 6A, 6B in ranking order), but three of the previously rare types: 15B, 11A and 13 were represented already by 21.5% of all strains and also a few other rare non-vaccine types (e.g. 10A or 37) were detected.The calculated vaccine coverage was 55.6% for PCV-7, 69.6% for PCV-13 and 86.7% for Pneumovax. In this cohort, only 15.9% of the children (n = 57) were vaccinated. The carriage rate of PCV-7 vaccinated children was significantly lower (30.4%) than that of the non-vaccinated group (39.2%). The clonality of the isolates was significant within each group, revealing the extensive bacterium exchange among children.

At the 25th anniversary of the identification of HIV virus as the causative agent of AIDS, virologist and clinician authors provide an overview of the discovery and identification of HIV, its significance in the development of clinical diagnosis of HIV/AIDS, which led to the development of effective antiretroviral treatment. Besides the epidemiological and sociological aspects of the infection, authors provide a detailed chronology of the special aspects of the fight against HIV/AIDS in Hungary, from the diagnosis of the first HIV and AIDS cases, through the establishment of the nationwide screening network and counseling units to the appearance of drug resistant virus mutants, and the recent penetration of African HIV strains to the country. Further actions are urged locally and worldwide for the better understanding the interactions of the human host organism and the HIV virus for the more effective treatment. For these political consensuses, a large scale long term financial support, views based on scientific and public health evidences, and cooperation of the whole society worldwide are needed.

Unlabelled: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement for type I diabetes mellitus patients with end stage renal disease. Several patients have some complications of diabetes without renal failure. For these patients pancreas transplantation alone is a therapeutic option. The first pancreas transplantation alone was performed 6 years after the launch of our pancreas transplant program. The patient was a 40-years-old man. Enteric drainage was used with portal venous drainage. Anti IL-2. R antibody, daclizumab was given as prolonged induction therapy. In spite of the technical and immunological difficulties there were neither technical failures nor acute rejection. 3 years after the transplantation the patient has a good quality of life without insulin therapy with excellent renal function., Conclusion: PTA transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients without end stage renal disease.

The presence of the vanA gene was determined in enterococci from healthy poultry, originating from the Hungarian resistance monitoring system between 2001 and 2004. Enterococci (n = 562) were collected from intestinal samples of slaughtered broiler chickens. The presence of van genes was detected by polymerase chain reaction (PCR). The vancomycin-resistant enterococcus (VRE) strains carried only the vanA gene. Genus- and species-level identification of the vanA gene carrier strains was carried out by PCR using specific primers. In 2001, 25 out of the 289 isolated strains (8.6%) were vanA carriers (1 Enterococcus mundtii, 13 E. durans and 11 E.faecium). In 2002 (n = 87), 20 (23%) strains were vanA positive (11 E. durans and 9 E. faecium). In 2003 and 2004, none of the strains (n = 95 and 91, respectively) were positive for the most common van genes. In 2003, there was only one strain for which higher minimum inhibitory concentrations (MIC) of vancomycin (4 mg/L) and teicoplanin (8 mg/L) were found. In 2004 there were three strains for which the MIC of vancomycin was 8 mg/L, and 2 strains and 1 strain with teicoplanin MICs of 4 mg/L and 8 mg/L, respectively. The potential similarity of these strains was studied by pulsed-field gel electrophoresis (PFGE). The VRE strains were not closely related to one another. The annual data of vancomycin resistance indicate an association between the recovery of vancomycin-resistant enterococci and the use of avoparcin in animal feeds. This study indicates that with the reduced use of antibiotics in food animals, it is possible to decrease the rate of resistant bacteria. Although the use of avoparcin had been banned in 1998, the VRE strains disappeared only five years later.

Introduction: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement., Aims: Analysis of the five years' experience of the first Hungarian SPK transplants., Material: From 29 October 1998. through 31 December 2003. 32 SPK transplants were performed from 53 type 1 diabetes mellitus patients with ESRD on the waiting list. Enteric drainage was performed in all transplanted patients in 20 combined with systemic venous drainage, whereas in 12 patients portal venous drainage was used. In 18 patients only maintenance immunosuppression was administered without ATG induction therapy. Anti IL-2R antibody, daclizumab was given as induction therapy in 14 patients., Results: 24 patients out of 32 transplanted are insulin independent with excellent renal function. 2 patients were lost in the perioperative period due to septic complication. 2 patients died 5 months after transplantation. 1 patient became insulin dependent in 7 month following the SPK transplant, while preserving a marginal renal function. One patient became insulin dependent 2 years after the SPK transplant and was returned to chronic hemodialysis treatment one more year later. 2 patients are insulin independent but lost his renal graft due to therapy resistant rejection., Conclusion: SPK transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients with ESRD.