Evaluation and selection of candidates for renal transplantation at the Clinical Hospital Center in Rijeka

On December 31, 2001, 2486 patients with terminal renal failure received dialysis treatment in Croatia. Only one third of the patients are registered on the national waiting list for cadaveric kidney transplant. In most of the others, transplantation is impossible because of comorbidity. This is mainly due to the steadily growing age of the dialytic population and therefore a higher incidence of cardiovascular disease and diabetes. Still, evaluation of the potential recipients of cadaveric kidney transplant, registered on the waiting list, often reveals contraindications for transplantation. The aim of this study was to determine the incidence and type of contraindications in transplant candidates, found during immediate preoperative evaluation. Analysis of these data should help in determining how contraindications can be early detected and prevented. Before registering onto the national waiting list transplant candidates need to be thoroughly investigated including detailed history, physical examination, routine diagnostic procedures and additional examinations, if needed, to exclude or evaluate the possibly existing contraindications for transplantation. During the period from January 1997 until June 2002, 145 potential recipients from the national waiting list were referred to the Rijeka University Hospital Center and evaluated for kidney transplantation. Eighty-eight patients underwent transplantation. Preoperative evaluation revealed contraindications for transplantation in 52 (35.9%) candidates. Twenty-two (15.2%) patients had a positive cross-match with donor lymphocytes, 6 (4.1%) patients refused transplantation, and in 24 (16.6%) patients serious comorbidity was the reason for not being accepted for transplantation and for their withdrawal from the national waiting list. Comorbidity was mainly due to cardiovascular disease (12 patients--8.3%) and infection (8 patients--5.5%). These data show a high incidence of contraindications found during the immediate preoperative evaluation of potential kidney recipients. It was the case in more than one third of patients. During the evaluation of potential candidates for kidney transplantation special attention should be addressed to the presence of cardiovascular morbidity and infection. Peripheral vascular occlusive disease, cardiac status and/or cerebrovascular disease should be evaluated. Measures used to treat or reduce the development of complications include an optimal control of blood pressure, serum phosphate, hyperparathyroidism, dyslipidemia, and renal anemia. The sites of infection must be treated and eradicated, because immunosuppressive treatment is a threat to the transplant recipient's life. The second most common cause of refusal of potential candidates was a positive cross-match with donor lymphocytes. Sensitization to human leukocyte antigens can be prevented by the avoiding of blood transfusions and use of erythopoietin in treating renal anemia. To minimize the morbidity and mortality, the potential kidney recipients should undergo rigorous selection and thorough evaluation before including them into the waiting list for kidney transplantation. Afterwards, regular examinations are obligatory to reveal contraindications, proceed to medical interventions and treat concomitant diseases in time, which can influence the patient's survival. In case that contraindications for transplantation arise, the patient must be temporarily or definitely removed from the waiting list.     

Evaluation of anti-parvovirus B19 activity in sera by assay using quantitative polymerase chain reaction

Human parvovirus B19 (B19) infects cells of erythroid lineage. Production of neutralizing antibodies (Abs) is indispensable for recovery from B19-related disease state. In this study, we used a convenient method to measure neutralizing activities in human sera by using a real-time quantitative PCR based assay. Erythroid cell line KU812Ep6 was incubated with test sera before infection with B19 virus. The copy number of B19-DNA in cultures was decreased in the presence of the sera from patients who recovered from acute B19 infection, whereas no decrease in B19-DNA was in cultures incubated with sera from healthy volunteers who had no B19 infection. The decrease in B19-DNA copy number was calculated and the inhibition percentage was expressed as neutralizing activity to B19. A clinical study showed that the levels of neutralizing ability were high in patients who recovered soon after acute B19 infection, but were low in some patients with a prolonged clinical course for recovery from B19 infection. This method is simple and convenient compared with methods described previously, showing its usefulness to evaluate the neutralizing activity to B19.     

Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network

The metabolic network in the yeast Saccharomyces cerevisiae was reconstructed using currently available genomic, biochemical, and physiological information. The metabolic reactions were compartmentalized between the cytosol and the mitochondria, and transport steps between the compartments and the environment were included. A total of 708 structural open reading frames (ORFs) were accounted for in the reconstructed network, corresponding to 1035 metabolic reactions. Further, 140 reactions were included on the basis of biochemical evidence resulting in a genome-scale reconstructed metabolic network containing 1175 metabolic reactions and 584 metabolites. The number of gene functions included in the reconstructed network corresponds to approximately 16% of all characterized ORFs in S. cerevisiae. Using the reconstructed network, the metabolic capabilities of S. cerevisiae were calculated and compared with Escherichia coli. The reconstructed metabolic network is the first comprehensive network for a eukaryotic organism, and it may be used as the basis for in silico analysis of phenotypic functions.     

Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production

Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be essential for immunoglobulin A (IgA) production. We found that the severe IgA deficiency in lymphotoxin-deficient (LT(-/-)) mice could be fully reversed by reconstitution with LT-expressing bone marrow, despite the absence of both LNs and PPs. The number of IgA precursors from LT(-/-) mice was not reduced, and they were able to migrate into the lamina propria (LP) of wild-type mice but not of LTbetaR(-/-) mice. Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTalpha(-/-) and LTbetaR(-/-) mice. IgA deficiency in LTalpha(-/-) mice was reversed by the transplantation of a segment of RAG-1 (recombination-activating gene 1) deficient intestine, which confirmed the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut microenvironment for IgA production.     

Impaired recognition of fear in a Chinese man with bilateral cingulate and unilateral amygdala damage

LJM, a 41-year-old schizophrenic Chinese man with bilateral anterior cingulate gyrus (Brodmann's area 24) lesions and also a small lesion in right amygdala after an operation, was compared with normal as well as brain-damaged and schizophrenic controls in identification of morphed facial expressions of six basic emotions. In repeated administrations of the test for recognition of facial emotions, over a 1- year period, LJM performed significantly worse for expressions of fear compared with the three groups of controls. Recognition of other emotions was not significantly different from that of the controls, except that his recognition of disgust during the first session (but not in two subsequent sessions) was worse than normal and brain-damaged controls but not worse than schizophrenic controls. The dissociation between recognition of fear and other emotions supported the view that the brain has separable networks for processing different emotions, and that the right amygdala as well as the anterior part of bilateral cingulate gyrus are possible substrates involved in the special network for perception of fear. The results from the various groups of Chinese subjects indicate that they perceive emotions in a categorical manner, and that the six basic emotions are likely to be cross-cultural universals.     

Triptolide inhibits IL-12 production and T cell-stimulatory capacity of dendritic cells

Extracts of Tripterygium wilfordii Hook F.(TWHF ) are effective in traditional Chinesemedicine for treatment of autoimmune diseasessuch as rheumatoid arthritis, systemic lupus ery thematosus, nephritis and asthma [1, 2]. Trip tolide, a diterpenoid triepoxide, is derived fromTWHF and is responsible for most of the immuno suppressive and anti inflammatory effects ofTWHF. Triptolide has been shown to be effectivein the treatment of autoimmune diseases, …     

The frequency of occurrence of autoantibodies against beta1-adrenoceptors and its clinical relevance in patients with hepatitis virus myocarditis

The aim of this study was to examine the frequency of occurrence of autoantibodies against beta1-adrenoceptors in patients with hepatitis virus myocarditis (HVM) and its possible correlation with clinical characteristics. A total of 103 patients with viral myocarditis were divided into a positive group (HVM group, n=29) and a negative group (Non-HVM group, n=74) according to the laboratory findings regarding their type of hepatitis virus. The study parameters included UCG, ECG, biochemical findings and screening of autoantibodies against beta1-adrenoceptor. It was shown that the positive rate of the hepatitis virus was 28.16% (29/103) in patients with viral myocarditis. The severity of myocardial or liver injuries and the frequency of occurrence of autoantibodies against beta1-adrenoceptors in patients with viral myocarditis were more pronounced, before treatment, in the HVM group than in the Non-HVM group. The positive rates of the antibodies against the hepatitis virus and the autoantibodies against beta1-adrenoceptors were highly consistent in patients with HVM (p<0.05). In conclusion, the frequency of occurrence of the autoantibodies against beta1-adrenoceptors may be one important marker of HVM and, thus, possibly involved in the pathogenesis of the HVM.     

THE EFFECT OF ANISODAMINE ON THE MICROVASCULAR PERMEABILITY OF THE LUNGS DURING ARDS

INTRODUCTIONAdultRespiratoryDistressSyndrome(ARDS)isanacuteprogressiverespiratoryfailurecausedbymanyreasons.Thetherapeuticactionofthissyndromeisuncertain,becausethemechanismisnotwellknown.Thatis,theprognosisiscritical,themortailityisquiteheigh(50%f)ti--63'Butintherecenttenyears,manyscholarsinourcountryhavehadmuchexperienceintheaspectofusinganisodaminetorescueARDSpatientsandhavedecreasedthemortality(')'Howeveverthescholarsexplaintheprincipleofitindifferentways'Thechangesofmicrovascula…     

Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival

Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise, we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.Abbreviations APC Antigen-presenting cells - CTL Cytotoxic T lymphocytes - DC Dendritic cells - DC-IL-10 IL-10 gene-modified immature dendritic cells - iDC Immature dendritic cells - IL-10 Interleukin-10 - MLR Mixed leukocyte reaction - MOI Multiplicity of infection