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1.
Eur J Clin Microbiol Infect Dis ; 33(8): 1273-87, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24615580

ABSTRACT

Fungi cause opportunistic, nosocomial, and community-acquired infections. Among fungal infections (mycoses) zygomycoses are exceptionally severe, with a mortality rate exceeding 50%. Immunocompromised hosts, transplant recipients, and diabetic patients with uncontrolled keto-acidosis and high iron serum levels are at risk. Zygomycota are capable of infecting hosts immune to other filamentous fungi. The infection often follows a progressive pattern, with angioinvasion and metastases. Moreover, current antifungal therapy frequently has an unfavorable outcome. Zygomycota are resistant to some of the routinely used antifungals, among them azoles (except posaconazole) and echinocandins. The typical treatment consists of surgical debridement of the infected tissues accompanied by amphotericin B administration. The latter has strong nephrotoxic side effects, which make it unsuitable for prophylaxis. Delayed administration of amphotericin and excision of mycelium-containing tissues worsens survival prognoses. More than 30 species of Zygomycota are involved in human infections, among them Mucorales is the most abundant. Prognosis and treatment suggestions differ for each species, which makes fast and reliable diagnosis essential. Serum sample PCR-based identification often gives false-negative results; culture-based identification is time-consuming and not always feasible. With the dawn of Zygomycota sequencing projects significant advancement is expected, as in the case of treatment of Ascomycota infections.


Subject(s)
Fungi, Unclassified/physiology , Zygomycosis/microbiology , Animals , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Fungi, Unclassified/drug effects , Host-Pathogen Interactions , Humans , Risk Factors , Zygomycosis/epidemiology , Zygomycosis/therapy
2.
Nat Genet ; 20(3): 233-8, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9806540

ABSTRACT

The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).


Subject(s)
ATP-Binding Cassette Transporters/genetics , Cholestasis, Intrahepatic/genetics , Mutation , ATP Binding Cassette Transporter, Subfamily B, Member 11 , ATP-Binding Cassette Transporters/chemistry , ATP-Binding Cassette Transporters/metabolism , Amino Acid Sequence , Animals , Bile Acids and Salts/metabolism , Cholestasis, Intrahepatic/metabolism , Chromosome Mapping , Chromosomes, Human, Pair 2/genetics , Consanguinity , DNA, Complementary/genetics , Female , Humans , Infant , Liver/metabolism , Male , Molecular Sequence Data , Pedigree , Rats , Sequence Homology, Amino Acid
3.
Persoonia ; 30: 11-47, 2013 Jun.
Article in English | MEDLINE | ID: mdl-24027345

ABSTRACT

The order Mucorales comprises predominantly fast-growing saprotrophic fungi, some of which are used for the fermentation of foodstuffs but it also includes species known to cause infections in patients with severe immune or metabolic impairments. To inventory biodiversity in Mucorales ITS barcodes of 668 strains in 203 taxa were generated covering more than two thirds of the recognised species. Using the ITS sequences, Molecular Operational Taxonomic Units were defined by a similarity threshold of 99 %. An LSU sequence was generated for each unit as well. Analysis of the LSU sequences revealed that conventional phenotypic classifications of the Mucoraceae are highly artificial. The LSU- and ITS-based trees suggest that characters, such as rhizoids and sporangiola, traditionally used in mucoralean taxonomy are plesiomorphic traits. The ITS region turned out to be an appropriate barcoding marker in Mucorales. It could be sequenced directly in 82 % of the strains and its variability was sufficient to resolve most of the morphospecies. Molecular identification turned out to be problematic only for the species complexes of Mucor circinelloides, M. flavus, M. piriformis and Zygorhynchus moelleri. As many as 12 possibly undescribed species were detected. Intraspecific variability differed widely among mucorealean species ranging from 0 % in Backusella circina to 13.3 % in Cunninghamella echinulata. A high proportion of clinical strains was included for molecular identification. Clinical isolates of Cunninghamella elegans were identified molecularly for the first time. As a result of the phylogenetic analyses several taxonomic and nomenclatural changes became necessary. The genus Backusella was emended to include all species with transitorily recurved sporangiophores. Since this matched molecular data all Mucor species possessing this character were transferred to Backusella. The genus Zygorhynchus was shown to be polyphyletic based on ITS and LSU data. Consequently, Zygorhynchus was abandoned and all species were reclassified in Mucor. Our phylogenetic analyses showed, furthermore, that all non-thermophilic Rhizomucor species belong to Mucor. Accordingly, Rhizomucor endophyticus was transferred to Mucor and Rhizomucor chlamydosporus was synonymised with Mucor indicus. Lecto-, epi- or neotypes were designated for several taxa.

4.
Persoonia ; 30: 57-76, 2013 Jun.
Article in English | MEDLINE | ID: mdl-24027347

ABSTRACT

The Mucorales (Mucoromycotina) are one of the most ancient groups of fungi comprising ubiquitous, mostly saprotrophic organisms. The first comprehensive molecular studies 11 yr ago revealed the traditional classification scheme, mainly based on morphology, as highly artificial. Since then only single clades have been investigated in detail but a robust classification of the higher levels based on DNA data has not been published yet. Therefore we provide a classification based on a phylogenetic analysis of four molecular markers including the large and the small subunit of the ribosomal DNA, the partial actin gene and the partial gene for the translation elongation factor 1-alpha. The dataset comprises 201 isolates in 103 species and represents about one half of the currently accepted species in this order. Previous family concepts are reviewed and the family structure inferred from the multilocus phylogeny is introduced and discussed. Main differences between the current classification and preceding concepts affects the existing families Lichtheimiaceae and Cunninghamellaceae, as well as the genera Backusella and Lentamyces which recently obtained the status of families along with the Rhizopodaceae comprising Rhizopus, Sporodiniella and Syzygites. Compensatory base change analyses in the Lichtheimiaceae confirmed the lower level classification of Lichtheimia and Rhizomucor while genera such as Circinella or Syncephalastrum completely lacked compensatory base changes.

5.
Persoonia ; 31: 188-296, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24761043

ABSTRACT

Novel species of microfungi described in the present study include the following from South Africa: Camarosporium aloes, Phaeococcomyces aloes and Phoma aloes from Aloe, C. psoraleae, Diaporthe psoraleae and D. psoraleae-pinnatae from Psoralea, Colletotrichum euphorbiae from Euphorbia, Coniothyrium prosopidis and Peyronellaea prosopidis from Prosopis, Diaporthe cassines from Cassine, D. diospyricola from Diospyros, Diaporthe maytenicola from Maytenus, Harknessia proteae from Protea, Neofusicoccum ursorum and N. cryptoaustrale from Eucalyptus, Ochrocladosporium adansoniae from Adansonia, Pilidium pseudoconcavum from Greyia radlkoferi, Stagonospora pseudopaludosa from Phragmites and Toxicocladosporium ficiniae from Ficinia. Several species were also described from Thailand, namely: Chaetopsina pini and C. pinicola from Pinus spp., Myrmecridium thailandicum from reed litter, Passalora pseudotithoniae from Tithonia, Pallidocercospora ventilago from Ventilago, Pyricularia bothriochloae from Bothriochloa and Sphaerulina rhododendricola from Rhododendron. Novelties from Spain include Cladophialophora multiseptata, Knufia tsunedae and Pleuroascus rectipilus from soil and Cyphellophora catalaunica from river sediments. Species from the USA include Bipolaris drechsleri from Microstegium, Calonectria blephiliae from Blephilia, Kellermania macrospora (epitype) and K. pseudoyuccigena from Yucca. Three new species are described from Mexico, namely Neophaeosphaeria agaves and K. agaves from Agave and Phytophthora ipomoeae from Ipomoea. Other African species include Calonectria mossambicensis from Eucalyptus (Mozambique), Harzia cameroonensis from an unknown creeper (Cameroon), Mastigosporella anisophylleae from Anisophyllea (Zambia) and Teratosphaeria terminaliae from Terminalia (Zimbabwe). Species from Europe include Auxarthron longisporum from forest soil (Portugal), Discosia pseudoartocreas from Tilia (Austria), Paraconiothyrium polonense and P. lycopodinum from Lycopodium (Poland) and Stachybotrys oleronensis from Iris (France). Two species of Chrysosporium are described from Antarctica, namely C. magnasporum and C. oceanitesii. Finally, Licea xanthospora is described from Australia, Hypochnicium huinayensis from Chile and Custingophora blanchettei from Uruguay. Novel genera of Ascomycetes include Neomycosphaerella from Pseudopentameris macrantha (South Africa), and Paramycosphaerella from Brachystegia sp. (Zimbabwe). Novel hyphomycete genera include Pseudocatenomycopsis from Rothmannia (Zambia), Neopseudocercospora from Terminalia (Zambia) and Neodeightoniella from Phragmites (South Africa), while Dimorphiopsis from Brachystegia (Zambia) represents a novel coelomycetous genus. Furthermore, Alanphillipsia is introduced as a new genus in the Botryosphaeriaceae with four species, A. aloes, A. aloeigena and A. aloetica from Aloe spp. and A. euphorbiae from Euphorbia sp. (South Africa). A new combination is also proposed for Brachysporium torulosum (Deightoniella black tip of banana) as Corynespora torulosa. Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

6.
Clin Exp Immunol ; 163(2): 157-64, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21155991

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory disease, with a clinical manifestation both systemic and in joints. It has been suggested that age at disease onset and/or patients' age have influence on disease activity and clinical outcome. The reasons for the different course of RA in older people are not known; however, the activation status of peripheral blood lymphocytes could be responsible. Our aim was to relate expression of activation markers in peripheral blood CD4(+) T cells of RA patients with patients' age and/or onset age and disease activity measured by DAS28. Seventy RA patients were included into the immunological study. Two separation criteria were performed: based on age of RA onset and on the biological age of patients. We examined different activation markers, CD69, CD25, CD95 and human leucocyte antigen D-related (HLA-DR), on the CD4(+) T cell surface. Division of RA patients in 10-year intervals at 40, 50 and 60 years revealed that RA patients with later disease onset were characterized by higher DAS28. This phenomenon was not limited to the division at 60 years of age but, surprisingly, the major differences were found for the 40-year onset division. Analysis of all four components of DAS28 revealed that disease activity in older disease onset was dependent on all components. Older-onset RA patients had a higher percentage of CD4(+) CD25(+) and CD4(+) CD95(+) T cells. Summarizing the major differences in DAS28 and activation status of CD4(+) T cells observed for onset of disease at 40 years seems to be the most informative about the immunological status of RA patients.


Subject(s)
Arthritis, Rheumatoid/immunology , CD4-Positive T-Lymphocytes/immunology , Lymphocyte Activation , Adult , Age of Onset , Antigens, CD/analysis , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/analysis , Antigens, Differentiation, T-Lymphocyte/immunology , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biomarkers/blood , Cohort Studies , Female , HLA-DR Antigens/analysis , HLA-DR Antigens/immunology , Humans , Interleukin-2 Receptor alpha Subunit/analysis , Interleukin-2 Receptor alpha Subunit/immunology , Lectins, C-Type/analysis , Lectins, C-Type/immunology , Male , Methotrexate/therapeutic use , Middle Aged , Prednisone/therapeutic use , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , fas Receptor/analysis , fas Receptor/immunology
7.
Transpl Infect Dis ; 13(5): 471-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21689252

ABSTRACT

Monitoring of circulating Epstein-Barr virus (EBV) DNA in pediatric transplant patients has been shown to be useful in post-transplant patient management. It still remains unclear which blood sample type is more suitable, and how EBV DNA levels in whole blood (WB) correlate with those in peripheral blood mononuclear cells (PBMCs). The aim of this study was to compare EBV DNA load in WB and PBMCs of pediatric transplant recipients. After liver, kidney, or combined liver-kidney transplantation, 172 matched WB and PBMCs samples were collected from 84 children (130 samples from 42 patients consisted of multiple collections). The EBV DNA level in PBMCs was determined by home-made real-time polymerase chain reaction using TaqMan chemistry. In parallel, the viral load (VL) in WB was measured by a commercial LightCycler EBV Quant Kit. The EBV DNA levels and dynamics of VL changes were assessed and compared between WB and PBMCs. The overall correlation between EBV DNA level in PBMCs and WB was statistically significant and high, r(2) =0.87 (P<0.001). However, the sensitivity of EBV detection was lower in WB (93.9%). Longitudinal analysis of EBV DNA load dynamics in PBMCs and WB indicated that EBV DNA load fluctuations were larger in WB, but the trend of decreases and increases, with minor exceptions, was similar in both sample types. The high correlation of EBV DNA levels, as well as the similar dynamics of EBV DNA changes in both sample types, make WB a good alternative to EBV DNA monitoring in PBMCs of pediatric transplant recipients. However, the subtle increase of the VL may be detected earlier in PBMCs.


Subject(s)
Herpesvirus 4, Human/genetics , Kidney Transplantation/adverse effects , Leukocytes, Mononuclear/virology , Liver Transplantation/adverse effects , RNA, Viral/blood , Viral Load , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Young Adult
8.
Eur J Pediatr Surg ; 18(2): 111-6, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18437656

ABSTRACT

Biliary atresia (BA) is a rare but potentially devastating disease. The European Biliary Atresia Registry (EBAR) was set up to improve data collection and to develop a pan-national and interdisciplinary strategy to improve clinical outcomes. From 2001 to 2005, 100 centers from 22 countries registered with EBAR via its website (www.biliary-atresia.com). In June 2006, the first meeting was held to evaluate results and launch further initiatives. During a 5-year period, 60 centers from 19 European countries and Israel sent completed registration forms for a total of 514 BA patients. Assuming the estimated incidence of BA in Europe is 1:18,000 live births, 35% of the expected 1488 patients from all EBAR participating countries were captured, suggesting that reporting arrangements need improvement. At the meeting, the cumulative evaluation of 928 BA patients including patients from other registries with variable follow-up revealed an overall survival of 78% (range from 41% to 92%), of whom 342 patients (37%) have had liver transplants. Survival with native liver ranged from 14% to 75%. There was a marked variance in reported management and outcome by country (e.g., referral patterns, timing of surgery, centralization of surgery). In conclusion, EBAR represents the first attempt at an overall evaluation of the outcome of BA from a pan-European perspective. The natural history and outcome of biliary atresia is of considerable relevance to a European population. It is essential that there is further support for a pan-European registry with coordination of clinical standards, further participation of parent support groups, and implementation of online data entry and multidisciplinary clinical and basic research projects.


Subject(s)
Biliary Atresia/epidemiology , Registries , White People , Biliary Atresia/surgery , Europe/epidemiology , Humans , Incidence , Infant, Newborn , International Cooperation , Survival Analysis , Treatment Outcome
9.
Transplant Proc ; 39(10): 3186-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18089349

ABSTRACT

Alpha1-antitrypsin deficiency (alpha1-ATD) is a genetic disorder that may predispose to chronic liver disease. The clinical manifestations and prognosis of this disorder are variable. The aim of the study was to evaluate the clinical presentation and liver tests in two groups of children with alpha1-ATD: those with a good prognosis who survived long term with their native liver, and those with a bad one, requiring liver transplantation (OLT) or dying before OLT. We studied 59 children homozygous for alpha1-ATD admitted to our hospital with cholestasis or chronic hepatitis since infancy. Patients without liver transplantation were regarded to be the good prognosis group I (n=45). In contrast the 11 children who required liver transplantation and the three who died before OLT were the bad prognosis cohort (Group II, n=14). We analyzed the laboratory parameters of cholestasis, hepatitis, and liver insufficiency in both groups. In the group with a good prognosis, eight children still suffered from cholestasis at the ages of 9 to 14 years while nine had hepatitis at the ages of 9 to 14 years. We observed a temporarily increased international normalized ratio (1.2 to 1.5) in eight subjects at the ages of 1 month to 17 years, and slight hypoalbuminemia (30 to 35 mg/dL) in nine children at the ages of 1 month to 10 years. OLT was performed in 11 children at the ages of 10 to 17 years. Our center's experience suggested that in the PiZZ patients with portal hypertension, esophageal varices, or deterioration of hepatic function, liver transplantation should not be delayed.


Subject(s)
Liver Failure/surgery , Liver Transplantation/statistics & numerical data , alpha 1-Antichymotrypsin/deficiency , Adolescent , Adult , Child , Child, Preschool , Esophageal and Gastric Varices/surgery , Homozygote , Humans , Hypertension, Portal/surgery , Infant , Liver Diseases/epidemiology , Liver Diseases/surgery , Liver Failure/enzymology , Liver Failure/genetics , Patient Selection , Poland , Prognosis , Waiting Lists
10.
Transplant Proc ; 39(5): 1523-5, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17580179

ABSTRACT

Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.


Subject(s)
Antioxidants/metabolism , Dietary Carbohydrates/metabolism , Dietary Fats/metabolism , Liver Transplantation/physiology , Atherosclerosis/epidemiology , Child , Child, Preschool , Cyclosporine/therapeutic use , Drug Therapy, Combination , Follow-Up Studies , Glutathione/blood , Glutathione Peroxidase/blood , Humans , Immunosuppressive Agents/therapeutic use , Lipoproteins/blood , Postoperative Complications/epidemiology , Retrospective Studies , Tacrolimus/therapeutic use , Time Factors
11.
Transplant Proc ; 39(10): 3219-21, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18089357

ABSTRACT

Immunosuppressive and antibacterial regimens in children after liver transplantation create a gut microflora imbalance that can be indirectly measured by the activity of fecal enzymes. The aim of this study was to specify the influence of diet supplementation with probiotic Lactobacillus casei DN on the activity of beta-glucuronidase, beta-glucosidase, and urease. Twenty-five children after liver transplantation (13 girls, 12 boys) ages 3 to 17 years were enrolled in the study. Two months after bacteria application the levels of all 3 enzymes decreased, reaching statistical significance for beta-glucuronidase and beta-glucosidase. Complete rebound in enzyme activity was observed months after the end of probiotic supplementation. We concluded that Lactobacillus casei DN-114001 consumption decreased fecal enzyme activity, a beneficial effect limited to the period of bacteria intake.


Subject(s)
Feces/enzymology , Feces/microbiology , Lacticaseibacillus casei , Liver Transplantation/physiology , Adolescent , Cellulases/metabolism , Child , Child, Preschool , Female , Glucuronidase/metabolism , Humans , Male , Placebos , Urease/metabolism
12.
Transplant Proc ; 39(5): 1511-2, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17580175

ABSTRACT

Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.


Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines , Hepatitis B/prevention & control , Liver Transplantation/immunology , Child , Child, Preschool , Hepatitis B/immunology , Humans , Infant , Living Donors
13.
Geobiology ; 15(5): 704-714, 2017 09.
Article in English | MEDLINE | ID: mdl-28603946

ABSTRACT

The aim of this study was to determine the amount of organic and inorganic carbon in foraminifera specimens and to provide quantitative data on the contribution of foraminifera to the sedimentary carbon pool in Adventfjorden. The investigation was based on three calcareous species that occur commonly in Svalbard fjords: Cassidulina reniforme, Elphidium excavatum and Nonionellina labradorica. Our results show that the species investigated did not contribute substantially to the organic carbon pool in Adventfjorden, because they represented only 0.37% of the organic carbon in the sediment. However, foraminiferal biomass could have been underestimated as it did not include arenaceous or monothalamous taxa. Foraminiferal carbonate constituted up to 38% of the inorganic carbon in the sediment, which supports the assumption that in fjords where non-calcifying organisms dominate the benthic fauna foraminifera are among the major producers of calcium carbonate and that they play crucial roles in the carbon burial process. The results presented in this study contribute to estimations of changes in foraminiferal carbon levels in contemporary environments and could be an important reference for palaeoceanographic studies.


Subject(s)
Carbon/metabolism , Estuaries , Foraminifera/metabolism , Geologic Sediments , Seasons , Geologic Sediments/chemistry , Geologic Sediments/parasitology , Svalbard
14.
Transplant Proc ; 48(10): 3323-3327, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27931577

ABSTRACT

BACKGROUND: α1-Antitrypsin deficiency (ATD) is the most common genetic cause of liver injury in young children. Asymptomatic hepatitis is observed in most patients. However, the course of liver disease due to ATD is unpredictable, and some children develop liver cirrhosis. Liver transplantation (Ltx) dramatically improves their outcome and in some cases is required in the first years of life. The aim of the study was to evaluate the course of the disease in children with ATD treated with Ltx in a single center. METHODS: We retrospectively reviewed the clinical features (ascites, esophageal varices, esophageal bleeding) and laboratory parameters of liver function in children with ATD who were treated with Ltx. RESULTS: Twenty-two Ltxs were performed in 20 children (13 boys, 7 girls). Median age at transplantation was 12 years (range 0.5 to 17.1). Four children were transplanted in the first 2 years of life and 16 patients were over 7 years old. The indications for Ltx in younger children were progressive cholestasis with coagulopathy and ascites. In older patients, the indications were as follows: liver failure presenting with variceal bleeding in 7 patients, ascites in 5 patients, hypersplenism in all but 1 patient. In the group of children transplanted over 7 years old, the frequency of cholestasis decreased intermittently in the second year of life: 4 patients (25%) compared to 15 patients (94%) and 10 patients (63%) in the neonatal and pretransplant period, respectively. In the group of children transplanted earlier, cholestasis and hepatitis were maintained until Ltx. Of transplanted patients, 50% were malnourished at the transplantation, and 50% were followed for more than 10 years. Five-year post-transplant survival was 100% (n = 14), and 10-year survival was 90%. Two patients died as adults with biliary post-transplant complications and problems with compliance. CONCLUSIONS: Our experience suggests that transient normalization of liver parameters in some patients with ATD do not exclude the liver disease progression to cirrhosis and unfavorable outcome of liver disease in childhood. In our group of patients, median age at transplantation was high compared to other centers. The long-term prognosis in children after transplantation is very good, but early post-transplant complications and probable problems with compliance in young adults may lead to graft failure.


Subject(s)
Liver Failure/surgery , Liver Transplantation/methods , alpha 1-Antitrypsin Deficiency/surgery , Adolescent , Child , Child, Preschool , Cholestasis/etiology , Cholestasis/surgery , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/etiology , Graft Survival , Humans , Hypersplenism/etiology , Infant , Liver Failure/etiology , Male , Poland , Prognosis , Retrospective Studies , alpha 1-Antitrypsin Deficiency/complications
15.
Immunol Lett ; 75(3): 179-84, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11166373

ABSTRACT

The immunological background of the pathological changes that appear in infantile cholestasis (infections, inflammatory process in the liver) is largely unknown. With the use of double color flow cytometry, we assessed the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 29 infants with extra and intra-hepatic cholestasis (12 and 17 patients, respectively), aged from 1 to 8.6 months. Control group consisted of 15 age-matched, healthy infants. We examined: (1) the expression of CD3, CD4, CD8, CD19 lymphocyte surface receptors; and (2) the distribution of lymphocyte subsets with distinctive surface Ag characteristics of 'naive' (CD45RA+) and 'memory' (CD45RO+) cells in both CD4+ and CD8+ cell populations. The surface markers expression was evaluated in terms of percentage of positive cells and receptor density. The following changes in the expression of lymphocyte surface markers are described: (1) a decrease in the percentage of total CD3+, CD4+ cells but normal percentage of CD8+ cells and elevated proportion of CD19+ B cells; (2) a reduction of the proportion of 'naive' CD4+ lymphocytes but normal percentage of 'naive' CD8+ as well as 'memory' CD4+ and CD8+ cell subsets; (3) a decrease in density of CD3, CD4+, CD8 receptors, and D45RA isoform in a subset of 'naive' CD4+ cells. We conclude that deficiency of 'naive' CD4+ T cell subset which possess important effector and immunoregulatory functions, and low expression of certain lymphocyte receptors known to be engaged in T cell activation, possibly reflect a defect of cell mediated immunity that may account for viral and bacterial infections, often observed in infants with cholestasis.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cholestasis, Extrahepatic/immunology , Cholestasis, Intrahepatic/immunology , Leukocyte Common Antigens/metabolism , CD4-Positive T-Lymphocytes/metabolism , Flow Cytometry , Humans , Infant , Phenotype , Protein Isoforms/metabolism , T-Lymphocyte Subsets/immunology
16.
Acta Biochim Pol ; 47(1): 141-7, 2000.
Article in English | MEDLINE | ID: mdl-10961687

ABSTRACT

Some sterically hindered N-substituted derivatives of daunorubicin are known to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. In consequence, poor oxygen radical generation by these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives of daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introduction of a heterocyclic ring, even if it is bulky but flexible, on the nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group), does not induce the steric hindrance effect on the interaction of daunorubicin derivatives with these flavoprotein enzymes.


Subject(s)
Amidines/chemistry , Daunorubicin/pharmacology , NADH Dehydrogenase/metabolism , NADPH-Ferrihemoprotein Reductase/metabolism , Xanthine Oxidase/metabolism , Daunorubicin/chemistry , Free Radicals , Kinetics
17.
Transplant Proc ; 35(8): 3026-8, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14697969

ABSTRACT

The aim of this study was to examine whether liver transplantation reverses the abnormal distribution of lymphocyte subsets previously observed in biliary atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell subset and an increase in the B and natural killer cell subpopulations. Eight biliary atresia children aged 1.08 to 6 years were studied before and 1 year after LTx for comparison with 15 age-matched healthy controls. The posttransplant immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor density were assessed by the use of double color flow cytometry (EPICS-XL MCL fluorocytometer). Biliary atresia patients were compared after LTx with subjects before LTx, essentially showing no statistically significant changes in lymphocyte subsets. We conclude that LTx of biliary atresia children does not reverse the abnormal lymphocyte subset distribution present before transplantation. Hence, these changes may reflect either their independence from the liver status or may result from immunosuppressive treatment that contributes to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+ naive T cells.


Subject(s)
Biliary Atresia/surgery , CD4-Positive T-Lymphocytes/immunology , Leukocyte Common Antigens/blood , Liver Transplantation/immunology , T-Lymphocytes/immunology , Antigens, CD/blood , Biliary Atresia/blood , Biliary Atresia/immunology , Child , Child, Preschool , Humans , Immunosuppressive Agents/therapeutic use , Infant , Lymphocyte Count , Reference Values , T-Lymphocyte Subsets/immunology
18.
Transplant Proc ; 36(10): 3077-82, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15686699

ABSTRACT

Liver transplantation is recognized as the appropriate treatment for end-stage liver disease. Four patients undergoing liver transplantation for classical end-stage liver disease developed de novo autoimmune hepatitis (AIH) in the graft. Recurrence of AIH after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in one other patient. Markedly elevated serum transaminases were observed, together with an elevated serum IgG and/or globulin fraction and histological feature typical of AIH on liver biopsy.


Subject(s)
Hepatitis, Autoimmune/pathology , Liver Transplantation/pathology , Adolescent , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Liver Transplantation/immunology , Male , Reoperation
19.
Transplant Proc ; 35(6): 2245-7, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14529902

ABSTRACT

INTRODUCTION: The number of available cadaveric donor organs has reached a plateau. One current solution has been to increase number of living related liver transplantations. MATERIAL AND METHODS: Since October 1999 in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 40 living related liver transplantation have been carried out. RESULTS: In 31 (77.5%) cases, a normal arterial supply was observed: the common hepatic artery arose from a celiac trunk. In two cases (5.0%), there was a partial arterial blood supply by the right accessory hepatic artery originating from the superior mesenteric artery. In two cases (5.0%), a right hepatic artery arose completely from the superior mesenteric artery (replaced artery). In one case (2.5%), a common hepatic artery originated from the superior mesenteric artery. In two cases (5.0%), an accessory left segmental artery originated from the left gastric artery. In two cases (5.0%), the function of an absent left hepatic artery was assumed by a replaced left hepatic artery originating from the left gastric artery. In two (5.0%) cases, there were two separate ducts draining the right hemiliver. There were two (5.0%) cases of an accessory duct draining segment IV, originating within the confluence of the right and left hepatic ducts. In one (2.5%) case, the common hepatic duct showed a trifurcation. CONCLUSION: During harvesting from a living donor knowledge of anatomical variants must be used to optomize the liver graft.


Subject(s)
Liver Circulation/physiology , Liver Transplantation/physiology , Family , Hepatic Artery/anatomy & histology , Humans , Living Donors , Mesenteric Artery, Superior/anatomy & histology , Portal System/anatomy & histology , Tissue and Organ Harvesting/methods
20.
Transplant Proc ; 35(6): 2250-2, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14529904

ABSTRACT

The aim of the study was to estimate the risk of harvesting a liver fragment from a living-related adult donor. Liver fragments were harvested from 44 donors. Liver segments II and III were harvested from 36 donors. Liver segments II, III, IV were harvested from 6 donors, 2 donors gave segments V, VI, VII, and VIII. After preliminary donor selection volumetric assessment of liver segments by computed tomography and arteriography was performed to visualize the cenac trunk and superior mesenteric artery. None of the donors died. No complications were observed during the operation. Only one case, a bile collection, was observed after surgery. We treated this patient with a satisfactory result by sonography-guided drainage. We observed temporary elevation of bilirubin and transaminase levels and a decrease in prothrombin index value. Blood transfusion was not necessary during any of the procedures. Mean hospitalization time after the surgery was 9.4 days. Mean graft weight/recipient weight ratio was 2.54%. The risk of the harvesting liver fragment from a living-related adult donor seems to be minimal.


Subject(s)
Hepatectomy/methods , Living Donors , Tissue and Organ Harvesting/methods , Body Weight , Drainage , Family , Hepatectomy/ethics , Humans , Length of Stay , Liver Transplantation/physiology , Mesenteric Artery, Superior/surgery , Organ Size , Tissue and Organ Harvesting/ethics , Tomography, X-Ray Computed
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