Search

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications., (© 2022 The Ecological Society of America.)

This article was migrated. The article was marked as recommended. The idea of incorporating an interdisciplinary field about the Human Condition of the patient and its intrinsic dignity, under the title of Medical Humanities or simply Humanities into the core curriculum of medical education seems reasonable. We hope it may become a reality as remedy for the difficulties of the doctor-patient relationship in modern medicine, which is extremely technological., (Copyright: © 2018 Pera C and Pera M.)

Purpose: To evaluate the effect of different maintenance recall intervals in patients with chronic periodontitis treated by full-mouth ultrasonic debridement., Materials and Methods: Twenty-eight patients participated in the study and were divided into two groups: group 1 (n = 14) underwent full-mouth ultrasonic debridement followed by monthly supportive periodontal therapy; group 2 (n = 14) underwent full-mouth ultrasonic debridement followed by supportive periodontal therapy delivered at 3-month intervals. Plaque index (PI), bleeding on probing (BOP), pocket probing depth (PD), gingival recession (GR) and clinical attachment level (CAL) were evaluated at baseline and after 3 and 6 months., Results: Subjects in group 1 had statistically significantly lower PI scores than did subjects in group 2 at six months. However, no differences in BOP, PPD, GR and CAL were observed between groups at any of the time points evaluated. Nonetheless, while full-mouth BOP and PPD scores progressively decreased over time in group 1, the same parameters were significantly reduced at 3 months in group 2, but remained stable thereafter. The proportion of moderate and deep pockets decreased progressively over time in the group of monthly recalls, while the proportion of moderate to deep sites decreased significantly in group 2 only at 3 months; no additional reductions were seen at 6 months., Conclusion: Supportive periodontal therapy both at one- and three-month intervals promotes short-term stability of clinical improvements obtained after full-mouth ultrasonic debridement in patients with chronic periodontitis.

Objective: To evaluate the therapeutic potential of one-stage, full-mouth, ultrasonic debridement (FMUD) as a treatment for type 2 diabetic patients with generalized severe chronic periodontitis., Method and Materials: Sixteen patients diagnosed with generalized severe chronic periodontitis and type 2 diabetes mellitus were allocated to the diabetic group; another 15 subjects with periodontitis but without metabolic disorders were placed in the nondiabetic group. Both groups were treated using the FMUD protocol, a unique 45-minute session of ultrasonic debridement of all sites presenting periodontal disease. Patients were analyzed for the following parameters: plaque and bleeding indices, gingival recession, probing depth, and clinical attachment level. Further, diabetic subjects were assessed using fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) tests. Patients were evaluated at 3 and 6 months for all parameters. ANOVA and the Tukey test were used for data analysis (P < .05)., Results: Both groups showed improved periodontal health after treatment. There were no significant differences between the groups for any of the parameters assessed (P > .05). Diabetic subjects treated with FMUD had a clinical response similar to that of nondiabetic subjects at all pocket depths. No adverse effects or medical disturbances were observed in either group during treatment. FPG and HbA1c levels remained unaltered after treatment., Conclusion: Within the limitations of this study, FMUD promoted clinical improvements in patients with type 2 uncontrolled diabetes and generalized severe chronic periodontitis.

Background: This study evaluates the effect of triclosan/copolymer dentifrice on the 6-month clinical response of patients with generalized severe chronic periodontitis (GSCP) treated with one-stage, full-mouth ultrasonic debridement (FMUD)., Methods: Thirty patients diagnosed with GSCP (≥8 teeth presenting probing depth [PD] ≥5 mm and bleeding on probing [BOP]) were selected and randomly allocated to a control group (n = 15) subjected to FMUD and daily use of a placebo dentifrice or to a test group (n = 15) subjected to FMUD and daily use of a triclosan/copolymer dentifrice. Patients were analyzed for the following parameters: full-mouth plaque index (FMPI), full-mouth BOP score (FMBS), gingival recession, PD, and clinical attachment level (CAL). Patients were evaluated at 3 and 6 months by a calibrated and masked examiner., Results: Initially, the groups presented similar periodontal conditions, with no significant differences in any of the parameters evaluated (P >0.05). In both groups, improvements in all periodontal parameters (P <0.05) were seen at the completion of the experimental period. Additionally, the test group showed lower FMPI (3 months) and FMBS (3 and 6 months) than the control group (P <0.05). Moreover, the CAL gain was significantly greater in the test group, especially at initially deep pockets (PD ≤7 mm). Whereas in the control group the CAL gain in deep pockets was 2.7 ± 0.6 mm, in the test group the CAL gain was 3.6 ± 1.4 mm (P <0.05)., Conclusion: Within the limits of the present study, the use of triclosan/copolymer dentifrice promoted additional clinical benefits in the treatment of GSCP treated by one-stage FMUD.

Aim: To compare the adhesive potential, the mechanics implicated in adhesive failure, and the effect on the enamel of four brands of lingual brackets., Methods: One hundred sixty premolars and four types of commercially available lingual brackets (STB, ORG, Magic, and Stealth) were selected. Forty brackets per manufacturer were used, half bonded directly and half indirectly. Each of these bonding groups was further subdivided: 10 brackets were bonded without treatment, while the other 10 were sandblasted. Thus, a total of four groups were created for each type of bracket: (a) sandblasted and directly bonded, (b) sandblasted and indirectly bonded, (c) not sandblasted and directly bonded, and (d) not sandblasted and indirectly bonded. Immediately after bonding, each bracket was tested for adhesion strength, and each appliance was then examined via electron microscopy to calculate the ARI., Results: Statistical analysis showed a significant difference among the four bracket types; a general improvement in lingual appliance mechanical features provoked by sandblasting, albeit with some exceptions; and no significant effect of bonding method on the degree of bond strength. The ARI revealed that the most common area of adhesion crisis was at the adhesive-bracket interface., Conclusion: Overall, STB brackets performed better, and sandblasting proved to be an efficient way of improving the mechanical features of lingual brackets. Bonding technique, on the other hand, did not seem to exert a great influence on bonding success, and the bracket-adhesive interface was identified as the area most prone to failure.

The objective of this study was to test the hypothesis that cooperative learning strategies will help to increase nutrition knowledge of nurses and nursing assistants caring for the elderly in different institutional communities of the Basque Country, Spain. The target population was a sample of volunteers, 16 nurses and 28 nursing assistants. Training consisted of 12 nutrition education sessions using cooperative strategies conducted over a period of 3 consecutive weeks. The assessment instruments included two pretest and two posttest questionnaires with questions selected in multiple-choice format. The first questionnaire was about general knowledge of applied nutrition (0-88 point scale) and the second one on geriatric nutrition knowledge (0-18 point scale). Data were analyzed using SPSS vs. 11.0. The outcomes indicated a significant increase in general nutrition knowledge (difference between the pre- and post-test mean score: 14.5+/-10.1; P<0.001) and in geriatric nutrition knowledge for all participants (difference between the pre- and post-test mean score: 4.6+/-4.6; P<0.001). So the results indicated that cooperative learning strategies could improve the nutrition knowledge of nursing staff. Additionally, the results of this study provide direction to continuing nutrition education program planners regarding appropriate content and methodology for programs.

The triggering cause of keloid formation on a healing wound remains an enigma. In fact, the hypotheses put forward so far to explain this phenomenon seem inconsistent with some clinical features of the disease. The recently established bonds between infectious agents and some pathologies of unknown origin such as peptic ulcer disease, Kaposi's sarcoma or cervical cancer among others led us to consider a potential infectious origin for keloids. This paper presents an infection-based hypothesis (specifically, a viral hypothesis) intended to account for most of their clinical features. Essentially, we hypothesize that healthy individuals carrying a virus, whether known or unknown, associated to some adjuvant, and having some genetic susceptibility, may develop keloids during the scar maturation process in the following manner: the virus would make the bone marrow or lymphatic system its reservoir, residing there in a silent state, and reach the wound via two different mechanisms. The primary mechanism might use an internal circuit through which the viral genome would be transported from its myeloid reservoir to the wound via bone marrow or circulating fibrocytes chemotactically attracted to the damaged skin region. The secondary mechanism might involve an external circuit by which infecting virions via saliva would be shed in the wound directly (preferentially in the sternal or deltoid region) or indirectly (other satellite regions) via the hands or some fomites. A combination of both mechanisms might also be possible. Once in the wound, the virus would switch from a silent state to a latent state by effect of some chemical stimulus probably generated during the tissue repair process; in the new state, the transcription of some of the powerful viral proteins might cause thorough derailment of the normal repair process. As a result, keloid growth might depend both on individual susceptibility and on the viral load deposited into the wound; the greater the susceptibility and viral load were, the more markedly the keloid would develop and the more aggressive it would be.

Background and Objectives: Advanced ovarian cancer typically spreads in a diffuse intra-abdominal fashion. This characteristic suggests that combined radical surgery and intraperitoneal chemotherapy may be a useful treatment procedure. The purpose of this study was to review patients submitted to surgical debulking and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) and to evaluate the potential prognostic survival factors for advanced epithelial ovarian cancer in our center., Methods: A series of patients (N = 33) diagnosed of peritoneal carcinomatosis for epithelial ovarian cancer (stage III) from January 1997 to December 2004 submitted to radical surgery-peritonectomy and HIIC with paclitaxel was included in this study; 19 primary ovarian cancer and 14 recurrent ovarian cancer., Results: Cytoreduction R0 (P = 0.018) and negative lymph nodes (P = 0.005) were covariables for major prognostic survival. Patients with optimal cytoreduction R0 obtained survival rates of 63% at 5 years in recurrent ovarian cancer and 60% in primary ovarian cancer, 71% and 63%, respectively with associated subtotal infra-abdominal peritonectomy, and even better results if negative lymph nodes., Conclusions: Radical surgery-peritonectomy with HIIQ has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival, and prolonged disease-free interval in patients with peritoneal carcinomatosis so much for recurrent or primary ovarian cancer., ((c) 2006 Wiley-Liss, Inc.)

The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.

This paper describes the effort to deploy a Medical Data Management service on top of the EGEE grid infrastructure. The most widely accepted medical image standard, DICOM, was developed for fulfilling clinical practice. It is implemented in most medical image acquisition and analysis devices. The EGEE middleware is using the SRM standard for handling grid files. Our prototype is exposing an SRM compliant interface to the grid middleware, transforming on the fly SRM requests into DICOM transactions. The prototype ensures user identification, strict file access control and data protection through the use of relevant grid services. This Medical Data Manager is easing the access to medical databases needed for many medical data analysis applications deployed today. It offers a high level data management service, compatible with clinical practices, which encourages the migration of medical applications towards grid infrastructures. A limited scale testbed has been deployed as a proof of concept of this new service. The service is expected to be put into production with the next EGEE middleware generation.

Liver cirrhosis is a critical stage of chronic liver diseases that can produce liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative stress plays a key role in cell damage and fibrosis induced during liver cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on the development of parenchymal destruction and stellate cell activation in experimental liver cirrhosis. Melatonin was administered to rats with liver cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was assessed by serological analysis, as well as hematoxylin-eosin staining and the in situ apoptosis detection assay in liver sections. Oxidative stress was evaluated by lipoperoxide and reduced glutathione levels, and by the measurement of catalase and superoxide dismutase activities in liver and serum respectively. The activation of stellate cells was evaluated by alpha-smooth muscle actin expression in liver sections. Our results showed that TAA induced oxidative stress with extensive tissue damage and enhanced alpha-smooth muscle actin expression in liver. Melatonin prevented the oxidative stress-related changes associated with TAA toxicity. In conclusion, the study showed that melatonin prevents the tissue damage and fibrosis associated with TAA-induced liver cirrhosis in rats.

Prognosis after liver transplantation depends on a combination of recipient and donor variables. The purpose of this study is to define an allocation system of steatotic donor livers relative to recipient model for end-stage liver disease (MELD) score. We reviewed 500 consecutive OLT, computing the MELD score for each recipient. Fatty infiltration in grafts was categorized in no steatosis, 10-30%, 30-60% and > or = 60% steatosis. MELD score did not affect preservation injury and graft dysfunction, which were increased with fat content. Recipient and graft survivals lowered when increasing MELD score. Outcome in low-risk recipients (MELD < or = 9) was not altered with steatosis, except those with > or = 60%. Survival functions in moderate-risk recipients (MELD 10-19) were moderately affected with 10-30% steatosis and severely with those with >30. Exactly 30-60% steatotic grafts work poorly in high-risk recipients (MELD > or = 20), and very poorly with > or = 60% steatosis. Prognosis of candidates is optimally influenced when divergence of recipient-donor risks is presented.

Background: Troponin I concentrations are frequently elevated following percutaneous coronary intervention (PCI) even in procedures without complications and are considered, by some, as predictive of long-term morbidity and mortality. We assessed whether post-PCI troponin I concentrations bore any relationship to clinical, angiographic and in-laboratory minor adverse events indicative of myocardial injury and evaluated, in follow-up, whether these levels are useful as a predictive markers of adverse events., Methods: Patients (n=147) who were scheduled for PCI for stent placement were prospectively studied. In-laboratory events recorded were protracted chest pain, electrocardiographic changes, slow flows, dissections and lateral branch affectation. Troponin I and creatinine kinase MB fraction (CK-MB) mass were measured at baseline and post-procedure. Mean clinical follow-up was for 10.4+/-3.6 months., Results: During PCI, at least one adverse event occurred in 34% of patients and, in 38% of them, there was an elevation of troponin I as compared to 5.1% of those patients without any adverse event (relative risk=7.4; P<0.001). Elevation of troponin I concentrations occurred in 16.3% of all patients, 79.2% associated with an AE. CK-MB was elevated in 15.6% of patients. On multivariate analysis, protracted chest pain, lateral branch involvement and slow flow remained statistically significant in relation to post-procedure elevations of troponin I concentrations. Clinical follow-up showed a poorer prognosis in patients who had had elevated troponin I concentrations., Conclusions: In-laboratory adverse event predict elevated post-procedure troponin I concentrations which are associated with myocardial injury. These elevations, in turn, predict poorer medium-term clinical outcomes.

Human leukocyte antigen (HLA) class I genes present some of the most complex single nucleotide polymorphism (SNP) patterns in the human genome. HLA typing is therefore extremely challenging. In this article, we use the ligation detection reaction (LDR) combined with a universal array (UA) as a robust and efficient method to analyze SNPs within the HLA-A region that includes HLA-A alleles of interest for immunotherapy in tumor diseases. The LDR, combined with a UA platform, has been optimized for the detection of 27 alleles distributed within exons 2 and 3 of HLA-A. The assay involves the amplification by PCR of the HLA-A genomic region (1,900 bp), the cycled ligation reaction, followed by the capture of ligated products through hybridization onto a UA. Each slide was designed to allow the detection of up to eight samples in parallel. The PCR/LDR/UA HLA-A assay was evaluated by analyzing 62 individuals (31 homozygous and 31 heterozygous) previously typed by direct sequencing. We demonstrate that the microarray genotyping procedure described here is a robust and efficient method for unambiguous detection of HLA alleles. HLA genotyping by PCR/LDR/UA is in perfect agreement with typing obtained by direct sequencing. Our results clearly demonstrate that the combination of enzymatic processing (LDR) and a demultiplexing hybridization onto a UA is a robust tool for SNP discrimination within the highly polymorphic HLA region. We demonstrate the specificity and efficiency of such an approach, suggesting the feasibility of a PCR/LDR/UA low resolution HLA typing procedure., (Copyright 2004 Wiley-Liss, Inc.)

We present our results in the identification of polymorphic sites within the second exon of the human leukocyte antigen A (HLA-A) region using the DNA microarray technology. Allele specific detection was performed by polymerase chain reaction followed by ligase detection reaction (LDR) in combination with a universal array, a powerful method for high throughput DNA sequence analysis. By this approach we confirmed 32 human samples previously characterized by direct DNA sequencing, thus demonstrating the interest of this approach.

Purpose: The purpose of this study was to assess the accumulated effects of marginal donor quality factors on liver preservation injury (LPI)., Methods: The most recent 400 consecutive liver transplantations at our institution were reviewed. Marginal liver donor criteria included the following: older than 60 years, an intensive care unit stay under ventilatory support for more than 4 days, a cold ischemia time more than 14 hr, high inotropic drug use, prolonged hypotensive episodes for more than 1 hr and less than 60 mm Hg, a peak serum sodium more than 155 mEq/L, and high levels of bilirubin, alanine transferase, or amino transferase. The type of steatosis (macrovesicular or microvesicular) was quantified in four categories: no steatosis, mild (<30%), moderate (30-60%), and severe (> 60%). LPI was stratified histologically in four levels: no damage, mild, moderate, and severe injury. These variables were included in a logistic regression analysis for prediction of the probability of the appearance of LPI., Results: Five variables showed an independent influence on LPI: high inotropic drug use (odds ratio [OR]=1.56), donor age (OR=1.017 per year), moderate to severe macrovesicular steatosis (OR=3.63), cold ischemia time (OR=1,109 per hour), and prolonged stay in an intensive care unit (OR=1.79). Severe LPI was present in 32.7% of the grafts from donors without any factor of the model; in 46.8% from donors with one factor (P =0.09); in 66.2% from donors with two factors (P =0.006); and in 78.3% from donors with at last three factors (P =0.002) (global P=0.0001; chi2 =21.8)., Conclusions: LPI can be potentially predicted based on donor and graft conditions. Accumulation of factors is correlated with an increased effect on LPI.

The hypothesis was tested that amino acid substitutions in specific positions within human leukocyte antigen class I heavy chain would have different impacts on transplant-related mortality (TRM) in patients receiving transplanted bone marrow from unrelated donors. One hundred patients and their unrelated donors were typed by sequence-based typing for the human leukocyte antigen (HLA)-A, -B, and -C loci. All pairs were matched for DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 loci. Forty pairs were also matched at class I, and 60 pairs had one or more mismatches at class I loci. It was found that substitutions at positions 116 and 114 of class I heavy chain significantly increased the risk for TRM in univariate and bivariate Cox analyses. Conversely, no association between number of multiple mismatches or number of amino acid substitutions and TRM was seen when positions 116 and 114 were adjusted for. Variables predictive of TRM in multivariate Cox analysis were number of cells infused, diagnosis (chronic myeloid leukemia [CML] or non-CML), and amino acid substitution at position 116 or 152. The only variable predictive of severe acute graft-versus-host disease (GVHD) in multivariate Cox analysis was substitution at position 116. Actuarial risk for acute GVHD grade III-IV, TRM, and relapse in pairs with substitutions at position 116 (n = 37) compared to other pairs (n = 63) was, respectively, 36% versus 14% (P =.01), 59% versus 28% (P =.001), and 25% versus 31% (P =.4). In conclusion these data suggest that substitutions at position 116 of class I heavy chain increase the risk for acute GVHD and TRM in patients who receive transplanted bone marrow from unrelated donors.

Objective: To investigate myocardial function in patients with obstructive jaundice before and after internal biliary drainage., Summary Background Data: Increased plasma levels of atrial natriuretic peptide (ANP) have been found in patients with biliary obstruction., Methods: Thirteen patients with newly diagnosed obstructive jaundice and no previous heart, lung, or renal disease were studied using a Swan-Ganz catheter. Hemodynamic measurements were taken before and 4 days after internal biliary drainage. Levels of ANP and brain natriuretic peptide (BNP) were obtained and liver function tests were also determined., Results: Plasma levels of ANP and BNP were increased twofold to fourfold in the basal state and declined after biliary drainage. Independent variables predicting left ventricular systolic work were total bilirubin concentrations, duration of jaundice, and BNP. In addition, bilirubin concentrations correlated with pulmonary vascular resistance, mean arterial pulmonary pressure, and right ventricular systolic work. Internal biliary drainage resulted in an improvement in left ventricular systolic work. A correlation was found between decreasing ANP concentrations and increasing cardiac output., Conclusions: Increased plasma levels of natriuretic peptides in patients with obstructive jaundice may reflect a subclinical myocardial dysfunction correlating with the degree of jaundice. After internal biliary drainage, there is a measurable improvement of cardiac function.

Background: A preoperative tissue diagnosis of pancreatic cancer is desirable but difficult to obtain., Methods: Pancreatic brush cytology, salvage cytology, and collection of pancreatic juice were attempted prospectively during ERCP in 34 patients with pancreatic cancer and 11 with chronic pancreatitis. K-ras-2 codon 12 was analyzed for presence and type of point mutations., Results: Brush cytology coupled with salvage cytology had a sensitivity of 74%. The addition of cytologic analysis of pancreatic juice did not substantially improve sensitivity (76%). K-ras-2 was mutated in both cancer (87%) and pancreatitis (40%). The specificity for cytology was 100% and for K-ras-2 mutations 60%. Combining cytology with mutation analysis increased sensitivity to 93% but reduced the positive predictive value. The negative predictive value never exceeded 75%. None of the patients with chronic pancreatitis had cancer develop (median follow-up 60 months)., Conclusions: Pancreatic ductal brushing with salvage cytology is useful in the diagnosis of cancer, whereas cytologic analysis of pancreatic juice can be abandoned. At present, K-ras-2 mutation is not useful for differentiating pancreatic cancer from chronic pancreatitis or the identification of patients with chronic pancreatitis at risk for malignant transformation.

The aims of the present study were first to compare the effects of melatonin and vitamin E on the cholestasis syndrome and their protective effect on liver injury, and second, to evaluate the activity of antioxidant enzymes after treatment with these antioxidant drugs. Cholestasis was achieved in adult male Wistar rats by double ligature and section of the extra-hepatic biliary duct. Hepatic and plasma oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and reduced glutathione (GSH) in plasma and homogenates of hepatic tissue. Serum bilirubin, alkaline phosphatase (AP), and gamma-glutamyl-transpeptidase (GGT) were used to evaluate the severity of cholestasis, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Both vitamin E and melatonin were administrated 1 day before and 7 days after bile duct ligation. Acute ligation of the bile duct was accompanied by a significant increased in MDA and a decrease in GSH levels in both plasma and liver, as well as a significant reduction in antioxidant enzymes activities. The overall analysis of both treatments showed that melatonin (500 microg/kg daily) offered significantly better protection against cholestasis and a superior protective effect on hepatic injury than did vitamin E (15 mg/kg daily). Although vitamin E treatment resulted in a reduction of parameters of oxidative stress, the results were significantly better after a much lower daily dose of melatonin. Moreover, melatonin treatment was associated with a significant recovery of antioxidative enzymes. In conclusion, the present paper demonstrates a correlation between the intensity of biliary tract obstruction and increased free radical generation, as well as a direct correlation between the level of oxidative stress and the biochemical markers of liver injury. Melatonin (at a much lower dose than vitamin E) was much more efficient than vitamin E in reducing the negative parameters of cholestasis, the degree of oxidative stress and provided a significantly greater hepatoprotective effect against the liver injury secondary to the acute ligation of the biliary duct.

The identification of ricin toxin A-chain (RTA) epitopes and the molecular context in which they are recognized will allow strategies to be devised that prevent/suppress an anti-RTA immune response in patients treated with RTA-based immunotoxins. RTA-specific human T-cell lines and T-cell clones were produced by in vitro priming of PBMC. The T-cell clones used a limited set of Vbeta chains (Vbeta1, Vbeta2 and Vbeta8) to recognize RTA epitopes. The use of RTA deletion mutants demonstrated that T-cell lines and T-cell clones from three out of four donors responded to RTA epitopes within the domain D124-Q223, whereas one donor recognized the region I1-D124. The response to RTA peptides of T-cell lines and T-cell clones from two donors allowed the identification of immunogenic segments (D124-G140 and L161-T190) recognized in the context of different HLA-DRB1 alleles (HLA-DRB1*0801, and HLA-DRB1*11011 and B1*03011, respectively). The response to L161-T190 was investigated in greater detail. We found that the HLA-DRB1*03011 allele presents a minimal epitope represented by the sequence I175-Y183 of RTA, whereas the HLA-DRB1*11011 allele presents the minimal epitope M174-I184. RTA peptides and an I175A RTA point mutant allowed us to identify I175 as a crucial residue for the epitope(s) recognized by the two HLA-DRB1 alleles. Failure of T-cell clones to recognize ribosome inactivating proteins (RIPs) showing sequences similar but not identical to RTA further confirmed the role of I175 as a key residue for the epitope recognized in the context of HLA-DRB1*11011/03011 alleles.

Background: Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage., Study Design: Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage., Results: Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively)., Conclusions: Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.

Downregulation of HLA class I antigen expression has been reported in a significant proportion of primary breast carcinomas suggesting an escape mechanism from CTL mediated lysis leading to tumor dissemination and metastasis. We have previously reported the biochemical and immunohistochemical analysis of HLA total class I (W6/32 mAb), alpha-chain (Q1/28,TP25.99 mAbs) and beta(2)-microglobulin (Namb-1 mAb) subunits expression in 25 primary breast carcinomas. This study at protein level resulted in the observation of three different HLA class I expression patterns by both techniques: high, low, and absent downregulation patterns. To better characterize the HLA class I antigens downregulation we extended such analysis also at RNA level by RT-PCR using HLA-A, HLA-B, HLA-C, and beta(2)-microglobulin specific primers either in breast cancer or normal tissues derived from the same patient. None (100%) of the alpha-chain genes analyzed in patient tumor tissues showed significant reduction of expression. In 10 patients out of 25 (40%) the beta(2)-microglobulin gene showed complete loss of expression compared with the corresponding normal tissue counterpart, which showed a constitutive expression, whereas in 2 patients (12.5%) its expression was comparable with the normal counterpart. Sequence analysis at genomic level revealed no defects affecting beta(2)-microglobulin gene in those patients showing lack of expression. Also TAP1 and TAP2 genes expression were investigated in order to confirm or exclude involvement of the MHC class I molecules assembling machinery. The RT-PCR approach mainly confirmed our beta(2)-microglobulin biochemical analysis indicating that in breast cancer specimens it is possible to address the HLA class I gene downregulation as a phenomenon occurring at post-transcriptional level mainly affecting the beta(2)-microglobulin gene expression.

The liver transplantation unit from Córdoba, Spain, performed its first liver transplantation in 1989. Since then, 500 liver transplants have been performed in our institution up to November 2001. Our one-year recipient and graft survival rates are 77% and 76%, respectively. These recipient and graft survival rates are lower when compared with other results in the English language literature, and we present evidence here that the disparity results from 4 especially problematic aspects of our program: 1) the expanded use of donors, 2) the policy of allocation and prioritization in our institution, 3) the recurrence of primary liver disease and 4) de-novo neoplasms. Liver transplantation with unstable, hypernatremic donors or donors with a lengthy hospitalization and grafts with a prolonged cold ischemia time leads to diminished graft survival. When several marginal criteria accumulate in a donor, the results are even poorer. Consequently, the delayed non-function rate is especially high in our series. Attention to severe liver preservation injury as a primary mechanism of graft losses with marginal donors is given. The impact of the policy of the "sickest-first" principle in our center with a long waiting list seems to benefit urgent but not elective patients. Survival in elective patients is poorer than expected considering their clinical condition. The use of the sickest-first or urgency principle in our unit has not been efficient or equitable and may partially explain the poorer survival of our patients. Finally, the recurrence of primary disease and incidence of de-novo tumors after transplantation in our unit are similar those reported in English language literature.

Unlabelled: Homozygous familial hypercholesterolemia is an inherited metabolic disease that leads to decreased catabolism of low-density lipoprotein cholesterol. As a result coronary artery disease ensues by the first or second decade. Because most low-density lipoprotein receptors (50-75%) are located in the liver, liver transplantation has been introduced as a therapeutic option in this disorder., Aims: To report our experience in the treatment of homozygous familial hypercholesterolemia with ortothopic liver transplantation. We evaluated metabolic results and patient survival., Method: We treated two affected siblings. One of them received a sequenced heart-liver transplantation because of cardiac failure due to severe coronary disease., Results: The operative and postoperative course was favourable in both patients, with a decrease in cholesterol levels to normal values. Four years later both were alive and both had normal liver and heart functions. Neither patient needed cholesterol-lowering drugs, and the disease had not progressed., Conclusions: As shown by our results and those reported by others, liver transplantation is the treatment of choice for homozygous familial hypercholesterolemia until gene therapy becomes a viable option. Transplantation should be done before of cardiovascular complications develop.

The HLA-DRB3/B4/B5 sequence-based typing method developed in this study in combination with PCR-SSP, enabled us to identify a new DRB3*02 allele, that was named as DRB3*0209 (GenBank accession number AF148518). This name has been officially assigned by the WHO Nomenclature Committee in May 1999. The new allele differs from DRB3*0207 by one substitution in codon 51 from AGG to ACG and another in codon 60 from TAC to TCC, resulting in aminoacid changes from Arg-->Thr (codon 51) and from Tyr-->Ser (codon 60). The DRB3*0209 allele was discovered in two related North Italian families. The fact that it was present in an hemizygous situation in three members of the paternal family and in one member of the secondary related family enabled us to isolate and sequence the new DRB3 allele without cloning, to identify its association with the DRB1 locus, and to generate an Epstein-Barr virus (EBV)-transformed cell line, now present in our ECBR (European Collection for Biomedical Research) Cell Line Bank.

The aim of this work was to analyze whether the treatment of acute rejection of orthotopic liver transplants (OLT), either with corticoids or OKT3, has any effect on the levels of hepatitis B virus (HBV)-DNA and HBsAg in individuals which were originally affected by cirrhosis or fulminant hepatic failure as a result of B virus. We have found that HBV-DNA is present in macrophages, B cells and both CD4+ and CD8+ T cells after OLT in all cases studied. Interestingly, the levels of HBV-DNA and HBsAg in the serum analyzed were increased extremely rapidly in the patients treated with OKT3 in an acute rejection episode. However, the serum levels of HBV-DNA and HBsAg found were lower when the patients were treated with steroids, and were not found in non-treated patients. As the serum levels of HBV-DNA increase, the process of liver reinfection could be accelerated; therefore, these results may help to understand how OKT3 and corticoids immunosuppressive therapy may accelerate the reinfection of OLT by HBV. In conclusion, our results suggest that special care must be taken in the use of OKT3 in the treatment of acute liver rejection episodes in chronic or fulminant HBV transplanted patients.

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Althought it is a valuable tool for the identification of HLA alleles, sequence-based typing (SBT) presents difficulties when used to determine HLA-DQA1 and -DQB1 alleles. Specifically, some HLA-DQA1 alleles have a three-base deletion at codon 56 of exon 2 that interferes with the sequencing read. Moreover, the frequently used primers for HLA-DQB1 may co-amplify the HLA-DQB2 pseudogene. To overcome these problems, we amplified DQA1 exon 2 using five group-specific polymerase chain reactions (PCRs) which allowed separation of deleted from non-deleted DQA1 alleles. DQB1 exon 2 was amplified using two group-specific amplifications. To increase typing resolution, we also analyzed DQA1 exons 1, 3 and 4 and DQB1 exon 3 by PCR using sequence-specific primers (PCR-SSP) or SBT analysis. Using this method we found some important associations between DQA1 and DQB1 alleles: DQA1*05011 and DQB1*0201, DQA1*0505 and DQB1*03011, DQA1*01021 and DQB1*06, DQA1*01022 and DQB1*0502.

The aim of this study is to assess the effect of accumulation of marginal liver graft criteria on the immediate outcome of liver transplantation (LT). The last 325 consecutive LT performed in 293 patients were analyzed retrospectively with respect to donor acceptance criteria. A marginal liver score was elaborated on the basis of the following features: donor > 60 years, ICU stay > 4 days, cold ischemia times > 13 h, hypotensive episodes < 60 mmHg > 1 h, bilirubin > 2.0 mg/dl, ALT > 170 U/l, and AST > 140 U/l were scored with the value 1. The use of dopamine doses > 10 microg/kg per min and peak serum sodium > 155 mEq/l were labeled with value 2. The cut-off point at 6 months after LT revealed 42 deaths (14%), with 65 graft losses (20%) and 32 (9%) retransplants. Recipient survival was not affected by the combined effect of marginal criteria. However, recipients transplanted with marginal livers with score 3 or more showed a decrease in graft survival (log-rank 6.21; P = 0.045) and an increase in delayed non-function rate (10 out of 33 vs 4 out of 156; P = 0.03). The use of marginal liver donors with more than three risk factors must be carefully reviewed or refused because of the cumulative dysfunction of these grafts.