Conservative Treatment of Chronic Pancreatitis: A Practical Approach.

BACKGROUND: Chronic pancreatitis is a long-standing, inflammatory condition of the pancreas that leads to the progressive damage and loss of function of pancreatic parenchyma and to the development of possible locoregional and systemic medical complications. MATERIALS AND METHODS: In this review, we tried to summarize the current evidence on non-surgical treatment trying to suggest a practical approach to the management of chronic pancreatitis. RESULTS: Besides the unclear pathophysiological mechanism and a poorly unknown epidemiology, chronic pancreatitis is a complex syndrome that displays different possible challenges for physicians. Despite being traditionally considered as a benign disease, chronic pancreatitis encompasses 10-year mortality rates which are superior to the ones reported for some of the most common cancers. CONCLUSIONS: Chronic pancreatitis encompasses the management of multiple and complex medical co-morbidities that needs to be understood and addressed in a multidisciplinary specialist context.

Ecophysiological traits of highly mobile large marine predators inferred from nucleic acid derived indices.

Nucleic acid-derived indices such as RNA/DNA ratios have been successfully applied as ecophysiological indicators to assess growth, nutritional condition and health status in marine organisms given that they provide a measure of tissue protein reserves, which is known to vary depending on changes in the environment. Yet, the use of these biochemical indices on highly mobile large predators is scarce. In this study, we tested the applicability of using nucleic acids to provide insights on the ecophysiological traits of two marine mammal species (common bottlenose dolphins and short-finned pilot whales) and explored potential related factors (species, sex, season, and residency pattern), using skin tissue (obtained from biopsy darts) of apparently healthy and adult free-ranging animals. Significantly higher RNA/DNA ratios were obtained for bottlenose dolphins (p < 0.001), and for visitor pilot whales when compared with resident pilot whales (p = 0.001). No significant changes were found between the sexes. Based on the percentile approach, the samples contain individuals in a general good condition (as the 10th percentile is not closer to the mean than the 75th percentile), suggesting that the studied region of Macaronesia may be considered an adequate habitat. The combination of this effective tool with genetic sexing and photographic-identification provided an overall picture of ecosystem health, and although with some limitations and still being a first approach, it has the applicability to be used in other top predators and ecosystems.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Major postoperative complications after pancreatic resection for P-NETS are not associated to earlier recurrence.

BACKGROUND: The oncological impact of surgical complications has been studied in visceral and pancreatic cancer. AIM: To investigate the impact of complications on tumour recurrence after resections for pancreatic neuroendocrine tumours. METHODS: We have retrospectively analysed 105 consecutive resections performed at the Royal Free London Hospital from 1998 to 2014, and studied the long-term outcome of nil-minor (<3) versus major (≥3) Clavien-Dindo complications (CD) on disease-free (DFS) and overall survival (OS). RESULTS: The series accounted for 41 (39%) pancreaticoduodenectomies, two (1.9%) central, 48 (45.7%) distal pancreatectomies, eight (7.6%) enucleations, four (3.8%) total pancreatectomies. Sixteen (15.2%) were extended to adjacent organs, 13 (12.3%) to minor liver resections. Postoperative complications presented in 43 (40.1%) patients; CD grade 1 or 2 in 23 (21.9%), grades ≥3 in 20 (19%). Among 25 (23.8%) pancreatic fistulas, 14 (13.3%) were grades B or C. Thirty-four (32.4%) patients developed exocrine, and 31 (29.5%) endocrine insufficiency. Seven patients died during a median 27 (0-175) months follow up. Thirty-day mortality was 0.9%. OS was 94.1% at 5 years. Thirty tumours recurred within 11.7 (0.8-141.5) months. DFS was 44% at 5 years. At univariate analysis, high-grade complications were not associated with shorter DFS (p = 0.744). At multivariate analysis, no parameter was independent predictor for DFS or OS. The comparison of nil-minor versus major complications showed no DFS difference (p = 0.253). CONCLUSION: From our series, major complications after P-NETs resection are not associated to different disease recurrence; hence do not require different follow up or adjuvant regimens.

Reproductive phenology of Mauritia flexuosa L. (Arecaceae) in a coastal restinga environment in northeastern Brazil / Fenologia reprodutiva de Mauritia flexuosa L. (Arecaceae) em ambiente de Restinga no Nordeste do Brasil

Abstract The buriti, Mauritia flexuosa, is the most common palm in Brazil, where it has considerable ecological and economic importance. However, few data are available on the phenology of the species, mainly in coastal restinga ecosystems. The present study monitored the reproductive phenology of M. flexuosa in the restinga of Barreirinhas, in the Brazilian Northeast, and investigated the relationship between phenophases and climatic variables. The presence/absence of flowers and fruits was recorded monthly in 25 individuals of each sex between August, 2009, and October, 2012. There was no difference in the phenology of male and female specimens, with flowering and fruiting occurring exclusively in the dry season. We believe that the specific abiotic characteristics of the study environment, such as the intense sunlight and availability of water in the soil, contribute to the reproductive success of M. flexuosa in the dry season, with consequent germination and establishment of seedlings occurring during the subsequent rainy season.

Resumo Popularmente conhecido como buriti, Mauritia flexuosa é a palmeira mais abundante no Brasil, com grande importância ecológica e econômica, porém ainda são poucos os estudos sobre a sua fenologia, não existindo nenhum em ambiente de Restinga. O presente trabalho teve como objetivo estudar a fenologia reprodutiva de M. flexuosa na Restinga de Barreirinhas, no Nordeste do Brasil, verificando como as fenofases se correlacionam com os fatores climáticos. Foram acompanhados mensalmente 25 indivíduos de cada sexo, de agosto/2009 a outubro/2012, verificando a presença/ausência de floração e frutificação. Não houve diferença no padrão fenológico entre indivíduos femininos e masculinos de M. flexuosa, com floração e queda dos frutos exclusivamente na estação seca. Acreditamos que as características abióticas específicas do ambiente estudado, como a forte incidência solar e a disponibilidade de água no solo, contribuíram para o sucesso reprodutivo de M. flexuosa na estação seca, com consequente germinação e estabelecimento de plântulas no período chuvoso.

The influence of Ouabain on human dendritic cells maturation.

Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were stimulated with TNF-α for 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.

Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate.

OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept. METHODS: In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [∼10 mg/kg] on day 1) or IV abatacept (∼10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed. RESULTS: Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept-treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept-treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval -4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept-treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept-treated group and 65.2% and 4.9%, respectively, in the IV abatacept-treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)-treated patients (2.6%) and 18 IV abatacept (SC placebo)-treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept-treated patients and 2.3% of IV abatacept-treated patients. CONCLUSION: SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.

mCD14 expression in human monocytes is downregulated by ouabain via transactivation of epithelial growth factor receptor and activation of p38 mitogen-activated protein kinase.

BACKGROUND AND AIMS: The steroid ouabain is found in plasma and in many mammalian tissues, and is now considered as a hormone. In the immune system, ouabain regulates a number of lymphocyte functions, but little is known about its effects on monocyte function. Monocytes are important for adequate immune responses. The aim of this work was to analyze the effect of ouabain on mCD14 expression, a surface molecule involved in the response against Gram-negative bacteria and phagocytosis. METHODS: Human peripheral blood mononuclear cells obtained from healthy donors were separated by density gradient centrifugation. Monocytes were separated by adherence and treated for 24 h with 100 nM ouabain. mCD14, CD1a and P-p38 expression was analyzed by flow cytometry. Inhibitors of cell-signaling pathways, i.e. SB202190, reduced glutathione, rottlerin, tyrphostin A23, genistein, chelerythrine chloride, PD98059, PP1 and Ly 294002, were used concomitantly with ouabain to observe their effect on mCD14 expression. RESULTS: Ouabain induced a significant decrease in mCD14 expression. This feature was not related to receptor endocytosis or cell death. Furthermore, mCD14 downregulation did not reflect a shift in differentiation into dendritic cells because this hormone failed to induce CD1a expression. Amongst several inhibitors of cell-signaling pathways triggered by ouabain, only epidermal growth factor receptor (EGFR) and p38 mitogen-activated protein kinase (MAPK) inhibitors (tyrphostin A23 and SB202109) significantly reverted the effect of ouabain on mCD14 expression. Accordingly, the levels of P-p38 were increased on monocytes after ouabain treatment. However, incubation with epidermal growth factor did not alter mCD14 expression. CONCLUSION: These findings suggest that ouabain downregulates mCD14 expression on monocytes through EGFR transactivation and p38 MAPK activation.

Evaluation of research products released during a national project funded by the Italian Ministry of Health.

Evaluation of research products released during activities that have received public funds should be a mandatory practice. In this study, we evaluated the research products released during the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project), funded by the Italian Ministry of Health. The SITF Project prefigured the participation of Italian transplantation centers with more advanced experience in the field of liver transplantation. The research products released during the SITF Project were evaluated according to Guidelines for Research Evaluation of the Committee for Evaluation of Research (CIVR) from the Italian Ministry of Education, University and Research. Thus, we considered as the research products released during the SITF Project the number of articles published in English language in peer-reviewed scientific journals by each operative unit (OU), as returned by PubMed. The articles were included on the basis of relationship with the research lines of the SITF Project and availability of the impact factor (IF) calculated by Thomson Scientific for each journal. Following these criteria, 62 research products were released during the executive phase of the SITF Project (January 1, 2004-December 31, 2005). All research products were original articles, with no reviews or letters. The articles were published in 10 different scientific journals (mean IF, 2.64+/-1.74). Spearman's rank test found a weak negative correlation between journal IF and number of published articles (r= -.2919; P= .413). Although the OU involved in the coordination of the SITF Project released a relatively high number of articles (n=8; IF, 0.923+/-0.352), several other OUs obtained better results for number of articles (9-11) and/or IF (3.071+/-2.248 or 2.959+/-1.779). In projects that benefit from public funds, the potential negative impact of coordination activities to scientific production should be adequately considered.

Prioritizing surgical waiting lists.

RATIONALE, AIMS AND OBJECTIVES: This paper deals with the problem of surgical waiting lists and is aimed, in particular, at comparing two different prioritization approaches: (1) the clinical assessment of treatment urgency aimed at categorizing patients into urgency-related groups (URGs) with a given recommended maximum waiting time for treatment; and (2) the implementation of an original prioritization scoring algorithm aimed at determining the relative priority of each patient in the waiting list and the corresponding order of admission. METHODS: A modelling exercise based on a cohort of 236 patients enrolled on the waiting list of a surgical department in an Italian public university hospital, from 1 January to 30 June 2004, is presented. The comparison is based on a measure called need-adjusted-waiting-days, which allows to take into proper account both urgency and priority. RESULTS: The results show that both methods should be implemented simultaneously for increasing the department's performance in terms of both efficiency--outcome gained from a given amount of resources--and equity--how patients are admitted according to their need. CONCLUSIONS: Waiting list prioritization should not be limited to classifying patients into URGs, but to using a scoring system as well, in order to schedule patient admissions in an explicit and transparent way.

Cytosolic glutathione peroxidase from liver of pacu (Piaractus mesopotamicus), a hypoxia-tolerant fish of the Pantanal.

Pacu (Piaractus mesopotamicus Holmberg, 1887, Characiformes) dwells in waters of Pantanal, in which it has adapted for alternate concentrations of dissolved oxygen. Intracellular antioxidant protection should be vital for such an adaptation. Accordingly, we found that cytosol from liver of pacu has the highest antioxidant glutathione peroxidase activity so far reported for fish and murine species. To clarify whether this activity was due to a selenium independent glutathione S-transferase or to a glutathione peroxidase, we purified it and studied its kinetics. The substrates cumene hydroperoxide and hydrogen peroxide were promptly reduced by the enzyme, but peroxidized phosphatidylcholine had to undergo previous fatty acid removal with phospholipase A(2). Augmenting concentrations (from 2 to 6 mM) of reduced glutathione activated the pure enzyme. Curves of velocity versus different micromolar concentrations of hydrogen peroxide in the presence of 2, 4 or 8 mM reduced glutathione indicated that at least 2.5 mM reduced glutathione should be available in vivo for an efficient continuous destruction of micromolar concentrations of hydrogen peroxide by this peroxidase. Molecular exclusion HPLC and SDS-polyacrylamide gel electrophoresis indicated that the purified peroxidase is a homotetramer. Data from internal sequences showed selenocysteine in its primary structure and that the enzyme was a homologue of the type-1 glutathione peroxidase found in rat, bull, trout, flounder and zebra fish. Altogether, our data establish that in liver cells of pacu, a hypoxia-tolerant fish from South America, there are high levels of a cytosolic GPX-1 capable of quenching hydrogen peroxide and fatty acid peroxides, providing an effective antioxidant action.

Vanadate-induced cell death is dissociated from H2O2 generation.

Vanadium is an environmentally toxic metal with peculiar and sometimes contradictory cellular effects. It is insulin-mimetic, it can either stimulate cell growth or induce cell death, and it has both mutagenic and antineoplastic properties. However, the mechanisms involved in those effects are poorly understood. Several studies suggest that H(2)O(2) is involved in vanadate-induced cell death, but it is not known whether cellular sensitivity to vanadate is indeed related to H(2)O(2) generation. In the present study, the sensitivity of four cell lines from different origins (K562, K562-Lucena 1, MDCK, and Ma104) to vanadate and H(2)O(2) was evaluated and the production of H(2)O(2) by vanadate was analyzed by flow cytometry. We show that cell lines very resistant to H(2)O(2) (K562, K562-Lucena 1, and Ma104 cells) are much more sensitive to vanadate than MDCK, a cell line relatively susceptible to H(2)O(2), suggesting that vanadate-induced cytotoxicity is not directly related to H(2)O(2) responsiveness. In accordance, vanadate concentrations that reduced cellular viability to approximately 60-70% of the control (10 mumol/L) did not induce H(2)O(2) formation. A second hypothesis, that peroxovanadium (PV) compounds, produced once vanadate enters into the cells, are responsible for the cytotoxicity, was only partially confirmed because MDCK cells were resistant to both vanadate and PV compounds (10 micromol/L each). Therefore, our results suggest that vanadate toxicity occurs by two distinct pathways, one dependent on and one independent of H(2)O(2) production.

Modulation of multidrug resistance protein (MRP1/ABCC1) expression: a novel physiological role for ouabain.

Besides being a (Na(+),K(+))-ATPase inhibitor, high doses of the hormone ouabain have also been reported to modulate both the expression and activity of proteins belonging to the ATP binding cassette family of transporters, such as ABCC7 (CFTR), ABCB1 (P-glycoprotein), and ABCC1 (MRP1). Although these proteins are present in the kidney, only ABCB1 has a putative physiological role in this organ, secreting endobiotics and xenobiotics. In the present work, we studied the relationship between ouabain and ABCC1 expression and function, aiming to establish a physiological role for ouabain. It was observed that prolonged (24 h) but not short (30 min) incubation with 1 nmol/L or higher ouabain concentrations decreased the expression of ABCC1 protein and induced its mRNA expression. This decrease was rapidly reversible, reaching control levels after incubation of cells in ouabain-free medium for 3 h, denoting a hormonal action. Moreover, concentrations equal or higher than 100 nmol/L ouabain also induced impairment of ABCC1 activity, increasing the accumulation of carboxyfluorescein diacetate, an ABCC1 fluorescent substrate. Because ouabain is now accepted as an endogenous hormone, our results suggest that ABCC1 is regulated by hormones related to body volume control, which may have implications for the treatment of hypertensive cancer patients. Moreover, providing ABCC1 is expressed in several other tissues, such as brain, testis, and the immune system, and is related to the transport of glutathione, it is possible that ouabain release may control a number of functions within these organs and tissues by modulating both the expression and the activity of ABCC1.

Efeito de duas tecnicas de alongamento muscular dos isquiotibiais na amplitude de extensao ativa do joelho e no pico de torque / Effect of two hamstring muscle stretching techniques on the range of motion of active knee extension and on peak torque

Os exercicios de alongamento sao amplamente utilizados na fisioterapia. No entanto, seus reais beneficios nao estao compoletamente esclarecidos. Objetivo: o proposito deste estudo foi investigar o efeito do alongamento dos isquiotibiais na amplitude de movimento de extensao ativa do joelho e no pico de torque desse grupo muscular. Metodo: participaram da pesquisa 14 individuos de ambos os sexos, com idade media de 222,92+-0,9 anos, sedentarios, os quais foram submetidos a 5 ciclos de alongamentos diarios, com 30, segundos cada, por um periodo de tres semanas. Foram utilizados dois protocolos de alongamento: o primeiro grupo (G1), representado pelos membros inferiores esquerdos, realizou manobras passivas/estaticas. para a avalicao da ADM utilizou-se um goniometro universal e para o pico de torque, um dinamometro isocinetico da marca Cybex - 6000. Analise estatistica foi realizada por meio dos testes ANOVA e post-hoc Dunn`s, considerando o nivel de significancaia (<-5 por cento). Resultados: observou-se o aumento na ADM em ambos os grupos: 149+-14º para 162+-11º(p<0,01) para o G1 e de 148+-14º para 162+-11º(p<0,01) para o G2. No entanto nao houve difrenca entre os grupos. Ocorreu aumento sgnificativo no torque dos membros do grupo G1 apos a aplicacao da tecnica de alongamento do tipo FNP a 60º/s(de 89+-36Nm para 96+-40Nm) e a 240º/s(de 59+-24Nm para 68+-27Nm) - p<0,01. Por outro lado, nao houve diferenca estatisticamente significativa no torque dos membros do G2. Conclusoes: Esses dados sugerem que o programa de alongamento muscular utilizando a tecnica contrair-relaxar pode influenciar na ADM e no torque muscular. Entretanto, a tecnica de alongamento estatico/passivo produziu ganhos apenas na ADM

Orthotopic liver transplantation in a young adult (33 years old) using an 84-year-old donor.

Shortage of liver donors and the increasing number of patients on the waiting list for liver transplantation have led to a widening of the definition of liver donor suitability. Although the age limit for liver donors is controversial, current opinion is towards using liver allografts from donors older than 60 years. However, to date only a few cases that showed a good performance of liver graft by donors older than 60 years have been described. In this case report, orthotopic liver transplantation in a 33-year-old patient who received a graft from an 84-year-old donor is presented. A careful evaluation of the conventional donor-related risk factors (hemodynamics, hepatic function and histologic features) was carried out. Moreover, free radical scavenger glutathione was measured before cold ischemia and at the time of reperfusion in hepatic biopsies. After a 1-year follow-up, the recipient exhibits good general conditions and normal liver function values.

Blockade of adenosine receptors with aminophylline limits ischemic preconditioning in human beings.

BACKGROUND: Ischemic preconditioning is characterized by the limitation of infarct size or ischemic signs after one or more brief episodes of ischemia, a process that probably involves stimulation of adenosine receptors. One human model of ischemic preconditioning is repetitive occlusion of a coronary artery during angioplasty. By using this method of inducing ischemia, we tested the hypothesis that blockade of adenosine receptors with aminophylline would abolish ischemic preconditioning in human beings. METHODS: Twenty-six patients undergoing angioplasty were randomly assigned to receive either aminophylline (6 mg/kg IV) or placebo before repetitive coronary occlusion (two 2-minute occlusions separated by 5 minutes). ST-segment changes on the surface electrocardiogram were used as a measure of myocardial ischemia. Serum theophylline levels and the conduction response to an intravenous bolus of adenosine were used to assess the efficacy of adenosine receptor blockade. RESULTS: Repetitive coronary occlusion resulted in a reduction in ST-segment shift in 9 of 13 patients given placebo. In contrast, 9 of 13 patients receiving aminophylline had an increase in ST-segment shift on the second occlusion (P =.002). Patients receiving aminophylline (mean serum theophylline level of 8.38 +/- 0.45 mg/dL) did not have significant conduction block with intravenous adenosine. CONCLUSIONS: Repetitive coronary occlusion reduces the signs of ischemia in human beings, a process limited by blockade of adenosine receptors.

BJ46a, a snake venom metalloproteinase inhibitor. Isolation, characterization, cloning and insights into its mechanism of action.

Fractionation of the serum of the venomous snake Bothrops jararaca with (NH4)2SO4, followed by phenyl-Sepharose and C4-reversed phase chromatographies, resulted in the isolation of the anti-hemorrhagic factor BJ46a. BJ46a is a potent inhibitor of the SVMPs atrolysin C (class P-I) and jararhagin (P-III) proteolytic activities and B. jararaca venom hemorrhagic activity. The single-chain, acidic (pI 4.55) glycoprotein has a molecular mass of 46 101 atomic mass units determined by MALDI-TOF MS and 79 kDa by gel filtration and dynamic laser light scattering, suggesting a homodimeric structure. mRNA was isolated from the liver of one specimen and transcribed into cDNA. The cDNA pool was amplified by PCR, cloned into a specific vector and used to transform competent cells. Clones containing the complete coding sequence for BJ46a were isolated. The deduced protein sequence was in complete agreement with peptide sequences obtained by Edman degradation. BJ46a is a 322-amino-acid protein containing four putative N-glycosylation sites. It is homologous to the proteinase inhibitor HSF (member of the fetuin family, cystatin superfamily) isolated from the serum of the snake Trimeresurus flavoviridis, having 85% sequence identity. This is the first report of a complete cDNA sequence for an endogenous inhibitor of snake venom metalloproteinases (SVMPs). The sequence reveals that the only proteolytic processing required to obtain the mature protein is the cleavage of the signal peptide. Gel filtration analyses of the inhibitory complexes indicate that inhibition occurs by formation of a noncovalent complex between BJ46a and the proteinases at their metalloproteinase domains. Furthermore, the data shows that the stoichiometry involved in this interaction is of one inhibitor monomer to two enzyme molecules, suggesting an interesting mechanism of metalloproteinase inhibition.

A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS).

OBJECTIVE: To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). METHODS: Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. RESULTS: We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73-0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43-0.83). CONCLUSION: The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

The evolution of particles in the plume from a large coal-fired boiler with flue gas desulfurization.

Airborne measurements were made of gaseous and particulate species in the plume of a large coal-fired power plant after flue gas desulfurization (FGD) controls were installed. These measurements were compared with measurements made before the controls were installed. The light scattering and number and volume distributions of plume excess particles were determined by nephelometry and optical particle counting techniques. The plume impact based on optical techniques was much lower than that observed in earlier measurements. Indeed, plume excess volumes as a function of particle size were of the same magnitude as the variability of the background volume distribution. In situ excess plume scattering actually decreased with distance from the source, in contrast to pre-FGD conditions. The upper limit for the dry rate of SO2-to-SO4(2-) conversion was estimated from plume excess volume measurements to be about 4% hr-1. This is slightly greater than the upper limit, 3.5% hr-1, estimated by earlier researchers, but the same as that estimated using the present technique with the earlier data. The cross-plume profile of volume suggests SO2-to-SO4(2-) conversion is highest at the plume edges. The greatest benefit of SO2 reduction on plume excess volume and visibility appears to occur far down-wind of the source.