Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Effects of feed restriction during pregnancy on maternal reproductive outcome, foetal hepatic IGF gene expression and offspring performance in the rabbit.

Primiparous female rabbits have high nutritional requirements and, while it is recommended that they are subjected to an extensive reproductive rhythm, this could lead to overweight, affecting reproductive outcomes. We hypothesised that restricting food intake during the less energetic period of gestation could improve reproductive outcome without impairing offspring viability. This study compares two groups of primiparous rabbit does in an extensive reproductive programme, one in which feed was restricted from Day 0 to Day 21 of gestation (R021), and another in which does were fed ad libitum (control) throughout pregnancy. The mother and offspring variables compared were (1) mother reproductive outcomes at the time points pre-implantation (Day 3 postartificial insemination [AI]), preterm (Day 28 post-AI) and birth; and (2) the prenatal offspring characteristic IGF system gene expression in foetal liver, liver fibrosis and foetus sex ratio, and postnatal factor viability and growth at birth, and survival and growth until weaning. Feed restriction did not affect the conception rate, embryo survival, or the number of morulae and blastocysts recovered at Day 3 post-AI. Preterm placenta size and efficiency were similar in the two groups. However, both implantation rate (P < 0.001) and the number of foetuses (P = 0.05) were higher in the R021 mothers than controls, while there was no difference in foetal viability. Foetal size and weight, the weights of most organs, organ weight/BW ratios and sex ratio were unaffected by feed restriction; these variables were only affected by uterine position (P < 0.05). Conversely, in the R021 does, foetal liver IGBP1 and IGF2 gene expression were dysregulated despite no liver fibrosis and a normal liver structure. No effects of restricted feed intake were produced on maternal fertility, prolificacy, or offspring birth weight, but control females weaned more kits. Litter weight and mortality rate during the lactation period were also unaffected. In conclusion, pre-implantation events and foetal development were unaffected by feed restriction. While some genes of the foetal hepatic IGF system were dysregulated during pregnancy, liver morphology appeared normal, and the growth of foetuses and kits until weaning was unmodified. This strategy of feed restriction in extensive reproductive rhythms seems to have no significant adverse effects on dam reproductive outcome or offspring growth and viability until weaning.

Quantifying citrate-enhanced phosphate root uptake using microdialysis.

AIMS: Organic acid exudation by plant roots is thought to promote phosphate (P) solubilisation and bioavailability in soils with poorly available nutrients. Here we describe a new combined experimental (microdialysis) and modelling approach to quantify citrate-enhanced P desorption and its importance for root P uptake. METHODS: To mimic the rhizosphere, microdialysis probes were placed in soil and perfused with citrate solutions (0.1, 1.0 and 10 mM) and the amount of P recovered from soil used to quantify rhizosphere P availability. Parameters in a mathematical model describing probe P uptake, citrate exudation, P movement and citrate-enhanced desorption were fit to the experimental data. These parameters were used in a model of a root which exuded citrate and absorbed P. The importance of soil citrate-P mobilisation for root P uptake was then quantified using this model. RESULTS: A plant needs to exude citrate at a rate of 0.73 µmol cm-1 of root h-1 to see a significant increase in P absorption. Microdialysis probes with citrate in the perfusate were shown to absorb similar quantities of P to an exuding root. CONCLUSION: A single root exuding citrate at a typical rate (4.3 × 10-5 µmol m-1 of root h-1) did not contribute significantly to P uptake. Microdialysis probes show promise for measuring rhizosphere processes when calibration experiments and mathematical modelling are used to decouple microdialysis and rhizosphere mechanisms.

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes]. / Conducta terapéutica en la diabetes tipo 2. Cuanto más breve, mejor.

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

Role of nerve growth factor in the reproductive physiology of female rabbits: A review.

Rabbit does are reflex ovulators such that coitus is needed to release GnRH and elicit the LH surge that triggers the ovulation of mature oocytes. However, the mechanisms eliciting ovulation in this species remain unclear. One of the most promising recently discovered candidates with a role in female reproductive physiology is nerve growth factor beta (ß-NGF). This neurotrophin and its high-affinity receptor TrkA and low affinity receptor p75, is present in all compartments of the ovary, oviduct and uterus suggesting a physiologic role in ovarian folliculogenesis, steroidogenesis, ovulation, luteogenesis and embryo development. Besides, evidence exists that ß-NGF found in seminal plasma could exert a modulatory role in the female hypothalamus-pituitary-ovarian axis contributing to the adrenergic and cholinergic neuronal stimulus of GnRH neurons in an endocrine manner during natural mating. Probably, the paracrine and local roles of the neurotrophin in steroidogenesis and ovulation reinforce the neuroendocrine pathway that leads to ovulation. This review updates knowledge of the role of ß-NGF in rabbit reproduction, including its possible contribution to the mechanisms of action that induce ovulation, and discusses perspectives for the future applications of this neurotrophin on rabbit farms.

Cell fishing: A similarity based approach and machine learning strategy for multiple cell lines-compound sensitivity prediction.

The prediction of cell-lines sensitivity to a given set of compounds is a very important factor in the optimization of in-vitro assays. To date, the most common prediction strategies are based upon machine learning or other quantitative structure-activity relationships (QSAR) based approaches. In the present research, we propose and discuss a straightforward strategy not based on any learning modelling but exclusively relying upon the chemical similarity of a query compound to reference compounds with annotated activity against cell lines. We also compare the performance of the proposed method to machine learning predictions on the same problem. A curated database of compounds-cell lines associations derived from ChemBL version 22 was created for algorithm construction and cross-validation. Validation was done using 10-fold cross-validation and testing the models on new data obtained from ChemBL version 25. In terms of accuracy, both methods perform similarly with values around 0.65 across 750 cell lines in 10-fold cross-validation experiments. By combining both methods it is possible to achieve 66% of correct classification rate in more than 26000 newly reported interactions comprising 11000 new compounds. A Web Service implementing the described approaches (both similarity and machine learning based models) is freely available at: http://bioquimio.udla.edu.ec/cellfishing.

Validation of a novel integral disease index for evaluating the grade of activity in Mexican patients with ulcerative colitis: A prospective cohort study. / Validación de un nuevo índice integral de enfermedad para evaluar el grado de actividad en pacientes mexicanos con colitis ulcerosa: un estudio de cohorte prospectivo.

INTRODUCTION AND AIM: Ulcerative colitis is a chronic condition characterized by inflammation affecting the colon. To objectively and integrally measure disease activity in patients with ulcerative colitis and thus optimize pharmacologic treatment, a novel integral disease index was created that includes the clinical, biochemical, endoscopic, and histologic characteristics necessary for achieving that task. The aim of the present study was to validate the novel integral disease index in patients with ulcerative colitis. MATERIALS AND METHODS: A cohort study on a total of 222 patients with histologic confirmations of ulcerative colitis diagnosis was conducted. The variables included in the disease index were: number of bowel movements per day; values for hemoglobin, high-sensitivity C-reactive protein, and serum albumin; and endoscopic and histologic findings measured through the subscales of the Mayo and Riley scores, respectively. The data analysis was performed utilizing the STATA SE 11.1 statistics program. RESULTS: The correlation of the novel disease index was very good (r=0.817, p <.001 with the Truelove and Witts criteria and r=0.957, p <.0001 with the Mayo score, respectively). Good internal consistency was found with a Cronbach's alpha coefficient of 0.78 and an acceptable mean inter-item correlation (r=0.47, p <.05). The total efficacy of the novel index was 87.2% correctly classified patients, with an AUC according to the three scenarios described of 0.93, 0.92, and 0.96, respectively. CONCLUSIONS: The novel integral disease index (Yamamoto-Furusho Index) provides an integral view of disease activity in patients with ulcerative colitis and is useful for optimizing pharmacologic treatment.

Application of Bayesian statistics to estimate nitrous oxide emission factors of three nitrogen fertilisers on UK grasslands.

Trapezoidal integration by linear interpolation of data points is by far the most commonly used method of cumulative flux calculations of nitrous oxide (N2O) in studies that use flux chambers; however, this method is incapable of providing accurate uncertainty estimates. A Bayesian approach was used to calculate N2O emission factors (EFs) and their associated uncertainties from flux chamber measurements made after the application of nitrogen fertilisers, in the form of ammonium nitrate (AN), urea (Ur) and urea treated with Agrotain® urease inhibitor (UI) at four grassland sites in the UK. The comparison between the cumulative fluxes estimated using the Bayesian and linear interpolation methods were broadly similar (R2 = 0.79); however, the Bayesian method was capable of providing realistic uncertainties when a limited number of data points is available. The study reports mean EF values (and 95% confidence intervals) of 0.60 ±â€¯0.63, 0.29 ±â€¯0.22 and 0.26 ±â€¯0.17% of applied N emitted as N2O for the AN, Ur and UI treatments, respectively. There was no significant difference between N2O emissions from the Ur and UI treatments. In the case of the automatic chamber data collected at one site in this study, the data did not fit the log-normal model, implying that more complex models may be needed, particularly for measurement data with high temporal resolution.

[Prevalence and factors associated with preventable adverse drug events leading to hospital admission]. / Prevalencia y factores asociados a los acontecimientos adversos prevenibles por medicamentos que causan el ingreso hospitalario.

OBJECTIVE: To determine the prevalence of adverse drug events (ADEs) leading to hospital admission, and to assess those that were potentially preventable, identifying the drug classes involved, types of medication errors and the factors associated with the preventable ADEs. METHOD: An observational study, over a six-month period on ADEs that lead or contributed to hospital admissions, carried out in 6 medical units of a university hospital. RESULTS: A total of 259 ADEs were detected of which 159 (61.4%) were assessed to be potentially preventable. The overall prevalence of admissions directly due to ADEs was of 6.7% (177) and to preventable ADEs of 4.7% (125). In addition, 82 ADEs that contributed to hospital admission were detected. Risk factors for preventable ADEs were patient age of 65-74 (OR = 1.40) or = 75 years (OR = 2.70), self-medication (OR = 15.55), prescription in primary care (OR = 2,88) and the use of narrow therapeutic index drugs (OR = 2.40). The drug classes most frequently involved in preventable ADEs were NSAID and aspirin (32.5%), diuretics (15.3%), antihypertensives (9.1%) and digoxin (7.7%). Inadequate therapy monitoring (20.7%), prescription of an inappropriate drug (15.7%) or of an excessive dosage (12.0%), lack of preventive treatment (15.7%), non-adherence (10.6%) and inappropriate self-medication (10.1%) were the most commonly identified types of error. CONCLUSIONS: A high proportion (4.7%) of hospital admissions are caused by potentially preventable ADEs. Results obtained justified the need to adopt measures directed at improving surveillance and prescription quality, and educating patients in safe drug use, focusing especially on older patients and narrow therapeutic index drugs.

Nitric oxide production by mononuclear leukocytes in alcoholic cirrhosis.

Nitric oxide is now established as a biological mediator of clinical relevance. The present study investigated the production of nitric oxide by lympho-mononuclear leukocytes from alcoholic patients with either hepatitis or cirrhosis. The study included 42 patients, 12 without any liver disease and 30 alcoholic patients, 13 of whom had histologically confirmed cirrhosis and 17 alcoholic hepatitis. Cells were obtained from peripheral blood by density gradient and incubated in sterile conditions in RPMI 1640 for 6 h at 37 degrees C. Culture supernatants were assayed for nitrite concentration using the Griess reaction. Cells from cirrhotic but not from hepatopathic patients showed significantly higher nitrite production than controls (cirrhotic, 0.36 +/- 0.07; hepatopathic, 0.13 +/- 0.02; control: 0.25 +/- 0.05 nmol/10(6) cells/6 h). In cirrhotic patients L-Nitro-arginine methylester inhibited nitrite production (0.18 +/- 0.05). These data suggest that alcoholic cirrhotic but nonhepatopathic patients show an increased nitric oxide production by blood lymphomononuclear cells. This production could be involved in the systemic vasodilation in cirrhotic patients.

Occurrence of eight UV filters in beaches of Gran Canaria (Canary Islands). An approach to environmental risk assessment.

Due to the growing concern about human health effects of ultraviolet (UV) radiation, the use of UV filters has increased in recent decades. Unfortunately, some common UV filters are bioaccumulated in aquatic organisms and show a potential for estrogenic activity. The aim of the present study is to determine the presence of some UV filters in the coastal waters of six beaches around Gran Canaria Island as consequence of recreational seaside activities. Eight commonly used UV filters: benzophenone-3 (BP-3), octocrylene (OC), octyl-dimethyl-PABA (OD-PABA), ethylhexyl methoxy cinnamate (EHMC), homosalate (HMS), butyl methoxydibenzoyl methane (BMDBM), 4-methylbenzylidene camphor (4-MBC) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), were monitored and, with the exception of OD-PABA, all were detected in the samples collected. 99% of the samples showed some UV filters and concentration levels reached up to 3316.7 ng/L for BP-3. Environmental risk assessment (ERA) approach showed risk quotients (RQ) higher than 10, which means that there is a significant potential for adverse effects, for 4-MBC and EHMC for those samples with highest levels of UV filters.

Preoperative use of statins does not improve outcomes and development of acute renal failure after cardiac surgery. A propensity score analysis of ARIAM-Andalucía database.

BACKGROUND: Statin use prior to cardiac surgery has been reported to improve outcomes in the postoperative period because of other effects apart from decreasing lipid levels. Objective of the study was to analyse mortality and acute renal failure (ARF) during the cardiac surgery postoperative period in patients treated with or without statins. METHODS: This prospective cohort study comprised adult patients who underwent cardiac surgery at 11 institutions in the Andalusian community from March 2008 to July 2012 included in the ARIAM adult cardiac surgery project. We performed a first analysis in the whole cohort and in a second analysis statin users prior to surgery were pair matched with non-users according to their propensity score based on demographics, comorbidities, medication and surgical data. We analysed differences in outcomes, ARF, need for renal replacement therapy (RRT) and a composite end point with mortality or major morbidity in both groups. RESULTS: The study included 7276 patients, of whom 3749 were treated with statins. Overall, hospital mortality was 10.1%, 10.5% developed ARF and 2.5% required RRT. In the whole non-matched cohort, statins were associated with lower hospital mortality (OR 0.79; 95% CI, 0.67-0.93) and less ARF (OR 0.79; 95% CI, 0.68-0.93). However, after propensity score analysis in the matched cohort of 3056 patients (1528 in each group), statin use was not consistently associated with less ARF (OR 0.94; 95% CI, 0.74-1.19), hospital mortality (OR 0.83; 95% CI, 0.68-1.1) or composite outcome (OR 0.857; 95% CI, 0.723-1.015). CONCLUSION: Despite better outcomes for the statin users in the whole cohort, the matched analysis showed that statin use before cardiac surgery was not associated with a lower risk of ARF. Nor was presurgery statin use associated with lower hospital mortality.

[Localized tracheobronchial amyloidosis. The usefulness of computed tomography]. / Amiloidosis traqueobronquial localizada. Utilidad de la tomografía computarizada.

Tracheobronchial amyloidosis is the most common form of localized bronchopulmonary amyloidoses, although its diagnosis is rare in daily practice. We describe two new cases of localized tracheobronchial amyloidosis, one in the form of a single node and one diffuse. We discuss in particular the contribution of computed axial tomography, mainly for diagnosing the diffuse form, in which a finding of a thickened tracheobronchial wall and intraluminal nodes should lead to the suspicion of this entity. The treatment of choice in most cases is resection with an Nd-YAG laser.

[Absence of increase of cyclic adenosine monophosphate (cAMP) in the cerebrospinal fluid of febrile patients (author's transl)]. / Ausencia de elevación del adenosín monofosfato cíclico en el líquido cefalorraquídeo de enfermos febriles.

Recent studies point toward the importance of cyclic adenosine 3',5'-monophosphate (cAMP) in the genesis of fever. Experimental fever induction in animals using bacterial pyrogens is accompanied with an increase of nucleotid concentration in the cerebrospinal fluid up to duplicate normal basal values. This aspect, however, has not been studied in human pathology. The concentration of cAMP in the cerebrospinal fluid of 11 patients with fever higher than 38.5 degrees C was studied. there were no significant differences between values found in these patients (14.03 +/- 5.82 pM/ml) and those corresponding to normality (15.44 +/- 3.36 pM/ml). We think that these results did not refute the role of cAMP in the pathogenesis of fever; they are only laboratory findings in discordance to experimental results.

[Polymorphism of the IL1RN gene in Spanish patients with ulcerative colitis]. / Estudio de polimorfismos del gen IL1RN en pacientes españoles con colitis ulcerosa.

BACKGROUND: The etiology of the inflammatory bowel disease is unknown. Previous studies have shown an association between the allele 2 of IL1RN, the gene that encodes for the interleukin 1 receptor antagonist (IL-1ra), and the inflammatory bowel disease. PATIENTS AND METHODS: We have analyzed the incidence of the IL1RN alleles in 41 patients with ulcerative colitis and in 40 healthy subjects. RESULTS: Our results show the same allelic distribution between the subjects with ulcerative colitis and the healthy population. CONCLUSIONS: These results suggest that the allelic variants of the VNTR of the IL-1ra gene are not associated to a higher susceptibility to ulcerative colitis in Spanish population.

[Nodular lymphoid hyperplasia of the small bowel with IgA deficiency and hemolytic anemia (author's transl)]. / Hiperplasia nodular linfoide del intestino delgado con déficit de IgA y anemia hemolítica.

The syndrome of nodular lymphoid hyperplasia of the small bowel with hypogammaglobulinemia is one of the hypogammaglobulinemic enteropathies. Chronic diarrhea and malabsorption are the most characteristic features of this disease, and they are frequently associated to hypogammaglobulinemia of various types (acquired, congenital non sex-linked) and to selective IgA deficiency. The immunological deficiency gives rise to the more characteristic features of the disease, namely: a) hypogammaglobulinemia; b) respiratory infections and dental caries; c) Giardia lamblia infestation of the small bowel; d) the characteristic radiological features; and, e) the histological aspect of the intestinal mucosa with absence of plasma cells. Periodical follow-up is needed because of the increased incidence of tumors in immunological deficiency states. A new case of nodular lymphoid hyperplasia associated to hemolytic anemia and granulomatous hepatitis is reported, and its possible pathogenesis is discussed.

[Medullary aplasia, sarcoidosis, and malacoplakia. A case report (author's transl)]. / Aplasia medular, sarcoidosis y malacoplaquia. A propósito de un caso.

A 49-year-old man presented medullary aplasia, sarcoidosis, and malacoplakia as evidenced by biopsy. This is apparently the first case of this association to be described in the literature. Medullary aplasia is basically an aplasia of the erythroid series, though it may be a pure aplasia of the red cells alone. A histologic study of the left testicle removed because of an infectious orchiepidydimitis led to the discovery of malacoplakia. Skin nodules appeared later; two of them were extirpated and revealed the existence of sarcoidosis. There was no evidence of sarcoidosis at any other level. The immune mechanism involved in pure red cell aplasia with or without thymoma are well known. The association of malacoplakia and sarcoidosis, two similar conditions, is closely related to alterations in cell immunity. The possibility that common immune factors were present in this patient. After eliminating different therapeutic approaches used in other cases, an immunosuppresive therapy was applied.

[Detection and clinical course of metabolic multiple vascular risk syndrome]. / El descubrimiento y la evolución del síndrome metabólico de multirriesgo vascular.

The potential associations between the factors making up the vascular multi-risk metabolic syndrome (VMMS) or syndrome X (hypertension, diabetes, lipidic disorders, hyperinsulinemia and obesity) are studied: a) in patients with recent cerebral infarct or acute myocardial infarct; b) in patients hospitalized for the management of their hypertension, diabetes or obesity; c) at two years of evolution since the initial diagnosis of hypertension, diabetes or obesity. The results confirm that the VMMS, either complete or incomplete, is detected starting from the clinical management of any of its components (hypertension, diabetes, obesity) or complications (cerebral or myocardial infarct). These results and the ones regarding the evolution at two years of the risk factors associations, allows a discussion of the physiopathologic reality of the VMMS as an entity or a causal association.

[Sudden death as presentation form of papillary fibroelastoma of mitral valve]. / Muerte súbita como presentación de un fibroelastoma papilar de la válvular mitral.

We describe the case of a 35-year-old male, who presented with sudden death, secondary to anterior miocardial infarction due to embolism. Echocardiography, transthoracic and transesophageal, revealed a tumor in the anterior mitral leaflet. Tumor, histopathologically an papillary fibroelastoma, was excised and the mitral valve was replaced with a mechanical prosthetic valve. We revised the current literature on intracardiac papillary fibroelastoma.

[Non-Hodgkin's disease of the skull in a patient with AIDS]. / Linfoma no hodgkiniano de cráneo en un paciente con SIDA.

The involvement of bone in non-Hodgkin's lymphoma (NHL) is rare and usually occurs in the late stages of the disease. The involvement of the cranial vault is exceptional and we have found only eleven cases previously reported in the revised literature, none of them in an AIDS patient. We report a case of a 38 years old man, intravenous drug abuser with AIDS diagnosed who presented with coma. Computed tomography scan showed a left frontal intra-parenchymatous haematoma and multiple osteolytic lesions in the whole of the cranial vault, that involved outertable, diploe and innertable. Intra-parenchymatous haematoma was removed and a biopsy of the osteolytic lesions was performed. Histology showed features of a large B-cell NHL. Patient died of infectious pulmonary complications. The incidence of NHL in patients with congenital or acquired immunodeficiencies is increasing and Epstein-Barr virus and other factors have been involved in its pathogenesis. That's the first AIDS patient reported to have a NHL involving the cranial vault. Tumour was limited to the cranial vault without involvement of soft-tissue. An intra-parenchymatous haematoma was associated without an explained cause.