The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction.

Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI). We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites. Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI. To elicit cellular targeting as well as to block RI binding, transferrin was conjugated to a mutant human RNase, rhRNase(Gly89)-->Cys) and a mutant EDN (Thr87-->Cys). The transferrin-rhRNase(Gly89-->Cys) thioether conjugate was 5000-fold more toxic to U251 cells than recombinant wild-type hRNase. In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase. Thus, we endowed two human RI-sensitive RNases with greater cytotoxicity by increasing their resistance to RI. This strategy has the potential to generate a novel set of recombinant human proteins useful for targeted therapy of cancer.

Outcome of pregnancy in a hypothyroid woman with resistance to thyroid hormone treated with triiodothyronine.

Epidemiological and research data have shown the significant role of maternal thyroid hormone in fetal neurologic development. It has been suggested that maternal hypothyroxinemia is potentially damaging for the neurodevelopment of the fetus, independently of T3 levels. We present a pregnant woman with resistance to thyroid hormone and iatrogenic hypothyroidism who was treated with triiodothyronine during the whole pregnancy. Even though maternal hypothyroxinemia was severe the children showed a normal neuropsychological development.

An isolated pituitary metastasis as presentation of a differentiated hepatocellular carcinoma mimicking a nonfunctioning macroadenoma.

The differential diagnosis of sellar masses may be complex. Metastatic disease constitutes 1% of all pituitary lesions and sometimes mimics the clinical-radiological presentation of pituitary adenoma. The definitive diagnosis usually relies on histology, but occasionally even histological features of pituitary metastasis may resemble those of adenomas. We present a patient initially diagnosed with pituitary adenoma, but whose clinical course finally revealed pituitary metastasis of a hepatocellular carcinoma. The existing literature on this topic is reviewed.

Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery.

The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience.

Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity.

A number of biochemical properties differ dramatically among homologues within the pancreatic ribonuclease superfamily. Human pancreatic ribonuclease (hRNase) has high enzyme activity, extreme sensitivity to ribonuclease inhibitor (RI) and is non-toxic, whereas a homologous RNase from frog eggs, called onconase, has much lower enzyme activity, is not sensitive to RI and is cytotoxic to cancer cell lines and animals. To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification. A recombinant version of onconase with an N-terminal methionine instead of the native pyroglutamyl residue had decreased cytotoxicity and enzyme activity. Cleavage of the recombinant onconase Met-1 residue, and cyclization of the Gln1 residue to reform the pyroglutamyl N terminus, reconstituted cytotoxicity and enzyme activity. Thus a unique role of the pyroglutamyl residue in the active site of amphibian RNases is indicated. Replacement of one to nine residues of onconase with the homologous residues of hRNase increased the enzymatic activity against most of the substrates tested with a simultaneous shift in the enzyme specificity from high preference for poly(U) to slight preference for poly(C). Cytotoxicity of the chimera decreased, dissociating cytotoxicity from enzymatic activity. The molecular basis for the low binding affinity of onconase for RI has been examined experimentally with the recombinant RNases and by fitting onconase and RNase A structures to the coordinates from the recently published RNase A-RI complex.

Identification and characterization of human eosinophil cationic protein by an epitope-specific antibody.

The eosinophil cationic protein (ECP) is a basic secretion protein involved in the immune response system. ECP levels in biological fluids are an indicator of eosinophil-specific activation and degranulation and are currently used for the clinical monitoring and diagnosis of inflammatory disorders. A polyclonal epitope-specific antibody has been obtained by immunizing rabbits with a conjugated synthetic peptide. A sequence corresponding to a large exposed loop in the human ECP three-dimensional structure (D115-Y122) was selected as a putative antigenic epitope. The antibody was purified on an affinity column using recombinant ECP (rECP) as antigen. The antibody (D112-P123 Ab) specifically recognizes rECP and its native glycosylated and nonglycosylated forms in plasma, granulocytes, and sputum. The antibody detects as little as 1 ng of rECP, can be used both in reducing and nonreducing conditions, and does not cross-react with the highly homologous eosinophil-derived neurotoxin or other proteins of the pancreatic ribonuclease superfamily.

[Prognostic morbidity and mortality factors in hospital enteral nutrition: prospective study]. / Factores pronósticos de morbi-mortalidad en nutrición enteral hospitalaria: estudio prospectivo.

OBJECTIVE: To determine the prognostic factors that may best for see the outcome of an enteral nutritional intervention and to assess the assistance quality of a nutrition unit. SETTING AND SUBJECTS: Patients that required enteral nutrition during hospital admission at a third level center. INTERVENTIONS: Observational prospective study in which 160 patients were included by means of consecutive sampling, for a 6-months follow-up period. Underlying pathology, disability degree, nutritional assessment, type of enteral nutrition, complications, nursing care, and clinical course of patients were determined. RESULTS: severe caloric and protein hyponutrition was diagnosed in 48.4 and 52.9% of patients; stress degree was moderate in 52.2% and severe in 36.5%. In 88.2% of patients variation of protein parameters was unchanged or improved, with a 0.26 g/dL increase in albumin levels and 2.4 m/dL in prealbumin (p < 0.05). Multivariate analysis adjusted for plasma albumin at admission showed that besides this biochemical parameter, a severe stress degree, a decreased alertness level, and worsening of protein variation during admission are independent prognostic mortality factors during an enteral nutritional intervention in the hospitalized patient (p < 0.05). CONCLUSIONS: alertness level, degree of caloric hyponutrition, stress degree, plasma albumin levels, and variation of protein parameters during nutritional support are independent prognostic factors for the nutritional intervention outcomes. The development of global monitoring systems of assistance activity and quality of Nutrition Units is paramount in order to improve the efficiency of enteral nutritional support at the hospital setting, to advance in patients care and promote the development of nutritional therapy.

CEO1, a new protein from Arabidopsis thaliana, protects yeast against oxidative damage.

The Saccharomyces cerevisiae strain WYT, deficient in the YAP1 transcription factor, was used in a molecular screen to identify genes from Arabidopsis thaliana that could overcome the oxidative stress-sensitive phenotype of these yeast cells. A cDNA named CEO1 increased the tolerance to oxidative damage caused by tert-butylhydroperoxide of both the Yap1(-) mutant and the wild-type yeast. Additionally, in Yap1(-) yeast, CEO1 also induced cross-tolerance to oxidative damage caused by hydrogen peroxide and diamide. CEO1 was assigned as being part of a small gene family that, until now, is exclusively restricted to plants. In Arabidopsis, CEO1 was produced in all organs, especially in roots and stems. By using the yeast two-hybrid system, proteins that specifically interact with CEO1 in yeast were identified, and putative DNA-binding proteins were consistently recovered.

[Anal manifestations of lichen planus]. / Manifestaciones anales del liquen plano.

Lichen planus (LP) is an entity endowed with a striking polimorphysm and with a diversity of topographic localizations. In spite of the diagnostic difficulties that the combination of these factors occasionally produce, the histopathology of the lesion is tipical and diagnostic. Our presentation seems to be justified since, to the best of our knowledge, the anal localization of the disease has not been reported and it is also rare. The finding of these anal manifestation has not been casual. With the certitude that there was no reason why LP could not appear in a semimucosa so much alike that of the lips we have systematically examined the anal region of patients bearing lesions of LP elsewhere. Anal lesions that appeared to correspond to LP were detected and their histopathology confirmed the existence of LP in some of these cases. The structural changes permit the grouping of cases in four categories: Tipical LP of the anal semimucosa. LP of the anal semimucosa masked by coexistent lichen simplex chronicus (neurodermatitis). Serial sections of the paraffin block or biopsy of a nearby area usually prove diagnostic. Neurodermatitis associated to a lichenoid tissue reaction: Focal effacement of the basal membrane associated to lymphoid infiltrate of the upper dermis. Neurodermatitis without lichenoid features. It is our interpretation that this localization of LP may be due to a Köbner's phenomenon provoked by scratching induced by pruritus, as it occurred in our cases, or by other microtraumas so common to the area.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fluid therapy in cardiac surgery. An update]. / Fluidoterapia en cirugía cardiaca. Puesta al día.

The anesthetist has 2 major tools for optimizing haemodynamics in cardiac surgery: Vasoactive drugs and the intravascular volume. It is necessary to identify which patients would benefit from one or the other therapies for a suitable response to treatment. Hemodynamic monitoring with the different existing parameters (pressure, volumetric static, volumetric functional and echocardiography) allows the management of these patients to be optimized. In this article a review is presented on the most recent and relevant publications, and the different tools available to control the management of the fluid therapy in this context, and to suggest a few guidelines for the haemodynamics monitoring of patients submitted to cardiac surgery. A systematic search has been made in PubMed, limiting the results to the publications over the last five years up to February 2012.

The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane.

Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.

Comparison of two low-calorie diets: a prospective study of effectiveness and safety.

OBJECTIVE: To evaluate the cost-effectiveness and safety of two distinct low calorie diets (LCD). DESIGN: Prospective controlled study. METHODS: 67 obese patients [body mass index (BMI) 40 kg/m2] were included in two study groups. Group A: 26 patients followed a 458 kcal diet given in three meals for 1 month. Group B: 41 patients followed a 800 kcal diet for 3 months and with outpatient control. MEASUREMENTS: Anthropometric, cardiovascular risk and nutritional profile changes were evaluated, as well as total direct and indirect costs, and the incidence of complications. RESULTS: No significant initial differences were observed between the two study groups. Eighty-six point two per cent of the patients completed the therapy correctly. After treatment a significant decrease was observed in the following variables for both groups, but no differences were detected between Groups A and B: mean weight loss (A= 9.28 kg, B= 8.7 kg), ponderal loss percentage (A/B= 7.2/6.8%), glycemia (A/B= 18.6/12.1 mg/dl), systolic blood pressure (SBP) (A/B= 11.8/6.5 mmHg), diastolic blood pressure (DBP) (A/B 5.9/6.8 mmHg), and final insulin-resistance (IR) index (A= 4.4, B= 4.3). Group A had the highest drop in total cholesterol (37.7 vs 8.1 mg/dl) and triglycerides (54.4 vs 2.5 mg/dl). No changes were observed in ureic acid, renal function and serum albumin. Thirty-six patients (55.3%) suffered trivial complications associated to the VLCD (16.9% gastrointestinal, 20% anxiety), with no differences between groups. Group A patients were on sick leave due to asthenia, and two patients in this group had serious complications (transient ischemic attack and atrial fibrillation). The total cost of Group A treatment was 3018.9 against 582.6 euros for Group B. CONCLUSIONS: The 3-month 800 kcal/day VLCD was more cost-effective and safer than the 1-month 458 kcal/day diet.

Guía de práctica clínica para la elección del fluido de restauración volémica perioperatoria en los pacientes adultos intervenidos de cirugía no cardiaca / Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery

Esta Guía de Práctica Clínica responde a preguntas clínicas sobre seguridad en la elección de fluido (cristaloide, coloide o Hidroxietilalmidón 130) en pacientes que precisan restauración volémica en el periodo perioperatorio de cirugía no cardiaca. A partir del resumen de la evidencia, se elaboraron las recomendaciones siguiendo la metodología GRADE. En esta población se sugiere la fluidoterapia basada en la administración de cristaloides, (recomendación débil, calidad de la evidencia baja). En las situaciones en las que la restauración volémica no se alcance sólo con cristaloides, se sugiere utilizar coloides sintéticos (Hidroxietilalmidón 130 o gelatina fluida modificada) en lugar de Albúmina 5% (recomendación débil, calidad de la evidencia baja). La elección y dosificación de coloide deberán basarse en las características del producto, comorbilidad del paciente y experiencia del anestesiólogo (AU)

The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience (AU)

Teratogenicity with angiotensin II receptor antagonists in pregnancy.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AT-II)-receptor-antagonists have been demonstrated to cause fetotoxicity when administered to women during the second and third trimester of pregnancy. Although use of ACE inhibitors during the first trimester of pregnancy seems to be safe, with no associated teratogenicity, there is not sufficient information regarding the safety of first-trimester exposure to AT-II-receptor-antagonists. We report a case of exencephaly and unilateral renal agenesia in a fetus of a diabetic woman who became pregnant while taking irbesartan.