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Introduction: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement in patients with severe aortic stenosis (AS) and unacceptably high surgical risk., Methods: We present our first two years' experience with TAVI. A total of 76 AS patients were evaluated for TAVI and 23 of them underwent a TAVI procedure. These patients had a mean EuroSCORE of 22.4% and a mean age of 81.5 years, and were prospectively followed for a mean of 12.9 ± 11 months., Results: The percutaneous aortic valve was successfully implanted in 100% of the patients. Mortality at 30 days was 4%. The most common complications were access site-related bleeding and transfusion (22%), followed by new permanent pacemaker implantation (9%). After a mean follow-up of 12.9 months, survival was 87%. In a maximum follow-up of 30 months there were no cases of prosthesis dysfunction or cardiovascular death., Conclusions: Two years after the introduction of a TAVI program in our center, the procedure has established itself as a safe and effective alternative for patients with severe AS and unacceptably high surgical risk., (Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: Gross haematuria is a common manifestation of autosomal dominant polycystic kidney disease (ADPKD). It can be spontaneous or the result of trauma, renal calculi, tumour, or infection. Spontaneous cyst bleeding is important in this particular group of patients, since it can be prolonged by local activation of fibrinolysis by urokinase. The management of haematuria in ADPKD is usually conservative, including bed rest, blood transfusion, correction of blood disorders, and use of vasopressin and erythropoiesis-stimulating agents. In some patients, the management of gross or life-threatening haematuria may require embolisation and/or nephrectomy. Nonetheless, other methods have been tried to avoid prolonged hospitalisation and nephrectomy and preserve kidney function, such as the use of anti-fibrinolytics. Tranexamic acid was recently suggested as a tool to treat gross haematuria in ADPKD in isolated cases., Objective: The aim of this study was to evaluate prospectively the response to tranexamic acid in a group of 8 patients with ADPKD and gross haematuria unresponsive to conventional treatment., Results: The massive bleeding stopped within 2 to 5 days in all patients. The haemoglobin level and renal function subsequently stabilised. There were no side effects or thromboembolic events. In this case series, the largest prospective study so far published and the only one including different degrees of renal function, tranexamic acid is confirmed as a promising tool for treating haematuria due to intracystic bleeding in ADPKD., Conclusions: In summary, tranexamic acid can be used safely in ADPKD patients with chronic renal impairment or preserved renal function to treat severe haematuria poorly responsive to conventional therapy. Tranexamic acid can be administered orally or IV; and dose adjustment for renal impairment is important. Tranexamic acid therapy may preserve renal function in ADPKD directly, by stopping haematuria episodes, or indirectly, by preventing embolisation and/or nephrectomy. The major limitation of this study is the small sample size and the lack of an untreated control group. We suggest a prospective, randomised controlled study to confirm the efficacy of this treatment, its long-term safety, and the optimal dosage. Further larger and multicentre studies are needed to evaluate the cost-benefit ratio and the limits of this therapy in the clinical setting.

The generation of azomethine ylides from the readily accessible hemiaminals 3 and 8 or from iminium salt 10 was studied. Compounds 8 gave anti- and syn-cycloadducts containing the quinocarcin core through a catalyst-free dehydration process.

The main motivation of this paper is to propose a method to extract the output structure and find the input data manifold that best represents that output structure in a multivariate regression problem. A graph similarity viewpoint is used to develop an algorithm based on LDA, and to find out different output models which are learned as an input subspace. The main novelty of the algorithm is related with finding different structured groups and apply different models to fit better those structures. Finally, the proposed method is applied to a real remote sensing retrieval problem where we want to recover the physical parameters from a spectrum of energy.

Resveratrol is a plant-derived polyphenol that extends lifespan and healthspan in model organism. Despite extensive investigation, the biological processes mediating resveratrol's effects have yet to be elucidated. Because repression of translation shares many of resveratrol's beneficial effects, we hypothesized that resveratrol was a modulator of protein synthesis. We studied the effect of the drug on the H4-II-E rat hepatoma cell line. Initial studies showed that resveratrol inhibited global protein synthesis. Given the role of the mammalian Target of Rapamycin (mTOR) in regulating protein synthesis, we examined the effect of resveratrol on mTOR signaling. Resveratrol inhibited mTOR self-phosphorylation and the phosphorylation of mTOR targets S6K1 and eIF4E-BP1. It attenuated the formation of the translation initiation complex eIF4F and increased the phosphorylation of eIF2α. The latter event, also a mechanism for translation inhibition, was not recapitulated by mTOR inhibitors. The effects on mTOR signaling were independent of effects on AMP-activated kinase or AKT. We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling.

Looking for optimised analogues of compound 2 that might be useful in colon cancer therapy, we here explore the in vitro cytotoxicity against MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma and HT-29 human colon carcinoma cell lines of several analogues and derivatives. The effect of the R2-substituent and/or the introduction of an arylmethyl side-chain at C-3, as well as the presence of a double bond in the skeleton or a methoxy group at C-1 have been investigated. New 6,15-iminoisoquino[3,2-b]3-benzazocine compounds, related to the saframycin family, in which the C(7)-N(8)-C(9)-substructure contains a lactam function, a fused oxazolidine or an aminonitrile function were also studied, and many of them showed low micromolar GI50 values., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Saframycins, safracins, renieramycins, cribrostatins, and esteinascidins are 6,15-iminoisoquino[3,2-b]3-benzazocine compounds that constitute the largest subgroup among the antitumor antibiotics belonging to the tetrahydroisoquinoline family. Their structural complexity has led to widespread synthetic attention to obtain them in both racemic and enantiopure forms. Publication in 1996 of the first total synthesis of ecteinascidin 743 by Corey's group was an important milestone, but the development of preparative protocols for these structures has continued, offering new possibilities to exploit the biological activity of the above-mentioned natural products and their analogues. This minireview is intended to update this progress following a methodological rather than a chronological organization. Besides of a brief description of the different strategies evolved from retrosynthetic analyses, which have been organized according to the order of bonding events that will link the precursors, semisynthetic approaches and a brief account of the total syntheses of ecteinascidin 743, have been analyzed.

One way animals may cope with nutrient deprivation is to broadly repress translation by inhibiting 5'-cap initiation. However, under these conditions specific proteins remain essential to survival during fasting. Such peptides may be translated through initiation at 5'UTR Internal Ribosome Entry Sites (IRES). Here we show that the Drosophila melanogaster Forkhead box type O (dFoxO) transcription factor is required for adult survival during fasting, and that the 5'UTR of dfoxO has the ability to initiate IRES-mediated translation in cell culture. Previous work has shown that insulin negatively regulates dFoxO through AKT-mediated phosphorylation while dFoxO itself induces transcription of the insulin receptor dInR, which also harbors IRES. Here we report that IRES-mediated translation of both dFoxO and dInR is activated in fasted Drosophila S2 cells at a time when cap-dependent translation is reduced. IRES mediated translation of dFoxO and dInR may be essential to ensure function and sensitivity of the insulin signaling pathway during fasting.

Background/aim: The research on congenital diaphragmatic hernia (CDH) is often carried out on the nitrofen fetal rat model in which most investigations involve microdissections and fastidious assessment of serial sections of different anatomic areas. Current microscopic magnetic resonance (MMR) equipment allows detailed anatomic studies of alive, fresh or fixed fetuses. The purpose of the present study was to demonstrate that CDH itself and most of the associated malformations are adequately imaged and measured by MMR., Materials and Methods: Fetuses from pregnant rats treated with either i.g. vehicle (control, n = 10) or 100 mg nitrofen (only those with CDH, n = 18) on E9.5 were recovered on E21 (term = E22) and total body was scanned by MMR under sedation in a 7 T MRI system (Bruker Medical, Ettlingen, Germany). CDH was detected with a coronal multislice fast spin echo sequence with a long repetition time and short effective echo time. Oblique MPR and 3D reconstructions were used. All studies were processed with attention to the hernia and its contents and the structure of the tracheobronchial tree and the lung, the heart and great vessels, the thymus and cervico-thoracic vertebrae. The findings in both groups were compared., Results: Congenital diaphragmatic hernia, lung hypoplasia and parenchymal features were clearly depicted. Tracheal ring anomalies were also demonstrated. The thymus was significantly smaller in CDH pups (2.9 x 1 x 2.4 mm) than in controls (4 x 1.3 x 2.8 mm) (p < 0.01). MRI was particularly performant for imaging cardiovascular anomalies: 4 double aortic arches, 3 Fallots, 3 right aortic arches, 3 ventricular septal defects and 1 aberrant subclavian artery., Conclusions: Microscopic magnetic resonance involves refined and expensive equipment but it provides a powerful research tool for the study of CDH and other malformations in rat fetuses. Further work on this area is warranted.

The actual incidence of ascending aorta complications (AACs) in adults with bicuspid aortic valve (BAV) and the role of associated coarctation of the aorta (COA) as an independent risk factor for AACs remain unknown. From the Adult Congenital Heart Disease database at La Paz Hospital, 631 patients in whom a BAV was diagnosed by echocardiography or surgical inspection since December 1989 were identified. These patients were then further subdivided into 2 groups according to the presence of an associated COA. AACs included aortic aneurysms (ascending aorta > or =55 mm) and aortic dissection, rupture, or perforation. Patients with a BAV and COA had a greater prevalence of AACs (8.0%) than those with an isolated BAV (3.7%; p = 0.037). The coexistence of COA was the only significant predictor of AACs (odds ratio 4.7, 95% confidence interval 1.5 to 15; p = 0.01). From the total patient group with a BAV, the clinical and echocardiographic data were reviewed for 341 patients without an AAC at baseline (97 with and 244 without COA) who had undergone serial examinations >1 year apart. The median follow-up was 7 years (interquartile range 3.5 to 10.2; total 2,436 patient-years). A new AAC occurred in 13 patients (0.5/100 patient-years). The incidence of AACs was 1.3/100 patient-years in the COA group versus 0.2/100 patient-years in the non-COA group (hazard ratio 7.5, 95% confidence interval 2.0 to 28, p = 0.002). All acute aortic events (dissection or rupture) at follow-up occurred in patients with a BAV and COA. In conclusion, the long-term incidence of AACs in patients with isolated BAV is low, but patients with BAV and associated COA are at increased risk.

Ablation of germ-line precursor cells in Caenorhabditis elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin-like growth factor (IGF) signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of this systemic regulation of aging by the reproductive system are not understood, and it is unknown whether such effects are evolutionarily conserved. Here we report that eliminating germ cells (GCs) in Drosophila melanogaster increases lifespan and modulates insulin signaling. Long-lived germ-line-less flies show increased production of Drosophila insulin-like peptides (dilps) and hypoglycemia but simultaneously exhibit several characteristics of IIS impedance, as indicated by up-regulation of the Drosophila FOXO (dFOXO) target genes 4E-BP and l (2)efl and the insulin/IGF-binding protein IMP-L2. These results suggest that signals from the gonad regulate lifespan and modulate insulin sensitivity in the fly and that the gonadal regulation of aging is evolutionarily conserved.

The purpose of this paper was to develop a statistical methodology to optimize tablet manufacturing considering drug chemical and physical properties applying a crossed experimental design. The assessed model drug was dried ferrous sulphate and the variables were the hardness and the relative proportions of three excipients, binder, filler and disintegrant. Granule properties were modeled as a function of excipient proportions and tablet parameters were defined by the excipient proportion and hardness. The desirability function was applied to achieve optimal values for excipient proportions and hardness. In conclusion, crossed experimental design using hardness as the only process variable is an efficient strategy to quickly determine the optimal design process for tablet manufacturing. This method can be applied for any tablet manufacturing method.

Background: The organization of the different tissues of an animal requires mechanisms that regulate cell-cell adhesion to promote and maintain the physical separation of adjacent cell populations. In the Drosophila imaginal wing disc the iroquois homeobox genes are expressed in the notum anlage and contribute to the specification of notum identity. These genes are not expressed in the adjacent wing hinge territory. These territories are separated by an approximately straight boundary that in the mature disc is associated with an epithelial fold. The mechanism by which these two cell populations are kept separate is unclear., Results: Here we show that the Iro-C genes participate in keeping the notum and wing cell populations separate. Indeed, within the notum anlage, cells not expressing Iro-C tend to join together and sort out from their Iro-C expressing neighbours. We also show that apposition of Iro-C expressing and non-expressing cells induces invagination and apico-basal shortening of the Iro-C- cells. This effect probably underlies formation of the fold that separates the notum and wing hinge territories. In addition, cells overexpressing a member of the Iro-C contact one another and become organized in a network of thin strings that surrounds and isolates large groups of non-overexpressing cells. The strings appear to exert a pulling force along their longitudinal axis., Conclusion: Apposition of cells expressing and non-expressing the Iro-C, as it occurs in the notum-wing hinge border of the Drosophila wing disc, influences cell behaviour. It leads to cell sorting, and cellular invagination and apical-basal shortening. These effects probably account for keeping the prospective notum and wing hinge cell populations separate and underlie epithelial fold formation. Cells that overexpress a member of the Iro-C and that confront non-expressing cells establish contacts between themselves and become organized in a network of thin strings. This is a complex and unique phenotype that might be important for the generation of a straight notum-wing hinge border.

Background: Little information is available on the clinical efficacy of sublingual immunotherapy (SLIT) using extracts derived from mammalian epithelia., Objectives: To assess clinical efficacy of cat SLIT based on natural exposure challenge test (NCT)., Material and Methods: Fifty cat allergic patients with rhinoconjunctivitis with or without asthma were included in a randomized double blind placebo controlled clinical trial of cat SLIT during 1 year. Twenty-five patients received active treatment and 25 placebo. Sublingual immunotherapy efficacy was assessed by natural exposure challenge to a cat in a cat-room and by skin tests. Airborne Fel d 1 levels, symptom scores and peak expiratory flow (PEF) values were monitored., Results: Thirty-three (66%) out of 50 patients completed the treatment. Fel d 1 content of the maximum concentration was 0.51 microg per ml. During the build up phase, the accumulated dose was 1.7 mug of Fel d 1 and during the entire length of the study was 17.1. No adverse reports were reported. The active group showed a marked reduction (62%) in symptoms during the NCT (P < 0.001) with no changes in placebo group. Active group also showed a reduced PEF response to cat exposure (P < 0.05), and an improvement in skin test reactivity to a standardized cat extract (P < 0.05), without significant changes in placebo group. Mean Fel d 1 exposure during the NCT was 6.2 +/- 2.21 ng/m(3)., Conclusions: The results suggest that the cat SLIT used in this study was able to improve cat allergy based on natural exposure challenge.

A series of pyrazino[2,1-b]isoquinoline and 6,15-iminoisoquino[3,2-b]-3-benzazocine compounds related to renieramycins, cribrostatin 4, and phthalascidin was synthesized and their in vitro cytotoxic activities were evaluated against three human cancer cell lines. Pyrazino[2,1-b]isoquinolines, 6,15-iminoisoquino[3,2-b]-3-benzazocines, and other more complex octacyclic compounds have been obtained and derived to precursors of iminium ion species. Hydrogenolysis of the lactam function in pentacyclic compounds gave 1-(3-isoquinolyl)isoquinolines. The micromolar cytotoxic activity of representative structures was apparently uninfluenced by the ability to generate intermediates which would permit covalent bonding to DNA.

Aortobronchial fistula (ABF) is an uncommon complication of aortic coarctation repair which may occur years after successful coarctation correction. It is invariably fatal if not diagnosed and treated. ABF diagnosis poses a challenge for clinicians and radiologists because of the difficulty in detecting the fistula and the risks associated with some of the diagnostic procedures. Two cases of ABF occurring 1 and 20 years after reparative surgery of aortic coarctation are reported. The advantages and disadvantages of different imaging procedures for the evaluation of patients with suspected ABF are reviewed and the role of computed tomography angiography and magnetic resonance imaging is underlined.

During development, the imaginal wing disc of Drosophila is subdivided into territories separated by developmental boundaries. The best characterized boundaries delimit compartments defined by cell-lineage restrictions. Here, we analyze the formation of a boundary that does not rely on such restrictions, namely, that which separates the notum (body wall) and the wing hinge (appendage). It is known that the homeobox genes of the Iroquois complex (Iro-C) define the notum territory and that the distal limit of the Iro-C expression domain demarks the boundary between the notum and the wing hinge. However, it is unclear how this boundary is established and maintained. We now find that msh, a homeobox gene of the Msx family, is strongly expressed in the territory of the hinge contiguous to the Iro-C domain. Loss- and gain-of-function analyses show that msh maintains Iro-C repressed in the hinge, while Iro-C prevents high level expression of msh in the notum. Thus, a mutual repression between msh and Iro-C is essential to set the limit between the contiguous domains of expression of these genes and therefore to establish and/or maintain the boundary between body wall and wing. In addition, we find that msh is necessary for proper growth of the hinge territory and the differentiation of hinge structures. msh also participates in the patterning of the notum, where it is expressed at low levels.

Inhibition of glycolysis at the phosphofructo-1-kinase step slows cell growth. For this reason, overexpression of fructose-2,6-bisphosphatase is a potential target for antineoplasic treatments. However, therapeutic objectives may be compromised by side effects of glycolysis restriction, including enhanced resistance to oxidants and tumor necrosis factor-alpha (TNF-alpha), as well as increased activity of the nuclear factor kappa B (NF-kappaB). In this study we evaluated aspirin as an adjuvant drug for glycolysis restriction by overexpression of fructose-2,6-bisphosphatase. The effect of aspirin on antioxidant defences and NF-kappaB activity were evaluated both in control cells and in fructose-2,6-bisphosphatase-overexpressing cells. Interestingly, aspirin-induced inhibition of NF-kappaB activity was greater in transfectants with restricted glycolysis than in control cells. Our results indicate that aspirin is a suitable complement to therapy based on glycolysis restriction to overcome resistance associated with increased NF-kappaB activity and oxidative stress.

Introduction: Up to 5% of the population suffers from neuropathic pain (NP). A bibliographical search in several databases revealed that, to date, there are no protocols to guide physicians who are not specialists in pain that enable them to treat NP and thus improve patients' quality of life., Aims: The aim of this study is to provide Spanish-speaking physicians who are not specialists in pain with a set of guidelines for the treatment of NP. A bibliographical search was performed in order to base the results and conclusions on the evidence-based medicine methodology., Development: First, we review the most effective clinical and paraclinical methods for diagnosing NP, and the LANSS pain scale is reported as the most appropriate method of clinically evaluating NP. The anatomical paths and the physiology of pain are then described and we review the molecular variables involved. Finally, we point out the current therapeutic options and propose an algorithm for the treatment of NP., Conclusions: There is no specific set of guidelines for the treatment of NP. At the present time, the keystone of NP treatment consists in the use of antidepressant and anticonvulsive drugs. There is a need for further clinical trials to prove the effectiveness of using combined medication.

Aims: The aim of this study is to develop a set of guidelines for the clinical management of neuropathic pain (NP), a disorder suffered by up to 5% of the population, specifically for use by the Spanish-speaking community, in order to improve the quality of medical care and to standardise the treatments offered in medical centres., Development: The paper describes the methodology used to search for guidelines concerning the clinical management of NP in databases, written communications and other resources, and the results of this search are presented. The research group is split into three groups: anatomical-physiological, diagnosis and therapeutic approach, each of which defines the nature of the papers that used to design the protocol.

Transfection of genes that code for enzymes of energy metabolism provides alternative models to study the adaptive response to energy restriction induced by endogenous changes instead of by unfavorable environmental conditions. Overexpression of the glycolytic enzyme fructose-2,6-bisphosphatase reduced the content of fructose 2,6-bisphosphate, inducing energy limitation in the mink lung epithelial cell line Mv1Lu. This metabolic stress reduced the ATP available in transfected cells by 20%, which downregulated active ion transport and protein turnover. Ion homeostasis and cell function require concomitant reductions in cell membrane ion permeability and protein damage. Our results indicate that glutathione content linked these features of the adaptive response to the endogenously induced metabolic downregulation.

A gas chromatographic procedure was used for analysis of conjugated linoleic acid (CLA) isomers cis-9, trans-11-octadecadienoic; trans-10, cis-12 octadecadienoic; and trans-9, trans-11-octadecadienoic (c9t11, t10c12, t9t11) produced by lactobacilli. Four different cultures, two strains each of Lactobacillus acidophilus and Lactobacillus casei were tested for their ability to produce CLA from free linoleic acid in MRS broth supplemented with linoleic acid. Different concentrations of linoleic acid (0, 0.05, 0.1, 0.2 and 0.5 mg/ml) were added to MRS broth, inoculated with the lactobacilli, and incubated at 37 degrees C. Viable counts and amounts of individual isomers of CLA (c9t11, t10c12, t9t11) were measured at 0, 24, 48, and 72 h. All the cultures were able to produce free CLA in media supplemented with linoleic acid. Maximum production of CLA (80.14 to 131.63 microg/ml) was observed at 24 h of incubation in broth containing 0.02% of free linoleic acid. No significant (P > 0.05) increases in total CLA levels were observed after 24 h of incubation. The ability of the cultures to produce CLA in skim milk supplemented with 0.02% free linoleic acid also was studied. In this medium, the total amounts of free CLA after 24 h of incubation ranged from 54.31 to 116.53 microg/ml. The use of lactic acid bacteria able to form free CLA in cultured dairy products may have potential health or nutritional benefits. Free CLA in the products likely would be more readily available for absorption from the digestive tract than if it were incorporated into the cells of the starter culture.

The Tufted(1) (Tft(1)) dominant mutation promotes the generation of ectopic bristles (macrochaetae) in the dorsal mesothorax of Drosophila. Here we show that Tft(1) corresponds to a gain-of-function allele of the proneural gene amos that is associated with a chromosomal aberration at 36F-37A. This causes ectopic expression of amos in large domains of the lateral-dorsal embryonic ectoderm, which results in supernumerary neurons of the PNS, and in the notum region of the third instar imaginal wing, which gives rise to the mesothoracic extra bristles. Revertants of Tft(1), which lack ectopic neurons and bristles, do not show ectopic expression of amos. One revertant is a loss-of-function allele of amos and has a recessive phenotype in the embryonic PNS. Our results suggest that both normal and ectopic Tft(1) bristles are generated following similar rules, and both are subjected to Notch-mediated lateral inhibition. The ability of Tft(1) bristles to appear close together may be due to amos having a stronger proneural capacity than that of other proneural genes like asense and scute. This ability might be related to the wild-type function of amos in promoting development of large clusters of closely spaced olfactory sensilla.

Glycolysis-depleted cells, obtained by stable transfection of fructose 2,6-bisphosphatase in mink lung epithelial cells (Mv1Lu), were less sensitive to serum withdrawal- and TNF-alpha-induced apoptosis than cells transfected with the empty vector pcDNA3 (control cells). We compared the differences in the redox status of the two transfectants and the changes produced by TNF-alpha treatment. The activities of the antioxidant enzymes catalase and glutathione peroxidase, as well as the content of reduced glutathione (GSH) and the activity of the nuclear transcription factor kappa B (NF-kappa B), were higher in pFBPase-2 clones than in control cells in all the conditions tested. TNF-alpha challenge sharpened the differences in glutathione peroxidase activity, GSH/GSSG ratios, and NF-kappa B activation between transfectants. These data indicate that glycolysis restriction at the PFK step protects cells against apoptotic stimuli by increasing the GSH content and NF-kappa B activity. This acquired feature may compromise antineoplastic treatments based on glycolytic depletion.

Several strains of Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus, which produced exocellular polysaccharides (EPS), varied in the amount produced. The streptococci tended to produce the most EPS per milliliter of culture; however, when compared on the basis of amounts per 10(7) cfu, the lactobacilli produced the most. Lactobacillus delbrueckii ssp. bulgaricus strains Lb-18 and Lb-10442 and S. thermophilus St-143 produced significantly larger amounts per 107 cfu than did other strains tested. These three cultures plus two strains of the streptococci that produced the greatest amounts of EPS per ml of culture were tested for the ability to bind bile acids from laboratory media. The two cultures of L. delbrueckii ssp. bulgaricus (Lb-18 and Lb-10442) bound significantly higher amounts of cholic acid than did the three strains of streptococci. These two cultures of lactobacilli bound up to 15.3% of the cholic acid present in laboratory media, up to 452 microg/mg of EPS and 2.9 microg/10(7) cfu. None of the cultures tested in this study were able to bind the conjugated bile acid, glycocholic acid.

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.

Background: although grass pea belongs to the leguminoseae family, allergic reactions to its flour have rarely been described. Clinical and immunological studies were performed to confirm a type I hypersensitivity mechanism in a case of occupational asthma to grass pea flour exposure, used in the industrial processing of parquet., Methods: occupational asthma was diagnosed according to patient history, PEFR monitoring and a specific bronchial challenge test. Skin prick test with an aqueous grass pea flour extract, specific IgE determinations (CAP assay) and IgE immunoblot tests were performed., Results: skin prick test with the extract showed a positive immediate response, and negative response in controls. Specific IgE to grass pea was positive (9.57 KU/l). Immunoblotting demonstrated the presence of specific serum IgE that recognized 3 proteins in the extract (MW 46, 32 and 28 kDa). PEFR monitoring showed positive results. Bronchial challenge test with the extract elicited an isolated immediate response., Conclusions: as far as we know this is the first time that IgE mediated occupational asthma caused by grass pea is reported and it is also the first time that its allergens are characterized. Grass pea flour might constitute a relevant occupational allergen in this unreported source of exposure in parquet manufacturers.

According to Weiss et al. [12], the main providers of asthma care in the United States in 1992 were general and family medicine + internal medicine (46%), pediatrics (19%), allergy (25%), pulmonary medicine (5%), and others (5%). In an overall climate of a shift of referral from primary care to the specialties, specialists will have to provide evidence that their intervention in the control of patients provides truly better clinical and economical outcomes than that of general practitioners. In order to support this hypothesis, we estimated: (1) the development of the costs of medication for asthma in a population of 40 million people (Spain) and (2) the correlation between these costs and the intervention of a specialized attendance. In Spain the annual costs incurring from allergic diseases are estimated to be approximately 1,500 million Euros and, the cost due to asthma alone is about 900-1,200 million Euros. There are two main ways to explain the size of these figures. First, the prevalence of allergic diseases is rising year by year. Second, the relevance of allergology in the control of asthma is often greatly reduced. This has resulted in a reduction in the etiological diagnosis and treatment with specific immunotherapy (SIT). However, SIT is the only specific causal treatment of allergic asthma that is able to modify the natural history of disease or disease progression. So, it is possible to hypothesize that this reduction in a proper etiological diagnosis and treatment could be a cause (among others) of increasing costs.

Objective: To describe an additional case of incomplete sagittal septum of the bladder., Methods: A case of incomplete sagittal septum of the bladder in a young, asymptomatic patient with paralysis of both lower limbs is presented and literature is briefly reviewed., Results: The diagnosis was made by intravenous urography performed five years after the accident that had caused the paralysis. Radiological evaluation showed an "apple heart" bladder with reduced capacity. No treatment was required., Conclusions: Incomplete sagittal septum of the bladder is rare. To our knowledge, only 7 cases have been previously reported. Incomplete sagittal septum is like complete septum, but both cavities communicate anteriorly or distally, according to the direction and depth the septum protrudes into the bladder.

The incidence and prevalence of allergic diseases are constantly increasing in our times. The only etiologic treatments currently available are allergen avoidance and immunotherapy. Many scientific data demonstrate that immunotherapy with allergens is an effective and safe treatment for allergic rhinitis and asthma in adequately selected patients and that it reduces treatment costs for the patients in the long run. Other promising aspects of immunotherapy are its capacity to produce prolonged clinical remissions over time, that it is the only treatment capable of stopping the natural development of the respiratory allergic disease, and the possibility that immunotherapy could avoid evolution to asthma in a significant percent of patients with rhinitis.

Percutaneous vertebroplasty is an effective treatment for many focal vertebral lesions. Methyl methacrylate is too viscous to be handled without difficulty in the conventional way because injection time is short. The operator is left with little time and must fumble with multiple syringes. We describe a special screw-system syringe that decreases the effort needed to inject the cement. In addition, it can standardize the injection pressures and control the injected volume because the threaded plunger affords greater control of injection pressure and volume delivered than does the conventional method.

Although health-related quality of life and patient satisfaction are shifting doctors' attention to the patient, the scant number of publications on quality of life questionnaires and allergen immunotherapy contrasts with the quickly growing number of those dealing with this topic and pharmacotherapy. We delivered an original, self-administered patient satisfaction questionnaire to 95 patients (age = 17.7 +/- 7.9 years) suffering from allergic rhinoconjunctivitis (45%) and/or asthma (55%), who had been receiving allergen immunotherapy for more than 1 year (22.2 +/- 10.5 months). The anonymous, voluntary questionnaire was filled in at home; although only 32% were returned, we found no significant differences relating to age, sex, asthma, allergen sensitization or allergen immunotherapy regimen between the source sample and those who replied. Patient expectations, which were scored on a scale of 1 to 10 points, were rather poor, in sharp contrast with patient perception score after treatment (5.4 +/- 1.8 vs. 8.0 +/- 2.0, p < 0.0001). Perception scores did not differ between patients receiving seasonal or perennial allergen immunotherapy, nor did they depend on the duration of treatment. In addition, patient age, sex, diagnosis or sensitization did not appear to influence perceptions. In conclusion, our data suggest that when a voluntary, anonymous questionnaire is used, patients express a poor opinion of allergen immunotherapy, in contrast with high satisfaction after treatment, provided that allergen immunotherapy lasts long enough.

Objective: The aim of this study was to develop a quantitative skin test assay for measurement of the biologic activity of food allergen extracts, as well as to report the results obtained with a peach extract labeled in food biological units (FBUs)., Methods: We prepared a biologically quantified peach extract. The biologic activity was measured in FBUs by assigning 100 FBU/ml to the biologic activity of the extract that elicited a wheal area with a geometric mean equal to that produced by the prick-prick method by using the food itself in a population of 30 patients allergic to food. We evaluated 265 patients, including 70 patients allergic to peach and 195 control subjects (100 nonatopic subjects and 95 subjects allergic to pollen). The biologically quantified peach extract was used during the study and was compared with four commercial peach extracts, which were labeled in weight per volume., Results: The sensitivity of the nonstandardized commercial peach extracts varied from 4.3% to 74%, with biologic activity being very low in all of them. The sensitivity of the biologically quantified peach extract was 100%, with a 100% concordance between the prick-prick and the skin prick test results., Conclusion: These data demonstrate that if peach allergen preparations were biologically standardized in FBUs, the quality of these food extracts used for diagnosis would be improved.

Unlabelled: Cancellations have an important role in the effectiveness of the surgical schedule., Objective: Analyze the evolution of the cancellations during the years 1994-1997, after institution of several corrective measures., Material and Method: We started in 1994 together with the Quality Unit of the Hospital, a program to reduce surgical cancellations. It consisted in improvement of parents information, surgical schedule centralization, and increasing the awareness of the importance of constant improvement. Cancellations have been divided in: inevitables and inevitables, and analyzed for the entire Service and for each speciality., Results: A significant reduction of cancellations have been obtain (from 12.38% in 1992 to 3.35% in 1997). The inevitable causes (no presentation, inadequate preparation and lack of time in the surgical room) have shown the most improvement. Although the inevitable causes (intercurrent disease) were also significantly improved, after obtaining prior information of the health of the child, by telephone call or parents advise. ENT is the speciality with greatest improvement by significant reduction of the non presentation and intercurrent disease., Conclusion: After corrective measures conjointly with a realistic surgical schedule, prior telephone call and improvement quality concept, have permitted a significant reduction of cancellations.

To compare the effects of the sustained exposure to inhaled nitric oxide (NO) on pulmonary gas exchange, cardiovascular function and lung mechanics in newborn lambs with pulmonary hypertension induced by tracheal instillation of meconium. Fifteen newborn lambs (<6 d old) were studied in three groups (n = 5): control, and pulmonary hypertension (5 mL x kg[-1] of a 20% meconium solution) with or without inhaled NO (20 ppm) exposure. Heart rate, systemic and pulmonary arterial pressures, arterial pH and blood gases, cardiac output, and pulmonary mechanics were measured. The exposure to inhaled NO in lambs with pulmonary hypertension, induced by experimental meconium aspiration, produced a transient response. There were a transient improvement in gas exchange, a decrease in pulmonary arterial pressure and airway resistance, without changes in cardiovascular profile. The transient and incomplete response to inhaled NO in experimental MAS might be related to the fact that hypoxemia is not only due to pulmonary vasoconstriction but also to parenchymal lung disease. We hypothesize that this poor and transient response could probably be avoided if strategies that increase lung recruitment, were applied before inhaled NO exposure.

Objective: Analysis of colorectal anastomosis stricture incidence after anterior resection of the rectum performed with the EEA-Stapler. To find out if differences existed in stricture incidence considering factors such, as age, neoplasia, postoperative radiotherapy, tumor stage and anastomic level., Design: Longitudinal descriptive study., Patients and Method: 67 patients who underwent rectal anterior resection using the EEA-Stapler were evaluated. Data from sex, age, indication for operation, postoperative radiotherapy, tumor staging and anastomic level were recorded and compared with presence of stricture anastomosis. Stenosis was evaluated and graded as follows: grade O, no stenosis; grade I, no symptoms, X-ray or endoscopic finding; grade II, symptoms, the patients require ballon catheter dilation; and grade III, invalidant symptoms, the patients require surgery., Results: Twelve patients (20%) were recorded as grade II and 3 patients (5%) as grade III. There were no statistically significant differences between prevalence of stricture and sex, age, neoplasic or non-neoplasic conditions, previous radiotherapy, level of anastomosis, and tumor stage., Conclusion: Stenosis after colorectal anastomosis with stapler devices must not be considered as an uncommon complication. In 20% of patients it may be a serious state that may require repeated catheter balloon dilations or surgery. Such condition is not dependent on diverse factors studied.

Objective: Extracorporeal membrane oxygenation (ECMO) is a technique used for cardiorespiratory support in the treatment of newborns with severe respiratory insufficiency. ECMO has not been used yet in newborns in Spain. The aim of this work was to develop an experimental veno-arterial ECMO model in newborn lambs for training the NICU medical and nursing staff before the clinical application of this technique., Material and Methods: Six newborn lambs were anesthetized, traqueotomized and connected to a neonatal ventilator. The right jugular vein and left carotid artery were cannulated and the catheters were located in the right atrium and aortic arch, respectively. A venous-arterial ECMO was performed during three hours, with an experimental ECMO circuit developed by us. Arterial pH and blood gases, systemic and airway pressures, heart rate, and rectal temperature were monitored., Results: The experimental ECMO circuit developed by use had a very low cost, but was capable of maintaining adequate gas exchange, acid-base balance and a normal rectal temperature., Conclusions: The development of an experimental ECMO model in newborn lambs may allow the establishment of an initial training program and to maintain the expertise of the NICU staff of a perinatal center planning to start an ECMO program.

Objective: Continuous hemofiltration is an extracorporeal technique used to eliminate water and solutes by convective transport through a hemofilter. The aim of this study was to develop an experimental model of arterio-venous and veno-venous continuous hemofiltration in order to gain experience before its clinical application in human neonates., Materials and Methods: Twelve white New Zealand adult rabbits were anesthetized, tracheotomized and connected to a continuous flow neonatal ventilator. Continuous arterio-venous hemofiltration (n = 6) was performed via catheters placed in the carotid artery and jugular vein and veno-venous hemofiltration (n = 6) by a double-lumen catheter located in the inferior vena cava. Heart rate, arterial pressure, pH and blood gases, and the volume of ultra-filtrate were monitored and recorded for a three hour period., Results: In both groups a high rate of ultrafiltration was achieved. The volume of ultrafiltration decreased somewhat during the second hour and remained stable thereafter. No hemodynamic changes were detected., Conclusions: The development of an experimental model for continuous arterio-venous and veno-venous hemofiltration in rabbits, facilitated the implantation of these techniques in human neonates. The model may be used to train the staff of the Neonatal Intensive Care Unit and to eliminate difficulties with vascular access and the care of extracorporeal lines.

We report a case of delayed cutaneous reaction to intramuscular treatment with cefonicid, a second generation cephalosporin. An isolated late skin test response was observed to cefonicid only and not to other beta-lactams. A patch test with cefonicid 1% was positive after 48 and 96 hours.

Twenty-eight patients (14 in an active treatment group and 14 in a placebo group) with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a placebo-controlled, randomized, double-blind study to evaluate the risk-benefit quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I antigen. The cat extract was biologically standardized and quantified with monoclonal antibodies (100 biological units: 33 microgram of Fel d I antigen, 650 micrograms of albumin, and 99 micrograms of Fel d Bd/K30 antigen). After 1 year of treatment, the systemic reactions to cat extract immunotherapy were mild and infrequent. Improvement was observed in the active treatment group in comparison with the placebo group in the medication-symptoms score (p < 0.001); in skin prick test (p < 0.001), conjunctival provocation test (p < 0.001), and allergen bronchoprovocation test (p < 0.05) results, and in nonspecific bronchial hyperreactivity measured with methacholine, which was not statistically significant. This study demonstrates the favorable risk-benefit quotient of the dose of 13.2 micrograms of Fel d I antigen, which may serve as a future reference in defining the optimum dose and appropriate proportion of antigens that should be administered in cat extract immunotherapy.