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BACKGROUND The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations. AIM To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). METHODS This observational study included 308 patients diagnosed with CRC and 308 ageand sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. RESULTS The adjusted models for potential confounding factors showed a direct association between milk and dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR third tertile vs first tertile = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR third tertile vs first tertile = 0.40, 95%CI: 0.20-0.80). CONCLUSION Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern. Supported by the Department of Health and Consumer Affairs, Basque Government, No. 2011111153; Saiotek, Basque Government, No. S-PE12UN058; Pre-doctoral grant from the Basque Government, No. PRE_2015_2_0084; and United States Department of Agriculture—Agricultural Research Service, No. 58-1950-4-003.

Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze differences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p &lt, 0.05), a lower intake of vitamin B2 (0.86 &plusmn, 0.23 vs. 0.92 &plusmn, 0.23 mg/1000 kcal, p &lt, 0.01) and calcium:phosphorus ratio (0.62 &plusmn, 0.12 vs. 0.65 &plusmn, 0.13, p &lt, 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p &lt, 0.001) or cholesterol (35.4% vs. 25.0%, p &lt, 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC. This work was supported by two projects (from the Department of Health and Consumer Affairs, Basque Government 2011111153; and Saiotek, Basque Government S-PE12UN058), by a pre-doctoral grant from the Basque Government (PRE_2016_2_0046), by the CIBERehd and by the U.S. Department of Agriculture-Agricultural Research Service (ARS), under agreement. 581950-4-003. Neither Basque Government nor U.S. Department of Agriculture-Agricultural Research Service (ARS) had a role in the design, analysis or writing of this article. CIBERehd is funded by the Instituto de Salud Carlos III.

Background: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. Objectives: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. Method: We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 mu g of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG(4) levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. Results: There were significant reductions in the combined symptom and medication score for the 0.37-mu g dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG(4) levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. Conclusion: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG(4) levels.

12 p.- 3 fig.- 2 tab., The surveillance and pathogen fighting functions of the complement system have evolved to protect mammals from life-threatening infections. In turn, pathogens have developed complex molecular mechanisms to subvert, divert and evade the effector functions of the complement. The study of complement immunoevasion by pathogens sheds light on their infection drivers, knowledge that is essential to implement therapies. At the same time, complement evasion also acts as a discovery ground that reveals important aspects of how complement works under physiological conditions. In recent years, complex interrelationships between infection insults and the onset of autoimmune and complement dysregulation diseases have led to propose that encounters with pathogens can act as triggering factors for disease. The correct management of these diseases involves the recognition of their triggering factors and the development and administration of complement-associated molecular therapies. Even more recently, unsuspected proteins from pathogens have been shown to possess moonlighting functions as virulence factors, raising the possibility that behind the first line of virulence factors there be many more pathogen proteins playing secondary, helping and supporting roles for the pathogen to successfully establish infections. In an era where antibiotics have a progressively reduced effect on the management and control of infectious diseases worldwide, knowledge on the mechanisms of pathogenic invasion and evasion look more necessary and pressing than ever, We gratefully acknowledge the support received during the preparation of this review. MCV has received funding from the Spanish Ministerio de Economía y Competitividad (CTQ2015-66206-C2-2-R and SAF2015-72961-EXP).

32 p.-2 fig. High-Throughput Protein Production in Yeast. In: Vincentelli R. (eds) High-Throughput Protein Production and Purification. Methods in Molecular Biology, vol 2025. Humana, New York, NY (2019), Yeasts are versatile single-celled fungi that grow to high cell densities on inexpensive media. With well-studied genetics and metabolism and a wealth of knowledge available about their propagation and growth in academic as well as industrial settings, yeasts have long been used for recombinant protein production of isolated proteins and multisubunit complexes. They can be easily adapted to high-throughput protein expression pipelines. Importantly, the outcome from small-scale expression evaluations in high-throughput mode is scalable to laboratory and industrial scales using well-established procedures. In this chapter, we offer a state-of-the-art perspective on currently available high-throughput pipelines for protein production in S. cerevisiae and P. pastoris and discuss future challenges and avenues for improvement., MCV has received funding from the SpanishMinisterio de Economía y Competitividad (CTQ2015-66206-C2-2-R and SAF2015-72961-EXP) and the Regional Government of Madrid (S2017/BMD-3673).

Increases in the frequency of micronuclei (MN) in exposed cells can be used as a measure of genotoxicity. Hair dyes contain chemicals that are eliminated by urine and could be genotoxic to urothelial cells. To address this question, we evaluated whether hair dye use is associated with an increase in the frequency of MN in urothelial cells, and whether this association is modified by NAT1 (N-acetyltransferase 1), NAT2 (N-acetyltransferase 2) and GSTM1 (glutathione-S-transferase M1) genotypes. We included 92 women participating as controls in a bladder cancer case-control study in Spain. Of those, 72 had adequate number of cells to be included in the MN analysis. There were no significant differences in the mean MN frequency in women using hair dyes in the last month (9.88 MN/1000 cells), in comparison with the MN in unexposed women (9.50 MN/1000 cells). No statistically significant differences in MN frequency were observed by type of hair dye or color of the hair dye. Comparison of subjects in the highest quartile of MN frequency (> or = 12 MN/1000 cells) and those in the lowest quartile (< or = 4 MN/1000 cells) suggested an association between hair dye use and elevated MN frequency (OR 14.2 (95% CI 0.81-247.8; P=0.069)). None of the polymorphisms examined significantly modified association between hair dye use and frequency of MN. Findings of an increased frequency of MN in urothelial cells of hair dye users suggest a possible genotoxic effect of hair dye compounds and need confirmation in larger studies.

An increased bladder cancer risk has been suggested among users of hair dyes. We evaluated this association among females in a hospital-based case-control study in Spain (152 female incident cases, 166 female controls). The effect of hair dye use was also evaluated among potentially susceptible subgroups defined by NAT1, NAT2, CYP1A2 , GSTM1, GSTT1 and GSTP1 genotypes. Use of any hair dye (OR = 0.8, CI 0.5–1.4) or of permanent hair dyes (OR = 0.8, CI 0.5–1.5) was not associated with increased risk. Small non-significant increases in risks were observed in a lagged analysis that ignores exposures within ten years of diagnosis (OR = 1.3, CI 0.8–2.2). No trend in risk with increasing exposure was seen for duration of use, average use or cumulative use. None of the polymorphisms examined significantly modified the hair dye associated risk. Overall, this study does not support an association between hair dye use and bladder cancer.

The organisation of information in a web site is more useful if it adapts to the way the user thinks and behaves. This is especially important in e-learning sites, where usability is directly linked to the way the user learns. The best way to manage an intuitive and easy-to-use web site it is to organise the site as the student would: that is, following the way the user thinks and manages information. One method is to apply the card sorting technique based on observation of how the users form groupings and associate a predetermined number of categories. In this paper the authors present the results of applying this technique to an e-learning project at the University of Granada (Cevug). Sixty people were studied as they organised twelve categories included in the WebCT platform and a quantitative analysis was made of the results by different statistical techniques: clustering and MDS.

Background: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case–control studies. Methods: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. Results: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8–1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0–3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. Conclusion: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens. Yes

Multicenter Study; Research Support, Non-U.S. Gov't; Cross-reactivity of plant foods is an important phenomenon in allergy, with geographical variations with respect to the number and prevalence of the allergens involved in this process, whose complexity requires detailed studies. We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity between fruit and pollen allergies. A representative panel of 16 purified TLPs was printed onto an allergen microarray. The proteins selected belonged to the sources most frequently associated with peach allergy in representative regions of Spain. Sera from two groups of well characterized patients, one with allergy to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant allergens (PAG), were obtained from seven geographical areas with different environmental pollen profiles. Cross-reactivity between members of this family was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed noticeable allergenic activity in the studied populations. Pru p 2.0201, the peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be allergens of probable relevance to fruit allergy, being mainly associated with pollen sensitization, and strongly linked to specific geographical areas such as Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited >50% positive response to Pru p 2.0201 and to chestnut TLP in these specific areas. Therefore, their recognition patterns were associated with the geographical area, suggesting a role for pollen in the sensitization of these allergens. Finally, the co-sensitizations of patients considering pairs of TLP allergens were analyzed by using the co-sensitization graph associated with an allergen microarray immunoassay. Our data indicate that TLPs are significant allergens in plant food allergy and should be considered when diagnosing and treating pollen-food allergy. Yes

An abnormal fibrinogen was discovered in the plasma of a clinically asymptomatic woman. Laboratory evaluation of five members of the affected family showed low fibrinogen values in kinetic assays whereas the fibrinogen levels, tested by immunological procedures were normal. The patient's plasma had an inhibitory effect on the thrombin time of normal plasma. The calcium ions totally corrected the thrombin and reptilase times. Either low or high ionic strength prolonged the thrombin time of the proposita's purified fibrinogen. Kinetic analysis of clotting by monitoring transmission at 350 nm showed abnormally slow clotting with thrombin and reptilase. Assays were preformed in whole plasma as well as in purified fibrinogen. A delay in the rate of polymerization was evident when purified patient monomers were compared with those of normals. Immunoelectrophoretic, chromatofocusing, and isoelectrofusing experiments detected neither structural nor immunological abnormalities of fibrinogen. The rate of release of fibrinopeptide A by thrombin, measured by a specific immunoenzymatic method was also normal. HPLC analysis showed normal liberation of fibrinopeptides after prolonged thrombin action. Cross-linking of fibrin by factor XIII and lysis of fibrinogen by plasmin were normal. In view of these results, the defect of this dysfibrinogenemia, designated as Fibrinogen Oviedo I, probably could be due to conformational modifications in the D section of the molecule.

Background/objective: Textile manufacturing is a complex industry that has frequently been associated with bladder cancer. However, results have not been consistent. This study investigated the risk of bladder cancer in Spanish textile workers. Methods: We analysed data from a multicentre hospitalbased case-control study carried out in Spain (1998– 2001) including 1219 cases of bladder cancer and 1271 controls. Of those, 126 cases and 122 controls reported a history of employment in the textile industry. Lifetime occupational history was obtained using a computerassisted personal interview. Occupations, locations and materials used in the textile industry were assessed using a detailed questionnaire and expert assessment. Results: Overall, no increased risk of bladder cancer was found for textile workers, including duration of employment analysis. Increased risks were observed for weavers (OR = 1.82, 95% CI 0.95 to 3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working for more than 10 years appeared to be associated with an increased risk for weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62, 95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials. Statistically significant higher risks were also found for specific combinations of occupations or locations with exposure to synthetics and cotton. Conclusions: There was no overall increased risk for textile workers, but increased risks were found for specific groups of workers. Our findings indicate that observed risks in previous studies may be better evaluated by analysis of materials used or section worked within the industry and occupation.

Resumen basado en el de la publicación Se analiza la conducta infantil asertiva en una tarea de oposición asertiva frente al adulto, examinando las relaciones entre dos conjuntos de variables: a) valoraciones sociales de carácter general consistentes en informes sobre habilidades sociales a partir del profesor, los iguales y el propio alumnado, y b) medidas específicas del comportamiento en la situación tomadas a partir del profesor y de la grabación por un video. Se examinan los contrastes entre las fuentes evaluadoras empleadas. Los resultados apuntan a que la valoración por informe del profesor y el sociométrico se asocian a la evaluación del comportamiento asertivo hecha por el profesor y por las analistas del video. El informe del propio alumnado se asocia con las restantes medidas solo en la valoración del comportamiento asertivo con adultos por informe. En las restantes medidas de competencia social y asertividad, de carácter más general, la evaluación del propio alumno se relaciona negativamente con la del profesor y con la del análisis del video. La discusión enfatiza la necesidad de tener en cuenta estas diferencias entre alumnado y profesorado en la valoración de la conducta social, en la orientación e intervención psicoeducativa, ya que no tomarlas en cuenta puede incidir negativamente en la evaluación del ámbito de las relaciones sociales y del clima del centro escolar. Madrid Biblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; biblioteca@mecd.es ESP

International audience; OBJECTIVE: A recent study suggested that risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. We pooled primary data from 14 case-control studies of bladder cancer from Europe and North America and evaluated differences in risk of smoking by gender. METHODS: The pooled analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30-79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking were adjusted for age and study. Exposure-response was evaluated in a stratified analysis by gender and by generalized additive models. RESULTS: The odds ratios for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR = 3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women (OR = 3.9). ORs increased with duration and intensity in both genders and the exposure-response patterns were remarkably similar between genders. CONCLUSION: These results do not support the hypothesis that women have a higher relative risk of smoking-related bladder cancer than men.

Summary Background P53 is the most widely investigated molecular marker in bladder cancer. We aimed to review comprehensively the evidence for use of changes in P53 to predict bladder-cancer recurrence, progression, and mortality. Methods We reviewed 168 publications from 117 studies. Estimates of significance were extracted from association tests, and hazard ratios with 95% CI from actuarial curves and Cox regression analyses. A meta-analysis was done on the studies that applied Cox models. Findings The methods used to assess significance varied widely between studies. 27% (nine of 34) of studies that assessed the prognostic value of P53 overexpression in recurrence by use of multivariate tests showed a significant association. The corresponding values for progression and mortality were 50% (12 of 24) and 29% (ten of 35), respectively. In the studies that used Cox models, the overall risk of recurrence was 1·6 (95% CI 1·2–2·1), of progression was 3·1 (1·9–4·9), and of mortality was 1·4 (1·2–1·7). These findings could be overestimates because of publication and reporting bias. Interpretation After 10 years of research, evidence is not sufficient to conclude whether changes in P53 act as markers of outcome in patients with bladder cancer.

Background: Many reported associations between common genetic polymorphisms and complex diseases have not been confirmed in subsequent studies. An exception could be the association between NAT2 slow acetylation, GSTM1 null genotype, and bladder-cancer risk. However, current evidence is based on meta-analyses of relatively small studies (range 23–374 cases) with some evidence of publication bias and study heterogeneity. Associations between polymorphisms in other NAT and GST genes and bladder-cancer risk have been inconsistent. Methods: We investigated polymorphisms in NAT2, GSTM1, NAT1, GSTT1, GSTM3, and GSTP1 in 1150 patients with transitional-cell carcinoma of the urinary bladder and 1149 controls in Spain; all the participants were white. We also carried out meta-analyses of NAT2, GSTM1, and bladder cancer that included more than twice as many cases as in previous reports. Findings: In our study, the odds ratios for bladder cancer for individuals with deletion of one or two copies of the GSTM1 gene were 1·2 (95% CI 0·8–1·7) and 1·9 (1·4–2·7) respectively (p for trend

This paper presents a proposal of methodological adaptation for the development of accessible web sites. This proposal is based on the «Inclusive Design» concept and extends User-Centered Design methodology in order to satisfy the needs of a wider range of users than those represented by the «average-user», involving in the development process users with disabilities and users in negative contexts of use.

8 pages, 5 figures, 4 tables.-- PMID: 12594192 [PubMed].-- PMCID: PMC1732410., STUDY OBJECTIVE: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer., DESIGN: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes., SETTING: Populations in Europe and North America., PARTICIPANTS: Those included in six case-control studies (6084 incident bladder cancer cases, 10,816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria., MAIN RESULTS: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes., CONCLUSIONS: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods., CM Villanueva has a fellowship from the Department of University, Research and Society of the Information, of the Generalitat de Catalunya (Government of Catalonia). This project is partially funded by the CIRIT grant no 1999SGR 00241 (Generalitat de Catalunya), by FIS contract 01/1326E, and by the DG SANCO Project 2001/CAN/112.

Ultra-Levura (Upsamedica, Spain) is a yeast (Saccharomyces boulardii) widely used as a biotherapeutic agent. To date, few adverse effects have been reported, although fungemia with Saccharomyces cerevisiae can occur in weak and immunosuppressed patients. Reported here are two cases of fungemia with Saccharomyces cerevisiae. One patient had been treated with Ultra-Levura and the other contracted the infection from the first. This is the first report of infection with Saccharomyces boulardii (Saccharomyces cerevisiae) in a patient who was not being treated with the agent.

A prospective clinical microbiological study of pleural fluid samples was conducted to investigate the etiology of pleural effusions and to evaluate two different methods for transport and culture of these samples. A total of 245 pleural fluid specimens were inoculated into a transport vial, an aerobic and an anaerobic blood culture vial, and a sterile tube. One hundred nine samples were from infectious patients and 128 from noninfectious patients. Gram stain had a sensitivity of 48% and a specificity of 100% as compared to culture. Of the total, 15.5% of the samples were positive for microorganisms, and 60% of the positive samples were nonpurulent pleural fluid. Single-organism growth was found in 23 samples (60.5%). Sixty-three microorganisms were isolated: 25 (39.7%) aerobic, 22 (35%) anaerobic, 13 (20.6%) mycobacteria, and three (4.7%) fungi. Of the 25 positive samples, excluding those samples that grew mycobacteria, nine (36%) were positive exclusively in the blood culture vials. Twelve organisms were isolated, only one of which did not grow in the anaerobic vial. Two (8%) samples were positive by conventional culture only, and 14 (56%) were positive by both methods. The microorganism isolation rate obtained with use of blood culture vials was significantly greater than that obtained with the conventional method of transport and culture. Sixty-three percent of the empyema patients had an associated underlying pathology, pneumonia being the most frequent. In conclusion, for microbiological study of pleural fluid, it seems appropriate to inoculate all samples, including nonpurulent samples, into both a sterile tube and an anaerobic blood culture vial.

Purpose: The response of endothelium to ionizing radiation was studied. Methods and Materials: The abdominal aorta in different experimental groups of rats was irradiated, and the response of arterial rings from the irradiated segments to norepinephrine, acetylcholine (ACh), and nitroglycerin (NTG) was studied. Nonirradiated thoracic segments in the same experimental animals were used as as a control for comparisons. Two age-matched nonirradiated control groups were also studied. Results: A poor endothelium-dependent vasodilator response was obtained with ACh in the irradiated rings and also in those not directly irradiated; the endothelium-independent vasodilator response to NTG was preserved during the first 3 days after irradiation. By 6 months, both the endothelium-dependent response and endothelium-independent response were impaired. Conclusions: Alterations in nitric oxide synthesis and/or release by the endothelium were observed during the early phase of radiation in irradiated and nonirradiated segments. In the delayed phase of radiation, endothelium-independent muscular relaxation was also affected.

This volume brings together a selection of 28 out of the 76 papers read at ICHEL-7 in Valencia. The book opens with a general section, in which Richard Hogg examines the relationship between linguistics and philology, Enrique Bernardez analyzes syntactic change from the point of view of catastrophe theory, Roger Sell suggests a pragmatic analysis of historical data, and Norman Blake and Jacek Fisiak re-open the debate on periodization in the history of English. The rest of the papers is grouped in four sections: Phonology and Writing, Morphology and Syntax, Lexicology and Semantics, and Varieties of English and Studies on Individual Texts. An index of names and a subject index complete the volume.

The clinical features of Hashimoto’s encephalopathy may be confused with those of Creutzfeldt–Jakob disease (CJD).1 The diagnosis of encephalopathy associated with Hashimoto’s thyroiditis is established by the detection of antithyroid antibodies and variable degrees of thyroid dysfunction.1,2 The definitive diagnosis of CJD requires histologic confirmation. Nevertheless, in an adequate clinical setting, the presence of 14-3-3 protein in the CSF is a useful marker for the in vivo diagnosis of CJD, because false-positive results are seen in disorders that are usually not considered in the differential diagnosis.3,4 We report a patient with Hashimoto’s encephalopathy with two unusual features: the presence of opsoclonus and the detection of 14-3-3 brain protein in the CSF. A 41-year-old woman was admitted in January 1997 because of a generalized epileptic seizure. She had been well until November 1996, when her family noticed abnormal behavior with irritability, paranoid ideation, and insomnia. During the ensuing weeks, she developed memory loss and reduced speech that led to mutism. One week before admission, her gait became unsteady, and she developed focal epileptic seizures in the right arm and uncoordinated ocular …

INTRODUCTION Perforating artery disease is still the main cause of lacunar infarcts (LI), while the relationship between this type of ischemia and carotid stenosis (CS) is controversial. OBJECTIVE To assess the association between CS and LI in patients with criteria of localized ischemia in the carotid territory separately analyzing isolated LI and multiples LIs. PATIENTS AND METHODS Three hundred and thirty patients with a first episode of cerebral infarct in the area supplied by the carotid artery were registered prospectively. There were 205 LI (135 isolated and 70 multiple) which could be differentiated from 125 non-lacunar infarcts (NLI). The vascular risk factors were determined and the degree of carotid stenosis measured by duplex-colour ultrasound exploration. RESULTS In the isolated LI group the frequency of presentation of CS greater than 50% was 22% for the artery ipsilateral to the LI and 8% for the contralateral artery. For significant CS (> 70%) frequencies of 14% (ipsilateral) and 8% (contralateral) were observed. On comparative analysis with the NLI group, the presence of stenosis greater than 50 to 70% was significantly higher in these for both ipsilateral and contralateral arteries. In the LI group, isolated CS was significantly more frequent on the side which was homolateral to the ischemia as compared to its isolated presence on the contralateral side (22/30 vs 4/12; OR: 5.5 [95% CI: 1.2-23]). Ipsilateral CS greater than 70% behaved as a factor which was significantly associated with the multiple LI subtype with a unilateral pattern. CONCLUSION CS should be considered a risk factor for LI.

Different coagulation and fibrinolysis parameters were investigated in 149 patients with metastatic and non-metastatic tumours and results were compared with those obtained in a healthy population. Results showed a significant increase of thrombin-antithrombin complexes, fibrinopeptide A (FPA) and fibrin monomers in the group of patients (p less than 0.001). There was also a significant prolongation of euglobulin lysis time (p less than 0.005) and an increase of plasminogen activator inhibitor activity (p less than 0.0001), fibrinogen degradation products (p less than 0.001), and D-dimer (p less than 0.05) in the group of patients as compared to controls; FPA levels were also increased in patients with metastases (p less than 0.005). This study demonstrates clotting activation, at the level of fibrinogen to fibrin conversion, and impairment of fibrinolysis in patients with malignancy.

A 70-yr-old man with multiple myeloma IgD developed a plasma cell leukemia producing a serum IgD monoclonal peak and lambda light chains in the urine. When the serum and the urine were heated at 56 degrees C for 30 min both monoclonal bands disappeared. The precipitate failed to redissolve on heating to 100 degrees C. Ion exchange chromatography with a linear gradient of phosphate buffer, pH 8, 0.020-0.300 mol/l and column electrofocusing showed that the serum pyroglobulin was eluted with buffer concentration between 0.040-0.125 mol/l and had an isoelectric point of 5.02, while the pyroglobulin of the urine was eluted with 0.020-0.033 mol/l and had a pI = 7.16. The serum and urine pyroglobulins had a total antigenic community with their correspondent purified proteins. The isolated lambda chains did not change when they were heated at 56 degrees C for 30 min, nevertheless, the heated purified IgD shows some changes in its isoelectric point, molecular mass and antigenicity. These changes in the purified IgD suggest that the pyroprecipitability could be due to conformational features.

A dysfibrinogenemia (fibrinogen Sevilla) was detected in a 64-yr-old woman with no previous history of hemorrhagic diathesis or thrombosis. Thrombin and reptilase times were prolonged. The aggregation of fibrin monomers showed a prolonged latency time with a defective slope although fibrinopeptide release and clot stabilization were found to be normal. Plasmin proteolysis was abnormal with a much slower plasmic degradation in patient's purified fibrinogen. By chromatofocussing the patient's fibrinogen showed an abnormality in pattern elution with a second peak eluting at a pH slightly more basic than the normal one (pH 5.5). Likewise, the isoelectrofocussing of purified non-reduced patient's fibrinogen in agarose gel showed an abnormal distribution in its focussed bands, especially in a group which focussed in a pI-interval between 5.20-5.85. By two-dimensional electrophoresis we did not find any abnormality in the fibrinogen-reduced chains. These results could indicate that the abnormal monomer aggregation, as well as the defective plasmin lysis, could be due to conformational aspects of fibrinogen rather than to structural defects.

The aim of the present study was to assess the effects of daily stress perception on cognitive performance and morning basal salivary cortisol and alpha-amylase levels in healthy children aged 9–12. Participants were classified by whether they had low daily perceived stress (LPS,n= 27) or a high daily perceived stress (HPS,n= 26) using the Children Daily Stress Inventory (CDSI). Salivary cortisol and alpha-amylase were measured at awakening and 30 minutes later. Cognitive performance was assessed using the Cognitive Drug Research assessment system. The HPS group exhibited significantly poorer scores on speed of memory (p < .05) and continuity of attention (p< .05) relative to the LPS group. The HPS group also showed significantly lower morning cortisol levels at awakening and at +30 minutes measures in comparison with the LPS group (p< .05), and mean morning cortisol levels were negatively correlated with speed of memory (p< .05) in the 53 participants. No significant differences were observed between both groups in alpha-amylase levels. These findings suggest that daily perceived stress in children may impoverish cognitive performance via its modulating effects on the HPA axis activity.