Biomarcadores precoces de fracaso renal agudo tras angiografía coronaria o cirugía cardíaca en pacientes con síndrome coronario o fallo cardíaco agudos / Early biomarkers of acute kidney failure after heart angiography or heart surgery in patients with acute coronary syndrome or acute heart failure

Antecedentes: El fracaso renal agudo (FRA) es una complicación frecuente tras la cirugía cardíaca y la angiografía coronaria que ensombrece el pronóstico de estos pacientes. El diagnóstico se basa en el ascenso de la creatinina sérica, que es tardío. Es necesaria la identificación y validación de nuevos biomarcadores precoces que permitan intervenciones más tempranas y eficaces. Objetivos: Evaluar la sensibilidad y especificidad de interleuquina-18 (IL-18) en orina, neutrophil gelatinase-associated lipocalin en orina (uNGAL) y cistatina C en suero para la detección precoz del FRA en una población de pacientes con síndrome coronario agudo o fallo cardíaco y sometidos a cirugía cardíaca o cateterismo. Métodos: Se incluyeron en el estudio 135 pacientes ingresados en una unidad de cuidados intensivos por síndrome coronario agudo o fallo cardíaco por patología coronaria o valvular y a los que se realizaron una angiografía cardíaca o una cirugía cardíaca de revascularización o recambio valvular. Se determinaron los biomarcadores a las 12 horas de la intervención y se monitorizó la creatinina sérica durante los siguientes seis días para el diagnóstico del FRA. Resultados: Para NGAL se obtuvo un área bajo la curva ROC (AUC) de 0,983 y para cistatina C e IL-18 de 0,869 y 0,727, respectivamente. Para un punto de corte de NGAL en orina de 31,9 ng/ml la sensibilidad fue del 100% y la especificidad del 91%. Conclusiones: uNGAL es un marcador precoz de FRA en pacientes con síndrome coronario o fallo cardíaco agudo y sometidos a cirugía cardíaca y angiografía cardíaca, con una capacidad predictiva superior a cistatina o a IL-18 (AU)

Background: Acute kidney injury (AKI) is a common complication in cardiac surgery and coronary angiography, which worsens patients' prognosis. The diagnosis is based on the increase in serum creatinine, which is delayed. It is necessary to identify and validate new biomarkers that allow for early and effective interventions. Aims: To assess the sensitivity and specificity of neutrophil gelatinase-associated lipocalin in urine (uNGAL), interleukin-18 (IL-18) in urine and cystatin C in serum for the early detection of AKI in patients with acute coronary syndrome or heart failure, and who underwent cardiac surgery or catheterization. Methods: The study included 135 patients admitted to the intensive care unit for acute coronary syndrome or heart failure due to coronary or valvular pathology and who underwent coronary angiography or cardiac bypass surgery or valvular replacement. The biomarkers were determined 12 hours after surgery and serum creatinine was monitored during the next six days for the diagnosis of AKI. Results: The area under the ROC curve (AUC) for NGAL was 0.983, and for cystatin C and IL-18 the AUCs were 0.869 and 0.727, respectively. At a cut-off of 31.9ng/ml for uNGAL the sensitivity was 100% and the specificity was 91%. Conclusions: uNGAL is an early marker of AKI in patients with acute coronary syndrome or heart failure and undergoing cardiac surgery and coronary angiography, with a higher predictive value than cystatin C or IL-18 (AU)

Insuficiencia cardiaca en el seno de un síndrome coronario agudo como predictor de infarto a largo plazo / Acute coronary syndrome complicated by heart failure as predictor of long-term infarction

Antecedentes. La insuficiencia cardiaca (Killip>I) en pacientes con síndrome coronario agudo (SCA) es un reconocido factor de riesgo para mortalidad; sin embargo, su relación con la aparición de nuevos episodios isquémicos agudos no ha sido bien establecida. Objetivo. El objetivo del presente trabajo fue evaluar la asociación entre Killip>I al ingreso y la aparición de infarto agudo de miocardio (IAM) tras el alta hospitalaria por SCA. Pacientes y métodos. Se estudió de forma prospectiva y consecutiva 972 y 426 supervivientes a un SCA sin elevación del segmento ST (SCASEST) e IAM con elevación del segmento ST (IAMCEST) respectivamente. Se determinó la presencia de Killip>I en el momento del ingreso junto con variables pronósticas clásicas. La asociación entre Killip>I e IAM se determinó mediante regresión de Cox adaptada para episodios competitivos. Resultados. Durante una mediana de seguimiento de 3 años, 135 (13,9%) y 53 (12,4%) pacientes con SCASEST y IAMCEST presentaron un IAM. Los pacientes con SCASEST y IAMCEST con Killip>I (15,6 y 21,3% respectivamente) presentaron más frecuentemente IAM (28,3 vs 6,3 y 10,6 vs 3,3 por 100 pacientes-año seguimiento, p<0 001 respectivamente el análisis multivariante ajustado por factores de riesgo y controlado episodios competitivos muerte revascularización confirmó que scasest iamcest killip I mostraron un incremento en el riesgo de IAM (HR=1,76; IC 95%: 1,15-2,68; p<0 009 y hr="1,90;" ic 95 : 1 07-3 36 p="0,029" respectivamente. Conclusiones. En pacientes con SCASEST y IAMCEST, la presencia de Killip>I al ingreso se asocia de manera independiente con mayor riego de IAM en el seguimiento(AU)

Background. Heart failure (Killip>I) in patients with acute coronary syndrome (ACS) is a recognized risk factor for death. However, its relationship with the risk of new acute ischemic events has not been well established. Objective. The aim of this study has been to evaluate the association between Killip>I on admission and the risk of a new acute myocardial infarction (AMI) during follow-up due to ACS. Patients and methods. A total of 972 and 426 survivors of an ACS with non-ST segment evaluation (Non-STE-ACS) and AMI with ST segment elevation (STEMI) were studied prospectively and consecutively. The presence of Killip>I was determined on admission together with the classical prognostic variables. The relationship between Killip>I and subsequent post-discharge AMI was established with the Cox regression adapted for competitive events. Results. During a median follow-up of 3 years, 135 (13.9%) and 53 (12.4%) patients with Non-STE-ACS and STEMI presented a new AMI. Patients with Non-STE-ACS and STEMI with Killip>I (15.6% and 21.3% respectively) showed a higher incidence of AMI (28.3 vs 6.3 and 10.6 vs 3.3 per 100 patients-years of follow-up, p<0 001 respectively in the multivariate analysis adjusted for traditional risk factors and controlled competitive events death revascularization confirmed that killip I subjects with Non-STE-ACS and STEMI showed a significantly higher risk of AMI (HR: 1.76; CI 95%: 1.15-2.68; p=0.009 and HR: 1.90; 95% CI: 1.07-3.36; p=0.029 respectively). Conclusions. In patients with Non-STE-ACS and STEMI, the presence of Killip>I on admission is independently associated to an increased risk of long-term AMI(AU)

[Acute coronary syndrome complicated by heart failure as predictor of long-term infarction]. / Insuficiencia cardiaca en el seno de un síndrome coronario agudo como predictor de infarto a largo plazo.

BACKGROUND: Heart failure (Killip>I) in patients with acute coronary syndrome (ACS) is a recognized risk factor for death. However, its relationship with the risk of new acute ischemic events has not been well established. OBJECTIVE: The aim of this study has been to evaluate the association between Killip>I on admission and the risk of a new acute myocardial infarction (AMI) during follow-up due to ACS. PATIENTS AND METHODS: A total of 972 and 426 survivors of an ACS with non-ST segment evaluation (Non-STE-ACS) and AMI with ST segment elevation (STEMI) were studied prospectively and consecutively. The presence of Killip>I was determined on admission together with the classical prognostic variables. The relationship between Killip>I and subsequent post-discharge AMI was established with the Cox regression adapted for competitive events. RESULTS: During a median follow-up of 3 years, 135 (13.9%) and 53 (12.4%) patients with Non-STE-ACS and STEMI presented a new AMI. Patients with Non-STE-ACS and STEMI with Killip>I (15.6% and 21.3% respectively) showed a higher incidence of AMI (28.3 vs 6.3 and 10.6 vs 3.3 per 100 patients-years of follow-up, p<0.001, respectively). In the multivariate analysis, adjusted for traditional risk factors and controlled for competitive events (death and revascularization), confirmed that Killip>I subjects with Non-STE-ACS and STEMI showed a significantly higher risk of AMI (HR: 1.76; CI 95%: 1.15-2.68; p=0.009 and HR: 1.90; 95% CI: 1.07-3.36; p=0.029 respectively). CONCLUSIONS: In patients with Non-STE-ACS and STEMI, the presence of Killip>I on admission is independently associated to an increased risk of long-term AMI.

Plasma Brain Natriuretic Peptide Levels in Cardiac Function Assessment in Chronic Dialysis Patients.

BACKGROUND: Brain natriuretic peptide (BNP) is elevated in patients with end-stage renal disease and could reflect left ventricular dysfunction. AIM: To evaluate the plasma levels of BNP in two groups of asymptomatic patients on different dialysis programs and to correlate their variations with echocardiographic parameters. METHODS: Group A consisted of 36 patients on chronic hemodialysis (HD), and group B included 38 patients on continuous ambulatory peritoneal dialysis (CAPD). ECG and echocardiography were performed, and concomitantly plasma BNP levels were determined before and after a regular 4-hour session in HD patients and before performing a dialysate exchange in patients on CAPD. RESULTS: BNP values in group A were found to be higher than in group B (419 ± 76 vs. 193 ± 56 pg/ml; p < 0.03). The cutoff point which discriminated both groups was 194 pg/ml (sensitivity: 64% and specificity: 76%; p = 0.001). Significant differences were found with respect to the following echocardiographic data (group A vs. group B): left atrial (LA) size (40 ± 13 vs. 34 ± 1 mm), LA volume (59 ± 16 vs. 41 ± 32 ml), transmitral flow E/A (1.17 ± 0.01 vs. 0.9 ± 0.06), the movement of the mitral valve annulus e/a (tissue Doppler imaging; 1.19 ± 0.15 vs. 1.05 ± 0.13) and left ventricular mass index (133 ± 10 vs. 108 ± 11). CONCLUSION: Patients on CAPD had lower levels of BNP, and echocardiographic findings indicated decreased volume overload. In asymptomatic patients, marked increases in BNP levels may reflect early stages of pathological processes that precede the development of apparent cardiac manifestations (left ventricular hypertrophy). Only echocardiographic parameters of cardiac dysfunction should be used as diagnostic criteria.

Selection for thermostability can lead to the emergence of mutational robustness in an RNA virus.

Mutational robustness has important evolutionary implications, yet the mechanisms leading to its emergence remain poorly understood. One possibility is selection acting on a correlated trait, as for instance thermostability (plastogenetic congruence). Here, we examine the correlation between mutational robustness and thermostability in experimental populations of the RNA bacteriophage Qß. Thermostable viruses evolved after only six serial passages in the presence of heat shocks, and genome sequencing suggested that thermostability can be conferred by several alternative mutations. To test whether thermostable viruses have increased mutational robustness, we performed additional passages in the presence of nitrous acid. Whereas in control lines this treatment produced the expected reduction in growth rate caused by the accumulation of deleterious mutations, thermostable viruses showed no such reduction, indicating that they are more resistant to mutagenesis. Our results suggest that selection for thermostability can lead to the emergence of mutational robustness driven by plastogenetic congruence. As temperature is a widespread selective pressure in nature, the mechanism described here may be relevant to the evolution of mutational robustness.

A genetic background with low mutational robustness is associated with increased adaptability to a novel host in an RNA virus.

Although mutational robustness is central to many evolutionary processes, its relationship to evolvability remains poorly understood and has been very rarely tested experimentally. Here, we measure the evolvability of Vesicular stomatitis virus in two genetic backgrounds with different levels of mutational robustness. We passaged the viruses into a novel cell type to model a host-jump episode, quantified changes in infectivity and fitness in the new host, evaluated the cost of adaptation in the original host and analyzed the genetic basis of this adaptation. Lineages evolved from the less robust genetic background demonstrated increased adaptability, paid similar costs of adaptation to the new host and fixed approximately the same number of mutations as their more robust counterparts. Theory predicts that robustness can promote evolvability only in systems where large sets of genotypes are connected by effectively neutral mutations. We argue that this condition might not be fulfilled generally in RNA viruses.

Experimental evolution of plant RNA viruses.

Undoubtedly, viruses represent a major threat faced by human and veterinary medicines and by agronomy. The rapid evolution of viruses enables them to escape from natural immunities and from state-of-the-art antiviral treatments, with new viruses periodically emerging with deadly consequences. Viruses have also become powerful and are increasingly used tools in the field of experimental evolution. A growing body of evidence points that the evolution of viruses is mainly determined by key features such as their compacted genomes, enormous population sizes, and short generation times. In addition, RNA viruses also present large selection coefficients, antagonistic epistasis, and high mutation rates. Most of this knowledge comes from studies that have used either bacteriophages or animal viruses in cell cultures as experimental systems. However, plant viruses provide almost identical advantages for evolutionary studies and, in addition, offer an invaluable tool for studying the interplay between viruses and pluricellular hosts. Without seeking to be exhaustive, here we summarize some peculiarities of plant viruses and review recent experiments that have explored important questions on evolution, such as the role of deleterious mutation and neutrality, the effect of different transmission modes in the evolution of virulence, and the heterogeneous selective constraints imposed by multiple hosts.

Theory of lethal mutagenesis for viruses.

Mutation is the basis of adaptation. Yet, most mutations are detrimental, and elevating mutation rates will impair a population's fitness in the short term. The latter realization has led to the concept of lethal mutagenesis for curing viral infections, and work with drugs such as ribavirin has supported this perspective. As yet, there is no formal theory of lethal mutagenesis, although reference is commonly made to Eigen's error catastrophe theory. Here, we propose a theory of lethal mutagenesis. With an obvious parallel to the epidemiological threshold for eradication of a disease, a sufficient condition for lethal mutagenesis is that each viral genotype produces, on average, less than one progeny virus that goes on to infect a new cell. The extinction threshold involves an evolutionary component based on the mutation rate, but it also includes an ecological component, so the threshold cannot be calculated from the mutation rate alone. The genetic evolution of a large population undergoing mutagenesis is independent of whether the population is declining or stable, so there is no runaway accumulation of mutations or genetic signature for lethal mutagenesis that distinguishes it from a level of mutagenesis under which the population is maintained. To detect lethal mutagenesis, accurate measurements of the genome-wide mutation rate and the number of progeny per infected cell that go on to infect new cells are needed. We discuss three methods for estimating the former. Estimating the latter is more challenging, but broad limits to this estimate may be feasible.

Simple-sequence repeat markers used in merging linkage maps of melon (Cucumis melo L.).

A set of 118 simple sequence repeat (SSR) markers has been developed in melon from two different sources: genomic libraries (gSSR) and expressed sequence-tag (EST) databases (EST-SSR). Forty-nine percent of the markers showed polymorphism between the 'Piel de Sapo' (PS) and PI161375 melon genotypes used as parents for the mapping populations. Similar polymorphism levels were found in gSSR (51.2%) and EST-SSR (45.5%). Two populations, F2 and a set of double haploid lines (DHLs), developed from the same parent genotypes were used for map construction. Twenty-three SSRs and 79 restriction fragment length polymorphisms (RFLPs), evenly distributed through the melon genome, were used to anchor the maps of both populations. Ten cucumber SSRs, 41 gSSRs, 16 EST-SSR, three single nucleotide polymorphism (SNP) markers, and the Nsv locus were added in the DHL population. The maps developed in the F2 and DHL populations were co-linear, with similar lengths, except in linkage groups G1, G9, and G10. There was segregation distortion in a higher proportion of markers in the DHL population compared with the F2, probably caused by selection during the construction of DHLs through in vitro culture. After map merging, a composite genetic map was obtained including 327 transferable markers: 226 RFLPs, 97 SSRs, three SNPs, and the Nsv locus. The map length is 1,021 cM, distributed in 12 linkage groups, and map density is 3.11 cM/marker. SSR markers alone cover nearly 80% of the map length. This map is proposed as a basis for a framework melon map to be merged with other maps and as an anchor point for map comparison between species of the Cucurbitaceae family.

Amebic liver abscess with bacterial superinfection in a patient with no epidemiologic risk factors.

The amebic liver abscess is uncommon in developed countries like Spain, but the incidence is increasing probably due to the migratory movements of the population. We report a case of an amebic abscess, initially unsuspected due to the absence of epidemiologic risk factors and the negative serology for amebiasis, in the early stages of the disease.

[Acute renal failure in critically ill patients. A prospective epidemiological study]. / Fracaso renal agudo en la unidad de cuidados intensivos. Estudio observacional prospectivo.

AIMS: To determine factors which may predict mortality in patients admitted to intensive care unit who present acute renal failure. METHODS: Prospective observational study of the patients admitted to a multidisciplinary intensive care unit over a year. The inclusion criteria were a creatinine plasmatic value > or = 2 mg/dl (177 micromol/l) or an increase (30% or higher) of its basal value on admittance. RESULTS: One hundred and twenty-seven patients (age = 65.83 +/- 15.06 years; 38% male) with acute renal failure, were prospectively enrolled in the study (13% of intensive care unit admissions). The univariate analysis showed that hospital origin, acute tubular necrosis, late ARF, oliguria, maintained hypotension, sedation or coma, oncological disease and need of mechanical ventilation were significantly associated with mortality (p < 0.05). This association was also found for sepsis (OR: 41.5), multiorganic failure (OR: 3.58) and respiratory, cardiovascular or haematological failure according to the SOFA score. The multivariate analysis found that four clinical variables had an independent predictive value for mortality risk: acute tubular necrosis [OR: 4.57 (2.32-9.00)], use of vasoactive drugs [OR: 2.32 (1.22-4.40)], oliguria [OR: 2.15 (1.12-4.13)] and the acute renal failure starting during admission [OR: 2.06 (1.09-3.88)]. CONCLUSION: Data related to renal failure have worse prognosis than other demographic or clinical data in critically ill patients with acute renal failure. Multicentric studies with unified criteria are needed to analyse the most important prognostic factors.

Identification of quantitative trait loci involved in fruit quality traits in melon (Cucumis melo L.).

Two populations [an F(2) and a set of 77 double haploid lines (DHLs)] developed from a cross between a 'Piel de Sapo' cultivar (PS) and the exotic Korean accession PI 161375 were used to detect QTLs involved in melon fruit quality traits: earliness (EA), fruit shape (FS), fruit weight (FW) and sugar content (SSC); and loci involved in the colour traits: external colour (ECOL) and flesh colour (FC). High variation was found, showing transgressive segregations for all traits. The highest correlation among experiments was observed for FS and the lowest for FW and SSC. Correlations among traits within experiments were, in general, not significant. QTL analysis, performed by Composite Interval Mapping, allowed the detection of nine QTLs for EA, eight for FS, six for FW and five for SSC. Major QTLs ( R(2)>25%) were detected for all traits. QTLs for different traits were no clearly co-localised, suggesting low pleiotropic effects at QTLs. Sixty-one per cent of them were detected in two or more experiments. QTLs for FS were detected in more trials than QTLs for FW and SSC, confirming that FS is under highly hereditable polygenic control. ECOL segregated as yellow:green in both experimental populations. The genetic control of ECOL was found to be complex, probably involving more than two loci with epistatic interactions. One of these loci was mapped on linkage group 9, but the other loci could not be clearly resolved. FC segregated as white:green:orange. The locus responsible for the green FC was mapped on linkage group 1, and it was proposed to correspond to the previously described locus gf. The genetic control of orange FC was complex: two loci in linkage groups 2 and 12 were associated with orange flesh, but larger population sizes would be necessary to elucidate completely the genetic control of orange flesh in this cross. Exotic alleles from PI161375 showed beneficial effects on EA, FW and SSC, indicating the usefulness of PI 161375 as a new source of genetic variability to improve European and American cultivars.

Relationships between heart rate variability, functional capacity, and left ventricular function following myocardial infarction: an evaluation after one week and six months.

BACKGROUND: Relationships between heart rate (HR) variability and different prognostic markers such as ejection fraction, functional capacity, and patency of the infarct-related artery, as well as the comparison of their time courses are not fully elucidated. HYPOTHESIS: The aim of study was to assess prospectively the early postinfarction changes in HR variability and its evolution over a period of 6 months: the relationships between HR variability and functional capacity in exercise testing; left ventricular function in cardiac catheterization: status of the infarct-related artery; and the comparison of their time courses. METHODS: In 42 patients with anterior myocardial infarction, a study was made of the early changes in HR variability analyzed by the complex demodulation method, its evolution over a period of 6 months. and the relationships between HR variability and (1) functional capacity in exercise testing, (2) left ventricular function in cardiac catheterization, and (3) status of the infarct-related artery. RESULTS: At 1 week HR variability parameters correlated directly with functional capacity indicators such as METS, percent change in HR from rest to peak exercise (%deltaHR), difference between initial and peak HR (HR range), percent peak theoretical HR (% peak HR), left ventricular ejection fraction (EF), and, inversely, with end-systolic volume (ESV). Stepwise multiple regression analysis to establish HR variability parameters (recorded at 1 week) as related to functional capacity and left ventricular function at 1 week and 6 months postinfarction established the following variables: (1) At 1 week: standard deviation (SD) of the RR cycles in relation to %deltaHR (r = 0.60, p <0.0001), HR range (r = 0.43, p < 0.01), and EF (r = 0.79, p < 0.0001). (2) At 6 months, the sole accepted HR variability parameter was the SD in relation to %deltaHR (r = 0.38, p < 0.05) and HR range (r = 0.45, p < 0.01). No variability parameter was accepted in relation to METS, % peak HR, or ESV. Relationship between EF or ESV and HR variability parameters was not significant when both were evaluated at 6 months. At that time, there was a significant increase in all HR variability parameters among all surviving patients (n = 39), with the exception of the LF/HF ratio and mean RR cycle. The percent increase in HR variability between the first week and 6 months was greater among those patients with the lowest basal EF. No relation was established between HR variability and patency of the infarct-related artery. CONCLUSION: The decrease in HR variability observed following myocardial infarction is associated with a diminished functional capacity and an increased alteration of the EF. This does not affect the recovery of HR variability, which was observed in all surviving patients.

Tracing the origin of the compensasome: evolutionary history of DEAH helicase and MYST acetyltransferase gene families.

Dosage compensation in Drosophila is mediated by a complex of proteins and RNAs called the "compensasome." Two of the genes that encode proteins of the complex, maleless (mle) and males-absent-on-the-first (mof), respectively, belong to the DEAH helicase and MYST acetyltransferase gene families. We performed comprehensive phylogenetic and structural analyses to determine the evolutionary histories of these two gene families and thus to better understand the origin of the compensasome. All of the members of the DEAH and MYST families of the completely sequenced Saccharomyces cerevisiae and Caenorhabditis elegans genomes, as well as those so far (June 2000) found in Drosophila melanogaster (for which the euchromatic part of the genome has also been fully sequenced) and Homo sapiens, were analyzed. We describe a total of 39 DEAH helicases in these four species. Almost all of them can be grouped in just three main branches. The first branch includes the yeast PRP2, PRP16, PRP22, and PRP43 splicing factors and their orthologs in animal species. Each PRP gene has a single ortholog in metazoans. The second branch includes just four genes, found in yeast (Ecm16) and Drosophila (kurz) and their orthologs in humans and Caenorhabditis. The third branch includes (1) a single yeast gene (YLR419w); (2) six Drosophila genes, including maleless and spindle-E/homeless; (3) four human genes, among them the ortholog of maleless, which encodes RNA helicase A; and (4) three C. elegans genes, including orthologs of maleless and spindle-E. Thus, this branch has largely expanded in metazoans. We also show that, for the whole DEAH family, only MLE and its metazoan orthologs have acquired new protein domains since the fungi/animals split. We found a total of 17 MYST family proteins in the four analyzed species. We determined putative orthologs of mof in both C. elegans and H. sapiens, and we show that the most likely ortholog in yeast is the Sas2 gene. Moreover, a paralog of mof exists in Drosophila. All of these results, together with those found for a third member of the compensasome, msl-3, suggest that this complex emerged after the fungi/animals split and that it may be present in mammalian species. Both gene duplication and the acquisition of new protein modules may have played important roles in the origin of the compensasome.

Transmission bottlenecks and the evolution of fitness in rapidly evolving RNA viruses.

We explored the evolutionary importance of two factors in the adaptation of RNA viruses to their cellular hosts, size of viral inoculum used to initiate a new infection, and mode of transmission (horizontal versus vertical). Transmission bottlenecks should occur in natural populations of viruses and their profound effects on viral adaptation have been previously documented. However, the role of transmission mode has not received the same attention. Here we used a factorial experimental design to test the combined effects of inoculum (bottleneck) size and mode of transmission in evolution of vesicular stomatitis virus (VSV) in tissue culture, and compared our results to the predictions of a recent theoretical model. Our data were in accord with basic genetic principles concerning the balance between mutation, selection and genetic drift. In particular, attenuation of vertically transmitted viruses was a consequence of the random accumulation of deleterious mutations, whereas horizontally transmitted viruses experiencing similar bottlenecks did not suffer the same fitness losses because effective bottleneck size was actually determined by the number of host individuals. In addition, high levels of viral fitness in horizontally transmitted populations were explained by competition among viral variants.

Basic phenotypic analysis of six novel yeast genes reveals two essential genes and one which affects the growth rate.

Phenotypic analysis was performed on six mutants of Saccharomyces cerevisiae deleted in one of the following open reading frames (ORFs), located on chromosome II: YBR254c, YBR255w, YBR257w, YBR258c, YBR259w and YBR266c. Disruption of the ORFs was carried out in the diploid strain FY1679 using the kanMX4 marker flanked by short sequences homologous to the target locus. Tetrad analysis following sporulation of the heterozygous disruptants showed that YBR254c and YBR257w are essential genes. YBR257w was later characterized and renamed POP4, its gene product being involved in 5.8S rRNA and tRNA processing (Chu et al., 1997). The tetrad analysis performed for the heterozygous disruptant for YBR266c showed that two of the four viable spores gave colonies of smaller size, reflecting a slower growth rate. Growth analysis of the disruptant haploids confirmed this defect at 30 degrees C and also at 15 degrees C. However, complementation tests failed to confirm that the deletion of YBR266c is responsible for this growth defect. Growth analysis of the disruptant haploid ybr255w(delta) showed a slower growth rate on YPD and minimal medium at 15 degrees C. Finally, no phenotypic effect could be detected associated to the disruption of ORFs YBR258c and YBR259w.

[The RICVAL study. Acute myocardial infarct in the city of Valencia. Data on 1,124 patients during the first twelve months of the registry (December, 1993--November, 1994)]. / Estudio RICVAL. El infarto agudo de miocardio en la ciudad de Valencia. Datos de 1,124 pacientes en los primeros 12 meses del Registro (diciembre de 1993-noviembre de 1994). Investigadores del RICVAL.

BACKGROUND AND OBJECTIVES: Information on the management of acute myocardial infarction in Spain is still scarce. The Register of Acute Myocardial Infarction of Valencia City (RICVAL) was established to collect, in a prospectively and uniformly way, data of patients with acute myocardial infarctions discharged from Valencia coronary care units, in order to obtain updated information on the management of these patients. Data of the first twelve months of the register are presented. METHODS: Using standardised variables, demographic, clinical, procedural and outcome data from patients with acute myocardial infarction were collected at the eight hospitals collaborating in the RICVAL, from 1 December 1993 to 30 November 1994. RESULTS: The eight participating hospitals cover 1,665,720 people. During 12 months, 1,124 patients were discharged from the participating coronary care units. Mean age was 65.1 years and 23.9% were female. The case fatality rate was 16.9%. Left ventricular failure (Killip 2, 3 and 4) was present in 42%. Thrombolytic therapy was applied in 43.5% with a median time delay of 210 minutes from chest pain onset. The delay time in initiating thrombolysis was longer in the women and in the elderly. CONCLUSION: Analysis of present data shows the feasibility of an acute myocardial infarction register in Valencia City. The RICVAL study will allow a better knowledge of demographic, clinical, procedural and outcome data in patients with myocardial infarction. The case fatality rate is still high when we consider that an acceptable level of thrombolytic therapy has been reached. The long delay time in initiating thrombolysis, particularly in the elderly and in the women, must be emphasized.

A comparative study of the incorporation of a 1,6-beta-glucan and an O-glycosylated protein epitope into the cell wall of Candida albicans.

The topological distribution of two epitopes in the cell wall of Candida albicans, the kinetics of their incorporation into the regenerating protoplast wall, and the effect of different antibiotics upon their incorporation and localization have been studied. To do so, two monoclonal antibodies that react against an O-glycosylated mannoprotein (1B12) and against a 1,6-beta-glucan epitope (JRR1) were used. The results show that the JRR1 epitope is localized in an internal layer of the cell wall, in contrast to the 1B12 epitope, which is superficial, and that the incorporation of the JRR1 epitope into walls of regenerating protoplasts precedes that of the 1B12 epitope. The JRR1 epitope is normally found in the culture medium of control cells, but not in that of papulacandin-B-treated cells, and tunicamycin interferes with the incorporation of the 1B12 epitope into the cell walls. Finally, the results support the hypothesis that mannoproteins are not 1,6-beta-glycosylated before their secretion.

Ventricular tachycardia in Duchenne's muscular dystrophy.

We report a case of a 31-year-old man with severe Duchenne's muscular dystrophy and sustained ventricular tachycardia. Serial electrophysiologic studies demonstrated the inefficiency of antiarrhythmic drugs in our patient who died after the implant of an automatic cardioverter defibrillator. A literature review is made.