Primera onda pandémica de COVID-19 en Navarra, febrero-junio 2020 / First wave of the COVID-19 pandemic in Navarre, Spain, February-June 2020

Fundamento. En 2020 se declaró la pandemia de COVID-19. La escasez de pruebas diagnósticas limitó la monitorización de la primera onda pandémica. El objetivo fue estimar y describir esta onda en Navarra (España). Métodos. La primera onda pandémica en Navarra, desde febrero a junio de 2020, se caracterizó a partir de la vigilancia epidemiológica reforzada, de la encuesta seroepidemiológica nacional y del registro de mortalidad. Resultados. Se confirmaron 10.358 personas con COVID-19 (1,6 % de la población), 1.943 requirieron ingreso hospitalario (3 por 1.000 habitantes), 139 ingresaron en UCI (21 por 100.000) y 529 fallecieron (80 por 100.000). La mortalidad aumentó exponencialmente con la edad, superando el 1 % en mayores de 85 años. El 58 % de las defunciones ocurrieron en residentes en centros socio-sanitarios. El registro de mortalidad recibió notificación de 733 muertes por COVID-19 confirmado o probable, mientras que el exceso de mortalidad fue de 613 defunciones (20,9 %) concentradas entre mediados de marzo y finales de abril. Al final de la onda, se estima que el 6,7 % (n = 44.000) de la población tenía anticuerpos detectables frente al SARS-CoV-2 y el 10,3 % había pasado la infección. La incidencia de infección estimada aumentó abruptamente en la primera quincena de marzo y descendió rápidamente durante el confinamiento domiciliario en la segunda quincena de marzo. Conclusiones. La primera onda pandémica produjo un número enorme de casos, hospitalizaciones y defunciones en Navarra en pocas semanas. El marcado descenso de los contagios durante el confinamiento domiciliario sugiere una eficacia y un impacto considerables de esta medida en la contención de la transmisión.(AU)

Background. The COVID-19 pandemic was declared in 2020. The shortage of diagnostic tests limited monitoring of the first wave of the pandemic. This study estimates and describes the wave in Navarre (Spain). Methods. Enhanced epidemiological surveillance, seroepidemiological survey estimates and mortality registries were used to characterise the first wave of the COVID-19 pandemic from February to June 2020 in Navarre. Results. A total of 10,358 persons (1.6 % of population) were confirmed with COVID-19, 1,943 cases were hospitalized (3 per 1,000 inhabitants), 139 were admitted to the ICU (21 per 100,000 inhabitants), and 529 people died from confirmed COVID-19 (80 per 100,000). Mortality increased exponentially with age, exceeding 1 % in people over 85 years. 58 % of deaths occurred amongst nursing home residents. The mortality registry received reporting of 733 confirmed or probable COVID-19 deaths, while the excess deaths during this period were 613 (20.9 %) concentrated from mid-March to the end of April. It is estimated that, at the end of June, 6.7 % (n = 44,000) of the population had detectable antibodies against SARS-CoV-2 and 10.3 % had had the infection. The estimates of SARS-CoV-2 infection incidence increased sharply in the first half of March and decreased quickly during the home lockdown in the second half of March. Conclusions. The first wave of the pandemic produced a high number of cases, hospitalizations and deaths in Navarre in a few weeks. The pronounced decrease of SARS-CoV-2 infections during the home lockdown suggests considerable efficacy and impact of this measure for transmission control.(AU)

[First wave of the COVID-19 pandemic in Navarre, Spain, February-June 2020].

BACKGROUND: The COVID-19 pandemic was declared in 2020. The shortage of diagnostic tests limited monitoring of the first wave of the pandemic. This study estimates and describes the wave in Navarre (Spain). METHODS: Enhanced epidemiological surveillance, seroepidemiological survey estimates and mortality registries were used to characterise the first wave of the COVID-19 pandemic from February to June 2020 in Navarre. RESULTS: A total of 10,358 persons (1.6?% of population) were confirmed with COVID-19, 1,943 cases were hospitalized (3 per 1,000 inhabitants), 139 were admitted to the ICU (21 per 100,000 inhabitants), and 529 people died from confirmed COVID-19 (80 per 100,000). Mortality increased exponentially with age, exceeding 1?% in people over 85 years. 58?% of deaths occurred amongst nursing home residents. The mortality registry received reporting of 733 confirmed or probable COVID-19 deaths, while the excess deaths during this period were 613 (20.9?%) concentrated from mid-March to the end of April. It is estimated that, at the end of June, 6.7?% (n?=?44,000) of the population had detectable antibodies against SARS-CoV-2 and 10.3?% had had the infection. The estimates of SARS-CoV-2 infection incidence increased sharply in the first half of March and decreased quickly during the home lockdown in the second half of March. CONCLUSIONS: The first wave of the pandemic produced a high number of cases, hospitalizations and deaths in Navarre in a few weeks. The pronounced decrease of SARS-CoV-2 infections during the home lockdown suggests considerable efficacy and impact of this measure for transmission control.

Utilidad de imagen de banda estrecha en un caso de melanoma mucoso de septum nasal / Utility of narrow band Imaging in a nasal septum mucosal melanoma case

En los últimos años, se está utilizando la fibrolaringoscopía con imagen de banda estrecha (NBI) como técnica novedosa para observar el patrón específico de microvas-cularización de una lesión concreta a evaluar. Es conocida por su utilidad en el diagnóstico de otras lesiones de vías aerodigestivas superiores, fundamentalmente laríngea y digestiva. Los melanomas mucosos son tumores infrecuentes, que suelen localizarse a nivel del área rinosinusaly que comportan un manejo y pronóstico distinto con respecto a los melanomas cutáneos. Se presenta el caso clínico de una paciente mujer con anamnesis, exploración y fibrolaringoscopía con imagen de banda estrecha, compatible con melanoma mucoso de fosa nasal izquierda. El tratamiento realizado fue quirúrgico, sin necesidad de tratamiento coadyuvante, y no presenta evidencia de enfermedad al año postseguimiento.

In recent years, it is being used fibrolaryngoscopy with narrowband image (NBI) as a novel technique to observe the specific pattern of microvasculature of a particular lesion. NBI is known for its usefulness in the diagnosis of other lesions of the upper aerodigestive tract, (primarily laryngeal and digestive lesions). Mucosal melanomas are rare tumors, which are usually located at the level of rhino-sinusal area and involving a different prognosis and management regarding cutaneous melanomas. We report a female patient case with anamnesis, clinical examination and NBI compatible with mucosal melanoma of left nostril. Surgical treatmentwas performed without adjuvant therapy, and there is no evidence of disease at one year post-monitoring.

Dolor cervical atípico: síndrome de Eagle / Atypical neck pain: Eagle syndrome

Presentamos el caso de un varón de 45 años con dolor cervical derecho muy localizado, característico y persistente. El estudio radiológico nos permitió diagnosticar claramente un síndrome de Eagle. Por lo anterior el paciente fue sometido a cirugía de extirpación de apófisis estiloides derecha. El paciente evolucionó sin mayores complicaciones ni incidencias, y obteniendo la resolución del cuadro.

Here we introduce a 45-year-old man suffering from an intense, unique and permanent pain, located in his right neck. Radiology showed us signs leading to the diagnosis of Eagle Syndrome. Surgery of right Styloid apophysis removal, with no complications, letting the patient free of symptoms.

Productivity costs of work loss associated with osteoarthritis in Canada from 2010 to 2031.

OBJECTIVE: To estimate and project the productivity costs of work loss (PCWL) associated with osteoarthritis (OA) in Canada using the Population Health Model (POHEM). DESIGN: We integrated an employment module based on 2006 Canadian Census into the previously developed microsimulation model of OA. The Canadian Community Health Survey (CCHS) Cycle 2.1 with an OA sample aged 25-64 (n = 7067) was used to calibrate the results of the employment module and to estimate the fraction of non-employment associated with OA. Probabilities of non-employment together with attributable fractions were then implemented in POHEM to estimate PCWL associated with OA from 2010 to 2031. RESULTS: Among the OA population, 44.4% and 59.4% of non-employment due to illness was associated with OA for those not working full-year and part-year, respectively. According to POHEM projections, the size of the working age population with OA increased from 1.5 million in 2010 to 1.7 million in 2031. The PCWL associated with OA increased from $12 billion to $17.5 billion in constant 2008 Canadian dollars. Around 38% of this increase was due to the increase in OA prevalence and changes in demographics, while the rest was due to increase in real wage growth. Male and female OA patients between 55 and 64 years of age had the highest total projected PCWL, respectively. CONCLUSIONS: The total PCWL associated with OA in Canada is estimated to be substantial and increasing in future years. Results of this study could be used to inform policies aiming to increase employment sustainability among individuals with OA.

Strong induction of iodothyronine deiodinases by chemotherapeutic selenocompounds.

The biological activity of thyroid hormones (TH) is regulated by selenoenzymes of the iodothyronine deiodinase (DIO) family catalysing TH activating and inactivating reactions. Besides TH metabolism, several studies indicate an important role of DIO isoenzymes in tumorigenesis and cancer growth. It is therefore of therapeutic importance to identify modulators of DIO expression. We have synthesized and studied a series of selenocompounds containing a methyl- or benzyl-imidoselenocarbamate backbone. One of these novel compounds had chemotherapeutic activities in a murine xenograft tumour model by an unknown mechanism. Therefore, we tested their effects on DIO expression in vitro. In HepG2 hepatocarcinoma cells, DIO1 activity was strongly (up to 10-fold) increased by the methyl- but not by the corresponding benzyl-imidoselenocarbamates. Steady-state mRNA levels remained unaltered under these conditions indicating a post-transcriptional mode of action. The effects were further characterized in HEK293 cells stably expressing DIO1, DIO2 or DIO3. Even within the artificial genetic context of the expression vectors, all three DIO isoenzymes were up-regulated by the methyl- and to a lesser extent by the benzyl-imidoselenocarbamates. Consistent stimulating effects were observed with methyl-N,N'-di(quinolin-3-ylcarbonyl)-imidoselenocarbamate (EI201), a selenocompound known for its anti-tumour activity. DIO inducing effects were unrelated to the intracellular accumulation of selenium, yet the precise mode of action remains elusive. Collectively, our data highlight that these selenocompounds may constitute interesting pharmacological compounds for modifying DIO expression potentially affecting the balance between cell differentiation and proliferation.

Innovative lead compounds and formulation strategies as newer kinetoplastid therapies.

The protozoan diseases leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease (CD) are responsible for substantial global morbidity and mortality in tropical and subtropical regions. Environmental changes, drug resistance and immunosuppression are contributing to the emergence and spread of these diseases. In the absence of safe and efficient vaccines, chemotherapy, together with vector control, remains the most important measure to control kinetoplastid diseases. Nevertheless, the current chemotherapeutic treatments are clearly inadequate because of their toxic effects, generation of resistances as well as route and schedules of administration not adapted to the field-conditions. This review overlooks the strategies that can be addressed to meet immediately the patient needs such as the reconsideration of current regimens of administration and the rational combination of drugs in use. In the medium-long term, due to new methodologies of medicinal-chemistry, the screening from natural products and the identification of new therapeutic targets, new lead compounds have great chance to advance through the drug development pipeline to clinic. Modern pharmaceutical formulation strategies and nanomedicines also merit a place in view of the benefits of a single dose of liposomal Amphotericin B (AmBisome®) against visceral leishmaniasis. BBB-targeted nanodevices could be suited for selective delivery of drugs against HAT encephalitic phase. Bioadhesive nanoparticles can be proposed to enhance the bioavailability of drugs after oral administration by reason of improving the drug solubility, and permeability across the intestinal epithelia.

Osteoarthritis patients' perceptions of "appropriateness" for total joint replacement surgery.

OBJECTIVE: To understand patients' perspectives on 'appropriateness' for hip and knee total joint arthroplasty (TJA). METHODS: Focus groups were conducted, stratified by history of a previous TJA, in English-speaking men and women aged 40+ years with moderate to severe hip and knee osteoarthritis. Participants discussed: their appropriateness for TJA; the ideal candidate; patients' role in TJA decision making; and the relationship between appropriateness and willingness to consider TJA. Participants self-completed a questionnaire assessing demographics, arthritis severity (Western Ontario McMaster University Osteoarthritis index - WOMAC), perceived TJA candidacy and willingness to consider TJA. Focus groups were audio-taped and transcribed verbatim. Content analysis was performed. RESULTS: Eleven focus groups were conducted with 58 participants in total: mean age 72 years; 79% female; 25 (43%) with prior TJA; mean WOMAC summary score 43.1. Half reported willingness to consider TJA and 43% felt they were appropriate for TJA. Appropriateness was equated with candidacy for the procedure. Pain intensity and the ability to cope with pain were identified as the most important factors determining surgical candidacy, but felt to be inadequately evaluated by physicians. TJA appropriateness and willingness were felt to be distinct, yet related, concepts; those unwilling had stricter criteria about candidacy than those who were willing. CONCLUSIONS: Participants equated appropriateness for TJA with surgical candidacy. Patients' pain experience (intensity, impact on quality of life, ability to cope) was seen as most important in determining appropriateness, but felt to be inadequately evaluated currently. Enhanced patient-physician communication, possibly through use of patient decision aids, has potential to improve patient selection for TJA.

Sub-lethal levels of amyloid ß-peptide oligomers decrease non-transferrin-bound iron uptake and do not potentiate iron toxicity in primary hippocampal neurons.

Two major lesions are pathological hallmarks in Alzheimer's disease (AD): the presence of neurofibrillary tangles formed by intracellular aggregates of the hyperphosphorylated form of the cytoskeletal tau protein, and of senile plaques composed of extracellular aggregates of amyloid beta (Aß) peptide. Current hypotheses regard soluble amyloid beta oligomers (AßOs) as pathological causative agents in AD. These aggregates cause significant calcium deregulation and mediate neurotoxicity by disrupting synaptic activity. Additionally, the presence of high concentrations of metal ions such as copper, zinc, aluminum and iron in neurofibrillary tangles and senile plaques, plus the fact that they accelerate the rate of formation of Aß fibrils and AßOs in vitro, suggests that accumulation of these metals in the brain is relevant to AD pathology. A common cellular response to AßOs and transition metals such as copper and iron is the generation of oxidative stress, with the ensuing damage to cellular components. Using hippocampal neurons in primary culture, we report here the effects of treatment with AßOs on the (+)IRE and (-)IRE mRNA levels of the divalent metal transporter DMT1. We found that non-lethal AßOs concentrations decreased DMT1 (-)IRE without affecting DMT1 (+)IRE mRNA levels, and inhibited non-transferrin bound iron uptake. In addition, since both iron and AßOs induce oxidative damage, we studied whether their neurotoxic effects are synergistic. In the range of concentrations and times used in this study, AßOs did not potentiate iron-induced cell death while iron chelation did not decrease AßOs-induced cell death. The lack of synergism between iron and AßOs suggests that these two neurotoxic agents converge in a common target, which initiates signaling processes that promote neurodegeneration.

The quinoline imidoselenocarbamate EI201 blocks the AKT/mTOR pathway and targets cancer stem cells leading to a strong antitumor activity.

Methylimidoselenocarbamates have previously proven to display potent antitumor activities. In the present study we show that these compounds act as multikinase inhibitors. We found that the most effective compound, quinoline imidoselenocarbamate EI201, inhibits the PI3K/AKT/mTOR pathway, which is persistently activated and contributes to malignant progression in various cancers. EI201 blocked the phosphorylation of AKT, mTOR and several of its downstream regulators (p70S6K and 4E-BP1) and ERK1/2 in PC-3, HT-29 and MCF-7 cells in vitro, inducing both autophagy and apoptosis. EI201 also contributes to the loss of maintenance of the selfrenewal and tumorigenic capacity of cancer stem cells (CSCs). 0.1 µmol/L EI201 triggered a reduction in size and number of tumorspheres in PC-3, HT-29 and MCF-7 cells and 4 µmol/L induced the elimination of almost all the tumorspheres in the three studied cell lines. In addition, EI201 suppressed almost 80% prostate tumor growth in vivo (p < 0.01) compared to controls at a relatively low dose (10 mg/kg) in a mouse xenograft model. There was a significant decrease in the subcutaneous primary tumor [18F]-FDG uptake (76.5% reduction, p < 0.05) and in the total tumor burden (76.8% reduction, p < 0.05) after EI201 treatment compared to vehicle control, without causing toxicity in mice. Taken together, our results support further development of EI201 as a novel multi-kinase inhibitor that may be useful against cancers with aberrant upregulation of PI3K/AKT and MAPK signaling pathways.

The antioxidant N-acetylcysteine prevents the mitochondrial fragmentation induced by soluble amyloid-ß peptide oligomers.

BACKGROUND: Soluble amyloid-ß peptide oligomers (AßOs), which are centrally involved in the pathogenesis of Alzheimer's disease, trigger Ca(2+) influx through N-methyl-D-aspartate receptors and stimulate reactive oxygen species generation in primary hippocampal neurons. We have previously reported that AßOs promote Ca(2+) release mediated by ryanodine receptors (RyR), which in turn triggers mitochondrial fragmentation. We have also reported that the antioxidant N-acetylcysteine (NAC) prevents AßOs-induced Ca(2+) signal generation. OBJECTIVES: To determine if RyR-mediated Ca(2+) release activated by the specific agonist 4-chloro-m-cresol (4-CMC) induces fragmentation of the mitochondrial network, and to ascertain if NAC prevents the mitochondrial fragmentation induced by AßOs and/or 4-CMC. METHODS: Mature primary rat hippocampal neurons were incubated for 24 h with sublethal concentrations of AßOs (500 nM) or for 1-3 h with 4-CMC (0.5-1 mM), ± 10 mM NAC. Mitochondrial morphology was assessed by confocal microscopy of fixed neurons stained with anti-mHsp70. Intracellular Ca(2+) levels were determined by time series microscopy of neurons preloaded with Fluo-4 AM. RESULTS: Preincubation of neurons for 30 min with NAC prevented the mitochondrial fragmentation induced by AßOs or 4-CMC. In addition, we confirmed that preincubation with NAC abolished the stimulation of RyR-mediated Ca(2+) release induced by AßOs or 4-CMC. CONCLUSION: The present results strongly suggest that the general antioxidant NAC prevents AßO-induced mitochondrial fragmentation by preventing RyR-mediated Ca(2+)-induced Ca(2+) release.

Selenium and clinical trials: new therapeutic evidence for multiple diseases.

The understanding of the essential role of selenium (Se) in human health has increased substantially in recent decades. Micronutrient deficiencies are very common in the general population and may be even more common in patients with different pathologies due to genetic or environmental causes and prescription drug use. Selenium is used by people in the prevention and/or treatment of different disorders including cardiovascular disease, osteoarthritis, rheumatoid arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral sclerosis, pancreatitis, depression, and diabetes amongst others. Several mechanisms have been suggested to mediate the biological effects of Se and these include antioxidant defence systems, synthesis and stability of metabolites that act as intermediates implicated in diverse selenoproteins expression pathways oxidative metabolism, immune system modulation, DNA intercalators, kinase regulation, enzymatic cofactor, and gene expression. A number of clinical trials in recent years have provided convincing evidence of the central role of this element, either alone or in combination with other micronutrients or antioxidants, in the prevention and treatment of multiple diseases. Based on these studies this review focuses on the advances made so far in the study of mechanisms and applications of selenium compounds that could be suitable for chronic diseases.

Labour market income inequality and mortality in North American metropolitan areas.

OBJECTIVE: To investigate relations between labour market income inequality and mortality in North American metropolitan areas. METHODS: An ecological cross sectional study of relations between income inequality and working age (25-64 years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using four measures of income inequality. Two labour market income concepts were used: labour market income for households with non-trivial attachment to the labour market and labour market income for all households, including those with zero and negative incomes. Relations were assessed with weighted and unweighted bivariate and multiple regression analyses. RESULTS: US metropolitan areas were more unequal than their Canadian counterparts, across inequality measures and income concepts. The association between labour market income inequality and working age mortality was robust in the US to both the inequality measure and income concept, but the association was inconsistent in Canada. Three of four inequality measures were significantly related to mortality in Canada when households with zero and negative incomes were included. In North American models, increases in earnings inequality were associated with hypothetical increases in working age mortality rates of between 23 and 33 deaths per 100 000, even after adjustment for median metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality provides more evidence regarding the robust nature of the relation between income inequality and mortality in the US. It also provides a more refined understanding of the nature of the relation in Canada, pointing to the role of unemployment in generating Canadian metropolitan level health inequalities.

Evaluación clínica objetiva y estructurada en geriatría. Resultados del primer proyecto realizado en España / Objetive and structured clinical evaluation in geriatrics. Results of the first project performed in Spain

OBJETIVO: Presentar los resultados de la primera prueba piloto de evaluación clínica objetiva y estructurada (ECOE) para evaluar los conocimientos y habilidades en geriatría desarrollada por la Sociedad Catalano-Balear de Geriatría y Gerontología (SCBGG) .MATERIAL Y MÉTODOS: Expertos de la SCBGG, con el asesoramiento técnico del Institut d'Estudis de la Salut (IES), diseñaron la prueba que consistió en un circuito de 22 situaciones clínicas paradigmáticas de la especialidad y en las que se utilizaron diversos instrumentos evaluativos. Participaron voluntariamente 38 médicos invitados por la SCBGG, que al finalizarla cumplimentaron un cuestionario de opinión a propósito de la misma. Para el análisis de los datos se utilizó el programa estadístico SPSS/PC+ para Windows. RESULTADOS: La puntuación media (desviación estándar [DE]) en la edición de 2000 fue de 52,6 (5,8) y en la de 2001, de 49,1 (8,6). El estadístico alfa de Cronbach (coeficiente global de fiabilidad) fue de 0,71 en la primera y de 0,84 en la segunda. En 2001 se realizó el análisis de resultados según la formación de los participantes, y obtuvieron mejores resultados aquellos formados por vía MIR. La opinión de los participantes en las dos ediciones fue muy positiva. CONCLUSIONES: La primera prueba ECOE en geriatría se presenta como un método evaluativo de la competencia profesional fiable, válido, factible y bien aceptado por los profesionales que han participado en ella (AU)

Transcriptional regulation of the orf19 gene and the tir-cesT-eae operon of enteropathogenic Escherichia coli.

To establish an intimate interaction with the host epithelial cell surface, enteropathogenic Escherichia coli (EPEC) produces Tir, a bacterial protein that upon translocation and insertion into the epithelial cell membrane constitutes the receptor for intimin. The tir gene is encoded by the locus for enterocyte effacement (LEE), where it is flanked upstream by orf19 and downstream by the cesT and eae genes. With the use of a series of cat transcriptional fusions and primer extension analysis, we confirmed that tir, cesT, and eae form the LEE5 operon, which is under the control of a promoter located upstream from tir, and found that the orf19 gene is transcribed as a monocistronic unit. We also demonstrated that the LEE-encoded regulator Ler was required for efficient activation of both the tir and the orf19 promoters and that a sequence motif located between positions -204 and -157 was needed for the Ler-dependent activation of the tir operon. Sequence elements located between positions -204 and -97 were determined to be required for the differential negative modulatory effects exerted by unknown regulatory factors under specific growth conditions. Upon deletion of the upstream sequences, the tir promoter was fully active even in the absence of Ler, indicating that tir expression is subject to a repression mechanism that is counteracted by this regulatory protein. However, its full activation was still repressed by growth in rich medium or at 25 degrees C, suggesting that negative regulation also occurs at or downstream of the promoter. Expression of orf19, but not of the tir operon, became Ler independent in an hns mutant strain, suggesting that Ler overcomes the repression exerted by H-NS (histone-like nucleoid structuring protein) on this gene.

Efficacy of a diagnostic strategy for patients with chest pain and no ST-segment elevation in the emergency room.

PURPOSE: To evaluate the efficacy of a systematic model of care for patients with chest pain and no ST segment elevation in the emergency room. METHODS: From 1003 patients submitted to an algorithm diagnostic investigation by probability of acute ischemic syndrome. We analyzed 600 ones with no elevation of ST segment, then enrolled to diagnostic routes of median (route 2) and low probability (route 3) to ischemic syndrome. RESULTS: In route 2 we found 17% acute myocardial infarction and 43% unstable angina, whereas in route 3 the rates were 2% and 7%, respectively. Patients with normal/non-specific ECG had 6% probability of AMI whereas in those with negative first CKMB it was 7%; the association of the 2 data only reduced it to 4%. In patients in route 2 the diagnosis of AMI could only be ruled out with serial CKMB measurement up to 9 hours, while in route 3 it could be done in up to 3 hours. Thus, sensitivity and negative predictive value of admission CKMB for AMI were 52% and 93%, respectively. About one-half of patients with unstable angina did not disclose objective ischemic changes on admission. CONCLUSION: The use of a systematic model of care in patients with chest pain offers the opportunity of hindering inappropriate release of patients with ACI and reduces unnecessary admissions. However some patients even with normal ECG should not be released based on a negative first CKMB. Serial measurement of CKMB up to 9 hours is necessary in patients with medium probability of AMI.

Chest pain in the emergency room. Importance of a systematic approach.

OBJECTIVE: To evaluate the efficiency of a systematic diagnostic approach in patients with chest pain in the emergency room in relation to the diagnosis of acute coronary syndrome (ACS) and the rate of hospitalization in high-cost units. METHODS: One thousand and three consecutive patients with chest pain were screened according to a preestablished process of diagnostic investigation based on the pre-test probability of ACS determinate by chest pain type and ECG changes. RESULTS: Of the 1003 patients, 224 were immediately discharged home because of no suspicion of ACS (route 5) and 119 were immediately transferred to the coronary care united because of ST elevation or left bundle-branch block (LBBB) (route 1) (74% of these had a final diagnosis of acute myocardial infarction [AMI]). Of the 660 patients that remained in the emergency room under observation, 77 (12%) had AMI without ST segment elevation and 202 (31%) had unstable angina (UA). In route 2 (high probability of ACS) 17% of patients had AMI and 43% had UA, whereas in route 3 (low probability) 2% had AMI and 7% had UA. The admission ECG has been confirmed as a poor sensitivity test for the diagnosis of AMI (49%), with a positive predictive value considered only satisfactory (79%). CONCLUSION: A systematic diagnostic strategy, as used in this study, is essential in managing patients with chest pain in the emergency room in order to obtain high diagnostic accuracy, lower cost, and optimization of the use of coronary care unit beds.

New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA.

The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented. The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.