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Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, pharmacoeconomics, and place in therapy of ranibizumab are reviewed. Summary. Ranibizumab is the humanized fragment of the murine monoclonal antibody that binds all the active forms of the vascular endothelial growth factor, leading to the inhibition of the neovascular process underlying age-related macular degeneration (AMD). In animal studies, intravitreal administration of ranibizumab resulted in penetration of the drug into all layers of the retina and subsequent slow absorption into the systemic circulation. Improvement in visual acuity by 15 or more letters has been observed in 33.8–40.3% of patients treated with ranibizumab in pivotal clinical trials, compared with 5% of patients treated with sham injections and photodynamic therapy (PDT). The addition of PDT to ranibizumab has not been shown to offer any benefit in terms of efficacy and has been found to worsen ocular adverse reactions. The most common adverse ocular reactions reported in patients receiving ranibizumab during clinical trials include conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation. Ranibizumab’s efficacy in the treatment of neovascular AMD is well established; however, questions remain regarding the drug’s optimal dosing strategy, duration of therapy, and combined therapy with other agents. While ranibizumab has been defined as the best available weapon against AMD, it is also the most expensive. Conclusion. The efficacy of ranibizumab in the treatment of AMD is well established, but more studies are needed to determine ranibizumab’s optimal dosage interval, duration of therapy, and combined use with other agents.

Background: Adverse drug reaction (ADR) spontaneous reporting is the primary method of postmarketing drug surveillance: although it is an important part of postmarketing drug surveillance, it is underused. Before 2004, almost no ADRs were reported in our 400-bed hospital. As an electronic hospital information system was available in our hospital, we developed a tool (ADR-RS-IHIS) for ADR reporting integrated into the hospital information system to facilitate reporting through easy use, automatic input of certain information, increased accessibility, real-time review, and intervention. Objective: To analyze the efficacy of the ADR-RS-IHIS in increasing ADR reporting to the national drug surveillance system, propose and implement improvements to increase ADR reporting, and evaluate the impact of these improvements, Methods: Every ADR reported through the ADR-RS-IHIS was evaluated retrospectively. Two study phases for evaluating ADR-RS-IHIS efficacy were identified. Phase I took place April 2004-August 2006; in April 2006, an interim analysis was performed to propose improvements. Phase II took place September 2006-April 2007 for evaluation of the impact made by the proposed improvements. Efficacy in the phase I and improvement impact on phase II were measured as the number of ADRs reported to the national drug surveillance system Results: The rate of ADRs reported per month to the national system increased from 0 before 2004 to 0.91 in phase I and 1.62 in phase II (2.25 if delayed reporting was considered). Improvement measures included: allowing nurses to report ADRs in the same way as physicians and pharmacists, automatic form filling of certain information from the electronic hospital information system, easier ADR report analysis, and automatic notification to the allergy department regarding suspected allergies. Conclusions: An ADR reporting system integrated into the electronic hospital information system is effective for increasing the number of ADRs reported to the national drug surveillance system. Allowing nurses to report ADRs in a manner similar to that of physicians and pharmacists, as well as automatic entry of certain data into the form, contributes to the improvement of the system.

Genomic studies have revealed surprising new insights into the genetics of human B-cell lymphomas. Of particular note the lysine-specific methyl transferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and in diffuse large B-cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations in lymphoma are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and promotes lymphoma development in vivo. Integrative analyses of KMT2D function indicate specific and focal effects on H3K4 methylation and gene expression. These include B-cell growth and differentiation signals such as the CD40, JAK/STAT, and B-cell receptor pathways. Moreover, KMT2D targets include frequently mutated tumor suppressor genes such as TNFAIP3/A20, SOCS3, and TNFRSF14/HVEM. In this manner, KMT2D deficiency disrupts the physiological process of B-cell differentiation, facilitates malignant outgrowth, and can impede therapies acting on the CD40 and B-cell receptor pathways. Citation Format: Ana Ortega-Molina, Isaac W. Boss, Andres Canela, Heng Pan, Yanwen Jiang, Chunying Zhao, Man Jiang, Deqing Hu, Ji-Eun Lee, Hua-Tang Chen, Daisuke Ennishi, David W. Scott, Christoffer Hother, Shichong Liu, Xing-Jun Cao, Wayne Tam, Rita Shaknovich, Benjamin A. Garcia, Randy D. Gascoyne, Kai Ge, Ali Shilatifard, Olivier Elemento, Andre Nussenzweig, Ari M. Melnick, Hans-Guido Wendel. Functional characterization of the tumor suppressor lysine-specific methyltransferase KMT2D in lymphoma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr IA18.

espanolEl estudio morfologico comparado de Scrophularia schousboei Lange y S. sublyrata Brot. ha puesto de manifiesto que la variabilidad morfologica indicada para S. schousboei corresponde en realidad a la observable en plantas jovenes o de primer ano de S. sublyrata, por lo que se deduce que ambos nombres han sido aplicados a plantas de la misma especie pero de distinta edad, debiendose denominar el taxon como S. syblyrata Brot., por ser este el epiteto disponible mas antiguo EnglishComparative study of plant morphology and life cycle of both Srophularia schousboei Lange and S. sublyrata Brot. shows that the first taxon was described by Lange using young plants of S. sublyrata Brot. So, only S. sublyrata is recognized and S. schousboei must be included in synonymy.

The cost of parenteral admixtures has an important impact on the hospital budget. Recently, a Viaflex® with vial adapter (named 'minibag plus' in some countries) has been commercialized in order to facilitate parenteral admixture preparation. In the present study a preparation using Viaflex® with a vial adapter has been economically compared with a preparation with a traditional Viaflex® (without adapter) in a centralized unit or in nursing wards in a unit‐dose drug distribution system. A cost‐analysis was conducted from the hospital point of view. Direct costs were considered: these included supplies and human resources. Differences in the whole process between the two types of Viaflex® were analysed. The process included: purchasing, reception, storage, medical order record, preparation in the Pharmacy Service (PS), delivery from the PS to the nursing unit, preparation by the nurse, return of unused material to the PS. Human resource costs were estimated by time counting and multiplying by the average salary. To estimate wasted material, drug and supplies delivered from the PS and returned to the PS were counted during 26 days. With the new Viaflex® costs are reduced by 30% in comparison with drug dilution using the traditional Viaflex® in a centralized unit of the PS, and by 13.4% in comparison with preparation with the traditional Viaflex® in the nursing ward. In addition it can be estimated that contamination risk with the new Viaflex® is lower than preparation in the nursing ward with the traditional Viaflex®. Therefore, owing to its lower cost we recommend the use of Viaflex® with vial adapter for drug dilution for those vials that are compatible with the system.

Follicular lymphoma (FL) is a common and incurable form indolent B-cell lymphoma. Genomic studies have now catalogued many recurrent mutations in FL. Epigenetic regulators have emerged as the most common targets of somatic point mutations. For example, the histone methyltransferase KMT2D (MLL4/MLL2) is the most frequently mutated gene in FL with reported mutational frequencies of up to 84%. However, the transcriptional and biological consequences of KMT2D loss of function are currently unknown. Using a well-described murine model of FL, we showed that deficiency of KMT2D promotes the initiation of indolent FL in vivo. To explore the mechanism of KMT2D-mediated tumor suppression we used cross species comparisons of gene expression, histone H3K4 methylation marks and KMT2D genomic occupancy. These analyses converge on a relatively small group of conserved target genes. Strikingly, they include bona fide tumor suppressors and regulators of B-cell proliferation (e.g. TNFAIP3/A20, SOCS3, ARID1A, and TNFRSF14). Our results indicate that KMT2D restrains FL development through simultaneous effects on multiple key regulators of B-cell behavior. Note: This abstract was not presented at the meeting. Citation Format: Ana Ortega-Molina, Isaac Boss, Heng Pan, Yanwen Jiang, Deqing Hu, Xin Gao, Rita Shaknovich, Ali Shilatifard, Ari M. Melnick, Hans-Guido Wendel. Characterization of the tumor suppressor function of the lysine-specific methyltransferase KMT2D in follicular lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-064. doi:10.1158/1538-7445.AM2015-LB-064

Follicular lymphoma (FL), a form of non-Hodgkin lymphoma, is the second most common form of B-cell lymphoma and remains incurable in the majority of cases despite recent advances in therapy. Following an indolent phase, 50% of patients suffer disease transformation to an aggressive form of lymphoma (transformed FL; tFL). This dramatic switch in disease behavior typically culminates in rapid deterioration and patient demise. Accordingly, much effort has been focused on understanding the genetics of transformation and has resulted in the identification of key genetic lesions (e.g. MYC activation, loss of p53, cell cycle controls, activation of NFKB (TNFAIp3/A20)). However, exactly how tumor metabolism, which is altered by these genetic lesions, contributes to disease aggressiveness is not known and therefore the metabolic changes that occur upon FL transformation are poorly understood. We have developed a murine model of FL transformation that recapitulates key genetic and pathological aspects of human FL (Oricchio et al, 2011). This model allows us to study the genetics and metabolism of FL transformation. Specifically, we will systematically define the metabolic profiles of genetically defined murine lymphomas that represent different stages of transformation and cross-compare metabolic changes to primary patient samples. This ensures focus on clinically relevant changes and provides metabolic annotation of distinct tumor genotypes. This study builds on the complementary strengths of the Le lab (Johns Hopkins) in cancer metabolism and the Wendel lab (MSKCC) in modeling FL genetics. Our study shows that MYC transformed FL exhibits a distinct metabolic profile as compared to indolent follicular lymphoma or normal spleen. The most altered pathways examined thus far are glycolysis and amino acid metabolism. We believe that the transformed lymphoma is more reliant upon glycolysis and may be exhibiting aerobic glycolysis, also known as the Warburg Effect. This is substantiated from previous experiments in which a Burkitt lymphoma line, also overexpressing MYC, was found to have altered glycolytic intermediates levels. We next plan to examine the metabolic profile of other transformed follicular lymphoma models of known genetic backgrounds. We will also cross validate the transformed mouse models with follicular lymphoma patient samples of known genetic backgrounds to identify potential metabolic markers. Citation Format: Brad Poore, Ana Ortega-Molina, Christopher Nguyen, Liang Zhao, Anne Blackwell, Thomas Hartung, Hans-Guido Wendel, Anne Le. Metabolic characterization of follicular lymphoma transformation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1183. doi:10.1158/1538-7445.AM2015-1183

• Background and Aims There are few embryological reports on wild legumes and even fewer on their seminal appendages. There are no existing studies on the complete ontogeny of these appendages in Cytiseae, a very important Papilionoideae tribe in Mediterranean ecosystems. In this work megasporogenesis, megagametogenesis and aril ontogeny were studied in Cytisus multiflorus and C. striatus, endemics from the western Mediterranean region. • Methods Ovaries and ovules from flower buds, flowers at anthesis and hand cross-pollinated flowers were sectioned with a rotary microtome and studied under light and fluorescence microscopy. • Key Results A monosporic Polygonum-type of megagametogenesis is observed in both species but with megasporogenesis characterized by formation of a triad of cells after incomplete meiosis. The original cell wall of the megaspore mother cell and triad, including the transverse walls between the latter, are surrounded by a callose layer that isolates them from the surrounding diploid tissue; this callose layer gradually disappears during embryo sac formation. There are no antipodals in the mature embryo sac. Aril ontogeny starts in pre-anthesis with the formation of the aril primordium, and its normal development will occur only after fertilization, more specifically after endosperm initiation. After fertilization, a reactivation of meristem capacity takes place in the aril cells resulting in slow and sparse growth. Later, this type of development gradually decreases but the aril cells continue to grow by cell expansion, which in the last period of seed development is the only type of growth of the aril. In the mature seed, the seminal appendage acquires an irregular U-shape in transverse section, showing vacuolated cells with a large central vacuole that stores lipids and some proteins. • Conclusions Meiotic triad formation is due to a failure in meiosis II of the chalazal cell of the dyad. In Cytisus seeds the aril has a funicular origin with predominantly post-fertilization development, but a normal growth of the endosperm is needed for proper aril development.

Presentamos un paciente de 62 anos portador de protesis mitral que fue ingresado con un infarto anterior y tratado con r-tPA. Unos dias despues desarrollotrombosis de la protesis con aparicion de insuficiencia cardiaca. El enfermo se considero como de alto riesgo quirurgico, y fue tratado conexito con una nueva dosis de r-tPA, desapareciendola insuficiencia cardiaca y la imagen ecocardiografica de trombosis protesica.

Background: Amelogenesis Imperfecta (AI) is a group of conditions where there is an abnormal formation of enamel in terms of quantity, structure and composition. AI is clinically and genetically heterogeneous, there are sex linked and autosomal versions, dominant and/ or recessive, with phenotypes of hypoplastic, hypocalcified or hypomature enamel. Only recently, through clinical, genetic and molecular studies of affected families, phenotypic-genotypic correlations are being established in this group of anomalies. Aim: To carry out a genetic, clinical and molecular analysis of a Chilean family affected with an enamel malformation, which probably would correspond to Amelogenesis Imperfecta Dominant Autosomal (AIDA), of hypoplastic type, resulting from g.6395G>A mutation in the enamelin gene. Patients and Methods: A genealogical pattern was created for five generations. Five members of this family group were clinically examined, and four of them had a molecular analysis that consisted of the detection of a mutation in the enamelin gene using PCR. Results: In this family, the enamel malformation presents a dominant autosomal pattern of inheritance. The clinical examination of the group allowed a diagnosis of Amelogenesis Imperfecta, of the hypoplastic local type. However, the molecular analysis revealed that the members analyzed did not exhibit the g.6395G>A mutation reported for the enamelin gene (ENAM). Conclusions: The enamel phenotype in this family could be explained by the presence of one of four other mutations recently described in this or another gene, thereby supporting the findings of allelic heterogeneity reported in the literature (Rev Med Chile 2005; 133: 1331-40). (Key Words: Amelogenesis imperfecta; Dental enamel hypoplasia; Mutation)

RESUMEN. Sobre el tratamiento de Galium L. (Rubiaceae) en Flora Iberica. El estudio taxonómico del género Galium para Flora Iberica ha revelado la existencia en el territorio de 51 especies y 14 subespecies. Éstas han sido agrupadas en 10 secciones, previamente descritas, reconociéndose para algunas de ellas nuevas series: Galium sect. Galium ser. Trichogaliopsis (Lange) Ortega-Olivencia & Devesa, Galium sect. Galium ser. Andalusiana Ortega-Olivencia & Devesa, Galium sect. Platygalium ser. Platygalium (DC.) Ortega-Olivencia & Devesa, Galium sect. Platygalium ser. Ephedrogalium Ortega-Olivencia & Devesa y Galium sect. Leiogalium ser. Pulchra Ortega-Olivencia & Devesa. La serie Ephedrogalium comprende sólo G. ephedroides Willk., taxón para el de se ha estudiado la anatomía foliar, al objeto de evidenciar el número de nervios que poseen sus hojas -tres- y que justifica su inclusión en la sección. Para Galium idubedae (Pau ex Debeaux) Pau ex Ehrend. (Galium sect. Leptogalium Lange) se describe una nueva variedad: Galium idubedae var. humile C. Vicioso ex Ortega-Olivencia & Devesa.Palabras clave. Flora Iberica, Galium, Rubiaceae, taxonomía.SUMMARY. Treatment of Galium L. (Rubiaceae) in Flora Iberica. A taxonomic study of the genus Galium has shown the presence of 51 species and 14 subspecies in Flora Iberica. These taxa are gathered in 10 previously known sections, and in some of them new series are recognized: Galium sect. Galium ser. Trichogaliopsis (Lange) Ortega-Olivencia & Devesa, Galium sect. Galium ser. Andalusiana Ortega-Olivencia & Devesa, Galium sect. Platygalium ser. Platygalium (DC.) Ortega- Olivencia & Devesa, Galium sect. Platygalium ser. Ephedrogalium Ortega-Olivencia & Devesa and Galium sect. Leiogalium ser. Pulchra Ortega-Olivencia & Devesa. Ser. Ephedrogalium only comprises G. ephedroides, a species where a study of the foliar anatomy has been carried. Its leaves show three nerves and that character justifies its inclusion into section Platygalium. Also, a new variety is described in G. idubedae (Pau ex Debeaux) Pau ex Ehrend. (Galium sect. Leptogalium Lange): Galium idubedae var. humile C. Vicioso ex Ortega-Olivencia & DevesaKey words. Flora Iberica, Galium, Rubiaceae, taxonomy.

El objetivo del trabajo es considerar el desarrollo alcanzado por el conocimiento en estrategia empresarial en Castilla y León y su posición en el conjunto nacional, ofreciendo una visión complementaria a la de anteriores estudios. Para dicho análisis se han considerado, durante la década de los 90, congresos y revistas de alcance regional y nacional. Los resultados obtenidos nos muestran la necesidad de contar con más foros de encuentro en Castilla y León y con medios especializados en el campo de la estrategia. Además, los investigadores castellano-leoneses parecen mostrar un interés poco frecuente por la ejecución estratégica y por los aspectos de delimitación teórica, un tanto marginados en el conjunto nacional. El objetivo del trabajo es considerar el desarrollo alcanzado por el conocimiento en estrategia empresarial en Castilla y León y su posición en el conjunto nacional, ofreciendo una visión complementaria a la de anteriores estudios. Para dicho análisis se han considerado, durante la década de los 90, congresos y revistas de alcance regional y nacional. Los resultados obtenidos nos muestran la necesidad de contar con más foros de encuentro en Castilla y León y con medios especializados en el campo de la estrategia. Además, los investigadores castellano-leoneses parecen mostrar un interés poco frecuente por la ejecución estratégica y por los aspectos de delimitación teórica, un tanto marginados en el conjunto nacional.

Odontogenic tumors are infrequent lesions. Thus, the review of a large number of cases becomes a necessity for both the pathologist and the clinician. Studies on odontogenic tumors have been published in many parts of the world, but there is little information available in the English language literature on the relative frequency of odontogenic tumors in Latin America. The aim of this study was to determine the relative frequency of this heterogeneous group of lesions in a Chilean population, and to compare these data with previous reports.We reviewed the records of 28,041 specimens from 1975 to 2000 in the Oral Pathology Referral Institute (IREPO), and using the criteria for histological typification published by the World Health Organization in 1992, we reclassified the odontogenic tumors.We confirmed a total of 362 odontogenic tumors. The frequency of odontogenic tumors as a percentage of all pathological specimens in our institute was 1.29%. The most frequent histological type was odontomas (44.7%), followed by ameloblastomas (20.4%) and myxomas (8.8%).Odontogenic tumors are uncommon lesions in the Chilean population and malignant odontogenic tumors are very rare. The relative frequency of various types of odontogenic tumors, as well as the age and gender distribution are similar to those reported in the North American series and different from those found in recently published Asian and African series.

To study the prevalence of diabetic retinopathy (DR) in a sample of 3544 patients living in a rural area of the province of Valladolid, Spain; as well as to estimate the current eye care to the diabetic population.Participants received a comprehensive ocular examination in their local area where they resided and a grading of DR was made using standard protocols. Physicians then provided us with the systemic and demographic data.The population studied included 175 younger-onset and 3344 older-onset patients, all of whom were under physicians' care, distributed in an 18-county-area far from the urban center. Mean duration of the disease was 7.89 +/- 7.7 years (range 0 to 59 years). 73% of participants had not received ophthalmologic care the preceding year and 63.6% had not received a dilated eye examination either. The prevalence of DR was 20.9%; macular edema was found in 5.7% of the patients. Differences in participation were found among counties and these also correlated with differences in prevalence of DR. Prevalence of DR in the younger-onset group was 25.6% and 14.81% in insulin- and non-insulin-dependent patients, respectively. In the older-onset group, it was present in 48.6% and 14.7% of insulin- and non-insulin-dependent patients. Patients with retinopathy were older, with a longer duration of disease, were insulin dependent and had had less eye care.Deficient screening of ophthalmic disease in diabetic patients should be improved, especially in isolated areas, in order to reduce DR in this group. Insulin-dependent older-onset patients with a longer duration of diabetes had a higher frequency of these complications.

ObjectivesThis study aimed to evaluate the effect of primary angioplasty (PA) over the risk of free wall rupture (FWR) in reperfused acute myocardial infarction (AMI).BackgroundIt has been suggested that PA reduces the risk of FWR compared with thrombolysis. However, few studies have evaluated this issue, and there are no data demonstrating this hypothesis.MethodsA total of 1,375 patients with AMI treated with PA (n = 762, 55.4%) or thrombolysis (n = 613, 44.6%) within 12 h after symptoms onset were included. The diagnosis of FWR was made either in the presence of sudden death due to electromechanical dissociation with large pericardial effusion on an echocardiogram or when demonstrated post mortem or at surgery. A multivariable analysis was performed including type of reperfusion strategy.ResultsThe overall incidence of FWR was 2.5% (n = 34): 1.8% and 3.3% in patients treated with PA and with thrombolysis, respectively (p = 0.686). The following characteristics were associated with a higher rate of FWR in the univariable analysis: age >70 (5.2% vs. 1.2%, p < 0.001), female gender (5.1% vs. 1.8%, p = 0.006), anterior location (3.3% vs. 1.4%, p = 0.020) and treatment >2 h after symptoms onset (3.6% vs. 1.7%, p = 0.043). In the multivariable analysis, age >70 (odds ratio [OR]: 4.12, 95% confidence interval [CI]: 2.04 to 8.62, p < 0.001) and anterior location (OR: 2.91, 95% CI: 1.36 to 6.63, p = 0.008) were independent risk factors of FWR, whereas treatment with PA was an independent protective factor (OR: 0.46, 95% CI: 0.22 to 0.96, p = 0.0371).ConclusionsIn patients with AMI, PA reduces the risk of FWR in comparison with thrombolysis.

Floristic news of Spanish Scrophularia Palabras clave. Flora, corología, Scrap/in/aria, España. Key words. Flora, chorology, Scrophularia, Spain.

Background Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention. Methods and Results 16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, p value

Background The atrium is the major site of ANP synthesis, which has been said to increase in heart failure as a result of increased production in the left ventricular (LV) myocardium. This is a key issue related to its diagnostic and prognostic capabilities. We aimed to evaluate protein levels of proANP and ANP and the enzymes that cleave the natriuretic peptides, corin and furin, in the LV tissue of heart transplant patients with dilated (DCM) and ischemic (ICM) cardiomyopathy compared with control donors (CNT). We also evaluate mRNA levels of ANP gene (NPPA) by RNA sequencing in the same tissue. Methods and Results Seventy-three human LV tissue samples from ICM (n = 30) and DCM (n = 33) patients and CNT (n = 10) were analyzed by Western blot and RNA sequencing. Comparing protein levels according to etiology, neither DCM nor ICM showed levels of proANP or ANP different from those of CNT. However, NPPA was increased in both groups compared to CNT (DCM 32 fold, p

OBJECTIVES: Diastolic dysfunction is an early finding during myocardial ischemia. However, regional diastolic function has not been studied in patients with microvascular angina (MA). The purpose of this study was to assess the regional diastolic function in patients with MA through use of the new echocardiographic technique, pulsed-wave Doppler tissue imaging (DTI). METHODS: Regional diastolic function was studied by DTI in 81 myocardial segments of seven patients with MA and in 54 segments of six healthy control subjects. RESULTS: Myocardial segments in patients with MA had, in comparison with controls, an increased regional isovolumetric relaxation time (126 +/- 34 vs 99 +/- 34 msec, P < 0.0001), a higher e/a ratio (1.1 +/- 0.7 vs 0.8 +/- 0.3, P = 0.0048), and a lower peak velocity of the late diastolic wave a (6.9 +/- 2.9 vs 8.4 +/- 1.7 cm/msec, P = 0.0009). Moreover, peak velocity of systolic wave s was higher in patients with MA (5.8 +/- 1.4 vs 5.3 +/- 1.2 cm/msec, P = 0.0424). CONCLUSIONS: Patients with MA have an impaired regional diastolic function (an increased regional isovolumetric relaxation time and a lower a wave) and a higher velocity of the regional systolic wave s. These findings may have physiopathological implications.

Nitric oxide (NO) is implicated in many different biological functions. This is due to its widespread distribution in tissue and to its ability to react with a range of molecules in the organism, of which haemoglobin (Hb), soluble guanylyl cyclase (GC), and superoxide anion are of particular note. In this review we describe the biological pathways of NO and their involvement in its physiological effects and toxicity. This endothelial factor rapidly diffuses into the vascular compartment, and the reaction with the Hb haem group is the main metabolic pathway for endogenous NO. Hb is, therefore, a scavenger for this mediator, which prevents it from reaching the tissue components. NO also reacts with the GC haem group, and this combination is fundamental to its acute vasorelaxing effect. Although molecular oxygen plays a very small part in the oxidization process of NO in biological systems, NO reacts with the superoxide anion to generate peroxynitrite at a rate that is limited only by its diffusion coefficient. This reaction is important in pathological conditions because the peroxynitrite thus formed is a selective oxidant and nitrating agent that interacts with numerous biological molecules, thereby damaging them. In addition, of particular note are the interactions of NO with thiol groups, which may mediate several relevant effects in the organism. NO may also activate endogenous ribosyltransferases, which facilitate the transfer of adenosine diphosphate-ribose groups from nicotine adenine dinucleotide to the G protein amino acid residues. These last two processes may also be involved in the control of arterial tone and more precisely so when chronic NO production takes place.

A clinical and economic evaluation of red blood cell (RBC) utilization in cancer patients during chemotherapy is described. Using a randomized sampling process, 100 patients who had received chemotherapy with or without cisplatin were selected (50 in each group). Multiple logistic regression was then used to identify risks factors for transfusion requirements. Twenty-five percent of patients in the cisplatin and 12% in the noncisplatin group received at least one blood transfusion during chemotherapy (p=.09). Depressed hemoglobin levels and cisplatin dosage were identified as risk factors for transfusion requirements. Combining all transfused patients revealed an overall cost of Can $599 (95% Cl: $513–$683) per transfusion. The results of the current study indicated that anemia is a common complication of cancer chemotherapy that can be costly to manage.

Three hundred twenty seven patients with medically stabilized unstable angina and a negative exercise test were followed-up during a mean of 39 months. Male gender, diabetes mellitus, and previous myocardial infarction, but not exercise parameters, were predictors of death or acute myocardial infarction.

African swine fever (ASF) virus induces immune cell alterations that may be detected by changes in peripheral blood cells phenotypic antigens and activation markers which were examined by flow cytometry, analyzing both cell proportion and/or expression intensity of superficial antigens. These studies were conducted in pigs with experimental acute of chronic ASF infection to determine whether changes among important surface activation markers and phenotypic antigens, and their correlative lymph node status, reflected similar or disparate aspects of immune pathology. In acute infection produced by virulent viruses, macrophage and B lymphocyte populations decreased in peripheral blood after a short activation period at the beginning of the infection. A significative decrease of interleukin 2 receptor (IL 2R) expression was also observed in those pigs. These variations correlated with lymph node cell depletion due to an intense lymphoid cell death by apoptosis, affecting mainly the B lymphocyte subpopulation as determined by immunohistochemistry. Nevertheless, pigs infected with an attenuated isolate undergoing chronic persistent infection, presented a distinct pattern of modification, according with a different clinicopathological evolution. Changes consisted in systemic immune activation coincident with the highest viremia titer, with an augmentation in CD8+ T lymphocyte, macrophage, and B cell populations, and MHC (major histocompatibility complex) antigens. Percentage elevation of circulating immune subpopulations was accompanied by cell accumulation with lymphoid hyperplasia but a conserved distribution of B lymphocytes in lymphoid organs of chronically infected pigs.

Two of the moisture-loving Scrophularia species have been known as S. lyrata Willd. and S. auriculata L. The differences between the two taxa, which were assessed by Grau (in Mitt. Bot. Staatssamml. Mtinchen 12: 622-627. 1976), and reiterated by Ortega-Olivencia & Devesa (in Ruizia 11: 52. 1993), are to be found above all in the morphology of leaves, bracts, bracteoles, and staminode. The former, S. lyrata, includes plants which are often pubescent, with basal and medial leaves clearly lyrate, having 2-6 lateral lobules; bracts and bracteoles normally obovate and obtuse, with a broad, undulate, generally dark-purple scarious margin; and staminode orbicular or obovate (never more broad than long). It possesses 2n = 58 chromosomes, and is distributed through the Iberian Peninsula, Sardinia, Sicily, Crete, Morocco, and Algeria. The latter, S. auriculata, includes plants which are often glabrescent, with basal and medial leaves that are generally simple or with 1-2 basal lobules; bracts and bracteoles generally lanceolate and acute, with a narrow scarious margin frequently relegated to the apex, barely or not at all undulate, normally hyaline or greyish-brown; and staminode generally broader than long, subreniform or flabellate. It possesses 2n = 84 chromosomes, and is present in W and SW Europe, Corsica, Italy, and Morocco. Dandy (in Watsonia 7: 165. 1969) and later Dalgaard (in Opera Bot. 51: 31. 1979) typified S. auriculata, taking sheet 773.4 of the LINN herbarium as lectotype, a type which matches the concept defined above. However, the only Linnaean annotations that appear on this sheet are "HU" [= Hortus Upsaliensis] and "auriculata", and the sheet lacks the Species Plantarum (Linnaeus, 1753: 620) account number (in this case "4") typical of material incorporated within the collection by 1753. This makes it almost certain that this cultivated

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP. # 1 Fetal Lung Maturity Testing Clinical Chemistry No. CC 08-1 (CC-367) {#article-title-2} Neonatal respiratory distress syndrome (RDS) is a disorder of pulmonary immaturity with a high mortality characterized by low levels of pulmonary surfactant. Gestational age determines risk based on concentration of pulmonary surfactant, ie, as gestation progresses the concentration of pulmonary surfactant increases. As a result, newborns delivered at fewer than 28 weeks have a more than 60% risk of RDS, whereas those delivered at more than 34 weeks have a less than 5% risk of RDS. In situations where gestational age alone is not sufficient to determine RDS risk and preterm delivery is medically needed, amniotic fluid analysis can be performed to determine pulmonary surfactant concentration. Four common methods are the lecithin-sphingomyelin ratio, phosphatidylglycerol measurement, surfactant-albumin ratio, and lamellar body count. All of these tests have excellent negative predictive values but poor positive predictive values, ie, they are great at confirming maturity but poor at confirming immaturity. # 2 Alkaline Phosphatase Isoenzyme Analysis: Guiding the Differential Diagnosis of Elevated Serum Total Alkaline Phosphatase Clinical Chemistry No. CC 08-2 (CC-368) {#article-title-3} The measurement of alkaline phosphatase (ALP) has long been used in clinical medicine, primarily to aid the diagnosis and monitoring of liver and bone diseases. Its diagnostic utility is limited by the enzyme’s wide tissue distribution and by a variety of potential nonpathologic causes. Isoenzyme analysis is one of several tools available to the clinician hoping to further characterize an elevated total ALP. It provides differentiation among liver, bone, intestinal, placental, and tumor-related forms as the cause of an elevation. The case presents a patient with persistent elevated ALP and atypical bands in the isoenzyme electrophoresis gel. An atypical ALP may be the result of a macroenzyme, which, if present, complicates interpretation of the test result and may cause additional, unnecessary testing or procedures. Recognizing and reporting a macroenzyme is an important service the clinical laboratorian can provide a clinician. # 3 Indirect Phlebotomy: Is It Good Practice? Clinical Chemistry No. CC 08-3 (CC-369) {#article-title-4} Indirect phlebotomy, the collection of blood samples through vascular infusion devices, is a common practice adopted to minimize needle-stick pain and discomfort in hospitalized patients. However, this practice can lead to alteration of the specimen and medical errors associated with misrepresentation of the blood test values. Among the possible problems, dilution or concentration of a particular analyte may occur, depending on the contents of the line’s infusate. Although some studies may indicate that blood collection from lines can be acceptable for isolated laboratory tests, there are insufficient data to demonstrate the reliability of line draws as routine practice. Use of lines for specimen collection should be reserved only for those patients with truly poor vascular access or those patients who require multiple phlebotomies in a short time period. Samples should be collected from lines only under a direct physician order, with careful attention to technique and established protocols that take many variables into account, including the analytes, contents of the line, type of line, discard blood volume, time interval between interruption of infusion and sampling, and catheter size. Even with careful attention to these details, clinicians must remain wary of the potential for medical errors related to misinterpretation of laboratory test results based on such samples.

Aims: The knowledge of parameters as the quantity of anthocyanins and tannins present during grape maturation, their evolution during the ripening period and extractability data could improve the management of red wine fermentation and help predict the color of wines.Methods and results: Grapes from Vitis vinifera var. Cabernet Sauvignon, Syrah, Merlot and Monastrell were harvested in 2002, 2003 and 2004 from a commercial vineyards and their physicochemical characteristics together with the anthocyanin and tannin evolution during ripening were followed. The results showed that differences were found in the evolution of these compounds due to variety and year.Conclusions: Some of the studied parameters seemed to be clearly related to variety (berry weight and extractability index) and others seemed to be clearly affected by soil and edaphoclimatic conditions. The high extractability index in Monastrell reflects the difficulty involved in extracting their anthocyanins. The short maturation period observed for Merlot grapes and the high seed tannin index could lead to excessively astringent wines.Significance and impact of the study: This study demonstrate that the ripening period of some varieties (Merlot) in very warm conditions is too short, promoting the rapid accumulation of sugar in the pulp and an incomplete seed maturation that may lead to excessively astringent wines. Other varieties, e.g. Monastrell, show longer maturation period that usually permits pulp and seed maturity to be reached at the moment of harvest. The extractability index seems to be closely related to the grape variety and this is also an important fact to take into account when planning a vinification process.

Background: We sought to examine the relationship between health-related quality of life (HRQL) and a first emergencyrehospitalizationandmortalityinpatientswith heart failure (HF) having a wide variation in ventricular ejection fraction and functional status. Methods: Prospective study conducted with 394 patients admitted for HF-related emergencies at 4 Spanish hospitals. Baseline HRQL was measured with a generic questionnaire, the Medical Outcomes Study 36-item Short Form Survey (SF-36), and with an HF-specific instrument, the Minnesota Living With Heart Failure (MLWHF)questionnaire.Coxproportionalhazardsmodels were used to calculate hazard ratios (HRs) for hospitalization and death on the basis of HRQL scores. Results: During a median follow-up of approximately 6 months, 138 patients (35.0%) underwent a first emergency rehospitalization and 70 (17.8%) died. After adjustment for biomedical, psychosocial, and health care variables, the frequency of hospital readmission was higher in patients with worse scores on the SF-36 physical functioning (HR, 1.65; 95% confidence interval [CI], 1.11-2.44; P=.01), general health (HR, 1.73; 95% CI, 1.19-2.52; P=.003), and mental health (HR, 1.65; 95% CI, 1.10-2.47;P=.02) subscales. Results were similar for the mortality end point. For the MLWHF questionnaire, worse overall and worse physical and emotional summary scores were associated with higher mortality. Conclusions: Worse HRQL is associated with hospital readmission and death in patients with HF. The magnitude of this association, for both physical and mental HRQL components, is comparable to that for other wellknownpredictorsofhospitalreadmissionanddeath,such as personal history of diabetes, previous hospitalizations, and treatment with angiotensin-converting enzyme inhibitors. Arch Intern Med. 2005;165:1274-1279