Relationship between infrared skin radiation and functional tests in patients affected by Emery-Dreifuss muscular dystrophy: Part 2.

HYPOTHESIS: This study represents a second part of a recently published study about a new form of evaluation and development of rare genetic neurodegenerative diseases. The objective is to provide a more global vision of thermography with respect to the Emery-Dreifuss pathology, through the analysis of the data collection carried out for one year. The basic hypothesis is that thermography could become a valid tool for the diagnosis and follow-up of this pathology because is a very specific tool for registering temperature changes produced by a constant degenerative evolution of this muscular dystrophy.

Melatonin Treatment Enhances Aß Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis.

BACKGROUND: It has been postulated that inadequate clearance of the amyloid ß protein (Aß) plays an important role in the accumulation of Aß in sporadic late onset Alzheimer's disease (AD). While the blood brain barrier (BBB) has taken the center stage in processes involving Aß clearance, little information is available about the role of the lymphatic system. We previously reported that Aß is cleared through the lymphatic system. We now assessed lymphatic Aß clearance by treating a mouse model of AD amyloidosis with melatonin, an Aß aggregation inhibitor and immuno-regulatory neurohormone. OBJECTIVE: To confirm and expand our initial finding that Aß is cleared through the lymphatic system. Lymphatic clearance of metabolic and cellular "waste" products from the brain into the peripheral lymphatic system has been known for a long time. However, except for our prior report, there is no additional experimental data published about Aß being cleared into peripheral lymph nodes. METHODS: For these experiments, we used a transgenic mouse model (Tg2576) that over-expresses a mutant form of the Aß precursor protein (APP) in the brain. We examined levels of Aß in plasma and in lymph nodes of transgenic mice as surrogate markers of vascular and lymphatic clearance, respectively. Aß levels were also measured in the brain and in multiple tissues. RESULTS: Clearance of Aß peptides through the lymphatic system was confirmed in this study. Treatment with melatonin led to the following changes: 1-A statistically significant increase in soluble monomeric Aß40 and an increasing trend in Aß42 in cervical and axillary lymph nodes of treated mice. 2- Statistically significant decreases in oligomeric Aß40 and a decreasing trend Aß42 in the brain. CONCLUSION: The data expands on our prior report that the lymphatic system participates in Aß clearance from the brain. We propose that abnormalities in Aß clearance through the lymphatic system may contribute to the development of cerebral amyloidosis. Melatonin and related indole molecules (i.e., indole- 3-propionic acid) are known to inhibit Aß aggregation although they do not reverse aggregated Aß or amyloid fibrils. Therefore, these substances should be further explored in prevention trials for delaying the onset of cognitive impairment in high risk populations.

The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

Preclinical studies support a critical role of 5-HT4 receptors (5-HT4Rs) in depression and anxiety, but their influence in depression- and anxiety-like behaviours and the effects of antidepressants remain partly unknown. We evaluated 5-HT4R knockout (KO) mice in different anxiety and depression paradigms and mRNA expression of some neuroplasticity markers (BDNF, trkB and Arc) and the functionality of 5-HT1AR. Moreover, the implication of 5-HT4Rs in the behavioural and molecular effects of chronically administered fluoxetine was assessed in naïve and olfactory bulbectomized mice (OBX) of both genotypes. 5-HT4R KO mice displayed few specific behavioural impairments including reduced central activity in the open-field (anxiety), and decreased sucrose consumption and nesting behaviour (anhedonia). In these mice, we measured increased levels of BDNF and Arc mRNA and reduced levels of trkB mRNA in the hippocampus, and a desensitization of 5-HT1A autoreceptors. Chronic administration of fluoxetine elicited similar behavioural effects in WT and 5-HT4R KO mice on anxiety-and depression-related tests. Following OBX, locomotor hyperactivity and anxiety were similar in both genotypes. Interestingly, chronic fluoxetine failed to reverse this OBX-induced syndrome in 5-HT4R KO mice, a response associated with differential effects in hippocampal neuroplasticity biomarkers. Fluoxetine reduced hippocampal Arc and BDNF mRNA expressions in WT but not 5-HT4R KO mice subjected to OBX. These results demonstrate that the absence of 5-HT4Rs triggers adaptive changes that could maintain emotional states, and that the behavioural and molecular effects of fluoxetine under pathological depression appear to be critically dependent on 5-HT4Rs.

Absceso del psoas como presentación de tuberculosis vertebral: reporte de un caso / Psoas abscess as spinal tuberculosis presentation: case report

Introducción: El absceso del psoas es un cuadro infrecuente cuyo principal agente etiológico es el Staphyloccocus aureus, y que con baja frecuencia puede ser de etiología tuberculosa como complicación de una afección vertebral por Mycobacterium tuberculosis. Presentación del caso: Mujer de 58 años, mapuche, con antecedentes de enfermedad pulmonar obstructiva crónica y alcoholismo crónico, consultó por cuadro de dos meses de evolución de dolor lumbar, baja de peso y paresia de extremidad inferior derecha que impedía la marcha. Tomografía computada (TC) de columna evidenció espondilodiscitis y absceso del psoas derecho, iniciándose tratamiento antibiótico cubriendo Staphyloccocus aureus. Los hemocultivos y los cultivos de la colección resultaron negativos por lo que se decidió mantener tratamiento ambulatorio. Paciente consultó cuatro meses después por exacerbación de su disnea basal de dos semanas de evolución, radiografía de tórax y TC de tórax de alta resolución compatibles con tuberculosis pulmonar con diseminación miliar bilateral, por lo cual, se inició tratamiento antituberculoso, realizándose baciloscopías que resultaron negativas. Además, se solicitó identificación del bacilo de Koch mediante reacción de polimerasa en cadena que resultó positiva, con lo que se confirmó el diagnóstico de tuberculosis miliar y mal de Pott. Se decidió reevaluar con TC de columna una vez finalizado el tratamiento antituberculoso para decidir conducta quirúrgica. Discusión: Es importante la sospecha activa de etiología tuberculosa ante una espondilodiscitis y un absceso del psoas, pese a su baja frecuencia. El inicio del tratamiento en forma precoz puede modificar la progresión de una infección que puede ser invalidante e incluso mortal.

Introduction: The Psoas abscess is an infrecuent condition which main ethiology is the Staphyloccocus aureus and with less frequency can be a vertebral tuberculosis complication caused by Mycobacterium tuberculosis. Case Report: a 58 years old female, Mapuche, with Chronic Obstructive Pulmonar Disease and chronic alcoholism antecedents, was admitted in the emergency room with a two month old lumbar pain, loss of weight and right inferior extremity paresia which didn't allowed her to walk. The column's Computed Tomography (CT) showed spondylodiscitis and a right psoas abscess, the antibiotherapy, covering Staphyloccocus aureus, was started. The hemoculives and abscess' cultives were negative, so it was decided to continue with ambulatory treatment. The patient was admitted four month later because of two weeks of exacerbation of her basal dysnea. The thorax Radiography and high resolution CT were compatibles with pulmonary tuberculosis with bilateral miliar disemination. Antituberculosis treatment was started, bacilloscopies were negative, also, a Polymerase Chain Reaction identification of Koch's bacillus was performed, resulting positive, confirming the diagnosis of miliar tuberculosis and Pott's disease. Once antituberculosis treatment was finished, a new column's CT was requested to decided surgical conduct. Discussion: Is important to actively suspect of tuberculosis ethiology in presence of spondylodiscitis and psoas abscess, despite it's low frequency. The early treatment start may modify the progresion of an infección that can be invalidating and even mortal.

RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis.

Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants.

Avaliação preliminar da atividade antimicrobiana do extrato de erva-mate (Ilex paraguariensis A. St. - Hil.) obtido por extração com CO2 supercrítico / Preliminary evaluation of the antimicrobial activity of "erva mate" (Ilex paraguariensis A. St. - Hil.) extract obtained by using supercritical CO2

Ilex paraguariensis A. St. - Hil. (erva-mate) é uma árvore pertencente à família Aquifoleaceae, nativa da região sul da América do Sul e de grande importância cultural e econômica para os três estados da região sul do Brasil. O presente trabalho determinou o potencial antimicrobiano do extrato de erva-mate obtido por fluido supercrítico, frente a alguns microrganismos. As folhas de Ilex paraguariensis foram coletadas na região norte do RS. O extrato bruto da planta desidratada foi obtido pelo método de extração com fluido supercrítico, utilizando dióxido de carbono (CO2) como solvente. Foi obtida a solução mãe desse extrato (100 mg mL-1) que a seguir foi diluído (50; 25; 12,5; 6,25 mg mL-1) para avaliação da atividade antimicrobiana por meio da técnica de difusão do disco em ágar Müeller Hinton, sobre cepas de Acinetobacter baumannii (ATCC 19606), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) e Enterococcus faecalis (ATCC 29212). As análises foram efetuadas em triplicata, utilizando como controle negativo disco estéril sem impregnação e como controle positivo discos de antibióticos comerciais variáveis de acordo com a espécie bacteriana. Após 16 a 24h de incubação a 35ºC os halos com significância foram medidos. Observou-se atividade antimicrobiana frente a S. aureus (halos de inibição variaram entre 7 e 18 mm) e para P. aeruginosa (halos entre 6 e 11 mm), ambos nas concentrações de 100 até 25 mg mL-1. O extrato obtido por extração em fluido supercrítico de Ilex paraguariensis apresentou atividade antimicrobiana frente a S. aureus e P. aeruginosa.

Ilex paraguariensis A. St. - Hil. ("erva mate") is a tree of the Aquifoliaceae family, native to the south region of South America and of great cultural and economic importance for the three states of the south region of Brazil. The present study aimed to determine the antimicrobial potential of "erva mate" extract obtained by supercritical fluid against some microorganism strains. The leaves of Ilex paraguariensis were collected in the north region of Rio Grande do Sul State. The crude extract of dehydrated plant was obtained by supercritical fluid extraction, using carbon dioxide (CO2) as solvent. The extract mother solution (100 mg mL-1) was diluted (50; 25; 12, 5; 6.25 mg mL-1) for antimicrobial activity evaluation, by means of disk diffusion method on Müeller-Hinton agar, against strains of Acinetobacter baumannii (ATCC 19606), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212). The analyses were done in triplicate, using as negative control sterile disk without impregnation and as positive control, commercial antibiotic disks according to the bacterial species. After 16-24h incubation at 35ºC, the diameters of inhibition zones were measured. Antimicrobial activity was observed against S. aureus (inhibition zones between 7 and 18 mm) and P. aeruginosa (inhibition zones between 6 and 11 mm), both at the concentrations of 100 mg mL-1 to 25 mg mL-1. The extract of Ilex paraguariensis obtained by supercritical fluid presented antimicrobial activity against S. aureus and P. aeruginosa.

Utility of intravascular ultrasound examination during carotid stenting.

BACKGROUND: Intravascular ultrasound (IVUS) examination may provide useful information during endovascular procedures. However, its actual clinical utility for carotid stenting remains unclear. We evaluated the usefulness of IVUS as a complementary tool during endovascular procedures in the carotid arteries and its impact on the modification of the therapeutic strategy. METHODS: Between April 2006 and April 2007, 18 symptomatic patients (nine with transient ischemic attack, nine with stroke) underwent angioplasty and stenting of >70% stenosis of the internal carotid artery (ICA). Target lesions were identified with preoperative duplex scanning and further confirmed at angiography. Intraoperative IVUS examination was performed in all patients. Multilevel measurement of the artery as well as virtual histology images, before and after stenting, were obtained. RESULTS: The technique was 100% successful. There were no complications at the femoral puncture site and no neurological or other events. Compared with angiography, IVUS findings showed an average arterial diameter that was greater than 1.64+/-0.22mm. Based on virtual histology information, endovascular treatment was excluded in two patients and carotid endarterectomy was performed. Type or size of the stent was modified after IVUS examination in eight cases. CONCLUSION: IVUS examination provides complementary information to that obtained using conventional diagnostic procedures. It may be useful for characterizing the composition and measurement of the target lesion, choosing the type and size of the stent, and evaluating the results after the procedure.

Simple DNA extraction protocol for a 16S rDNA study of bacterial diversity in tropical landfarm soil used for bioremediation of oil waste.

Landfarm soil is used to bioremediate oil wastes from petrochemical industries. We developed a simplified protocol for microbial DNA extraction of tropical landfarm soil using only direct lysis of macerated material. Two samples of tropical landfarm soil from a Brazilian refinery were analyzed by this protocol (one consisted of crude oil-contaminated soil; the other was continuously enriched for nine months with petroleum). The soil samples were lysed by maceration with liquid nitrogen, eliminating the need for detergents, organic solvents and enzymatic cell lysis. Then, the DNA from the lysed soil sample was extracted using phenol-chloroform-isoamyl alcohol or guanidium isothiocyanate, giving high DNA yields (more than 1 micro g DNA/g soil) from both soil types. This protocol compared favorably with an established method of DNA template preparation that included mechanical, chemical and enzymatic treatment for cell lysis. The efficiency of this extraction protocol was confirmed by polymerase chain reaction amplification of the 16S rRNA gene, denaturing gradient gel electrophoresis and cloning assays. Fifty-one different clones were obtained; their sequences were classified into at least seven different phyla of the Eubacteria group (Proteobacteria - alpha, gamma and delta, Chloroflexi, Actinobacteria, Acidobac teria, Planctomycetes, Bacteroidetes, and Firmicutes). Forty percent of the sequences could not be classified into these phyla, demonstrating the genetic diversity of this microbial community. Only eight isolates had sequences similar to known sequences of 16S rRNA of cultivable organisms or of known environmental isolates and therefore could be identified to the genus level. This method of DNA extraction is a useful tool for analysis of the bacteria responsible for petroleum degradation in contaminated environments.

Proposed reference value of the CA 125 tumour marker in men. Potential applications in clinical practice.

INTRODUCTION: CA 125 is a tumour marker usually used to monitor the clinical course of the patients with ovary cancer. The frequently used reference value of this marker is 35 U/mL. However, some arguments to allow us to question us the validity of the classical reference value: i) a second generation of immunoassays, ii) diverse studies related to the factors that influence in the CA 125 serum concentrations and iii) the new applications of CA 125 in pathologies different to the ovary cancer. OBJECTIVES: 1) To propose a reference value of CA 125 in men; 2) To evaluate the CA 125 serum concentration according to different variables, some of which can be altered in pathologies where CA 125 level can be monitored and/ or altered. MATERIAL AND METHODS: 65 healthy men were included (age: 40.21+/-10.60 years). A survey containing different parameters and an analytic that contained a hemogram, hepatic, renal, pancreatic profile, ionogram, thyroid function, tumour markers and NT-Pro-BNP was carried out to exclude the presence of a pathological situation. The percentile 95 (P(95)) was calculated to obtain the reference value. Correlations among the CA 125 and the different variables were analyzed by the Spearman test. RESULTS: The median [ranges] and the P(95) were: 7.50 [3.00-25.00] and 20.17 U/mL, respectively. 78% of the values of CA 125 were < or =10 U/mL, 94% were < or =15 U/mL and 95% were < or =20 U/mL. Furthermore, the studied variables don't seem to influence in the concentrations of this marker. CONCLUSIONS: The proposed reference value obtained in healthy male subjects is significantly lower than the one used in the clinical practice. This value should be kept in mind when extending the use of this marker to other pathologies which was not used up to now.

Application of Origanum majorana L. essential oil as an antimicrobial agent in sausage.

This work reports on the antimicrobial activity in fresh sausage of marjoram (Origanum majorana L.) essential oil against several species of bacteria. The in vitro minimum inhibitory concentration (MIC) was determined for 10 selected aerobic heterotrophic bacterial species. The antimicrobial activity of distinct concentrations of the essential oil based on the highest MIC value was tested in a food system comprising fresh sausage. Batch food samples were also inoculated with a fixed concentration of Escherichia coli and the time course of the product was evaluated with respect to the action of the different concentrations of essential oil. Results showed that addition of marjoram essential oil to fresh sausage exerted a bacteriostatic effect at oil concentrations lower than the MIC, while a bactericidal effect was observed at higher oil concentrations which also caused alterations in the taste of the product.

[Pituitary adenomas invading the cavernous sinus. Transcranial transcavernous approach]. / Adenomas hipofisarios con invasiòn intracavernosa. Resultados del abordaje trancraneal al seno cavernoso.

UNLABELLED: Pituitary adenomas represent a significant proportion (+o-13%) of all intracranial tumors. Surgical treatment is as rule performed by transsphenoidal approach. However, a small but not insignificant subgroup of pituitary adenomas (5 to 7%) invade the lateral parasellar structures and the cavernous sinus in particular, and poses obvious problems to the therapeutic strategy, since transsphenoidal removal of these adenomas is usually incomplete. OBJECTIVE: To evaluate the results of transcranial removal of a consecutive series of pituitary adenomas invading the cavernous sinus. MATERIAL AND METHOD: A retrospective study of 9 patients harbouring pituitary adenomas invading the cavernous sinus who had been submitted to transcranial surgery was conducted. These patients were operated on in the time span June 1999 - December 2003, in the Nuova Clinica Latina (now NCL- Neurological Centere of Latium), Rome Italy, and the Hospital "Hermanos Ameijeiras", La Habana, Cuba, using a fronto-orbitozigomatic (FOZ) craniotomy, anterior clinoidectomy and a limited dissection of the cavernous sinus through the antero-medial triangle. RESULTS: Total macroscopical removal was achieved in 8 cases, partial in 1, who showed improvement or normalization of the hormonal levels and of the preoperative symptoms. Transitory complications occurred in 6 patients, one of them showed a permanet neurological deficit (paresis of the III cranail nerve). CONCLUSIONS: Transcranial transcavernous approach is an effective technique for attempting total removal of intracavernous pituitary adenomas. It allows to achieve remission of symptoms and hormonal control in the medium-long term. However complications are relatively frequent, and permanent sequelae are not negligible.

Isolation of Besnoitia besnoiti from infected cattle in Portugal.

Besnoitia besnoiti, an obligate intracellular protozoan parasite belonging to the phylum apicomplexa, is the causative agent of bovine besnoitiosis. Besnoitiosis is responsible for significant losses in the cattle industry of Africa and Mediterranean countries due to the high morbidity rate, abortion and infertility in males. The acute stage of disease is associated with the proliferative forms (tachyzoites) and is characterized by fever, whimpery, general weakness and swelling of the superficial lymph nodes. During the following chronic stage, a huge number of cysts are formed mainly in the subcutaneous tissues. This process is non-reversible, and chronic besnoitiosis is characterized by hyper-sclerodermia, hyperkeratosis, alopecia and, in bulls, atrophy, sclerosis and focal necrosis that cause irreversible lesions in the testis. In this paper we report on the identification of large cysts in the skin of a cow and a bull in Portugal, which presented loss of hair and enlargement and pachydermis all over the body. The observation of a two-layered cyst wall within the host cell, the encapsulation of the host cell by a large outer cyst wall, and the subcutaneous localization of the cysts within the host, were characteristic for B. besnoiti. The parasites were isolated from the infected animals and successfully propagated in Vero cells without prior passages in laboratory animals. Morphological characterization of B. besnoiti tachyzoites and the amplification of the 149 bp segment from the internal transcribed spacer 1 (ITS1), aided with specific primers, confirmed the identification of B. besnoiti.

Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial.

BACKGROUND: Little information is available on the outcome of controlled ovarian hyperstimulation (COH) using GnRH antagonist in oocyte donation cycles especially in comparison with the short GnRH agonist protocol. This study was aimed at comparing the two stimulation protocols in oocyte donation (OD) cycles. METHODS: A total of 113 donors randomly received COH using either GnRH antagonist or GnRH agonist. The primary endpoint was the mean number of mature oocytes retrieved per started donor cycle. Secondary endpoints were the mean number of cumulus-oocyte-complexes (COCs) retrieved, the mean proportion of mature oocytes, pregnancy and implantation rates in recipients. RESULTS: Oocytes were distributed to 166 recipients. The mean number (+/- SD) of COC (11.6 +/- 5.8 versus 12.1 +/- 6.7), mature oocytes (8.4 +/- 4.4 versus 8.9 +/- 5.3) and the proportion of mature oocytes (70.8 versus 75.7%) retrieved per started donor cycle were similar in the antagonist and agonist groups, respectively. The implantation rate (26.1 versus 30.1%), clinical (40.2 versus 45.6%) and ongoing pregnancy rate per recipient cycle (32.2 versus 37.9%) were comparable in antagonist and agonist protocols, respectively. CONCLUSIONS: Similar mean number of mature oocytes and comparable pregnancy rates are achieved after OD in which donors received COH using GnRH antagonist or short GnRH agonist protocols.

A mutation in myotilin causes spheroid body myopathy.

BACKGROUND: Spheroid body myopathy (SBM) is a rare, autosomal dominant, neuromuscular disorder, which has only been previously reported in a single large kindred. Identification of the mutated gene in this disorder may provide insight regarding abnormal neuromuscular function. METHODS: The authors completed a detailed clinical evaluation on an extensive kindred diagnosed with SBM. Genome-wide linkage analysis was performed to localize the disease gene to a specific chromosomal region. Further marker genotyping and screening of a positional, functional candidate gene were completed to detect the disease-causing mutation. Pathologic analysis of muscle biopsy was performed on three individuals. Biochemical studies were performed on one muscle biopsy specimen from an affected individual. RESULTS: Linkage to chromosome 5q23-5q31 was detected with a lod score of 2.9. Genotyping of additional markers in a larger sample of family members produced a maximum lod score of 6.1 and narrowed the critical interval to 12.2 cM. Screening of the candidate gene titin immunoglobulin domain protein (TTID, also known as MYOT) detected a cytosine-to-thymine mutation in exon 2 of all clinically affected family members. Similar pathologic changes were present in all muscle biopsy specimens. Immunohistologic and biochemical analysis revealed that the TTID protein, also known as myotilin, is a component of the insoluble protein aggregate. CONCLUSIONS: A novel mutation in the TTID gene results in the clinical and pathologic phenotype termed "spheroid body myopathy." Mutations in this gene also cause limb-girdle muscular dystrophy 1A and are associated with myofibrillar myopathy.

[Prognostic value of syncope in the presentation of pulmonary embolism]. / El síncope como forma de presentación de la embolia de pulmón: valor pronóstico.

OBJECTIVE: Although the prognostic value of syncope has not been specifically addressed, it has generally been considered an indicator of poor prognosis in pulmonary embolism. The objective of this study was to carry out a prospective evaluation of the risk of recurrence and/or death in patients with pulmonary embolism that presents with syncope. PATIENTS AND METHODS: A total of 168 patients had a confirmed diagnosis of pulmonary embolism. Twelve were lost to follow up and did not enter statistical analysis. The mean follow-up period was 5 months. RESULTS: The prevalence of syncope in the patients studied was 22%. Of the 34 patients who presented syncope, objectively confirmed recurrence occurred in 2 (5.9%). In the patients who did not present syncope, recurrence was confirmed in 8 (6.6%; P=.8). Death occurred in 2 patients (5.9%) from the group presenting syncope and 15 (12.3%) from the remaining patients in the series (P=.4). The relative risk of recurrence and/or death associated with presentation of syncope was 0.5 (95% confidence interval, 0.2-1.8). A similar risk was obtained following adjustment for the presence or absence of cancer or deep vein thrombosis. CONCLUSIONS: Patients with pulmonary embolism that presents with syncope do not have an increased risk of recurrence and/or death.

[Carotid stenosis in high risk patients. The SAPPHIRE study versus a decision analysis. Which is the best therapeutic option?]. / Estenosis carotídea en enfermos de alto riesgo. Estudio SAPPHIRE frente a un ánalisis de decisión. Cuál es la mejor opción terapéutica?

INTRODUCTION: In the results from the SAPPHIRE study on high surgical risk patients with carotid stenosis there are no differences between carotid stent-angioplasty (CSA) and carotid endarterectomy (CEA). AIMS: The aim of this study was to analyse the cost-effectiveness of these two interventions based on the data from the above-mentioned study and on our own experience in carotid surgery. PATIENTS AND METHODS: We evaluated 108 CSA carried out between 1999 and 2003. The morbidity and mortality rates in the subgroup of high risk patients, according to the criteria used in the SAPPHIRE study, were analysed according to whether they were symptomatic or asymptomatic. Data concerning endovascular treatment were taken from the literature. A cost-effectiveness study was conducted considering four possible perioperative events: absence of sequelae, AMI, established CVA and death. The computer software package DATAPro was used after fitting the decision to the theoretical quality of life for each of these groups. Cost-effectiveness was estimated based on the cost of each procedure. RESULTS: Of the 108 patients, 41 (37.96%) belonged to the high risk subgroup; 46.3% of them were asymptomatic and 53.7% were symptomatic. In the 30 days following the intervention, one CVA (5.2%) and one AMI (4.5%) were observed. No deaths occurred. The decision analysis for symptomatic patients showed CEA to be the most effective therapeutic option. Similar results were obtained for asymptomatic patients. The average cost for CEA was 3,963 euros and rose to 5,158 euros in the case of CSA. CONCLUSIONS: In our study, CEA is the preferred technique in high risk patients owing to its having a better cost-benefit ratio.

Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene.

Abnormal accumulation of ferritin was found to be associated with an autosomal dominant slowly progressing neurodegenerative disease clinically characterized by tremor, cerebellar ataxia, parkinsonism and pyramidal signs, behavioral disturbances, and cognitive decline. These symptoms may appear sequentially over a period of 4 decades. Pathologically, intranuclear and intracytoplasmic bodies were found in glia and subsets of neurons in the central nervous system as well as in extraneural tissue. Biochemical analyses of these bodies isolated from the striatum and cerebellar cortex revealed that ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH1) were the main constituents. Molecular genetic studies revealed a 2-bp insertion mutation in exon 4 of the FTL gene. The resulting mutant polypeptide is predicted to have a carboxy terminus that is altered in amino-acid sequence and length. In tissue sections, the bodies were immunolabeled by anti-ferritin and anti-ubiquitin antibodies and were stained by Perls' method for ferric iron. Synthetic peptides homologous to the altered and wild-type carboxy termini were used to raise polyclonal antibodies. These novel antibodies as well as an antibody recognizing FTH1 immunolabeled the bodies. This study of this disorder has provided additional knowledge and insights in the growing area of ferritin-related neurodegeneration.

[Screening program for alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease, using dried blood spots on filter paper]. / Programa de cribado para el déficit de alpha 1-antitripsina en pacientes con EPOC mediante el uso de gota de sangre en papel secante.

Alpha-1 antitrypsin (AAT) deficiency is an under-diagnosed disease and screening programs have therefore been recommended for patients with chronic obstructive pulmonary disease (COPD). We present the results of the pilot phase of a screening program for AAT deficiency in order to evaluate the technique used, the procedures for transporting samples and the results obtained. Over a period of one month, five centers collected samples from all COPD patients for whom plasma concentrations of AAT or Pi phenotype had not yet been determined. Capillary blood spots were dried on filter paper and then sent by surface mail to a central laboratory for study. An immunonephelometric assay was used to determine AAT and DNA phenotyping was done by use of a Light Cycler. Samples were analyzed from 86 COPD patients (76 men, 10 women) with a mean age of 68.2 years. AAT deficiency was ruled out for 74 patients (86%) who had concentrations above the cutoff established, although one of them was MZ heterozygote by genotype. Among the 12 remaining patients (13.9%), only two also had a Z allele. The rest were individuals with concentrations below the established threshold and no evidence of a Z allele (10 patients, 11.6%). The Z allele frequency observed (3/172; 1.74%) was very similar to that found in the general population. The results of this pilot study allowed us to confirm that the method used to collect samples worked well. The sampling method is applicable, easy and well-accepted by participating physicians. It allowed AAT concentrations and Z allele deficiency to be determined. The method correlates well with standard techniques used for samples in whole blood.

[Importance of serum interleukin-6 as a mediator of systemic inflammation in patients with alpha-1 antitrypsin deficiency]. / Importancia de la medición de la interleucina 6 en suero como mediador de inflamación sistémica en pacientes con deficiencia de alfa-1-antitripsina.

The objective of this study was to determine whether high concentrations of circulating interleukin-6 (IL-6) and/or the soluble receptor of IL-6 (SRIL-6) may mediate systemic inflammatory activity in patients with alpha-1 antitrypsin deficiency (AATD). To that end we assessed serum concentrations of IL-6 and SRIL-6 for 7 patients with AATD in stable phase. The patients' mean age was 51 years (SD 5.2); mean FEV1% was 35.5% (SD 15%). IL-6 and SRIL-6 concentrations were compared with those of 23 non-AATD patients with COPD but with similar changes in lung function (mean age 63 years, SD 10.1; FEV1% 38.3%, SD 11%). The AADT patients had mean IL-6 concentrations of 4.7 pg/mL (interquartile range [IR( 4.0) and RSIL-6 levels of 129.1 ng/mL (IR 31.5). The COPD patients had IL-6 concentrations of 4.1 pg/mL (IR 4.2) and SRIL-6 levels of 140.8 ng/mL (IR 71). No significant differences between the AADT group and the COPD group were observed for either cytokine (non-parametric Mann Whitney U test, p > 0.05). Only one AADT patient had an IL-6 concentration that was higher than normal. In conclusion, the serum IL-6 and SRIL-6 concentrations of patients with AADT are not different from those of patients with COPD, similarly altered respiratory function and normal alpha-1 antitrypsin levels. These results do not point to a role for alpha-1 antitrypsin in systemic inflammatory stimulation in patients with AADT.