A clinical distortion index for compressed echocardiogram evaluation: recommendations for Xvid codec.

This paper introduces a new clinical distortion index able to measure the decrease in diagnostic content in compressed echocardiograms. It is calculated using cardiologists' answers to a clinical testbed composed of two types of tests: one blind and the other semi-blind. This index may be used to compare clinical performance among video codecs from a clinical perspective. It can also be used to classify compression rates into useful and useless ranges, thus providing recommendations for echocardiogram compression. A study carried out in order to illustrate its use with Xvid video codec is also presented. The results obtained showed that, for 2D and M modes, the transmission rate should be at least 768 kbit s(-1) and for color Doppler mode and pulsed/continuous Doppler, 256 kbit s(-1).

[Pilot Drug Utilization Study of systemic antifungal agents in the Hospital Clínico San Carlos. Proposal of a study method]. / Estudio piloto de utilización de antifúngicos sistémicos en el Hospital Clínico San Carlos. Propuesta de un método de estudio.

INTRODUCTION: The study aims to define a method for the evaluation of the usage of systemic antifungal agents, and test it, in order to be able to develop larger studies. METHOD: Drug Use Study, pilot, observational, prescription- indication. We proposed a definition of antifungal type of treatment using as host factors the EORTC (European Organization for Research and Treatment of Cancer) criteria, the patient's clinical data as well as any evidence of fungal infection. Adequate use was evaluated by three standards of comparison: summary of product characteristics, hospital recommendations and an experts' committee. RESULTS: 60 antifungal prescriptions were recovered: fluconazole: 39; itraconazole: 6; liposomal amphotericin B: 5; caspofungin: 5; voriconazole: 5. Treatment was started as follows (N;%): microbiological (28;46.7), empirical (22;36.7) and prophylactic use (7;11.7). The indication for antifungal treatment was considered adequate in more than 90% of the cases for the three standards of comparison, whereas selection in 75-83% of the cases. CONCLUSIONS: The method is considered satisfactory for the evaluation of antifungal treatments and is proposed for being used in larger studies. For all the antifungal agents evaluated, a high degree of appropriateness of use was found, though some conditions are considered improvable.

Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial.

The effects of the CYP3A4 inducer, Hypericum perforatum, on the pharmacokinetics of a single oral dose of ivabradine were assessed. An open-label, 2-period, nonrandomized, phase-I, pharmacokinetic interaction design was used. Twelve healthy volunteers received a single oral dose of ivabradine (10 mg) followed by H perforatum (300 mg orally, 3 times a day) for 14 days, combining the last dose with another single dose of ivabradine. Pharmacokinetic data for ivabradine (S16257) and its main active metabolite (S18982) prior to and after the administration of H perforatum were analyzed. After repeated administration of H perforatum, highest observed concentration in plasma (C(max)) and area under the concentration-time curve (AUC) were significantly decreased for ivabradine (32.7 +/- 16.6 vs 15.4 +/- 7.0 ng/mL, P < .01; 114 +/- 39.1 vs 43.7 +/- 12.0 ng x h/mL, P < .01, respectively), and for S18982 (C(max), 6.8 +/- 3.7 vs 5.1 +/- 2.0 ng/mL, P < .05; AUC, 56.2 +/- 23.4 vs 38.3 +/- 25.1 ng x h/mL, P < .01). Tendencies toward shorter time to C(max) and lower apparent terminal half-life values were found. Pharmacokinetic results are consistent with an induction of ivabradine metabolism by H perforatum.

Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial.

The effects of omeprazole and lansoprazole (CYP3A4 inhibitors) on the pharmacokinetics of a single dose of ivabradine (metabolized via CYP3A4) and its active metabolite (S18982) were assessed. Pharmacodynamics and safety were secondary objectives. An open-label, randomized, crossover, phase I, pharmacokinetic interaction design was used. Volunteers received a single oral dose of ivabradine (10 mg), were randomized to receive either omeprazole (40 mg) or lansoprazole (60 mg) for 5 days, and were administered an ivabradine dose on the sixth day. Crossover was performed after washout. Pharmacokinetic parameters for ivabradine did not vary significantly after omeprazole (C(max): 45.0 +/- 36.6 vs 42.7 +/- 27.6 ng/mL, P = .98; AUC: 128 +/- 87 vs 126 +/- 63 ng/mL, P = .82) or lansoprazole administration (C(max): 45.0 +/- 36.6 vs 41.3 +/- 29.4 ng/mL, P = .70; AUC: 128 +/- 87 vs 123 +/- 50, P = .73). Analyses of S18982 pharmacokinetic parameters showed similar results. Coadministration of either omeprazole or lansoprazole did not significantly affect the pharmacokinetics of a single dose of ivabradine. No pharmacodynamic interaction or safety concerns were evidenced.

Health economics assessment study of teicoplanin versus vancomycin in Gram-positive infections.

The objective of this study, conducted at Hospital Clínico San Carlos, Madrid, Spain, was to compare the cost of treatment of Gram-positive infections with teicoplanin and vancomycin under normal conditions. Using a prospective observational study design for drug utilization and economic assessment, we evaluated the comparability of the sample, adverse events, features of treatment with teicoplanin/vancomycin and factors influencing the consumption of resources until the end of glycopeptide treatment or discharge (whichever occurred later) using Health System perspective. Costs were assigned using the hospital's evaluation at the time of the study. Analyses made: multivariate, sensitivity (by modifying staff or acquisition costs) and simulation of reduction of stay by early discharge in the teicoplanin group. Study participants included 201 patients who had been using teicoplanin (n=100) or vancomycin (n=101) for at least four days. Data collected daily outside morning work timetable. Costs of acquisition, administration and monitoring by course of treatment (mean+/-SD, in euros) were lower in the vancomycin group (teicoplanin euro647.62+/-euro572.75 vs. vancomycin euro378.11+/-euro225.90); when total costs (including hospital stay) were considered, no differences were found (teicoplanin euro4,432.04+/-euro3,383.46 vs. vancomycin euro4,364.44+/-euro2,734.24). Conditions of use and results were similar for both antibiotics. The economic results of acquisition, administration and monitoring were advantageous for vancomycin; when global costs of care were taken into account, these differences were not evident. Tolerability was significantly advantageous in the teicoplanin group (with regard to phlebitis and elevation of creatininemia), without differences in clinical or economic outcomes. The formulation of teicoplanin did not take advantage of its potential benefits of administration.

Fatal portal thrombosis after laparoscopic Nissen fundoplication.

Portal and mesenteric vein thrombosis is a very uncommon complication of laparoscopic surgery, especially after anti-reflux procedures. We report the case of a twenty-year-old man with a history of alcohol and cocaine consumption. A Nissen fundoplication was performed. The patient received a single 20-mg dose of enoxaparin (Clexane, Aventis Pharma, Spain) two hours before surgery for antithrombotic prophylaxis. On the seventh postoperative day the patient had a portal and mesenteric venous thrombosis, which was confirmed at laparotomy, with both extensive small-intestine necrosis and partial colon necrosis. Despite anticoagulant therapy, the patient died 24 hours later. Surgical findings were confirmed at necropsy. Portal and mesenteric venous thrombosis is an uncommon but severe and even fatal complication after laparoscopic anti-reflux surgery. When other pro-thrombotic, predisposing conditions such as laparoscopic surgery and cocaine consumption are present, the usual prophylactic doses of low molecular weight heparin might not be sufficient to protect against this life-threatening complication.

[Pericardial mesothelioma: apropos of a case]. / Mesotelioma pericárdico: a propósito de un caso.

We report a case of primary pericardial malignant mesothelioma in a 53-year old male with no asbestos previous exposure. The first clinical sign was a massive pericardial effusion causing hemodynamic disturbances. CT confirmed the initial ecochardiographic diagnosis. The patient underwent pericardiocentesis which improved his hemodynamic status as well as showed malignant cellularity in the liquid examination. Surgical treatment, including pericardiectomy and tumor resection, together with chemotherapy restored normal hemodynamics, the patient being now asymptomatic. We want to emphasize the rarity of this tumor and its insidious clinical presentation even leading to hemodynamic impairment, as well as the great value of echocardiography and CT in its diagnosis, although, in some cases, thoracotomy has been the only valid diagnostic procedure.

Effects of several neuroleptic compounds on the blastogenic response of spleen cells from mice.

The effects of chlorpromazine, haloperidol, clozapine and clotiapine on the mitogenic activation of spleen and bone-marrow cells were investigated. The use of two types of treatments (in vitro with 1.5 to 3 x 10(-3) mM for three days and in vivo with 0.3 mM for four days) permitted the demonstration that chlorpromazine was the most effective drug to inhibit DNA synthesis in mitogen stimulated mouse spleen cell cultures. However, in more prolonged in vivo treatments with a lower dose (0.075 mM for two weeks), clozapine and clotiapine frequently appeared as the most active inhibitors of mitogen-induced lymphoblastic transformation. In any case splenic T lymphocytes were more affected than B cells of the same origin. (3H) TdR uptake in DXS-stimulated bone-marrow cell cultures was also variably inhibited by in vivo drug treatments of mice as compared to groups of untreated animals. Occasionally, the effect of the drugs in vivo depend on the length of the treatment, rather than the dose administered. All these inhibitory effects did not appear as a phenomenon of cytotoxicity since doses used in vitro inhibit by less than 5% the cell viability. It is suggested that the variable depressions of the different mitogenic responses, produced by these neuroleptic drugs, may reflect an alteration in the cyclic AMP levels as a consequence of its inhibition of a phosphodiesterase activator.

[Malignant fibrous histiocytoma of soft tissue: description of 10 cases]. / Histiocitoma fibroso maligno de partes blandas: descripción de 10 casos.

We analyze the clinical and histological features of 10 cases of malignant fibrous histiocytoma of soft tissue. Nine belonged to the pleomorphic-verticillate variety and one was myxoid. The initial clinical feature was a palpable mass in all cases except three with retroperitoneal localization, where constitutional symptoms predominated. After therapy (surgery in all, associated with radiotherapy in four), seven patients had local relapse and two had distant metastases. 50% died, with a mean survival of 13 months. We discuss the prognostic factors and the therapeutic approach, with emphasis on aggressive therapy and the need for radical surgery and postoperative adjuvant therapy.

[Neuroimaging and efficacy of treatment in advanced African trypanosomiasis]. / Neuroimagen y eficacia del tratamiento en la tripanosomiasis africana avanzada.

INTRODUCTION: West African trypanosomiasis (WAT) is rare in Spain. Delay in its diagnosis and treatment leads to irreversible diffuse meningoencephalitis and finally death of the patients. CLINICAL CASE: We described a patient in whom the diagnosis of advance WAT had been delayed. He had headache, alteration of the level of consciousness and sleep pattern, psychiatric disorders, crises, extrapyramidal, sensitive and endocrinological clinical alterations. Biochemical investigation showed slight anemia with marked thrombocytopenia, and raised ESR and IgM. Initially serology was negative for trypanosomes, although examination of the CSF confirmed the diagnosis. MR showed extensive lesions of the basal nuclei, brainstem and white matter. Both the clinical abnormalities and the lesions shown on MR disappeared after treatment with intravenous difluoromethylornithine. The patient is now symptom-free and at work as usual. DISCUSSION: Find diagnosis of WAT requires isolation of the parasite from the blood, the bone marrow or CSF. When other complementary tests (such as serology) are negative, the diagnosis should not be ruled out. There are few neuroimaging studies of WAT, and only by CT. We have found no MR studies of patients with WAT, in the literature. We emphasize the close correlation between the clinical and radiological findings in this case, and the excellent result obtained after treatment.

Better sexual acceptability of agomelatine (25 and 50 mg) compared with paroxetine (20 mg) in healthy male volunteers. An 8-week, placebo-controlled study using the PRSEXDQ-SALSEX scale.

Sexual dysfunction (SD) is a common and underestimated effect of antidepressants. Healthy volunteers are the most adequate group to study this adverse event avoiding influence of depression itself. Sexual acceptability of agomelatine (a melatonergic agonist and 5HT(2C) antagonist) paroxetine and placebo by using the Psychotropic-Related Sexual Dysfunction Salamanca Sex Questionnaire (PRSEXDQ-SALSEX) was explored. A total of 92 healthy male volunteers were randomised to agomelatine (25 or 50 mg), paroxetine 20 mg or placebo for 8 weeks. SD, defined as at least one sexual impairment in one of the following PRSEXDQ-SALSEX items (decreased libido, delayed orgasm/ejaculation, anorgasmia/no ejaculation and erectile dysfunction), was evaluated at baseline and after 2, 4 and 8 weeks. At the last post-baseline assessment, SD was significantly lower in each agomelatine group (22.7% on 25 mg and 4.8% on 50 mg) than in the paroxetine group (85.7%; p < 0.0001). In the placebo group, 8.7% of volunteers reported a SD. The percentages of volunteers with moderate or severe SD were 4.5% for agomelatine 25 mg, 4.8% for agomelatine 50 mg, 61.9% for paroxetine 20 mg and 0% in the placebo group (p < or = 0.0001 agomelatine versus paroxetine). There is a much lower risk of having SD with agomelatine than paroxetine in healthy male volunteers, which confirms the better sexual acceptability profile of agomelatine compared with the SSRIs.

Recomendaciones para el tratamiento del dolor neuropático / Recommendations for the treatment of neuropathic pain

Con la introducción y el desarrollo de nuevos productos que han demostrado ser eficaces en el dolor neuropático (DN), se ha generado una clara necesidad de tener un algoritmo basado en la evidencia para tratar las diferentes condiciones del DN. El objetivo de este artículo es elaborar unas recomendaciones para el tratamiento del DN que estén avaladas por la evidencia científica y que estén consensuadas por un grupo multidisciplinario de expertos en metodología y en tratamiento del dolor. La evidencia se ha obtenido de estudios de metanálisis que recogen la mayor información disponible para cada tipo de DN. La búsqueda bibliográfica se llevó a cabo por 5 revisores, que se centraron individualmente en las diferentes formas de presentación del DN. Las bases de datos consultadas fueron la Cochrane Library, EMBASE (año 2000 en adelante) y PUBMED(año 2000 en adelante), y se seleccionaron metaanálisis y ensayos clínicos aleatorizados y controlados. Finalmente, los autores, especialistas en dolor, evaluaron e hicieron las recomendaciones clínicas para el tratamiento del DN. En algunos tipos de DN, de los cuales no hay suficiente información, se han incluido recomendaciones basadas en publicaciones científicas sin evidencia, con el objetivo de que estas recomendaciones proporcionen la mayor información posible acerca de su tratamiento. Se han revisado estudios de eficacia y seguridad de neuralgia postherpética (NPH), neuropatía diabética dolorosa (NDD) y neuralgia del trigémino(NT) como paradigmas de DN periférico, y también se ha recogido la escasa información existente acerca del DN central(DNC) y el dolor simpático (DS). Con los resultados obtenidos con este estudio bibliográfico y las evidencias extraídas, se ha elaborado un algoritmo de decisión con los fármacos disponibles actualmente en la farmacopea española para la NPH y la NDD; por otro lado, y de forma independiente, para la NT y, finalmente, para el DNC y el DS.

The introduction and development of new products with demonstrated efficacy in neuropathic pain has generated a clear need for an evidence-based algorithm to treat the different types of neuropathic pain. The present article aims to provide recommendations on the treatment of neuropathic pain supported by the scientific evidence and agreed on by consensus by a multidisciplinary group of experts in methodology and pain management. The evidence was obtained from meta-analyses including the greatest amount of information available for each type of neuropathic pain. The literature search was performed by 5 reviewers, who focussed individually on the distinct forms of presentation of neuropathic pain. The databases consulted were the Cochrane Library, EMBASE (from 2000 onwards), and PUBMED (from 2000 onwards). Meta-analyses and randomized, controlled clinical trials were selected. Finally, retrieved articles were evaluated and clinical recommendations for the treatment of neuropathic pain were designed by the pain specialists. For some types of neuropathic pain, there is insufficient information. In these types of pain, recommendations based on scientific publications without evidence were included to provide the reatest possible amount of information on their treatment. Studies of safety and efficacy in postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia (TN) were reviewed as paradigms of peripheral neuropathic pain. The scarce available information on central neuropathic pain (CNP) and sympathetic pain (SP) was also gathered. Based on the results obtained with this literature review and the evidence extracted, a decision algorithm was designed with the drugs currently available in the Spanish pharmacopeia for PHN and PDN, and separate decision algorithms were designed for TN and finally for CNP and S P.

[NKCELPRO: a program for microcomputer applicable to the study of responses of spontaneous cytotoxicity]. / NKCELPRO: programa para microordenador aplicable al estudio de respuestas de citotoxicidad espontánea.

A microcomputer program (NKCELPRO) which expedites the exact quantification of various parameters referring to NK cell activities is described. The program is written in BASIC language and computes the activities of cell-mediated cytotoxicity by collating and reducing radioactive count data obtained from 51Cr releasing assays. The information generated by this program includes statistics such as the average values, fitting by last square regression line with its correlation coefficient, as well as determination of the percent specific lysis and lytic units/10(7) effector cells according to any reference value previously defined by the operator. Special program features allow for a certain flexibility in the experimental protocol design as well as in the graphic expression of the results. Data storage on a disk with filing purposes for subsequent studies is also available.

The influence of glutamic acid and arginine on the competence of Bacillus subtilis growing in a chemostat.

Using a new method to get stable steady state levels of competence in B. subtilis, we have obtained in our experimental conditions 0.1% competence as determined by the frequency of transfection with phage SPP1 DNA. The effect of growth rate (DT) and certain amino acids on the competence levels was also determined.

Physical dependence to morphine diminishes the interferon response in mice.

Morphine pellet implantation in mice was demonstrated to diminish resistance to encephalomyocarditis virus infections. The variations in the response to three different interferon (IFN) inducers--Newcastle disease virus, Escherichia coli lipopolysaccharide and a tilorone analogue--were evaluated. A close relationship between morphine dependence and IFN response was detected. A clear inhibition in IFN induction appeared as a concomitant phenomenon with the syndrome of morphine dependence. In the response intensity, the mice strain tested was more important than the total drug dose in the pellet. This effect of morphine on IFN responses presented a characteristic age-related pattern and, perhaps, may also be influenced by the H-2 murine phenotype.

Transfection of Streptococcus pneumoniae with bacteriophage DNA.

It was possible to transfect Streptococcus pneumoniae with DNA obtained from a newly isolated bacteriophage, diplophage-4 (Dp-4). Optimal frequency of transfection (0.9%) required the use of a nuclease-defective mutant; with wild-type bacteria, the transfection frequency was about 100-fold lower. Transfection requires physiological conditions that appear to be similar to the competent state needed for genetic transformation (A. Tomasz, J. Bacteriol. 91:1050--1061, 1966).

Transfer of antibacterial immunity by "Immune" RNA from animals treated with pseudomonas lipopolysaccharide.

The humoral primary immune response to Pseudomonas aeruginosa lipopolysaccharide was studied. Mice immunized with various doses of LPS developed anti-LPS antibodies. Antibody activity was due to 19S and 7S immunoglobulins. Extracts rich in RNA from spleen cells of immune mice were able to transfer specific anti-LPS response to normal recipients. Immunogenic antigen contamination of RNA was ruled out by a variety of controls.

Indomethacin esters acting as anti-inflammatory and immunosuppressive drugs.

Administration of indomethacin and ten different indomethacin derivatives led to a variable depression in the mice immume response to sheep red blood cells (SRBC) as shown either by direct hemolytic-plaque assay or hemagglutination tests. Compounds with a lower toxicity than indomethacin and predominant immunosuppressive or anti-inflammatory activity were obtained. According to the variations in the primary immune response and to their variable anti-inflammatory actions, the structure-activity relationships are documentted and some possible explanations, relative to their immunodepressive effect, are discussed.