Antiagregación plaquetaria dual y nivel de hemoglobina: un estudio observacional / Dual antiplatelet therapy and haemoglobin level: an observational study

Introducción. Determinar el grado de asociación entre la terapia de antiagregación plaquetaria dual (TAAD) (clopidogrel y ácido acetilsalicílico) y el nivel de hemoglobina (Hb) en la práctica clínica. Material y métodos. Estudio retrospectivo. Se incluyeron todos los pacientes con TAAD durante al menos 6 meses, siendo el tamaño muestral necesario de 63 pacientes. Se determinó la Hb antes de la TAAD y el valor más próximo al cierre del estudio, la duración del tratamiento y las prescripciones o enfermedades que pudieran disminuir la Hb. Se calculó la variación de Hb tras TAAD y la aparición o empeoramiento de anemia previa. Se comparó la Hb previa y la posterior mediante prueba t para muestras apareadas. La aparición de anemia fue la variable dependiente en un análisis de regresión logística. Resultados. Se incluyeron 122 casos. Noventa y dos eran varones (75,4%), con una edad media de 74,5 (DE 9,9) años. La duración de la TAAD era de 19,3 (11,8) meses, siendo la Hb previa de 14,3 (1,4) y la posterior de 12,8 (1,9) g/dl. Había anemia pretratamiento en 11 casos (9,1%) y postratamiento en 56 (45,9%). La comparación de medias mostró un descenso de 1,5 (1,6) (IC95% 1,2-1,8; p<0,001) g/dl, asociándose la anemia postratamiento a la edad, causas concomitantes de anemia, hemorragias en el seguimiento y, de forma inversa, al nivel de Hb pretratamiento. Conclusiones. La TAAD se asocia con un descenso de la Hb, apareciendo anemia o empeoramiento de la misma en cerca de la mitad de los sujetos, y siendo este efecto más probable en los pacientes con hemorragias en el seguimiento y en presencia de otras causas de anemia (AU)

Introduction. To determine the degree of association between dual antiplatelet therapy (DAPT) (clopidogrel plus acetylsalicylic acid) and haemoglobin (Hb) in clinical practice. Material and methods. A retrospective longitudinal analysis was conducted on all patients on DAPT for at least 6 months. The required sample size was 63 patients. Hb value was determined before DAPT and at least 6 months after, as well as length of treatment, drugs, and diseases that might reduce the Hb. Changes in Hb after DAPT and the emergence or worsening of pre-existing anaemia was determined. Before and after Hb was compared using the t-test for paired samples. The occurrence of anaemia was considered dependent variable in a logistic regression analysis. Results. A total of 122 cases were included. There were 92 (75.4%) males, and the mean age was 74.5 (SD 9.9) years. DAPT duration was 19.3 (11.8) months. The pre-treatment Hb was 14.3 (1.4) g/dl and 12.8 (1.9) g/dl post-treatment. The prevalence of pre-DAPT anaemia was 9.1% (11 cases), and 45.9% post-treatment (56 cases). Comparison of means showed a decrease of 1.5g/dl (1.6) (95% CI; 1.2-1.8, P<.001). Anaemia post-treatment was associated with concomitant causes of anaemia, bleeding in the follow-up, and inversely with pre-treatment Hb level. Conclusions. DAPT is associated with a decrease in Hb. Anaemia or worsening of previous anaemia appeared in about half of the subjects, and this effect was most likely in patients with bleeding in the follow-up and if other causes of anaemia were present (AU)

Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy.

AIMS: Pulmonary vein isolation is the mainstay of treatment in catheter ablation of paroxysmal atrial fibrillation (AF). Cryoballoon ablation has been introduced more recently than radiofrequency ablation, the standard technique in most centres. Pulmonary veins frequently display anatomical variants, which may compromise the results of cryoballoon ablation. We aimed to evaluate the mid-term outcomes of cryoballoon ablation in an unselected population with paroxysmal AF from an anatomical viewpoint. METHODS AND RESULTS: Consecutive patients with paroxysmal AF who underwent a first procedure of cryoballoon ablation or radiofrequency were enrolled in this single-centre study. All patients underwent systematic standardized follow-up. Comparisons between radiofrequency and cryoballoon ablation (Arctic Front™ or Arctic Front Advance™) were performed regarding safety and efficacy endpoints, according to pulmonary vein (PV) anatomical variants. A total of 687 patients were enrolled (376 radiofrequency and 311 cryoballoon ablation). Baseline characteristics and distribution of PV anatomical variants were generally similar in the groups. After a mean follow-up of 14 ± 8 months, there was no difference in the incidence of relapse (17.0% cryoballoon ablation vs. 14.1% radiofrequency, P = 0.25). We observed no interaction of PV anatomical variants on mid-term procedural success. CONCLUSION: Our findings suggest that mid-term outcomes of cryoballoon ablation for paroxysmal AF ablation are similar to those of radiofrequency, regardless of PV anatomy. The presence of anatomical variants of PVs should not discourage the referral of patients with paroxysmal AF for cryoballoon ablation.

[Dual antiplatelet therapy and haemoglobin level: An observational study]. / Antiagregación plaquetaria dual y nivel de hemoglobina: un estudio observacional.

INTRODUCTION: To determine the degree of association between dual antiplatelet therapy (DAPT) (clopidogrel plus acetylsalicylic acid) and haemoglobin (Hb) in clinical practice. MATERIAL AND METHODS: A retrospective longitudinal analysis was conducted on all patients on DAPT for at least 6 months. The required sample size was 63 patients. Hb value was determined before DAPT and at least 6 months after, as well as length of treatment, drugs, and diseases that might reduce the Hb. Changes in Hb after DAPT and the emergence or worsening of pre-existing anaemia was determined. Before and after Hb was compared using the t-test for paired samples. The occurrence of anaemia was considered dependent variable in a logistic regression analysis. RESULTS: A total of 122 cases were included. There were 92 (75.4%) males, and the mean age was 74.5 (SD 9.9) years. DAPT duration was 19.3 (11.8) months. The pre-treatment Hb was 14.3 (1.4) g/dl and 12.8 (1.9) g/dl post-treatment. The prevalence of pre-DAPT anaemia was 9.1% (11 cases), and 45.9% post-treatment (56 cases). Comparison of means showed a decrease of 1.5g/dl (1.6) (95% CI; 1.2-1.8, P<.001). Anaemia post-treatment was associated with concomitant causes of anaemia, bleeding in the follow-up, and inversely with pre-treatment Hb level. CONCLUSIONS: DAPT is associated with a decrease in Hb. Anaemia or worsening of previous anaemia appeared in about half of the subjects, and this effect was most likely in patients with bleeding in the follow-up and if other causes of anaemia were present.

Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome.

BACKGROUND: Despite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known. OBJECTIVE: To study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS. METHODS: ECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months. RESULTS: Thirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025). CONCLUSIONS: Type 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.

Subarachnoid haemorrhage associated with midventricular Tako-Tsubo syndrome.

BACKGROUND: A new form of Tako-Tsubo cardiomyopathy has recently been described as a midventricular localisation, opposite to the apical typical form. CASE REPORT: We report the case of a patient who presented with a sudden cardiac death and an acute coronary syndrome. However, coronary arteries were normal and the left ventriculography showed a midventricular ballooning Tako-Tsubo syndrome associated with a hawk's beak. A cerebral CT scan revealed a massive subarachnoid haemorrhage in relation with a left sylvian aneurysm rupture leading to the death of the patient. CONCLUSION: This case relates for the first time, the association of a subarachnoid haemorrhage and the recently described midventricular form of Tako-Tsubo syndrome with a hawk's beak. It is an illustration of the complexity of the relationships between brain and heart.

Primary electrical diseases diagnosis, genetic and management.

Primary electrical diseases or channelopathies are inherited genetic alterations of the cell ionic and electrical behavior leading to various cardiac arrhythmias carrying the risk of sudden death. A descriptive review of the successively described channelopathies is made in this article, with emphasis on the clinical manifestations, the genetic background and the currently accepted therapeutic options.

Cambio en la accesibilidad a la píldora poscoital y análisis de la influencia sobre la incidencia en las infecciones de transmisión sexual / Change in the accesibility of the emergency contraceptive pills and analysis concerning the influence on the incidence of sexually transmitted disease

Introducción: En España se ha puesto en marcha la dispensación gratuita de la píldora poscoital en los servicios de urgencias de atención primaria, lo que permite el acceso rápido y gratuito a las usuarias. Objetivos: Evaluar la influencia que ha tenido la administración gratuita de la píldora poscoital en atención primaria sobre su consumo, y comparar su evolución con las tendencias evolutivas de la incidencia de infecciones de transmisión sexual(ITS). Material y método: Estudio observacional y descriptivo. Se incluyeron datos de consumo de la píldora poscoital en farmacias y centros de salud e ITS de declaración obligatoria durante un periodo de 6 años (2002-2007). Variables de medida: tasa de consumo anual (consumo en número de envases de píldora poscoital por 1.000 habitantes y año), incidencia (número de nuevos casos acontecidos en un año) y tasa de incidencia (por 100.000 habitantes) para la sífilis e infecciones gonocócicas. Resultados: Tasa de consumo de la píldora poscoital al inicio del estudio (dispensación en oficinas de farmacia) de 3,02 frente a 12,44 en el año 2007. La tendencia al aumento de la tasa de consumo total de la píldora poscoital se relacionó de manera significativa (p= 0,024) y de tipo lineal con la tendencia al aumento de la incidencia de sífilis. Conclusiones: Se detecta un elevado incremento del consume de la píldora poscoital y una probable asociación con el aumento de la incidencia de sífilis (AU)

Introduction: In Spain they have implemented, the free dispensing of the emergency contraceptive pills in the primary care emergency departments, which allows the rapid and free access for the users. Objective: To evaluate the influence that free administration of emergency contraception in Primary Care has had on its consumption and compare the evolution of consumption of the above mentioned over time with incidence of sexually transmitted diseases (STDs). Materials and Method: Descriptive observational study Data on the consumption of the emergency contraceptive pill from drugstores and health centres of Obligatorily Declared sexually transmitted diseases were collected over 6 years (2002-2007). Main outcome measures: Annual level of consumption (consumption in number of emergency contraceptive pill boxes per 1,000 inhabitants per year, incidence (number of new cases detected in a year), and incidence rate (incidence per 100,000 inhabitants) for syphilis and gonococcal infections. Results: The consumption rate of the emergency contraceptive pill at the beginning of the study (distributed in drugstores) was3.02 versus to 12.44 in the year 2007. The tendency of the consumption rate of the emergency contraceptive pill to increase was found to be significant (p=0.024) and lineally related with the tendency of the syphilis rate to increase. Conclusions: An increased consumption of the emergency contraceptive pill and a probable association with the increase in the occurrence of syphilis was detected (AU)

A non-invasive tape absorption method for recovery of inflammatory mediators to differentiate normal from compromised scalp conditions.

BACKGROUND/AIMS: A simple non-invasive tape (Sebutape) adsorption method was used to recover inflammatory proteins from normal and compromised human scalp (i.e. dandruff and seborrheic dermatitis) in order to assess the inflammatory and immunologic changes relevant to these clinical conditions. METHODS: The scalps of subjects identified by a dermatologist as having either dandruff (n = 18), seborrheic dermatitis (n = 19) or normal scalp (n = 16) were visually graded to obtain total adherent scalp flaking scores (TASFS). Sebutape samples were then collected from both the high and low TASFS scalp sites using a one-minute tape application. To recover inflammatory molecules, tapes were extracted in buffered saline with sonication and the tape extracts analysed using commercial immunoassay methods for pro-inflammatory cytokines [i.e. interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-8 and tumor necrosis factor-alpha (TNF-alpha)] and the immunologic cytokines [i.e. IL-2, IL-4, IL-10, IL-12, IL-15 and interferon gamma (IFN-gamma)]. Nitric oxide (NO) was also assayed on tape extracts using the Greiss reaction. To account for differences in protein loading on the tapes all cytokine and NO results were normalized using the total protein (TP) amounts recovered in tape extracts. RESULTS: The IL-1alpha/TP levels recovered from dandruff and seborrheic scalps were significantly decreased (P = 0.03) compared to normal appearing scalp levels. The scalp levels of IL-1ra/TP and the ratio of IL-ra to IL-1alpha were significantly (P = 0.002) or directionally (P = 0.07) higher in seborrheic dermatitis scalps and dandruff scalps, respectively, compared to normal scalps. The IL-1ra and the IL-1ra/IL-1alpha ratio values correlated well with the TASFS. The TNF-alpha/TP levels recovered from dandruff scalps were significantly higher (P = 0.02) than levels recovered from seborrheic dermatitis and normal scalp subjects. IL-2/TP was significantly increased (P = 0.01) and IFN-gamma and NO significantly decreased (P = 0.05) in the seborrheic dermatitis scalp samples compared to normal controls. CONCLUSION: The Sebutape method has proven useful for distinguishing normal from diseased scalp conditions. The cytokines recovered from the scalp tape samples showed distinct patterns that differentiated dandruff, seborrheic dermatitis and normal scalp populations. These methods may also prove useful for monitoring the clinical efficacy of therapeutic actives for treating dandruff and seborrhea.

Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG](2) with a topoisomerase poison in the presence of Co(2+) ions.

The structure of the duplex d[CG(5-BrU)ACG](2) bound to 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0 A resolution. It shows an unexpected and previously unreported intercalation cavity stabilized by the drug and novel binding modes of Co(2+) ions at certain guanine N7 sites. For the intercalation cavity the terminal cytosine is rotated to pair with the guanine of a symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like structure. The mode of binding of the drug is shown to be disordered, with the major conformations showing the side chain bound to the N7 position of adjacent guanines. The other end of the duplex exhibits a terminal base fraying in the presence of Co(2+) ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The stabilization of the structure by the intercalating drug shows that this class of compound may bind to DNA junctions as well as duplex DNA or to strand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. This suggests a structural basis for the dual poisoning of topoisomerase I and II enzymes by this family of drugs.

Determination by MAD-DM of the structure of the DNA duplex d[ACGTACG(5-BrU)]2 at 1.46 A and 100 K.

A four-wavelength MAD experiment on a new brominated octanucleotide is reported here. d[ACGTACG(5-BrU)], C77H81BrN30O32P7, Mr (DNA) = 2235, tetragonal, P43212 (No. 96), a = 43.597, c = 26.268 A, V = 49927.5 A3, Z = 8, T = 100 K, R = 10.91% for 4312 reflections between 15.0 and 1.46 A resolution. The self-complementary brominated octanucleotide d[ACGTACG(5-BrU)]2 has been crystallized and data measured to 1.45 A at both 293 K and a second crystal flash frozen at 100 K. The latter data collection was carried out to the same resolution at the four wavelengths 0.9344, 0.9216, 0.9208 and 0.9003 A, around the Br K edge at 0.92 A and the structure determined from a map derived from a MAD data analysis using pseudo-MIR methodology, as implemented in the program MLPHARE. This is one of the first successful MAD phasing experiments carried out at Sincrotrone Elettra in Trieste, Italy. The structure was refined using the data measured at 0.9003 A, anisotropic temperature factors and the restrained least-squares refinement implemented in the program SHELX96, and the helical parameters are compared with those previously determined for the isomorphous d(ACGTACGT)2 analogue. The asymmetric unit consists of a single strand of octamer with 96 water molecules. No countercations were located. The A-DNA helix geometry obtained has been analysed using the CURVES program.

Structure of the DNA octanucleotide d(ACGTACGT)2.

d(ACGTACGT), C(78)H(84)N(30)O(32)P(7).20H(2)O, M(r) (DNA) = 2170, tetragonal, P4(3)2(1)2 (No 96), a = 42.845 (1), b = 42.845(1), c = 24.804 (1) A, V = 45532.5 (2) A(3), z = 8,lambda(MoKalpha) = 0.71069 A, micro (MoKalpha) = 0.10 mm(-1), T = 295 K, R = 0.18 for 1994 unique reflections between 5.0 and 1.9 A resolution. The self-complementary octanucleotide d(ACGTACGT)(2) has been crystallized and its structure determined to a resolution of 1.9 A. The asymmetric unit consists of a single strand of octamer with 20 water molecules. It is only the second example of an octanucleotide having terminal A.T base pairs whose structure has been determined by X-ray crystallography. The sequence adopts the modified A-type conformation found for all octanucleotide duplexes studied to date with the helix bent by approximately 15 degrees and an average tilt angle of 0 degrees. Unusually the data collection was carried out using a 3 kW molybdenum sealed-tube source. The conformational details are discussed in comparison with other closely related sequences.

Dose-response assessments of Kathon biocide. (II). Threshold prophetic patch testing.

Biocidal preservative agents are important in preventing the growth of pathogenic and nonpathogenic organisms in a variety of personal care, household and industrial products. Nearly all effective, commonly used preservative materials possess skin sensitization potential. In a series of 13 prophetic human repeat insult patch tests involving a total of 1450 subjects, no skin sensitization was induced at concentrations of 10 ppm, 6 ppm or 5 ppm (1121 subjects) or at 15 ppm (200 subjects) of a new isothiazolinone preservative mixture (Kathon CG). Delayed contact hypersensitivity was induced in 1 of 84 subjects at 12.5 ppm and in 2 of 45 subjects at 20 ppm. These results add further support to the previously reported conclusion that use of this new biocide at the very low concentrations required for effective preservation of rinse-off products involves an extremely low risk of clinical dermatoses.

Toxicological evaluation of commercial alkyldimethylamine oxides: two-year chronic feeding and dermal studies.

Chronic feeding and dermal studies were conducted with commercial alkyldimethylamine oxides (ADAO) in rats and mice. Rats were dosed with 0.01, 0.1, or 0.2% w/v ADAO (on a 100% active basis) in their diet for 104 weeks. Mice were exposed to ADAO via a dermal application of 0.1 ml of an aqueous solution of ADAO at concentrations of 0.05, 0.13, or 0.26% w/v ADAO (on a 100% active basis) once daily three times per week for 104 weeks. No compound-related carcinogenic effects were observed in either chronic test.

Dose-response assessments of Kathon biocide (I). Diagnostic use and diagnostic threshold patch testing with sensitized humans.

Nearly all effective, commercially available preservatives possess skin sensitization potential. This manuscript describes a program of diagnostic patch and practical use testing of consumer products that contained Kathon CG, a relatively new biocide. A series of threshold diagnostic patch tests demonstrated that the minimal elicitation concentration in occluded patch testing of allergic subjects considerably exceeded the concentrations of the biocide typically present in normal diluted use of the test products. Use testing further confirmed a threshold exposure for eliciting allergic reactions. It showed that even subjects who have delayed contact hypersensitivity to Kathon CG used rinse-off personal care products preserved with this agent without experiencing elicitation of these allergies.

Possible pre-dissociation of diorganotin dihalide complexes: relationship between antitumour activity and structure.

An examination of crystallographic data has indicated that the structure/activity relationship for diorganotin dihalide complexes is different from that of other metal dihalides, in that the Sn-N bond lengths appear to determine the antitumour activity.

The role of sulphide and sulphide oxidation in the copper molybdenum antagonism in rats and guinea pigs.

The sulphide metabolism of rats fed molybdate up to levels of 1000 ppm molybdenum was examined and large decreases in hepatic sulphite oxidase activity observed; overall sulphide oxidation capacity was also reduced. Molybdate but not tungstate caused increases in the total plasma copper of guinea pigs but in particular the appearance of a new TCA-insoluble fraction. The effect was increased by the addition of 500 ppm sulphur as sulphide, to the molybdate diet whereas the addition of 500 ppm S as sulphate was ineffective. 100 ppm Mo was less effective as thiomolybdate (MoS4=) than as molybdate. The significance of these results in relation to the role of sulphide in the Cu-Mo-S interaction is discussed.

Inhibition by gold of human lymphocyte stimulation. An in vitro study.

Transformation of lymphocytes stimulated by mitogen, purified protein derivative, and in the mixed lymphocyte culture was significantly inhibited by gold sodium thiomate and gold sodium thiosulphate at concentrations of 5 X 10(-4) to 5 X 10(-5) mol/1.

The competition of molybdate and sulphate ions for a transport system in the ovine small intestine.

The transport of molybdate and sulphate by segments of ovine small intestine in vitro was examined and kinetic constants derived for the late ileum where transport was highest. Sulphate inhibited the uptake of molybdate, probably by competition for sites on a common transport system. The significance of the results with respect to the problem of molybdate toxicity in animals is discussed, and related to the known protective effect of sulphate.