Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial.

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Autologous Stem Cell Transplantation in Patients With Primary Systemic Amyloidosis: Experience of a Tertiary Hospital.

BACKGROUND: Systemic immunoglobulin light-chain (AL) amyloidosis is a plasma cell dyscrasia that results from the deposition of insoluble fragments of immunoglobulin light or heavy chains. The subsequent disruption of organ function resulting from the extracellular deposition of these fragments ultimately leads to death. The median overall survival (OS) of patients ranges from 12 and 18 months down to 5 months in patients with cardiac involvement. Autologous hematopoietic stem cell transplantation (ASCT) is a treatment modality that achieves good response. The affected solid organ transplant (SOT) could improve performance status and have a favorable impact on survival. METHODS: Retrospective analysis of 11 AL amyloidosis patients who received ASCT from 2005 to 2013, 2 of them also underwent SOT. RESULTS: The 5-year OS depending on the number of organs involved (1 vs ≥2) was 100% versus 60% (P = .13). With a median follow-up of 4.8 years (range, 1.6-8), 81% of patients are alive maintaining complete hematologic response (n = 6) and very good partial response (n = 3). The 5-year progression-free survival was 80% (range, 42%-94%). Two patients underwent cardiac and renal transplantation as a bridge to ASTC. None of the double transplant patients has died. CONCLUSION: ASCT is an effective treatment option in patients with AL amyloidosis. In those with advanced single organ damage, SOT should be considered to improve the clinical outcome.

Sedation with sevoflurane in postoperative cardiac surgery: influence on troponin T and creatinine values.

INTRODUCTION: To compare the potential beneficial effects on markers of myocardial injury (troponin T) and renal function between sedation with sevoflurane vs propofol after cardiac surgery using extracorporeal cardiopulmonary bypass. METHODS: A prospective study with sequential selection of patients undergoing coronary or coronary and valve cardiac surgery. Intraoperative anesthesia consisted in sevoflurane and remifentanil, while in the postoperative period patients were divided in two groups to receive sedation with either sevoflurane through the AnaConDa© system or propofol. The patients were sedated during a minimum of 120minutes. Markers of myocardial injury and plasmatic creatinine were measured 4, 12, 24, and 48hours after surgery. RESULTS: Data from 129patients, 62sedated with propofol and 67with sevoflurane, were analyzed. The analysis of the troponin T levels showed differences 12 and 48 hours after admission. Mean values at 12hours were 0.89 (standard deviation 0.55) µg.L(-1) in the propofol group and 0.69 (standard deviation 0.40) µg. L(-1)in the sevoflurane group (p = 0.026). TnT levels at 48hours were 0.60 (standard deviation 0.46) µg.L-(1)in the propofol group and 0.37 (standard deviation 0.26) µg.L(-1)in the sevoflurane group (p = 0,007). No differences were found in the groups in the creatinine levels before discharge. CONCLUSIONS: The post-operative sedation with sevoflurane after cardiac surgery with cardiopulmonary bypass is a valid alternative to propofol. It does not increase the number of side effects related to kidney damage in patients with no prior renal disease, leading to reduced troponin T levels 12and 48hours after admission.

Influence of pharmacogenetic polymorphisms in routine immunosuppression therapy after renal transplantation.

Pharmacogenetics is the study of the cause of various individual responses to the same pharmacologic therapy. Genetic alterations in a single nucleotide in the genes responsible for transport and metabolism of an immunosuppression drug may modify patient response. Although pharmacogenetics is of interest, its clinical relevance remains to be demonstrated. The objective of the present study was to evaluate the effect of single-nucleotide polymorphisms (SNPs) in renal transplant recipients and their donors relative to blood concentrations of tacrolimus in the first 2 weeks posttransplantation. Seventy-one blood samples each from renal transplant recipients and their donors were analyzed using a genetic analysis system (MassARRAY; Sequenom, Inc, San Diego, California) in an attempt to characterize the more relevant SNPs of the ABCB1 and CYP3A5 genes for correlation with recipient trough concentrations of drug. Two-way analysis of variance and Bonferroni post hoc tests were used. In agreement with theoretical predictions, the wild-type genotype in ABCB1 SNPs (CC) tended to stabilize drug concentrations within the therapeutic range, whereas the T variant induced a mean increase in blood concentrations of more than 60%. These findings are in agreement with statistical tests that compared mean concentrations in various recipient-donor populations and found significant differences between them (P<.001) in CC vs TT, and P<.01 in CT vs TT). Donor genotype did not seem to be relevant. However, further studies are required to achieve more robust conclusions.

[Postoperative analgesia in knee arthroplasty using an anterior sciatic nerve block and a femoral nerve block]. / Analgesia postoperatoria en la artroplastia de rodilla mediante los bloqueos ciático por vía anterior y femoral.

OBJECTIVE: To evaluate the efficacy of a nerve block as an alternative technique for analgesia after knee arthroplasty and to indicate the usefulness and advantages of the anterior approach to the sciatic nerve block. MATERIAL AND METHODS: Between April 2004 and March 2006, we studied a series of consecutive patients undergoing knee arthroplasty in which a subarachnoid block was used as the anesthetic technique and postoperative analgesia was provided by means of a combined peripheral femoral nerve block and an anterior sciatic nerve block. We evaluated the mean length of time free from pain, quality of analgesia, and length of stay in hospital. RESULTS: Seventy-eight patients were included in the study. The mean (SD) length of time free from pain for the group was 42.1 (3.9) hours. Patients reported mild pain after 34.8 (4.1) hours and moderate to severe pain after 42.4 (3.5) hours. By the third day, 62.8% of patients were able to bend the knee to 90 degrees. There were no complications resulting from the technique and the level of patient satisfaction was high. CONCLUSIONS: A combined femoral-sciatic nerve block is effective in knee arthroplasty. It controls postoperative pain and allows for early rehabilitation. The anterior approach to the sciatic nerve is relatively simple to perform without removing the pressure bandaging from the thigh after surgery. This approach also makes it unnecessary to move the patient.

Analgesia postoperatoria en la artroplastia de rodilla mediante losbloqueos ciático por vía anterior y femoral / Postoperative analgesia in knee arthroplasty using an anterior sciatic nerve block and a femoral nerve block

OBJETIVO: Valorar la eficacia de los bloqueos nerviososcomo técnica alternativa de analgesia postoperatoriaen las prótesis de rodilla, señalando la validez y ventajasdel abordaje por vía anterior del bloqueo ciático.MATERIAL Y MÉTODO: Estudiamos un grupo de pacientesconsecutivos, desde abril de 2004 a marzo de 2006,intervenidos de artroplastia de rodilla, utilizando el bloqueosubaracnoideo como técnica anestésica y los bloqueosperiféricos combinados femoral y ciático mediantesu abordaje anterior como técnica analgésicapostoperatoria. Valoramos el tiempo medio libre dedolor, calidad de la analgesia y estancia hospitalaria.RESULTADOS: Incluimos 78 pacientes. El intervalolibre de dolor del conjunto de todos los pacientes fue de42,1±3,9 h. Los pacientes que refirieron dolor leve, fue alas 34,8±4,1 h y dolor moderado-intenso a las 42,4±3,5 h.Alcanzaron 90º de flexión de la rodilla, al tercer día, el62,8% de los pacientes. No hubo complicación derivadade la técnica y el grado satisfactorio de los pacientes fuealto.CONCLUSIONES: El bloqueo combinado femoral y ciáticoen cirugía protésica de la rodilla es eficaz, controlael dolor postoperatorio, permite una rehabilitación precoz.El abordaje anterior del ciático es relativamentesencillo de realizar sin retirar el vendaje compresivo delmuslo tras la cirugía y además evita movilizar al paciente (AU)

OBJECTIVE: To evaluate the efficacy of a nerve block asan alternative technique for analgesia after kneearthroplasty and to indicate the usefulness and advantagesof the anterior approach to the sciatic nerve block.MATERIALAND METHODS: Between April 2004 and March2006, we studied a series of consecutive patients undergoingknee arthroplasty in which a subarachnoid block was usedas the anesthetic technique and postoperative analgesia wasprovided by means of a combined peripheral femoral nerveblock and an anterior sciatic nerve block. We evaluated themean length of time free from pain, quality of analgesia,and length of stay in hospital.RESULTS: Seventy-eight patients were included in thestudy. The mean (SD) length of time free from pain forthe group was 42.1 (3.9) hours. Patients reported mildpain after 34.8 (4.1) hours and moderate to severe painafter 42.4 (3.5) hours. By the third day, 62.8% ofpatients were able to bend the knee to 90°. There wereno complications resulting from the technique and thelevel of patient satisfaction was high.CONCLUSIONS: A combined femoral-sciatic nerve blockis effective in knee arthroplasty. It controls postoperativepain and allows for early rehabilitation. The anteriorapproach to the sciatic nerve is relatively simple toperform without removing the pressure bandaging fromthe thigh after surgery. This approach also makes itunnecessary to move the patient (AU)

Trastorno del sueño asociado al tratamiento con rimonabant / Sleep disorders associated with treatment with rimonabant

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Trastorno de conducta durante el sueño REM / Behavior disorders during REM sleep

El trastorno de conducta durante la fase REM es una parasomnia caracterizada por la ausencia de atonía muscular en esta fase de sueño. Clínicamente se acompaña de movimientos bruscos y violentos de las extremidades y el tronco en relación con sueños agresivos. Se describe el caso de una paciente de 80 años de edad que presentaba conductas violentas y ensoñaciones agresivas. La clínica de la paciente y el estudio polisomnográfico efectuado con monitorización de varios músculos y videograbación confirmaron el diagnóstico. El tratamiento con clonacepam fue eficaz en la paciente, con resolución de su clínica. Dada la escasa frecuencia de este trastorno en mujeres, consideramos relevante la exposición de este caso (AU)

Behavior disorder during the REM phase of sleep is a parasomnia characterized by the lack of the atonia or muscular paralysis. Clinically, said disorder occurs with sudden and violent movements in extremities and trunk related to aggressive dreams. The case of a patient, 80, with violent behaviour and dreams is reported. Her medical profile and the polysomnographic study carried out with monitoring of some muscles and video recording confirmed the diagnosis. The treatment with clonacepam was effective, with resolution of the disorder (AU)

El problema sanitario de España: saneamiento y medio rural en los primeros decenios del siglo XX / No disponible

En los primeros decenios del siglo XX, la situación socio-sanitaria de la sociedad española fue descrita como catastrófica, tanto en el ámbito urbano como en el rural. En aquel contexto, el saneamiento del medio aparece como una de las claves del proceso de regeneración que asumió la higiene en su papel de mediadora. A través de las obras los higienistas G. De Membrillera y Luis Muñoz Antuñano, publicadas en 1921, nos hemos acercado al ánálisis de la situación sanitaria de la España rural durante este periodo

During the early of the 20th century, the Spanish socio-sanitary situation was described as catastrophic, both in the urban as well as in the rural setting. In that context, sanitation emerged as one of the key elements of the regeneration process taken on by hygiene, in its role as mediator. Through the works of hygienists G. de Membrillera and Luis Muñoz Antuñano, published in 1921, we have approached the analysis of the sanitary situation of rural Spain during this period

Púrpura trombocitopénica trombótica, lupus eritematoso sistémico y tratamiento de rescate con ciclofosfamida / Thrombotic thrombocytopenic purpura, systemic lupus erythematosus and rescue treatment with cyclophosphamide

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Binding properties and immunolocalization of a fatty acid-binding protein in Giardia lamblia.

We describe here a fatty acid-binding protein (FABP) isolated and purified from the parasitic protozoon Giardia lamblia. The protein has a molecular mass of 8 kDa and an isoelectric point of 4.96. A Scatchard analysis of the data at equilibrium revealed a dissociation constant of 3.12 x 10(-8) M when the labeled oleic acid was displaced by a 10-fold greater concentration of unlabeled oleic acid. Testosterone, sodium desoxycholate, taurocholate, metronidazol, and alpha-tocopherol, together with butyric, arachidonic, palmitic, retinoic, and glycocholic acids, were also bound to the protein. Assays with polyclonal antibodies revealed that the protein is located in the ventral disk and also appears in the dorsal membrane, the cytoplasm, and in the vicinity of the lipid vacuoles.

Narcolepsia en niños / Narcolepsy in children

Introducción. La narcolepsia es un trastorno neurológico caracterizado por somnolencia excesiva durante el día, con episodios recurrentes e irresistibles de sueño, que asocia en las formas completas cataplejía, alucinaciones hipnagógicas y parálisis del sueño. La incidencia comunicada en el adulto es 4-10/ 10.000. Un porcentaje considerable de adultos reconoce su inicio antes de los 15 años de edad. Es imprescindible la confirmación neurofisiológica de los períodos cortos de inicio de sueño REM. Caso clínico. Varón de 11 años, con hipersomnolencia diurna, trastorno de conducta y aumento de peso, que se evaluó en Unidad de Trastornos del Sueño mediante polisomnografía y test de latencias múltiples, confirmándose la sospecha de narcolepsia. Conclusiones. La narcolepsia es una enfermedad de inicio en la infancia y que habitualmente pasa desapercibida o erróneamente diagnosticada y tratada. Existen actualmente criterios válidos para identificar y diagnosticar a los niños con el trastorno. El tratamiento de estos pacientes debe orientarse a la adaptación del entorno al niño y la prevención de problemas psicosociales que origina, dada la pobre respuesta a los fármacos empleados (AU)

Polyphasic taxonomy of a novel yeast isolated from antarctic environment; description of Cryptococcus victoriae sp. nov.

In 1992 some samples of mosses, lichens and soils were collected from Botany Bay, Southern Victoria Land (77 degrees 01' S 162 degrees 32' E) and, as a result of a routine screening programme some yeasts were isolated. One of them, designated as strain G5, showed marked differences when compared to other antarctic yeasts. According to morphological and physiological characteristics, we were able to identify the strain G5 as a yeast belonging to the genus Cryptococcus. Some characteristics of this genus are the growth response to myo-inositol, celobiose, raffinose and D-glucuronate, no-fermentation, the absence of mycelium and pseudomycelium, asexual reproduction, Diazolium blue B test (DBB) and urea hydrolisis positive and the growth without vitamines. This strain (G5) formed cream colonies of slimy appearance with cells of 3 x 2 microns in size, that grew between 4 degrees C and 20 degrees C. The G + C content of strain G5 was 50.3 mol%. The molecular characterization by whole-cell proteins and RFLP analysis of the 5.8S rRNA gene and the two ribosomal internal transcribed spacers (5.85-ITS region), revealed that this strain was different from other antarctic species of this genus. The phylogenetic tree deduced from the 5.8S rRNA gene sequence showed the strain G5 as a member of the genus Cryptococcus, clearly separated from other basidiomycetous yeasts. On the basis of the physiological, genotypical and phylogenetical data, the new isolate G5 was described as Cryptococcus victoriae, sp. nov., with the type strain G5 (= CECT 11114).

HAT1 and HAT2 proteins are components of a yeast nuclear histone acetyltransferase enzyme specific for free histone H4.

We have analyzed the histone acetyltransferase enzymes obtained from a series of yeast hat1, hat2, and gcn5 single mutants and hat1,hat2 and hat1,gcn5 double mutants. Extracts prepared from both hat1 and hat2 mutant strains specifically lack the following two histone acetyltransferase activities: the well known cytoplasmic type B enzyme and a free histone H4-specific histone acetyltransferase located in the nucleus. The catalytic subunits of both cytoplasmic and nuclear enzymes have identical molecular masses (42 kDa), the same as that of HAT1. However, the cytoplasmic complex has a molecular mass (150 kDa) greater than that of the nuclear complex (110 kDa). The possible functions of HAT1 and HAT2 in the yeast nucleus are discussed. In addition, we have detected a yeast histone acetyltransferase not previously described, designated HAT-A4. This enzyme is located in the nucleus and is able to acetylate free and nucleosome-bound histones H3 and H4. Finally, we show that the hat1, gcn5 double mutant is viable and does not exhibit a new phenotype, thus suggesting the existence of several histone acetyltransferases with overlapping functions.

[The effect of changes in nutritional status induced by age on oxidative liver metabolism]. / Influencia de los cambios en el estado nutritivo inducidos por la edad sobre el metabolismo oxidativo hepático.

INTRODUCTION: The hepatic oxidative metabolism is essential for the biotransformation of a large number substances, among which are found many drugs which are commonly used in clinical practice. The nutritional status of individuals has been shown to be of influence on this function. Aging produces a deterioration of the hepatic oxidative metabolism, without the cause for this situation having been clarified. Also, aging modifies the body composition of the individuals. The objective of this study is to evaluate whether the modifications which arise in the nutritive status due to age, can alter the hepatic oxidative capacity. MATERIAL AND METHODS: 165 elderly people of both sexes were studied, with an average age of 82 years, and 24 young people, with an average age of 29 years. All participants were subjected to a clinical questionnaire, along with an evaluation of anthropometric, biochemical, and immunological nutritive parameters. The study of the oxidative metabolism was conducted by evaluating the kinetics of antipyrine. RESULTS: The elderly people showed a decrease in the antipyrine clearance rate (Ap Cl) (P < 0.001), and a lengthening of their life-span (P < 0.05) with respect to the younger people. There was a significant correlation in the elderly people, between the Ap Cl and age, weight, size, the distribution volume, and the muscular area of the arm. A multiple regression analysis showed a predictive value which was independent for age, the AST, the lymphocytes, and size. CONCLUSION: Elderly people have a marked depression of the hepatic oxidative metabolism. The factors which participate in their nutritional situation, are of influence on this function. It is necessary to keep all the above in mind when it comes to prescribing drugs which require this type of biotransformation, in order to avoid adverse effects or drug interactions.