Apolipoprotein E and Recovery from Traumatic Brain Injury

The outcome from traumatic brain injury (TBI) is variable and only partly explained by known prognostic factors. This is especially true for predicting long-term outcome. Genetic factors may influence the brain`s susceptibility to injury or capacity for repair and regeneration. To examine the association of apolipoproteinE (apoE) genotype with long-term outcome, hippocampal volumes and general brain atrophy, we determined the apoE genotype from 61 TBI patients who had been injured over on average 31 years earlier. The long-term outcome was evaluated with repeated neuropsychological testing and by applying various measures of everyday functioning and quality of life. Magnetic resonance imaging (MRI) based volumetric analyses of the hippocampus and lateral ventricles were performed. In the prospective study, the purpose was to examine the association between apoE genotype and visibility of traumatic brain lesions during the first year after TBI and the ability of apoE genotype, the Glasgow Coma Score (GCS), MRI findings and duration of posttraumatic amnesia (PTA) to predict the one-year outcome. Thirty-three patients with TBI were studied and the outcome was evaluated with the Head Injury Symptom Checklist (HISC) and the Glasgow Outcome Scale extended version (GOS-E) scores one year after the injury. MRI and apoE genotyping were carried out. After three decades, neither hippocampal nor lateral ventricle volumes differed significantly in those patients with the apoE ε4 allele vs those without this allele, but the TBI patients with the apoE ε4 allele showed significantly poorer general cognitive level than those without this allele. This decline was wholly accounted for by a subgroup of patients who had developed incident or clinical dementia. In the prospective study the apoE genotype was not associated with visible MRI changes or outcome. The duration of PTA and acute MRI were the best predictors of one-year outcome in TBI. A portion of the TBI patients with the apoE ε4 allele seem to be at risk of long-term cognitive decline. This association may involve mechanisms other than those responsible for the development of brain atrophy. The early MRI and PTA have an important role in assessing the injury severity and prognosis.

Bile duct stones, strictures and iatrogenic lesions: studies on early diagnosis and treatment.

Aims: This study was carried out to investigate the role of common liver function tests, and the degree of common bile duct dilatation in the differential diagnosis of extrahepatic cholestasis, as well as the occurrence, diagnosis and treatment of iatrogenic bile duct injuries. In bile duct injuries, special attention was paid to gender and severity distribution and long-term results. Patients and methods: All consecutive patients with diagnosed common bile duct stones or malignant strictures in ERCP between August 2000 and November 2003. Common liver function tests were measured in the morning before ERCP on all of these 212 patients, and their common bile duct diameter was measured from ERCP films. Between January 1995 and April 2002, 3736 laparoscopic cholecystectomies were performed and a total of 32 bile duct injuries were diagnosed. All pre-, per-, and postoperative data were collected retrospectively; and the patients were also interviewed by phone. Results: Plasma bilirubin proved to be the best discriminator between CBD stones and malignant strictures (p≤0.001 compared to other liver function tests and degree of common bile duct dilatation). The same effect was seen in Receiver Operating Characteristics curves (AUC 0.867). With a plasma bilirubin cut-off value of 145 μmol/l, four out of five patients could be classified correctly. The degree of common bile duct dilatation proved to be worthless in differential diagnostics. After laparoscopic cholecystectomy the total risk for bile duct injury was 0.86%, including cystic duct leaks. 86% of severe injuries and 88% of injuries requiring operative treatment were diagnosed in females. All the cystic duct leakages and 87% of the strictures were treated endoscopically. Good long-term results were seen in 84% of the whole study population. Conclusions: Plasma bilirubin is the most effective liver function test in differential diagnosis between CBD stones and malignant strictures. The only value of common bile duct dilatation is its ability to verify the presence of extrahepatic cholestasis. Female gender was associated with higher number of iatrogenic bile duct injuries, and in particular, most of the major complications occur in females. Most of the cystic duct leaks and common bile duct strictures can be treated endoscopically. The long-term results in our institution are at an internationally acceptable level.

Diazepam e nordiazepam em plasma: métodos de extração líquido-líquido e em fase sólida no pré-tratamento de amostras para análise cromatográfica em fase líquida

Analysis of diazepam (DZP) and its active metabolite nordiazepam (NDZP) in plasma is commonly performed in clinical medicine to ensure proper therapeutic effects while minimizing the incidence of toxicity. This study aimed to optimize analytical parameters and compare two pre-treatment techniques, liquid-liquid (LLE) and solid phase extraction (SPE), as well as liquid chromatographic conditions to analyze simultaneously DZP and NDZP in plasma from 20 patients treated with a daily dose of 10 mg. Both techniques showed to be well in line with the international criteria for analytical validation, which permitted to quantify DZP (66.2 - 1148.6 ng mL-1) and NDZP (138.5 - 808.6 ng mL -1) in all samples. The correlation coefficients between SPE and LLE were respectively 0.9729 for DZP and 0.9643 for NDZP.

Hospital doctors' views and concerns about pharmacovigilance

Purpose: The aim of the study was to evaluate the opinions and concerns of hospital doctors about adverse drug reactions (ADRs) and pharmacovigilance. Methods: A qualitative study was undertaken using focus groups in sessions on pharmacovigilance activities conducted in thirteen clinical services of a tertiary university hospital. A total of 296 physicians participated in these sessions by giving their opinions or expressing their doubts about ADR and pharmacovigilance activities which were recorded by different observers and subsequently analysed. Results: Doctors remarked on: a) the importance, concern, frequency and specific types of ADRs that were observed in clinical practice; b) problems of clinical decision making related to the suspected ADRs; c) methods for improving detection and reporting ADRs; d) monitoring of specific ADRs or ADRs caused by specific drugs; e) and measures to prevent and minimize the risk of ADRs. Physicians expressed doubts related to: a) the basic concepts of ADRs; b) the methods of ADR identification and evaluation; c) the objectives and procedures of pharmacovigilance programmes; d) and the impact of pharmacovigilance activities. Conclusions: Hospital doctors believe that ADRs are a matter for concern in their daily clinical practice, and monitoring ADRs as well as measures for preventing the risk of ADRs are needed. Nevertheless, doctors have doubts about what an ADR is, the accuracy of diagnostic methods, the development of pharmacovigilance activities and their impact on clinical practice. Pharmacovigilance should be better explained through a continuous feedback and close relationship with hospital doctors.

Síntese e controle de qualidade da ureia enriquecida em 13C para diagnóstico da Helicobacterpylori (HP)

The aim of the study was to synthesize the urea (13CO(NH2)2), with 99% 13C atoms, and to perform a quality analysis for the diagnosis (breath test) of Helicobacter pylori. Furthermore, the process was submitted to economic analysis. The reaction was performed in a stainless steel reactor, lined with polytetrafluoroethylene, under low pressure and temperature. The synthesis method was shown to be appropriate (2.35 g; 81.9% yield), evidenced by physico-chemical and microbiological results, according to Brazilian legislation. The production and diagnosis costs were competitive compared with national and international market values, rendering this a valuable tool in clinical medicine.

Effects of cytochrome P450 enzyme inhibitors and inducers on the metabolism of S-ketamine

The human body eliminates foreign compounds primarily by metabolizing them to hydrophilic forms to facilitate effective excretion through the kidneys. Cytochrome P450 (CYP) enzymes in the liver and intestine contribute to the metabolism of many drugs. Pharmacokinetic drugdrug interactions occur if the activity of CYPs are inhibited or induced by another drug. Prescribing multiple drugs to the improve effectiveness of therapy or to treat coexisting diseases is a common practice in clinical medicine. Polypharmacy predisposes patients to adverse effects because of the profound unpredictability in CYP enzymatic-mediated drug metabolism. S-ketamine is a phencyclidine derivative which functions as an antagonist of the N-methyl-Daspartate (NMDA) receptor in the central nervous system. It is a unique anaesthetic producing “dissociative anaesthesia” in high doses and analgesia in low doses. Studies with human liver microsomes suggest that ketamine is metabolized primarily via CYP3A4 and CYP2B6 enzymes. In this thesis, in healthy volunteers, randomized and controlled cross-over studies were conducted to investigate the effects of different CYP inducers and inhibitors on the pharmacokinetics and pharmacodynamics of oral and intravenous S-ketamine. The plasma concentrations of ketamine and its metabolite, norketamine, were determined at different timepoints over a 24 hour period. Other pharmacodynamic variables were examined for 12 hours. Results of these studies showed that the inhibition of the CYP3A4 pathway by clarithromycin or grapefruit juice increased the exposure to oral S-ketamine by 2.6- and 3.0-fold. Unexpectedly, CYP3A4 inhibition by itraconazole caused no significant alterations in the plasma concentrations of oral S-ketamine. CYP3A4 induction by St. John´s wort or rifampicin decreased profoundly the concentrations of oral S-ketamine. However, after rifampicin, there were no significant differences in the plasma concentrations of S-ketamine when it was administered intravenously. This demonstrated that rifampicin inhibited the metabolism of Sketamine at the intestinal level. When CYP2B6 was inhibited by ticlopidine, there was a 2.4- fold increase in the exposure of S-ketamine. These studies demonstrated that low dose oral Sketamine is metabolized both via CYP3A4 and CYP2B6 pathways. The concomitant use of drugs that affect CYP3A4 or CYP2B6, during oral S-ketamine treatment, may cause clinically significant drug-drug interactions.

Galectin-1, an alternative signal for T cell death, is increased in activated macrophages

Galectin-1 belongs to an evolutionarily conserved family of animal ß-galactoside-binding proteins, which exert their functions by crosslinking the oligosaccharides of specific glycoconjugate ligands. During the past decade, attempts to identify the functional role of galectin-1 suggested participation in the regulation of the immune response. Only in the last few years has the molecular mechanism involved in these properties been clearly elucidated, revealing a critical role for galectin-1 as an alternative signal in the generation of T cell death. In the present study we will discuss the latest advances in galectin research in the context of the regulation of the immune response, not only at the central level but also at the periphery. Moreover, we will review the purification, biochemical properties and functional significance of a novel galectin-1-like protein from activated rat macrophages, whose expression is differentially regulated according to the activation state of the cells. The novel role of a carbohydrate-binding protein in the regulation of apoptosis is providing a breakthrough in galectin research and extending the interface between immunology, glycobiology and clinical medicine.

Oxidized LDL lipids as a risk factor for atherosclerosis

University of Turku, Faculty of Medicine, Department of Clinical Medicine, Department of Physical Activity and Health, Paavo Nurmi Centre, Doctoral Programme of Clinical Investigation, University of Turku, Turku, Finland. Annales Universitatis Turkuensis. Medica – Odontologica, Turku, Finland, 2014. Background: Atherosclerosis progression spans an entire lifetime and has a wide pool of risk factors. Oxidized LDL (oxLDL) is a crucial element in the progression of atherosclerosis. As a rather new member in the atherosclerosis risk factor family, its interaction with the traditional pro-atherogenic contributors that occur at different ages is poorly known. Aims: The aim of this study was to investigate oxLDL and its relation to major contributing risk factors in estimating atherosclerosis risk in data consisting mostly of adult men. The study subjects of this study consisted of four different sets of data, one of which contained also women. The age range of participants was 18-100 years and totaled 2337 participants (of whom 69% were men). Data on anthropometric and hormonal parameters, laboratory measures and medical records were assessed during 1998-2009. Results: Obesity was paralleled with high concentrations of oxLDL, which consequentially was reduced by weight reduction. Importantly, successful weight maintenance preserveed this benefit. A shift from insulin sensitivity to insulin resistance increased oxLDL. Smokers had more oxLDL than non-smokers. A combination of obesity and smoking, or smoking and low serum total testosterone,resulted in even higher levels of oxLDL than any of the three conditions alone. Proportioning oxLDL to HDL-c or apoA1 stood out as a risk factor of all-cause mortality in the elderly. Conclusions: OxLDL was associated with aging, androgens, smoking, obesity, insulin metabolism, weight balance and other circulating lipid classes. Through this variety of metabolic environments containing both constant conditions (aging and gender) as well as lifestyle issues, these findings supported an essential and multidimensional role that oxLDL plays in atherosclerosis pathogenesis.

Biochemical Studies on the Protective Effect of Taurine on Experimentally Induced Fulminat Hepatic Failure in Rats

Fulminant hepatic failure (FHF) is a dramatic and challenging syndrome in clinical medicine. Although an uncommon disorder, it is usually fatal and occurs in previously healthy person. While the causes of FHF remain unclear, viral hepatitis and drug-induced liver injury account for the majority of cases. Hepatitis E causes large-scale epidemics of hepatitis in the Indian subcontinent, involving hundreds of thousands of cases with high mortality. FHF is associated with several clinical features like jaundice, shrunken liver, easy bruising, low levels of serum proteins, fatigue, multi-organ failure etc and metabolic derangements like hypoglycemia, hyperlipidemia, hyponatremia, defective protein synthesis, reduced energy production, decreased rate of urea production etc. These disturbances are predominantly attributed to oxidative stress, membrane destabilization and osmolytic imbalances. The options available for these patients are quite minimal with liver transplantation being one of them. But the procedure is ridden with issues causing it to find less favor among the patients and the caregivers. Use of hepatoprotective and cytoprotective drugs, is being considered to be a more acceptable alternative as a strategy to enhance liver regeneration. In this regard use of taurine a naturally occurring amino acid that plays a crucial role in many physiological processes would prove to be effective. In the present study, hepatoprotective effect of taurine on a rat model of induced FHF was studied. Taurine supplementation has effectively counteracted the metabolic and structural aberrations in the liver caused by D-galactosamine intoxication.

Inauguració dels estudis de Medicina

El passat dia 9 de gener la Universitat de Girona va presentar els estudis de Medicina. A l’acte, que va tenir lloc a l’Escola Politècnica Superior, hi va assistir un públic nombrós en el qual hi havia representada des de la classe política fins als estudiants matriculats en el primer curs de la nova Facultat. La Sala de Graus era plena a vessar, la qual cosa va demostrar l’interès que aquests estudis han despertat, perquè, com va dir la consellera Marina Geli, són una aposta per reforçar els serveis de salut dels vuit-cents mil habitants de la demarcació de Girona

How to improve the formal analytic reasoning and scientific motivation in the intellectual training of medical students

A review article of the The New England Journal of Medicine refers that almost a century ago, Abraham Flexner, a research scholar at the Carnegie Foundation for the Advancement of Teaching, undertook an assessment of medical education in 155 medical schools in operation in the United States and Canada. Flexner’s report emphasized the nonscientific approach of American medical schools to preparation for the profession, which contrasted with the university-based system of medical education in Germany. At the core of Flexner’s view was the notion that formal analytic reasoning, the kind of thinking integral to the natural sciences, should hold pride of place in the intellectual training of physicians. This idea was pioneered at Harvard University, the University of Michigan, and the University of Pennsylvania in the 1880s, but was most fully expressed in the educational program at Johns Hopkins University, which Flexner regarded as the ideal for medical education. (...)

Los conceptos de salud financiera, riesgo y epidemiología en los estados financieros de las compañías del sector de extracción de petróleo crudo y gas natural en Colombia

El presente proyecto tiene como objeto identificar cuáles son los conceptos de salud, enfermedad, epidemiología y riesgo aplicables a las empresas del sector de extracción de petróleo y gas natural en Colombia. Dado, el bajo nivel de predicción de los análisis financieros tradicionales y su insuficiencia, en términos de inversión y toma de decisiones a largo plazo, además de no considerar variables como el riesgo y las expectativas de futuro, surge la necesidad de abordar diferentes perspectivas y modelos integradores. Esta apreciación es pertinente dentro del sector de extracción de petróleo y gas natural, debido a la creciente inversión extranjera que ha reportado, US$2.862 millones en el 2010, cifra mayor a diez veces su valor en el año 2003. Así pues, se podrían desarrollar modelos multi-dimensional, con base en los conceptos de salud financiera, epidemiológicos y estadísticos. El termino de salud y su adopción en el sector empresarial, resulta útil y mantiene una coherencia conceptual, evidenciando una presencia de diferentes subsistemas o factores interactuantes e interconectados. Es necesario mencionar también, que un modelo multidimensional (multi-stage) debe tener en cuenta el riesgo y el análisis epidemiológico ha demostrado ser útil al momento de determinarlo e integrarlo en el sistema junto a otros conceptos, como la razón de riesgo y riesgo relativo. Esto se analizará mediante un estudio teórico-conceptual, que complementa un estudio previo, para contribuir al proyecto de finanzas corporativas de la línea de investigación en Gerencia.

Enfoque del paciente con sospecha de neuroinfección en urgencias

Las infecciones del sistema nervioso son importantes fuentes de morbilidad y mortalidad en el mundo, debido a diferentes factores como son el amplio uso de antibióticos que aunque contribuyen con éxito al manejo de infecciones, pero el mal uso por automedicación o tratamientos incompletos favorecen la emergencia de organismos resistentes y la existencia de “mimos infecciosos” que incluyen el síndrome de reconstitución inflamatoria (IRIS). Adicionalmente el crecimiento de las poblaciones inmunocomprometidas por el síndrome de inmunodeficiencia adquirida (SIDA) y por tratamientos agresivos para trasplante sólido o hematopoyético han mejorado la sobrevida de diferentes tipos de malignidades y alteraciones reumatológicas pero son poblaciones que tienen más susceptibilidad a contraer infecciones y encefalitis mediadas inmunológicamente, como son la encefalomielitis diseminada aguda (ADEM) o la encefalitis contra el receptor de N-metil-D aspartato (NMDA).

Factores de riesgo para morbilidad materna extrema en gestantes

Introducción: La morbilidad materna extrema es un término usado para definir cualquier condición obstétrica severa que amenaza la vida y requiere una intervención médica urgente con el fin de prevenir la probable muerte materna. Con el presente estudio se pretendió evaluar los factores de riesgo para morbilidad materna extrema en las gestantes del Hospital Universitario Mayor. Metodología Se realizó un estudio de casos y controles, comparando pacientes con MME y sin MME en una relación de 1:1. Se realizó un muestreo aleatorio simple teniendo en cuenta 95% de la población apareadas por diagnóstico de ingreso. Resultados Se incluyeron un total de 110 pacientes (55 en cada grupo). Ambas poblaciones fueron comprables. Ser de estrato socioeconómico bajo (p 0,000), haber tenido 2 o menos partos (p 0,000), ser tipo de sangre negativo (p0.000) realizar entre 0-3 controles prenatales (p 0,000), tener antecedente de preeclampsia (p 0,000), hipotiroidismo (p 0,000), o trastorno bipolar (p 0,000), son factores de riesgo significativos para presentar MME. Entre los factores protectores están tener más de tres partos OR 0,60 (IC95%: 0,17-0,82, p=0,00) y 7 o más controles prenatales OR 0,23 (IC95%: 0,09-0,55, p=0,000). Resultados concordantes con la literatura Discusión: Es importante dar a conocer los resultados del presente estudio para promover las campañas de prevención primaria, secundaria y terciaria con el fin de evitar las altas complicaciones que se pueden presentar en las mujeres en edad fértil de nuestra población.

Factores asociados con la duración del circuito extracorpóreo en terapias continúas de reemplazo renal en la Fundación Cardioinfantil

Introducción: las terapias continuas de reemplazo renal son una importante medida a utilizar en los pacientes con lesión renal aguda que ingresan a la unidad de cuidado intensivo, la pérdida temprana del circuito por coagulación del mismo es una situación que afecta a este grupo de pacientes. Materiales y métodos: se realizo un estudio de casos y controles de una duración de tres meses tomando los pacientes que eran sometidos a terapia continua de reemplazo renal en la fundación Cardioinfantil, se eligieron como casos aquellos pacientes que no lograban completar 72 horas de terapia por perdida del circuito relacionada con coagulación, y aquellos que si se tomaron como controles, se analizaron ambos grupos en función de diferentes variables demográficas, clínicas y del circuito, tomando como análisis primario el primer filtro utilizado y haciendo un análisis secundario incluyendo todos los filtros. Resultados: se recolectaron 24 pacientes para el análisis primario y 101 filtros para el análisis secundario, el 37,5% de los filtros duró > 72 horas y 62,5%, menos de este tiempo. El puntaje APACHE II (OR: 0,76, p 0.003) y sitio de inserción femoral derecho (OR: 0.14, p 0.007) se encontraron protectoras para la disfunción temprana. Discusión: aunque no se alcanzó la muestra total, se encontró asociación protectora del acceso femoral derecho, que fue novedosa, pero requiere confirmación. El APACHE II, también protector, puede corresponder a un sesgo, se necesitan más estudios para aclarar estos hallazgos y determinar la presencia de otras variables que intervengan.