Epigenetics in hepatoblastoma

Hepatoblastoma (HB) is the most frequent pediatric primary liver tumor. When the tumoral lesions can be resected, prognosis is generally favorable. However, the...     

Expression of concentrative nucleoside transporters SLC28 (CNT1, CNT2, and CNT3) along the rat nephron: effect of diabetes

BACKGROUND: The renal reabsorption of natural nucleosides and a variety of nucleoside-derived drugs relies on the function of the apically located, Na(+)-dependent, concentrative nucleoside transporters CNT1, CNT2, and CNT3 (SLC28A1, SLC28A2, and SLC28A3). The aims of this study were to determine the segmental localization of the three SLC28 family members and to establish whether streptozotocin-induced diabetes alters their expression. METHODS: SLC28 expression was measured by real-time polymerase chain reaction (PCR) on microdissected sections of rat nephrons. Diabetes was induced by streptozotocin treatment and the biochemical profiles of control, diabetic, and insulin-treated rats were established. The effect of diabetes on SLC28 expression was assessed in those segments that significantly express SLC28 genes. RESULTS: CNT1-3 mRNAs were expressed in the proximal tubule and glomerulus. In addition, CNT2 and CNT3 mRNAs were expressed in the outer medullary and cortical collecting duct, respectively. Diabetes reduced expression of the three CNTs in almost all nephron segments, and this effect was not prevented by an insulin treatment that normalized all blood and urine parameters. Diabetes increased CNT1 and CNT3 expression in the glomerulus and insulin treatment decreased it. CONCLUSION: The relative distribution of SLC28 gene expression suggests a role for the proximal tubule in renal nucleoside clearance and an accessory role for CNT2 and CNT3, in adenosine-mediated regulation of collecting duct functions. Diabetes probably may impair nucleoside clearance independently of insulin.     

Análisis y minimización del riesgo de rotura de stock aplicado a la gestión en farmacia hospitalaria

ObjectiveTo determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout.MethodsWe statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments.ResultsIn the period being studied, the daily order was 11.4 ± 14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units.ConclusionsThe method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.     

Prevalence of drug interactions in hospital healthcare

Aim of the review To study the prevalence of drug interactions in hospital healthcare by reviewing literature. Method A review was carried out of studies written in Spanish and English on the prevalence of drug interactions in hospital care published in Pubmed between January 1990 and September 2008. The search strategy combined free text and MeSH terms, using the following keywords: ??Drug interaction??, ??prevalence?? and ??hospital??. For each article, we classified independent variables (pathology, age of population, whether patients were hospitalized or not, geographical location, etc.) and dependent variables (number of interactions per 100 patients studied, prevalence of patients with interactions, most common drug interactions, and others). Results The search generated 436 articles. Finally, 47 articles were selected for the study, 3 provided results about drug interactions with real clinical consequences, 42 about potential interactions, and 2 described both. The prevalence of patients with interactions was between 15 and 45?% and the number of interactions per 100 patients was between 37 and 106, depending on the group of studies analyzed. There was a considerable increase in these rates in patients with heart diseases and elderly persons. Conclusion There is a large number of studies on the prevalence of drug interactions in hospitals but they report widely varying results. The prevalence is higher in patients with heart diseases and elderly people.     

Practical guidelines for dose individualization of anticancer targeted drugs

For drugs such as anticancer agents every effort should be made to minimize inter-patient variability in drug exposure in order to maximize the benefit while maintaining an acceptable risk level of serious adverse effects. Anticancer drugs generally have a preferential route of elimination, either in urine or in bile and feces. In consequence, dose individualization to renal and liver function permits excessive toxicity to be avoided and expected therapeutic benefit to be achieved. However, less is known about the most appropriate starting doses of antineoplastic agents in these individuals. In this review, we discuss trials that have specifically assessed new targeted agents dosing strategies (mainly monoclonal antibodies and tyrosine kinase inhibitors) in the setting of overt biochemical renal and liver dysfunction and we proportionate recommendations and practical guidelines for dose individualization.     

HCV seroconversion among never-injecting heroin users at baseline: No predictors identified other than starting injection

BACKGROUND: Heroin users who do not inject constitute a large pool of drug users with a potentially important impact on public health. We aimed to estimate the incidence of hepatitis C virus (HCV) among heroin users who had never injected (NIDUS) at baseline, and the effect of starting injecting during follow-up, other percutaneous exposures, sharing snorting paraphernalia, cocaine/crack use, and risky sexual behaviour on HCV-seroconversion. METHODS: Prospective cohort of 305 HCV-negative NIDUs at baseline, aged 18-30 and street-recruited in three Spanish cities in 2001-2003. Computer-assisted personal interviews were conducted and dried blood-spot samples were collected. Bivariate and multivariable Poisson models were used. RESULTS: Among the 305 never-injectors who were HCV-negative at baseline, 197 (64.6%) were followed-up and 21 seroconverted [HCV-incidence rate=5.8/100 person-years at risk (pyar) (95% CI: 3.6-8.9)]. HCV incidence in new-injectors was 28.4/100pyar [(95% CI, 14.7-49.7) vs. 2.8/100pyar (95% CI, 1.3-5.4)] among NIDUs. Of the risk exposures considered, starting injecting was the only predictor of HCV-seroconversion [adjusted relative risk=10.1, 95% CI: 3.8-26.7]. CONCLUSION: The HCV-seroconversion rate was 10 times higher among new-injectors than never-injectors. No predictors other than starting injecting were found for HCV-seroconversion. Harm reduction interventions to prevent HCV infection should include prevention of drug injection.     

Monotherapy or Combination Therapy for Fibromyalgia Treatment?

Fibromyalgia is a chronic pain disease whose clinical symptomatology also includes different symptom domains: fatigue, sleep disturbances, morning stiffness, dyscognition, and psychological distress. These associated symptoms usually vary in frequency and intensity from patient to patient. Because the efficacy of monotherapy is limited, more severely affected patients frequently require drug combinations. There is, however, scarce scientific information concerning the benefits and risks of such combinations. To date, only ten studies investigating the efficacy and tolerability of two-drug combinations have been published; some of these studies are old and/or studied drugs that are now known to be of little or no interest in fibromyalgia management. Thus, when polytherapy is considered, therapeutic decisions must be based on data from monotherapy trials and a sound knowledge of the pharmacological profile of each drug. Well-designed clinical trials exploring specific drug combinations selected on the basis of potential additive or synergistic effects should be performed.     

Tratamiento del lupus eritematoso cutáneo resistente

Lupus erythematosus (LE) is an autoimmune inflammatory disease that includes a broad spectrum of manifestations, ranging from systemic disease (systemic lupus erythematosus [SLE]) to purely cutaneous forms (cutaneous lupus erythematosus [CLE]).Cutaneous involvement occurs in 90% of patients with SLE.Based on morphological and histopathological features, CLE can be divided into three categories: chronic CLE, subacute CLE and acute CLE.The precise etiology of LE is not fully understood, but the disease occurs when environmental factors, drugs and infectious agents trigger an abnormal immune response in an individual with predisposing genetic factors.To assess cutaneous involvement, several scores have been developed over the years. A recent study, called CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index), staged mucocutaneous damage and disease activity separately, allowing assessment of therapeutic response to be standardized.The management of CLE is challenging. Although treatment traditionally consists of photoprotection, topical steroids and antimalarial agents, these measures are sometimes ineffective in subgroup of patients, giving rise to what is called resistant CLE.This article reviews the topical and systemic treatment options, both the classical and new treatment alternatives currently available.     

Actualización en fascitis necrotizante

Necrotizing fasciitis is defined as a rapidly progressive infection of the skin and soft tissue that usually involves severe systemic toxicity. The incidence of this infection has increased in the last few decades and is estimated to affect one out of every 100,000 inhabitants in western European countries. This disease is the most serious form of skin and soft tissue infection, due to rapid destruction and necrosis of the fascia and subcutaneous fat, and the development of shock and multiorgan failure in about one third of patients.Although there are several predisposing factors for the development of the disease, especially for type I, or polymicrobial, necrotizing fasciitis, many patients are young and have no underlying chronic diseases, as is the case for type II, or streptococcal, necrotizing fasciitis. The diagnosis is mainly clinical, and urgent surgical consultation is required as soon as possible once suspicion is high, as the main determinant of mortality is the delay in surgical treatment. Overall mortality remains high, affecting more than 25% of patients. Surgical debridement is the mainstay of treatment, along with hemodynamic support and broad-spectrum antibiotics.