Stair climbing - An insight and comparison between women with and without joint hypermobility: A descriptive study.

Generalized joint hypermobility (GJH) is a frequent entity in rheumatology with higher prevalence among women. It is associated with chronic widespread pain, joint dislocations, arthralgia, fibromyalgia and early osteoarthritis. Stair climbing is an important functional task and can induce symptoms in hypermobile persons. The aim of this study was to compare ground reaction forces (GRF) and muscle activity during stair climbing in women with and without GJH. A cross-sectional study of 67 women with normal mobility and 128 hypermobile women was performed. The hypermobile women were further divided into 56 symptomatic and 47 asymptomatic. GRFs were measured by force plates embedded in a six step staircase, as well as surface electromyography (EMG) of six leg muscles. Parameters derived from GRF and EMG were compared between groups using t-test and ANOVA. For GRF no significant differences were found. EMG showed lower activity for the quadriceps during ascent and lower activity for hamstrings and quadriceps during descent in hypermobile women. For symptomatic hypermobile women these differences were even more accentuated. The differences in EMG may point towards an altered movement pattern during stair climbing, aimed at avoiding high muscle activation. However, differences were small, since stair climbing seems to be not demanding.

Laparoscopically assisted ventriculoperitoneal shunt placement: a prospective randomized controlled trial

OBJECT In ventriculoperitoneal (VP) shunt surgery, laparoscopic assistance can be used for placement of the peritoneal catheter. Until now, the efficacy of laparoscopic shunt placement has been investigated only in retrospective and nonrandomized prospective studies, which have reported decreased distal shunt dysfunction rates in patients undergoing laparascopic placement compared with mini-laparotomy cohorts. In this randomized controlled trial the authors compared rates of shunt failure in patients who underwent laparoscopic surgery for peritoneal catheter placement with rates in patients who underwent traditional mini-laparotomy. METHODS One hundred twenty patients scheduled for VP shunt surgery were randomized to laparoscopic surgery or mini-laparotomy for insertion of the peritoneal catheter. The primary endpoint was the rate of overall shunt complication or failure within the first 12 months after surgery. Secondary endpoints were distal shunt failure, overall complication/ failure, duration of surgery and hospitalization, and morbidity. RESULTS The overall shunt complication/failure rate was 15% (9 of 60 cases) in the laparoscopic group and 18.3% (11 of 60 cases) in the mini-laparotomy group (p = 0.404). Patients in the laparoscopic group had no distal shunt failures; in contrast, 5 (8%) of 60 patients in the mini-laparotomy group experienced distal shunt failure (p = 0.029). Intraoperative complications occurred in 2 patients (both in the laparoscopic group), and abdominal pain led to catheter removal in 1 patient per group. Infections occurred in 1 patient in the laparoscopic group and 3 in the mini-laparotomy group. The mean durations of surgery and hospitalization were similar in the 2 groups. CONCLUSIONS While overall shunt failure rates were similar in the 2 groups, the use of laparoscopic shunt placement significantly reduced the rate of distal shunt failure compared with mini-laparotomy.

Ethical procedures and patient consent differ in Europe.

BACKGROUND Research ethics approvals, procedures and requirements for institutional research ethics committees vary considerably by country and by type of organisation. OBJECTIVE To evaluate the requirements and procedures of research ethics committees, details of patient information and informed consent based on a multicentre European trial. DESIGN Survey of European hospitals participating in the prospective observational study on chronic postsurgical pain (euCPSP) using electronic questionnaires. SETTING Twenty-four hospitals in 11 European countries. PARTICIPANTS From the 24 hospitals, 23 local investigators responded; 23 answers were analysed. OUTCOME MEASURES Comparison of research ethics procedures and committee requirements from the perspective of clinical researchers. Comparison of the institutions' procedures regarding patient information and consent. Description of further details such as costs and the duration of the approval process. RESULTS The approval process lasted from less than 2 weeks up to more than 2 months with financial fees varying between 0 and 575 &OV0556;. In 20 hospitals, a patient information sheet of variable length (half page up to two pages) was provided. Requirements for patients' informed consent differed. Written informed consent was mandatory at 12, oral at 10 and no form of consent at one hospital. Details such as enough time for consideration, possibility for withdrawal and risks/benefits of participation were provided in 25 to 30% of the institutions. CONCLUSION There is a considerable variation in the administrative requirements for approval procedures by research ethics committees in Europe. This results in variation of the extent of information and consent procedures for the patients involved. TRIAL REGISTRATION euCPSP in Clinicaltrials.gov identifier: NCT01467102; PAIN-OUT in Clinicaltrials.gov identifier: NCT02083835.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (abdominal pain and bloating at 3 (p = 0.002) and 6 months (p = 0.01). CONCLUSION Readaptation of the dorsolateral peritoneal layer following PLND and cystectomy has a beneficial long-term impact on bowel function and postoperative pain without compromising oncological radicality. This article is protected by copyright. All rights reserved.

Anterior fixation of unstable pelvic ring fractures using the modified Stoppa approach: mid-term results are independent on patients' age

PURPOSE Open surgical management of unstable pelvic ring injuries has been discussed controversially compared to percutaneous techniques in terms of surgical site morbidity especially in older patients. Thus, we assessed the impact of age on the outcome following fixation of unstable pelvic ring injuries through the modified Stoppa approach. METHODS Out of a consecutive series of 92 patients eligible for the study, 63 patients (mean age 50 years, range 19-78) were evaluated [accuracy of reduction, complications, failures, Majeed-Score, Oswestry Disability Questionnaire (ODI), Mainz Pain Staging System (MPSS)] at a mean follow-up of 3.3 years (range 1.0-7.9). Logistic multivariate regression analysis was performed to assess the outcome in relation to increasing patient age and/or Injury Severity Score (ISS). RESULTS Out of 63 patients, in 36 an "anatomic" reduction was achieved. Ten postoperative complications occurred in eight patients. In five patients, failure of fixation was noted at the anterior and/or posterior pelvic ring. In 49 patients, an "excellent" or "good" Majeed-Score was obtained; the mean ODI was 14 % (range 0-76 %); 50 patients reported either no or only minor chronic pelvic pain (MPSS). Only an increasing ISS conferred an increased likelihood of the occurrence of a non-anatomical reduction, a "poor" or "fair" Majeed-Score, or an ODI >20 %. CONCLUSIONS Increasing age did not impact the analysed parameters. Open reduction and internal fixation of the anterior pelvic ring through a modified Stoppa approach in unstable pelvic ring injuries did not result in an unfavourable outcome with increasing age of patients.

H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis

Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.

Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics.

BACKGROUND Endometriosis, the growth of endometrial tissue outside the uterine cavity, is associated with chronic pelvic pain, subfertility and an increased risk of ovarian cancer. Current treatments include the surgical removal of the lesions or the induction of a hypoestrogenic state. However, a reappearance of the lesion after surgery is common and a hypoestrogenic state is less than optimal for women of reproductive age. Additional approaches are required. Endometriosis lesions exist in a unique microenvironment characterized by increased concentrations of hormones, inflammation, oxidative stress and iron. This environment influences cell survival through the binding of membrane receptors and a subsequent cascading activation of intracellular kinases that stimulate a cellular response. Many of these kinase signalling pathways are constitutively activated in endometriosis. These pathways are being investigated as therapeutic targets in other diseases and thus may also represent a target for endometriosis treatment. METHODS To identify relevant English language studies published up to 2015 on kinase signalling pathways in endometriosis, we searched the Pubmed database using the following search terms in various combinations; 'endometriosis', 'inflammation', 'oxidative stress', 'iron', 'kinase', 'NF kappa', 'mTOR', 'MAPK' 'p38', 'JNK', 'ERK' 'estrogen' and progesterone'. Further citing references were identified using the Scopus database and finally current clinical trials were searched on the clinicaltrials.gov trial registry. RESULTS The current literature on intracellular kinases activated by the endometriotic environment can be summarized into three main pathways that could be targeted for treatments: the canonical IKKβ/NFκB pathway, the MAPK pathways (ERK1/2, p38 and JNK) and the PI3K/AKT/mTOR pathway. A number of pharmaceutical compounds that target these pathways have been successfully trialled in in vitro and animal models of endometriosis, although they have not yet proceeded to clinical trials. The current generation of kinase inhibitors carry a potential for adverse side effects. CONCLUSIONS Kinase signalling pathways represent viable targets for endometriosis treatment. At present, however, further improvements in clinical efficacy and the profile of adverse effects are required before these compounds can be useful for long-term endometriosis treatment. A better understanding of the molecular activity of these kinases, including the specific extracellular compounds that lead to their activation in endometriotic cells specifically should facilitate their improvement and could potentially lead to new, non-hormonal treatments of endometriosis.

Long-term hyperexcitability of sensory and motor axons in Aplysia californica: Induction by axotomy, serotonin, and transient depolarization

Neuropathic pain is a debilitating neurological disorder that may appear after peripheral nerve trauma and is characterized by persistent, intractable pain. The well-studied phenomenon of long-term hyperexcitability (LTH), in which sensory somata become hyperexcitable following peripheral nerve injury may be important for both chronic pain and long-lasting memory formation, since similar cellular alterations take place after both injury and learning. Though axons have previously been considered simple conducting cables, spontaneous afferent signals develop from some neuromas that form at severed nerve tips, indicating intrinsic changes in sensory axonal excitability may contribute to this intractable pain. Here we show that nerve transection, exposure to serotonin, and transient depolarization induce long-lasting sensory axonal hyperexcitability that is localized to the treated nerve segment and requires local translation of new proteins. Long-lasting functional plasticity may be a general property of axons, since both injured and transiently depolarized motor axons display LTH as well. Axonal hyperexcitability may represent an adaptive mechanism to overcome conduction failure after peripheral injury, but also displays key features shared with cellular analogues of memory including: site-specific changes in neuronal function, dependence on transient, focal depolarization for induction, and requirement for synthesis of new proteins for expression of long-lasting effects. The finding of axonal hyperexcitability after nerve injury sheds new light on the clinical problem of chronic neuropathic pain, and provides more support for the hypothesis that mechanisms of long-term memory storage evolved from primitive adaptive responses to injury. ^

In vivo longitudinal studies of spinal cord injury and vascular endothelial growth factor treatment

Approximately 12,000 new cases of spinal cord injury (SCI) are added each year to the estimated 259,000 Americans living with SCI. The majority of these patients return to society, their lives forever changed by permanent loss of sensory and motor function. While there are no FDA approved drugs for the treatment of SCI or a universally accepted standard therapy, the current though controversial treatment includes the delivery of high dosages of the corticosteroid methyliprednisolone sodium succinate, surgical interventions to stabilize the spinal column, and physical rehabilitation. It is therefore critically important to fully understand the pathology of injury and determine novel courses and rationally-based therapies for SCI. ^ Vascular endothelial growth factor (VEGF) is an attractive target for treating central nervous system (CNS) injury and disease because it has been shown to influence angiogenesis and neuroprotection. Preliminary studies have indicated that increased vasculature may be associated with functional recovery; therefore exogenous delivery of a pro-angiogenic growth factor such as VEGF may improve neurobehavioral outcome. In addition, VEGF may provide protection from secondary injury and result in increased survival and axonal sprouting. ^ In these studies, SCI rats received acute intraspinal injections of VEGF, the antibody to VEGF, or vehicle control. The effect of these various agents was investigated using longitudinalmulti-modal magnetic resonance imaging (MRI), neuro- and sensory behavioral assays, and end point immunohistochemistry. We found that rats that received VEGF after SCI had increased tissue sparing and improved white matter integrity at the earlier time points as shown by advanced magnetic resonance imaging (MRI) techniques. However, these favorable effects of VEGF were not maintained, suggesting that additional treatments with VEGF at multiple time points may be more beneficial, Histological examinations revealed that VEGF treatment may result in increased oligodendrogenesis and therefore may eventually lead to remyelination and improved functional outcome. ^ On the neurobehavioral studies, treatments with VEGF and Anti-VEGF did not significantly affect performance on tests of open-field locomotion, grid walk, inclined plane, or rearing. However, VEGF treatment resulted in significantly increased incidence of chronic neuropathic pain. This phenomenon could possibly be attributed to the fact that VEGF treatment may promote axonal sprouting and also results in tissue sparing, thereby providing a substrate for the growth of new axons. New connections made by these sprouting axons may involve components of pathways involved in the transmission of pain and therefore result in increased pain in those animals. ^

Prevalence and determinants of colonic polyps in children undergoing colonoscopy: A large hospital-based cross-sectional study

Background. Colorectal polyps are abnormal growths in the wall of the colon including the rectum. The study aims to estimate the prevalence and type of colonic polyps in children undergoing colonoscopic examination at Texas Children's Hospital (TCH) in Houston, Texas during 2000-2007. Also, to examine the factors associated with colonic polyps and the potential determinants of colonic polyps in children undergoing colonoscopy and compare those who had colonic polyps with those who did not on colonoscopy, and determine the significant risk factors of colonic polyps in these children. ^ Methods. We conducted a cross sectional study to analyze data collected at TCH. We obtained demographic, clinical, and histopathology information on consecutive patients who underwent colonoscopy during 2000-2007 from endoscopic records contained in the PEDS-CORI registry (Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative), and abstracted data from the accompanying histopathology reports. ^ Results. We identified 2,693-unique patients, under 18 years of age, who underwent colonoscopy. Approximately 65.5% were white non-Hispanic, and 10.8% African-American. The mean age was 8.7 years and 51.8% were female patients. Polyps were present in 174 patients (6.5%). The most common two histological types were juvenile (60.6%), inflammatory (17.4%). We found that the prevalence of polyps was higher in younger aged children (12.9% in 0-5 years) than in older aged children (4% in 15-17 years), and slightly higher in males than in females (7.9% and 5.4% respectively). For males only, the odds of polyps were statistically significantly higher in Blacks and Hispanics compared to white non Hispanics (OR of 2.2 and 2.1, respectively, and 95% CI of 1.3, 3.9 and 1.3, 3.5 respectively). The indications for colonoscopy were different for children with polyps compared to those without polyps, i.e., 47.0% vs. 19.8% respectively for lower GI bleeding, 2.7% vs. 21.4% respectively for abdominal pain/bloating, and, or 0.9% vs. 9.6% respectively for diarrhea. ^ Conclusion. Colorectal polyps occur in about 1 in 15 children and adolescents undergoing first colonoscopy. The demographic variable of younger age is strongly associated with having polyps irrespective of ethnicity. Lower GI bleeding is strongly related to the presence of colorectal polyps in children and adolescents undergoing colonoscopy.^

Natural history of placebo treatment in adults acquiring travelers' diarrhea in Mexico

The natural history of placebo treated travelers' diarrhea and the prognostic factors of recovery from diarrhea were evaluated using 9 groups of placebo treated subjects from 9 clinical trial studies conducted since 1975, for use as a historical control in the future clinical trial of antidiarrheal agents. All of these studies were done by the same group of investigators in one site (Guadalajara, Mexico). The studies are similar in terms of population, measured parameters, microbiologic identification of enteropathogens and definitions of parameters. The studies had two different durations of followup. In some studies, subjects were followed for two days, and in some they were followed for five days.^ Using definitions established by the Infectious Diseases society of America and the Food and Drug Administration, the following efficacy parameters were evaluated: Time to last unformed stool (TLUS), number of unformed stools post-initiation of placebo treatment for five consecutive days of followup, microbiologic cure, and improvement of diarrhea. Among the groups that were followed for five days, the mean TLUS ranged from 59.1 to 83.5 hours. Fifty percent to 78% had diarrhea lasting more than 48 hours and 25% had diarrhea more than five days. The mean number of unformed stools passed on the first day post-initiation of therapy ranged from 3.6 to 5.8 and, for the fifth day ranged from 0.5 to 1.5. By the end of followup, diarrhea improved in 82.6% to 90% of the subjects. Subjects with enterotoxigenic E. coli had 21.6% to 90.0% microbiologic cure; and subjects with shigella species experienced 14.3% to 60.0% microbiologic cure.^ In evaluating the prognostic factors of recovery from diarrhea (primary efficacy parameter in evaluating the efficacy of antidiarrheal agents against travelers' diarrhea). The subjects from five studies were pooled and the Cox proportional hazard model was used to evaluate the predictors of prolonged diarrhea. After adjusting for design characteristics of each trial, fever with a rate ratio (RR) of 0.40, presence of invasive pathogens with a RR of 0.41, presence of severe abdominal pain and cramps with a RR of 0.50, number of watery stools more than five with a RR of 0.60, and presence of non-invasive pathogens with a RR of 0.84 predicted a longer duration of diarrhea. Severe vomiting with a RR of 2.53 predicted a shorter duration of diarrhea. The number of soft stools, presence of fecal leukocytes, presence of nausea, and duration of diarrhea before enrollment were not associated with duration of diarrhea. ^

Azithromycin efficacy in treatment of Chlamydia trachomatis

Adolescents 15 – 19 years of age have the highest prevalence of Chlamydia trachomatis out of any age group, reaching 28.3% among detained youth [1]. The 2010 Center for Disease Control guidelines recommend one dose of azithromycin for the treatment of uncomplicated chlamydia infections based on 97% cure rate with azithromycin. Recent studies found an 8% or higher failure rate of azithromycin treatment in adolescents [2-5]. We conducted a prospective study beginning May, 2012 in the Harris County Juvenile Justice Center (HCJJC) medical department. Study subjects were detainees with positive urine NAAT tests for chlamydia on intake. We provided treatment with Azithromycin, completed questionnaires assessing risk factors and performed a test of cure for chlamydia three weeks after successful treatment. Those with treatment failure (positive TOC) received doxycycline for seven days. The preliminary results summarized herein are based on data collected from May 2012 to January 2013. Of the 97 youth enrolled in the study to date, 4 (4.1%) experienced treatment failure after administration of Azithromycin. Of these four patients, all were male, African-American and asymptomatic at the time of initial diagnosis and treatment. Of note, 37 (38%) patients in the cohort complained of abdominal pain with administration of Azithromycin. Results to date suggest that the efficacy of Azithromycin in our study is higher than the recent reported studies indicating a possible upper bound of Azithromycin. These results are preliminary and recruitment will continue until a sample size of 127 youth is reached.^

Estudio Multimodal de la Funcionalidad Cortical en ratones Transgénicos con Síndrome X Frágil y la modulación del dolor

El dolor es un síntoma frecuente en la práctica médica. En España, un estudio realizado en el año 2000 demostró que cada médico atiende un promedio de 181 pacientes con dolor por mes, la mayoría de ellos con dolor crónico moderado1. Del 7%-8% de la población europea está afectada y hasta el 5% puede ser grave2-3, se estima, que afecta a más de dos millones de españoles4. En la consulta de Atención Primaria, los pacientes con dolor neuropático tienen tasas de depresión mucho mayores 5-6-7. El dolor neuropático8 es el dolor causado por daño o enfermedad que afecta al sistema somato-sensorial, es un problema de salud pública con un alto coste laboral, debido a que existe cierto desconocimiento de sus singularidades, tanto de su diagnóstico como de su tratamiento, que al fallar, el dolor se perpetúa y se hace más rebelde a la hora de tratarlo, en la mayoría de las ocasiones pasa a ser crónico. Los mecanismos fisiopatológicos son evolutivos, se trata de un proceso progresivo e integrado que avanza si no recibe tratamiento, ocasionando graves repercusiones en la calidad de vida de los pacientes afectados9. De acuerdo a Prusiner (premio nobel de medicina 1997), en todas las enfermedades neurodegenerativas hay algún tipo de proceso anormal de la función neuronal. Las enfermedades neurodegenerativas son la consecuencia de anormalidades en el proceso de ciertas proteínas que intervienen en el ciclo celular, por lo tanto da lugar al cúmulo de las mismas en las neuronas o en sus proximidades, disminuyendo o anulando sus funciones, como la enfermedad de Alzheimer y el mismo SXF. La proteína FMRP (Fragile Mental Retardation Protein), esencial para el desarrollo cognitivo normal, ha sido relacionada con la vía piramidal del dolor10-11-12. El Síndrome de X Frágil13-14 (SXF), se debe a la mutación del Gen (FMR-1). Como consecuencia de la mutación, el gen se inactiva y no puede realizar la función de sintetizar la proteína FMRP. Por su incidencia se le considera la primera causa de Deficiencia Mental Hereditaria sólo superada por el Síndrome de Down. La electroencefalografía (EEG) es el registro de la actividad bioeléctrica cerebral que ha traído el desarrollo diario de los estudios clínicos y experimentales para el descubrimiento, diagnóstico y tratamiento de un gran número de anormalidades neurológicas y fisiológicas del cerebro y el resto del sistema nervioso central (SNC) incluyendo el dolor. El objetivo de la presente investigación es por medio de un estudio multimodal, desarrollar nuevas formas de presentación diagnóstica mediante técnicas avanzadas de procesado de señal y de imagen, determinando así los vínculos entre las evaluaciones cognitivas y su correlación anatómica con la modulación al dolor presente en patologías relacionadas con proteína FMRP. Utilizando técnicas biomédicas (funcionalestructural) para su caracterización. Para llevar a cabo esta tarea hemos utilizado el modelo animal de ratón. Nuestros resultados en este estudio multimodal demuestran que hay alteraciones en las vías de dolor en el modelo animal FMR1-KO, en concreto en la modulación encefálica (dolor neuropático), los datos se basan en los resultados del estudio estructural (imagen histología), funcional (EEG) y en pruebas de comportamiento (Laberinto de Barnes). En la Histología se muestra una clara asimetría estructural en el modelo FMR1 KO con respecto al control WT, donde el hemisferio Izquierdo tiene mayor densidad de masa neuronal en KO hembras 56.7%-60.8%, machos 58.3%-61%, en WT hembras 62.7%-62.4%, machos 55%-56.2%, hemisferio derecho-izquierdo respectivamente, esto refleja una correlación entre hemisferios muy baja en los sujetos KO (~50%) con respecto a los control WT (~90%). Se encontró correlación significativa entre las pruebas de memoria a largo plazo con respecto a la asimetría hemisférica (r = -0.48, corregido <0,05). En el estudio de comportamiento también hay diferencias, los sujetos WT tuvieron 22% un de rendimiento en la memoria a largo plazo, mientras que en los machos hay deterioro de memoria de un 28% que se corresponden con la patología en humanos. En los resultados de EEG estudiados en el hemisferio izquierdo, en el área de la corteza insular, encuentran que la latencia de la respuesta al potencial evocado es menor (22vs32 15vs96seg), la intensidad de la señal es mayor para los sujetos experimentales FMR1 KO frente a los sujetos control, esto es muy significativo dados los resultados en la histología (140vs129 145vs142 mv). Este estudio multimodal corrobora que las manifestaciones clínicas del SXF son variables dependientes de la edad y el sexo. Hemos podido corroborar en el modelo animal que en la etapa de adulto, los varones con SXF comienzan a desarrollar problemas en el desempeño de tareas que requieren la puesta en marcha de la función ejecutiva central de la memoria de trabajo (almacenamiento temporal). En el análisis del comportamiento es difícil llegar a una conclusión objetiva, se necesitan más estudios en diferentes etapas de la vida corroborados con resultados histológicos. Los avances logrados en los últimos años en su estudio han sido muy positivos, de tal modo que se están abriendo nuevas vías de investigación en un conjunto de procesos que representan un gran desafío a problemas médicos, asistenciales, sociales y económicos a los que se enfrentan los principales países desarrollados, con un aumento masivo de las expectativas de vida y de calidad. Las herramientas utilizadas en el campo de las neurociencias nos ofrecen grandes posibilidades para el desarrollo de estrategias que permitan ser utilizadas en el área de la educación, investigación y desarrollo. La genética determina la estructura del cerebro y nuestra investigación comprueba que la ausencia de FMRP también podría estar implicada en la modulación del dolor como parte de su expresión patológica siendo el modelo animal un punto importante en la investigación científica fundamental para entender el desarrollo de anormalidades en el cerebro. ABSTRACT Pain is a common symptom in medical practice. In Spain, a study conducted in 2000 each medical professional treats an average of 181 patients with pain per month, most of them with chronic moderate pain. 7% -8% of the European population is affected and up to 5% can be serious, it is estimated to affect more than two million people in Spain. In Primary Care, patients with neuropathic pain have much higher rates of depression. Neuropathic pain is caused by damage or disease affecting the somatosensory system, is a public health problem with high labor costs, there are relatively unfamiliar with the peculiarities in diagnosis and treatment, failing that, the pain is perpetuated and becomes rebellious to treat, in most cases becomes chronic. The pathophysiological mechanisms are evolutionary, its a progressive, if untreated, causing severe impact on the quality of life of affected patients. According to Prusiner (Nobel Prize for Medicine 1997), all neurodegenerative diseases there is some abnormal process of neuronal function. Neurodegenerative diseases are the result of abnormalities in the process of certain proteins involved in the cell cycle, reducing or canceling its features such as Alzheimer's disease and FXS. FMRP (Fragile Mental Retardation Protein), is essential for normal cognitive development, and has been linked to the pyramidal tract pain. Fragile X Syndrome (FXS), is due to mutation of the gene (FMR-1). As a consequence of the mutation, the gene is inactivated and can not perform the function of FMRP synthesize. For its incidence is considered the leading cause of Mental Deficiency Hereditary second only to Down Syndrome. Electroencephalography (EEG) is the recording of bioelectrical brain activity, is a advancement of clinical and experimental studies for the detection, diagnosis and treatment of many neurological and physiological abnormalities of the brain and the central nervous system, including pain. The objective of this research is a multimodal study, is the development of new forms of presentation using advanced diagnostic techniques of signal processing and image, to determine the links between cognitive evaluations and anatomic correlation with pain modulation to this protein FMRP-related pathologies. To accomplish this task have used the mouse model. Our results in this study show alterations in multimodal pain pathways in FMR1-KO in brain modulation (neuropathic pain), the data are based on the results of the structural study (histology image), functional (EEG) testing and behavior (Barnes maze). Histology In structural asymmetry shown in FMR1 KO model versus WT control, the left hemisphere is greater density of neuronal mass (KO females 56.7% -60.8%, 58.3% -61% males, females 62.7% -62.4 WT %, males 55% -56.2%), respectively right-left hemisphere, this reflects a very low correlation between hemispheres in KO (~ 50%) subjects compared to WT (~ 90%) control. Significant correlation was found between tests of long-term memory with respect to hemispheric asymmetry (r = -0.48, corrected <0.05). In the memory test there are differences too, the WT subjects had 22% yield in long-term memory, in males there memory impairment 28% corresponding to the condition in humans. The results of EEG studied in the left hemisphere, in insular cortex area, we found that the latency of the response evoked potential is lower (22vs32 15vs96seg), the signal strength is higher for the experimental subjects versus FMR1 KO control subjects, this is very significant given the results on histology (140vs129 145vs142 mv). This multimodal study confirms that the clinical manifestations of FXS are dependent variables of age and sex. We have been able to corroborate in the animal model in the adult stage, males with FXS begin developing problems in the performance of tasks that require the implementation of the central executive function of working memory (temporary storage). In behavior analysis is difficult to reach an objective conclusion, more studies are needed in different life stages corroborated with histologic findings. Advances in recent years were very positive, being opened new lines of research that represent a great challenge to physicians, health care, social and economic problems facing the major developed countries, with a massive increase in life expectancy and quality. The tools used in the field of neuroscience offer us great opportunities for the development of strategies to be used in the area of education, research and development. Genetics determines the structure of the brain and our research found that the absence of FMRP might also be involved in the modulation of pain as part of their pathological expression being an important animal model in basic scientific research to understand the development of abnormalities in brain.

Spontaneous rupture of malarial spleen: two case reports and review of literature

Malaria has long been among the most common diseases in the southeast Anatolia region of Turkey. In 1992, 18676 cases were diagnosed in Turkey, and Diyarbakir city had the highest incidence (4168 cases), followed by SanliUrfa city (3578 cases). Malaria was especially common during 1994 and 1995, with 84 345 and 82 094 cases being diagnosed in these years, respectively. Spontaneous rupture of malarial spleen is rare. We saw two cases during 1998, which are reported herein. Both patients were male, and were receiving chloroquine treatment for an acute attack of malaria. One of the patients had developed abdominal pain and palpitations, followed by fainting. The other patient had abdominal pain and fever. Explorative laparotomy revealed an enlarged spleen in both patients. Splenectomy was performed in both patients. We have identified 15 episodes of spontaneous rupture of the spleen in the English language literature published since 1961. Because of increased travel to endemic areas and resistance to antimalarial drugs, malaria is a major medical problem that is becoming increasingly important to surgeons worldwide. Malaria is a particularly important problem in the southeast Anatolia region of Turkey. Prophylactic precautions should be taken by tourists who travel to this region, especially during the summer.