Search

Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants.

Genome editing in plants typically relies on T-DNA plasmids that are mobilized by Agrobacterium-mediated transformation to deliver the CRISPR/Cas9 machinery. Here, we introduce a series of CRISPR/Cas9 T-DNA vectors for minimal lab settings, such as in the classroom or citizen science projects. Spacer sequences targeting genes of interest can be inserted as annealed short oligonucleotides in a single straightforward cloning step. Fluorescent markers expressed in mature seeds enable reliable selection of transgenic as well as transgene-free individuals using a combination of inexpensive LED lamps and colored-glass alternative filters. Testing these tools on the Arabidopsis GROWTH-REGULATING FACTOR (GRF) gene family, we found that Cas9 expression from an EGG CELL1 (EC1) promoter resulted in tenfold lower mutation rates than expression from a UBIQUITIN10 (UBQ10) promoter. A collection of bona fide null mutations in all nine GRF genes could be established with little effort. Finally, we explored the effects of simultaneously targeting two, four and eight GRF genes on the rate of induced mutations at each target locus. Multiplexing caused strong interference effects: while mutation rates at some loci remained consistently high, mutation rates at other loci dropped dramatically with increasing number of single guide RNA species. Our results suggest potential detrimental genetic interaction between induced mutations as well as competition of CRISPR RNAs for a limiting amount of Cas9 apoprotein.

The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p < 0.001) and had more frequently the diffuse subtype of SSc (45 vs. 24%; p = 0.004) than patients without DUs. Patients with DUs showed significantly higher scores in the Cochin Hand Function Scale overall (p < 0.002) and for each of its five dimensions. They also showed higher scores in the Systemic Sclerosis Health Assessment Questionnaire items related to hand function such as, dress and self-care (p < 0.013), eat (p < 0.013) and grip (p < 0.03), and higher Visual Analogic Scale scores for pain (p < 0.013), trouble related with Raynaud's Phenomenon (p < 0.001) and sense of severity (p < 0.004). Impact on daily activities was significantly higher in patients with DUs (p = 0.002), with a non-significant trend to experience higher impact on work productivity (p = 0.07). A high correlation was found between DUs patients and physicians opinion on the impact of DUs (daily life: Pearson R = 0.86; work productivity: Pearson R = 0.87). Study findings show an impaired hand function and increased disability for daily life activities and work productivity in SSc patients with DUs compared with patients without DUs in Spanish population.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group. A multinational case-control study in kidney transplant recipients finds that pretransplant diagnosis of chronic obstructive pulmonary disease, delayed graft function, bloodstream infection and acute graft rejection identify patients at the highest risk for early invasive pulmonary aspergillosis.

Metabolic syndrome (MS) has become a health and financial burden worldwide. Susceptibility of genetically determined metabotype of MS has not yet been investigated. We aimed to identify a distinctive metabolic profile of blood serum which might correlates to the early detection of the development of MS associated to genetic polymorphism.

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by H-1-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a H-1 NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA.

Background: Persistent vegetative states (PVS) and locked-in syndrome (LIS) are well-differentiated disorders of consciousness that can be reached after a localized brain injury in the brainstem. The relations of the lesion topography with the impairment in the whole-brain architecture and functional disconnections are poorly understood. Methods: Two patients (PVS and LIS) and 20 age-matched healthy volunteers were evaluated using diffusion tensor imaging (DTI). Anatomical network was modeled as a graph whose nodes are represented by 71 brain regions. Inter-region connections were quantified through Anatomical Connection Strength (ACS) and Density (ACD). Complex networks properties such as local and global efficiency and vulnerability were studied. Mass univariate testing was performed at every connection using network based statistic approach. Results: LIS patients' network showed significant differences from controls in the brainstem-thalamus-frontal cortex circuitry, while PVS patients showed a widespread disruption of anatomical connectivity in both hemispheres. Both patients showed a reorganization of network attributes, with decreased global and local efficiency, significantly more pronounced in PVS.

This paper describes the automatic three-dimensional (3D) graphic possibilities that are supplied by the Neurosurgical Deep Recording System (NDRS) to facilitate anatomic-physiological targeting during stereotactic and functional neurosurgery using depth recording. This software has been developed to substitute the complex electronic equipment ordinarily used for deep brain electrical recording, display and processing by a personal computer. It may also help to improve on-line graphic analysis, automatic management of the recorded information and flexibility to implement different forms of signal analysis. It can automatically show a 2D or 3D representation of the electrode track, with the electrophysiological findings superimposed as well as the corresponding sagittal, coronal and axial views of a brain atlas using automatic scaling. The NDRS has already successfully been applied during more than 300 neurosurgeries in Spain and Cuba, enabling improved targeting accuracy and safety.

Background Gingival enlargement (GE) is a frequent side effect associated with the administration of cyclosporine (CsA) and the calcium channel blockers (CCB). The aims of this study were to determine and compare GE prevalence and severity in 3 groups of renal transplant recipients who had been medicated with CsA versus CsA in combination with nifedipine versus CsA in combination with amlodipine. Patients and Methods A cohort of 93 patients included 31 medicated with CsA, 31 with CsA plus nifedipine, and 31 with CsA plus amlodipine. The presence and severity of GE were assessed using the index developed by Harris and Ewart. Results There were significant differences in GE prevalence and GE severity among the 3 groups. A greater proportion (90.3%) of the CsA-nifedipine group was categorized as having GE compared with the CsA-amlodipine group (58.1%) or the CsA group (51.6%). A greater percentage of subjects in the CsA-nifedipine group displayed severe GE (22.6%) when compared with the CsA (0%) or the CsA-amlodipine group (16.1%). Conclusion The prevalence and severity of GE in subjects maintained on CsA-nifedipine was significantly greater than that among subjects treated with CsA-amlodipine or CsA only. The GE prevalence and severity was greater in the CsA-amlodipine group than the CsA group. This observation should lead clinicians to avoid the use of these drugs together with CsA or to choose amlodipine instead of nifedipine.

Background Cytomegalovirus (CMV) infection is frequent in kidney transplant recipients. Although involvement of the gastrointestinal tract with CMV has been described, intra-oral localization is rare. The aim of this study was to analyze the incidence, clinical characteristics, treatment, and outcome of renal transplant recipients with oral lesions due to CMV. Patients and Methods We analyzed the records of 453 patients who underwent kidney transplantation between February 1989 and March 2007. Incident cases and characteristics of CMV oral lesions were ascertained retrospectively in the outpatient records. Results The cumulative incidence of 6 cases with oral ulcerations was 1.32%. The median follow-up (n = 453) was 61.84 ± 50.68 months. The interval for the incidence of CMV oral ulcers after renal transplantation was 12.83 ± 23.51 months. The affected oral locations included the buccal mucosa, hard palate, soft palate, tongue, and floor of the mouth. CMV cases showed no significant difference with regard to gender distribution, age at renal transplantation, renal transplant indication, type of immunosuppressive treatment, and donor/recipient CMV serological status before transplantation. The number of acute rejection episodes was significantly greater and time since transplantation was significantly shorter in CMV cases. Conclusion CMV infection, which is common in renal transplant recipients, only rarely affects the mouth. Herein we have reported 6 patients who suffered oral ulcers due to CMV infection. An early diagnosis of these lesions is important to a successful outcome for these patients.

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects. (C) 2014 Elsevier Inc. All rights reserved.

Exercise has been associated with several beneficial effects and is one of the major modulators of metabolism. The working muscle produces and releases substances during exercise that mediate the adaptation of the muscle but also improve the metabolic flexibility of the complete organism, leading to adjustable substrate utilization. Metabolomic studies on physical exercise are scarce and most of them have been focused on the effects of intense exercise in professional sportsmen. The aim of our study was to determine plasma metabolomic adaptations in mice after a long-term spontaneous exercise intervention study (18 mo). The metabolic changes induced by long-term spontaneous exercise were sufficient to achieve complete discrimination between groups in the principal component analysis scores plot. We identified plasma indicators of an increase in lipolysis (elevated unsaturated fatty acids and glycerol), a decrease in glucose and insulin plasma levels and in heart glucose consumption (by PET), and altered glucose metabolism (decreased alanine and lactate) in the wheel running group. Collectively these data are compatible with an increase in skeletal muscle insulin sensitivity in the active mice. We also found an increase in amino acids involved in catecholamine synthesis (tyrosine and phenylalanine), in the skeletal muscle pool of creatine phosphate and taurine, and changes in phospholipid metabolism (phosphocholine and choline in lipids) between the sedentary and the active mice. In conclusion, long-term spontaneous wheel running induces significant plasma and tissue (heart) metabolic responses that remain even when the animal is at rest.

We used (1)H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG; n = 55) and (2) healthy subjects (CG; n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30 µL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.

We used (1) H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG;n = 55) and (2) healthy subjects (CG;n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30 mu L) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80 degrees C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.

To identify factors related with the risk to develop microalbuminuria using combined genomic and metabolomic values from a general population study. One thousand five hundred and two subjects, Caucasian, more than 18 years, representative of the general population, were included. Blood pressure measurement and albumin/creatinine ratio were measured in a urine sample. Using SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54 ± 19, 50.6% men, ACR30 mg/g in 81 subjects) with high genotyping call rate were analysed. A characteristic metabolomic profile, which included products from mitochondrial and extra mitochondrial metabolism as well as branched amino acids and their derivative signals, were observed in microalbuminuric as compare to normoalbuminuric subjects. The comparison of the metabolomic profile between subjects with different UAE status for each of the genotypes associated to microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the rs4359_CC of ACE gene, with minimal or no statistically significant differences. Subjects with and without microalbuminuria, who shared the same genotype and metabolomic profile, differed in age. Microalbuminurics with the CC genotype of the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism were seven years older and seventeen years younger, respectively as compared to the whole microalbuminuric subjects. With the same metabolomic environment, characteristic of subjects with microalbuminuria, the TT genotype of the rs10492025 polymorphism seems to increase and the CC genotype of the rs4359 polymorphism seems to reduce risk to develop microalbuminuria.

SETTING Subtherapeutic plasma isoniazid (INH) concentrations and the development of bacterial resistance may be attributed to poor quality and reduced bioavailability of fixed-dose combination (FDC) formulations. The bioavailability of INH from a generic and that of a branded FDC formulation had not been compared in the Mexican population. OBJECTIVE To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) in comparison with a 3FDC reference with doses of 300 mg INH in 20 healthy Mexican adults, and to generate data regarding the oral relative bioavailability of the drug in this population. DESIGN A single-dose, randomised-sequence, open-label, two-period crossover study. RESULTS Both formulations were well tolerated. The pharmacokinetic parameters of INH showed wide inter-individual variability. The average relative bioavailability calculated for maximum serum concentration area under the concentration-time curve (AUC), AUC(0-24h) and AUC(0-∞) of the test 3FDC formulation vs. the 3FDC reference were respectively 64.84% (90%CI 56.01-75.06), 59.05% (90%CI 50.27-69.36) and 57.26% (90%CI 46.93-69.84). CONCLUSIONS The 3FDC test and reference formulations were not bioequivalent because the 90%CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%) based on the rate and extent of absorption.

Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Órganos Sólidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient's individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin.

espanolCaso clinico: Presentamos el caso de una mujer de 74 anos que desarrollo una escleroqueratitis necrotizante en su ojo izquierdo tras cirugia de catarata no complicada. No tenia antecedentes de enfermedad autoinmune sistemica. El analisis histopatologico de la lesion mostro granulomatosis necrotizante con abundantes celulas plasmaticas. Discusion: La escleroqueratitis necrotizante inducida por cirugia (ENIC) es una grave afeccion que requiere tratamiento precoz y agresivo tratando de prevenir sus potencialmente devastadoras consecuencias. La reseccion conjuntival junto con implante de membrana amniotica pueden ser necesarias para interrumpir temporalmente el proceso inmunologico local. No obstante, es esencial asociar un tratamiento inmunosupresor sistemico. EnglishClinical case: We report the case of a 74-year-old female who developed a necrotizing sclerokeratitis affecting her left eye after uncomplicated cataract surgery. She had no previous history of systemic autoimmune disease. Histopathology of the lesion revealed necrotic granulomatosis with an increased number of plasma cells. Discussion: Surgically induced necrotizing sclerokeratitis (SINS) is a serious entity which requires prompt and aggressive therapy to prevent its potential devastating ocular consequences. Conjunctival resection and amniotic membrane grafting may be necessary to temporarily interrupt local immunologic events in severe cases. However, associated systemic immunomodulatory therapy seems to be mandatory.

Objective We evaluated the incidence of urological complications after simultaneous renal and pancreatic transplantation. Patients and Methods We retrospectively reviewed urological complications following 107 simultaneous kidney-pancreas transplantations performed at our institution between March 1995 and June 2008. The 46 women and 61 men were of mean age 37.8 years (range, 25–66). The mean duration of diabetes mellitus was 23.0 years (range, 9–48) and the mean duration of dialysis was 19.9 months (range, 0–70). The exocrine pancreatic secretions were drained to bladder in 58 cases, or enterically in 49 patients. The mean length of follow-up was 51.7 months. Results The most frequent urological complication was urinary tract infection, reported in 63.8% of patients: 42 bladder-drained and 25 enteric-drained ( P = .011). Hematuria occurred in 13 patients (12.5%): 12 bladder-drained and 1 enteric-drained ( P = .002). Five bladder-drained patients developed bladder calculi. Among 58 bladder-drained patients, reflux pancreatitis occurred in 28 patients and urine leaks related to the pancreatic graft occurred in 7 patients. Conversion of exocrine secretions from bladder to enteric diversion was required in 6 patients. One- and 3-year patient survival rates were 92.7% and 89.1%, respectively. Moreover, 1 and 3-year kidney graft survival rates were 90.6% and 84.4%, and pancreas graft survival rates were 78.1 and 70.3%, respectively. Conclusion Simultaneous kidney-pancreas transplantation with bladder drainage is associated with a high frequency of urological complications. Appropriate treatment can resolve most complications. In our opinion, both enteric and bladder drainage seemed to be safe and effective alternatives to manage pancreatic exocrine secretions.

espanolCaso clinico: Se presenta el caso de un paciente de 64 anos con disminucion de agudeza visual bilateral, progresiva e indolora. La exploracion oftalmologica revelo papilitis con vitritis en ambos ojos, en distinto estadio. Con la sospecha de neuritis optica paraneoplasica se solicito estudio de autoanticuerpos que mostro positividad al marcador CRMP-5-IgG. Tras realizar mediastinoscopia, se diagnostico un carcinoma microcitico pulmonar. Discusion: El autoanticuerpo CRMP-5-IgG define una entidad paraneoplasica consistente en neuritis optica con vitritis. La serologia positiva evita la biopsia vitrea y agiliza la busqueda del cancer. En nuestro caso permitio el diagnostico de un tumor que era desconocido. EnglishCase report: The case of a 64-year-old patient with bilateral, progressive and painless diminution of visual acuity is presented. Ophthalmologic evaluation revealed optic neuritis and vitreous cells in both eyes, at different stages. Suspecting a paraneoplastic optic neuritis, the study of antibodies was requested. This showed positivity to the marker CRMP-5-IgG. After mediastinoscopy, a small cell lung carcinoma was diagnosed. Discussion: Autoantibody CRMP-5-IgG defines a paraneoplastic entity of combined optic neuritis and vitreous inflammatory cells. The serological positivity avoids the vitreous biopsy and expedites the search for cancer. In our case, it allowed the diagnosis a previously unidentified tumor.

This paper describes the automatic 3D-graphic possibilities that are supplied by the NDRS computer system (neurosurgical deep recording system) to facilitate the anatomic-physiological targeting during stereotactic and functional neurosurgery using deep recording. This software has been developed to substitute with a personal computer, the complex electronic equipment for deep brain electrical activity recording, display and processing. It also allows greater possibilities for on-line graphic analysis, automatic management of the recorded information and flexibility to implement different forms of signal analysis. Its new version can automatically show a 2D- and 3D-representation of the electrode track, with the superimposed electrophysiological findings, and the corresponding sagittal, coronal and axial view of a brain atlas, after its automatic scaling. The NDRS has already been successfully used in Spain and Cuba in more than 300 neurosurgeries, allowing to increase the targeting accuracy and safety.

The “Neurosurgical Deep Recording System” (NDRS) is a software for physiological targeting during stereotactic and functional neurosurgery using deep brain recording [1]. It substitutes with a personal computer (PC) complex equipment for signal recording.

In the last article of our series, the Genetics Group, coordinated by Osvaldo Mutchinick, deals with the history of genetics and how future research will impact diagnosis and treatment of diseases

Objetivos. Se evalua la efectividad de localizacion anatomica (ELAN) bilateral del nucleo subtalamico (NST), se describe el metodo de cartografiado electrofisiologico y se analiza la simetria de los nucleos contralaterales (SC) en 11 pacientes con enfermedad de Parkinson, sometidos a subtalamotomia bilateral. Pacientes y metodos. Para evaluar la ELAN se calcula el porcentaje tanto de los primeros trayectos (p1) como del total de trayectos (pt) que hicieron blanco, asi como la distancia promedio (d) del resto al NST. Se define el error de localizacion anatomica (e) como la diferencia entre las coordenadas del primer trayecto y las del punto medio del nucleo, determinado por la informacion electrofisiologica, asi como la significacion estadistica de este error. La SC se analiza con el contraste de la hipotesis de igualdad en la maxima altura del nucleo a lo largo de un trayecto, la posicion promedio del centro electrofisiologico y la distribucion espacial de todos los registros intranucleares en todos los pacientes encontrado en cada hemisferio. Resultados. Los valores de p1, pt y d obtenidos fueron 86,36%, 86,13% y 1,41 ± 1,01 mm, respectivamente. El valor de e fue mayor en la direccion anteroposterior (1,11 ± 0,83 mm), aunque sin significacion estadistica (test ANOVA de Kruskal Wallis para la mediana y test de Wilcoxon para muestras apareadas; p = 0,05). El numero promedio de trayectos de registros para el primer proceder fue 6,45, y para el segundo, 6. La asimetria de los nucleos contralaterales no fue significativa (test ANOVA de Kruskal Wallis para la mediana y test de Wilcoxon para muestras apareadas; p = 0,05). Conclusiones. Un metodo indirecto con imagenes de TAC y un novedoso metodo de cartografiado electrofisiologico con registro multiunitario, para el primer y el segundo nucleo, son seguros y brindan una alta efectividad en la localizacion anatomofuncional del nucleo. Los nucleos de un mismo paciente son simetricos. Se observo poca variabilidad espacial entre pacientes, no relacionada con las diferencias en la distancia intercomisural.

Introduction. A series of quantitative scales have been established internationally to evaluate the functional state of patients affected by movement disorders, such as Parkinson's disease. The values of these parameters offered by each patient, measured at different moments during his or her illness, allow us to conduct studies into their evolution as well as perform statistical studies about the casuistics. Aim. To provide a tool that enables us to study this vast amount ofmaterial in an efficient, sure and, above all, automated manner. Materials and methods. We selected the most interesting variables from the international protocols. We also designed and developed a database application for use under the Windows environment using Delphi 3.0 language and compiler and Structured Query Language. Results. We designed, developed and validated a database system so as to be able to handle automatically the information on the clinical evolution of patients who had undergone functional neurosurgery. This system not only enables us to collect all relevant pre- and post-surgical information but also allows fast searches and selection, data processing using descriptive statistical techniques and the exportation of the data in a standard format. The system, which also allows final double-blind clinical evaluation of each patient to be performed, has been used successfully in the Movement Disorders Clinic at the CIREN for over three years. Conclusions. This system allows for a considerable saving in the amount of time and effort needed for the post-surgical evolution ofpatients, while also increasing the reliability of the results obtained.

Summary. Objectives. Barrow’s D-type carotid-cavernosa fistula (FCC) with progressive symptoms and in whom endovascular procedures have failed meet criteria for a direct approach. We report a case of this type of vascular lesion in whom partial endovascular embolization was done together with a direct approach to the FCC, using a method of localization involving a transoperative imaging guide. Digital subtraction angiography and Estereoflex stereotactic system was used. Patients and methods. A female patient had had a previous minor head injury. She had a progressive neurological disorder with marked visual defect, and had been diagnosed on angiography as having FCC with afferents from branches of the internal carotid artery (ACI) and external carotid artery (ACE). After failure of endovascular treatment orbito-zygomatic craniotomy was done with extraintradural dissection and exposure of the antero-lateral triangle of the cavernous sinus (SC). The fistula was closed completely by anterior packing with the venous component. Transoperative stereotactic angiographic checks were done to localize and control the packing. Conclusions. The Barrow’s type D FCC in which embolization treatment has failed may be treated using a direct approach to the anterolateral triangle of the SC. The AC1 remained permeable, fistula was occluded and there was minimal morbidity. [REV NEUROL 2002; 34: 204-7]

Introduction The combination of stereotaxic techniques, advances in neuroimaging and the creation of continually improving software has permitted stereotaxic biopsy of cerebral lesions at the most varied sites. Improvement in the method of permanent interstitial radiation (brachytherapy) improves the precision with which the radioactive sources may be inserted, releasing a maximum dose of radiation to the tumour with minimum radiation to the surrounding tissue. Patients and methods We treated 237 patients (aged 1 to 78 years) with intracranial lesions, all included in the protocol of our centre. Stereotaxic systems of Leksell, Riechert-Mundinger, Micromar and Estereoflex were used. The procedure was in three stages: acquisition of the image, surgical planning and surgical operation. The imaging guide was the computerized axial tomography (CAT). Results Stereotaxic biopsy guided by CAT images was done in 153 patients. These were divided into three groups, taking the biopsy findings as the reference: group A (primary tumors, 128), group B (metastatic tumors, 15) and group C (non-malignant lesions, 10). Ninety six permanent implants of 192Ir were inserted, with a low dose of 4-7 cGy/h and a total dose of 80-120 Gy. Conclusions Stereotaxic biopsy is a very effective procedure with a significantly low range of complications. The permanent implant with a low dose rate, well situated and using a source of 192Ir is a safe, simple, effective method for the treatment of primary and recurrent glial tumours, and non-glial tumours which fulfil criteria for this type of brachytherapy.

INTRODUCTION: The Neurosurgical Deep Recording System (NDRS) using a personal computer takes the place of complex electronic equipment for recording and processing deep cerebral electrical activity, as a guide in stereotaxic functional neurosurgery. It also permits increased possibilities of presenting information in direct graphic form with automatic management and sufficient flexibility to implement different analyses. OBJECTIVE: This paper describes the possibilities of automatic simultaneous graphic representation in three almost orthogonal planes, available with the new 5.1 version of NDRS so as to facilitate the analysis of anatomophysiological correlation in the localization of deep structures of the brain during minimal access surgery. MATERIAL AND METHODS: This new version can automatically show the spatial behaviour of signals registered throughout the path of the electrode inside the brain, superimposed simultaneously on sagittal, coronal and axial sections of an anatomical atlas of the brain, after adjusting the scale automatically according to the dimensions of the brain of each individual patient. This may also be shown in a tridimensional representation of the different planes themselves intercepting. RESULTS: The NDRS system has been successfully used in Spain and Cuba in over 300 functional neurosurgery operations. The new version further facilitates analysis of spatial anatomophysiological correlation for the localization of brain structures. CONCLUSION: This system has contributed to increase the precision and safety in selecting surgical targets in the control of Parkinson s disease and other disorders of movement.

INTRODUCTION: The microsurgical techniques for resection of intracranial lesions are limited where anatomical references do not exist or cannot be used as guides in the dissection of deeply located lesions or in more superficial eloquent areas. The stereotaxic guide, guided by imaging gives precise volumetric and geometric definition in intracranial lesions. Its application in the resection of intracranial tumors has special characteristics due to their biological condition and varied localization. OBJECTIVES: Spatial orientation during surgery is essential. We show this application of stereotaxic surgery in the Centro Internacional de Restauracion Neurologica (CIREN) in La Havana, Cuba, between May 1994 and February 1988, describing 65 microsurgical operations done using stereotaxis in 62 patients with intracranial cerebral tumors. PATIENTS AND METHODS: The procedure was divided into three stages: acquiring an image, computerized axial tomography and surgical planning, with the STASSIS planning system and microsurgical procedures, including systems of stereotaxis: Leksell, Micromar and Estereoflex. RESULTS: Of the total, 27 of these patients had glial tumors, 33 non-glial tumors and only 2 had non-neoplastic lesions of different sites and sizes. A total of 30 resections were done. Surgical morbidity was minimal and there was no surgical mortality. CONCLUSIONS: The main advantages of this method are: exact localization of the site for craniotomy, easy spatial orientation and ease in distinguishing the delimitation between the tumour and the healthy tissue. It has been shown that Estereoflex may be used in cerebral microsurgery.