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INTRODUCTION: PLA2G6-associated neurodegeneration (PLAN) comprises a continuum of three phenotypes with overlapping clinical and radiologic features. METHODS: Observational clinical study in a cohort of infantile and childhood onset PLAN patients and genetic analysis of the PLA2G6 gene. We analysed chronological evolution in terms of age at onset and disease course through a 66-item questionnaire. We performed qualitative and quantitative assessment of MRI abnormalities and searched for clinical and radiological phenotype and genotype correlations. RESULTS: Sixteen PLAN patients (mean age: 10.2 years, range 3-33) were evaluated, with a median onset (years) of signs/symptoms as follows: neurological regression (1.5), oculomotor abnormalities (1.5), hypotonia (1.8), gait loss (2.2), pyramidal signs (3.0), axonal neuropathy (3.0), dysphagia (4.0), optic atrophy (4.0), psychiatric symptoms (4.0), seizures (5.9), joint contractures (6.0), dystonia (8.0), bladder dysfunction (13.0) and parkinsonism (15.0). MRI assessment identified cerebellar atrophy (19/19), brain iron deposition (10/19), clava hypertrophy (8/19) and T2/FLAIR hyperintensity of the cerebellar cortex (6/19). The mid-sagittal vermis relative diameter (MVRD) correlated with age at onset of clinical variants, meaning that the earlier the onset, the more severe the cerebellar atrophy. All patients harboured missense, nonsense and frameshift mutations in PLA2G6, including four novel variants. CONCLUSIONS: Cerebellar atrophy was a universal radiological sign in infantile and childhood onset PLAN, and correlated with the severity of the phenotype. Iron accumulation within the globus pallidum and substantia nigra was also a common and strikingly uniform feature regardless of the phenotype.

Background Infant botulism (IB) is caused by the intestinal colonization by Clostridium botulinum in the first year of life and its subsequent production of neurotoxins. Traditionally, IB has been associated to honey consumption. IB cases tend to cluster in geographic regions. In Europe, IB is a rare disorder. From 1976 through 2006, 65 cases were identified in 13 European countries. In Spain, in the last 15 years, most of the cases have been reported in one region, Andalusia (Southern Spain). A specific treatment for IB type A and type B (BabyBIG) is available outside of the United States since 2005. Methods and aims: We performed a retrospective review of IB cases detected in Andalusia since 1997 and compare them with the cases of IB reported in Europe. Results We identified 11 confirmed cases of IB in Andalusia since 1997, and 14 cases in Spain. Nine out of 11 cases were detected since 2007; none of these infants had been exposed to honey consumption. One case in 1997 and another in 2000 were associated to honey. Two cases were treated with BabyBIG in 2007. In the period 2006–2012 the cases of IB reported in Europe were 54. Conclusions We identified a considerable increase in the incidence of IB since 2006. A tendency to a reduction in the number of cases of IB linked to honey consumption has also been identified. An increase in the exposure to these bacteria from the environment could be presumed. Clinicians should maintain a high index of suspicion for this treatable disorder.

Background The effectiveness of radial access ( RA ) in ST ‐elevation myocardial infarction ( STEMI ) has been predominantly established in primary percutaneous coronary intervention ( pPCI ) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral ( FA ) access in STEMI undergoing either a pharmacoinvasive ( PI ) strategy or pPCI . Methods and Results Within ST rategic Reperfusion Early After Myocardial Infarction ( STREAM ), we evaluated the relationship between arterial access site and primary outcome (30‐day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received. A total of 1820 STEMI patients were included: 895 PI (49.2%; rescue PCI [n=379; 42.3%], scheduled PCI [n=516; 57.7%]) and 925 pPCI (50.8%). Irrespective of treatment strategy, there was comparable utilization of either access site ( FA : PI 53.4% and pPCI 57.6%). FA STEMI patients were younger, had lower presenting systolic blood pressure, lesser Thrombolysis In Myocardial Infarction risk, and more ∑ ST ‐elevation at baseline. The primary composite endpoint occurred in 8.9% RA versus 15.7% FA patients ( P RA persisted (adjusted odds ratio [ OR ], 0.59; 95% CI , 0.44–0.78; P pPCI (adjusted OR , 0.63; 95% CI , 0.43–0.92) and PI cohorts (adjusted OR , 0.57 95% CI , 0.37–0.86; P interaction=0.730). There was no difference in nonintracranial major bleeding with either access group ( RA vs FA , 5.2% vs 6.0%; P =0.489). Conclusions Regardless of the application of a PI or pPCI strategy, RA was associated with improved clinical outcomes, supporting current STEMI evidence in favor of RA in PCI . Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 00623623.

Medullary thyroid cancer (MTC) represents approximately 5% of all thyroid cancers. Surgery is the only curative treatment, which includes total thyroidectomy and in most cases, neck dissection.To report our 10-year experience with surgical treatment of MTC.Review of medical records and pathology reports of a university hospital. We retrieved data from 28 patients aged 47.2 ± 16 years (21 women) operated for a MTC treated between June 2002 and June 2012.In 20 patients, MTC was diagnosed in the preoperative period. Total thyroidectomy was performed in all cases and included a neck dissection in 24 patients. Median follow-up was 48 (2-120) months. Twenty-five patients (89.2%) achieved complete remission of the disease and three had disease recurrence. There were no deaths during the follow up.The diagnosis of MTC is mainly based on cytology. Total thyroidectomy with neck dissection is the treatment of choice. An early-stage diagnosis is associated with low rates of recurrence and absence of mortality.

Executive functions are crucial for organizing and integrating cognitive processes. While some studies have assessed the effect of carotid artery stenting (CAS) on cognitive functioning, results have been conflicting. The object of this study was to assess the effect of CAS on cognitive status, with special interest on executive functions, among patients with severe asymptomatic internal carotid artery (ICA) stenosis.The authors prospectively assessed the neuropsychological status of 20 patients with unilateral asymptomatic extracranial ICA stenosis of 60% or more by using a comprehensive assessment battery focused on executive functions before and after CAS. Individual raw scores on neuropsychological tests were converted into z scores by normalizing for age, sex, and years of education. The authors compared baseline and 3-month postoperative neuropsychological scores by using Wilcoxon signed-rank tests.The mean preoperative cognitive performance was within normal ranges on all variables. All patients underwent a successful CAS procedure. Executive function scores improved after CAS, relative to baseline performance as follows: set shifting (Trail-Making Test Part B: -0.75 ± 1.43 vs -1.2 ± 1.48, p = 0.003) and processing speed (digit symbol coding: -0.66 ± 0.85 vs -0.97 ± 0.82, p = 0.035; and symbol search: -0.24 ± 1.32 vs -0.56 ± 0.77, p = 0.049). The benefit of CAS for working memory was marginally significant (digit span backward: -0.41 ± 0.61 vs -0.58 ± 0.76, p = 0.052). Both verbal (immediate Rey Auditory Verbal Learning Test: 0.35 ± 1.04 vs -0.22 ± 0.82, p = 0.011) and visual (delayed Rey-Osterrieth Complex Figure: 0.27 ± 1.26 vs -0.22 ± 1.01, p = 0.024) memory improved after CAS.The authors found a beneficial effect on executive function and memory 3 months after CAS among their prospective cohort of consecutive patients with unilateral and asymptomatic ICA stenosis of 60% or more.

Segawa disease is a rare dystonia due to autosomal dominant guanosine triphosphate cyclohydrolase I (adGTPCH) deficiency, affecting dopamine and serotonin biosynthesis. Recently, the clinical phenotype was expanded to include psychiatric manifestations, such as depression, anxiety, obsessive–compulsive disorder, and sleep disturbances. Although cognitive and neuropsychiatric symptoms may be attributable to dopamine deficiency in the prefrontal cortex and frontostriatal circuitry, intelligence is considered normal in Segawa disease. Our aim was to investigate neuropsychiatric symptoms and intelligence quotients (IQ) in a series of individuals with adGTPCH deficiency. The assessment included a structured clinical interview following the DSM-IV-TR’s guidelines, Beck’s Depression Inventory, the State-Trait Anxiety Inventory, the Maudsley Obsessive–Compulsive Questionnaire, the Barratt Impulsiveness Scale-11 (BIS-11), the Oviedo Sleep Questionnaire, the Pittsburgh Sleep Quality Index, and the Wechsler Adult Intelligence Scale-Third Edition. Equivalent tests were applied to pediatric patients as appropriate for their age group. Fourteen patients with adGTPCH deficiency were evaluated (seven adult and seven pediatric patients). Depression, anxiety, and obsessive–compulsive symptoms were not more common than expected in the general population. However, the seven adults showed impulsivity in the BIS-11; nine individuals had an IQ in the range of borderline intellectual functioning to mild mental retardation, and sleep disturbances were found in four individuals. We found no differences between these results and the motor impairment. In conclusion, our findings would suggest that cognitive impairment, and impulsivity in adults, may be associated with Segawa disease.

Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency is an inborn error of neurotransmitter metabolism, with a prevalence of 0.5 per million, caused by mutations/deletions in the GCH1 gene. The finding of the mutation Q89X in the GCH1 gene in 23 patients from two pedigrees in an area inhabited by a population of 800,000 prompted us to consider that our cohort may have descended from a single founder. Twelve Q89X mutation-positive cases belonging to two families and 100 unrelated control subjects from the same geographical region were studied. Six microsatellite markers located near GCH1 were analyzed to validate a possible mutation-related founder haplotype. Haplotype analysis revealed two different haplotypes for six microsatellite markers that segregated with the Q89X mutation. A common haplotype in 10 out of 12 mutation carriers studied was identified. Two subjects carried a second haplotype, most probably because of a recombination event. However, at least 186 different haplotypes were established in the control subjects. In contrast with the frequencies of 83.3% and 16.7%, respectively, found for both mutation-segregating haplotypes, the frequency of none of the control haplotypes exceeded 1.5%. Dystonia was the most frequent symptom in our series, and parkinsonism was present in five patients. The large number of Q89X mutation carriers in our community is because of a founder effect. The same mutation in GCH1 causes a wide phenotypic spectrum of clinical variability occurring in this population of affected patients.

Since 1975, the Durie-Salmon staging system (DS) has been a widely accepted prognostic classification of multiple myeloma (MM) patients. Recently, the new International Staging System (ISS) was developed using only the values of albumin and beta2-microglobulin.To compare survival of patients with MM treated in six medical centers in Chile according to the DS system and the new ISS.Retrospective analysis of demographic information, clinical features and survival rate of patients treated between 1998 and 2002, and grouped according to both systems.Information of 81 patients aged 38 to 90 years (43 women) was retrieved. According DS system 11% were in stage I 12% in stage II and 73% in stage III According to ISS, 34% were in stage I 35% in stage II and 31% in stage III Median of survival of all patients was 32 months. Both staging systems had a prognostic value. However, median survival for the three stages of the ISS system was significantly different (67, 29 and 14 months in stages III and III, respectively, p =0.02). Patients in advanced stages II and III of the ISS, had a higher frequency of anemia, hypercalcemia, renal failure and hypoalbuminemia. In stages II and III of ISS the presence of renal failure was associated with a non significantly different lower survival.The ISS is a simple and effective grouping method for patients with MM, that predicts survival. The presence of renal insufficiency might identify a subgroup of patients included in stages II and III of ISS with a higher mortality.

Mortality rate records are the only data available in Chile about the prognosis of patients with multiple myeloma (MM).To characterize clinical features, survival rate and factors related to mortality in cases with MM treated in six large medical centers in Chile.Retrospective analysis of demographic data, clinical features and survival rate records of patients with MM, collected between 1998 and 2002. Survival curves were generated and a multivariate analysis of factors associated to early mortality was carried out.Data from 245 patients aged 38 to 95 years (129 women) was collected. Fifty two percent had an IgG myeloma, 25% had and IgA and 6.1% had light chains myeloma. According to Durie and Salmon staging system, 8,2% were in Stage 112.6% in Stage II, 60.5% in Stage III and in 18.8% the information about staging was not available. Fifty percent had an hemoglobin level below 10 g/dL, 30% had a serum creatinine over 2 mg/dL and 28% had a serum calcium level over 10.5 mg/dL. Median survival was 33 months. Twenty percent of patients died within the first six months after diagnosis (early mortality). Predictive factors for early mortality were male sex, thrombocytopenia, anemia, renal failure, hypercalcemia, a beta2-microglobulin5.5 mg/L and a serum albumin level3.5 g/dL. There was a correlation between the number of bad prognosis factors present and the probability of early mortality.This group of Chilean patients with MM presented a short survival time, and 20% died within the first six months after diagnosis. More than a half of cases were diagnosed at an advanced stage (Durie and Salmon Stage III). Several factors were associated to early mortality, two of which (beta 2-microglobulin and serum albumin), are included in the new International Staging System for MM.

The emergence of new virulent and drug resistant strains of Mycobacterium tuberculosis has forced researchers to focus on the worldwide geographical distribution of the genetics variants of this pathogen. Mycobacterium bovis, a close related pathogen, contributes with human tuberculosis and therefore, it is particularly important in countries with significant bovine tuberculosis prevalence. Spoligotyping is currently one of the most widely used strategies for genotyping members of the M. tuberculosis complex. In this work, of a total of 41 isolates, 25 were from different patients from the Xth Region from Chile. These isolates formed 15 clusters of spoligotypes. Twenty four percent of the spoligotypes corresponded to the worldwide distributed spoligotype 53 (SpolDB4). A significant number of spoligotypes were identical to profiles found in Brazil followed by Argentina and Spain. Although the patients where from rural areas, no cases of zoonosis were observed. To establish the geographical distribution, persistence and routes of dissemination of the pathogen, a greater number of epidemiologically relevant isolates are being analyzed using the MIRUs-VNTRs.

Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease.

To analyse the quality of prescription and compliance with nursing treatment orders (NTOs) in primary care teams (PCTs), in order to identify potential problems and establish interventions.Observational, crossover study.Three health districts in Santa Coloma de Gramenet.NTO forms for injectable medication referred to nursing from PCTs between March 1 and November 30, 1996.1,088 NTO sheets containing 1,119 prescriptions were evaluated. 64.61% of the NTOs came from PCTs. Compliance with the NTO on the length of treatment (63.33%), on length and guidelines taken together (58.00%) and on allergies to medicine (28.31%) was deficient. The most prescribed therapeutic groups were medicines for the locomotive apparatus (36.10%) and drugs for infections (24.66%). 56.03% of prescriptions had high intrinsic value. It was difficult to justify 72.48% of prescriptions.Deficiencies were detected in compliance with NTOs, due to the absence of information which was vital for correct administration. There was low-quality prescription and over-use of parenteral administration.

To ascertain the role of total enteral nutrition, compared with total parenteral nutrition, as adjunct therapy to steroids in patients with severe acute ulcerative colitis, a prospective randomized trial was conducted in 42 of such patients. Inclusion criteria were the persistence of a moderate or severe attack of the disease (Truelove's index) after 48 h on full steroid treatment (prednisone 1 mg/kg/day). Patients were randomized to receive polymeric total enteral nutrition or isocaloric, isonitrogenous total parenteral nutrition as the sole nutritional support. Remission rate and need for colectomy were similar in both groups. No significant changes in anthropometric parameters were observed in either nutritional group at the end of the study. Median increase in serum albumin was 16.7% (-0.5% to +30.4%) in the enteral feeding group, and only 4.6% (-12.0% to +13.7%) in the parenteral nutrition patients (p = 0.019). Adverse effects related to artificial nutritional support were less frequent (9% vs. 35%, p = 0.046) and milder in enterally fed patients. Postoperative infections occurred more often with parenteral nutrition (p = 0.028). These results suggest that total enteral nutrition is safe and nutritionally effective in severe attacks of ulcerative colitis. It is also cheaper and associated with fewer complications than parenteral nutrition. Total enteral nutrition should be regarded as the most suitable type of nutritional support in these patients.

Objective To compare the main characteristics of two inception cohorts (Italian [ITC] and Spanish [SPC]) cohorts of patients with systemic lupus erythematosus (SLE) at the time of diagnosis and at one year of follow-up. Methods Demographic, clinical and immunological characteristics, and treatments at SLE diagnosis and at 12 months of follow-up of ITC and SPC were compared. Results One hundred and sixty-four patients in the ITC and 231 patients in the SPC were compared. the patients from ITC were younger at SLE diagnosis (41.1±15.0 years vs. 46.4±15.6 years; p

The aim of this study was to investigate the effect of total paracentesis plus albumin or dextran-70 infusion on the nutritional status in cirrhotics with tense ascites. Seventeen patients were studied. Eight patients (group I) were treated with total paracentesis and albumin infusion, and in 9 cases (group II) dextran-70 infusion was associated to total paracentesis. The nutritional status was assessed before and two days after the procedure by measuring triceps skinfold thickness, mid-arm muscle circumference and serum albumin. No changes in anthropometric parameters were observed in either group. Patients in group I showed a significant increase in serum albumin levels (from 26.6 +/- 1.4 to 28.9 +/- 1.3 g/l; p = 0.007), whereas this parameter decreased in group II (from 25.5 +/- 1.3 to 23.1 +/- 1.4 g/l; p = 0.005). However, serum albumin levels returned to initial values in both groups one month after total paracentesis. There were no differences between both groups regarding the appearance of complications and mortality rate during admission. These results suggest that total paracentesis plus either i.v. albumin or dextran-70 has no long-term effect on the protein-energy nutritional status.

Tacripyrines (1-14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent AChE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC50 105 ( 15 nM) is associated to a 30.7 ( 8.6% inhibition of the proaggregating action of AChE on the A and a moderate inhibition of A self-aggregation (34.9 ( 5.4%). Molecular modeling indicates that binding of compound 11 to the AChE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD., J.M.C. thanks Dr. Ma. Luz de la Puente (Analytical Technologies Department, Lilly SA), and Dr. Ma. Angeles Martínez-Grau (Lilly SA) for the resolution of compound 11. J.M.C. and also R.L. thank MEC for a fellowship (AP20020576) and B.L. thanks CSIC for a I3P Training Contract. The present work has been supported by Fundación Teófilo Hernando, MEC grants BFI2003-02722; SAF2006- 08764-C02-01, SAF-2006-08540, SAF2006-1249, and CTQ2005- 09365, CAM (S/SAL-0275-2006), ISCIII [Red RENEVAS (RD06/0026/1002)], CSIC-GRICES project (2007PT-13), and Fundación La Caixa (Barcelona, Spain).