Baseline Characteristics of Fabry Disease "Amenable" Migalastat Patients in Argentinian Cohort.

Fabry disease (FD) is a multisystem lysosomal storage disorder induced by genetic variants in the alpha-galactosidase A (αGalA) gene. Some FD patients have GLA variants with a reduction in overall αGalA enzymatic activity due to mutated proteins with reduced stability, caused by protein misfolding and premature degradation, but the αGalA catalytic activity remains conserved ("amenable" genetic variants). To correct this misfolding and to prevent premature degradation, migalastat, a small iminosugar molecule was developed. We report the clinical characteristics of FD "amenable" cohort patients from Argentina, prior to starting treatment with migalastat. Seventeen Fabry adult patients were recruited from 13 Argentinian Centers; 8 males (47.1%) and 9 females (52.9%) were included. All genotypes included were missense-type "amenables" mutations. Some classic FD typical early manifestations were more frequent in patients with "classic" versus "late-onset" FD phenotype (pain, p=0.002; cornea verticillata, p=0.019). There was a statistically significant difference in estimated glomerular filtration rate in the "classic" versus "late-onset" phenotype (p=0.026) but no difference between genders (p=0.695). Left ventricular mass was similar between genders (p=0.145) and phenotypes (p=0.303). Cardiovascular risk factors were present among "late-onset" females (obesity 50% and smoke 25%). In patients who started "de novo" migalastat, the main indications were (i) heart disease, (ii) kidney damage, and (iii) pain, while in "switched from prior enzyme replacement therapy" patients, the most frequent indication was "patient decision;" this coincides with publications by other authors.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review.

BACKGROUND: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. METHODS: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. RESULTS: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. CONCLUSION: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review

Abstract Background: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. Methods: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. Results: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. Conclusion: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

Use of a Spinal Traction Device during Work Shift in Assembly Line Workers.

Increasing back discomfort and spinal shrinkage during the workday is a problem that affects assembly line workers. The aim of this research was to analyze the effect of a spinal traction system on discomfort, spinal shrinkage, and spinal sagittal alignment in assembly line workers, who are in prolonged standing conditions during a workday. A total of 16 asymptomatic males were recruited to assess spinal shrinkage, spinal sagittal alignment, and back discomfort during the workday. The measurement was carried out in two days of work, a normal day, and the other using a spinal traction device utilized in two breaks during the workday. Assembly line workers lost height significantly on both control and intervention days. No differences were found between days. No changes were found in spinal sagittal alignment on the control day. Lumbar lordosis angle increased significantly at the end of the intervention day. The use of a spinal traction device during the workday in two breaks time did not significantly reduce the spinal shrinkage of healthy workers. Lumbar lordosis angle increased significantly at the end of the spinal traction intervention day. Prospective studies would be necessary to clarify the possible benefits of the traction device.

A model to differentiate WAD patients and people with abnormal pain behaviour based on biomechanical and self-reported tests.

The prevalence of malingering among individuals presenting whiplash-related symptoms is significant and leads to a huge economic loss due to fraudulent injury claims. Various strategies have been proposed to detect malingering and symptoms exaggeration. However, most of them have been not consistently validated and tested to determine their accuracy in detecting feigned whiplash. This study merges two different approaches to detect whiplash malingering (the mechanical approach and the qualitative analysis of the symptomatology) to obtain a malingering detection model based on a wider range of indices, both biomechanical and self-reported. A sample of 46 malingerers and 59 genuine clinical patients was tested using a kinematic test and a self-report questionnaire asking about the presence of rare and impossible symptoms. The collected measures were used to train and validate a linear discriminant analysis (LDA) classification model. Results showed that malingerers were discriminated from genuine clinical patients based on a greater proportion of rare symptoms vs. possible self-reported symptoms and slower but more repeatable neck motions in the biomechanical test. The fivefold cross-validation of the LDA model yielded an area under the curve (AUC) of 0.84, with a sensitivity of 77.8% and a specificity of 84.7%.

Vínculos, identidad y desarrollo psíquico / Bonds, identity and psychic development

Es a través de la necesaria relación con un otro como se estructura el psiquismo y se construye la identidad: desde la relación dual pasando por la aparición del tercero que da lugar al grupo primario o familia siendo después incluido el sujeto en sucesivos grupos en los que tiende a reproducir su posición en el grupo primero. Reflexionaré asimismo sobre las funciones de la terapia como relación con un otro haciendo un paralelismo con las 'tareas maternas' propuestas por Winnicott y en particular sobre el trabajo en aquellos trastornos en los que la acción aparece como principal forma de vínculo (AU)

It is through the necessary relation to others that the psyche is structured and identity is constructed: from the dual relationship through the emergence of the third that gives rise to the primary group or family then being included the subject in successive groups in which he/ she tends to play the same position. I also reflect on the roles of therapy as a relationship with another drawing a parallel with the 'maternal tasks' proposed by Winnicott and particularly on the work with those disorders in which the action appears as the main way to bond (AU)

Analysis of class I and II histone deacetylase gene expression in human leukemia.

Histone deacetylase (HDAC) inhibitors are well-characterized anti-leukemia agents and HDAC gene expression deregulation has been reported in various types of cancers. This study sought to characterize HDAC gene expression patterns in several types of leukemia. To do so, a systematic study was performed of the mRNA expression of all drug-targetable HDACs for which reagents were available. This was done by real-time PCR in 24 leukemia cell lines and 39 leukemia patients, which included AML, MDS and CLL patients, some of whom received HDAC inhibitor treatment. Among the samples analyzed, there was no discernible pattern in HDAC expression. HDAC expression was generally increased in CLL patients, except for HDAC2 and HDAC4. HDAC expression was also generally increased in VPA-treated MOLT4 cells. However, this increased expression was not seen in AML patients treated with vorinostat. In summary, increased HDAC expression was noted in CLL patients in general, but the HDAC expression patterns in myeloid malignancies appear to be heterogeneous, which implies that the role of HDACs in leukemia may be related to global expression or protein function rather than specific expression patterns.

A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes.

PURPOSE: Data suggest that activity of p38 MAPK and Tie2 kinases is dysregulated in myelodysplastic syndromes (MDS) and may be targets for novel therapies. A phase I study of ARRY-614, an oral dual inhibitor of p38 MAPK and Tie2, was conducted in patients with low or intermediate-1 International Prognostic Scoring System risk MDS to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary responses by International Working Group 2006 criteria. EXPERIMENTAL DESIGN: Forty-five patients received ARRY-614 either once daily or twice daily in dose escalation (400, 600, 900, or 1,200 mg once daily; 200 or 300 mg twice daily) or expansion cohorts. RESULTS: The 300 mg twice daily schedule was not tolerated, and an MTD was not reached for once daily dosing. Treatment-related adverse events were primarily grade 1-2, with the most common being rash, diarrhea, dry skin, fatigue and anorexia. Interpatient PK variability was high, although exposure was sufficient to achieve reduction in p38 MAPK activation in bone marrow and in the levels of circulating biomarkers. Disease responses were observed in 14 of 44 (32%) evaluable patients, 13 (93%) of whom had previously been treated with a hypomethylating agent. Responses were observed in all lineages, with 5 patients experiencing bilineage responses. Three of 25 red blood cell transfusion-dependent (TD) patients achieved transfusion independence (TI) and 5 of 7 platelet TD patients achieved TI. CONCLUSIONS: ARRY-614 was well tolerated and has sufficient activity to warrant further evaluation in this patient population. We recommend 1,200 mg once daily as the optimal dose for further study.

ESHAP as salvage therapy for relapsed or refractory Hodgkin's lymphoma.

The management of relapsed or refractory Hodgkin's lymphoma (RR-HL) remains a challenge for hematologists and oncologists. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for RR-HL. However, one of the most controversial aspects is which the best salvage protocol could be. We retrospectively analyzed 82 consecutive RR-HL who received etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent of patients (75/82) were transplanted. With a mean follow-up of 87 ± 53 months, the median progression-free survival (PFS) and time to tumor progression (TTP) for the whole population were 52 and 56 months, respectively, and the 5-year overall survival was 72.6 %. Achieving CR after ESHAP was associated with a longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5-year TTP, respectively, P < 0.01). However, there were no differences for overall survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity was low and <10 % of patients developed neutropenic fever, with no toxic deaths. Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient therapeutic option for patients with RR-HL who are candidates for ASCT, since it combines a high response rate and mobilizing potential with a low toxicity profile.

Psicoanálisis y TDAH: el origen de la hiperactividad y los problemas en las vivencias primeras / Psychoanalysis and ADHD: origin of hiperactivity and attentional problems in early experiences

En este artículo se explica el TDAH desde el punto de vista psicoanalítico teniendo en cuenta para ello la interacción entre la base biológica y las vivencias primeras. Se entiende la hiperactividad como una forma de estructuración psíquica cuyos ejes principales son las dificultades de autocontención, la fragilidad en el equilibrio narcisista y el déficit de mentalización. Se establecen por último dos vías de intervención: la preventiva con un trabajo sobre el vínculo madre-bebé y la psicoterapéutica con dos focos: la ansiedad de separación y el estilo vincular incluyendo la representación de sí mismo (AU)

In this work ADHD is explained from a psychoanalytic perspective, considering the interaction between biological basis and early experiences. Hyperactivity is understood as a particular way of psychic organization which relies on these main axes: self-containment difficulties, fragility of narcissistic balance, and metallization deficit. Finally, two intervention paths are exposed: the preventive one working with the motherbaby bond, and the psychotherapeutic one, with two focal points; separation anxiety and attachment style, including the self-representation (AU)

Chemical contamination baseline in the Western basin of the Mediterranean Sea based on transplanted mussels.

The MYTILOS project aimed at drawing up a preliminary report on coastal chemical contamination at the scale of the Western Mediterranean (continental coasts of the Balearic Islands, Sicily, Sardinia, Corsica and Maghreb) based on a transplanted mussels methodology validated along the French coasts since 1996 by Ifremer and the Rhône Méditerranée & Corsica water board. MYTILOS is backed up by the INTERREG III B/MEDOC programme, the PNUE/PAM-MEDPOL and Rhône Méditerranée & Corsica water board. Three cruises (2004, 2005, 2006) have taken place to assess the first state of chemical contamination along the Western Mediterranean shores with the same methodology. Approximately 120 days were spent at sea deploying and retrieving 123 mussel bags. The results obtained for all studied contaminants were equivalent to those obtained along the French coast according the RINBIO network. These similarities relate to both the highest measured levels and background levels throughout the 123 stations. The areas of greatest impact were mainly urban and industrial centers and the outlets of major rivers, with a far higher midsea impact on the dilution of organic compounds than on metals. Metal levels measured in midsea zones were found to be similar to those in natural shellfish populations living along the coast. On a global scale we can observe that the contaminants levels in the Mediterranean Sea are in the same range as in other areas worldwide. Overall, the research demonstrates the reliability of this methodology for marine pollution monitoring, especially in the Mediterranean sea.

Western Mediterranean coastal waters--monitoring PCBs and pesticides accumulation in Mytilus galloprovincialis by active mussel watching: the Mytilos project.

In order to evaluate the contamination levels in the Western Mediterranean basin, the active mussel watch methodology has been applied. This methodology consists of mussel transplantation (Mytilus galloprovincialis) from non impacted areas to selected coastal areas, characterised by potential impact from the continent due to contaminating sources. The areas of interest were selected along the entire coastal development of the Western Mediterranean sea, 122 sites in total. The time of mussel caging exposure was 12 weeks. The project was co-financed in the frame of the Interreg IIIB Meddoc Programme, aimed at determining the overall chemical quality of the Mediterranean sea, consistent with the Water Framework Directive 2000/60. Several partners representative of the coastal Mediterranean Countries were involved in the Project, with the purpose of building up a common surveillance network, adopting shared methodologies. In this paper we present the results of three yearly monitoring campaigns (2004, 2005, 2006) carried out along the coasts of Italy, France, Spain, Morocco, Algeria and Tunisia, including the coastal environment of Baleares, Sicily, Sardinia and Corsica. The contamination levels of Pesticides (DDT and its metabolites, Hexachlorocyclohexane isomers alpha and gamma) and Polychlorinated biphenyls, are reported and discussed. Statistical elaborations performed on the original data set were mainly aimed at validating the raw sample distributions, by means of the Johnson method. Both DD and PCB species frequency distributions have been approximated to appropriate theoretical distributions, belonging to the Log-normal and Bounded families. By integrating the related Probability Density Functions (p.d.f.), different accumulation values for DDT, DDD and DDE and PCB species have been estimated, corresponding to fixed percentage points of the area under the respective curves. By choosing appropriate probability level boundaries (33rd and 66th percentile), different regional zones have been ranked in terms of low, medium and high accumulation for Pesticides and PCBs.

We are family? Spanish law and lesbian normalization in Hospital Central.

After four decades of a repressive dictatorial regime during which homosexuality was banned and punished with prison sentence and electroshock, Spain became a democratic country in 1978. The social, political, and legal debates previous to the passing of the law on same-sex marriage in June 2005 fueled lesbian visibility in the media. Considering that the emergence of lesbian representation has been linked to these social and political changes, our contribution centers on the ways in which the prime time TV series Hospital Central unravels as a vehicle for the normalization of lesbian relationships and families as addressed to a mostly heterosexual audience.