Tratamiento de la enfermedad de injerto contra huésped crónica esclerodermiforme con imatinib: una perspectiva dermatológica / Sclerodermatous Chronic Graft-versus-Host Disease Treated With Imatinib: A Dermatological Perspective

INTRODUCCIÓN: La enfermedad de injerto contra huésped crónica (EICHc) es la causa más importante de mortalidad tardía no relacionada con la recidiva del trasplante alogénico de células progenitoras hematopoyéticas. La EICHc esclerodermiforme suele ser refractaria a los corticosteroides y supone todo un reto terapéutico. Se han descrito anticuerpos activadores contra el RFCDP en pacientes con EICHc esclerodermiforme. Estos anticuerpos inducen la fosforilación del RFCDP, produciendo fibrosis. Hay cada vez más evidencias de la efectividad de imatinib, un inhibidor de la tirosina cinasa, en el tratamiento de la EICHc esclerodermiforme. OBJETIVO: Evaluar la respuesta de la EICHc esclerodermiforme al imatinib. MATERIALES Y MÉTODOS: Estudio retrospectivo de 18 pacientes con EICHc cutánea esclerodermiforme refractaria a inmunosupresores tratada con imatinib en un único centro. La evaluación de la respuesta al tratamiento se realizó mediante valoración clínica del dermatólogo y percepción subjetiva del paciente tras uno, 3, 6, 9, 12 y 18 meses de iniciar el tratamiento con imatinib. La respuesta fue valorada como completa, parcial, significativa, sin cambios o progresión. El descenso de la dosis de esteroides se catalogó como completo, parcial o no posible. RESULTADOS: En nuestra serie, 4 (22%) pacientes lograron una respuesta completa, 9 (50%) alcanzaron una respuesta parcial, 2 (11%) tuvieron un grado significativo de respuesta, 2 (11%) no presentaron ningún cambio y uno (6%) experimentó avance de la enfermedad en el último seguimiento que se llevó a cabo. El tiempo medio transcurrido desde el inicio del imatinib hasta mostrar algún grado de respuesta fue de 2,75 meses (rango 1-9 meses). CONCLUSIONES: Este estudio apoya la evidencia de la utilidad del imatinib en el tratamiento de la EICHc esclerodermiforme

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. OBJECTIVE: To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. MATERIALS AND METHODS: Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. RESULTS: In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). CONCLUSIONS: This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD

Sclerodermatous Chronic Graft-versus-Host Disease Treated With Imatinib: A Dermatological Perspective. / Tratamiento de la enfermedad de injerto contra huésped crónica esclerodermiforme con imatinib: una perspectiva dermatológica.

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. OBJECTIVE: To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. MATERIALS AND METHODS: Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. RESULTS: In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). CONCLUSIONS: This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.

Migration of antimony from polyethylene terephthalate used in mineral water bottles.

The influence of storage time and temperature on Sb migration from PET bottles into mineral water was studied in short-term tests lasting up to 15 days and long-term studies lasting up to 220 days. Samples purchased were stored in three different coloured bottles: clear (CL), light blue (LB) and dark blue (DB). Sb migration was assayed by HG-AFS for total determination and HPLC-ICP-MS for speciation analysis. Migration studies showed that waters stored at 4 and 20 °C were not subject to Sb migration. At 40 °C there was a significant increase in Sb concentration, although the maximum limit established by the European Union (5.0 µgL(-)(1)) was not exceeded, whereas at 60 °C samples were subject to considerable Sb migration after 30 days of storage. In this case, the maximum limit established by the European Union was exceeded and both Sb (V) and Sb (III) were detected.

Uncertainty estimation in organic elemental analysis using information from proficiency tests.

We evaluate the uncertainty in organic elemental analysis of C, H, N, and S. We use data from six proficiency tests (PTs), in which some 35 Spanish laboratories participated. The uncertainty of the technique is estimated from the relative within-laboratory and between-laboratory variances for pure substances and samples with complex matrices (soil, powdered milk, oil, ash, and petroleum coke). We also calculate the relative standard uncertainties for individual laboratories when analysing pure substances using historical data from the participation of each laboratory in different editions of PTs. The uncertainty values obtained for the individual laboratories are comparable with the uncertainty of the technique and correlate with the combined z-scores. The evolution over time of those laboratories participating in common editions of PTs is also evaluated.

Comparison of three strategies to evaluate uncertainty from in-house validation data. A case study: mercury determination in sediments.

In the present paper, three approaches are compared for the evaluation of the combined uncertainty in the determination of mercury in aquatic sediments by an aqua regia extraction procedure. For this, the data obtained in validation studies from five certified reference materials (CRMs), covering a range of concentrations from 0.8 to 130 mg kg(-1) of mercury and analysed by three atomic spectroscopic techniques (cold vapour generation atomic fluorescence spectrometry, CV-AFS, cold vapour generation atomic absorption spectroscopy, and inductively coupled plasma mass spectroscopy), were considered. The combined uncertainty was firstly assessed by considering separately the data obtained for each CRM analysed (approach A). Moreover, this assessment was also performed with two other calculation approaches (B and C) based on the pooled data obtained from the validation step. The comparison of the results obtained for the different techniques showed a clear bias effect when using CV-AFS with nitric acid as a diluent. In relation to the strategies tested for the combined uncertainty assessment, approach C proved to be the easiest and friendliest method for uncertainty assessment.

Effect of chloride on heavy metal mobility of harbour sediments.

To evaluate the environmental impact of polluted sediments, several operationally defined sequential extraction procedures (SEPs) have been described. Salinity has long been recognised as an important variable determining the physicochemical behaviour of heavy metals in marine sediments. Thus, in the present paper, the modified BCR-SEP has been applied to harbour sediments in order to assess to what extent trace metal mobility (Cd, Cr, Cu, Ni, Pb and Zn) could be influenced by chloride content in sediments. For this, washed (W) and non-washed (NW) sediments were compared. The relative mobility order observed for the six trace metals studied was not seen to be influenced by the presence of chloride in the sediments, but an increase of mobility was observed for Cd and Zn (the most mobile metals) when chloride was present in the sediments. Characterisation of the sediments and of the pseudo-total metal contents by means of an aqua regia extraction was also assessed.

Assessment of metal mobility in dredged harbour sediments from Barcelona, Spain.

In order to assess heavy metal mobility in dredged harbour sediments, six superficial sediment samples covering a range of pollution levels and environments were collected in Barcelona Harbour. Samples were characterised in terms of major compounds (Al, Ca, Fe, Mn, Si, Ti, Mg, K and Na); total C, N and S contents; organic matter; and water content. Pseudo-total trace metal contents were assessed after aqua regia digestion (ISO 11466:1995). The modified BCR three-step sequential extraction procedure (BCR-SEP) was applied, and both major compounds (Al, Ca, Fe and Mn) and trace metals (Cd, Cr, Cu, Ni, Pb and Zn) were determined in the different extracts. Both the pseudo-total digestion method and the BCR-SEP were validated using two sediment certified materials from lakes (BCR CRM 701 and BCR CRM 601). The highest metal concentrations were observed in one of the sampling points which receives an urban discharge. The observed mobility order (percentage of metal extracted in the first step) of the six trace metals studied was Cd>Zn>Pb>Cu>Ni>Cr. The good agreement observed with the results obtained as the sum of the four steps (extractable+residue) and the pseudo-total content shows that laboratory working conditions were under control.

Two cases of linear IgA disease with clinical manifestations limited to the gingiva.

Linear IgA disease (LAD) is a chronic, subepithelial blistering disease that is associated with the presence of linear deposits of IgA along the basement membrane zone. Etiopathogenic aspects of LAD are only partially known. LAD is clinically characterized by vesiculobullous skin and mucous lesions. Although more than half of LAD patients present oral mucosal lesions, there are only a few cases reported of oral lesions as the only manifestation of LAD. This study presents 2 of these uncommon cases.

Mercury determination in solid phases from application of the modified BCR-sequential extraction procedure: a valuable tool for assessing its mobility in sediments.

The present paper presents a feasibility study for the evaluation of mercury mobility in sediments by application of the modified BCR three-step sequential extraction procedure (BCR-SEP). The aim of the study was to evaluate the effect of acidification, reduction and oxidation processes on mercury mobility from sediments, once the SEP was validated with other trace metals. As extractable mercury amounts were mostly found below detection limits of the advanced mercury analyser (AMA-254) used for measuring the extracts (L.D.<0.5 ng), the use of a solid sampling atomic absorption spectrometer with a specially designed furnace for Hg atomisation was found to be an optimal technique to quantify Hg in the solid residues coming from the SEP. With this approach, mercury was found to be hardly mobile and only for one of the moderately polluted sediments (BCR CRM 320), extractable mercury (exchangeable fraction, BCR procedure step 1) has been found. An oxidation step with H(2)O(2) was required to obtain extractability up to 64% of the total content in a highly polluted lagoon sediment.

[Trends in the prevalence of tuberculosis among six-year-olds in Albacete (Spain)]. / Evolución de la prevalencia de la infección tuberculosa en la población escolar de 6 años en Albacete.

OBJECTIVES: To analyze the prevalence and evolution of tuberculous infection among 6-year-olds in Albacete and its relation to socioeconomic status of the family. METHOD: A tuberculin test (2UT RT-23 Tween 80) was given to 6-year-old school children in and around Albacete in 1992 and 1999. We calculated the prevalence of tuberculosis and the relation to family socioeconomic level as assessed by the parents' level of education of the area of residence. RESULTS: The tuberculin test was given to 2,783 children, 1,532 in 1992 (8% bacille-Calmette-Guerin-vaccinated) and 1,251 in 1999. The prevalence of tuberculosis infection among non-vaccinated children was 0.78% in 1992 (3.37% among vaccinated children, p = 0.012) and 0.72% in 1999. No significant differences between the two screenings were found except for the vaccinated and non-vaccinated children. The annual decline was 1.1% and the annual decrease in risk of tuberculosis infection was 0.12%. No significant differences related to level of parental education or area of residence were detected. CONCLUSIONS: The prevalence of tuberculosis infection among 6-year-old school children in Albacete is low, although there is a very slight non-significant downward trend, which may be biased by the inclusion of bacille-Calmette-Guerin-vaccinated children. No differences related to family socioeconomic level were found.

Comparison of leaching tests for the study of trace metals remobilisation in soils and sediments.

Several leaching tests were applied and compared to study metal remobilisation on various unpolluted and contaminated soils and on several contaminated sediments. The trace elements considered were Cd, Cr, Cu, Ni, Pb and Zn, and leaching tests consisted of the application of reagents with contrasting characteristics and strengths in order to assess the information provided. An extraction with aqua regia permitted the estimation of the pseudo-total metal content in the sample. Mild extractants such as H2O, CaCl2 and NaNO3 showed low and similar leaching capacities. Acid (CH3COOH) and complexing (EDTA) agents were more effective in remobilising trace metals from soils and sediments. Cd and Zn showed similar extraction characteristics under both extractant solutions, whereas Cu and Pb were more sensitive to complexation, and Ni and Cr to acidification processes. Sequential chemical extractions provided additional information on the association of the trace elements with the different soil and sediment phases. Cd and Zn showed the highest mobility, Pb was associated to reducible solid phases, Cu and Ni to oxidisable phases, and Cr remained mostly in the residual fraction. The results obtained in this paper provided valuable information for choosing a leaching test, which is an instrument of environmental analysis for the estimation of trace metal mobility.

Application of focused-microwave wet digestion to the determination of trace metals in human gallstones by ICP/AES.

We propose an analytical digestion method for trace metal determination (Co, Cr, Cu, Fe, Mn, Ni and Zn) in gallstones, in an attempt to facilitate detection of their origin. The method consists of sample digestion with HNO3 and H2O2 by means of focused microwave. Metals are quantified by inductively coupled plasma atomic emission spectroscopy. The effect of calcium concentration in the analytical solutions was studied. Cu, Fe, Mn and Zn were detected in all the samples analysed and the highest concentrations were obtained for Cu and Fe, especially in black-pigmented gallstones. The reproducibility in terms of %RSD, determined in the gallstones with the lowest metal content, was below 5% for Cu, between 10% and 15% for Mn and Zn and up to 25% for Fe.

Application of a modified BCR sequential extraction (three-step) procedure for the determination of extractable trace metal contents in a sewage sludge amended soil reference material (CRM 483), complemented by a three-year stability study of acetic acid and EDTA extractable metal content.

This paper provides additional data on a sewage sludge amended soil certified reference material, CRM 483, which was certified in 1997 for its EDTA and acetic acid extractable contents of some trace metals, following standardised extraction procedures. The additional work aimed to test the long-term stability of the material and the applicability of an improved version of the BCR three-step sequential extraction procedure on the sewage sludge amended soil (CRM 483). The paper demonstrates the CRM 483 long-term stability for EDTA and acetic acid extractable contents of Cd, Cr, Cu, Ni, Pb and Zn and gives the results (obtained in the framework of an interlaboratory study) for the extractable contents of the same elements in the CRM 483, following the BCR three-step sequential extraction scheme. The aqua regia extractable contents following the ISO 11466 Standard are also given. The data are given as indicative (not certified) values.

Apoptosis-resistant T cells have a deficiency in NF-kappaB-mediated induction of Fas ligand transcription.

Apoptosis induced through the TCR in CD4+ T cells is mostly mediated by the inducible expression of Fas ligand (FasL) as a primary event leading to the commitment to death. To gain a better understanding of the transcriptional events that regulate this expression, we took advantage of our previously described mutant Jurkat cells. These cells are deficient in FasL expression and apoptosis induced upon TCR triggering, although their cytokine (IL-2 and IFN-gamma) production is normal. Here we show that both a FasL- and a consensus NF-kappaB-reporter construct are inefficiently induced in these cells compared to wild-type cells. In addition, we demonstrate that the inducible transcriptional activity of the FasL reporter is abolished by specific inhibitors of NF-kappaB activation. Thus, we could trace the deficit of the mutant cells to an inefficient NF-kappaB activation, evidencing a relevant role for NF-kappaB in the regulation of FasL expression in activated T cells. Furthermore, our results suggest that the induction of FasL versus cytokine gene expression is differentially sensitive to NF-kappaB deprivation.

Improvement of the BCR three step sequential extraction procedure prior to the certification of new sediment and soil reference materials.

The Standards, Measurements and Testing Programme (formerly BCR) of the European Commission proposed a three-step sequential extraction procedure for sediment analysis, following extensive expert consultations and two interlaboratory studies. This scheme was recently used to certify the extractable trace element contents of a sediment reference material (CRM 601). Although this procedure offers a means to ensure the comparability of data in this field, some difficulties concerning the interlaboratory reproducibility still remain, and a new project is currently being conducted to determine the causes of poor reproducibility in the extraction scheme. The final objective of the project is the certification of new sediment and soil reference materials for their extractable contents of Cd, Cr, Cu, Ni, Pb and Zn. This paper presents the results of a small-scale interlaboratory study, which aimed to test a revised version of the extraction schemes by comparing the original and the modified protocols using the CRM 601 sample. This work offers an improvement to the BCR sequential extraction procedure through intercomparison exercises. This improved procedure will allow the obtaining of CRMs to validate analytical data in the analysis of soils and sediments, and it will also facilitate comparability of data in the European Union.

Malignant fibrous histiocytoma of the scalp. Multidisciplinary treatment.

BACKGROUND: Malignant fibrous histiocytomas (MFH) are uncommon in the skin, and even less frequent on the scalp. On the scalp they are often very difficult to excise and it is even more difficult to close the resulting wound. OBJECTIVE: To review all malignant fibrous histiocytomas diagnosed and treated in our Department during the past 6 years, and to describe the multidisciplinary procedure employed to treat one special case of aggressive malignant fibrous histiocytoma on the scalp that recurred twice. RESULT: Malignant fibrous histiocytomas represent 0.01% of malignant cutaneous tumors in our area. The immediate results after a multidisciplinary treatment performed on a recurrent malignant fibrous histiocytoma located on the scalp were excellent, but recurrence was observed 6 months later. Two years later we have also treated another case of MFH on the scalp. The same surgical technique was performed, but the patient received high-dose-methotrexate-based neoadjuvant chemotherapy (HD-MTX). One year later, this patient is still alive and no signs of recurrence have been detected. CONCLUSION: When malignant fibrous histiocytoma occurs on the scalp it must be treated immediately by means of an excision with a large peripheral edge of 2 cm from the visual or CAT limits of the lesion, since the first treatment must be definitive.