Miocardiopatía no compactada / Non-compaction cardiomyopathy

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Processed meat consumption and risk of cancer: a multisite case-control study in Uruguay.

BACKGROUND: The role of processed meat in the aetiology of several cancers was explored in detail. METHODS: In the time period 1996-2004, a multisite case-control study was conducted in Montevideo, Uruguay. The study included 6 060 participants (3 528 cases and 2 532 controls) corresponding to cancers of the oral cavity, pharynx, oesophagus, stomach, colon, rectum, larynx, lung, female breast, prostate, urinary bladder, and kidney (renal cell carcinoma only). RESULTS: The highest odds ratios (ORs) were positively associated with cancers of the colon, rectum, stomach, oesophagus, and lung. With the exception of renal cell carcinoma, the remaining cancer sites were significantly associated with elevated risks for processed meat consumption. Furthermore, mortadella, salami, hot dog, ham, and salted meat were strongly associated with risk of several cancer sites. CONCLUSION: It could be concluded that processed meat intake could be a powerful multiorgan carcinogen.

A novel flow injection chemiluminescence determination of Cr(VI) with Dichlorotris(1,10-phenanthroline)ruthenium(II).

A selective novel reverse flow injection system with chemiluminescence detection (rFI-CL) for the determination of Cr(VI) in presence of Cr(III) with Dichlorotris (1,10-phenanthroline)ruthenium(II), (Ru(phen)(3)Cl(2)), is described in this work. This new method is based on the oxidation capacity of Cr(VI) in H(2)SO(4) media. First, the Ruthenium(II) complex is oxidized to Ruthenium(III) complex by Cr(VI) and afterwards it is reduced to the excited state of the Ruthenium(II) complex by a sodium oxalate solution, emitting light inside the detector. The intensity of chemiluminescence (CL) is proportional to the concentration of Cr(VI) and, under optimum conditions, it can be determined over the range of 3-300 µg L(-1) with a detection limit of 0.9 µg L(-1). The RSD was 8.4% and 1.5% at 5 and 50 µg L(-1), respectively. For the rFI-CL method various analytical parameters were optimized: flow rate (1 mL min(-1)), H(2)SO(4) carrier concentration (20% w/V), Ru(phen)(3)Cl(2) concentration (5mM) and sodium oxalate concentration (0.1M). The effect of Cr(III), Fe(III), Al(III), Cd(II), Zn(II), Hg(II), Pb(II), Ca(II) and Mg(II), was studied. The method is highly sensitive and selective, allowing a fast, on-line determination of Cr(VI) in the presence of Cr(III). Finally, the method was tested in four different water samples (tap, reservoir, well and mineral), with good recovery percentage.

Bone fractures after cardiac transplantation.

OBJECTIVE: Bone loss and bone fractures are disabling complications after heart transplantation. Severe bone loss happens mainly during the first year posttransplantation. Steroids and cyclosporine alter bone metabolism in several ways. To counterbalance these effects, antiresorptive therapy is provided to these patients. The objective of this study was to assess the frequency of bone fractures after heart transplantation, considering previous comorbidities, immunosuppressive therapy, and osteoprotective treatment. METHODS: From 1993 to 2005, 443 consecutive heart transplant recipients were followed for the occurrence of bone fractures, immunosuppressive therapy, clinical conditions, and antiresorptive treatment. RESULTS: There were 41 fractures in 34 patients (7.6%, group I). The remainder of patients formed group II. Fractures commonly involved the lumbar spine. Postmenopausal women had more fractures than other patients (20.6% vs 7.8%, P = .02). When the initial immunosuppressive regimen included tacrolimus, fractures did not happen (P = .01, vs other regimens). Osteoprotective therapy was administered to 91.2% of patients in group I and 79% in group II (P = .08). Mean interval from transplantation to the first fracture was 1131.5 days. Overweight patients had a 61.8% incidence of fracture. CONCLUSIONS: Our series showed a low frequency of bone fractures. Postmenopausal women and overweight patients had more fractures. An initial immunosuppressive regimen using tacrolimus was associated with lower fracture rates.

Psychometric field study of the new haemophilia quality of life questionnaire for adults: the 'Hemofilia-QoL'.

Although there is a worldwide interest in the assessment of health-related quality-of-life (HRQoL) in haemophilia patients, no non-disease specific instruments (for adults) are readily available. In this paper, a haemophilia-specific quality-of-life assessment measure for adults (the Hemofilia-QoL questionnaire) has been developed and tested for psychometric properties in 121 adults with haemophilia living in Spain. The Hemofilia-QoL questionnaire is a self-report modular instrument that assesses nine relevant HRQoL domains for patients with haemophilia (e.g. physical health, daily activities, joint damage, pain, treatment satisfaction, treatment difficulties, emotional functioning, mental health, relationships and social activity). Psychometric examination involved the assessment of data quality, scaling assumptions, reliability (internal consistency and test-retest) and validity (concurrent; external clinical criterion and sensitivity). The Hemofilia-QoL 36-item version questionnaire had acceptable internal consistency and retest reliability values. The questionnaire shows excellent concurrent validity (with the SF-36 Health Survey) and external clinical criterion validity (haemophilia clinical status) and sensitivity (health status changes) as well. The Hemofilia-QoL is now available for adult assessment and is ready for use in clinical research in Spain.

Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia.

A haemophilia-specific health-related quality-of-life questionnaire (named 'Hemofilia-QoL') was developed to assess quality-of-life in adults with haemophilia, and was psychometrically tested. Seventy-three interviews with haemophilia patients and health care professionals were used to generate the items included in the questionnaire, and expert ratings on the items formulated were used to screen them for potential omission. This was followed by psychometric testing in a sample of 35 patients. Preliminary psychometric testing of the revised questionnaire version, which contains 10 domains (physical health, physical role, joint damage, pain, treatment satisfaction, emotional role, mental health, social support), showed acceptable reliability (alpha = 0.94 for the Hemofilia-QoL total score) and validity, and this will be examined in a subsequent study with a larger patient sample.

Frequency of HLA-DPB1 disparities detected by reference strand-mediated conformation analysis in HLA-A, -B, and -DRB1 matched siblings.

The role of HLA-DPB1 as transplantation antigen is controversial. The frequency and relevance of HLA-DPB1 mismatch in hematopoietic stem cell transplantation are unknown. To ascertain the rate of HLA-DBP1 mismatch in siblings that had been matched for HLA-A, -B, and -DRB1, reference strand mediated conformation analysis (RSCA) a high resolution HLA typing method was used. Locus-specific primers were used to amplify the HLA-DPB1 locus. The PCR product was then hybridized with two fluorescein-labeled references and the duplexes were analyzed after electrophoresis in a short polyacrylamide gel. Among the 113 pairs of individuals tested, six HLA-DPB1 mismatches were identified, which corresponds to a frequency of 5.31 % (95% confidence interval 3.20%-7.42 %).

Individually adjusted prophylactic donor lymphocyte infusions after CD34-selected allogeneic peripheral blood stem cell transplantation.

T cell depletion of the graft increases graft failure and relapse rate in allogeneic PBSC transplantation. Delayed lymphocyte add-back after T cell-depleted transplants might prevent these complications. We present 22 consecutive allogeneic PBSC transplants from related histocompatible donors with positive selection of CD34+ cells. Recipients received prophylactic donor lymphocyte infusions (DLI) depending on their risk of relapse and of developing GVHD. Patients were considered at high risk of relapse with AML > first CR, ALL > second CR, and CML in accelerated or blastic phase. Patients were considered at high risk of developing GVHD if older than 35 years, or with a donor sensitized through previous pregnancy or blood transfusion. Patients at high risk of relapse and low risk of GVHD were scheduled to receive three DLI. Patients at low risk of relapse and high risk of GVHD did not receive DLI. The remaining patients were scheduled to receive two DLI. The DLI were administered on days +28 (2 x 10(5)/kg), +60 (2 x 10(5)/kg) and +90 (2 x 10(6)/kg) after transplant. G-CSF mobilized peripheral stem cells from healthy donors were positively selected by an immunomagnetic method. The mean CD34+ cells and CD3+ cells infused were 4.4 x 10(6)(range 1.9-10.6) and 0.085 x 10(5) (range 0.01-0.67). Cyclosporin A was given to prevent GVHD. All the patients engrafted. Twenty-two prophylactic DLI were performed in 12 patients: seven developed acute GVHD (one case grade III-IV) and none presented pancytopenia. At a mean follow-up of 585 days (range 89-1103), 14 patients were alive in CR, one patient was alive in relapse, four patients had died of relapse and three had died of transplant-related complication. Individually adjusted prophylactic DLI at the doses we used with an escalating schedule allowed an acceptable GVHD rate and a good engraftment of donor hematopoiesis.

Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation.

Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient-donor pairs mismatched for HA-1 antigen (15.8%). Grades II-IV acute GvHD occurred in 51.6% of the HA-1-mismatched pairs compared with 37.1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0.035, OR: 2.96, 95% CI: 1.07-8.14). No differences were observed between the two groups for grades III-IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.

El antígeno menor de histocompatibilidad HA-1 / The HA-1 minor histocompatibility antigen

Los antígenos menores de histocompatibilidad (mHAgs) son péptidos inmunogénicos procedentes de proteínas celulares polimórficas asociados a moléculas del complejo mayor de histocompatibilidad (MHC) de clase I o de clase II. Las disparidades en estos mHAgs entre donante y receptor de un transplante alogénico de progenitores hematopoyéticos (TPH) a partir de donante emparentado MHC idéntico están relacionadas con reacciones inmunes adversas del tipo enfermedad de injerto contra huésped (EICH) o rechazo del injerto. El mHAg HA-1 fue el primer antígeno menor no codificado por el cromosoma Y identificado por métodos celulares .Posteriores publicaciones establecieron su comportamiento inmunodominante en el contexto de TPH a partir de donante emparentado MHC idéntico. En el presente trabajo revisamos diferentes aspectos del mHAg HA-1, tales como estudios bioquímicos y genéticos, métodos de biología molecular para la asignación alélica y posibles aplicaciones clínicas (AU)

HLA-B44 subtyping in the Catalan population using reference strand mediated conformation analysis. Implications for the selection of unrelated bone marrow donors.

Cytotoxic T lymphocytes (CTLs) reactive against the disparity between HLA-B*4402 and HLA-B*4403 have been reported after unrelated donor bone marrow transplantation. These CTLs have been associated with acute graft-versus-host disease and graft rejection. This study describes the HLA-B44-subtyping in the Catalan population using reference-strand mediated conformation analysis. It has been performed on 297 unrelated HLA-B44+ cord blood units from the Barcelona Cord Blood Bank (Barcelona, Spain). We have found a predominance of HLA-B*4403 (66.04%) over HLA-B*4402 (33.02%), whereas the predominant HLA-B44 allele in Northern Europe and the United States is HLA-B*4402. This inverted proportion between HLA-B44 subtypes in Mediterranean populations compared with other Caucasian populations suggests that HLA-B44 subtyping should be performed when an HLA-B44+ unrelated donor marrow is identified.

Genomic typing of minor histocompatibility antigen HA-1 by reference strand mediated conformation analysis (RSCA).

Disparities in minor histocompatibility antigen (mHAg) HA-1 are involved in the development of acute graft-versus-host disease (GvHD) in adult recipient after HLA-identical sibling donor hematopoietic stem cell transplantation. The mHAg HA-1 is an HLA-A*0201-restricted nonapeptide, which derives from the cleavage of a protein encoded at chromosome 19. The sequence analysis of HA-1 cDNA identified two alleles, termed HA-1H and HA-1R, which differ in only two nucleotides at 3' end of exon A, at positions 500 and 504. DNA-based methods for HA-1 typing were developed in 1998, using polymerase chain reaction with sequence-specific primers (PCR-SSP) and restriction fragment length polymorphism (PCR-RFLP). Here, we report the usefulness of reference strand mediated conformation analysis (RSCA), which was developed for mutation detection and typing of polymorphic loci, to discriminate between the two HA-1 alleles. We performed genomic typing of HA-1 locus in 203 HLA-A*0201-positive samples using RSCA and we confirmed these results by PCR-SSP. The results demonstrate the high reproducibility of this method and their strong correlation with the results obtained by PCR-SSP (99%). Only two samples showed disparity between the RSCA typing and the PCR-SSP. Direct sequencing of these samples confirmed that the correct allele assignment was that obtained by the RSCA typing. Furthermore, HA-1- RSCA-based typing provides additional information about the intronic structure of both alleles. With this approach, we describe the almost constant presence (99.2%) of a 5-bp deletion at intronic position 214-218 associated to the HA-1H allele, previously unidentified. We conclude that HA-1 genomic typing by RSCA is easy to perform and that could be used as a routine typing method.

Follow-up of chimerism status after allogeneic HLA-mismatched stem cell transplantation by detection of non-shared HLA alleles.

BACKGROUND AND OBJECTIVES: Chimerism studies after allogeneic transplantation are usually performed using cytogenetic analysis, PCR-VNTR or PCR-STR. Here, we report an alternative method for following the chimerism status after an HLA-mismatched stem cell transplantation (SCT), detecting the presence of non-shared HLA alleles by reference-strand mediated conformation analysis (RSCA). DESIGN AND METHODS: We tested this new approach on allogeneic related haploidentical SCT, unrelated cord blood transplantation, and HLA-mismatched unrelated donor SCT. The quantification of the chimerism was performed by laser detection of fluorescent-labeled primers on an automated DNA sequencer. RESULTS: In all cases this technique was able to detect mixed chimeras. The technique detected above 5% of residual cells when the analysis was based on HLA-class I and above 3% for HLA-class II. This sensitivity is similar to that of the PCR-VNTR analysis. INTERPRETATION AND CONCLUSIONS: This method avoids the need to search for an informative locus (which is essential for PCR-VNTR or -STR). Moreover, we did not find the phenomenon of preferential amplification that is observed with most VNTR, thus avoiding the need for construction of standard curves to quantify mixed chimeras. We conclude that the detection of the non-shared HLA alleles by RSCA is a useful approach for chimerism follow-up after HLA-mismatched SCT.

Preformulation study of the vaccine candidate P64k against Neisseria meningitidis.

We have previously isolated, cloned and expressed in Escherichia coli the lpdA gene coding for a high-molecular-mass protein (P64k) common to many meningococcal strains. P64k is an outer membrane lipoamide dehydrogenase that is highly immunogenic in animals. Here we describe a preformulation study of the recombinant protein as a vaccine candidate against Neisseria meningitidis, in which six variants containing the candidate were tested. Three assays were used to identify the most suitable variant for further evaluation: percentage of adsorption, identification of P64k by SDS/PAGE, and immunogenicity in mice. All the preformulation variants studied showed more than 98% of adsorption of P64k on the aluminium gel. After desorption, P64k was also identified by SDS/PAGE in the six preformulation variants. Seroconversion was attained in all groups analysed. On the basis of these results, the most effective variant consisted of 20 microg/ml P64k plus 0.5 mg/ml aluminium hydroxide.

Pathologic rupture of the spleen as the initial manifestation of acute lymphoblastic leukemia: an additional case.

Pathological rupture of the spleen (PRS) is a rare, but well known complication of some hematological malignancies. In a recent review of the literature, Giagounidis et al. Identified 136 cases of pathologic rupture of the spleen since 1861. This number gives an idea of how seldom it occurs. In this review, 34% of the cases had occurred in acute leukemias, and 13% in acute lymphoblastic leukemias. In most cases, PRS occurs on the course of the disease. PRS as initial manifestation of ALL is a very rare feature: only six cases have been reported in the literature. Before now, in our hospital, we had only seen one case of a patient suffering from chronic myelomonocytic leukemia who presented splenic rupture as the initial manifestation of this disease. We now describe the seventh case, to our knowledge, of acute lymphoblastic leukemia presenting as pathologic splenic rupture.

Hematopoietic cell transplantation using plasma and DMSO without HES, with non-programmed freezing by immersion in a methanol bath: results in 213 cases.

A simplified cryopreservation method for bone marrow (BM) and peripheral blood progenitor cells (PBPC) was utilized in hematopoietic cell transplantation of 213 patients with hematological or solid neoplasms after ablative chemotherapy (187 with peripheral blood progenitor cells and 26 with bone marrow). Cells were cryopreserved, after addition of autologous fresh plasma with DMSO, without HES, by freezing to -80 degrees C in a methanol bath and non-programmed freezer. For the patients autotransplanted with PBPC, the median period necessary for recovery of more than 0.5 x 10(9)/l granulocytes was 11 days (range 6-44), and 15 (8-204) days were required to obtain more than 20 x 10(9)/l platelets. For the patients autotransplanted with BM, the median period necessary to recover >0.5 x 10(9)/l granulocytes was 12 days (range 9-33), and 24 (12-57) days to obtain more than 20 x 10(9)/l platelets. These results support this method as being very effective in achieving high-quality cryopreservation. The procedure, which uses a non-programmed freezer, simplifies and reduces enormously the cost of the technical measures currently in use, enabling its adoption in almost any clinical oncological institution.

Haematopoietic transplantation in pulmonary alveolar proteinosis associated with chronic myelogenous leukaemia.

Pulmonary alveolar proteinosis (PAP) is a disease of unknown etiopathogenesis sometimes associated with malignant haematological disorders. The potential reversibility of the process in these cases seems to be related to recovery from the underlying disease. GM-CSF has acquired an important, potentially pathogenic role and BMT presents one therapeutic option effective in certain forms of human PAP. We present the case of a 43-year-old female patient with Ph+ CML. During pretransplantation evaluation, unexpected pulmonary infiltrates were noted in the chest X-ray, PAP being diagnosed on biopsy. In view of the progressive respiratory symptomatology and her CML being in accelerated phase, the patient underwent haematopoietic transplantation. She died on day +12 from invasive pulmonary aspergillosis before a response could be observed. Pathogenic implications in PAP and the role of haematopoietic transplantation in this disease are discussed.