Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis.

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants-SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters' SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers.

Acute paraplegia as a presentation of acute aortic occlusion.

Acute aortic occlusion is a rare life-threatening event. We present a case of a heavy smoking, 54-year-old man who was admitted in the emergency room with sudden paraplegia, associated to severe lower back and lower limbs pain. A neurologic examination showed paralysis of the lower limbs and cold lower extremities. The pedal and femoral pulses were absent. A computed tomography revealed occlusion of the mesenteric superior artery, abdominal aorta, and both iliac arteries. Despite medical treatment, the patient died before evaluation of vascular surgery. Paraplegia is a rare presentation of acute aortic occlusion and clinicians should be alert to make an early intervention.

Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α.

BACKGROUND: Tumor cells have evolved complex strategies to escape immune surveillance, a process which involves NK cells and T lymphocytes, and various immunological factors. Indeed, tumor cells recruit immunosuppressive cells [including regulatory T-cells (Treg), myeloid-derived suppressor cells (MDSC)] and express factors such as PD-L1. Molecularly targeted therapies, such as imatinib, have off-target effects that may influence immune function. Imatinib has been shown to modulate multiple cell types involved in anti-cancer immune surveillance, with potentially detrimental or favorable outcomes. Imatinib and other tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) have dramatically changed disease course. Our study aimed to characterize the different populations of the immune system in patients with CML affected by their treatment. METHODS: Forty-one patients with CML [33 treated with TKIs and 8 with TKIs plus interferon (IFN)-α] and 20 controls were enrolled in the present study. Peripheral blood populations of the immune system [referred to as the overview of immune system (OVIS) panel, Treg cells and MDSCs] and PD-1 expression were evaluated by flow cytometry. The immunological profile was assessed using the mRNA Pan-Cancer Immune Profiling Panel and a NanoString nCounter FLEX platform. RESULTS: Patients receiving combination therapy (TKIs + IFN-α) had lower numbers of lymphocytes, particularly T cells [838/µL (95% CI 594-1182)] compared with healthy controls [1500/µL (95% CI 1207 - 1865), p = 0.017]. These patients also had a higher percentage of Treg (9.1%) and CD4+PD-1+ cells (1.65%) compared with controls [Treg (6.1%) and CD4+/PD-1+(0.8%); p ≤ 0.05]. Moreover, patients treated with TKIs had more Mo-MDSCs (12.7%) whereas those treated with TKIs + IFN-α had more Gr-MDSC (21.3%) compared to controls [Mo-MDSC (11.4%) and Gr-MDSC (8.48%); p ≤ 0.05]. CD56bright NK cells, a cell subset endowed with immune-regulatory properties, were increased in patients receiving TKIs plus IFN-α compared with those treated with TKIs alone. Interestingly, serum IL-21 was significantly lower in the TKIs plus IFN-α cohort. Within the group of patients treated with TKI monotherapy, we observed that individuals receiving 2nd generation TKIs had lower percentages of CD4+ Treg (3.63%) and Gr-MDSC (4.2%) compared to patients under imatinib treatment (CD4+ Treg 6.18% and Gr-MDSC 8.2%), but higher levels of PD-1-co-expressing CD4+ cells (1.92%). CONCLUSIONS: Our results suggest that TKIs in combination with IFN-α may promote an enhanced immune suppressive state.

Pregnancy in renal transplant patients: Renal function markers and maternal-fetal outcomes.

OBJECTIVES: We aimed to evaluate laboratory markers in women who got pregnant after renal transplantation. STUDY DESIGN: Cross-sectional prospective study. MAIN OUTCOME MEASURES: Renal function parameters and maternal and fetal data were assessed in renal transplant recipients. RESULTS: Forty-three women who got pregnant after renal transplantation (mean age, 28.5 years; mean gestational age, 35.6 weeks) were included. Most patients (53.5%) received a renal transplant from a deceased donor. Podocyturia was not significantly correlated with other renal function markers. Mean period from transplantation to pregnancy was approximately 5 years; this period was not associated with obstetric complications or changes in renal markers. A gradual increase was observed in the following parameters during pregnancy and puerperium: serum creatinine levels (P < 0.001), proteinuria (P < 0.001), urinary protein/creatinine ratio (P < 0.001), and albumin/creatinine ratio (P < 0.001). The sensitivity and specificity of protein/creatinine ratio in predicting preeclampsia were high (96.0% and 94.0%, respectively). Elevated serum creatinine levels, urinary albumin/creatinine ratio, and retinol-binding protein levels in the third trimester were associated with prematurity (P < 0.001). Preeclampsia was the main cause of renal function decline at the end of pregnancy (65.0% of cases). Approximately four (9.5%) pregnant women presented with premature rupture of membranes and 18 (42.0%) with a urinary tract infection. CONCLUSIONS: Proteinuria, urinary protein/creatinine ratio, and retinol-binding protein levels were elevated in patients with preeclampsia. Using these markers to assess renal function during pregnancy may be clinically useful for detecting and monitoring renal injury in renal transplant recipients.

Quisto mesentérico ­ uma raridade / Mesenteric cyst ­ a rarity

Os quistos mesentéricos são tumores intra-abdominais raros, com uma incidência descrita de 1/100 000 a 1/250 000 admissões hospitalares por dor abdominal. Localizam-se no mesentério do duodeno ao reto, principalmente no íleo. Os sintomas associados a estas massas não são específicos e a maioria dos casos são assintomáticos, sendo descobertos incidentalmente por exames de imagem ou durante exploração cirúrgica abdominal. O tratamento consiste na excisão cirúrgica e o diagnóstico é histológico. Apresenta-se o caso de um homem de 92 anos, internado num Serviço de Medicina Interna, que realizou uma angiotomografia axial computorizada abdominal que permitiu visualizar em localização sub-hepática uma lesão quística compatível com um quisto entérico de grandes dimensões constituído por 2 locas, sem comunicação, separadas pela vesícula biliar.

Mesenteric cysts are rare intra-abdominal tumors, with a reported incidence of 1/100 000 to 1/250 000 hospital admissions. They are located in the mesentery from duodenum to rectum, mainly in the ileum. The symptoms associated aren't specific and most cases are asymptomatic, being discovered incidentally during imaging tests or abdominal surgery. The treatment is the xcision of the cyst and the diagnosis is histological. We describe a case of a 92 years old man, admitted to the internal medicine service, which performed a computed tomography angiography that showed an infra hepatic cyst lesion compatible with an enteric multi-locular cyst, divided by the gallbladder.

Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.

[Serum Erythropoietin as Prognostic Marker in Myelodysplastic Syndromes]. / Eritropoietina Sérica como Marcador Prognóstico em Síndrome Mielodisplásica.

INTRODUCTION: This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and 2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System. MATERIAL AND METHODS: Our aim was to analyze serum's erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology. RESULTS: Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q- syndrome (p < 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p < 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum erythropoietin is an independent survival predictor (p < 0.001). DISCUSSION: Serum erythropoietin is a predictive factor for response to therapy with subcutaneous erythropoietin, and patients with myelodysplastic syndromes with higher values of erythropoietin have poorer response to administration of erythropoietin even at higher doses. Our sample shows that serum erythropoietin also has prognostic value, and in all myelodysplastic syndromes subtypes. Moreover, alone or in combination with other factors or prognostic indices, erythropoietin may enhance the prognostic indices such as the International Prognostic Scoring System, since high levels are associated with progression to acute leukemia and hence lower survival. CONCLUSION: This study suggests that increased erythropoietin levels at diagnosis can by itself be a poor prognosis factor inmyelodysplastic syndromes patients, with higher values in patients with progression to acute leukaemia and decreased overall survival.

Introdução: A síndrome mielodisplásica é uma doença heterogénea caracterizada por displasia, medula hipercelular, citopenias e risco de evolução para leucemia aguda. Outros factores de prognóstico, nomeadamente, fibrose medular, elevação da enzima desidrogenase do lactato e 2-microglobulina têm sido descritos, contudo, a decisão terapêutica baseia-se no score do International Prognostic Scoring System. Material e Métodos: Este trabalho teve como objectivo analisar a relevãncia da eritropoietina sérica ao diagnóstico, em doentes com síndrome mielodisplásica de novo, avaliando o seu impacto na sobrevivência global e a sua implementação como factor de prognóstico. Recolhemos dados clínicos e laboratoriais de 102 doentes com síndrome mielodisplásica de novo diagnosticada entre outubro/2009 e março/2014. A análise de sobrevivência foi efectuada recorrendo à metodologia de Kaplan-Meier, de acordo com os valores de eritropoietina. Resultados: A amostra, de 102 doentes, apresenta uma mediana de idades de 74 anos e relação masculino/feminino igual a 0,8. Os doentes com o subtipo citopenia refratária com displasia unilinha apresentam, em média, valores de eritropoietina significativamente mais baixos, em oposição aos doentes com o subtipo 5q- que apresentam a média de eritropoietina sérica mais elevada (p < 0,05). Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001). Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcut'nea, sendo que os doentes com síndrome mielodisplásica com valores mais elevados de eritropoietina apresentam uma pior resposta à administração de eritropoietina, mesmo com doses mais elevadas. A nossa amostra demonstra que a eritropoietina sérica apresenta também valor prognóstico, e em todos os subtipos de síndrome mielodisplásica. Além disso, isoladamente ou em associação com outros factores ou índices de prognóstico, poderá melhorar o valor prognóstico de índices como o International Prognostic Scoring System, uma vez que valores elevados de eritropoietina estão associados a progressão para leucemia aguda e, consequentemente, a menor sobrevivência.Conclusão: Os resultados sugerem que o aumento dos níveis séricos de eritropoietina ao diagnóstico pode constituir um factor de mau prognóstico em doentes com síndrome mielodisplásica, associando-se a maior risco de evolução para leucemia aguda e menor sobrevivência global.

Pursuing type 1 diabetes mellitus and related complications through urinary proteomics.

Diabetes mellitus is a chronic metabolic disease with multiple complications, and its successful management requires early diagnosis, to allow timely interventions. Here, we have comprehensively analyzed the proteome changes in urine of type 1 diabetic subjects with and without complications such as retinopathy and nephropathy. gel electrophoresis combined to liquid chromatography-tandem mass spectrometry (GeLC-MS/MS) analysis of midstream urine highlighted the mechanisms involved in disease pathogenesis as, for instance wound healing and blood coagulation in all diabetics or altered ganglioside metabolism in retinopathy, and also some urinary proteins with potential diagnosis value. From these, gelsolin and antithrombin-III appear as promising diagnosis markers for type 1 diabetes mellitus (T1DM), whereas ephrin type-B receptor 4 and vitamin K-dependent protein Z seem to be promising markers for advanced T1DM disease state presenting retinopathy and nephropathy (T1DM-R + N). Data also suggest urinary ganglioside GM2 activator and beta-hexosaminidase subunit beta as potential urinary markers of retinopathy in diabetics. Taken together, the present exploratory urinary proteomic analysis might be seen as an important starting point for studies targeting specific urinary proteins aimed at the implementation of new biomarkers for the early detection of T1DM-related microvascular complications.

Salivary proteome and peptidome profiling in type 1 diabetes mellitus using a quantitative approach.

In the present study, we applied iTRAQ-based quantitative approach to explore the salivary proteome and peptidome profile in selected subjects with type 1 diabetes, with and without microvascular complications, aiming to identify disease-related markers. From a total of 434 distinct proteins, bactericidal/permeability-increasing protein-like 1 and pancreatic adenocarcinoma up-regulated factor were found in higher levels in the saliva of all patients while increased content of other proteins like alpha-2-macroglobulin, defensin alpha 3 neutrophil-specific, leukocyte elastase inhibitor, matrix metalloproteinase-9, neutrophil elastase, plastin-2, protein S100-A8 and protein S100-A9 were related with microvascular complications as retinopathy and nephropathy. Protein-protein interaction network analysis suggests the functional clusters defense, inflammation and response to wounding as the most significantly associated with type 1 diabetes pathogenesis. Peptidome data not only support a diabetes-related higher susceptibility of salivary proteins to proteolysis (mainly of aPRP, bPRP1 and bPRP2), but also evidenced an increased content of some specific protein fragments known to be related with bacterial attachment and the accumulation of phosphopeptides involved in tooth protection. Overall, the salivary protein and peptide profile highlights the importance of the innate immune system in the pathogenesis of type 1 diabetes mellitus and related complications. This study provides an integrated perspective of salivary proteome and peptidome that should be further explored in future studies targeting specific disease markers.

Race adjustment for estimating glomerular filtration rate is not always necessary.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is very important in clinical practice, although it is not adequately tested in different populations. We aimed at establishing the best eGFR formulas for a Brazilian population with emphasis on the need for race correction. METHODS: We evaluated 202 individuals with chronic kidney disease (CKD) and 42 without previously known renal lesions that were additionally screened by urinalysis. Serum creatinine and plasma clearance of iohexol were measured in all cases. GFR was estimated by the Mayo Clinic, abbreviated Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, and creatinine clearance was estimated by the Cockcroft-Gault (CG) formula. Plasma clearance of iohexol was used as the gold standard for GFR determination and for the development of a Brazilian formula (BreGFR). RESULTS: Measured and estimated GFR were compared in 244 individuals, 57% female, with a mean age of 41 years (range 18-82). Estimates of intraclass correlation coefficients among the plasma clearance of iohexol and eGFR formulas were all significant (p < 0.001) and corresponded to the following scores: CG 0.730; obesity-adjusted CG 0.789; Mayo Clinic 0.804; MDRD 0.848; MDRD1 (without race adjustment) 0.846; CKD-EPI 0.869; CKD-EPI1 (without race adjustment) 0.876, and BreGFR 0.844. CONCLUSIONS: All cited eGFR formulas showed a good correlation with the plasma clearance of iohexol in the healthy and diseased conditions. The formulas that best detected reduced eGFR were the BreGFR, CKD-EPI, and CKD-EPI1 formulas. Notably, the race correction included in the MDRD and CKD-EPI formulas was not necessary for this population, as it did not contribute to more accurate results.

Protease profiling of different biofluids in type 1 diabetes mellitus.

OBJECTIVES: We aimed to disclose the proteolytic events underlying type 1 diabetes and related complication through protease profiling in the bodily fluids serum, urine and saliva. DESIGN AND METHODS: Zymography followed by LC-MS/MS was performed for protease identification and quantitative comparison of proteolytic activity between healthy, type 1 diabetic patients with no complications and with retinopathy and nephropathy. Western blotting was also accomplished for MMP-9 and MMP-2 identification and expression analysis. RESULTS: Only MMP-2 and MMP-9 were observed in serum with significantly increased levels and activity observed in diabetic patients. In urine and saliva other proteases besides MMPs were identified by MS and presented disease-dependent activity variations. Among these are complex MMP-9/Neutrophil gelatinase-associated lipocalin, aminopeptidase N, azurocidin and kallikrein 1 with more activity noticed in type 1 diabetes patients with nephropathy and/or retinopathy. CONCLUSION: Our data highlight the usefulness of urine and saliva for the monitoring of type-1 diabetes-related proteolytic events, where aminopeptidase N, azurocidin and kallikrein 1 appear as promising screening targets for type 1 diabetes-related complications.

Spontaneous pneumomediastinum: case report.

OBJECTIVE: The description of this case is due to the rarity of this clinical entity and its semiotic diversity, which implies a high level of suspicion for a correct diagnosis. METHODS: Description of a clinical case, based on the data referred to in the clinical process. RESULTS: The case describes a young male patient, attended to at the emergency room due to right chest pain, which further investigation revealed to be consistent with spontaneous pneumomediastinum. He underwent medical treatment, with favorable outcome. CONCLUSION: The clinical course is usually benign, self-limited, involves only conservative treatment, and use of drugs is recommended only in symptomatic patients.

Pneumomediastino espontâneo: relato de um caso / Spontaneous pneumomediastinum: case report

OBJETIVO: A descrição deste caso é motivada pela não frequência desta entidade clínica e sua diversidade semiológica, o que implica elevado nível de suspeição para o diagnóstico correto. MÉTODOS: Descrição de um caso clínico, com base nos dados referidos no processo clínico. RESULTADO: O caso refere-se a um jovem do sexo masculino, observado no serviço de urgência por apresentar dor torácica à direita, cuja investigação complementar foi compatível com pneumomediastino espontâneo. Ele, então, foi submetido a terapêutica médica, com evolução favorável. CONCLUSÃO: Habitualmente o curso clínico é benigno, autolimitado, o que implica em apenas um tratamento conservador, sendo o uso de fármacos recomendado somente nos doentes sintomáticos.

OBJECTIVE: The description of this case is due to the rarity of this clinical entity and its semiotic diversity, which implies a high level of suspicion for a correct diagnosis. METHODS: Description of a clinical case, based on the data referred to in the clinical process. RESULTS: The case describes a young male patient, attended to at the emergency room due to right chest pain, which further investigation revealed to be consistent with spontaneous pneumomediastinum. He underwent medical treatment, with favorable outcome. CONCLUSION: The clinical course is usually benign, self-limited, involves only conservative treatment, and use of drugs is recommended only in symptomatic patients.

A possible role for oxidation stress in lymphoid leukaemias and therapeutic failure.

The aim of this study was to evaluate the role of oxidative stress in the pathobiology of lymphoid leukaemias and its involvement in leukaemic relapse. For this purpose the generation of peroxides by mononuclear cells, the erythrocyte activity of superoxide-dismutase (SOD) and glutathione peroxidase (GL-PX), and the plasma levels of reduced glutathione (GSH) and vitamin E (VIT E) were determined in 52 patients with two different types of lymphoid leukaemias, chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL), 36 prior to chemotherapy and 16 treated patients. A decrease in SOD and GL-PX activities was observed in ALL patients prior to therapy, while a decrease in GSH and VIT E plasma levels was observed in untreated CLL, as compared to age-matched controls. An increase in peroxides formation occurred in both types of leukaemia, as compared to age-matched controls. There are significant differences for GSH, VIT E and peroxides generation between the different types of leukaemias. In relapsed ALL patients a decrease in peroxides generation was observed which may be due to the increase of the non-enzymatic defences GSH and VIT E. These data suggest the involvement of oxidative stress in acute and chronic lymphoid leukaemias and leukaemic relapse.

Incidência de parasitos da família Anisakidae em bacalhau (Gadus morhua) comercializado no Estado de Säo Paulo / Incidence of Anisakidae (Gadus morhua) parasites in the cod fish marketed in the State of Säo Paulo

Vermes da família Anisakidae säo nematóides parasitas do aparelho gástrico de mamíferos marinhos como focas, baleias e golfinhos. Larvas destes parasitas säo encontradas freguentemente em carne de salmäo, bacalhau, arenque, atum, hadoque, linguado (hospedeiros intermediários). A infecçäo humana resulta do hábito do homen se alimentar com peixe cru, insuficientemente cozido, congelado, salgado ou defumado, contendo larvas infectantes vivas do nematóide. As espécies mais comumente envolvidas na infecçäo humana säo Anisakis simplex e Pseudoterranova decipiens. O objetivo deste trabalho é registrar a ocorrência de larvas da família Anisakidae em bacalhau comercializado no Estado de Säo Paulo. Foram analisadas 22 amostras de bacalhau importado, provenientes da Delegacia do Consumidor (Decon), do Centro de Vigilância Sanitária do Estado de Säo Paulo e de empresas particulares, entre dezembro de 1997 e dezembro de 1998. Foram encontrados nematóides em 9 das amostras analisadas 40,19(por cento) sendo que 6 27,27(por cento) pertencem à família Anisakidae, gêneros Anisakis e Pseudoterranova. Os autores alertam as autoridades sobre a possibilidade desta infecçäo ocorrer devido ao aumento de consumo de sushi e sashimi. (AU)

Anisakid nematode parasites are adult worms that feed in the gastric tract of amphibians, areptiles, birds and mammals (whales and dolphins). Sea foods are the principal sources of human infections with these larval worms. These parasites are known to occur frequently in the flesh of cod, haddock, fluke, pacific salmon, herring, flounder, and monkfish.The disease is transmitted by raw, undercooked or insufficiently frozen fish and shellfish, and its incidence is expected to increase with the increase in the number of sushi and sashimi bars. The survey of cod marketed in the State of São Paulo is probably the first to be reported. This work deals with a parasitological survey of Anisakis from 22 samples. 9 (40,9%) were infected with nematodes, 6 of which (27,3%) belonged to the anisakidae family. Larve from two genera, Anisakis and Pseudoterranova, of the family Anisakidae, have been definitely identified from human cases. Although anisakiasis is not a major public health problem, there is a need for regulation in the fish industry and for consumer information. (AU)

Eumicetoma podal por Acremonium kiliense: registro de um caso / Podalic eumycotic mycetoma caused by Acremonium kiliense: report of one case

Os autores registram um caso de eumicetoma de gräos branco-amarelados, em paciente do sexo masculino, procedente da Bahia, com lesöes no pé esquerdo, provocadas por Acremonium kiliense (Grütz, 1925). O exame histopatológico näo demonstrou a presença de gräos, revelados, todavia, ao exame "a fresco", todos eles com estrutura de eumicetos. Discreta regressäo do quadro inflamatório com o uso de itraconazol, após tratamento prolongado