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Background: Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. Case description: A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. Discussion: The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. Conclusion: We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement. LEARNING POINTS: Hypertrophic pachymeningitis (HP) has several aetiologies; if the systemic investigation is not contributory to a diagnosis, a meningeal biopsy is necessary.This is the first case report of HP, associated with eosinophilic granulomatosis with polyangiitis (EGPA), and ANCA-negative serology.EGPA is probably a spectrum of diseases with predominant systemic involvement, but there may be cases where there is histological evidence, without the systemic context or positive serology.
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Abstract Objective: To determine the frequency of non-alcoholic fatty liver in individuals with not known history of liver disease, who died instantly in a traffic accident. Materials and Methods: It was a prospective and cross-sectional study of a series of autopsy cases, with a convenience sample obtained from the forensic medical service in the municipality of Boca del Río, Mexico, during the period from January to December 2016. The variables studied included age, sex, weight, height, abdominal circumference, thickness of the adipose panicle, cause of death and findings of liver biopsy. Results: A 78.1% of the 32 cases studied were men. The average age was 48 years old (range 20-80 years old). The body mass index range was 17-33. 34% of the cases had fatty liver. 27.3% of cases with fatty liver had a normal body mass index. Conclusions: This postmortem study showed a higher frequency of asymptomatic hepatic steatosis than previously reported in the Mexican population. It is necessary to establish timely national measures to detect and to prevent complications of this disease.
Resumen Objetivo: Determinar la frecuencia de hígado graso no alcohólico en individuos sin antecedentes conocidos de enfermedad hepática, que murieron instantáneamente en un accidente de tráfico. Materiales y Métodos: Fue un estudio prospectivo y transversal, de una serie de casos de autopsia, con una muestra por conveniencia obtenida en el servicio médico forense en el municipio de Boca del Río, México, durante el período de enero a diciembre de 2016. Las variables estudiadas incluyeron edad, sexo, peso, altura, perímetro abdominal, grosor del panículo adiposo, causa de muerte y hallazgos de la biopsia hepática. Resultados: De los 32 casos estudiados, el 78,1% eran hombres. La edad promedio fue de 48 años (rango 20-80 años). El rango del índice de masa corporal fue de 17-33. Un 34% de los casos tenían hígado graso. El 27.3% de los casos con hígado graso tenían un índice de masa corporal normal. Conclusiones: Este estudio postmortem mostró una frecuencia más alta de esteatosis hepática asintomática que la reportada previamente en la población mexicana. Es necesario establecer medidas nacionales oportunas para detectar y prevenir complicaciones de esta enfermedad.
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BACKGROUND: Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. METHODS: DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy-Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. RESULTS: We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13-3.51, TT vs. GG; OR, 1.53; 95% CI 1.12-2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. CONCLUSIONS: Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.
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Adiponectina/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Índice de Massa Corporal , Neoplasias da Mama/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , México , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Germline mutations in E-cadherin (CDH1) gene are associated with autosomal-dominantly inherited cancer syndrome characterized by diffuse gastric cancer, lobular breast cancer, and in some families, cleft lip/palate. However, there may be generations in which these neoplasms do not occur at all in a family and later on, one or another carcinoma arises, which makes it difficult for physicians to think about hereditary origin. METHODS: We report the first Mexican family with CDH1 mutation (variant c.377del). RESULTS: An asymptomatic young woman underwent a search for mutations in susceptibility genes for breast cancer due to the history of this neoplasm in her mother and maternal aunt. A CDH1 mutation was detected. After an endoscopy, a diffuse gastric carcinoma was found. Later on, three generations of this family were studied. The findings are presented. CONCLUSION: Medical communities should be aware of the contribution of this gene in the development of hereditary diffuse gastric carcinoma (HDGC) and breast cancer.
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Antígenos CD/genética , Neoplasias da Mama/genética , Caderinas/genética , Carcinoma/genética , Deleção de Genes , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Linhagem , Neoplasias Gástricas/patologiaRESUMO
The population that lives in areas where organochlorine pesticides were spread in the past is still exposed to them through contaminated food, particulate matter, and vapors. Due to their lipophilic properties and resistance to metabolic reactions, they accumulate in tissues and fluids rich in lipids. The aim of the study was to monitor the concentrations of organochlorine pesticides in forensic adipose tissue samples of adult inhabitants of Veracruz City, Mexico, and compare their time trend levels from 1988 to 2014. During the study, hexachlorobenzene (HCB); lindane; ß-hexachorocyclohexane; p,p'-dichlorodiphenyldichloroethylene (pp'DDE); p,p'-dichlorodiphenyldichloroethane (p,p'-DDT); and o,p'-dichlorodiphenyldichloroethane (o,p'-DDT) were determined. Our survey was divided into two periods: first, from the years 1988 to 1999, during which DDT was allowed to fight malaria and dengue vectors and the second from the years 2001 to 2014, after the DDT ban. A total of 1435 samples were analyzed. There were substantial differences in the forecasted time trend values of p,p'-DDE and p,p'-DDT in human adipose tissue samples in the two different periods. During the first period, p,p'-DDE decrease time trend was 1.198 mg/kg on lipid base per year; for the second one, decrease was 0.128 mg/kg on lipid base per year. p,p'-DDT decreased 0.507 mg/kg on lipid base during the first period and 0.039 mg/kg on lipid base for the second. The different concentrations may be explained by the cessation of fresh exposure after the first period and a more equilibrated decontamination tendency during the second period. This model was useful to show the decrease in the concentration of pesticides in human adipose tissue samples.
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Tecido Adiposo/química , Exposição Ambiental/análise , Poluentes Ambientais/análise , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Adulto , Feminino , Toxicologia Forense , Humanos , México , Fatores de TempoRESUMO
BACKGROUND: Low-penetrance susceptibility genes such as 5,10-methylenetetrahydrofolate reductase gene (MTHFR) have been considered in the progression of breast cancer (BC). Cancer is a result of genetic, environmental and epigenetic interactions; therefore, these genes should be studied in environmental context, because the results can vary between populations and even within the same country. The objective was to analyze the allelic and genotypic frequencies of the MTHFR C667T SNP in Mexican Mestizo patients with BC and controls from Northeastern Mexico. METHODS: 243 patients and 118 healthy women were studied. The analysis of the polymorphism was performed with a DNA microarray. Once the frequency of the polymorphism was obtained, Hardy-Weinberg equilibrium test was carried out for the genotypes. Chi square test was used to compare the distribution of frequencies. RESULTS: The allele frequency in patients was: C = 0.5406; T = 0.4594 and in controls C = 0.5678, T = 0.4322. Genotype in BC patients was: C / C = 29.9%, C / T = 48.3% and T / T = 21.8. The distribution in controls was: C / C = 31.4%, C / T = 50.8%, T / T = 17.8% (chi squared 0.77, p = 0.6801). CONCLUSIONS: Northeastern Mexican women in this study showed no association between MTFHR C667T SNP and the risk of BC. It seems that the contribution of this polymorphism to BC in Mexico varies depending on various factors, both genetic and environmental.
INTRODUCCIÓN: existen genes de susceptibilidad de baja penentrancia, como el gen de la 5,10-metilentetrahidrofolato reductasa (MTHFR), que participan en la progresión del cáncer de mama (CM). El cáncer es resultado de interacciones genéticas, ambientales y epigenéticas. Estos genes deben ser estudiados en el contexto del medio ambiente, ya que los resultados pueden variar de una población a otra, incluso dentro del mismo país. El objetivo fue analizar las frecuencias alélicas y genotípicas del polimorfismo C667T del gen de la MTHFR en pacientes mestizos mexicanos con CM y controles del noreste de México. MÉTODOS: se estudiaron 243 pacientes y 118 mujeres sanas. El análisis del polimorfismo se realizó con una microarreglo de ADN. Una vez que se obtuvo la fre cuencia del polimorfismo, la prueba de equilibrio de Hardy-Weinberg se llevó a cabo para los genotipos. Se utilizó chi cuadrada para comparar la distribución de frecuencias. RESULTADOS: la frecuencia de los alelos en los pacientes fue: C = 0.5406, T = 0.4594 y en los controles C = 0.5678, T = 0.4322. El genotipo en pacientes con CM fue: C / C = 29.9%, C / T = 48.3% y T / T = 21.8. La distribución en los controles fue: C / C = 31.4%, C / T = 50.8%, T / T = 17.8% (chi cuadrada 0.77, p = 0.6801). CONCLUSIONES: en este estudio no se observó relación entre el SNP MTFHR C667T y el riesgo de CM. Al parecer la contribución de este polimorfismo al CM en México varía dependiendo de varios factores tanto genéticos como ambientales.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , México , Pessoa de Meia-Idade , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Alzheimer disease neuropathology is characterized by the extracellular accumulation of Aß peptide and intracellular aggregation of hyperphosphorylated tau. With the progression of the disease, macroscopic atrophy affects the entorhinal area and hippocampus, amygdala, and associative regions of the neocortex. The locus coeruleus is depigmented. The deposition of Aß is first made of diffuse deposits. Amyloid focal deposits constitute the core of the senile plaque which also comprises a corona of tau-positive neurites. Aß deposits are found successively in the neocortex, the hippocampus, the striatum, the mesencephalon, and finally the cerebellum together with the pontine nuclei (Thal phases). Tau pathology affects in a stereotyped order some specific nuclei of the brainstem, the entorhinal area, the hippocampus, and the neocortex - first the associative areas and secondarily the primary cortices (Braak stages). Loss of synapses is observed in association with tau and Aß pathology; neuronal loss occurs in the most affected areas. Granulovacuolar degeneration and perisomatic granules are also linked to Alzheimer disease pathology. The physiopathology of Alzheimer disease remains unknown. Familial cases suggest that Aß deposition is the initial step, but tau pathology appears early in the course and seems to be better correlated with the symptoms.
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Doença de Alzheimer , Sistema Nervoso Central/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Sistema Nervoso Central/metabolismo , Humanos , Proteínas tau/metabolismoRESUMO
In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK-MB, myoglobin, troponins I and T (cTn-I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn-T and cTn-I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD.
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Creatina Quinase Forma MB/sangue , Morte Súbita Cardíaca , L-Lactato Desidrogenase/sangue , Mioglobina/sangue , Troponina I/sangue , Troponina T/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Patologia Legal , Humanos , Imunoensaio , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Prevention programs have not achieved the expected results in preventing mortality from breast and cervical cancer in Mexico. Therefore, we propose a complementary strategy. METHODOLOGY: An educational strategy for high school students in Mexico (2011-2013) was designed (longitudinal design, two measurements and a single intervention). The postintervention assessment included: 1) knowledge acquired by students about cancer prevention and 2) The performance of the student as a health promoter in their household. The strategy was based on analysis of cases and developed in three sessions. An assessment tool was designed and validated (Test-Retest). The levels of knowledge according to the qualifications expected by chance were determined. Wilcoxon test compared results before and after intervention. RESULTS: An assessment instrument with 0.80 reliability was obtained. 831 high school students were analyzed. Wilcoxon rank-sum test showed a significant learning after the intervention (Z = - 2.64, p = 0.008) with improvement of levels of knowledge in a 154.5%. 49% of students had a good performance as health promoters. CONCLUSIONS: The learning in preventive measures is important to sensitize individuals to prevention campaigns against cancer. This strategy proved to improve the level of knowledge of students in an easy and affordable way.
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BACKGROUND AND AIMS: Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. METHODS: There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). RESULTS: There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). CONCLUSIONS: YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Fosfoproteínas/metabolismo , Adulto , Idoso , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
AIM: Pharmacogenetic studies in breast cancer (BC) may predict the efficacy of tamoxifen and the toxicity of paclitaxel and capecitabine. We determined the frequency of polymorphisms in the CYP2D6 gene associated with activation of tamoxifen, and those of the genes CYP2C8, CYP3A5 and DPYD associated with toxicity of paclitaxel and capecitabine. We also included a IL-10 gene polymorphism associated with advanced tumor stage at diagnosis. PATIENTS & METHODS: Genomic DNAs from 241 BC patients from northeast Mexico were genotyped using DNA microarray technology. RESULTS: For tamoxifen processing, CYP2D6 genotyping predicted that 90.8% of patients were normal metabolizers, 4.2% ultrarapid, 2.1% intermediate and 2.9% poor metabolizers. For paclitaxel and the CYP2C8 gene, 75.3% were normal, 23.4% intermediate and 1.3% poor metabolizers. Regarding the DPYD gene, only one patient was a poor metabolizer. For the IL-10 gene, 47.1% were poor metabolizers. CONCLUSION: These results contribute valuable information towards personalizing BC chemotherapy in Mexican women.
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Hidrocarboneto de Aril Hidroxilases/genética , Neoplasias da Mama/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Interleucina-10/genética , Polimorfismo Genético/genética , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina , Citocromo P-450 CYP2C8 , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Genótipo , Humanos , México , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Espanha , Tamoxifeno/uso terapêuticoRESUMO
Breast density (BD) is a risk factor for breast cancer. Aims. To describe BD patterns in asymptomatic Mexican women and the pathological mammographic findings. Methods and Material. Prospective, descriptive, and comparative study. Women answered a questionnaire and their mammograms were analyzed according to BI-RADS. Univariate (χ(2)) and conditional logistic regression analyses were performed. Results. In 300 women studied the BD patterns were fat 56.7% (170), fibroglandular 29% (87), heterogeneously dense 5.7% (17), and dense pattern 8.6% (26). Prevalence of fat pattern was significantly different in women under 50 years (37.6%, 44/117) and older than 50 (68.8%, 126/183). Patterns of high breast density (BD) (dense + heterogeneously dense) were observed in 25.6% (30/117) of women ≤50 years and 7.1% (13/183) of women >50. Asymmetry in BD was observed in 22% (66/300). Compression cone ruled out underlying disease in 56 cases. In the remaining 10, biopsy revealed one fibroadenoma, one complex cyst, and 6 invasive and 2 intraductal carcinomas. 2.6% (8/300) of patients had non-palpable carcinomas. Benign lesions were observed in 63.3% (190/300) of cases, vascular calcification in 150 cases (78.9%), and fat necrosis in 38 cases (20%). Conclusions. Mexican women have a low percentage of high-density patterns.
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OBJECTIVE: To study the pre- and transoperative factors that influence patients' survival with GM. METHODS: Clinical and pathological records of all confirmed cases of GM diagnosed between 2000 and 2006 were included. Postoperative survival was divided in less or more than 8 months. χ2 test was used. RESULTS: One hundred and twenty patients (45 women and 75 men) were studied. Age range was from 7 to 85 years, 3.3% were 16 years old or younger and 12.5% were 70 years old or older. Headache was the most frequent complain, 40 patients developed hemiparesia and 6 had parestesias. Predominance of white matter hemispheric lesions was observed: right hemispheric tumors 65 (54%), left lesions 30 (25%) and bilateral tumors 7%. Histologically, 1.6% of GM had a sarcomatous component; 35% of patients survived less than 8 months. A difference between patients survival was the preoperative Karnofsky Performance Scale Score and the degree of cerebral edema during the surgical procedure. CONCLUSIONS: Pre-operative Karnofsky evaluation and edema during the surgical procedure were significant prognostic factors for survival.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.
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Perfilação da Expressão Gênica/métodos , Linfócitos , Músculo Esquelético , Gordura Subcutânea , Adulto , Humanos , Linfócitos/química , Masculino , México , Músculo Esquelético/química , RNA/análise , Gordura Subcutânea/químicaRESUMO
Objetivo: Describir la metodología de análisis de múltiples transcritos con técnicas de microarreglo en biopsias simultáneas de tejido muscular, adiposo y sangre en un mismo individuo, como parte de la estandarización del estudio GEMM (Genética de las Enfermedades Metabólicas en México). Material y métodos: Se incluyó a cuatro sujetos con índice de masa corporal (IMC) entre 20 y 41. Se registró estatura, talla y composición corporal. Se realizó biopsia muscular (vasto lateral), de tejido adiposo subcutáneo y muestra de sangre completa. El ARN total fue extraído de los tejidos y amplificado para análisis de microarreglos. Resultados: De 48 687 potenciales transcritos, 39.4% fue detectable en al menos uno de los tejidos. La expresión de leptina no fue detectable en linfocitos, débilmente expresada en músculo, alta expresión en el tejido adiposo y correlacionó con el IMC. El GLUT4 también ilustra la especificidad para el músculo sin verse afectado por el IMC. La concordancia en la expresión de transcritos fue 0.70 (p<0.001) para los tres tejidos. Conclusiones: Fue factible cuantificar simultáneamente la expresión genética de miles de transcritos, hubo concordancia en la expresión entre diferentes tejidos obtenidos en un mismo individuo, y confiabilidad del método al reproducir las relaciones biológicas esperadas. El estudio GEMM podrá analizar las correlaciones de los transcritos expresados dentro de un órgano y luego entre diferentes tejidos, y proveerá endofenotipos cuantitativos novedosos que proporcionarán un amplio panorama de información sobre las enfermedades metabólicas, incluyendo obesidad y diabetes tipo 2.
OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.
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Humanos , Masculino , Adulto , Linfócitos , Músculo Esquelético , Perfilação da Expressão Gênica/métodos , Gordura Subcutânea , Gordura Subcutânea/química , Linfócitos/química , México , Músculo Esquelético/química , RNARESUMO
UNLABELLED: Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1% of cases and one of its manifestation is osteoarthritis. AIM: To describe the clinical and pathological characteristics of 36 patients with osteoarthritis by Coccidioides immitis (COA). MATERIAL AND METHODS: The surgical pathology records of two medical institutions were reviewed; patients with clinical diagnosis of osteoarthritis and definitive histopathological diagnosis of COA were included in the study. Results were analyzed by contingence tables (RXC) and chi2 test. RESULTS: Twenty six adults (19 men, seven women) and 10 children (seven males, three females) were studied. The chi2 analysis demonstrated a predominance of disease in men (72.2%, p = 0.008). There was no difference between males and females in relation to history of mycotic disease or diagnosis of lung disease after the diagnosis of COA. Bone involvement (76% of cases) was more frequent that pure joint lesions and the predominant radiological lesion was of lytic type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them were men with multiple vertebral bone lesions. DISCUSSION: The COA was the only manifestation of disease in 83% of the patients. Therefore is important to consider this etiology in patients of endemic area. The clinical and radiological spectrum of COA is wide and may include a dentigerous and synovial cyst or simulates metastatic disease. The recognition of the clinical manifestations of COA may contribute to an opportune diagnosis and treatment.
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Artrite Infecciosa/epidemiologia , Doenças Ósseas Infecciosas/epidemiologia , Coccidioidomicose/epidemiologia , Adolescente , Idoso , Artrite Infecciosa/microbiologia , Artrite Infecciosa/patologia , Cistos Ósseos/epidemiologia , Cistos Ósseos/microbiologia , Cistos Ósseos/patologia , Doenças Ósseas Infecciosas/microbiologia , Doenças Ósseas Infecciosas/patologia , Criança , Pré-Escolar , Coccidioidomicose/patologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/microbiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/microbiologia , Osteólise/etiologia , Osteólise/microbiologia , Osteomielite/epidemiologia , Osteomielite/microbiologia , Osteomielite/patologia , Estudos RetrospectivosRESUMO
Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1% of cases and one of its manifestation is osteoarthritis. Aim. To describe the clinical and pathological characteristics of 36 patients with osteoarthritis by Coccidioides immitis (COA). Material and methods. The surgical pathology records of two medical institutions were reviewed; patients with clinical diagnosis of osteoarthritis and definitive histopathological diagnosis of COA were included in the study. Results were analyzed by contingence tables (RXC) and 
test. Results. Twenty six adults (19 men, seven women) and 10 children (seven males, three females) were studied. The analysis demonstrated a predominance of disease in men (72.2%, p - 0.008). There was no difference between males and females in relation to history of mycotic disease or diagnosis of lung disease after the diagnosis of COA. Bone involvement (76% of cases) was more frequent that pure joint lesions and the predominant radiological lesion was of lytic type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them were men with multiple vertebral bone lesions. Discussion. The COA was the only manifestation of disease in 83% of the patients. Therefore is important to consider this etiology in patients of endemic area. The clinical and radiological spectrum of COA is wide and may include a dentigerous and synovial cyst or simulates metastatic disease. The recognition of the clinical manifestations of COA may contribute to an opportune diagnosis and treatment.
La coccidioidomicosis (CM) es una enfermedad primariamente pulmonar. La diseminación sistémica ocurre en 1% de los casos y una de sus manifestaciones es la osteoartritis. Objetivo. Conocer las características clínicas y patológicas de 36 pacientes con osteoartritis por Coccidioides immitis (OAC). Material y métodos. Se revisaron los archivos de patología quirúrgica de dos instituciones y se incluyeron aquellos pacientes que consultaron por enfermedad osteoarticular y cuyo diagnóstico final histopatológico fue de CM. Los resultados se analizaron con tablas de contingencia (programa RXC) y prueba de . Resultados. Se estudiaron 26 adultos (19 hombres, siete mujeres) y 10 niños (siete hombres y tres mujeres). La prueba de mostró un predominio de casos en hombres (72.2%, p = 0.008). No hubo diferencia entre hombres y mujeres en relación con antecedentes de enfermedad micótica ni en el diagnóstico de enfermedad pulmonar posterior al diagnóstico de OAM. El compromiso óseo (76% de los casos) fue más frecuente que las lesiones articulares puras y la imagen radiológica predominante fue la osteolítica. De los casos estudiados, 30.5% (11 casos) presentaban lesiones óseas múltiples. De estos 11 casos, ocho eran hombres que en su mayoría presentaban lesiones vertebrales dorsales bajas y lumbares. Discusión. En 83% de los pacientes que se presentaron por OAC, esta fue la única manifestación de la enfermedad. El espectro clínico y radiológico de OAC es muy amplio y puede presentarse como un quiste dentígero, un quiste sinovial o simular enfermedad metastásica. El reconocimiento de esta variedad de presentaciones clínicas en individuos de zonas endémicas puede contribuir a un diagnóstico oportuno y tratamiento específico.
Assuntos
Adolescente , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Infecciosa/epidemiologia , Doenças Ósseas Infecciosas/epidemiologia , Coccidioidomicose/epidemiologia , Artrite Infecciosa/microbiologia , Artrite Infecciosa/patologia , Cistos Ósseos/epidemiologia , Cistos Ósseos/microbiologia , Cistos Ósseos/patologia , Doenças Ósseas Infecciosas/microbiologia , Doenças Ósseas Infecciosas/patologia , Coccidioidomicose/patologia , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/microbiologia , México/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/microbiologia , Osteólise/etiologia , Osteólise/microbiologia , Osteomielite/epidemiologia , Osteomielite/microbiologia , Osteomielite/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: This study describes the presence of mutations in BRCA1 and BRCA2 genes in a group of Mexican women and the clinical evolution of early onset breast cancer (EOBC). MATERIAL AND METHODS: A prospective hospital-based study was performed in a sample of 22 women with EOBC (7 in clinical stage IIA, 8 in IIB, and 7 in IIIA). The patients attended a tertiary care hospital in northeastern Mexico in 1997 and were followed up over a 5-year period. Molecular analysis included: 1) a mutation screening by heteroduplex analysis (HA) of BRCA1 and BRCA2 genes and 2) a sequence analysis. RESULTS: Of 22 patients, 14 (63.6%) showed a variant band detected by heteroduplex analysis of the BRCA1 and BRCA2 genes: 8 polymorphisms, 4 mutations of uncertain significance, and 2 novel truncated protein mutations, one in BRCAI (exon 11, 3587delT) and the other in the BRCA2 gene (exon 11, 2664InsA). CONCLUSIONS: These findings support future studies to determine the significance and impact of the genetic factor in this Mexican women population.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação , Adulto , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , México , Estadiamento de NeoplasiasRESUMO
OBJETIVO: Describir la presencia de mutaciones en los genes BRCA1 y BRCA2 y la evolución clínica de un grupo de mujeres con carcinoma mamario de inicio temprano (CMIT). MATERIAL Y MÉTODOS: Se realizó un estudio hospitalario, prospectivo, en una muestra de 22 pacientes con CMIT (siete en etapa clínica IIA, ocho en la IIB y siete en etapa IIIA). Las pacientes fueron atendidas en un hospital del noreste de México en 1997 y se realizó un seguimiento clínico durante cinco años. El análisis molecular incluyó: 1) análisis heterodúplex (AH) para detectar bandas variantes en la secuencia de ADN de los genes BRCA1 y BRCA2, y 2) análisis de secuenciación.RESULTADOS: De 22 pacientes, 14 (63.6%) mostraron banda variante por AH en los genes BRCA1 y BRCA2: ocho polimorfismos, cuatro mutaciones de significado incierto y dos mutaciones noveles con proteína truncada, una en BRCA1 (exón 11, 3587delT) y otra en BRCA2 (exón 11, 2664InsA). CONCLUSIONES: Estos hallazgos apoyan el desarrollo de futuros estudios para determinar el impacto del factor genético en la población mexicana con CMIT.
Assuntos
Adulto , Feminino , Humanos , Neoplasias da Mama/genética , Genes BRCA1 , Mutação , Neoplasias da Mama/patologia , Seguimentos , México , Estadiamento de NeoplasiasRESUMO
BACKGROUND: In northeastern Mexican population prevalence of positive cutaneous reaction to coccidioidin varies from 30 to 49%. Pregnancy is a risk factor for disseminated coccidioidomycosis. OBJECTIVES: 1) To describe the clinical spectrum of coccidioidomycosis in four women who acquired the disease during pregnancy or puerperium. 2) To discuss the autopsy findings. 3) To review the medical literature. MATERIAL AND METHODS: From 1983 to 2000, files of the Pathology Department of a reference tertiary hospital in northeastern Mexico were reviewed. Four cases of 4,598 autopsies corresponded to pregnant women with coccidioidomycosis. Clinical and autopsy charts, and the histological material were studied. RESULTS: Clinical spectrum included a septicemia case with fetal lost, an atypical pneumonia, a chronic meningitis with neuropsychiatric alterations and a patient with hypertensive pregnancy disease with secondary renal insufficiency and repeated episodes of pneumonia. All patients at autopsy showed multiple granulomas with abundant mycotic spherules. Lung involvement included bilateral 2-10 mm nodules. CONCLUSION: In pregnant women of endemic areas or who had traveled to these zones during pregnancy, coccidioidomycosis should be considered in the differential diagnosis of febrile syndrome with pneumonia, specially if it is accompanied of bilateral nodular infiltrates in lung, with or without erythema nodosum or meningitis.