RESUMO
BACKGROUND AND PURPOSE: Several diagnostic biomarkers are currently available for clinical use in early-onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. METHODS: There were a total of 40 subjects with early-onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non-neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid-positron emission tomography (PET) and 18 F-fluorodeoxyglucose-PET were performed. Neurologists provided pre- and post-biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure. RESULTS: Cerebrospinal fluid biomarkers and amyloid-PET increased diagnostic confidence in AD (77.4%-86.2% after CSF, 92.4% after amyloid-PET, P < 0.01) and non-neurodegenerative conditions (53.6%-75% after CSF, 95% after amyloid-PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated. CONCLUSIONS: Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early-onset cognitive impairment.
Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Demência Frontotemporal/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Demência Frontotemporal/líquido cefalorraquidiano , Demência Frontotemporal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons/métodosRESUMO
Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.
Assuntos
Comitês Consultivos , Alérgenos/administração & dosagem , Testes de Provocação Nasal/normas , Testes de Provocação Nasal/tendências , Rinite Alérgica/diagnóstico , Administração Intranasal , Assistência ao Convalescente , Anafilaxia , Alemanha , Humanos , Imunoglobulina E/sangue , Mucosa Nasal/imunologia , Obstrução Nasal/imunologia , Testes de Provocação Nasal/métodos , Sprays Nasais , Prurido/imunologia , Testes Cutâneos , Espirro/imunologiaRESUMO
AIM: The aim of the study was the analysis of reticular drusen (RDR) in patients with age-related macular degeneration using simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral domain optical coherence tomography (SD-OCT) at different time points. METHODS: Included in this retrospective analysis were 47 eyes from 32 patients (median age 80.1 years, range 66-89 years) with RDR at baseline and at least one follow-up visit. Registration of the cSLO near-infrared reflectance image and the SD-OCT B-scan (Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg) at different time points was carried out using the AutoRescan tool. RESULTS: While either no alterations or increase in the RDR area (n=19 eyes) or RDR density (n=15) were seen by cSLO imaging, the analysis of the SD-OCT B-scans at different time points revealed a more complex picture. An increase in two well visible lesions at the baseline visit was detected in 8 eyes at the first follow-up and in 3 eyes at the second follow-up examination. A regression was seen in 5 eyes at the first follow-up and in 3 eyes at the second follow-up visit. In most eyes (n=23), an increase of one with a parallel decrease of the second RDR lesion in the identical B-scan was identified at the first follow-up visit, whereas individual RDR showed an increase at the second follow-up examination that had initially shown a decrease in size at the first follow-up visit. CONCLUSIONS: The results indicate underlying dynamic processes in the development and changes of RDR over time. For a more accurate analysis, the exact registration of SD-OCT B-scans at different time points and the use of high-resolution very dense volume scans would be helpful in order to assess such discrete changes of miniscule intraretinal lesions over time.
Assuntos
Degeneração Macular/patologia , Microscopia Confocal/métodos , Drusas Retinianas/patologia , Lâmpada de Fenda , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Degeneração Macular/complicações , Masculino , Reprodutibilidade dos Testes , Drusas Retinianas/etiologia , Sensibilidade e EspecificidadeRESUMO
The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 µg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 µg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 µg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.
Assuntos
Testes Hematológicos/normas , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/normas , Calibragem , Testes Hematológicos/métodos , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Organização Mundial da SaúdeRESUMO
BACKGROUND: Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. PATIENTS AND METHODS: Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. RESULTS: High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). CONCLUSION: Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.
Assuntos
Proteínas da Matriz Extracelular/sangue , L-Lactato Desidrogenase/sangue , Melanoma/patologia , Proteínas de Neoplasias/sangue , Microglobulina beta-2/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/sangue , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Proteínas S100/sangueRESUMO
We compared the sensitivity and specificity of S-100 and MIA in advanced melanoma, in 96 patients with no evidence of disease (NED) and 86 patients with metastatic melanoma. Abnormal S100 (>0.2 microg/l) and MIA (>14 ng/ml) results were found in 1.1% and 3.2% of NED patients and in 59.3% and 54.6% of the patients with active melanoma (p<0.001). Using both tumor markers simultaneously, the sensitivity increased up to 69.8% with the same specificity 96.8%. S100 serum levels were not related to growth patterns. By contrast, MIA levels seemed to be related to the growth pattern, with higher levels in nodular melanoma (60.6+/-87.1 ng/ml) compared with acral-lentigous melanoma (11.9+/-5.4 ng/ml) (p=0.02). Likewise, S100 was related to the metastases site with significantly higher sensitivity and mean concentrations in patients with brain metastases (p=0.01) with the lowest in those with lung MI. MIA was related to the same metastases locations but without statistical significance. In summary, both S100 and ML4 are useful markers related to prognostic factors, being more effective when used in combination.
Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Melanoma/sangue , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Adulto , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Humanos , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Subunidade beta da Proteína Ligante de Cálcio S100 , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To study the clinical value of the determination of serum S-100 protein as a single tumor marker or in combination with tyrosinase RT-PCR in patients with melanoma receiving adjuvant interferon. PATIENTS AND METHODS: Patients were tested for serum S-100 protein luminoimmunometric assay and for blood tyrosinase mRNA (RT-PCR), before starting interferon and every 2-3 months thereafter. RESULTS: One hundred and six patients (stage IIA, 27; IIB, 19; III, 49; and IV, 11) were included in the study. Median follow-up was 51 months (range 2-76). In the univariate analysis, under treatment S-100 > or =0.15 microg/l and a positive RT-PCR correlated with a lower disease-free survival and overall survival (OS). In the multivariate analysis, clinical stage, under therapy positive RT-PCR and S-100 levels > or =0.15 mug/ml, were independent prognostic factors for OS. The hazard ratio for OS was 3.9 (95% CI, 1.67-9.15; p = 0.004) and 2.2 (95% CI, 1.05-4.6; p = 0.016) for S-100 > or =0.15 microg/l and positive RT-PCR, respectively. When both techniques where combined, a positive RT-PCR indicated a poorer clinical outcome only in patients with S-100 <0.15 microg/l. CONCLUSIONS: S-100 > or =0.15 microg/l and a positive RT-PCR during adjuvant interferon therapy indicate a high risk of death in resected melanoma patients. S-100 determination has a higher positive predictive value than RT-PCR, while tyrosinase RT-PCR adds prognostic information in patients with S-100 <0.15 microg/l.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Melanoma/sangue , Monofenol Mono-Oxigenase/genética , Proteínas S100/sangue , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Quimioterapia Adjuvante , Feminino , Humanos , Interferon alfa-2 , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/metabolismo , Estadiamento de Neoplasias , Valor Preditivo dos Testes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Anormalidades Múltiplas/genética , Hipertelorismo/genética , Hipospadia/genética , Proteínas dos Microtúbulos/genética , Mutação , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/patologia , Sequência de Aminoácidos , Embrião de Mamíferos/metabolismo , Feminino , Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Coração/embriologia , Humanos , Hipertelorismo/diagnóstico , Hipertelorismo/metabolismo , Hipospadia/diagnóstico , Hipospadia/metabolismo , Masculino , Dados de Sequência Molecular , Miocárdio/metabolismo , Linhagem , RNA Mensageiro/metabolismo , Rombencéfalo/embriologia , Rombencéfalo/metabolismo , Síndrome , Ubiquitina-Proteína LigasesRESUMO
CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases. Except for NSE, all tumor markers showed a clear relationship with tumor stage and histology and therefore enabled a better histological diagnosis. Abnormal CEA serum levels were mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Serpinas , Antígenos de Neoplasias/análise , Antígeno Ca-125/análise , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Citodiagnóstico , Feminino , Humanos , Queratina-19 , Queratinas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Fosfopiruvato Hidratase/análise , PrognósticoAssuntos
Aneuploidia , Testes Genéticos/métodos , Hibridização in Situ Fluorescente/métodos , Reação em Cadeia da Polimerase/métodos , Diagnóstico Pré-Natal/métodos , Marcadores Genéticos/genética , Testes Genéticos/normas , Humanos , Hibridização in Situ Fluorescente/normas , Reação em Cadeia da Polimerase/normas , Polimorfismo Genético/genética , Diagnóstico Pré-Natal/normas , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: The mechanisms of cardiac allograft vasculopathy and its predisposing factors are multifactorial and as yet not well established. To determine the influence of endothelial dysfunction on the development of intimal thickening, we prospectively analyzed the vasomotor response to acetylcholine and nitroglycerin, as well as other donor and recipient variables. Findings were correlated with the coronary intimal thickness, which was evaluated by means of intravascular ultrasonography. METHODS: Nineteen patients who had undergone heart transplantation 4.89 +/- 2.35 years previously and who had angiographically normal coronary arteries were included. Endothelial function was analyzed by quantitative coronary analysis of the vasomotor response of the left anterior descending artery to acetylcholine. An intimal thickness index, reflecting the percentage of intima obstructing the coronary lumen, was calculated. RESULTS: Nine (47%) patients showed endothelial dysfunction, and the remaining 10 (53%) patients had a normal response. Four (44%) of 9 patients with a weight gain of greater than 20% after the operation showed endothelial dysfunction compared with none of the 10 patients with normal responses (P <.04). The severity of the intimal thickness correlated with the years after transplant (r = 0.45, P <.05). Patients with endothelial dysfunction had more intimal thickening than those without (32% +/- 17% vs 17% +/- 12%, respectively; P <.05). Furthermore, the degree of intimal thickening correlated with the magnitude of the vasomotor response to acetylcholine (r = -0.60, P =.006). No relationship was found between intimal thickness and the vasodilatory response to nitroglycerin. As independent variables for intimal thickness, multivariate analysis detected the magnitude of the response to acetylcholine (P =.0005), years after transplant (P =.01), and ischemic time (P =.03). CONCLUSIONS: Cardiac allograft vasculopathy is a multifactorial disease the severity of which increases over time. Endothelial dysfunction is a predictive factor of intimal thickening severity. Predisposing factors that provoke endothelial injury, such as perioperative ischemic time and obesity, may contribute to the development of allograft vasculopathy.
Assuntos
Vasos Coronários/patologia , Endotélio Vascular/fisiopatologia , Transplante de Coração/patologia , Acetilcolina/farmacologia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroglicerina/farmacologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Túnica Íntima/patologia , Ultrassonografia de Intervenção , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
INTRODUCTION AND OBJECTIVES: To present the initial Spanish experience with the Tenax coronary stent, a laser sculpted from high-precision 316L stainless steel coated with hydrogen rich amorphous silicon carbide that reduces thrombogenecity and improves biocompatibility. PATIENTS AND METHODS: From July 1998 to July 1999, 206 patients (62 +/- 5 years) underwent implantation of 231 Tenax stents in 9 centers as the only revascularization procedure. The most frequent clinical indication was unstable angina (66%), and most of the lesions were complex (class B2 and C). The target vessels were the left anterior descending (51%) and right coronary arteries (36%). The ejection fraction was < 0.5 in 19% cases. RESULTS: Revascularization was complete in 70%, elective in 80%, and the implantation was direct in 25% of the cases. The procedure was successful in all the lesions, reducing stenosis from 62 +/- 16 to 16 +/- 10% and increasing the minimal luminal diameter from 0.81 +/- 0.40 to 2.61 +/- 0.59 mm. The TIMI flow was reduced in 30%, but normalized after the stent in all but one case. The incidence of cardiac events was minimal: 1 acute thrombosis (0.5%) resolved by a new angioplasty and 1 non-Q myocardial infarction (0.5%). At the 6-month clinical follow-up 10% of the patients presented complaints of angina greater than class II, and a new angioplasty was carried out in 1.9% of these cases. CONCLUSION: Clinical and angiographic data suggest that the hydrogenated silicon carbide coating of the Tenax coronary stent may indeed play a beneficial role in patient outcome, and should therefore be evaluated by prospective clinical trials.
Assuntos
Doença das Coronárias/cirurgia , Stents , Angina Instável/terapia , Materiais Biocompatíveis , Compostos Inorgânicos de Carbono , Doença das Coronárias/complicações , Seguimentos , Humanos , Revascularização Miocárdica , Implantação de Prótese , Sistema de Registros , Compostos de Silício , Stents/efeitos adversos , Resultado do TratamentoAssuntos
Sequestro Broncopulmonar/cirurgia , Cardiomiopatia Dilatada/etiologia , Pneumonectomia , Adulto , Sequestro Broncopulmonar/complicações , Sequestro Broncopulmonar/diagnóstico , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia , Feminino , Humanos , Tomografia Computadorizada por Raios XRESUMO
The results of the Registry of the Working Group on Hemodynamics and Interventional Cardiology of the Spanish Society of Cardiology for 2000 are presented. Date came from 100 centers representing all the cardiac catheterization laboratories in Spain; 93 centers performed mainly adult catheterization and 7 carried out only pediatric procedures. In 2000, 88,339 diagnostic catheterization procedures were performed (73,382 coronary angiograms), representing a total increase of 12.5% over 1999. The population-adjusted rate was 1,825 coronary angiograms per 106 inhabitants. With a total of 26,993 procedures and a rate of coronary interventions per 106 inhabitants of 671, coronary intervention increased by 17% over figures for 1999. Coronary stents were the devices used most often, with 29,504 implanted in 2000; stenting accounted for 77.2% of procedures, a 30.5% increase over 1999. The increase in direct stenting without predilatation was noteworthy. Direct stenting was done in 8,778 procedures (38.9% of the total), an increase of 131% compared to 1999. IIb-IIIa glycoprotein were used in 4,700 coronary interventions (17%). Angioplasty, performed in 3,128 cases of acute myocardial infarction, accounted for 11.6% of coronary interventions 33.5% more than in 1999. A decrease of 6.5% in valvuloplastics occurred, attributable to the performance of fewer mitral valve repairs (493 vs 525 in 2000 and 1999, respectively). Pediatric procedures increased by 20.5%, from 678 to 817 cases. In conclusion, we would like to underline the high rate of reporting by laboratories, through which the Registry has been able to compile data that are highly representative of the hemodynamic activity in Spain.
Assuntos
Serviço Hospitalar de Cardiologia/estatística & dados numéricos , Cardiologia , Hemodinâmica , Sistema de Registros , Inquéritos e Questionários , Humanos , Sociedades Médicas , EspanhaRESUMO
The renal-coloboma syndrome (RCS, MIM 120330) is an autosomal dominant disorder caused by PAX2 gene mutations. We screened the entire coding sequence of the PAX2 gene for mutations in nine patients with RCS. We found five heterozygous PAX2 gene mutations: a dinucleotide insertion (2G) at position 619 in one sporadic RCS case, a single nucleotide insertion (619 + G) in three unrelated cases, and a single nucleotide deletion in a familial case. In this familial case, three affected sibs showed a striking ocular phenotypic variability. Each of the sibs carried a 619insG mutation, whilst unaffected parents did not, suggesting the presence of germline mosaicism. Interestingly, the 619insG mutation has been previously reported in several patients and is also responsible for the Pax21Neu mouse mutant, an animal model of human RCS. This study confirms the critical role of the PAX2 gene in human renal and ocular development. In addition, it emphasises the high variability of ocular defects associated with PAX2 mutations ranging from subtle optic disc anomalies to microphthalmia. Finally, the presence of PAX2 germline mosaicism highlights the difficulties associated with genetic counselling for PAX2 mutations.
Assuntos
Coloboma/genética , Proteínas de Ligação a DNA/genética , Nefropatias/genética , Fatores de Transcrição/genética , Sequência de Bases , Coloboma/patologia , DNA/química , DNA/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Mutação em Linhagem Germinativa , Humanos , Nefropatias/patologia , Masculino , Dados de Sequência Molecular , Mosaicismo , Mutagênese Insercional , Mutação , Fator de Transcrição PAX2 , Linhagem , Polimorfismo Conformacional de Fita Simples , Deleção de Sequência , Homologia de Sequência do Ácido Nucleico , SíndromeRESUMO
A female with mitral valvular disease presented an acute myocardial infarction. She suddenly complained of recurrent chest pain with symptoms of pulmonary edema. The angiogram evidenced multiple coronary thromboemboli. A combined strategy using intracoronary thrombolysis, a platelet glycoprotein IIb/IIIa antagonist (abciximab) and percutaneous transluminal coronary angioplasty to help disrupt the thrombus was performed. Clinical and angiographic signs of coronary reperfusion were rapidly achieved. No bleeding complications appeared.
Assuntos
Angioplastia Coronária com Balão , Anticorpos Monoclonais/uso terapêutico , Trombose Coronária/terapia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Terapia Trombolítica , Abciximab , Idoso , Trombose Coronária/complicações , Feminino , Doenças das Valvas Cardíacas/complicações , Humanos , Valva Mitral , Infarto do Miocárdio/complicaçõesRESUMO
The CHARGE syndrome comprises ocular coloboma, heart malformation, choanal atresia, retarded growth and development, central nervous system malformations, genital hypoplasia, ear abnormalities, or deafness. The cause of the CHARGE syndrome remains unknown. In the present study, we analyzed the distribution pattern of the PAX2 gene in human embryos and found that PAX2 gene expression occurs in the primordia affected in the CHARGE syndrome. These data prompted us to consider the PAX2 gene a candidate gene in the CHARGE "association." We analyzed the PAX2 gene in 34 patients fulfilling the diagnostic criteria of the CHARGE syndrome for deletion and nucleotidic variations of the coding sequence and identified only polymorphisms. Our data suggest that mutation of the PAX2 gene is not a cause of the CHARGE association. However, the pattern of expression of PAX2 suggests that genes encoding downstream targets effectors could be candidate genes for the CHARGE syndrome.
Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/metabolismo , Fatores de Transcrição/genética , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/patologia , Sistema Nervoso Central/anormalidades , Sistema Nervoso Central/embriologia , Coloboma/embriologia , Coloboma/patologia , DNA/química , DNA/genética , Análise Mutacional de DNA , Surdez/embriologia , Surdez/patologia , Orelha/anormalidades , Orelha/embriologia , Éxons , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Hibridização In Situ , Fator de Transcrição PAX2 , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , SíndromeRESUMO
BACKGROUND: To estimate the rate of malformations observed during early human development, a series of 38,913 first-trimester abortions were studied. Neural tube defects (NTD) were found in 57 cases. METHODS: A histological study of serial sections performed in 25 embryos revealed a spectrum of axial structure abnormalities. Expression of the SHH gene was studied by in situ hybridization in one case of CRS and in two cases of SB. RESULTS: A cervical notochord duplication was always found in craniorachischisis (CRS, n = 8), but not in spina bifida (SB, n = 10) or diplomyelia (split cord malformation, n = 3). In the embryo with CRS, expression of SHH was found in both domains, corresponding to the duplicated part of the notochord, whereas a single signal was observed in the nonduplicated part. This expression was associated at the cervical level of the open neural tube with a broad SHH expression domain and with two or even three domains in its lumbar region, suggesting multiple functional floor plates. Similarly, in two embryos with SB, two domains of SHH expression were found in the ventral neural tube. CONCLUSIONS: Our findings suggest that notochord splitting in the cervical region might be involved in the pathogenesis of CRS. Interestingly, similar notochord abnormality and altered expression of the shh gene are observed in Lp mice with NTD. This suggests that the Lp gene could be a candidate gene for human CRS. Further studies are needed to establish the primary event responsible for the notochord splitting and for the abnormal expression of the SHH gene in the floor plate in embryos with CRS and SB.
Assuntos
Embrião de Mamíferos/metabolismo , Defeitos do Tubo Neural/genética , Biossíntese de Proteínas , Proteínas/genética , Transativadores , Aborto Induzido , Embrião de Mamíferos/anatomia & histologia , Feminino , Idade Gestacional , Proteínas Hedgehog , Humanos , Hibridização In Situ , Cariotipagem , Masculino , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/patologia , Disrafismo Espinal/genética , Disrafismo Espinal/metabolismo , Disrafismo Espinal/patologiaRESUMO
Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosomal dominant condition when SOX10 mutations are involved. We report on three unrelated WS4 patients with growth retardation and an as-yet-unreported neurological phenotype with impairment of both the central and autonomous nervous systems and occasionally neonatal hypotonia and arthrogryposis. Each of the three patients was heterozygous for a SOX10 truncating mutation (Y313X in two patients and S251X [corrected] in one patient). The extended spectrum of the WS4 phenotype is relevant to the brain expression of SOX10 during human embryonic and fetal development. Indeed, the expression of SOX10 in human embryo was not restricted to neural-crest-derived cells but also involved fetal brain cells, most likely of glial origin. These data emphasize the important role of SOX10 in early development of both neural-crest-derived tissues, namely melanocytes, autonomic and enteric nervous systems, and glial cells of the central nervous system.