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An early double case of acute Ophthalmia neonatorum in 3-day-old twins is reported. Culture of eye swabs showed a wide bacterial polymorphism, in which common bacteria, such as Klebsiella pneumoniae, Streptococcus pneumoniae, Corynebacterium ulcerans and other Enterobacteriaceae, coexisted with atypical Mycoplasmataceae and Chlamydiaceae from resident cervical-vaginal maternal microbiota. The neonates were in an apparently healthy state, but showed red eyes with abundant greenish-yellow secretion, mild chemosis and lid edema. The maternal cervical-vaginal ecosystem resulted differently positive to the same common cultivable, atypical bacteria culturally and molecularly determined. This suggested a direct maternal-foetal transmission or a further foetal contamination before birth. An extended culture analysis for common bacteria to atypical ones was decisive to describe the involvement of Mycoplasmas (M. hominis and U. urealyticum) within the scenario of the Ophthalmia neonatorum in a Caucasian couple. The introduction of a routine PCR molecular analysis for Chlamydiaceae and N. gonorrhoeae allowed to establish which of these were present at birth, and contributed to determine the correct laboratory diagnosis and to define an adequate therapeutic protocol obtaining a complete resolution after one year for culture and atypical bacteria controls. This study suggests to improve the quality of laboratory diagnosis as unavoidable support to a correct clinical diagnosis and therapy, in a standardized modality both for swabbing and scraping, to check the new-born microbial programming starting in uterus, overtaking the cultural age to the molecular age, and to revise the WHO guidelines of SAFE Strategy for trachoma eye disease, transforming it into SAFES Strategy where the S letter is the acronym of Sexual ecosystem and behavioural valuation/education.
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Infecciones por Chlamydiaceae , Chlamydiaceae/genética , ADN Bacteriano/genética , Neisseria gonorrhoeae/genética , Oftalmía Neonatal , Reacción en Cadena de la Polimerasa , Infecciones por Chlamydiaceae/diagnóstico , Infecciones por Chlamydiaceae/genética , Infecciones por Chlamydiaceae/microbiología , Infecciones por Chlamydiaceae/terapia , Femenino , Humanos , Recién Nacido , Oftalmía Neonatal/diagnóstico , Oftalmía Neonatal/genética , Oftalmía Neonatal/microbiología , Oftalmía Neonatal/terapia , GemelosRESUMEN
OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is a common and relevant problem affecting Western people. The role of estrogens and their receptors in the venous wall seems to support the major prevalence of CVD in women. The effects of the estrogens are mediated by three estrogen receptors (ERs): ERα, ERß, and G protein-coupled ER (GPER). The expression of ERs in the vessel walls of varicose veins is evaluated. METHODS: In this prospective study, patients of both sexes, with CVD and varicose veins undergoing open venous surgery procedures, were enrolled in order to obtain vein samples. To obtain control samples of healthy veins, patients of both sexes without CVD undergoing coronary artery bypass grafting with autologous saphenous vein were recruited (control group). Samples were processed in order to evaluate gene expression. RESULTS: Forty patients with CVD (10 men [25%], 30 women [75%], mean age 54.3 years [median 52 years, range 33-74 years]) were enrolled. Five patients without CVD (three men, two women [aged 61-73 years]) were enrolled as the control group. A significant increase of tissue expression of ERα, ERß and GPER in patients with CVD was recorded (p < .01), which was also related to the severity of venous disease. CONCLUSION: ERs seem to play a role in CVD; in this study, the expression of ERs correlated with the severity of the disease, and their expression was correlated with the clinical stage.
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Receptores de Estrógenos/análisis , Várices/metabolismo , Venas/química , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Crónica , Receptor alfa de Estrógeno/análisis , Receptor beta de Estrógeno/análisis , Femenino , Humanos , Masculino , Memoria Episódica , Persona de Mediana Edad , Receptores Acoplados a Proteínas G/análisisRESUMEN
BACKGROUND: Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. PATIENTS AND METHODS: From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. RESULTS: One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. CONCLUSIONS: 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.
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Braquiterapia/métodos , Melanoma/diagnóstico por imagen , Radioisótopos de Rutenio/uso terapéutico , Neoplasias de la Úvea/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Braquiterapia/mortalidad , Supervivencia sin Enfermedad , Femenino , Angiografía con Fluoresceína , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Oftalmoscopía , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Dosis de Radiación , Traumatismos por Radiación/etiología , Radiografía , Estudios Retrospectivos , Radioisótopos de Rutenio/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Neoplasias de la Úvea/diagnóstico por imagen , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Agudeza Visual/efectos de la radiación , Adulto JovenRESUMEN
BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Doxorrubicina/administración & dosificación , Hipertermia Inducida , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia del Cáncer por Perfusión Regional/métodos , Supervivencia sin Enfermedad , Extremidades/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perfusión , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules
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Melanoma/tratamiento farmacológico , Melanoma/patología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Extremidades , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Melanoma/mortalidad , Melfalán/farmacología , Persona de Mediana Edad , Metástasis de la Neoplasia , Perfusión , Pronóstico , Resultado del TratamientoRESUMEN
The detection of PHOX2B mutations in a small proportion of patients affected with either familial or sporadic neuroblastoma (NB), has arisen interest on the possible pathogenic role of this gene in the disease determination. In this light, we have carried out a quantitative expression analysis of PHOX2B and its paralogue PHOX2A on a panel of NB cell lines and NB tumour samples to identify a possible differential expression between NB cells and their normal counterpart (adrenal medulla cells). Our results revealed that both PHOX2A and PHOX2B are over-expressed in tumour samples and NB cell lines. Particularly, the expression levels of the two genes in NB cell lines show a highly significant correlation, suggesting their possible synergistic role or a coordinated expression regulation. Furthermore, PHOX2 gene over-expression in NB tumours and cell lines suggests these genes may be widely involved in NB development through either a direct mechanism of up-regulation or a failure in maintaining proper transcript levels after embryonic development.
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Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Neuroblastoma/genética , Factores de Transcripción/genética , Médula Suprarrenal/metabolismo , Línea Celular Tumoral , Análisis Mutacional de ADN , Proteínas de Homeodominio/metabolismo , Humanos , Neuroblastoma/metabolismo , Linaje , Factores de Transcripción/metabolismo , Regulación hacia ArribaRESUMEN
This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.
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Ganglios Linfáticos/patología , Melanoma/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Índice Mitótico , Pronóstico , Radiografía , Cintigrafía , Neoplasias Cutáneas/diagnóstico por imagen , Coloración y Etiquetado , Úlcera/patologíaRESUMEN
BACKGROUND: Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. OBJECTIVE: The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. METHOD: Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. RESULTS: We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. CONCLUSION: Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies.
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Terapia Genética/métodos , Enfermedades de la Retina/genética , Enfermedades de la Retina/terapia , Vectores Genéticos/administración & dosificación , HumanosRESUMEN
PurposeTo investigate the efficacy of early therapeutic deep anterior lamellar keratoplasty (DALK) in eradicating fungal keratitis that is poorly responsive to medical treatment.Patients and methodsTwenty-three eyes (23 patients) underwent early therapeutic DALK within 15 to 50 days from the onset of symptoms. The adopted eligibility criteria for early DALK included the following: active fungal keratitis affecting the optical zone with ulcer confined in the 6.00 mm central cornea; deeper than 150 µm but not exceeding 300 µm; and poorly responsive to medical treatment.ResultsThe big bubble technique was accomplished in 74% (17) of eyes, whereas manual dissection was performed in the remaining 26% (6) of eyes. Histopathological examination did not show any sign of fungal colonization in the peripheral and deep stromal lamellae in any case. All grafts were transparent postoperatively, and no recurrence of infection occurred. Median best spectacle corrected visual acuity significantly improved from 2.0 (1.0 interquartile range) logMAR to 0.1 (0.1 interquartile range) logMAR (P<0.01). The mean follow-up was 32±10 months. Neither episode of rejection nor graft failure was noted during the follow-up period.ConclusionEarly DALK could represent a safe therapeutic approach to eradicate fungal keratitis that affects the optical zone and is poorly responsive to medical treatment.
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Antifúngicos/uso terapéutico , Córnea/cirugía , Infecciones Fúngicas del Ojo/cirugía , Supervivencia de Injerto , Queratitis/cirugía , Queratoplastia Penetrante/métodos , Agudeza Visual , Adulto , Anciano , Córnea/microbiología , Córnea/patología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Hongos/aislamiento & purificación , Humanos , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Masculino , Microscopía Confocal , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Líquidos Corporales/metabolismo , Conjuntiva/metabolismo , Retinopatía Diabética/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Conjuntiva/patología , Retinopatía Diabética/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/terapia , Hipertermia Inducida , Neoplasias Peritoneales/terapia , Peritoneo/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Terapia Combinada , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Peritoneo/patología , Tasa de SupervivenciaRESUMEN
Alterations of the distal portion of the short arm of chromosome 1 (1p) are among the earliest abnormalities of human colorectal tumors. Loss of heterozygosity analysis has previously revealed a smallest region of overlapping deletion (SRO) B, at 1p35-36.1, deleted in 48% of sporadic tumors. From this region we have now cloned a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue. In rat liver, Afar is strongly inducible by the antioxidants ethoxyquin and butylated hydroxyanisole, which protect the rat against aflatoxin B1-induced liver tumorigenesis by detoxifying its genotoxic and cytotoxic dialdehyde. Human AFAR is expressed in a broad range of tissues and, therefore, is likely involved in endogenous detoxication pathways. Impaired detoxication of genotoxic aldehydes and ketones, which are involved in tumorigenesis of the colon and breast, may be a crucial factor both for tumor initiation and progression. We here provide a detailed contig of 1.5-2 Mbp/2.7 cM encompassing part of SRO B, including known genes and previously unmapped expressed sequence tags. PLA2G2A (secretory type II phospholipase A2), described previously as a candidate, is localized outside SRO B.
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Aldehído Reductasa/genética , Caspasas/genética , Cromosomas Humanos Par 1/genética , Eliminación de Gen , Proteínas de Neoplasias/genética , Aldehído Reductasa/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Caspasa 14 , Caspasas/química , Caspasas/aislamiento & purificación , Mapeo Cromosómico , Humanos , Datos de Secuencia Molecular , Proteínas de Neoplasias/química , Especificidad de Órganos , RatasRESUMEN
The presence of three distinct serum markers of carcinoma, tumor-associated glycoprotein 72 (TAG-72; as measured by the CA 72-4 assay), CA 19-9, and carcinoembryonic antigen (CEA), was evaluated in 194 patients diagnosed with either malignant (n = 94) or benign (n = 100) gastric disease. Of the 94 patients diagnosed with gastric carcinoma, the percentage of patients whose serum samples were positive for TAG-72, CA 19-9, or CEA was 42.6, 31.9, and 20.2%, respectively. Furthermore, fewer false positive samples were observed for TAG-72 than either CA 19-9 or CEA. The analysis of serum TAG-72, CA 19-9, and CEA levels in patients diagnosed with early (stage I and II) versus advanced (stage III and IV) disease revealed a significantly higher level of TAG-72 and CA 19-9 in the serum of patients with advanced stage gastric carcinoma. The serum samples were also analyzed to determine whether any advantage might be gained by simultaneously measuring two or more of the tumor markers. The data clearly indicate that the measurement of TAG-72 with CA 19-9 significantly increased the percentage of gastric carcinoma patients with positive serum levels of either antigen. This advantage was achieved with no significant increase in the number of false positives. Twenty-one patients were followed postsurgically for up to 3 years to determine whether the appearance or reappearance of TAG-72, CA 19-9, or CEA accurately predicted disease recurrence. Positive serum TAG-72 levels correlated with disease recurrence in 7 of 10 patients, compared with 5 and 2 patients for CA 19-9 and CEA, respectively. The findings suggest that serum TAG-72 as measured by the CA 72-4 assay may be a useful marker for late stage gastric carcinoma and its measurement alone or in combination with CA 19-9 may have utility in the clinical management of gastric carcinoma.
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Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/sangre , Glicoproteínas/sangre , Neoplasias Gástricas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Gastropatías/sangre , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only approximately 50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring.
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Adenocarcinoma/sangre , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/genética , Neoplasias Colorrectales/sangre , Células Neoplásicas Circulantes/inmunología , ARN Mensajero/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígenos de Carbohidratos Asociados a Tumores/genética , Biomarcadores de Tumor/genética , Antígeno CA-19-9/sangre , Antígeno CA-19-9/genética , Antígeno Carcinoembrionario/biosíntesis , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/metabolismo , ARN Mensajero/genética , Sensibilidad y EspecificidadRESUMEN
Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by a complex association between tremendous genotypic multiplicity and great phenotypic heterogeneity. The severity of the clinical manifestation depends on penetrance and expressivity of the disease-gene. Also, various interactions between gene expression and environmental factors have been hypothesized. More than 250 genes with ~4500 causative mutations have been reported to be involved in different RP-related mechanisms. Nowadays, not more than the 50% of RPs are attributable to identified genes, whereas the rest of molecular defects are still undetectable, especially in populations where few genetic screenings have been performed. Therefore, new genetic strategies can be a remarkably useful tool to aid clinical diagnosis, potentially modifying treatment options, and family counseling. Genome-wide analytical techniques (array comparative genomic hybridization and single-nucleotide polymorphism genotyping) and DNA sequencing strategies (arrayed primer extension, Sanger sequencing, and ultra high-throughput sequencing) are successfully used to early make molecular diagnosis detecting single or multiple mutations in the huge heterogeneity of RPs. To date, further research needs to be carried out to better investigate the genotype/phenotype correlation, putting together genetic and clinical findings to provide detailed information concerning the risk of RP development and novel effective treatments.
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Retinitis Pigmentosa/genética , Hibridación Genómica Comparativa , Análisis Mutacional de ADN/métodos , Estudios de Asociación Genética , Genotipo , Humanos , Técnicas de Diagnóstico Molecular/métodos , Fenotipo , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/fisiopatología , Selección Visual/métodos , Campos Visuales/fisiologíaRESUMEN
Endocrine orbitopathy (EO) can have important consequences, such as exophthalmos and restrictive strabismus. A retrospective study was performed of 35 patients with EO who underwent orbital decompression surgery and restrictive strabismus correction. Two surgical techniques for orbital decompression were analyzed: fat decompression by Olivari technique and three-wall bony expansion with fat decompression. Strabismus surgery was performed using adjustable or non-adjustable sutures under topical anaesthesia. Patients were divided into two groups according to the type of intra-orbital decompression performed, and the postoperative values resulting from the different fat decompression techniques were recorded. The preoperative and postoperative mean degrees of exophthalmos were 22.3 and 19.9mm, respectively, for the fat decompression group, and 24.3 and 19.8mm, respectively, for the bony expansion with transpalpebral fat decompression (combined form) group. The difference in residual prism dioptres between adjustable and non-adjustable suture techniques in patients who had previously undergone combined decompression was statistically significant. The management of patients with EO requires a multidisciplinary approach based on the collaboration of maxillofacial surgeons, ophthalmologists, and orthoptists. These results will allow the development of a more adequate strategy for the surgical treatment of restrictive strabismus in EO patients.
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Descompresión Quirúrgica/métodos , Exoftalmia/cirugía , Oftalmopatía de Graves/cirugía , Órbita/cirugía , Estrabismo/cirugía , Anciano , Anciano de 80 o más Años , Exoftalmia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estrabismo/etiología , Técnicas de SuturaRESUMEN
PURPOSE: To evaluate the prognostic role of MYCN oncogene amplification in children with neuroblastoma. PATIENTS AND METHODS: Of 694 children (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (42%) were evaluated at diagnosis for MYCN gene amplification. RESULTS: Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified (> or = three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate was higher for children aged less than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This association held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable characteristics, in particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplified MYCN survive. In a multivariate analysis, the prognostic role of MYCN amplification, age, and stage was confirmed, but the size of the effect of MYCN was dependent on age and stage. CONCLUSION: MYCN amplification is associated with a worse prognosis in children with neuroblastoma at all ages and stages except 4s. This association is most pronounced in children with otherwise favorable prognostic indicators, and in these children should be considered as an indication for more intensive intervention.
Asunto(s)
Amplificación de Genes/genética , Genes myc/genética , Neuroblastoma/genética , Adolescente , Biomarcadores de Tumor/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Neuroblastoma/sangre , Neuroblastoma/patología , PronósticoRESUMEN
PURPOSE: Carcinoembryonic antigen (CEA) is still a widely used test for monitoring breast cancer, although recent reports discourage its routine use because of low sensitivity. This is a prospective study evaluating the efficacy of CEA and CA 15.3 in monitoring breast cancer. EXPERIMENTAL DESIGN: Serum CEA and CA 15.3 were measured in 2191 patients with either benign (n = 738) or malignant (n = 1453) breast diseases. Five hundred and forty-nine patients were monitored during postsurgical follow-up for either a minimum of 5 years or until time of recurrence. Fifty-three patients with metastases were also monitored during chemotherapy. RESULTS: Elevated CEA and CA 15.3 levels were found in 16.7% and 33.0% of patients, respectively. CEA sensitivity rose to 41.3% and CA 15.3 sensitivity rose to 80.8% in metastatic patients. The adjunct of CEA increased the CA 15.3 sensitivity by 6% in the overall population and by only 2.1% for patients with metastases. During postsurgical follow-up, CEA was elevated in 38.0% and CA 15.3 in 70.2% of patients with recurrence. The combination of CEA and CA 15.3 increased the overall sensitivity by only 1.4%. Longitudinal monitoring of 53 metastatic patients undergoing chemotherapy demonstrated that, when positive, both CEA and CA 15.3 paralleled response to treatment, although CA 15.3 was a significantly more powerful marker for determining response to treatment. The cost effectiveness ratio of CEA was clearly less favorable than that of CA 15.3. CONCLUSIONS: CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients, and it provides no additional value when used in combination with CA 15.3.
Asunto(s)
Neoplasias de la Mama/patología , Antígeno Carcinoembrionario/sangre , Adenocarcinoma/sangre , Adenocarcinoma/economía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/economía , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Mucina-1/sangre , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Prospectivos , Radioinmunoensayo/economía , Sensibilidad y EspecificidadRESUMEN
Deletion of chromosome 1p and MYCN amplification have been reported as frequent abnormalities in human neuroblastoma. We studied loss of heterozygosity (LOH) in 50 (48 informative) Italian neuroblastoma patients by restriction fragment length polymorphisms (RFLPs) analysis using anonymous and hypervariable region (HVR) sequences. Twelve cases (25%) showed LOH at one or more loci. Locus D1S94 was the most frequently involved in LOH events (8/12) of deleted cases (66.6%). MYCN amplification was observed in 20% of patients which showed a significantly lower event-free survival probability (EFSp) (P = 0.004). We also studied the allelic distribution in the constitutional DNA of neuroblastoma patients (n = 44) and a matched group of healthy Italian subjects (n = 79) for loci D1S112 and D1S94. A significantly (P = 0.01) different allele frequency was detected for the two groups at locus D1S94, but not at D1S112. Moreover, the neuroblastoma population did not confirm the Hardy-Weinberg expectations at the former locus. This observation suggests the existence of an allelotype associated with neuroblastoma susceptibility.
Asunto(s)
Alelos , Cromosomas Humanos Par 1/genética , Ligamiento Genético/genética , Pérdida de Heterocigocidad/genética , Neuroblastoma/genética , Amplificación de Genes , Genes myc/genética , Genética de Población , Humanos , Italia , Polimorfismo de Longitud del Fragmento de Restricción , PronósticoRESUMEN
We report on a male infant with oral, facial, digital, and skeletal anomalies in association with severe psychomotor delay. This may represent a new oral-facial-digital syndrome.