RESUMEN
BACKGROUND: Since 2016, France is the only country in the World where continuous deep sedation until death (CDSUD) is regulated by law. CDSUD serves as a response to refractory suffering in palliative situations where the patients' death is expected to occur in the following hours or days. Little is known on the psychological adjustment surrounding a CDSUD procedure for healthcare providers (HCPs) and relatives. Our study aims to gather qualitative and quantitative data on the specific processes behind the psychological adjustment of both relatives and HCPs, after the administration of CDSUD for patients with cancer. METHODS: The APSY-SED study is a prospective, longitudinal, mixed-methods and multicenter study. Recruitment will involve any French-speaking adult cancer patient for who a CDSUD is discussed, their relatives and HCPs. We plan to include 150 patients, 150 relatives, and 50 HCPs. The evaluation criteria of this research are: 1/ Primary criterion: Psychological adjustment of relatives and HCPs 6 and 13 months after the death of the patient with cancer (psychological adjustment = intensity of anxiety, depression and grief reactions, CDSUD-related distress, job satisfaction, Professional Stress and Professional experience). Secondary criteria: a)occurrence of wish for a CDSUD in patients in palliative phase; b)occurrence of wish for hastened death in patients in palliative phase; c)potential predictors of adjustment assessed after the discussion concerning CDSUD as an option and before the setting of the CDSUD; d) Thematic analysis and narrative account of meaning-making process concerning the grief experience. DISCUSSION: The APSY-SED study will be the first to investigate the psychological adjustment of HCPs and relatives in the context of a CDSUD procedure implemented according to French law. Gathering data on the grief process for relatives can help understand bereavement after CDSUD, and participate in the elaboration of specific tailored interventions to support HCPs and relatives. Empirical findings on CDSUD among patients with cancer in France could be compared with existing data in other countries and with results related to other medical fields where CDSUD is also conducted. TRIAL REGISTRATION: This protocol received the National Registration Number: ID-RCB2021-A03042-39 on 14/12/2021.
Asunto(s)
Sedación Profunda , Neoplasias , Adulto , Humanos , Ajuste Emocional , Estudios Prospectivos , Personal de Salud , Estudios Observacionales como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
The human skin is constantly exposed to external factors that affect its integrity, UV radiation being one of the main stress factors. The repeated exposure to this radiation leads to increased production of Reactive Oxygen Species (ROS) which activate a series of processes involved in photoaging. Excessive UV exposure also exacerbates melanin production leading to a variety of pigmentation disorders. Xanthones are reported to exhibit properties that prevent deleterious effects of UV exposure and high levels of ROS in the organism, so in this work a wide library of xanthones with different patterns of substitution was synthesized and tested for their inhibitory activity against the skin enzymes tyrosinase, elastase, collagenase and hyaluronidase, many of which were evaluated for the first time. Most of the compounds were tyrosinase inhibitors, with the best one (xanthone 27) presenting an IC50 of 1.9 µM, which is approximately 6 times lower than the IC50 of the positive control kojic acid. Concerning the other enzymes, only one compound presented IC50 lower than 150 µM in elastase inhibition (xanthone 14 = 91.8 µM) and none in collagenase and hyaluronidase inhibition. A QSAR model for tyrosinase inhibitory activity was built using six molecular descriptors, with a partial negative surface area descriptor and the relative number of oxygen atoms being positively contributing to the tyrosinase inhibitory activity. Docking using AutoDock Vina shows that all the tested compounds have more affinity to mushroom tyrosinase than kojic acid. Docking results implied that the tyrosinase inhibitory mechanisms of xanthonic derivatives are attributed to an allosteric interaction. Taken together, these data suggest that xanthones might be useful scaffolds for the development of new and promising candidates for the treatment of pigmentation-related disorders and for skin whitening cosmetic products.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Melaninas/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Relación Estructura-Actividad Cuantitativa , Xantonas/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Melaninas/metabolismo , Estructura Molecular , Monofenol Monooxigenasa/metabolismo , Xantonas/síntesis química , Xantonas/químicaRESUMEN
OBJECTIVE: The aim of this article was to describe the diagnostic and therapeutic value of transcranial stimulation in pelvic and perineal disorders. METHODS: A literature review (Medline database and Google scholar) with no time limit was performed using keywords: "transcranial direct stimulation", "transcranial magnetic stimulation", "neurogenic bladder", "urinary incontinence", "Parkinson disease", "multiple sclerosis", "stroke", "muscle spasticity", "pelvic pain", "visceral pain". RESULTS: Twelve articles have been selected. Transcranial magnetic or electrical stimulation is a noninvasive neuromodulation technique widely used to establish brain maps to highlight causal relationships between brain and function. Regarding pelvic-perineal disorders, repeated transcranial stimulation has shown significant effects for the treatment of overactive bladder in Parkinson's disease (P<0.05) and multiple sclerosis, but also for the treatment of refractory chronic pelvic pain (P=0.026). Finally, therapeutic effects have also been demonstrated in irritable bowel syndrome. No evidence of efficacy was found on genito-sexual disorders. CONCLUSION: Data from the literature suggest that transcranial stimulation is a noninvasive treatment that may have a role in the management of pelvic and perineal disorders. Its promising field of action would require prospective and randomized studies on a larger scale.
Asunto(s)
Dolor Crónico/terapia , Terapia por Estimulación Eléctrica/métodos , Dolor Pélvico/terapia , Trastornos Urinarios/terapia , Humanos , Perineo , CráneoRESUMEN
This work addresses the analysis of individual cost data in the setting of interventional or observational studies using statistical analysis software once the costs per patient have been estimated. It is in fact necessary to be able to present and describe data in an appropriate manner in each of the studied health strategies and to test whether the difference in costs observed between treatment groups is due to chance or not. Furthermore, cost analysis differs from conventional statistical analysis in that cost data have a certain number of specific properties, including their use by health decision-makers. This work also addresses the difficulties that generally arise in regard to the distribution of cost; it explains why the mathematical average constitutes the only relevant measure for economists; and it outlines which analyses are required for inter-strategy cost comparisons. It also covers the issue of missing or censored data, features that are inherent to information collected regarding costs and to sensitivity analyses.
Asunto(s)
Análisis Costo-Beneficio/métodos , Costos de la Atención en Salud , Costos de Hospital/organización & administración , Análisis Costo-Beneficio/normas , Francia/epidemiología , Costos de la Atención en Salud/estadística & datos numéricos , Costos de Hospital/normas , Costos de Hospital/estadística & datos numéricos , Humanos , Asignación de Recursos/clasificación , Asignación de Recursos/economía , Asignación de Recursos/estadística & datos numéricosRESUMEN
BACKGROUND: To date, no curative treatment is available for Alzheimer's disease (AD). Therefore, efforts should focus on prevention strategies to improve the efficiency of healthcare systems. OBJECTIVE: Our aim was to assess the cost-effectiveness of three preventive strategies for AD compared to a placebo. DESIGN: The Multidomain Alzheimer Preventive Trial (MAPT) study was a multicenter, randomized, placebo-controlled superiority trial with four parallel groups, including three intervention groups (one group with Multidomain Intervention (MI) plus a placebo, one group with Polyunsaturated Fatty Acids (PFA), one group with a combination of PFA and MI) and one placebo group. SETTING: Participants were recruited and included in 13 memory centers in France and Monaco. PARTICIPANTS: Community-dwelling subject aged 70 years and older were followed during 3 years. INTERVENTIONS: We used data from the MAPT study which aims to test the efficacy of a MI along PFA, the MI plus a placebo, PFA alone, or a placebo alone. MEASUREMENT: Direct medical and non-medical costs were calculated from a payer's perspective during the 3 years of follow-up. The base case incremental Cost-Effectiveness Ratio (ICER) represents the cost per improved cognitive Z-score point. Sensitivity analyses were performed using different interpretation of the effectiveness criteria. RESULTS: Analyses were conducted on 1,525 participants. The ICER at year 3 that compares the MI + PFA and the MI alone to the placebo amounted to 21,443 and 21,543 respectively, per improved Z score point. PFA alone amounted to 111,720 per improved Z score point. CONCLUSION: Our study shows that ICERS of PFA combined with MI and MI alone amounted to 21,443 and 21,543 respectively per improved Z score point compared to the placebo and are below the WTP of 50,000 while the ICER of PFA alone amounted to 111,720 per improved Z score point. This information may help decision makers and serve as a basis for the implementation of a lifetime decision analytic model.
Asunto(s)
Enfermedad de Alzheimer , Cognición/fisiología , Análisis Costo-Beneficio/economía , Ácidos Docosahexaenoicos/administración & dosificación , Ejercicio Físico/fisiología , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Femenino , Francia , Humanos , Vida Independiente , Masculino , Mónaco , Proyectos de InvestigaciónRESUMEN
In this study we aim to determine the prevalence of the recently identified pathogenic BRCA1 variant c.-107A > T in the south-east German population. This variant causes the epigenetic silencing of the BRCA1 promotor and has been detected in two independent families from the UK without a germline BRCA1 or BRCA2 pathogenic variant. A total of 3297 individuals with suspicion of hereditary breast and ovarian cancer and fulfilling the clinical criteria necessary for genetic testing in Germany were analyzed for presence of the variant by a Kompetitive Allele-Specific PCR (KASP) assay or direct Sanger sequencing. Since we did not detect an individual carrying the variant we conclude that BRCA1 c.-107A > T is not a common variant in the south-east German population.
Asunto(s)
Regiones no Traducidas 5'/genética , Neoplasias de la Mama/genética , Represión Epigenética , Genes BRCA1 , Neoplasias Ováricas/genética , Regiones Promotoras Genéticas , Femenino , Genes BRCA2 , Tamización de Portadores Genéticos , Pruebas Genéticas , Técnicas de Genotipaje , Alemania , Humanos , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADNRESUMEN
OBJECTIVES: Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). METHODS: A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. RESULTS: The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6-100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. CONCLUSIONS: In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.
Asunto(s)
Enfermedades Transmisibles Importadas/diagnóstico , Malaria/diagnóstico , Microscopía/normas , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificación de Ácido Nucleico/normas , África , Enfermedades Transmisibles Importadas/parasitología , Francia , Humanos , Malaria/parasitología , Microscopía/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Plasmodium , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Sensibilidad y Especificidad , TemperaturaRESUMEN
INTRODUCTION: To assess parents' knowledge regarding how to deal with children's fever in comparison to the updated recommendations published in 2016 by the HAS and to collect their views on the fever advice card of the 2006 health record to offer suggestions for possible improvements in order to disseminate the message. METHODS: Observational, descriptive, quantitative national study conducted with an online questionnaire among adult parents with children born between 2006 and 2017 who had a French health record. RESULTS: A total of 3295 parents were included from 03/12/2017 to 04/02/2018. The concordance of knowledge compared to current recommendations has improved in 10 years, especially regarding physical treatment (31% of parents had all the right answers) and drugs (95% paracetamol monotherapy). Shortcomings mainly concern the definition of fever, the idea that the temperature is correlated with severity, and the lack of knowledge of the sign of severity "age less than 3 months." The use of the fever advice card in the health record is limited (33% of parents only). They approve by a large majority its promotion and the standardization of the message of healthcare professionals. CONCLUSIONS: The improvement of how parents manage their child's fever first requires an update of the knowledge of healthcare professionals to homogenize their messages and practices. One of their essential roles is to inform parents of the existence of the fever advice card updated in the 2018 health record, which most particularly contains information that remains poorly known by parents. The health record should be the medium of dialogue with families to promote children's health.
Asunto(s)
Fiebre/terapia , Conocimientos, Actitudes y Práctica en Salud , Registros de Salud Personal , Padres/psicología , Relaciones Profesional-Familia , Niño , Preescolar , Femenino , Francia , Encuestas de Atención de la Salud , Educación en Salud/métodos , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
INTRODUCTION: Pompe's disease, also called glycogen storage disease type II or acid maltase deficiency, is an autosomal recessive disease caused by an enzymatic deficiency of acid-alpha-glucosidase (GAA). This deficiency causes an accumulation of intralysosomal glycogen in different organs. The classic form appears in the newborn with a very severe hypotonia and cardiomyopathy, which lead to death before age two. Less frequently, the disease appears only in childhood or in adult life, so called late-onset Pompe's disease. This form causes a very progressive limb-girdle myopathy and restrictive respiratory failure. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. We report six cases of late-onset Pompe's disease from the Languedoc-Roussillon district. METHOD: Our work was a retrospective analysis of all cases of Pompe disease diagnosed in adults between 1975 and 2006 at the Montpellier and Nîmes University Hospital. We describe the clinical presentation and course of this form and explain the diagnostic approach. Results. The mean age at onset was 44.3 years (range: 36-60 years). The first symptom was fatigability (50%), gait difficulty (50%) and dyspnea (16%). The mean delay from symptom onset to diagnosis was 8.4 years (range: 17 years). Fatal outcome due to respiratory failure was noted in three patients. The mean time between symptom onset and death (four patients) was 20.75 years (range: 37 years). The diagnosis was made on the muscle biopsy showing a low level of GAA. Muscle was strictly normal on the morphologic study in one patient, pointing out the requirement for enzymatic analysis. Molecular confirmation was available in one patient. DISCUSSION: Late-onset Pompe's disease is a possible cause of limb-girdle myopathy. Respiratory involvement is a characteristic feature. Enzymatic assay of GAA activity on the muscle biopsy is required for certain diagnosis. CONCLUSION: It is very important to recognize the adult form of Pompe's disease, a possible cause of limb-girdle myopathy, in order to search for respiratory failure and propose non-invasive ventilation if necessary. Moreover, substitutive therapy (recombinant acid-alpha-glucosidase) has shown efficiency for the classical infantile form of Pompe's disease and such treatment could be proposed for the adult form if larger studies confirm its efficacy.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Adulto , Edad de Inicio , Biopsia , Progresión de la Enfermedad , Disnea/etiología , Disnea/fisiopatología , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Fatiga Muscular/fisiología , Músculos/patología , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , alfa-Glucosidasas/metabolismoRESUMEN
INTRODUCTION: Extrauterine growth restriction is associated with long-term effects on growth and neurodevelopmental outcomes in preterm infants. The objective of this study was to evaluate the effects of a change in nutritional policy on the postnatal growth of premature infants. METHOD: Prospective observational study carried out between 01/01/14 and 31/12/14 in all newborns under 33 weeks GA admitted to the Bordeaux University Hospital after modification of the nutrition policy at the beginning of January 2014. This cohort was compared to a retrospective historical cohort of children born between 01/01/12 and 31/12/12. In the second period, the nutrient intakes received were evaluated and compared with the recent recommendations (ESPGHAN 2005, 2010, Nutritional care of preterm infant). The impact of EUGR was compared between the two populations. RESULTS: A total of 144 children were included: 66 in the 2012 cohort and 78 in the 2014 cohort. Their initial characteristics were similar. The moderate EUGR rate was 86.4 % in 2012 vs. 39.7 % in 2014 and the severe EUGR rate was 21.2 % in 2012 vs. 5.1 % in 2014. In 2014, half of the newborns had an energy deficit and two-thirds had a protein deficit at the end of the 6 weeks of hospitalization. CONCLUSION: This study shows that optimization of the nutrition policy can reduce the incidence of EUGR.
Asunto(s)
Trastornos del Crecimiento/epidemiología , Política Nutricional , Nutrición Enteral , Femenino , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Recien Nacido Prematuro , Masculino , Nutrición Parenteral , Estudios Prospectivos , Factores de TiempoRESUMEN
We have shown previously that fatty acid synthetase (FAS) is specifically induced by progestins in human breast cancer cell lines. To test the potential value of FAS as a clinical marker in breast diseases, we measured FAS expression in frozen sections of 22 benign and 27 malignant mammary tumors using in situ hybridization with the [35S]UTP alpha S-labeled FAS anti-sense mRNA. The hybridized RNA was quantified with an IMSTAR computerized image analyzer. We found FAS RNA in epithelial cells, but no labeling was detected in the connective tissue. In breast cancer, we found no correlation between FAS expression and estrogen receptor and progesterone receptor concentrations or status. However, the level of FAS was significantly (P less than .02) higher in premenopausal than in post-menopausal patients and increased with the grade of tumor differentiation (P less than .005 between the poorly and well-differentiated tumors). In benign mastopathies, high levels of FAS RNA were found in some cysts (mostly with apocrine metaplasia). In lobules, the FAS RNA level increased proportionally to the degree of proliferation determined by histological examination (P less than .015) and correlated with the H4 histone level measured in an adjacent section using in situ hybridization (r = 0.85, P less than .001). In ductal structures, a lower correlation (r = 0.64, P less than .01) was found between FAS and H4 RNA levels. We conclude that FAS RNA is overexpressed in some mammary tumors and may be useful in predicting high-risk mastopathies and less aggressive breast cancers.
Asunto(s)
Enfermedades de la Mama/enzimología , Neoplasias de la Mama/enzimología , Ácido Graso Sintasas/biosíntesis , Progestinas/farmacología , Enfermedades de la Mama/patología , Neoplasias de la Mama/patología , Inducción Enzimática/efectos de los fármacos , Ácido Graso Sintasas/genética , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Menopausia , Persona de Mediana Edad , Hibridación de Ácido Nucleico , ARN/análisis , ARN Neoplásico/análisisRESUMEN
INTRODUCTION: We report a case of nemaline myopathy revealed in adulthood by a respiratory insufficiency. CASE REPORT: A 26-year-old patient, without past history, was admitted with respiratory and right cardiac insufficiency which appeared in a few days. There was a severe restrictive lung impairment with nocturnal hypoventilation. Minor skeletal abnormalities and areflexia suggested a congenital myopathy. Muscle biopsy revealed a nemaline myopathy. CONCLUSION: Respiratory insufficiency is common in nemaline myopathy with infancy or childhood onset, but very rare in adults. It may be explained by multiple mechanisms.
Asunto(s)
Miopatías Nemalínicas/etiología , Insuficiencia Respiratoria/diagnóstico , Adulto , Atrofia , Biopsia , Femenino , Humanos , Músculo Esquelético/patología , Miopatías Nemalínicas/patología , Fibras Nerviosas/patología , Insuficiencia Respiratoria/patologíaRESUMEN
A secreted glycoprotein with a molecular weight of 52,000 is induced by estrogen in breast cancer cells and has been purified to prepare monoclonal antibodies. The protein has been detected in some breast cancers but not in normal breast and uterus. In order to study its potential value as a marker, we have tested by immunohistochemistry frozen sections of several normal and malignant tissues and of benign mastopathies. Among different tissues tested, the Mr 52,000 protein was detected only in liver, sweat glands, and some sebaceous glands, and in malignant melanomas and some breast tumors. Other estrogen-responsive tissues (ovary, placenta, endometrium, etc.) gave negative results. Immunoradiometric assay of the Mr 52,000 protein in biological fluid revealed an elevated concentration in cyst fluid (0.5 to 7.4 micrograms/ml), pleural effusions of certain metastatic breast cancer, and sweat. By immunohistochemistry, the Mr 52,000 antigen was also detected in 42% of 129 benign mastopathies. Gynecomastia, fibrous disease, fibroadenoma, and adenosis were mainly negative, whereas ductal hyperplasia and cysts were positive. The Mr 52,000 protein was found mostly in proliferative ducts and in cysts but not in lobular hyperplasia and nonproliferative lesions without cyst. More Mr 52,000 protein was found in postmenopausal patients than in premenopausal patients. We conclude that the Mr 52,000 protein is a marker associated with mammary cysts and proliferative ducts. On the basis of the increased risk of breast cancer in proliferative mastopathies, we suggest that the Mr 52,000 protein is useful for predicting high-risk mastopathies acting as a marker associated with the proliferation of ductal tissue.
Asunto(s)
Enfermedades de la Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Factores de Edad , Líquidos Corporales/metabolismo , Enfermedades de la Mama/patología , Estrógenos/fisiología , Femenino , Enfermedad Fibroquística de la Mama/metabolismo , Humanos , Menopausia , Peso Molecular , Distribución TisularRESUMEN
BACKGROUND: Phenotypic changes during cancer progression are associated with alterations in gene expression, which can be exploited to build molecular signatures for tumor stage identification and prognosis. However, it is not yet known whether the relative abundance of transcript isoforms may be informative for clinical stage and survival. METHODS: Using information theory and machine learning methods, we integrated RNA sequencing and clinical data from The Cancer Genome Atlas project to perform the first systematic analysis of the prognostic potential of transcript isoforms in 12 solid tumors to build new signatures for stage and prognosis. This study was also performed in breast tumors according to estrogen receptor (ER) status and melanoma tumors with proliferative and invasive phenotypes. RESULTS: Transcript isoform signatures accurately separate early from late-stage groups and metastatic from non-metastatic tumors, and are predictive of the survival of patients with undetermined lymph node invasion or metastatic status. These signatures show similar, and sometimes better, accuracies compared with known gene expression signatures in retrospective data and are largely independent of gene expression changes. Furthermore, we show frequent transcript isoform changes in breast tumors according to ER status, and in melanoma tumors according to the invasive or proliferative phenotype, and derive accurate predictive models of stage and survival within each patient subgroup. CONCLUSIONS: Our analyses reveal new signatures based on transcript isoform abundances that characterize tumor phenotypes and their progression independently of gene expression. Transcript isoform signatures appear especially relevant to determine lymph node invasion and metastasis and may potentially contribute towards current strategies of precision cancer medicine.
Asunto(s)
Empalme Alternativo , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Melanoma/diagnóstico , ARN Mensajero/genética , Receptores de Estrógenos/genética , Neoplasias Cutáneas/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Teoría de la Información , Metástasis Linfática , Aprendizaje Automático , Masculino , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/metabolismo , Receptores de Estrógenos/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Análisis de Supervivencia , TranscriptomaRESUMEN
INTRODUCTION: Identifying tumor infiltration or compression in patients with non-Hodgkin's malignant lymphoma presenting peripheral neuropathy can be a difficult task. METHODS: We collected a series of patients with peripheral neuropathy with demonstrated lymphomatous infiltration or compression managed between October 1977 and October 2001 to search for clinico-pathological correlations. RESULTS: Ten cases were reviewed. Neurological manifestations were the inaugural symptom of the disease in 7 patients. Clinical presentations included 5 focal (3 cranial nerve palsies, 2 brachial radiculopathies) and 5 diffuse neuropathies (3 polyradiculoneuropathies, 1 polyneuropathy and 1 mononeuritis multiplex). The mechanisms of peripheral nerve involvement were classified into lymphomatous meningoradiculitis (5 cases), involvement of cranial nerves or spinal roots in their extraneuraxial course (3 cases) and infiltration of distal peripheral nerves (2 cases). Four long lasting survivals after treatment were observed. CONCLUSIONS: Prognosis depends much more on the haematological disease than on the neurological symptoms or tumor location.
Asunto(s)
Linfoma no Hodgkin/fisiopatología , Neoplasias del Sistema Nervioso Periférico/fisiopatología , Adulto , Anciano , Antígenos CD/inmunología , Enfermedades de los Nervios Craneales/epidemiología , Enfermedades de los Nervios Craneales/fisiopatología , Electromiografía , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Inmunohistoquímica , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/inmunología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Periférico/epidemiología , Neoplasias del Sistema Nervioso Periférico/inmunologíaRESUMEN
Fatty acid synthetase (FAS) is induced by progesterone in MCF7 and T47D breast cancer cell lines. We studied a possible in vivo regulation of expression of this gene by looking for FAS RNA in human endometrial biopsies at various periods of the menstrual cycle, using a cloned cDNA FAS probe. By Northern blot analysis, we detected the 8-kilobase FAS RNA throughout the cycle in 7 uterine samples. RNA in situ hybridization analysis of frozen sections from 22 endometrial biopsies showed that FAS RNA was present during follicular and luteal phases of the menstrual cycle in stromal and epithelial cells. RNA levels were quantified by counting autoradiographic silver grains using a computer-aided image analyzer. FAS RNA levels were significantly higher in epithelial cells than in fibroblasts (P less than 2 x 10(-5]. Furthermore, in both cell types, mean FAS RNA concentrations were higher in biopsies removed during the luteal phase than the follicular phase of the menstrual cycle (P = 2 x 10(-3) and 9 x 10(-5), respectively). A 2- to 3-fold increase in FAS RNA levels between days 8-14 and days 22-24 was detected in 2 normal patients who had previously undergone 2 successive biopsies. This increase was not observed in 2 patients with low plasma estradiol and progesterone concentrations, indicating a probable dysovulation. We conclude that FAS normally increases in both stromal and epithelial endometrial cells during the luteal phase. This increase is probably due to progesterone, which implies that FAS is induced in normal endometrium, as demonstrated in breast cancer.
Asunto(s)
Endometrio/enzimología , Ácido Graso Sintasas/genética , Regulación Enzimológica de la Expresión Génica , Ciclo Menstrual/genética , ARN Mensajero/aislamiento & purificación , Adulto , Autorradiografía , Northern Blotting , Células Cultivadas , Endometrio/metabolismo , Endometrio/fisiología , Epitelio/enzimología , Epitelio/metabolismo , Ácido Graso Sintasas/metabolismo , Femenino , Humanos , Sondas Moleculares , Hibridación de Ácido Nucleico , Progesterona/fisiología , Factores de TiempoRESUMEN
Using an immunoenzymatic assay, cathepsin-D concentrations were measured in the cytosol of human endometrium biopsies. The level of cathepsin-D was higher in the luteal phase than in the follicular phase (P less than 0.01), suggesting increased accumulation by progesterone. Induction by progestin was confirmed by immunoprecipitation of cathepsin-D from a lysate of epithelial endometrial cells previously treated in primary culture with R5020 (10 nM); estradiol (10 nM) had no effect. Immunohistochemistry showed that cathepsin-D is mainly localized in the epithelium and that its level is higher in the luteal phase. The plasma level of cathepsin-D was stable during the menstrual cycle, ranging between 2.5-10 pmol/mL, but increased slightly during pregnancy. The mean level of cathepsin-D was higher in 19 endometrial carcinoma than in 20 normal endometrium, but was not correlated with steroid receptor status. However, using 15 pmol/mg protein as a cut-off level, the cathepsin-D status (high or low) was correlated with the degree of myometrial invasion (greater than or equal to one third) by adenocarcinoma cells, whereas steroid receptor status was not. We conclude that cathepsin-D is induced by progesterone in human endometrium, as it is in normal rat uterus, and we suggest that a low concentration of cathepsin-D in the cytosol of endometrial adenocarcinoma may indicate a favorable prognosis, since it is correlated with low myometrial invasion.
Asunto(s)
Biomarcadores de Tumor/análisis , Catepsina D/análisis , Endometrio/metabolismo , Progesterona/farmacología , Biotransformación/efectos de los fármacos , Catepsina D/sangre , Citosol/efectos de los fármacos , Citosol/metabolismo , Endometrio/efectos de los fármacos , Femenino , Fase Folicular , Humanos , Fase Luteínica , Espectrometría de Fluorescencia , Coloración y Etiquetado , Neoplasias Uterinas/análisisRESUMEN
The RPE65 protein appears late during the retinal development. To study the basis for this regulation, the rat RPE65 cDNA was sequenced and the mRNA subsequently quantitated at various stages by competitive RT-PCR. RPE65 mRNA was detected as early as E18 (36 copies/ng of whole eye total RNA). It gradually accumulates up to P12 (27000 copies/ng) at which point it reaches a steady state level. This increase is interrupted for 3 days (P2-P4) during which the levels of mRNA remain stable. This timing and rate of accumulation parallels that of rat and mouse opsin mRNA and suggests that common factors may control the activation of genes in photoreceptors and retinal pigment epithelium cells.
Asunto(s)
Proteínas del Ojo/metabolismo , Ojo/embriología , Epitelio Pigmentado Ocular/metabolismo , Proteínas , ARN Mensajero/metabolismo , Animales , Proteínas Portadoras , ADN Complementario/análisis , Ojo/metabolismo , Proteínas del Ojo/genética , Ratones , Datos de Secuencia Molecular , Epitelio Pigmentado Ocular/embriología , Reacción en Cadena de la Polimerasa , Ratas , Ratas Wistar , Factores de Tiempo , cis-trans-IsomerasasRESUMEN
Two siblings and two other unrelated patients had congenital muscular weakness and dystrophic changes but normal immunocytochemical stainings for merosin, dystrophin, and dystrophin-related proteins on muscle biopsy. All had marked ataxia and cerebellar atrophy or hypoplasia. Cerebral white matter and cortical organization appeared normal.