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BACKGROUND: Work and workplace factors are important in fibromyalgia management. We investigated factors associated with sick leave in professionally active women living with fibromyalgia. METHODS: A questionnaire for fibromyalgia patients in employment was developed by pain and occupational physicians and patients' organizations. Women in full-time work, screened for fibromyalgia with the FiRST questionnaire, were recruited for a national online survey. Sick leave over the preceding year was analyzed. RESULTS: In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave. CONCLUSIONS: Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics. PERSPECTIVE: This is the first study to assess the impact of occupational and clinical factors on sick leave in women living with fibromyalgia. Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia.
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Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the α-ketoglutarate (α-KG) dehydrogenase complex (KGDHC), which converts α-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of α-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy.
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Aciltransferasas/fisiología , Carcinogénesis , Ciclo del Ácido Cítrico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Acilcoenzima A/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Supervivencia Celular , Humanos , Ácidos Cetoglutáricos/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Pez CebraRESUMEN
OBJECTIVES: Cognitive and behavioral approach of chronic pain presents encouraging results by improving physical, functional and psychological states of chronic pain patients. This specific treatment is partially based on the acquisition of new adaptive strategies to help the patients to manage more effectively chronic pain and to improve subsequently their subjective well-being. This requires in parallel to give up noxious emotional, cognitive and behavioral attitudes towards pain. Now, we have to admit that numerous therapeutic failures are directly imputable to difficulties introducing and making the indispensable changes continue in pursuit of the fixed therapeutic objectives. Readiness to change could play a considerable role in the success or not of chronic pain treatment. The main objective of this article is to present the data of the current literature concerning the specificities of the process of change in the field of the chronic pain. METHODS: We present a review of the literature describing at first, the psychological progress made by chronic pain patients longing to manage their suffering better via the trans-theoretical model of intentional change. Secondly, we develop the contributions of the technique of motivational interviewing in the improvement of chronic pain treatment. DISCUSSION: The identification of the motivational profile of chronic pain patients will determine how motivational interviewing can be conducted to improve their readiness for change. There are several strategies used with chronic pain patients in pre-contemplative and contemplative stages. Therapists may facilitate the problem recognition (help chronic pain patients to become aware of and identify the nature of the difficulties they face when trying to cope with their physical suffering); increase the personal concern (empowering chronic pain patients so that they feel fully involved in what they offer and invest in the therapy); develop the intention of change (ensure that the change becomes truly intentional); cultivate optimism (to help chronic pain patients to consider the present situation as being less desperate than it seems); ask open-ended questions (the direct questioning can be used to specify a request or reveal ambivalence about change); present personal feedback (the therapist provides the patient with a maximum of information that may help to appreciate the true value of the effectiveness of their current management of pain); review consequences of change versus non-change (to review the plausible positive (pros) and negative (cons) consequences of change); and summarizing (to summarize the key points discussed during the interview). In the active stage, therapists may use other strategies like: developing a plan for change (to suggest the adoption of certain coping strategies with pain); providing information advice (provide information advice in order to help chronic pain patients to determine how they will take concrete steps to initiate change); and using a change plan worksheet (help chronic pain patients to develop a synthetic view of the change process they will undertake). CONCLUSION: The various strategies discussed in this article are intended to accompany chronic pain patients to a process of change to help them consider a fundamental change in their ways of managing pain, when they are insufficient, ineffective and/or unintentionally aggravating their situation. It is important to help chronic pain patients to become aware of the nature of the adaptive problems they face, but also opportunities for change that are offered in order to encourage them to manage more efficiently and more autonomously their physical and mental suffering. In this context of openness to change, motivational interviewing can be an invaluable help to build a good therapeutic alliance in order to maximize the impact of supported global and multidimensional chronic pain by including a cognitive-behavioral approach for example.
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Adaptación Psicológica , Dolor Crónico/terapia , Terapia Cognitivo-Conductual/métodos , Entrevista Motivacional , Dolor Crónico/psicología , Humanos , Modelos Psicológicos , Motivación , Manejo del Dolor/métodosRESUMEN
La craneotomía con el paciente despierto es un procedimiento ancestral, que vuelve a estar de actualidad. Confinada durante mucho tiempo a la cirugía de la epilepsia, sus indicaciones se han ampliado, siendo una técnica ampliamente reconocida para la resección de lesiones próximas a regiones corticales fundamentales, y en neurocirugía funcional. Es un procedimiento seguro, que además de proporcionar excelentes resultados, ahorra dinero y recursos. El anestesiólogo ha de estar familiarizado con los fundamentos de la neuroanestesia, conocer la técnica concreta de infiltración, así como los protocolos de sedación, y manejarse cómodamente con la vía aérea. El objetivo principal es que el paciente colabore en los momentos en que el cirujano lo precise (anestesia basada en la analgesia). Esta revisión pretende sintetizar lo publicado hasta la fecha, pues cada vez son más los procedimientos de esta naturaleza que se van a realizar, sobre todo en la población pediátrica(AU)
Awake craniotomy was the earliest surgical procedure known, and it has become fashionable again. In the past it was used for the surgical management of intractable epilepsy, but nowadays, its indications are increasing, and it is a widely recognized technique for the resection of mass lesions involving the eloquent cortex, and for deep brain stimulation. The procedure is safe, provides excellent results, and saves money and resources. The anesthesiologist should know the principles underlying neuroanesthesia, the technique of scalp blockade, and the sedation protocols, as well as feeling comfortable with advanced airway management. The main anesthetic aim is to keep patients cooperating when required (analgesia-based anesthesia). This review attempts to summarize the most recent evidence from the clinical literature, a long as the number of patients undergoing craniotomies in the awake state are increasing, specifically in the pediatric population(AU)
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Humanos , Masculino , Femenino , Craneotomía/métodos , Craneotomía , Estado de Conciencia , Sedación Consciente/instrumentación , Sedación Consciente/métodos , Sedación Consciente , Anestesia Local/instrumentación , Anestesia Local/métodos , Anestesia Local , Sedación Consciente/estadística & datos numéricos , Sedación Consciente/tendencias , Neurocirugia/métodos , Neurofisiología/instrumentación , Neurofisiología/métodosRESUMEN
An increasing number of studies are simultaneously investigating species diversity (SD) and genetic diversity (GD) in the same systems, looking for 'species- genetic diversity correlations' (SGDCs). From negative to positive SGDCs have been reported, but studies have generally not quantified the processes underlying these correlations. They were also mostly conducted at large biogeographical scales or in recently degraded habitats. Such correlations have not been looked for in natural networks of connected habitat fragments (metacommunities), and the underlying processes remain elusive in most systems. We investigated these issues by studying freshwater snails in a pond network in Guadeloupe (Lesser Antilles). We recorded SD and habitat characteristics in 232 ponds and assessed GD in 75 populations of two species. Strongly significant and positive SGDCs were detected in both species. Based on a decomposition of SGDC as a function of variance-covariance of habitat characteristics, we showed that connectivity (opportunity of water flow between a site and the nearest watershed during the rainy season) has the strongest contribution on SGDCs. More connective sites received both more alleles and more species through immigration resulting in both higher GD and higher SD. Other habitat characteristics did not contribute, or contributed negatively, to SGDCs. This is true of the desiccation frequency of ponds during the dry season, presumably because species markedly differ in their ability to tolerate desiccation. Our study shows that variation in environmental characteristics of habitat patches can promote SGDCs at metacommunity scale when the studied species respond homogeneously to these environmental characteristics.
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Ecosistema , Variación Genética , Caracoles/genética , Alelos , Animales , Biodiversidad , Guadalupe , Estanques , Dinámica PoblacionalRESUMEN
The function and structure of LysM-domain containing proteins are very diverse. Although some LysM domains are able to bind peptidoglycan or chitin type carbohydrates in bacteria, in fungi and in plants, the function(s) of vertebrate LysM domains and proteins remains largely unknown. In this study we have identified and annotated the six zebrafish genes of this family, which encode at least ten conceptual LysM-domain containing proteins. Two distinct sub-families called LysMD and OXR were identified and shown to be highly conserved across vertebrates. The detailed characterization of LysMD and OXR gene expression in zebrafish embryos showed that all the members of these sub-families are strongly expressed maternally and zygotically from the earliest stages of a vertebrate embryonic development. Moreover, the analysis of the spatio-temporal expression patterns, by whole mount and fluorescent in situ hybridizations, demonstrates pronounced LysMD and OXR gene expression in the zebrafish brain and nervous system during stages of larval development. None of the zebrafish LysMD or OXR genes was responsive to challenge with bacterial pathogens in embryo models of Salmonella and Mycobacterium infections. In addition, the expression patterns of the OXR genes were mapped in a zebrafish brain atlas.
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Salmonella typhimurium/patogenicidad , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Animales , Encéfalo/metabolismo , Embrión no Mamífero/metabolismo , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Proteínas Mitocondriales , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Mycobacterium no Tuberculosas/fisiopatología , Filogenia , Dominios y Motivos de Interacción de Proteínas/genética , Proteínas/genética , Proteínas/fisiología , Salmonelosis Animal/genética , Salmonelosis Animal/fisiopatología , Alineación de Secuencia , Análisis Espacio-Temporal , Pez Cebra/embriología , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismo , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/metabolismoRESUMEN
Awake craniotomy was the earliest surgical procedure known, and it has become fashionable again. In the past it was used for the surgical management of intractable epilepsy, but nowadays, its indications are increasing, and it is a widely recognized technique for the resection of mass lesions involving the eloquent cortex, and for deep brain stimulation. The procedure is safe, provides excellent results, and saves money and resources. The anesthesiologist should know the principles underlying neuroanesthesia, the technique of scalp blockade, and the sedation protocols, as well as feeling comfortable with advanced airway management. The main anesthetic aim is to keep patients cooperating when required (analgesia-based anesthesia). This review attempts to summarize the most recent evidence from the clinical literature, a long as the number of patients undergoing craniotomies in the awake state are increasing, specifically in the pediatric population.
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Craneotomía/métodos , Bloqueo Nervioso/métodos , Procedimientos Neuroquirúrgicos/métodos , Adulto , Manejo de la Vía Aérea/métodos , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacocinética , Profilaxis Antibiótica , Niño , Sedación Consciente , Estimulación Encefálica Profunda/métodos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacocinética , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacocinética , Narcóticos/uso terapéutico , Selección de Paciente , Cuidados Preoperatorios , Cuero Cabelludo , VigiliaRESUMEN
The objective of this study was to compare patients' and physicians' expectations concerning the recovery time for acute back pain, and their determinants. A French national observational survey was performed between October and December 2005. Each physician was asked to include the first three patients aged between 20 and 70 years presenting with acute back pain (VAS > 40 mm) of less than 1 month's duration. A total number of 1982 patients, with a mean age of 48.4 +/- 11.8 years (52.2% men), were enrolled by 834 physicians. Patients and their physicians expected recovery to take the same amount of time in 60.3% of cases (Kappa = 0.43). In 17.4% of cases, patients predicted a shorter recovery time than physicians, and in 22.4% of cases, patients predicted a longer recovery time. Both patients and physicians expected recovery time to be longer in women, and in older, unmarried, obese, and non working patients. Expected recovery time was also longer in patients with no sports activities, low back pain (as opposed to pain at other sites), a high level of disability, a history of back pain, and no triggering factor. The intensity of pain and the number of days of sick leave taken did not affect the patient's prediction of recovery time, but did affect the physicians' expectations. Physicians considered professional status, analgesic intake and previous sick leave to be independent predictive factors, whereas patients did not. Expected recovery time, assessed shortly after the onset of acute back pain is influenced by most of the clinical and demographic factors usually considered risk factors for chronic low back pain. Patients' predictions of recovery time should be assessed in acute back pain, to identify risks for expected chronicity.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Recolección de Datos/métodos , Dolor de la Región Lumbar/psicología , Dolor de la Región Lumbar/rehabilitación , Recuperación de la Función/fisiología , Actividades Cotidianas/psicología , Adaptación Psicológica , Adulto , Factores de Edad , Analgésicos/uso terapéutico , Empleo , Femenino , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/psicología , Relaciones Médico-Paciente , Factores Sexuales , Ausencia por Enfermedad/estadística & datos numéricos , Factores de TiempoRESUMEN
The aim of this study was to review the evidence supporting the use of anti-depressants in painful rheumatological conditions. A systematic review of papers published between 1966 and 2007, in five European languages, on anti-depressants in rheumatological conditions was performed. Papers were scored using Jadad method and analgesic ES was calculated. We selected 78 clinical studies and 12 meta-analyses, from 140 papers. The strongest evidence of an analgesic effect of anti-depressants has been obtained for fibromyalgia. A weak analgesic effect is observed for chronic low back pain, with an efficacy level close to that of analgesics. In RA and AS, there is no analgesic effect of anti-depressants, but these drugs may help to manage fatigue and sleep disorders. There is no clear evidence of an analgesic effect inOA, but studies have poor methodological quality. Analgesic effects of anti-depressants are independent of their anti-depressant effects. Tricyclic anti-depressants (TCAs), even at low doses, have analgesic effects equivalent to those of serotonin and noradrenalin reuptake inhibitors (SNRIs), but are less well tolerated. Selective serotonin reuptake inhibitors (SSRIs) have modest analgesic effects, but higher doses are required to achieve analgesia. Anti-depressant drugs, particularly TCAs and SNRIs, have analgesic effects in chronic rheumatic painful states in which analgesics and NSAIDs are not very efficient, such as fibromyalgia and chronic low back pain. In inflammatory rheumatic diseases, anti-depressants may be useful for managing fatigue and sleep disorders. Further studies are required to compare anti-depressants with other analgesics in the management of chronic painful rheumatological conditions.
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Antidepresivos/uso terapéutico , Dolor/tratamiento farmacológico , Enfermedades Reumáticas/tratamiento farmacológico , Artritis/complicaciones , Artritis/tratamiento farmacológico , Enfermedad Crónica , Medicina Basada en la Evidencia , Fibromialgia/tratamiento farmacológico , Humanos , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Reumáticas/complicacionesRESUMEN
Assembly of the PSI (photosystem I) complex in eukaryotic photosynthetic organisms depends on the concerted interactions of the nuclear and chloroplast genetic systems. We have identified several nucleus-encoded factors of Chlamydomonas reinhardtii that are specifically required for the synthesis of the two large chloroplast-encoded reaction-centre polypeptides, PsaA and PsaB, of photosystem I and that function at plastid post-transcriptional steps. Raa1, Raa2 and Raa3 are required for the splicing of the three discontinuous psaA precursor transcripts; they are part of large RNA-protein complexes that are reminiscent of spliceosomal particles. Tab1 and Tab2 are involved in the initiation of translation of the psaB mRNA and are localized in the membrane and stromal phases of the chloroplast, where they are associated with high-molecular-mass complexes. Moreover, two chloroplast-encoded proteins, Ycf3 and Ycf4, are required for the primary steps of assembling the photosystem I subunits into a functional complex.
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Chlamydomonas reinhardtii/fisiología , Complejo de Proteína del Fotosistema I/fisiología , Procesamiento Postranscripcional del ARN , Animales , Chlamydomonas reinhardtii/genética , Mutación , Complejo de Proteína del Fotosistema I/genética , Empalme del ARNAsunto(s)
Candidiasis , Discitis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana EdadAsunto(s)
Enfermedades del Colon/diagnóstico , Neumatosis Cistoide Intestinal/diagnóstico , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Enfermedades del Colon/diagnóstico por imagen , Colonoscopía , Diagnóstico Diferencial , Femenino , Humanos , Metronidazol/uso terapéutico , Terapia por Inhalación de Oxígeno , Neumatosis Cistoide Intestinal/diagnóstico por imagen , RadiografíaRESUMEN
BACKGROUND: There is an inverse relationship between changes in the concentration of sodium in plasma (PNa) and intracellular fluid (ICF) volume. Intakes and losses of sodium (Na), potassium (K) and water can be divided into two volumes: isotonic and electrolyte-free water (EFW). Calculations of these volumes assess a tonicity balance, a tonicity imbalance results in a change of PNa: when EFW is added to body fluids, PNa decreases. Moreover, the concept of EFW permits a good understanding of the renal contribution to the defence of body tonicity. PURPOSE: To illustrate that the measurement of a tonicity balance provides the best estimate of changes in PNa in an ICU setting. METHODS: Twenty-two patients were admitted to the Post-Operative Intensive Care Unit. We investigated how well changes in EFW balance correlated with PNa variations and what is the best formula to calculate EFW in this setting. RESULTS: PNa changes depend on EFW balance; there is no significant relationship with other classical factors such as urinary osmolality or Na-free water. CONCLUSION: The utility of a tonicity balance is demonstrated. A formula is derived facilitating at the bedside the prediction of changes in PNa following fluid therapy: PNa2 = [(PNa1.TBW) + balance (Na + K)]/[TBW + balance H2O]. PNa changes can be understood and/or modified exclusively by a careful measurement of intakes and losses of Na, K and water.
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Líquido Intracelular/metabolismo , Sodio/sangre , Equilibrio Hidroelectrolítico/fisiología , Femenino , Humanos , Masculino , Modelos Biológicos , Periodo Posoperatorio , Potasio/metabolismoRESUMEN
BACKGROUND: Deep vein thrombosis is a common, important complication of major orthopedic surgery, particularly knee arthroplasty. Knee arthroscopy is performed more frequently and in younger patients than knee arthroplasty. However, the true risk of deep vein thrombosis in patients who undergo this procedure is unknown. OBJECTIVE: To determine the incidence of deep vein thrombosis after knee arthroscopy in a large cohort of patients. METHODS: Consecutive patients scheduled for knee arthroscopy were eligible for the study. Enrolled study patients received no thromboprophylaxis. They were discharged home the day of surgery and underwent unilateral contrast venography approximately 1 week after their operation. The primary outcome measure was the incidence of venous thromboembolism. Risk factors for deep vein thrombosis were evaluated. RESULTS: Among the 184 patients who had adequate venography, deep vein thrombosis was detected in 33 (17.9%; 95% confidence interval, 12.7%-24.3%). Of these, 9 were proximal (4.9%; 95% confidence interval, 2.3%-9.1%). No patient died and no patient presented with clinically suspected pulmonary embolism. Of 33 patients, only 20 (60.6%) with deep vein thrombosis had symptoms while 13 (39.4%) were asymptomatic. The risk of deep vein thrombosis was significantly higher among patients who had a tourniquet applied for more than 60 minutes. CONCLUSIONS: The results of our study demonstrate that 17.9% of patients develop deep vein thrombosis after knee arthroscopy (most being either proximal or extensive). It is reasonable to perform a randomized trial to determine whether the incidence of deep vein thrombosis can be safely reduced in patients undergoing knee arthroscopy.
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Artroscopía/efectos adversos , Articulación de la Rodilla , Tromboflebitis/diagnóstico por imagen , Tromboflebitis/etiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Flebografía , Factores de RiesgoRESUMEN
OBJECTIVES: Six cases of pancytopenia were analyzed retrospectively among 350 patients with rheumatoid arthritis treated with methotrexate. Pancytopenia is an uncommon but severe secondary effect of methotrexate. CASE REPORTS: Five patients were hospitalized for infectious complications or hemorrhage with favorable outcome. One patient died due to septic shock. There were risk factors in all 6 patients: 5 were over 65 years of age, creatinine clearance was under 50 ml/min in 4, hypoalbuminemia was found in 4 and methotrexate was combined with an antiinflammatory drug in 4 and with ranitidine in 2. The pharmacological imputability of methotrexate was probable in 4 of the 6 patients. DISCUSSION: Acute pancytopenia in patients treated with methotrexate can be prevented by recognizing risk factors, regular laboratory tests and supplementation of all patients with folic acid according to protocols to be established.
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Artritis Reumatoide/tratamiento farmacológico , Antagonistas del Ácido Fólico/efectos adversos , Metotrexato/efectos adversos , Pancitopenia/inducido químicamente , Anciano , Femenino , Ácido Fólico/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pancitopenia/prevención & control , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Symphysitis of the pubis due to Streptococcus occurred after endoscopic resection of the prostate in a 69-year-old man. Despite a well conducted antibiotic regimen, signs persisted one year later and required arthrography that showed a prostato-symphysis fistula. This procedure might be used to find an explanation of certain persistent cases of symphysitis. Fistulization between the prostate and the pubic symphysis would be a new pathogenic hypothesis for symphysitis of the pubis.
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Enfermedades Óseas/complicaciones , Fístula/complicaciones , Osteítis/etiología , Enfermedades de la Próstata/complicaciones , Sínfisis Pubiana/patología , Adenoma/cirugía , Anciano , Analgésicos/uso terapéutico , Enfermedades Óseas/tratamiento farmacológico , Fístula/tratamiento farmacológico , Humanos , Masculino , Osteítis/diagnóstico por imagen , Osteítis/tratamiento farmacológico , Osteítis/microbiología , Complicaciones Posoperatorias , Enfermedades de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Sínfisis Pubiana/diagnóstico por imagen , Sínfisis Pubiana/microbiología , Tomografía Computarizada por Rayos XRESUMEN
We assessed the effect of ketoprofen and prednisolone on the complement receptors (CR1 and CR3) and Fc gamma RIII expression on polymorphonuclears in an ex vivo study, using a randomized, single-blind, placebo-controlled, parallel design. Twenty-four healthy, male, Caucasian volunteers received either oral ketoprofen 100 mg twice daily, or prednisolone 5 mg twice daily, or placebo twice daily for 7.5 days. CR1, CR3 and Fc gamma RIII on unstimulated and FMLP-, C5a-, LTB4-, and GM-CSF-stimulated neutrophils were assessed using specific monoclonal antibodies and flow cytometry. No statistically significant drug effect was found for CR1, CR3, and Fc gamma RIII expression on polymorphonuclears. An in vitro study also yielded negative results. These findings do not support the hypothesis that the effect of non-steroidal antiinflammatory drugs on neutrophils is due to CR1, CR3, or Fc gamma RIII modulation.
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Cetoprofeno/farmacología , Antígeno de Macrófago-1/efectos de los fármacos , Prednisolona/farmacología , Receptores de Complemento 3b/efectos de los fármacos , Receptores de IgG/efectos de los fármacos , Administración Oral , Adolescente , Adulto , Anticuerpos Monoclonales , Complemento C5a/farmacología , Simulación por Computador , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Cetoprofeno/administración & dosificación , Cetoprofeno/sangre , Leucotrieno B4/farmacología , Antígeno de Macrófago-1/biosíntesis , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Distribución Normal , Prednisolona/administración & dosificación , Prednisolona/sangre , Receptores de Complemento 3b/biosíntesis , Receptores de IgG/biosíntesis , Método Simple Ciego , Población BlancaRESUMEN
Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported. Pheochromocytoma is of particular interest because of the risk of inaugural malignant hypertensive crisis but especially because of a great degree of interfamily variability (from 0 to 92% of affected members in previously reported large kindreds). We have studied a French series of 25 pheochromocytoma (11 males, 14 females) in VHL affected patients. Twenty pheochromocytoma (80%) occurred in a familial context, whereas 5 (20%) were consistent with "apparent sporadic cases". The mean age at pheochromocytoma diagnosis was 27 years (5-55 years). Bilateral tumours have been documented in 13 cases (52%). The prevalence of pheochromocytoma revealing VHL was 14 out 25 (56%). In these cases, VHL diagnosis was considered up to 25 years later. In 6 cases (2 deceased) pheochromocytoma was the only manifestation of VHL. Thus, search for VHL must be systematic in the presence of pheochromocytoma, in the interest of the patients themselves and of potential at-risk family members (prevention of hypertensive crisis linked to latent tumours). Basic check-up (neurological and somatic examination, ophthalmoscopy, familial inquiry) may be completed with cerebral CT scan or MRI and abdominal ultrasonography followed, if positive or doubtful, by abdominal MRI or selective angiography.