RESUMEN
Recruitment in preventive vaccine trials (PVT) is challenging due to common barriers to clinical research and lack of vaccine confidence. Identifying determinants of participation can help to improve recruitment. A prospective survey was conducted in 5 French clinical investigational sites. People asked to participate in a PVT were given a questionnaire whether they decided to participate or not in the trial. A total of 341 people answered the survey: 210 accepting and 131 declining to participate in a PVT. Acceptors were significantly younger (38.5 vs 54.9â¯years old), more likely to be involved in early phase trials, had a higher level of education (pâ¯<â¯0.005) and a significantly better general opinion concerning vaccines (92.3% versus 72.3%, pâ¯<â¯0.005) compared with those who declined. Factors associated with acceptance or refusal were evaluated in 224 people in the 4 sites where both groups were included. In a multivariate analysis, three factors: older age, having heard about PVT through multiple sources and financial incentives were significantly associated with refusal to participate in the PVT. A generally favourable opinion of vaccines was associated with acceptance. The main motivation for participation was altruism (93.2%) whereas fear of side effects was at the forefront of the barriers (36.6%). Information given by the physician was a key point for decision-making in 70.2% of those who accepted. In brief, vaccine hesitancy may decrease recruitment in PVTs; reinforcing altruism and quality of information given are key points in acceptance of participation in PVT.
Asunto(s)
Ensayos Clínicos como Asunto , Motivación , Selección de Paciente , Vacunas , Adulto , Anciano , Ensayos Clínicos como Asunto/psicología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Vacunas/administración & dosificación , Vacunas/inmunologíaRESUMEN
Ciliopathies are heterogeneous disorders sharing different clinical signs due to a defect at the level of the primary cilia/centrosome complex. Postaxial polydactyly is frequently reported in ciliopathies, especially in Bardet-Biedl syndrome (BBS). Clinical features and genetic results observed in a pair of dizygotic twins with BBS are reported. The following manifestations were present: retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment and renal dysfunction. X-rays of the hands confirmed the presence of a 4th mesoaxial extra-digit with Y-shaped metacarpal bones. The sequencing of LZTFL1 identified a missense mutation (NM_020347.2: p.Leu87Pro; c.260T>C) and a nonsense mutation (p.Glu260*; c.778G>T), establishing a compound heterozygous status for the twins. A major decrease of LZTFL1 transcript and protein was observed in the patient's fibroblasts. This is the second report of LZTFL1 mutations in BBS patients confirming LZTFL1 as a BBS gene. Interestingly, the only two families reported in literature thus far with LZTFL1 mutations have in common mesoaxial polydactyly, a very uncommon feature for BBS. This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17).
Asunto(s)
Síndrome de Bardet-Biedl/genética , Dedos/anomalías , Mutación/genética , Polidactilia/genética , Dedos del Pie/anomalías , Factores de Transcripción/genética , Adulto , Síndrome de Bardet-Biedl/fisiopatología , Análisis Mutacional de ADN , Femenino , Dedos/fisiopatología , Heterocigoto , Humanos , Linaje , Polidactilia/fisiopatología , Dedos del Pie/fisiopatología , GemelosRESUMEN
The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.
RESUMEN
Radiofrequency is increasingly used to manage liver tumors. This report describes the case of a 74-year-old man who received two courses of percutaneous radiofrequency thermal ablation for a hepatocellular carcinoma over a 4-month period. He subsequently required computed tomography-guided drainage for an area of intrahepatic necrosis. During the procedure, hemobilia developed, followed by respiratory distress and collapse. The diagnosis of bile pulmonary embolism was established on the basis of high biliary acid concentrations in pulmonary fluid aspiration and blood plasma. Radiofrequency thermoablation provides local control of advanced liver tumors with low recurrence and morbidity. However, this interventional procedure risks damage to liver parenchyma involving vascular and biliary structures, which may lead to biliary-venous fistula and possible bile emboli.
Asunto(s)
Conductos Biliares Intrahepáticos/lesiones , Bilis , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/efectos adversos , Neoplasias Hepáticas/cirugía , Embolia Pulmonar/etiología , Punciones/efectos adversos , Anciano , Anuria/etiología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Fístula Biliar/etiología , Carcinoma Hepatocelular/complicaciones , Drenaje/efectos adversos , Resultado Fatal , Hemobilia/etiología , Humanos , Complicaciones Intraoperatorias/etiología , Hígado/diagnóstico por imagen , Hígado/lesiones , Neoplasias Hepáticas/complicaciones , Masculino , Complicaciones Posoperatorias/etiología , Radiografía Intervencional , Síndrome de Dificultad Respiratoria/etiología , Tomografía Computarizada por Rayos X , Fístula Vascular/etiologíaRESUMEN
We report the case of a young man who presented with a clinical picture of acute pyelonephritis. Within 3 h of admission, the patient developed acute respiratory distress associated with tachycardia and shock, and he was transferred to the intensive care unit. Mechanical ventilation of the lungs and symptomatic treatment were started immediately. Abdominal ultrasound revealed the presence of an adrenal tumour with central necrosis indicating a probable phaeochromocytoma. There was no sign of pyelonephritis. Ventricular fibrillation followed by asystole occurred soon after admission. The suddenness of the patient's death did not allow time for further investigation and therapy. The severity of the clinical signs was probably related to a massive release of catecholamines because of necrosis of the tumour, which may have been worsened by the diagnostic procedures performed to investigate the clinical symptoms and signs of acute pyelonephritis.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Feocromocitoma/complicaciones , Pielonefritis/etiología , Enfermedad Aguda , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Proteína C-Reactiva/análisis , Catecolaminas/sangre , Humanos , Hipertensión/etiología , Masculino , Feocromocitoma/patologíaRESUMEN
The effects of acute and repeated gamma-hydroxybutyrate (GHB) and cocaine administration on D1 and D2 dopamine receptor mRNA expression were examined using in situ hybridization histochemistry in different rat brain structures rich in GHB receptors. Six hours after a single GHB administration (500 mg/kg i.p.), an increase in D1 and D2 mRNA expression was observed in almost all regions examined; whereas, acute cocaine injection (20 mg/kg i.p.) had no effect. Repeated exposure to GHB (500 mg/kg i.p. twice daily) for 10 days, followed by a 14-h withdrawal period, induced increasing effects on D1 and D2 dopamine receptor mRNA expression, similar to those caused by chronic treatment with cocaine (20 mg/kg i.p. once a day). These effects of GHB and cocaine on dopamine receptor mRNA expression could be a consequence, for both compounds, of the modulation of dopaminergic activity; thus, supporting the benefit of GHB in cocaine substitution therapy.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , ARN Mensajero , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Adyuvantes Anestésicos/farmacología , Animales , Autorradiografía , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Lóbulo Frontal/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiología , Hibridación in Situ , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Neostriado/fisiología , Vías Olfatorias/efectos de los fármacos , Vías Olfatorias/metabolismo , Vías Olfatorias/fisiología , Ratas , Ratas Wistar , Oxibato de Sodio/farmacología , Radioisótopos de AzufreRESUMEN
The effects of gamma-hydroxybutyrate (GHB) on prodynorphin (PD) and proenkephalin (PE) mRNA expression were examined using in situ hybridization histochemistry in discrete rat brain structures rich in GHB receptors. A single dose of GHB (500 mg/kg i.p.) increased striatal PE mRNA levels (+60%) between 15 and 90 min after injection. An increase in PD mRNA expression was observed in the frontal cortex (+90%) 6 h after GHB administration. Chronic exposure to GHB (500 mg/kg i.p. twice a day) for 10 days induced significant increases in both PE and PD mRNA levels in different brain regions examined, suggesting that PD and PE mRNA expressions are modulated by the endogenous GHBergic system.
Asunto(s)
Encefalinas/genética , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Oxibato de Sodio/administración & dosificación , Adyuvantes Anestésicos/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Encefalinas/biosíntesis , Encefalinas/metabolismo , Inyecciones Intraperitoneales , Masculino , Precursores de Proteínas/biosíntesis , Precursores de Proteínas/metabolismo , ARN Mensajero/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobutyric acid (GABA) metabolism which possesses neuromodulatory properties in brain, were investigated in the elevated plus maze in rats. The number of entries and the time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg i.p.). This is classically considered as indicative of an anxiolytic effect of the drug. There was no sedative effect at these doses as measured by the spontaneous locomotor activity in the actimeter or the total number of arm entries. The anxiolytic properties of GHB were reversed by neither the GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid) (300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/kg i.p.). However the anti-anxiety effect of GHB was antagonized by the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.), suggesting an interaction of GHB with the GABA(A) receptor complex which mediates the anti-anxiety effect of benzodiazepines.
Asunto(s)
Ansiolíticos/antagonistas & inhibidores , Ansiolíticos/farmacología , Flumazenil/farmacología , Moduladores del GABA/farmacología , Oxibato de Sodio/antagonistas & inhibidores , Oxibato de Sodio/farmacología , Animales , Anticonvulsivantes/farmacología , Conducta Animal/efectos de los fármacos , Benzocicloheptenos/farmacología , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Actividad Motora/efectos de los fármacos , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , RatasRESUMEN
Hypnosis can be a useful adjunct to other treatment modalities. For example, hypnosis may induce a level of relaxation that allows patients to cooperate more easily with conventional treatment. The often dramatic historical background of hypnosis has led to misconceptions about hypnotic technique and its clinical applications in modern medicine. Hypnosis is useful in the treatment of acute and chronic pain, somatoform and habit disorders, anxiety and depression. Persons who are attempting to stop smoking, patients with bulimia and those with psychogenic impotence may respond to hypnosis.
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Medicina Familiar y Comunitaria , Hipnosis , Humanos , Cicatrización de HeridasRESUMEN
There is controversy in the courts about the admissibility of statements by victims, eyewitnesses, and defendants following hypnosis. The scientific community has strongly influenced many court decisions about credibility, reliability, and admissibility of memory retrieval where hypnosis is used. The author presents two case histories of defendants whose memories were refreshed by hypnosis. He presents current court rulings on the use of hypnosis and discusses their impact on laboratory data involving memory and reliability.
Asunto(s)
Homicidio/legislación & jurisprudencia , Hipnosis , Memoria , Adulto , Amnesia , Estado de Conciencia , Femenino , Humanos , MasculinoAsunto(s)
Derecho Penal , Psiquiatría Forense , Hipnosis/métodos , Jurisprudencia , Adulto , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana EdadRESUMEN
A technique to cause cessation of impulse and to shorten the course of treatment for individuals who engage in exhibitionism is described. The patients were carefully selected. The psychodynamics were described and identified for each patient, and the results have been favorable to date. The great advantages of the methods used have been keeping the patient functional in society, shortening the duration of treatment, and reducing cost. The technique has been successful in the treatment of patients suffering from other forms of impulse disorders. Long-term follow-up studies are recommended for any patient receiving this method of hypnotic treatment.