RESUMEN
Inborn metabolic diseases or inborn errors of metabolism comprise a large number of rare and heterogeneous genetic diseases categorized in several subgroups depending on their pathophysiologic mechanisms. In this review, we focus on different metabolic diseases with respiratory symptoms in adults: lysosomal glycosphingolipidoses such as acid sphingomyelinase deficiency (Niemann-Pick types A and B disease), Gaucher, Fabry, Pompe diseases and mucopolysaccharidoses in general. We also address classical homocystinuria, which is a monogenic vascular disease, Hermansky-Pudlak syndrome, which is associated with disorders in the lysosomal-related-organelles, and lysinuric protein intolerance, which is due to an amino-acid transporter defect. Presentation and prognosis of these diseases are highly heterogeneous, and respiratory impairment may be central and prognostic. Many are primarily pediatric, and diagnoses are often delivered during childhood. Improved pediatric management has enabled better prognosis and new phenotype of the diseases in the adulthood. Some others can be diagnosed during adulthood. While some diseases call for specific, specialized treatment, all necessitate systematic multidisciplinary management. It is of paramount importance that a pneumologist be familiar with these phenotypes, most of which can benefit from early diagnosis and early therapeutic management with dedicated innovative treatments.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Enfermedades Metabólicas , Errores Innatos del Metabolismo , Humanos , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/terapia , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , FenotipoRESUMEN
INTRODUCTION: Bariatric surgery is a very effective treatment for obesity. After gastric bypass, micronutrient deficiencies frequently occur which can have dramatic consequences. CASE REPORT: We report the case of a 55-year-old woman who was admitted for psychomotor retardation, bilateral leg pitting edema and psoriasis-like rash that had been ongoing for 3 months. Pancytopenia, encephalopathy and heart failure rapidly occurred leading to multiorgan dysfunction syndrome and death. We retrospectively identified severe selenium deficiency with possible secondary cardiomyopathy, niacin deficiency resulting in pellagrous encephalopathy with skin lesions and gelatinous transformation of bone marrow. CONCLUSION: Micronutrient deficiency should systematically be assessed when new symptoms occur in a patient with a history of bariatric surgery. Selenium deficiency should be considered in the presence of any heart failure in this context.
Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Femenino , Derivación Gástrica/efectos adversos , Humanos , Persona de Mediana Edad , Nutrientes , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Estudios RetrospectivosRESUMEN
Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from 2001-2016, we investigated the timing of PDV introduction, risk factors associated with PDV emergence, and patterns of transmission following introduction. We identified widespread exposure to and infection with PDV across the North Pacific Ocean beginning in 2003 with a second peak of PDV exposure and infection in 2009; viral transmission across sympatric marine mammal species; and association of PDV exposure and infection with reductions in Arctic sea ice extent. Peaks of PDV exposure and infection following 2003 may reflect additional viral introductions among the diverse marine mammals in the North Pacific Ocean linked to change in Arctic sea ice extent.
Asunto(s)
Organismos Acuáticos/virología , Cetáceos/virología , Virus del Moquillo Focino/metabolismo , Moquillo , Calentamiento Global , Hielo , Nutrias/virología , Animales , Regiones Árticas , Moquillo/epidemiología , Moquillo/transmisión , Virus del Moquillo Focino/patogenicidadRESUMEN
Numerous systemic diseases (vasculitis, connective tissue disease or sarcoidosis) can display an involvement of the perianal skin, the rectum and/or the anus. Such knowledge is important in order to treat these complications specifically when possible. Lesions of the anorectum arising from systemic diseases can sometimes cause perforations in the peritoneal cavity (if concerning the higher portion of the rectum) and/or fistulization to the anal margin. Differential diagnosis, mostly infectious or inflammatory (Crohn's disease) must be ruled out in every case. Other systemic diseases can display specific manifestations as this is the case in scleroderma which can lead to anal incontinence. Despite the relative rarity of these manifestations, their ignorance would forbid global management of these complex diseases. It should thus be detected in each consultation and a regular follow-up must be provided with a proctologist and/or a gastroenterologist when needed.
Asunto(s)
Neoplasias del Ano/etiología , Enfermedades del Tejido Conjuntivo/complicaciones , Incontinencia Fecal/etiología , Lesiones Precancerosas/etiología , Sarcoidosis/complicaciones , Vasculitis/complicaciones , HumanosRESUMEN
INTRODUCTION: Cervical cancer is the twelfth most frequent cancer in women in France. Glassy cell carcinoma is a rare histological entity, rapidly aggressive, associated with a poor prognosis. CASE REPORT: A 30-year-old woman was admitted in an internal medicine department for polyarthralgia with high grade fever, evolving for 3 weeks. There was an inflammatory syndrome. The 18-FDG-PET-scan showed inflammatory lymph nodes as well as disseminated osteolytic lesions, and a primitive pelvic tumor. A 3cm tumor of the cervix was found during the gynaecologic examination. Histological analysis elicited a high-index mitotic carcinoma, glassy cell carcinoma type. Despite chemotherapy, the outcome was poor, with early death occurring after three months of follow-up. CONCLUSION: The glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients.
Asunto(s)
Carcinoma Adenoescamoso/patología , Neoplasias del Cuello Uterino/patología , Adulto , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Resultado Fatal , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Obesity and insulin resistance are positively correlated with plasma endothelin-1 (ET-1) levels; however, the mechanisms leading to increased ET-1 are not understood. Similarly, the full physiological complexity of ET-1 has yet to be described, especially in obesity. To date, one of the best treatments available for morbid obesity is bariatric surgery to quickly reduce body fat and the factors associated with obesity-related disease; however, the effects of vertical sleeve gastrectomy (SG) on plasma ET-1 have not been described. OBJECTIVES: To determine if SG will reduce plasma ET-1 levels and to determine if plasma ET-1 concentration is associated with weight loss after surgery. SETTING: The studies were undertaken at a University Hospital. METHODS: This was tested by measuring plasma ET-1 levels from 12 obese patients before and after SG. All data were collected from clinic visits before SG, 6 weeks after SG, and 6 months after surgery. RESULTS: At 6 weeks after SG, plasma ET-1 levels increased by 24%; however, after 6 months, there was a 27% decrease compared with presurgery. Average weight loss in this cohort was 11.3% ± 2.4% body weight after 6 weeks and 21.4% ± 5.7% body weight after 6 months. Interestingly, we observed an inverse relationship between baseline plasma ET-1 and percent body weight loss (R2 = .49, P = .01) and change in body mass index 6 months (R2 = .45, P = .011) post bariatric surgery. CONCLUSIONS: Our results indicate that SG reduces plasma ET-1 levels, a possible mechanism for improved metabolic risk in these patients. These data also suggest that ET-1 may serve as a predictor of weight loss after bariatric surgery.
Asunto(s)
Cirugía Bariátrica , Endotelina-1/sangre , Gastrectomía , Obesidad Mórbida/sangre , Obesidad Mórbida/cirugía , Pérdida de Peso , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cystathionine beta synthase (CBS) is one of the 225 genes on chromosome 21 (HSA 21) that are triplicated in persons with trisomy 21 (Down syndrome). Although most triplicate HSA21 genes have their orthologous genes on murine chromosome 16, the murine ortholog of hCBS is on murine chromosome 17 and thus is not present in the well-studied Ts65Dn mouse model of trisomy 21. Persons with trisomy 21 (T21) present deficits in neurotransmission and exhibit early brain aging that can partially be explained by monoamine neurotransmitter alterations. We used transgenic mice for the hCBS gene, which overexpress the CBS protein in various brain regions, to study if CBS overexpression induces modifications in the monoamine neurotransmitters in the hypothalamus, thalamus, hippocampus, and striatum from transgenic and control female and male mice aged 3-4 months and 11-12 months. Sex, age, and brain area each influenced neurotransmitter levels. Briefly, the serotonin pathway was modified by CBS overexpression in various brain areas in female mice but not in male mice. The dopamine pathway was modified in brain regions according to sex and age. These results may allow us to better understand the role of the transsulfuration pathway and especially CBS overexpression in the metabolism of biogenic amines and the catecholamine catabolism in persons with trisomy 21.
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Encéfalo/metabolismo , Cistationina betasintasa/metabolismo , Dopamina/metabolismo , Serotonina/metabolismo , Animales , Femenino , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Estadísticas no ParamétricasAsunto(s)
Coccidioidomicosis/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico , Linfocitos/patología , Meningitis Fúngica/diagnóstico , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Biopsia , Coccidioidomicosis/tratamiento farmacológico , Femenino , Humanos , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Meningitis Fúngica/tratamiento farmacológico , Tomografía Computarizada por Rayos XRESUMEN
The emergence of multi-resistant bacteria (MRB) in developing countries (DCs) is a worrying phenomenon at regional and international levels with a risk of international spread through travelers. The French guidelines recommend a systematic screening in case of hospitalization, for the travelers who have been repatriated and for those with a history of hospitalization in a foreign country during the past year. A simple travel in DCs is not considered as a risk factor for colonization or infection with a MRB. We report the case of a 56-year-old man with acute prostatitis and epididymitis due to Extended-spectrum ß-lactamase-producing Escherichia coli. He was returning from Southeast Asia with no history of hospitalization or recent use of antibiotics. However, he had unprotected sex during his travel. This case report leads us to discuss the different ways of acquiring this resistant bacterium during travel as well as the usefulness of expanding the screening of carriage for MRB in all travelers in case of hospitalization.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/diagnóstico , Escherichia coli/aislamiento & purificación , Viaje , Infecciones Urinarias/diagnóstico , Asia Sudoriental , Farmacorresistencia Bacteriana Múltiple/genética , Epididimitis/diagnóstico , Epididimitis/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/microbiología , Humanos , Masculino , Persona de Mediana Edad , Prostatitis/diagnóstico , Prostatitis/microbiología , Enfermedades Bacterianas de Transmisión Sexual/complicaciones , Enfermedades Bacterianas de Transmisión Sexual/diagnóstico , Enfermedades Bacterianas de Transmisión Sexual/microbiología , Tailandia , Medicina del Viajero , Infecciones Urinarias/complicaciones , Infecciones Urinarias/microbiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
This retrospective casenote audit involving 374 patients requiring intubation for an anaesthetic found that when the availability of sugammadex became unrestricted, its use increased from 7.1 to 65.3% (P <0.0001) of all muscle relaxant reversals, while neostigmine use decreased from 59.6 to 12.5%. Rocuronium use decreased slightly (90.8 to 79.2%, P=0.006) but vecuronium use increased (2.1 to 8.3%, P=0.02). Cisatracurium and suxamethonium use were unchanged. Total rocuronium dose (55.9 ± 24.1 vs 60.4 ± 22.3 mg) and the number of doses (1.9 ± 1.48 to 1.96 ± 1.27) were unchanged, but the time between the last dose and reversal decreased (91.7 ± 68.1 to 62 ± 52.4 minutes, P=0.0002). There appeared to be no change in postoperative nausea and vomiting, or post-anaesthesia care unit time or oxygen saturation levels. Anaesthetic theatre time fell from 143.5 ± 85.8 to 120 ± 71.2 minutes (P=0.01) and remained significant when adjusted for confounding variables (ratio of means 1.17, 95% confidence interval 1.03 to 1.34, P=0.02), although inferences in relation to causality are limited by the retrospective and observational design of the study. Hospital stay also appeared to fall (4.2 ± 3.5 to 3.4 ± 3.0 days, P=0.035), but was not statistically significant when adjusted for confounding variables (ratio of means 1.04, 95% confidence interval 0.89 to 1.2, P=0.59). These observations suggest that the unrestricted availability of sugammadex will change how steroid-based neuromuscular blocking drugs are used and reversed, but further research is needed to determine if patient outcomes will improve.
Asunto(s)
Anestesia , Hospitales de Enseñanza , Relajantes Musculares Centrales/antagonistas & inhibidores , Bloqueo Neuromuscular/métodos , gamma-Ciclodextrinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Androstanoles , Inhibidores de la Colinesterasa/uso terapéutico , Utilización de Medicamentos , Femenino , Auditoría Financiera , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Neostigmina/uso terapéutico , Fármacos Neuromusculares Despolarizantes , Fármacos Neuromusculares no Despolarizantes , Quirófanos/organización & administración , Estudios Retrospectivos , Rocuronio , Programas Informáticos , Succinilcolina , Sugammadex , Resultado del Tratamiento , gamma-Ciclodextrinas/economíaRESUMEN
OBJECTIVES: Angioplasty is often used in the management of lower limb ischaemia and can reduce the need for infrainguinal bypass in some patients. There is an associated failure rate with this technique and bypass surgery is often used in this situation as a secondary limb salvage procedure. We aimed to evaluate the outcome of infrainguinal bypass grafting following failed attempt at angioplasty. METHODS: All cases of infrainguinal bypass at a single centre over a seven year period were identified and notes reviewed. Cases were divided into four groups according to their indication for surgery; acute ischaemia, chronic critical ischaemia, failed angioplasty and an 'other' group including aneurysmal disease and claudicants. The failed angioplasty group was compared with the other three groups. Survival analysis was performed using Kaplan Meier curves and groups compared in terms of long term patency and survival. RESULTS: Primary patency was 61.2% in the failed angioplasty group at 12 months compared with 60.6% in the other groups (P=1.11). There was also no significant difference in primary patency at 60 months (50% vs 40.6%, P=0.26). Survival at 12 months was also comparable between the groups (failed angioplasty group 74.2% compared with 77.3% in the other groups, P=0.662) as was 60 months survival (33.3% and 35.4% respectively, P=0.166). DISCUSSION: In this study, outcome of infrainguinal bypass following failed angioplasty was comparable to outcome of surgery performed for another indication. This paper supports the use of distal bypass surgery for limb salvage in cases where minimal access techniques have failed.
Asunto(s)
Angioplastia/efectos adversos , Implantación de Prótesis Vascular/métodos , Arteria Femoral/cirugía , Enfermedades Vasculares Periféricas/terapia , Arteria Poplítea/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Arteria Femoral/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Conducto Inguinal , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Enfermedades Vasculares Periféricas/fisiopatología , Arteria Poplítea/diagnóstico por imagen , Pronóstico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Ultrasonografía Doppler Dúplex , Grado de Desobstrucción Vascular/fisiologíaRESUMEN
SOD1 is one of several overexpressed genes in trisomy 21. In order to dissect possible genetic causes of the syndrome, wild-type SOD1/SOD1 transgenic mice were compared to FVB/N non-transgenic controls at 5 months of age in tests of exploratory activity and motor coordination. Wild-type SOD1/SOD1 transgenic mice had fewer stereotyped movements in an open-field and fell sooner from a rotorod than controls. In contrast, wild-type SOD1/SOD1 transgenic mice had fewer falls on a wire suspension test. There was no intergroup difference for ambulatory movements in the open-field, exploration of the elevated plus-maze, emergence from a small compartment, and motor coordination on a stationary beam. These results indicate that homozygous mice expressing human SOD1 are impaired in their ability to adjust their posture in response to a moving surface and make fewer small-amplitude movements without any change in general exploratory activity.
Asunto(s)
Conducta Exploratoria/fisiología , Ratones Transgénicos/fisiología , Desempeño Psicomotor/fisiología , Superóxido Dismutasa/genética , Análisis de Varianza , Animales , Conducta Animal/fisiología , Humanos , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Tiempo de Reacción/genética , Prueba de Desempeño de Rotación con Aceleración Constante/métodos , Superóxido Dismutasa-1 , Factores de TiempoRESUMEN
Peptides derived from proteolytic processing of the amyloid precursor protein (APP) are important for the pathogenesis of Alzheimer's disease (AD). In the present study, we found that transgenic mice overexpressing wild-type human APP gene (hAPP/+) displayed a much higher expression of FAS, one of the death receptor subfamily. This FAS overexpression was significantly reduced in the cortex of mice overexpressing both wild-type hAPP gene and wild-type human superoxide dismutase-1 gene (hSOD-1). Moreover hSOD-1 transgenic expression was associated with an increase of Glial fibrillary acidic protein (GFAP) production. This study indicates that SOD-1 overexpression can inhibit FAS expression, which may be beneficial in AD.
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Precursor de Proteína beta-Amiloide/biosíntesis , Corteza Cerebral/metabolismo , Superóxido Dismutasa/metabolismo , Receptor fas/biosíntesis , Enfermedad de Alzheimer/fisiopatología , Animales , Corteza Cerebral/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/biosíntesis , Humanos , Masculino , Ratones , Ratones Transgénicos , Superóxido Dismutasa-1RESUMEN
SOD1 is one of several overexpressed genes in Down's syndrome. In order to dissect genetic causes of the syndrome, hemizygous human wild-type SOD1 transgenic mice were compared to FVB/N non-transgenic controls at 3 months of age in the SHIRPA primary screen of neurologic function as well as in tests of motor activity and coordination. The responsiveness of SOD1/wt transgenic mice to visual and somatosensory stimuli was reduced in placing, pinna, corneal, and toe-pinch tests. In addition, SOD1/wt transgenic mice crossed fewer segments on a stationary beam. On the contrary, there was no intergroup difference for motor activity and anxiety in open-field and emergence tests and for latencies before falling on the stationary beam, coat-hanger, and rotorod. These results indicate mild deficits in sensorimotor responsiveness in a mouse model expressing human SOD1 and that the overexpressed gene may be responsible for some Down symptoms.
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Trastornos de Ansiedad/genética , Síndrome de Down/genética , Síndrome de Down/psicología , Trastornos Somatosensoriales/genética , Superóxido Dismutasa/genética , Animales , Trastornos de Ansiedad/fisiopatología , Modelos Animales de Enfermedad , Síndrome de Down/fisiopatología , Conducta Exploratoria/fisiología , Femenino , Humanos , Conducta Impulsiva/genética , Conducta Impulsiva/fisiopatología , Masculino , Ratones , Ratones Transgénicos , Actividad Motora/genética , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/genética , Examen Neurológico/métodos , Dimensión del Dolor/métodos , Estimulación Física , Trastornos Somatosensoriales/fisiopatología , Superóxido Dismutasa-1RESUMEN
Sleep-wake homeostasis is crucial for behavioral performances and memory in the general population and in learning disability populations among them Down syndrome patients. We investigated, in a mouse model of Down syndrome, cortical EEG and sleep-wake architecture under baseline conditions and after a 4 hr sleep deprivation (SD). Young heterozygous transgenic mice (S/+) for the human Cu/Zn superoxide dismutase (hSOD-1) were obtained on FVB/N background. Baseline records for slow wave sleep (SWS) and wake (W) parameters were the same in S/+ and control mice whereas paradoxical sleep (PS) episode number decreased and PS latency increased after light off in S/+ mice. These data correlate well the polysomnographic phenotype of young DS patients.
Asunto(s)
Modelos Animales de Enfermedad , Síndrome de Down/enzimología , Polisomnografía/métodos , Fases del Sueño/fisiología , Superóxido Dismutasa/biosíntesis , Animales , Síndrome de Down/genética , Humanos , Masculino , Ratones , Ratones Transgénicos , Fases del Sueño/genética , Superóxido Dismutasa/genética , Superóxido Dismutasa-1RESUMEN
BACKGROUND: This study sought to identify potential cost-effective methods to improve trauma care in hospitals in the developing world. METHODS: Injured patients admitted to an urban hospital in Ghana over a 1-year period were analyzed prospectively for mechanism of injury, mode of transport to the hospital, injury severity, region of principal injury, operations performed, and mortality. In addition, time from injury until arrival at the hospital and time from arrival at the hospital until emergency surgery were evaluated. RESULTS: Mortality was 9.4%. Most deaths (65%) occurred within 24 hours of admission. Sixty percent of emergency operations were performed over 6 hours after arrival. Tube thoracostomy was performed on only 13 patients (0.6%). Only 58% of patients received intravenous crystalloid and only 3.6% received 1 or more units of blood. CONCLUSION: We identified several specific interventions as potential low-cost measures to improve hospital-based trauma care in this setting, including shorter times to emergency surgery and improvements in initial resuscitation. In addition to addressing each of these aspects of trauma care individually, quality improvement programs may represent a feasible and sustainable method to improve trauma care in hospitals in the developing world.
Asunto(s)
Prioridades en Salud , Garantía de la Calidad de Atención de Salud/métodos , Centros Traumatológicos/normas , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Ghana/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Garantía de la Calidad de Atención de Salud/economía , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Factores de Tiempo , Transporte de Pacientes , Resultado del Tratamiento , Heridas y Lesiones/epidemiología , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapiaRESUMEN
FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.