RESUMEN
A 4-year-old French bulldog was presented with neck pain and left forelimb lameness. CT scan revealed a bony defect in the craniodorsal rim of the endplate of C5 with a concomitant disc protrusion leading to ventral spinal cord compression. Ventral slot at C4-C5 was performed to remove the protruding material and the fragment. Based on CT and histological findings, this bone defect was consistent with osteochondritis dissecans. Neck pain was absent immediately after the operation and the dog recovered without complication. Only a slight proprioceptive deficit of the left forelimb persisted during the 6-month of follow-up. Based on our search of the veterinary literature, this is the first published report of an osteochondritis dissecans of cervical endplate treated surgically.
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Enfermedades de los Perros , Desplazamiento del Disco Intervertebral , Osteocondritis Disecante , Perros , Animales , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/veterinaria , Dolor de Cuello/veterinaria , Osteocondritis Disecante/diagnóstico por imagen , Osteocondritis Disecante/cirugía , Osteocondritis Disecante/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugíaRESUMEN
Metabolic engineering strategies are crucial for the development of bacterial cell factories with improved performance. Until now, optimal metabolic networks have been designed based on systems biology approaches integrating large-scale data on the steady-state concentrations of mRNA, protein and metabolites, sometimes with dynamic data on fluxes, but rarely with any information on mRNA degradation. In this review, we compile growing evidence that mRNA degradation is a key regulatory level in E. coli that metabolic engineering strategies should take into account. We first discuss how mRNA degradation interacts with transcription and translation, two other gene expression processes, to balance transcription regulation and remove poorly translated mRNAs. The many reciprocal interactions between mRNA degradation and metabolism are also highlighted: metabolic activity can be controlled by changes in mRNA degradation and in return, the activity of the mRNA degradation machinery is controlled by metabolic factors. The mathematical models of the crosstalk between mRNA degradation dynamics and other cellular processes are presented and discussed with a view towards novel mRNA degradation-based metabolic engineering strategies. We show finally that mRNA degradation-based strategies have already successfully been applied to improve heterologous protein synthesis. Overall, this review underlines how important mRNA degradation is in regulating E. coli metabolism and identifies mRNA degradation as a key target for innovative metabolic engineering strategies in biotechnology.
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Escherichia coli , Ingeniería Metabólica , Escherichia coli/genética , Redes y Vías Metabólicas , Estabilidad del ARN , Biología de SistemasRESUMEN
In living organisms, the same enzyme catalyses the degradation of thousands of different mRNAs, but the possible influence of competing substrates has been largely ignored so far. We develop a simple mechanistic model of the coupled degradation of all cell mRNAs using the total quasi-steady-state approximation of the Michaelis-Menten framework. Numerical simulations of the model using carefully chosen parameters and analyses of rate sensitivity coefficients show how substrate competition alters mRNA decay. The model predictions reproduce and explain a number of experimental observations on mRNA decay following transcription arrest, such as delays before the onset of degradation, the occurrence of variable degradation profiles with increased non linearities and the negative correlation between mRNA half-life and concentration. The competition acts at different levels, through the initial concentration of cell mRNAs and by modifying the enzyme affinity for its targets. The consequence is a global slow down of mRNA decay due to enzyme titration and the amplification of its apparent affinity. Competition happens to stabilize weakly affine mRNAs and to destabilize the most affine ones. We believe that this mechanistic model is an interesting alternative to the exponential models commonly used for the determination of mRNA half-lives. It allows analysing regulatory mechanisms of mRNA degradation and its predictions are directly comparable to experimental data.
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Estabilidad del ARN , Semivida , ARN Mensajero/genéticaRESUMEN
INTRODUCTION: Though several assessment tools for resident professional skills based on workplace direct observation have been validated, they remain scarcely used in France. The objective of this study was to evaluate the reliability and the validity of a workbook including several assessment forms for different components of the professional competency. METHODS: Three assessment forms have been tested over a period of 6 months in a multicentric study including 12 French internal medicine departments: the French version of the mini-CEX, an interpersonal skills assessment form (OD_CR) and the multisource feedback form (E_360). Reliability has been assess using the intra-class correlation coefficient (ICC) and the Cronbach alpha coefficient. Arguments for validity have been provided looking at the ability of the forms to detect an increase in the scores over time and according to the level of experience of the resident. RESULTS: Twenty-five residents have been included. The Cronbach alpha was of 0.90 (n=70) with the mini-CEX, 0.89 with the OD_CR (n=62) and 0.77 with the E_360 (n=86). ICC showed a wide variation according to the items of the mini-CEX and the OD-CR probably due to the poor number of observations performed by residents. The scores of most of the items of these two forms increased between M1 and M6. The scores of the E_360 were high: 7.3±0.8 to 8.3±2.4 (maximum 9) and did not vary according to the level of experience. CONCLUSION: This study suggest that it would be difficult to ensure a sufficient reliability for professional skills assessment using these tools given our available current human and material resources. However, these assessment forms could be added to the resident portfolio as supports for the debriefing in order to document their progression during their formation.
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Evaluación Educacional/métodos , Medicina Interna/educación , Internado y Residencia , Competencia Clínica , Evaluación Educacional/normas , Escolaridad , Francia , Humanos , Medicina Interna/normas , Internado y Residencia/normas , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los Resultados , Proyectos de Investigación , Estudiantes de Medicina/estadística & datos numéricosRESUMEN
BACKGROUND: The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70. PATIENTS AND METHODS: This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years. RESULTS: Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively. CONCLUSION: Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.
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Medicina Interna , Enfermedades de Inicio Tardío/diagnóstico , Esclerodermia Sistémica/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Francia/epidemiología , Reflujo Gastroesofágico/complicaciones , Humanos , Enfermedades de Inicio Tardío/mortalidad , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Estudios Retrospectivos , Factores de Riesgo , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/mortalidad , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/mortalidad , Úlcera Cutánea/complicaciones , Telangiectasia/complicacionesRESUMEN
BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.
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Modelos Animales de Enfermedad , Endoscopía Gastrointestinal/educación , Hemostasis Endoscópica/educación , Hemostasis Endoscópica/métodos , Úlcera Péptica Hemorrágica/terapia , Úlcera Gástrica/terapia , Animales , Actitud del Personal de Salud , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Electrocoagulación , Epinefrina/uso terapéutico , Femenino , Hemostasis Endoscópica/instrumentación , Humanos , Úlcera Péptica Hemorrágica/patología , Reproducibilidad de los Resultados , Úlcera Gástrica/patología , Vasoconstrictores/uso terapéuticoRESUMEN
Superior vena cava syndrome is a rare disease, most often found to result from a malignant process, which causes extrinsic compression of the superior vena cava. In recent years, there has been an increase of superior vena cava syndrome related to medical devices (implantable site, pacemaker [PM], central venous line for parenteral nutrition...). We report the case of a 37-year-old patient who developed a superior vena cava syndrome 12 years after implantation of a PM. The diagnosis was established on venography after two negative venous-CT focused on the superior vena cava. The superior vena cava syndrome improved immediately after angioplasty and stenting covering the PM probes at the superior vena cava/brachiocephalic venous trunk junction.
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Electrodos Implantados/efectos adversos , Marcapaso Artificial/efectos adversos , Síndrome de la Vena Cava Superior/etiología , Adulto , Angioplastia , Anticoagulantes/uso terapéutico , Acuicultura , Bloqueo Atrioventricular/terapia , Venas Braquiocefálicas/diagnóstico por imagen , Cateterismo Cardíaco , Terapia Combinada , Disnea/etiología , Humanos , Masculino , Enfermedades Profesionales/etiología , Stents , Síndrome de la Vena Cava Superior/diagnóstico por imagen , Síndrome de la Vena Cava Superior/tratamiento farmacológico , Síndrome de la Vena Cava Superior/terapia , Síncope/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Vena Cava Superior/diagnóstico por imagenRESUMEN
This work explores the factors associated with contamination of public spas by Legionella spp., Pseudomonas aeruginosa and Escherichia coli. Physicochemical and microbiological parameters were measured in water samples from 95 spas inQuébec, Canada. Spa maintenance was documented by a questionnaire. Legionella spp. were detected in 23% of spas, P. aeruginosa in 41% and E. coli in 2%. Bacteria were found in concerning concentrations (Legionella spp. ≥ 500 CFU/l, P. aeruginosa ≥ 51 CFU/100 ml or E. coli ≥ 1 CFU/100 ml) in 26% ofspas. Observed physicochemical parameters frequently differed from recommended guidelines. The following factors decreased the prevalence of concerning microbial contamination: a free chlorine concentration ≥ 2 mg/l or total bromine ≥ 3 mg/l (p = 0.001), an oxidation-reduction potential (ORP) > 650 mV (p = 0.001), emptying and cleaning the spa at least monthly (p = 0.019) and a turbidity ≤ 1 NTU (p = 0.013). Proper regulations and training of spa operators are critical for better maintenance of these increasingly popular facilities.
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Baños , Exposición a Riesgos Ambientales , Escherichia coli/aislamiento & purificación , Agua Dulce/microbiología , Legionella/aislamiento & purificación , Pseudomonas aeruginosa/aislamiento & purificación , Baños/normas , Recuento de Colonia Microbiana , Monitoreo del Ambiente , Agua Dulce/química , Quebec , Abastecimiento de Agua/análisisRESUMEN
BACKGROUND: To evaluate the safety, pharmacokinetics (PKs), and pharmacodynamics of aflibercept, and to identify the recommended phase II dose (RP2D) of aflibercept in combination with pemetrexed and cisplatin. METHODS: Aflibercept was administered at escalating doses of 2, 4, or 6 mg kg(-1) in combination with fixed doses of pemetrexed (500 mg m(-2)) plus cisplatin (75 mg m(-2)) every 3 weeks. Blood samples were collected for PK analyses. Serum antiaflibercept antibodies were quantified to assess their impact on systemic aflibercept concentrations. RESULTS: Eighteen patients were enrolled. One patient dosed at 4 mg kg(-1) experienced grade 3 hypophosphatemia (dose-limiting toxicity; DLT), which prompted a cohort expansion. No further DLTs were observed in the 4 mg kg(-1) cohort or the 6 mg kg(-1) dose cohort. Most common adverse events (AEs) of all grades included (%): fatigue (89), anaemia (89), nausea (83), hyponatremia (78), and neutropenia (72). Grade ≥ 3 AEs consistent with anti-vascular endothelial growth factor therapy included (%): hypertension (22), pulmonary embolism (11), and deep vein thrombosis (6). Five patients (28%) experienced mild neurocognitive disturbance. No episodes of reversible posterior leukoencephalopathy syndrome (RPLS) were noted. CONCLUSION: The results of this phase I study allowed further evaluation of the combination of aflibercept with pemetrexed and cisplatin in a phase II study. The RP2D of aflibercept was 6 mg kg(-1), to be administered intravenously every 3 weeks in combination with pemetrexed and cisplatin.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Glutamatos/administración & dosificación , Guanina/análogos & derivados , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes de Fusión/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Guanina/administración & dosificación , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Náusea/inducido químicamente , Pemetrexed , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/sangreAsunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Artritis/etiología , Encefalopatías/etiología , Endocarditis Bacteriana/etiología , Enfermedad de Whipple/complicaciones , Anciano , Artritis/sangre , Encefalopatías/sangre , Endocarditis Bacteriana/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Tropheryma/aislamiento & purificación , Enfermedad de Whipple/sangre , Enfermedad de Whipple/diagnóstico , Enfermedad de Whipple/terapiaRESUMEN
This study was designed to examine circulating and urine cytokine levels in patients receiving long-term home total parenteral nutrition (TPN) support. Twelve patients who had been receiving home TPN for more than 1 year (range, 1.3-19.5 years) were enrolled for study. To avoid the potential confounding effects of intercurrent infection, patients were studied during periods of clinical stability without clinical evidence of infection. Ten normal healthy volunteers served as controls. Serum levels of albumin and C-reactive protein, temperature, body weight, and blood white cell counts were determined. The levels of soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin 6 (IL-6) were measured in serum and 24-hr urine. The results showed that the concentrations of sTNF-RII and IL-6 in 24-hr urine and serum were significantly higher in patients, indicating that long-term home TPN may be associated with a persistent low-grade inflammatory state.
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Mediadores de Inflamación/metabolismo , Nutrición Parenteral Total en el Domicilio , Adulto , Anciano , Estudios de Casos y Controles , Enteritis/terapia , Femenino , Humanos , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/metabolismo , Síndrome del Intestino Corto/terapia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This study examined the effects of a liquid meal on cholecystokinin (CCK) secretion in patients with severe short bowel syndrome (SSBS) receiving home total parenteral nutrition (TPN) support for 5-19 years after massive small bowel resection. Five patients with SSBS due to superior mesenteric artery or vein thrombosis were included. Five healthy volunteers served as controls. Blood was drawn before and 1 hr following consumption of 250 ml of a liquid diet containing 232 kcal with 8 g fat and 8 g protein. Plasma CCK activity was evaluated by amylase bioassay. All patients had stable weight with a normal BMI and serum albumin level, although there were mild abnormalities in their liver function tests. CCK secretion after stimulation was significantly decreased in patients. These results suggest that reduction in intestinal length influences CCK secretion in response to meal stimulation in SSBS patients.
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Colecistoquinina/metabolismo , Síndrome del Intestino Corto/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nutrición Parenteral Total , Índice de Severidad de la EnfermedadRESUMEN
R115777 is a nonpeptidomimetic enzyme-specific inhibitor of farnesyl protein transferase (FT) that was developed as a potential inhibitor of Ras protein signaling, with antitumor activity in preclinical models. This study was a phase 1 trial of orally administered R115777 in 35 adults with poor-risk acute leukemias. Cohorts of patients received R115777 at doses ranging from 100 mg twice daily (bid) to 1200 mg bid for up to 21 days. Dose-limiting toxicity occurred at 1200 mg bid, with central neurotoxicity evidenced by ataxia, confusion, and dysarthria. Non-dose-limiting toxicities included reversible nausea, renal insufficiency, polydipsia, paresthesias, and myelosuppression. R115777 inhibited FT activity at 300 mg bid and farnesylation of FT substrates lamin A and HDJ-2 at 600 mg bid. Extracellular signal-regulated kinase (ERK), an effector enzyme of Ras-mediated signaling, was detected in its phosphorylated (activated) form in 8 (36.4%) of 22 pretreatment marrows and became undetectable in 4 of those 8 after one cycle of treatment. Pharmacokinetics revealed a linear relationship between dose and maximum plasma concentration or area under the curve over 12 hours at all dose levels. Weekly marrow samples demonstrated that R115777 accumulated in bone marrow in a dose-dependent fashion, with large increases in marrow drug levels beginning at 600 mg bid and with sustained levels throughout drug administration. Clinical responses occurred in 10 (29%) of the 34 evaluable patients, including 2 complete remissions. Genomic analyses failed to detect N-ras gene mutations in any of the 35 leukemias. The results of this first clinical trial of a signal transduction inhibitor in patients with acute leukemias suggest that inhibitors of FT may have important clinical antileukemic activity. (Blood. 2001;97:3361-3369)
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Transferasas Alquil y Aril/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Quinolonas/uso terapéutico , Adulto , Anciano , Médula Ósea/metabolismo , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/farmacocinética , Farnesiltransferasa , Femenino , Genes ras , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Masculino , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación , Fosforilación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prenilación de Proteína , Quinolonas/efectos adversos , Quinolonas/farmacocinética , Recurrencia , Inducción de Remisión , Resultado del TratamientoRESUMEN
Aromatic fatty acids, of which phenylacetate is a prototype, constitute a class of low toxicity drugs with demonstrated antitumor activity in experimental models and in humans. Using in vitro models, we show here a tight correlation between tumor growth arrest by phenylacetate and activation of peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily. In support are the following observations: (a) the efficacy of phenylacetate as a cytostatic agent was correlated with pre-treatment levels of PPARgamma, as documented using established tumor lines and forced expression models; (b) in responsive tumor cells, PPARgamma expression was up-regulated within 2-9 h of treatment preceding increases in p21waf1, a marker of cell cycle arrest; (c) inhibition of mitogen-activated protein kinase, a negative regulator of PPARgamma, enhanced drug activity; and (d) phenylacetate interacted directly with the ligand-binding site of PPARgamma and activated its transcriptional function. The ability to bind and activate PPARgamma was common to biologically active analogues of phenylacetate and corresponded to their potency as antitumor agents (phenylacetate < phenylbutyrate < p-chloro-phenylacetate < p-iodo-phenylbutyrate), whereas an inactive derivative, phenylacetylglutamine, had no effect on PPARgamma. These findings point to PPARgamma as a novel target in cancer therapy and provide the first identification of ligands that have selective antitumor activity in patients.
Asunto(s)
Neoplasias/prevención & control , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética , Animales , Antimetabolitos Antineoplásicos/metabolismo , Antimetabolitos Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Línea Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/genética , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fenilacetatos/metabolismo , Fenilacetatos/farmacología , Fosforilación , Unión Proteica , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ensayo de Unión Radioligante , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional/efectos de los fármacos , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
Increased pharyngeal collapsibility and abnormal anatomic structures have been postulated to contribute to the pathophysiology of obstructive sleep apnea (OSA) syndrome. It is unclear whether the abnormal craniofacial and soft tissue features may affect the pharyngeal collapsibility and contribute to the apnea density. In the present study we examine the relationship between pharyngeal collapsibility and cephalometric variables in a group of 57 male OSA patients. Pharyngeal collapsibility was measured during the night of nasal continuous positive airway pressure (nCPAP) titration by analyzing the pressure-flow relationship. Pharyngeal critical pressure (Pcrit) was calculated as the extrapolated pressure at zero flow. The patients, age 52.0 +/- 9.0 yr, had an average apnea-hypopnea index (AHI) of 72.6 +/- 31.8 and a mean Pcrit of 2.4 +/- 1.0 cm H(2)O. A significant correlation was found between Pcrit and the soft palate length (SPl) (r = 0.27, p = 0.04), the distance from the hyoid bone to the posterior pharyngeal wall (H-Ph) (r = 0. 29, p = 0.03), and the distance from the hyoid bone to posterior nasal space (H-Pns) (r = 0.32, p = 0.02). While in obese patients Pcrit was related to SPl and neck circumference, the distance of the hyoid bone to the mandibular plane (H-MP) affected Pcrit in nonobese patients. Our results show that both pharyngeal soft tissue abnormalities and the lower position of the hyoid bone affect Pcrit in OSA patients, suggesting that an anatomic narrowing contributes to the upper airway collapsibility.
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Resistencia de las Vías Respiratorias/fisiología , Cefalometría , Enfermedades Pulmonares Obstructivas/fisiopatología , Adulto , Anciano , Femenino , Humanos , Enfermedades Pulmonares Obstructivas/diagnóstico , Masculino , Persona de Mediana Edad , Faringe/fisiopatología , Polisomnografía , Factores de RiesgoRESUMEN
Although Burkitt's lymphoma (BL) is a readily treated malignancy, recurrences, as well as disease arising in immunosuppressed patients, are notoriously resistant to conventional therapeutic approaches. The EBV is associated with a significant proportion of these lymphomas that evade immune surveillance through decreased expression of both viral and cellular antigens. Increasing the immunogenicity of BL cells may, therefore, represent a potentially beneficial therapeutic maneuver. Using in vitro models of EBV-transformed lymphoblastoid as well as BL cell lines, we demonstrate increased expression of genes coding for HLA class I and EBV latent proteins by the differentiation inducer phenylbutyrate (PB). The aromatic fatty acid also caused cytostasis associated with sustained declines in c-myc expression, a direct antitumor effect that was independent of the EBV status. We conclude, therefore, that differentiation therapy of BL with PB may lead to growth arrest with increased tumor immunogenicity in vivo. The findings may have clinical relevance because the in vitro activity has been observed with PB concentrations that are well tolerated and nonimmunosuppressive in humans, a desirable feature for the different patient populations afflicted with this disease.
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Linfoma de Burkitt/patología , Linfoma de Burkitt/virología , Regulación Viral de la Expresión Génica/efectos de los fármacos , Herpesvirus Humano 4/genética , Fenilbutiratos/farmacología , Linfoma de Burkitt/metabolismo , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , ADN Viral/biosíntesis , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Expresión Génica/efectos de los fármacos , Herpesvirus Humano 4/crecimiento & desarrollo , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Células Tumorales Cultivadas , Regulación hacia Arriba , Proteínas de la Matriz Viral/biosíntesis , Activación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS: The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS: Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS: Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.
Asunto(s)
Fallo Hepático/etiología , Nutrición Parenteral Total en el Domicilio/efectos adversos , Adulto , Anciano , Femenino , Humanos , Incidencia , Fallo Hepático/epidemiología , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Albúmina Sérica/análisisRESUMEN
Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.