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OBJECTIVE: To investigate dysphagia in patients recovering from SARS-CoV-2 admitted to acute inpatient rehabilitation by summarizing clinical swallow evaluation and videofluoroscopic swallow study findings. DESIGN: Retrospective cohort study. SETTING: Urban inpatient rehabilitation hospital. PARTICIPANTS: The first inpatients admitted with SARS-CoV-2 (N=40) who participated in a videofluoroscopic swallow study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient characteristics upon admission (duration of intubation, tracheostomy status, comorbidities, videofluoroscopic swallow study (VFSS) completion at previous level of care); admission International Dysphagia Diet level (IDDSI); Mann Assessment of Swallowing Ability (MASA), Functional Oral Intake Scale (FOIS), dysphagia severity rating; penetration aspiration scale (PAS) rated during VFSS; and IDDSI level recommended after completion of VFSS. RESULTS: Twenty percent of patients had been evaluated by videofluoroscopy in acute care. Nineteen of 37 (51%) individuals were upgraded to IDDSI level 7 regular diet with level 0 thin liquids and achieved a FOIS of 7 after the completion of the VFSS. Five individuals (13%) received a diet downgrade or remained on the same diet recommendations from their admission. Total numerical score (TNS) of less than 170 on the MASA predicted presence of aspiration in 27% of patients (6 of 22). Seventy-two percent of the sample (16 of 22) had a TNS less than 170 but did not demonstrate any instances of aspiration. The odds of patients having a PAS of 3 or greater increased by approximately 15% (odds ratio, 1.15; 95% confidence interval, 1.03-1.27; P=.013). Thus, with each additional day of intubation during acute care stay, there was a 15% greater likelihood of having airway invasion. CONCLUSIONS: Instrumental swallow evaluations are imperative to diagnose and treat dysphagia in the post-coronavirus disease population. Because of the heterogeneity of this population, high incidence of prolonged intubation, and limitations of the clinical swallowing evaluation, instrumental assessments need to be performed on a more consistent basis as infection prevention protocols evolve.
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COVID-19/rehabilitación , Cinerradiografía/métodos , Trastornos de Deglución/epidemiología , Intubación Intratraqueal/efectos adversos , Anciano , Deglución , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Femenino , Humanos , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Videofluoroscopic analyses of swallowing in survivors of traumatic cervical spinal cord injury (tCSCI) have been largely limited to case reports/series and qualitative observations. To elucidate the disrupted physiology specifically underlying dysphagia post-tCSCI, this prospective observational study analyzed videofluoroscopic swallow studies (recorded at 30 frames per second) across 20 tCSCI survivors. Norm-referenced measures of swallow timing or displacement, and calibrated area measures of laryngeal vestibule closure (LVC) were explored in relation to the severity of aspiration or pharyngeal residue. Videofluoroscopic performance was compared by injury level, surgical intervention, tracheostomy status, and in relation to clinical bedside assessments. Reduced pharyngeal constriction, delayed hyoid elevation, and impaired LVC characterized post-tCSCI dysphagia. Reduced extent of hyoid excursion and of pharyngoesophageal segment (PES) opening were not as prominent, only present in approximately half or less of the sample. Ten participants aspirated and 94% of aspiration events were silent. Severity of aspiration significantly correlated with pharyngeal constriction and prolonged pharyngeal transit times. Post-swallow residue correlated with delayed PES distention/closure and prolonged pharyngeal transit. Clinical inference regarding the integrity of the pharyngeal phase at bedside was limited; however, EAT-10 scores demonstrated promise as an adjuvant clinical marker of post-tCSCI dysphagia. This exploratory study further describes the pathophysiology underlying post-tCSCI dysphagia to promote deficit-specific rehabilitation and functional recovery.
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Médula Cervical , Trastornos de Deglución , Laringe , Humanos , Deglución/fisiología , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Médula Cervical/diagnóstico por imagen , Médula Cervical/lesiones , Cinerradiografía , Laringe/diagnóstico por imagen , FluoroscopíaRESUMEN
Hyperphenylalaninaemias are defined by a blood phenylalanine over 2mg/dl. The main cause is due to a mutation in the gene that codes the phenylalanine hydroxylase that catalyses the reaction that converts phenylalanine into tyrosine. The hyperphenylalaninaemias are classified into benign or mild hyperphenylalaninaemias, or mild, moderate or classic phenylketonurias. Due to its delayed detection outside the neonatal period it causes severe mental retardation. Its detection along with congenital hypothyroidism has been part of the National Neonatal Screening Program since 1992 in Chile. This article aims to answer the most common questions asked by the paediatrician when faced with a patient with hyperphenylalaninaemias.
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Tamizaje Neonatal/métodos , Fenilalanina/sangre , Fenilcetonurias/diagnóstico , Chile , Diagnóstico Tardío , Humanos , Recién Nacido , Mutación , Pediatría , Fenilalanina/metabolismo , Fenilalanina Hidroxilasa/genética , Fenilalanina Hidroxilasa/metabolismo , Fenilcetonurias/complicaciones , Fenilcetonurias/genética , Tirosina/metabolismoRESUMEN
OBJECTIVE: Voluntary cough testing (VCT) may be useful for determining aspiration risk in neurogenic dysphagia; however, has yet to be investigated in traumatic cervical spinal cord injury (tCSCI). The study explored if VCT may elucidate swallowing safety and kinematics related to airway protection in tCSCI survivors. METHODS: Ten inpatients, 13-73 days post-tCSCI (7 incomplete injuries), completed VCT and a modified barium swallowing study that was analyzed via the Penetration Aspiration Scale (PAS) and norm-referenced measures of swallowing events related to airway protection. Spearman rho correlations explored relations among cough airflow, median PAS, and airway protection. Mann-Whitney U tests explored group differences based on clinical airway invasion (PAS > 2) and receiver operating characteristic statistics probed the sensitivity/specificity of VCT measures. RESULTS: Safe (PAS > 2) and unsafe swallowers differed by cough volume acceleration (CVA) for the total sample and by inspiratory duration for incomplete injuries (p = 0.03, r > 0.7). A cut-off value of 24.8 L/s for CVA predicted airway invasion (AUC = 0.917, p = 0.03) with sensitivity = 100%/specificity = 75%. CVA correlated with delayed laryngeal vestibule closure during swallowing for both the total sample and for incomplete injuries (rs > 0.6, p < 0.05). Blunted peak flow and prolonged cough phases were associated with disordered laryngeal kinematics and prolonged bolus transit during swallowing (p < 0.05). CONCLUSIONS: Reduced CVA, blunted peak flow, and prolonged cough phases reflected PAS and disrupted mechanisms of airway protection in tCSCI survivors, demonstrating promise for VCT as a clinical assessment for post-tCSCI dysphagia. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1434-1441, 2023.
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Médula Cervical , Trastornos de Deglución , Laringe , Humanos , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Tos/etiología , Médula Cervical/lesiones , DegluciónRESUMEN
Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15-25 µmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings.
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BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1ß, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. METHODS: This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. RESULTS: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. CONCLUSION: If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.
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Enfermedad de la Orina de Jarabe de Arce/genética , Mutación , 3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida)/genética , Aciltransferasas/genética , Niño , Chile , Dihidrolipoamida Deshidrogenasa/genética , Pruebas Genéticas/estadística & datos numéricos , Humanos , Enfermedad de la Orina de Jarabe de Arce/patologíaRESUMEN
BACKGROUND: A clinical environment that provides meaningful and productive learning experiences is essential for students of all health care professions. To support the learning needs of undergraduate midwifery students and facilitate the continuity of care experiences a student led clinic was established in one South East Queensland maternity unit. AIM: This study explored the experiences and learning processes of previous and current midwifery students undertaking clinical practice within a student led clinic. METHOD: Qualitative descriptive. Ten students that elected to work in the midwifery student led clinic were invited to participate in a one off digitally recorded face to face or telephone interview. Thematic analysis was used to analyse the data set. University ethical approval was granted (NRS/17/15/HREC). FINDINGS: Findings suggest the student led clinic positioned students in the 'driver's seat'. Overwhelmingly students described the clinic as providing them with an array of opportunities to 'lead' care rather than being forced to 'sit and watch'. Students believed the experience of working in the clinic increased their midwifery knowledge, skills, confidence, critical thinking, and the ability to advocate for and empower women. CONCLUSION: High quality and supportive clinical teaching and learning experiences are vital for ensuring the student midwife develops into a competent practitioner who is fit for registration. The evidence from this small study highlights the benefits afforded to students of working in partnership not only with pregnant women but also with their university midwifery lecturer. The student's continuity of care learning experiences appeared to foster and cultivate their capability, identity, purpose, resourcefulness and connection; all the five senses of success.
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Instituciones de Atención Ambulatoria/organización & administración , Competencia Clínica/normas , Conocimientos, Actitudes y Práctica en Salud , Partería/educación , Aprendizaje Basado en Problemas , Estudiantes de Enfermería/psicología , Adulto , Continuidad de la Atención al Paciente , Bachillerato en Enfermería , Femenino , Humanos , Embarazo , Atención Prenatal , Investigación Cualitativa , QueenslandRESUMEN
Purpose Dysphagia in Parkinson's disease (PD) is a major cause of depression and reduced quality of life (QOL). PD-related dysphagia often involves lingual dysfunction and weak pressure generation. The relation of disordered lingual pressure generation to swallowing-related QOL in persons with PD remains unknown. Method Twenty-four persons with idiopathic PD completed the Swallowing Quality of Life (SWAL-QOL) questionnaire and an evaluation of anterior and posterior tongue strength. Peak pressures were compared to age- and sex-matched controls. The magnitude of and latency to peak pressure were explored in relation to SWAL-QOL scores. Results Persons with PD exhibited significant anterior (p = .019) but not posterior (p = .081) lingual weakness compared to controls. Persons with PD and reduced anterior tongue strength (< 42 kPa) reported lower SWAL-QOL total (p = .043), extended eating durations (p = .025), and a reduced desire to eat (p = .020). Prolonged latency to peak anterior pressure in PD inversely correlated with SWAL-QOL total (r = -.750, p < .001) and served as a significant, independent predictor of 67% of the variance in SWAL-QOL total when controlling for age, sex, and disease stage. Conclusion Overall, SWAL-QOL scores declined in the presence of lingual pressure dysfunction. Lingual weakness and prolonged pressure building patterns secondary to PD, especially of the anterior tongue, may represent clinically relevant disruptions to mealtime behaviors that undermine swallowing-related QOL. These preliminary findings support further investigation of lingual pressure patterns in PD to help identify debilitating dysphagia and develop treatment strategies.
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Trastornos de Deglución/fisiopatología , Enfermedad de Parkinson/fisiopatología , Calidad de Vida , Enfermedades de la Lengua/fisiopatología , Anciano , Estudios de Casos y Controles , Deglución/fisiología , Trastornos de Deglución/etiología , Trastornos de Deglución/psicología , Femenino , Humanos , Masculino , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Presión , Encuestas y Cuestionarios , Lengua/fisiopatología , Enfermedades de la Lengua/etiología , Enfermedades de la Lengua/psicologíaRESUMEN
There is a consensus on the importance of early and life-long treatment for PKU patients. Still, differences exist on target blood phenylalanine (Phe) concentrations for children with PKU in different countries and treatment centers. For the first time, long-term metabolic control and child development and cognitive functioning is compared between children with mean phenylalanine concentrations under 240 µmol/L (group A), between 240 and 360 µmol/L (group B) or over 360 µmol/L (group C) during their first year of life. METHODS: 70 patients diagnosed with PKU through neonatal screening with Phe > 900 µmol/L, were divided into 3 groups: A, B and C, according to mean Phe concentrations and standard deviation (SD). Metabolic control during childhood, psychomotor development and IQ were compared. RESULTS: In group A, Phe was maintained within the recommended range until 6 years of age, in Group B, until 3 years of age, and in group C, Phe was always over the recommended range. No significant differences were found between the three groups in mental development index (MDI) and motor development index (PDI) scores at 12, 24, and 30 months of age, but group C had the lowest scores on MDI at all age periods. At preschool and school age, IQ was higher in group A compared to group C. CONCLUSION: Results show that mean blood Phe concentrations between 120 and 240 µmol/L during first year of life have a positive impact in metabolic control and cognitive functioning during childhood.
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INTRODUCTION: Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by a blockage of branched-chain keto acid of BCAA (branched-chain keto acid dehydrogenase, BCKDH) leading to neurological damage induced by accumulation of leucine and metabolites. MSUD expenditure and energy requirement information is limited. OBJECTIVE: To determine if basal/total energy expenditure (BEE/TEE) is comparable between different determination methods and if values agree with recommendations of energy in MSUD children, and whether they relate to nutritional status. METHODS: Case-control study between MSUD (n = 16) and healthy children (n = 11) aged 6-18 years. Current nutritional status, physical activity level, body composition by DEXA and BEE/TEE by indirect calorimetry (BEEr) and predictive equations (FAO/WHO/ONU - WHO - and Schofield) were assessed; STATA 2013 (p < 0.05). RESULTS: When comparing the energy expenditure variables, there was no significant difference between groups. Moreover, compared to BEEr, equations underestimate according to BEE WHO and Schofield, respectively (P = 0.00; 0.02). The WHO equation had lower average calorie difference, greater concordance correlation and association with indirect calorimetry compared to the Schofield equation for both groups, being the best predictor of the BEE for MSUD group. CONCLUSION: Energy recommendations for MSUD children are according to energy expenditure; thus the use of WHO equation is a clinically and statistically feasible tool for its determination.
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Bovine leukemia virus (BLV) causes persistent lymphocytosis, a preneoplastic, polyclonal expansion of B lymphocytes. The expansion increases viral transmission to new hosts, but the mechanisms of this expansion have not been determined. We hypothesized that BLV infection contributes to B-cell expansion by signaling initiated via viral transmembrane protein motifs undergoing tyrosine phosphorylation. Viral mimicry of host cell proteins is a well-demonstrated mechanism by which viruses may increase propagation or decrease recognition by the host immune system. The cytoplasmic tail of BLV transmembrane protein gp30 (TM) has multiple areas of homology to motifs of host cell signaling proteins, including two immunoreceptor tyrosine-based activation motifs (ITAMs) and two immunoreceptor tyrosine-based inhibition motifs (ITIMs), which are homologous to B-cell receptor and inhibitory co-receptor motifs. Signaling by these motifs in B cells typically relies on tyrosine phosphorylation, followed by interactions with Src-homology-2 (SH2) domains of nonreceptor protein tyrosine kinases or phosphatases. Phosphorylation of tyrosine residues in the cytoplasmic tail of TM was tested in four systems including ex vivo cultured peripheral blood mononuclear cells from BLV infected cows, BLV-expressing fetal lamb kidney cell and bat lung cell lines, and DT40 B cells transfected with a fusion of mouse extracellular CD8alpha and cytoplasmic TM. No phosphorylation of TM was detected in our experiments in any of the cell types utilized, or with various stimulation methods. Detection was attempted by immunoblotting for phosphotyrosines, or by metabolic labeling of cells. Thus BLV TM is not likely to modify host signal pathways through interactions between phosphorylated tyrosines of the ITAM or ITIM motifs and host-cell tyrosine kinases or phosphatases.
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Linfocitos B/inmunología , Virus de la Leucemia Bovina/patogenicidad , Proteínas Oncogénicas de Retroviridae/metabolismo , Transducción de Señal , Tirosina/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Secuencia de Aminoácidos , Animales , Bovinos , Línea Celular , Leucosis Bovina Enzoótica/virología , Activación de Linfocitos , Ratones , Datos de Secuencia Molecular , Fosforilación , Receptores de Aminoácidos/química , Receptores de Aminoácidos/metabolismo , Receptores de Antígenos de Linfocitos B/química , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores Inmunológicos/química , Receptores Inmunológicos/metabolismo , Proteínas Oncogénicas de Retroviridae/química , Proteínas del Envoltorio Viral/químicaRESUMEN
A 23-year-old patient developed diffuse paresthesias and sensory loss. He had mildly reduced serum vitamin B12 (B12) concentration with unusually high levels of methylmalonic acid (MMA) and homocysteine and no evidence of B12 malabsorption. Following parenteral B12 administration, his neurological deficit promptly resolved and B12 and MMA levels normalized, but elevated levels of homocysteine persisted. One year later, he admitted to inhaling nitrous oxide (N2O). After halting N2O abuse his homocysteine level normalized. This case demonstrates the importance of serum homocysteine level measurements in cases of suspected N2O toxicity [corrected].
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Anestésicos por Inhalación/envenenamiento , Enfermedades Desmielinizantes/inducido químicamente , Homocisteína/sangre , Ácido Metilmalónico/sangre , Óxido Nitroso/envenenamiento , Adulto , Enfermedades Desmielinizantes/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Deficiencia de Vitamina B 12RESUMEN
Alternaria alternata is a fungal allergen linked to the development of severe asthma in humans. In view of the clinical relationship between A. alternata and asthma, we sought to investigate the allergic activity of this antigen after direct application to the lungs of Brown Norway rats. Here we demonstrate that a single intratracheal instillation of A. alternata induces dose and time dependent eosinophil influx, edema and Type 2 helper cell cytokine production in the lungs of BN rats. We established the temporal profile of eosinophilic infiltration and cytokine production, such as Interleukin-5 and Interleukin-13, following A. alternata challenge. These responses were comparable to Ovalbumin induced models of asthma and resulted in peak inflammatory responses 48h following a single challenge, eliminating the need for multiple sensitizations and challenges. The initial perivascular and peribronchiolar inflammation preceded alveolar inflammation, progressing to a more sub-acute inflammatory response with notable epithelial cell hypertrophy. To limit the effects of an A. alternata inflammatory response, MK-7246 was utilized as it is an antagonist for Chemoattractant Receptor-homologous molecule expressed in Th2 cells. In a dose-dependent manner, MK-7246 decreased eosinophil influx and Th2 cytokine production following the A. alternata challenge. Furthermore, therapeutic administration of corticosteroids resulted in a dose-dependent decrease in eosinophil influx and Th2 cytokine production. Reproducible asthma-related outcomes and amenability to pharmacological intervention by mechanisms relevant to asthma demonstrate that an A. alternata induced pulmonary inflammation in BN rats is a valuable preclinical pharmacodynamic in vivo model for evaluating the pharmacological inhibitors of allergic pulmonary inflammation.
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Alternaria/efectos de los fármacos , Antiinflamatorios/farmacología , Carbolinas/farmacología , Neumonía/tratamiento farmacológico , Receptores de Formil Péptido/metabolismo , Células Th2/efectos de los fármacos , Alérgenos/inmunología , Alternaria/inmunología , Animales , Asma/tratamiento farmacológico , Asma/inmunología , Asma/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Eosinófilos/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Interleucina-13/inmunología , Interleucina-13/metabolismo , Interleucina-5/inmunología , Interleucina-5/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Masculino , Ovalbúmina/inmunología , Ovalbúmina/farmacología , Neumonía/inmunología , Neumonía/metabolismo , Ratas , Ratas Endogámicas BN , Receptores de Formil Péptido/inmunología , Células Th2/inmunologíaRESUMEN
Abstract Since neonatal screening and early nutritional treatment began, it has been possible to reverse the neurological damage that phenylketonuria (PKU) causes. Scientific evidence gathered over more than 50 years on the monitoring of individuals with PKU indicates that a phenylalanine level of about 6 mg/dL (360 µmol/L) is ideal and points to the necessity of starting a long-term phenylalanine-restricted diet in which blood phenylalanine level should stay between 2 and 6 mg/dL (120-360 µmol/L). This article aims to establish the general basis for proper monitoring of people with PKU and provide a useful tool for clinicians overseeing treatment. We hope to establish similar criteria throughout Latin America and create a uniform protocol in order to have comparative monitoring results for the region.
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Alanine aminotransferase (ALT) activity is the most frequently relied upon reference standard for monitoring liver injury in humans and nonclinical species. However, limitations of ALT include a lack of specificity for diagnosing liver injury (e.g., present in muscle and the gastrointestinal tract), its inability to monitor certain types of hepatic injury (e.g., biliary injury), and ambiguity with respect to interpretation of modest or transient elevations (< 3× upper limit of normal). As an initial step to both understand and qualify additional biomarkers of hepatotoxicity that may add value to ALT, three novel candidates have been evaluated in 34 acute toxicity rat studies: (1) alpha-glutathione S-transferase (GSTA), (2) arginase 1 (ARG1), and (3) 4-hydroxyphenylpyruvate dioxygenase (HPD). The performance of each biomarker was assessed for its diagnostic ability to accurately detect hepatocellular injury (i.e., microscopic histopathology), singularly or in combination with ALT. All three biomarkers, either alone or in combination with ALT, improved specificity when compared with ALT alone. Hepatocellular necrosis and/or degeneration were detected by all three biomarkers in the majority of animals. ARG1 and HPD were also sensitive in detecting single-cell necrosis in the absence of more extensive hepatocellular necrosis/degeneration. ARG1 showed the best sensitivity for detecting biliary injury with or without ALT. All the biomarkers were able to detect biliary injury with single-cell necrosis. Taken together, these novel liver toxicity biomarkers, GSTA, ARG1, and HPD, add value (both enhanced specificity and sensitivity) to the measurement of ALT alone for monitoring drug-induced liver injury in rat.
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4-Hidroxifenilpiruvato Dioxigenasa/metabolismo , Arginasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Glutatión Transferasa/metabolismo , Isoenzimas/metabolismo , Hígado/enzimología , Alanina Transaminasa/metabolismo , Animales , Biomarcadores/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Modelos Lineales , Hígado/efectos de los fármacos , Hígado/patología , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Curva ROC , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sensibilidad y Especificidad , Distribución TisularRESUMEN
Las hiperfenilalaninemias se definen por un nivel sanguíneo de fenilalanina sobre 2 mg/dl. La principal causa es una mutación en el gen que codifica la fenilalanina hidroxilasa que cataliza la reacción que transforma la fenilalanina en tirosina. Las hiperfenilalaninemias se clasifican en benignas o leves, y las fenilcetonurias en leves, moderadas y clásicas. Debido a que su detección más allá del periodo neonatal causa retardo mental severo, desde 1992 en Chile su detección, junto con la del hipotirodismo congénito, es parte del Programa Nacional de Pesquisa Neonatal. Este artículo pretende responder las preguntas más comunes que se puede hacer el pediatra cuando enfrenta a un paciente con hiperfenilalaninemias.
Hyperphenylalaninaemias are defined by a blood phenylalanine over 2 mg/dl. The main cause is due to a mutation in the gene that codes the phenylalanine hydroxylase that catalyses the reaction that converts phenylalanine into tyrosine. The hyperphenylalaninaemias are classified into benign or mild hyperphenylalaninaemias, or mild, moderate or classic phenylketonurias. Due to its delayed detection outside the neonatal period it causes severe mental retardation. Its detection along with congenital hypothyroidism has been part of the National Neonatal Screening Program since 1992 in Chile. This article aims to answer the most common questions asked by the paediatrician when faced with a patient with hyperphenylalaninaemias.
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Humanos , Recién Nacido , Fenilalanina/sangre , Fenilcetonurias/diagnóstico , Tamizaje Neonatal/métodos , Pediatría , Fenilalanina Hidroxilasa/genética , Fenilalanina Hidroxilasa/metabolismo , Fenilalanina/metabolismo , Fenilcetonurias/complicaciones , Fenilcetonurias/genética , Tirosina/metabolismo , Chile , Diagnóstico Tardío , MutaciónRESUMEN
Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5(+), IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5(+) B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis.