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The establishment of national neonatal screening systems has resulted in improved quality of life and life expectancy in patients with phenylketonuria (PKU). This has led to the development of multidisciplinary treatment units for adult patients with PKU. We present a retrospective descriptive study of a cohort of 90 adult patients (>16 years) with PKU under active follow-up in two reference centers in Andalusia. We analyzed disease severity, treatment type, demographic variables, cardiovascular risk factors, vitamin and hormone profiles, and bone metabolism. The median (interquartile range)age was 29 (23−38) years, 47 (52.2%) were women and 43 (47.8%) were men. Eighty (88.9%) had classical PKU, five (5.6%) moderate PKU, and five (5.6%) mild PKU. Diagnosis was by neonatal screening in 62 (68.9%) of the patients. The rest had late diagnosis. Treatment with sapropterin was given to 18 (20%) patients and diet and nutrition therapy to 72 (80%). There was adequate metabolic control according to Phe levels in 43 (47.78%) patients. Body mass index was 26.61 (22.7−31.1) kg/m2. Twenty-six (29.2%) patients had obesity, 7 (7.9%) hypertension, 2 (2.2%) type 2 diabetes, 26 (28.89%) dyslipidemia, 14 (15.6%) elevated total cholesterol, 9 (15.8%) decreased high-density lipoprotein cholesterol and 16 (17.8%) hypertriglyceridemia. Seven (10.3%) patients had osteoporosis and 28 (41.17%) osteopenia. Twenty-six (30.6%) had vitamin D (25OH) deficiency and four (4.5%) vitamin B12 deficiency. Although we observed no differences with most vascular risk factors, we found a high prevalence of obesity in relation to the age of the cohort. A continued evaluation of comorbidities in these patients is therefore needed, despite adequate metabolic control.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Fenilcetonúrias , Adulto , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Morbidade , Fenilcetonúrias/epidemiologia , Qualidade de Vida , Estudos RetrospectivosRESUMO
PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.
Assuntos
Homocistinúria/diagnóstico , Acetilcarnitina/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Carnitina/análogos & derivados , Carnitina/metabolismo , Feminino , Glicina N-Metiltransferase/deficiência , Glicina N-Metiltransferase/metabolismo , Homocisteína/metabolismo , Homocistinúria/metabolismo , Humanos , Recém-Nascido , Masculino , Metionina/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Ácido Metilmalônico/metabolismo , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/metabolismo , Triagem Neonatal/métodos , Fenilalanina/metabolismo , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/metabolismoRESUMO
El egreso precoz del neonato ha devenido en una práctica cada vez más frecuente. Aunque una consulta de supervisión a las 48 horas del alta ha sido reglamentada para detectar complicaciones inadvertidas, su cumplimiento por parte de los padres puede ser inconstante. Objetivo: Determinar la observancia de la visita de seguimiento y las morbilidades detectadas en ella luego del alta precoz. Metodología: Estudio observacional, de diseño cohorte prospectivo, que abarcó 427 neonatos egresados antes de las 48 horas, en quienes se registraron la frecuencia de asistencia a la consulta, los hallazgos anormales y las causas de readmisión hospitalaria. Resultados: Setenta y dos (16,9%) de los egresados fueron prematuros, 64 (15.1%) fueron hijos de adolescentes y 233 (54,7%) nacieron por cesárea. Solo 86 (20%) de los 427 neonatos asistieron a la consulta. El cumplimiento de la visita fue inversamente proporcional al peso al nacer, y únicamente el 22,2% de los prematuros fue supervisado. Cuarenta y cinco (51,2%) de los niños consultados presentaron alguna anormalidad. Los hallazgos más comunes fueron problemas de lactancia e ictericia. 12 niños fueron readmitidos para recibir fototerapia. Conclusiones: Una fracción importante de recién nacidos que son egresados antes de las 48 horas no satisface los criterios mínimos para el alta precoz. El acatamiento de la consulta de seguimiento es bajo y no guarda relación con el riesgo individual del niño. Se deben definir las barreras particulares que interfieren con el cuidado posnatal inmediato del neonato expuesto al egreso precoz.
Early newborn discharge and immediate follow-up visit Background: Early newborn discharge has become a common clinical practice. Because of inherent risks related to it, an immediate follow-up visit has been proposed to prevent inadvertent complications. Parents compliance toward this visit may be inconsistent. Objective:To assess parents observance toward the follow-up visit and the frequency of abnormalities identified during that surveillance. Methods: A longitudinal observational analysis was undertaken in 427 early discharged infants, in whom attendance to the scheduled visit and morbidities were estimated. Results: 16.9% were preterm infants, 15.1% were born to teenage mothers, whereas 54.7% were born by C- section. Only 86 (20%) attended the follow-up visit. Compliance toward the visit was inversely proportional to birth weight. 45 (51.2%) newborns showed some abnormal finding, mainly breast feeding problems and jaundice. 12 infants were readmitted for phototherapy. Conclusions: A relevant proportion of newborns do not meet the standarized minimal criteria for early discharge. Adherence toward the early follow-up visit is extremely low. Barriers to the accomplishment of the visit must be defined in our population.
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Pancreatic neuroendocrine tumors (p-NETs) are a rare group of neoplasms but with increasing incidence. The atypical complications that arise in the setting of functional endocrine tumors are underreported and therefore have not received sufficient attention and the necessary mention in the oncology literature. The clinical implications of these complications pose management challenges starting with the difficulty in establishing diagnosis, accurate staging and optimal treatment of the primary process. We present the case of a middle-aged woman diagnosed with adrenocorticotropic hormone-producing carcinoma arising from the pancreas whose case was complicated by excessive uncontrolled hypercortisolism and reactivation of pulmonary opportunistic infections that confounded her management. We believe that this case illustration will be of value to practicing oncologists and other groups of physicians who are called upon to participate in the multidisciplinary treatment of these relatively rare but highly challenging cases.
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Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1ß, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.
Assuntos
Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/fisiologia , Biomarcadores/metabolismo , Fezes , Mucosa Intestinal/metabolismo , Lipocalinas/biossíntese , Lipocalinas/fisiologia , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/fisiologia , Animais , Quimiocina CXCL1/biossíntese , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Inflamação , Interleucina-10/metabolismo , Interleucina-1beta/biossíntese , Lipocalina-2 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Los pacientes con Enfermedad Renal Crónica Estadio V (ERC) conocida como insuficiencia renal terminal pueden manifestar una serie de lesiones gastrointestinales y sufrir complicaciones. Investigar los hallazgos clínicos y endoscópicos en pacientes pediátricos con esta condición. Durante un período de 5 años (Enero de 2004 a Diciembre de 2008), fueron evaluados en el servicio de Gastroenterología practicándoseles endoscopia digestiva superior antes del trasplante renal. Se estudiaron 75 pacientes 37 femeninos, 38 masculinos, edad promedio 12 años; 42,7% fueron asintomáticos y 57,3% experimentaron síntomas: pirosis (23,2%), reflujo (23,2%), dolor abdominal (18,7%), distensión abdominal (14%), vómitos (9,3%), náuseas (7%) y hematemesis (4,6%). La endoscopia reportó normal en 18 pacientes (24%). Endoscopia anormal: gastropatía erosiva (43,9%), duodenitis (24,5%), gastropatía nodular (14%), esofagitis (14%) y hernia hiatal (3,5%). Presencia de Helicobacter pylori en 22,7%. Se determinó que la evaluación endoscópica debe ser incluida en pacientes con protocolo pretrasplante renal, ya que estos presentan alteraciones gastrointestinales variadas...
Patients with Stage 5 Chronic Kidney Disease (CKD), known as end-stage renal disease (ESRD), may manifest a variety of gastrointestinal lesions and suffer complications. To investigate the clinical and endoscopic findings in pediatric patients with this condition. Over a period of 5 years (January 2004 to December 2008), the patients were evaluated in the pediatric gastroenterology service by upper gastrointestinal endoscopy before kidney transplant. We studied 75 patients: 37 female and 38 male, with a mean age of 12 years-old; 42.7% were asymptomatic and 57.3% experienced symptoms: heartburn (23.2%), reflux (23.2%), abdominal pain (18.6%), abdominal distension (14%), vomiting (9.3%), nausea (7%) and hematemesis (4.6%). Endoscopy reported normal in 18 patients (24%) and the remaining study was abnormal: erosive gastropathy (43.9%), duodenitis (24.5%), nodular gastropathy (14%), esophagitis (14%) and hiatal hernia (3.5%). Presence of Helicobacter pylori (22.7%). We determined that endoscopic evaluation should be included in patients with pre-renal transplant protocol, since they have various gastrointestinal disorders that may influence the evolution and prognosis of the transplant...
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Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Endoscopia Gastrointestinal , Falência Renal Crônica/complicações , Falência Renal Crônica , Diagnóstico por Imagem , GastroenterologiaRESUMO
We have established a clonal cell line derived from rat microglia that proliferates in response to macrophage-colony stimulating factor (CSF-1). Like primary neonatal microglia, these cells (named RTMGL1) exhibit a ramified morphology, bind isolectin B4, express CD68 and are weakly positive for CD11b and MHC class II. CSF-1-dependent proliferation requires intact signal transduction through several pathways. RTMGL1 synthesize multiple cyclooxygenase (COX) products including 11- and 15-hydroxyeicosatetraenoic acid (HETE) and express COX-2. RTMGL1 synthesize 5-HETE from arachidonic acid (AA) likely via a 5-lipoxygenase (LO). Thus, RTMGL1 have morphological and histological characteristics of primary microglia and metabolize AA via both COX and LO pathways.