RESUMEN
BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) lead to accumulation of high concentrations of potentially toxic fatty acid intermediates. Newborn screening and early intervention have reduced mortality, but most patients continue to experience frequent hospitalizations and significant morbidity despite treatment. The deficient energy state can cause serious liver, muscle, and heart disease, and may be associated with an increased risk of sudden death. Triheptanoin is a medium odd-chain fatty acid. Anaplerotic metabolites of triheptanoin have the potential to replace deficient tricarboxylic acid (TCA) cycle intermediates, resulting in net glucose production as a novel energy source for the treatment of LC-FAOD. STUDY DESIGN: A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks. RESULTS: Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period. CONCLUSIONS: In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.
Asunto(s)
Ácidos Grasos/toxicidad , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Resistencia Física/efectos de los fármacos , Triglicéridos/administración & dosificación , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo Lipídico/metabolismo , Errores Innatos del Metabolismo Lipídico/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Triglicéridos/farmacología , Prueba de Paso , Adulto JovenRESUMEN
Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD.
Asunto(s)
Cardiomiopatías/tratamiento farmacológico , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Triglicéridos/administración & dosificación , Adolescente , Cardiomiopatías/complicaciones , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Niño , Preescolar , Ensayos Clínicos como Asunto , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos/metabolismo , Femenino , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo Lipídico/complicaciones , Errores Innatos del Metabolismo Lipídico/patología , Masculino , Oxidación-Reducción/efectos de los fármacos , Triglicéridos/efectos adversosRESUMEN
Objective. To investigate the use of the six-minute walk test (6MWT) for stroke survivors, including adherence to 6MWT protocol guidelines and distances achieved. Methods. A systematic search was conducted from inception to March 2014. Included studies reported a baseline (intervention studies) or first instance (observational studies) measure for the 6MWT performed by stroke survivors regardless of time after stroke. Results. Of 127 studies (participants n = 6,012) that met the inclusion criteria, 64 were also suitable for meta-analysis. Only 25 studies made reference to the American Thoracic Society (ATS) standards for the 6MWT, and 28 reported using the protocol standard 30 m walkway. Thirty-nine studies modified the protocol walkway, while 60 studies did not specify the walkway used. On average, stroke survivors walked 284 ± 107 m during the 6MWT, which is substantially less than healthy age-matched individuals. The meta-analysis identified that changes to the ATS protocol walkway are associated with reductions in walking distances achieved. Conclusion. The 6MWT is now widely used in stroke studies. The distances achieved by stroke patients indicate substantially compromised walking ability. Variations to the standard 30 m walkway for the 6MWT are common and caution should be used when comparing the values achieved from studies using different walkway lengths.
RESUMEN
The medical and neurodevelopmental characteristics of 14 children with short-chain acyl-CoA dehydrogenase deficiency (SCADD) are described. Eight were detected as neonates by newborn screening. Three children diagnosed on the basis of clinical symptoms had normal newborn screening results while three were born in states that did not screen for SCADD. Treatment included frequent feedings and a low fat diet. All children identified by newborn screening demonstrated medical and neuropsychological development within the normative range on follow-up, although one child had a relative weakness in the motor area and another child exhibited mild speech delay. Of the three clinically identified children with newborn screening results below the cut-off value, two were healthy and performed within the normal range on cognitive and motor tests at follow-up. Four clinically identified children with SCADD experienced persistent symptoms and/or developmental delay. However, in each of these cases, there were supplementary or alternative explanations for medical and neuropsychological deficits. Results indicated no genotype-phenotype correlations. These findings suggest that SCADD might be benign and the clinical symptoms ascribed to SCADD reflective of ascertainment bias or that early identification and treatment prevented complications that may have occurred due to interaction between genetic susceptibility and other genetic factors or environmental stressors.
Asunto(s)
Acil-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/enzimología , Tamizaje Neonatal , Acil-CoA Deshidrogenasa/genética , Adaptación Psicológica , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/psicología , Boston , Preescolar , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/psicología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Examen NeurológicoRESUMEN
This article covers the diversity-oriented synthesis (DOS) of small molecules in order to generate a collection of pure compounds that are attractive for lead generation in a phenotypic, high-throughput screening approach useful for chemical genetics and drug discovery programmes. Nature synthesizes a rich structural diversity of small molecules, however, unfortunately, there are some disadvantages with using natural product sources for diverse small-molecule discovery. Nevertheless we have a lot to learn from nature. The efficient chemical synthesis of structural diversity (and complexity) is the aim of DOS. Highlights of this article include a discussion of nature's and synthetic chemists' strategies to obtain structural diversity and an analysis of molecular descriptors used to classify compounds. The assessment of how successful one diversity-oriented synthesis is vs another is subjective; therefore we use freely available software (www.cheminformatics.org/diversity) to assess structural diversity in any combinatorial synthesis.
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Química Farmacéutica/métodos , Química Farmacéutica/tendencias , Técnicas Químicas Combinatorias , Diseño de Fármacos , Humanos , Modelos Químicos , Conformación Molecular , Estructura Molecular , Preparaciones Farmacéuticas , Farmacogenética/métodos , Programas InformáticosRESUMEN
Delayed radiation-induced injuries are difficult to treat. The treatment of delayed radiation injuries with hyperbaric oxygen therapy (HBOT) is reported in small case series and case reports. This study reports the experience of a single institution with HBOT in delayed radiation injuries in patients with gynecological cancers. At least 20 sessions of 100% oxygen inhalation at 2.4 Atmospheric Absolutes (ATA) for 90 min in a hyperbaric chamber were carried out. Of the 14 patients included in the study, 10 patients have healed or showed improvement of more than 50%, resulting in a success rate of 71%. Mean follow-up was 31.6 months (range 6-70 months). The adverse events were acceptable. HBOT should be considered for patients with delayed radiation injuries, not responding to other treatments.
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Oxigenoterapia Hiperbárica , Traumatismos por Radiación/terapia , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Cistitis/etiología , Cistitis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proctitis/etiología , Proctitis/terapia , Traumatismos por Radiación/etiología , Radioterapia/efectos adversos , Estudios Retrospectivos , Factores de TiempoRESUMEN
We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of the 3' end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.
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Cromosomas Humanos X , Proteínas de Transporte de Membrana/deficiencia , Proteínas de Transporte de Membrana/genética , Errores Innatos del Metabolismo/genética , Preescolar , Ojo/patología , Eliminación de Gen , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Espectroscopía de Resonancia Magnética , Masculino , Errores Innatos del Metabolismo/diagnóstico , Proteínas del Tejido Nervioso/genética , Oxígeno/metabolismo , Fenotipo , Fosforilación , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genéticaRESUMEN
We report two infants identified by tandem mass spectrometry (MS/MS) of neonatal blood spot acylcarnitines and confirmed by molecular genetic analysis to have long-chain fatty acid oxidation defects. In both cases, acylcarnitine concentrations in confirmatory plasma samples were normal. None the less, molecular testing identified trifunctional protein (TFP) deficiency (McKusick 600890) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (McKusick 201475).
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Acil-CoA Deshidrogenasa de Cadena Larga/sangre , Carnitina/análogos & derivados , Errores Innatos del Metabolismo Lipídico/diagnóstico , Complejos Multienzimáticos/deficiencia , Tamizaje Neonatal/métodos , Carnitina/sangre , Carnitina/normas , Genotipo , Humanos , Recién Nacido , Masculino , Espectrometría de Masas , Proteína Trifuncional Mitocondrial , Mutación , Oxígeno/metabolismo , Factores de TiempoRESUMEN
Massachusetts currently offers an optional expanded newborn screening programme that tests for 20 biochemical genetic disorders in addition to the mandated newborn screening tests, including phenylketonuria (PKU) and nine other biochemical genetic disorders. We conducted a mail survey of 550 paediatricians listed in the 2000 Massachusetts Healthcare Directory to determine paediatricians' preparedness in discussing expanded newborn screening and its results with families, and to determine in what specific format physicians in Massachusetts would prefer to receive educational materials and updates. Of surveys mailed, 35% (190/550) were returned within the allotted 3 weeks: 25 paediatricians (14%) were unaware of expanded newborn screening; 78 respondents (42%) indicated feeling less than prepared talking about test results with families; 100 paediatricians (54%) indicated a lack of information about metabolic disorders; 134 (73%) preferred information sent in postal mailings, 62 (34%) preferred grand rounds, 60 (33%) preferred educational seminars, and 58 (32%) preferred websites. Other formats receiving preferences of less than 30% included e-mail (27%), phone calls (8%), video (6%), and distance learning (1%). Paediatricians are ill-prepared for expanded newborn screening for biochemical genetic disorders. To address this problem, paediatricians in Massachusetts indicated a preference for unsolicited periodic mailings including short reviews and brochures.
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Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Tamizaje Neonatal/métodos , Pediatría/métodos , Fenilcetonurias/diagnóstico , Fenilcetonurias/genética , Actitud del Personal de Salud , Comunicación , Educación a Distancia , Educación Médica Continua , Correo Electrónico , Humanos , Recién Nacido , Massachusetts , Encuestas y CuestionariosRESUMEN
Malignant perivascular epithelioid cell tumor (PEComa) is an extremely rare mesenchymal neoplasm mostly composed of HMB-45-positive epithelioid cells with clear-to-eosinophilic cytoplasm, a propensity for perivascular distribution and a coexpression of smooth muscle markers. The uterus seems to be one of the most prevalent sites of involvement, although only 14 cases of uterine PEComa have been described. We report the case of a 51-year-old woman with a PEComa arising in the broad ligament. She was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic radiation, and remains without evidence of disease 15 months after diagnosis. This is, to the best of our knowledge, the first report of a malignant PEComa arising in the broad ligament. To correctly diagnose PEComa, an extensive immunohistochemical panel is essential. As PEComas can behave in an aggressive manner, careful follow-up is warranted.
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Ligamento Ancho/patología , Carcinoma/patología , Neoplasias Peritoneales/patología , Carcinoma/radioterapia , Carcinoma/cirugía , Supervivencia sin Enfermedad , Células Epitelioides , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Persona de Mediana Edad , Ovariectomía , Neoplasias Peritoneales/radioterapia , Neoplasias Peritoneales/cirugíaRESUMEN
In 2001 we identified a new inborn error of metabolism caused by a defect in the X-linked creatine transporter SLC6A8 gene mapped at Xq28 (SLC6A8 deficiency, McKusick 300352). An X-linked creatine transporter defect was presumed because of (1) the absence of creatine in the brain as indicated by proton magnetic resonance spectroscopy (MRS); (2) the elevated creatine levels in urine and normal guanidinoacetate levels in plasma, ruling out a creatine biosynthesis defect; (3) the absence of an improvement on creatine supplementation; and (4) the fact that the pedigree suggested an X-linked disease. Our hypothesis was proved by the presence of a hemizygous nonsense mutation in the male index patient and by the impaired creatine uptake by cultured fibroblasts. Currently, at least 7 unrelated families (13 male patients and 13 carriers) with a SLC6A8 deficiency have been identified. Four families come from one metropolitan area. This suggests that SLC6A8 deficiency may have a relatively high incidence. The hallmarks of the disorder are X-linked mental retardation, expressive speech and language delay, epilepsy, developmental delay and autistic behaviour. In approximately 50% of the female carriers, learning disabilities of varying degrees have been noted.
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Cromosomas Humanos X , Ligamiento Genético , Proteínas de Transporte de Membrana/genética , Errores Innatos del Metabolismo/genética , Proteínas del Tejido Nervioso/genética , Transporte Biológico , Creatina/deficiencia , Creatina/metabolismo , Femenino , Humanos , Masculino , Proteínas de Transporte de Neurotransmisores en la Membrana PlasmáticaRESUMEN
UNLABELLED: In eight patients with disorders of fatty acid oxidation, analysis of uric acid and creatine kinase served as indicators of the underlying disorder in episodes of acute metabolic imbalance. Six patients had deficiency of medium-chain acyl-CoA dehydrogenase, one had long-chain hydroxyacyl-CoA dehydrogenase deficiency, and one very long-chain acyl-CoA dehydrogenase deficiency. The most common presentation was with symptomatic hypoglycemia; there was one Reye-like presentation and one of rhabdomyolysis. The mechanism of the elevation of uric acid and creatine kinase appears to be the breakdown of tissue. CONCLUSION: it is concluded that uric acid and creatine kinase provide a useful alerting signal to the presence of a disorder of fatty acid oxidation. Maximal levels of uric acid in this series were 6.2-21.5 mg/dl and of creatine kinase 879-27,557 U/l.
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3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Creatina Quinasa/análisis , Ácido Úrico/análisis , Acil-CoA Deshidrogenasa , Adolescente , Biomarcadores/análisis , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Oxidación-ReducciónRESUMEN
BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.
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Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Ácidos Carboxílicos/metabolismo , Ácidos Grasos/metabolismo , Errores Innatos del Metabolismo Lipídico/epidemiología , Tamizaje Neonatal/métodos , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Recolección de Muestras de Sangre/métodos , Humanos , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Espectrometría de Masas/métodos , Massachusetts/epidemiología , Valor Predictivo de las PruebasRESUMEN
Over the last 100 years the treatment of vulvar cancer has evolved dramatically. The adoption of radical surgical approaches brought high cure rates, but often with very significant physical and psychosexual morbidity. In the last 20 years, there has been an increasing emphasis on conservative and multimodality treatment. There is, however, good evidence that optimal outcomes are dependent on treatment in specialized multidisciplinary tertiary referral centers.
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Carcinoma/cirugía , Neoplasias de la Vulva/cirugía , Carcinoma/patología , Femenino , Ingle , Procedimientos Quirúrgicos Ginecológicos , Humanos , Escisión del Ganglio Linfático , Neoplasias de la Vulva/patologíaAsunto(s)
Acil-CoA Deshidrogenasas/deficiencia , Glicina/análogos & derivados , Heterocigoto , Acil-CoA Deshidrogenasas/genética , Caprilatos/sangre , Carnitina/sangre , Carnitina/deficiencia , Niño , Preescolar , Análisis Mutacional de ADN , Ácidos Dicarboxílicos/orina , Femenino , Glicina/orina , Humanos , Recién Nacido , Masculino , Mutación , Tamizaje NeonatalAsunto(s)
Aberraciones Cromosómicas/diagnóstico , Deleción Cromosómica , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 9/genética , Trisomía/genética , Adulto , Muestra de la Vellosidad Coriónica , Aberraciones Cromosómicas/genética , Bandeo Cromosómico , Trastornos de los Cromosomas , Pintura Cromosómica , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Linfangioma Quístico/diagnóstico por imagen , Masculino , Embarazo , Ultrasonografía PrenatalRESUMEN
The optimal management of endometrial hyperplasia is the subject of considerable debate. In this chapter the development of our current classification of endometrial hyperplasias is outlined in some detail in order to give an understanding of the complexity of the problem of determining the malignant potential of the hyperplasia which is the central issue in determining optimal treatment. While hysterectomy is still the definitive treatment for older women with hyperplasia, conservative therapy is perfectly acceptable in a defined group of younger women who are closely monitored.
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Hiperplasia Endometrial/terapia , Anticonceptivos Orales Combinados/uso terapéutico , Dilatación y Legrado Uterino/métodos , Hiperplasia Endometrial/diagnóstico , Femenino , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Histerectomía/métodos , Imagen por Resonancia Magnética/métodos , Congéneres de la Progesterona/uso terapéuticoRESUMEN
The introduction of tandem mass spectrometry to newborn screening has substantially expanded our ability to diagnose metabolic diseases in the newborn period. We report the first case of neonatal carnitine palmitoyltransferase deficiency II detected by expanded newborn screening with tandem mass spectrometry. The neonate presented with dysmorphic facial features, structural malformations, renal failure, seizures, and cardiac arrythmias and died on the third day of life. This experience illustrates the importance of expanded newborn screening to avoid missing a metabolic diagnosis in early infantile death.
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Anomalías Múltiples/diagnóstico , Carnitina O-Palmitoiltransferasa/deficiencia , Tamizaje Neonatal/métodos , Ácidos Grasos/metabolismo , Edad Gestacional , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/metabolismo , Oxidación-Reducción , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masa por Ionización de Electrospray/estadística & datos numéricosRESUMEN
Gastrointestinal problems are among the most common problems encountered in the management of women with far advanced gynaecological malignancy. They frequently have a multifactorial aetiology and may require a number of different strategies for effective management. Recognition of the central role of alimentary function in human life is essential to effective treatment. Elucidation of the probable cause of each problem is essential. A thorough knowledge of the natural history of the disease and the patient's current status and future prospects is needed to ensure the highest standard of care for the individual suffering from the problem.