RESUMEN
INTRODUCTION: Although imatinib is the first-line of therapy for Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML), in Japan, it is recommended by the manufacturer that lactating women treated with imatinib mesylate for CML should discontinue breastfeeding their infants. CASE: A 32-year-old pregnant patient was diagnosed with Ph-positive CML at 13 weeks of gestation. She received imatinib (400 mg/day) after 28 weeks of gestation. A female infant was delivered at a gestational age of 35 weeks and 3/7 days after preterm premature rupture of membranes. It was decided to feed only colostrum to the infant and formula feeding was done subsequently because of the risk of the transfer of imatinib to breast milk. The milk/plasma (M/P) ratio and the relative infant dose (RID) for imatinib were calculated to be 0.35 and 1.4%, respectively at 5 days of life. Moreover, the serum level of imatinib in the child of age 5 days was 27 ng/mL, which was much lower than the target trough value for CML (1000 ng/mL). CONCLUSION: The M/P ratio and RID values for maternally administered imatinib were within the safe range for breastfeeding, as reported in previous studies. In addition, it was found that the serum concentration of imatinib in the child was relatively low during short-term breastfeeding.
Asunto(s)
Antineoplásicos/uso terapéutico , Lactancia Materna , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Antineoplásicos/efectos adversos , Lactancia Materna/efectos adversos , Femenino , Humanos , Mesilato de Imatinib/efectos adversos , Mesilato de Imatinib/uso terapéutico , Lactante , Recién Nacido , Japón , Lactancia/efectos de los fármacos , Lactancia/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.
Asunto(s)
Dineínas Citoplasmáticas/genética , Mutación/genética , Síndrome de Costilla Pequeña y Polidactilia/genética , Heterocigoto , Humanos , Recién Nacido , Masculino , FenotipoRESUMEN
BACKGROUND AND PURPOSE: A thrombosed dural sinus malformation (DSM) is a rare condition, the clinical features of which have not yet been completely characterized. Here, we describe the clinical course of a patient with a thrombosed DSM and discuss the outcomes in live birth cases from a review of the literature. CASE DESCRIPTION: An ultrasonography examination of a 32-year-old woman at 25 weeks' gestation indicated a fetal posterior fossa mass. The size of the intracranial mass remained constant during the second trimester and was observed to decrease from 33 weeks of gestation. A postnatal diagnosis of thrombosis in the dural sinus was established by magnetic resonance imaging and venography. No brain damage or hydrocephalus was noted. Although the circumference of the infant's head was enlarged at birth, her neurological outcome was normal at 1 year of age. CONCLUSIONS: Although normal cranial circumference is reportedly an essential factor for a favorable prognosis, the patient in this report with a cranial circumference at + 2.0 SD (35.6 cm) had a favorable prognosis. Further studies focused on improving clinical diagnostic accuracy in this rare entity will facilitate appropriate counseling.
Asunto(s)
Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/embriología , Enfermedades Fetales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/embriología , Ultrasonografía Prenatal/métodos , Adulto , Diagnóstico Diferencial , Femenino , Humanos , EmbarazoRESUMEN
Since the mid-1980s, there have been increasing reports of severe invasive group A streptococcal (GAS) disease in children and adults. There are few reports, however, of neonatal invasive disease, particularly neonatal pleural empyema caused by GAS. Although many mechanisms have been reported for the pathophysiology of invasive GAS infections, similar reports for neonates were unable to be located. Reported herein is the case of a 3-day-old girl with pleural empyema caused by GAS that demonstrated a high invasive capacity for human epithelial cells.
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Antígenos Bacterianos/inmunología , Empiema Pleural/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/inmunología , Antibacterianos/uso terapéutico , Empiema Pleural/diagnóstico , Empiema Pleural/tratamiento farmacológico , Femenino , Humanos , Recién Nacido , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes/aislamiento & purificaciónRESUMEN
BACKGROUND: Glycated albumin (GA) reflects glycemic control in patients with neonatal diabetes mellitus (NDM). However, GA in NDM patients is apparently low in relation to glycemia. OBJECTIVE: To establish the reference intervals for GA in healthy infants. SUBJECTS AND METHODS: Fifty-eight healthy, full-term newborn infants were used to define the GA reference values and to investigate its relationship to plasma glucose (PG) and serum albumin. The infants were categorized into three groups according to age: group A, 5 (4-6) median (range) d: n = 18; group B, 33 (30-38) d: n = 19; and group C, 181 (50-352) d: n = 21. We also studied 212 non-diabetic adults [group D, 53 (28-78) yr old] and the 5 NDM patients previously reported for GA comparisons. RESULTS: In the infants, GA was strongly positively correlated with logarithmic transformation of age [log (age)] (p = 0.831, p < 0.0001). The GA in groups A, B, C, and D were 7.3 ± 1.0%, 8.6 ± 1.1%, 10.9 ± 0.8%, and 14.0 ± 1.1%, respectively. The GA was more strongly positively correlated with serum albumin (r = 0.768, p < 0.0001) than with PG (r = 0.596, p < 0.0001). When GA levels were compared with the age-dependent reference values, GA in the transient NDM patient was normalized although GA in the four permanent NDM patients decreased but remained high after insulin therapy. CONCLUSIONS: This study showed that the reference range for GA in infants is lower than that of adults and increases with age, with which we confirmed that GA in the NDM patients reflected the clinical course. Consequently, GA in NDM patients should be compared with the age-based reference values to assess the accurate glycemic status.
Asunto(s)
Envejecimiento/sangre , Albúmina Sérica/análisis , Adulto , Factores de Edad , Anciano , Glucemia/análisis , Estudios de Cohortes , Femenino , Hemoglobina Glucada/análisis , Productos Finales de Glicación Avanzada , Humanos , Lactante , Recién Nacido/sangre , Masculino , Persona de Mediana Edad , Albúmina Sérica GlicadaRESUMEN
Heterozygous COL2A1 mutations create a group of skeletal dysplasias collectively termed type II collagenopathies. Sporadic cases of type II collagenopathies are almost exclusively caused by de novo mutations. Very few cases with intrafamilial recurrence due to germinal mosaicism have been known. We report here on a family in which a severe form of skeletal dysplasia was recurrent in two sibs whose phenotype was most consistent with platyspondylic lethal skeletal dysplasia Torrance type (PLSD-T). A COL2A1 analysis showed that the two sibs had a heterozygous mutation in the encoded triple helical region of COL2A1, c.3545G>A (p.Gly1182Asp) in exon 50. The parents did not consent to a molecular analysis; however, the presence of the same mutation in the two sibs is proof of germinal mosaicism in one of the parents. PLSD-T has been shown to arise from a heterozygous dominant negative COL2A1 mutation in the encoded C-propeptide region. However, our observation suggests that the phenotype is also caused by a COL2A1 mutation in the encoded C-terminal triple helical region.