RESUMO
BACKGROUND: Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. CASE PRESENTATION: A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25-75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25-75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. CONCLUSIONS: This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.
Assuntos
Cútis Laxa , Elastina , Mutação da Fase de Leitura , Tomografia Computadorizada por Raios X , Humanos , Cútis Laxa/genética , Feminino , Adulto , Elastina/genética , Japão , Éxons/genética , Seguimentos , Testes de Função Respiratória , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Pulmão/patologia , População do Leste AsiáticoRESUMO
BACKGROUND: The level of maternal antibodies decreases more quickly in preterm than term infants, leaving them unprotected against measles. To protect premature infants from measles, an early vaccination trial was investigated. METHODS: Changes in the serum measles neutralization test (NT) antibody titer were examined in 152 infants (average gestational period, 29 weeks; average birthweight, 1203 g). RESULTS: The average antibody titer (2(n)) was 2(3.5) at birth and 2(2.2) at 1-3 months of age, and in all cases, NT antibody titer decreased to <1:4 (150 IU/mL). The AIK-C measles vaccine was given to 17 preterm infants at the age of 6 months, and induced sufficient serological responses without any serious adverse events. NT antibody level did not decay during 12 months after vaccination. CONCLUSION: Early immunization at 6 months of age is effective to protect preterm infants in the outbreak setting.
Assuntos
Doenças do Prematuro/prevenção & controle , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Vacinação/métodos , Anticorpos Antivirais/imunologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/imunologia , Japão/epidemiologia , Masculino , Sarampo/epidemiologia , Sarampo/imunologia , Estudos Retrospectivos , Fatores de TempoRESUMO
This report describes the long-term (23 years) follow-up of a pediatric patient with acute lymphoblastic leukemia and eosinophilia who underwent multiple valve replacements. An 8-year-old boy with this complex disease was admitted in January 1984 and treated with 6-week course of vincristine, L-asparaginase, and prednisolone, which induced complete remission. He developed atrioventricular valvular insufficiency and infectious endocarditis at 13.5 and 17.3 years of ages, respectively, with progressive development of congestive heart failure. At 18.6 years of age, he underwent prosthetic valve replacement of both atrioventricular valves; the mitral valve was replaced with a mechanical prosthetic valve and tricuspid valve with a bioprosthetic valve. Histopathological examination of the ventricular endomyocardium showed extensive fibrous degeneration and persistent infiltration of eosinophils and lymphocytes. The right-side prosthesis was replaced twice, at 22.4 and 29 years of ages, due to degeneration of bioleaflets and thrombosis of the mechanical valve, respectively. Although he tolerated all surgical procedures, he developed liver cancer at 31 years of age and died. Autopsy could not be performed. The present study indicates that a subset of patients in complete remission of acute lymphoblastic leukemia and eosinophilia can show persistent myocardial eosinophilic infiltration and are at risk of late cardiac disease.
Assuntos
Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Eosinofilia/complicações , Eosinofilia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Adulto , Criança , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Fatores de Tempo , Adulto JovemRESUMO
A 12-year-old boy was brought to the hospital with a 3-week history of watery diarrhea mixed with mucus and colicky abdominal pain. Stool culture identified Edwardsiella tarda O4: H4, and no other pathogenic bacteria were detected. Acute gastroenteritis caused by Edwardsiella tarda O4: H4 was diagnosed. This bacterium was shown to be sensitive to ampicillin hydrate. When this antibiotic was administered, the condition of the patient improved within a week. The patient had a history of eating raw shrimp and fish while traveling with his parents.
Assuntos
Edwardsiella tarda/classificação , Edwardsiella tarda/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Gastroenterite/microbiologia , Doença Aguda , Adulto , Criança , Diarreia/microbiologia , Fezes/microbiologia , Humanos , MasculinoRESUMO
A 12-year-old girl with occasional symptoms of chest discomfort was diagnosed with ventricular tachycardia on cardiac evaluation. No evidence of organic heart disease was apparent, but a laboratory evaluation revealed hypomagnesemia. Ventricular tachycardia disappeared after treatment with 200 mg/day of oral magnesium hydroxide, and no further chest discomfort was reported. In addition to routine cardiac evaluation for arrhythmia, serum magnesium levels should be checked in patients with suspected idiopathic benign ventricular tachycardia. Treatment with oral magnesium is a physiologic therapy and should be considered for patients with ventricular tachycardia due to hypomagnesemia.
Assuntos
Deficiência de Magnésio/complicações , Magnésio/administração & dosagem , Taquicardia Ventricular/tratamento farmacológico , Administração Oral , Criança , Feminino , Humanos , Magnésio/sangue , Taquicardia Ventricular/sangueRESUMO
Fibrates, including bezafibrate (BF), upregulate the expression of ATP binding cassette protein B4 (ABCB4) through gene transcription in mice. To determine the effects of BF on the expression levels of ABCB4 and on the stimulation of biliary phosphatidylcholine (PC) transport in human HepG2 hepatoblastoma cells, mRNA and protein levels as well as subcellular localization were investigated in the cells treated with BF. The canalicular accumulation of a fluorescent PC was assessed by confocal laser scanning microscopy. Treatment with 300 micromol/l BF for 24 h increased levels of ABCB4 mRNA but not protein by up to 151%. BF caused redistribution of ABCB4 into pseudocanaliculi formed between cells. In association with this redistribution, BF accelerated the accumulation of fluorescent PC in bile canaliculi (up to 163% of that in nontreated cells). Suppression of peroxisome proliferator-activated receptor alpha (PPARalpha) expression by either a small interfering RNA duplex or morpholino antisense oligonucleotide attenuated the BF-induced redistribution of ABCB4. These findings suggest that BF may enhance the capacity of human hepatocytes to direct PC into bile canaliculi via PPARalpha-mediated redistribution of ABCB4 to the canalicular membrane. This provides a rationale for the use of BF to improve cholestasis and/or cholangitis that is attributable to hypofunction of ABCB4.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Bezafibrato/farmacologia , Canalículos Biliares/metabolismo , Hepatócitos/efeitos dos fármacos , PPAR alfa/fisiologia , Fosfatidilcolinas/metabolismo , 4-Cloro-7-nitrobenzofurazano , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Linhagem Celular Tumoral , Hepatócitos/metabolismo , Humanos , RNA Mensageiro/análise , Distribuição Tecidual/efeitos dos fármacosRESUMO
A case of bronchopulmonary foregut malformation (BPFM) detected by multislice computed tomography with three-dimensional reconstruction (MSCT/3D) is reported. Concern for aspiration frequently limits the use of radiopaque contrast agents when anomalies of the lung and esophagus are suspected. MSCT/3D may make it possible to assess the communication and spatial relationship of malformed lung and esophagus in the early neonatal period without invasive or contrast radiological procedures such as bronchography or upper gastrointestinal series (UGI).
Assuntos
Brônquios/anormalidades , Broncopatias/diagnóstico por imagem , Sequestro Broncopulmonar/diagnóstico por imagem , Fístula Esofágica/diagnóstico por imagem , Adulto , Broncopatias/cirurgia , Sequestro Broncopulmonar/complicações , Fístula Esofágica/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Recém-Nascido , Masculino , Tomografia Computadorizada por Raios X , Gêmeos DizigóticosRESUMO
The insulinotropic effect of (+)-monocalcium bis [(2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl)propionate] dihydrate (CAS 145375-43-5, KAD-1229) was assessed by comparing it with those of glibenclamide (CAS 10238-21-8), nateglinide (CAS 105816-04-4), and repaglinide (CAS 135062-02-1) using HIT T15 cells, a hamster insulinoma cell line. Although their potencies were different, KAD-1229, glibenclamide, nateglinide, and repaglinide all concentration-dependently and significantly induced insulin release from these cells. Further, each agent displaced the binding of 3H-glibenclamide to the cell membrane and inhibited 86Rb+ efflux from the cells. These results indicate that KAD-1229, glibenclamide, nateglinide, and repaglinide each exert their insulinotropic effect by binding to the glibenclamide binding sites (sulfonylurea receptors) on pancreatic beta-cells and closing K+ channels. Diazoxide, a K+ channel opener, and nitrendipine, a Ca2+ blocker, suppressed the insulin release induced by KAD-1229 or glibenclamide. These results demonstrate that the insulinotropic actions of KAD-1229 and glibenclamide involve similar underlying pathways.
Assuntos
Hipoglicemiantes/farmacologia , Indóis/farmacologia , Insulina/biossíntese , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cricetinae , Glucose/metabolismo , Glibureto/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Isoindóis , Canais de Potássio/agonistas , Radioisótopos de Rubídio/metabolismoRESUMO
1. The effects of KAD-1229 (a novel non-sulphonylurea agent), voglibose (an alpha-glucosidase inhibitor) and nateglinide (a non-sulphonylurea antihyperglycaemic agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats. 2. KAD-1229 suppressed the increase in plasma glucose levels seen after a meal load and the area under the curve for plasma glucose levels (AUCglucose) up to 5 h after the meal load. 3. Voglibose also suppressed the increase in plasma glucose levels; however, a significant decrease in AUCglucose following voglibose was not observed. 4. Nateglinide suppressed the increase in plasma glucose levels at 30 min and 1 h after the meal load; however, plasma glucose levels was above control thereafter and the AUCglucose was not decreased. 5. The results indicate that KAD-1229 has an antihyperglycaemic effect and KAD-1229 is suggested to be a suitable agent for controlling post-prandial hyperglycaemia.