RESUMEN
BACKGROUND: At our institution, patients of all ages with extremely severe motor and intellectual disabilities (ESMID) receive comprehensive management similar to intensive care for "extremely ill patients." Some patients with ESMID develop frequent infections that are difficult to manage. The purpose of this study was to identify risk factors for frequent infections in these patients. METHODS: Thirty-seven patients with ESMID who were treated for infections at our institution between September 2018 and August 2019 were retrospectively investigated. Frequent infection was defined as three or more episodes of infection and antimicrobial treatment in one year. Infection status and potential risk factors for frequent infections (patient background factors, severity score, hematological parameters, anthropometry index, and parenteral nutritional status) were examined in univariate and multivariate analyses. RESULTS: Frequent infections occurred in 11 of the 37 patients (29.7%) during the study period, including respiratory and urinary tract infections. Univariate and multivariate analyses suggested hypoalbuminemia (p<0.01) and hypertriglyceridemia (p<0.01) were independent risk factors for frequent infections. CONCLUSIONS: Hypoalbuminemia and hypertriglyceridemia may be risk factors for frequent infections in patients with ESMID.
RESUMEN
OBJECTIVES: To determine the outcomes of patients with cystic biliary atresia by correlating the anatomy of the hepatic ducts with the choice of biliary reconstruction surgery. BACKGROUND: The Kasai hepatoportoenterostomy (Kasai) is the initial surgical procedure offered to most patients with biliary atresia. In contrast, a hepatic-cyst-jejunostomy has been reported to be effective in patients with the cystic form of biliary atresia. METHODS AND RESULTS: We performed an international multicenter retrospective review. Two hundred eighty-seven patients were included, and 33 cases of cystic biliary atresia were identified. Outcomes were the serum total bilirubin level 3 months post-surgery and native liver survival at 2 years of age and were compared between cases who received the Kasai versus hepatic-cyst-jejunostomy in correlation to the anatomy of proximal hepatic ducts. The patients were categorized into 3 anatomical groups: patent intact hepatic ducts (n = 10), patent hypoplastic hepatic ducts (n = 13), and obliterated hepatic ducts (n = 10). All 10 patients with patent intact hepatic duct group underwent hepatic-cyst-jejunostomy, and 9 experienced bile drainage and native liver survival. Among the 13 patients with hypoplastic hepatic ducts, 11 underwent the Kasai procedure, and 9 had bile drainage, whereas 2 underwent hepatic-cyst-jejunostomy, and one survived with the native liver. All of the patients with obliterated hepatic ducts underwent the Kasai procedure; 5 established biliary drainage and survived with the native liver. Of 5 who did not drain, 3 underwent liver transplantation. CONCLUSIONS: In patients with cystic biliary atresia, the subset with a connection between cyst and intrahepatic bile ducts via intact proximal hepatic ducts had favorable clinical outcomes following hepatic-cyst-jejunostomy.
Asunto(s)
Atresia Biliar , Quistes , Preescolar , Quistes/cirugía , Conducto Hepático Común/cirugía , Humanos , Yeyunostomía , Hepatopatías , Portoenterostomía Hepática , Estudios RetrospectivosRESUMEN
BACKGROUND: Biliary atresia (BA) is among the commonest indications for liver transplantation (LT) in children. We examined whether serum matrix metalloproteinase-7 (MMP-7) is useful for diagnosis of BA in Japanese infants, and whether serum MMP-7 concentrations before and after Kasai portoenterostomy (KP) predicted LT within a year. METHODS: Subjects under 6 months old at eight pediatric centers in Japan were enrolled retrospectively, including patients with cholestasis and normal controls (NC) without liver disease. Patients with cholestasis were divided into groups representing BA versus cholestasis from other causes (non-BA). Serum samples were collected from patients with BA at diagnosis and 1 and 4 weeks after KP, as well as from non-BA and NC. RESULTS: Serum MMP-7 concentrations were significantly higher in BA at diagnosis (median, 89.1 ng/ml) than in non-BA (11.0; p < 0.001) or NC (10.3; p < 0.001). Receiver operating characteristic (ROC) analysis of MMP-7 for BA versus non-BA yielded an area under the ROC curve of 0.99 (95% confidence interval, 0.96-1.00). An optimal cut-off value of 18.6 ng/ml for serum MMP-7 in diagnosing BA demonstrated sensitivity and specificity of 100% and 90%, respectively. Serum MMP-7 before and 1 week and 4 weeks after KP did not differ significantly between BA requiring only KP and BA requiring LT after KP. CONCLUSION: Serum MMP-7 is a useful marker for diagnosis of BA in Japanese infants, but it could not predict LT within a year.
RESUMEN
BACKGROUND: Reports of zinc and selenium deficiencies accompanying inflammatory bowel disease (IBD) mostly have originated from Western countries and concerned adult patients. Whether Japanese children with IBD have similar deficiencies remained unclear. AIM: We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. METHODS: Children under 17 years old undergoing care at 12 Japanese pediatric centers were retrospectively enrolled between November 2016 and February 2018 to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illnesses. Serum zinc and selenium were measured by atomic absorption spectrophotometry. Zinc and selenium deficiencies were defined by serum concentrations < 70 µg/dL and < 9.5 µg/dL, respectively. RESULTS: Subjects included 98 patients with CD (median age, 13 years), 118 with UC (11 years), and 43 NC (11 years). Serum zinc and selenium were significantly lower in CD (median, 64 and 12.6 µg/dL respectively) than in UC (69 and 14.6; P < 0.05 and P < 0.001) or NC (77 and 15.7; P < 0.01 and P < 0.001). Zinc deficiency was significantly more prevalent in CD (60.2%) than in NC (37.2%; P < 0.05), but not than in UC (51.7%; P = 0.22). Selenium deficiency was significantly more prevalent in CD (15.3%) than in UC (5.9%; P < 0.05) or NC (0%; P < 0.01). CONCLUSIONS: In Japanese children under 17 years old, serum zinc and selenium were significantly lower in CD than in UC or NC. Zinc and selenium should be monitored, and supplemented when deficient, in children with IBD, especially CD.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Desnutrición , Selenio , Adolescente , Adulto , Niño , Enfermedad Crónica , Enfermedad de Crohn/complicaciones , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Japón/epidemiología , Desnutrición/complicaciones , Estudios Retrospectivos , ZincRESUMEN
Diagnosis of biliary atresia (BA) can involve uncertainties. In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6 months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4ß-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68 days; range 26-170) and 10 non-BA cholestatic controls (59; 14-162), as well as 10 HC (57; 25-120). Total urinary oxysterols were significantly greater in BA (median, 153.0 µmol/mol creatinine; range 24.1-486.7; P < 0.001) and non-BA (36.2; 5.8-411.3; P < 0.05) than in HC (2.7; 0.8-7.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42-11.09; P < 0.01) was significantly greater than in non-BA (0.71; 0-5.62). In receiver operating characteristic (ROC) curve analysis for distinguishing BA from non-BA, the area under the ROC curve for urinary 27-hydroxycholesterol was 0.83. In conclusion, this first report of urinary oxysterol analysis in patients with BA indicated that 27-hydroxycholesterol may be a useful marker for distinguishing BA from other causes of neonatal cholestasis.
Asunto(s)
Atresia Biliar/orina , Hidroxicolesteroles/orina , Biomarcadores/orina , Femenino , Humanos , Lactante , Recién Nacido , Japón , Masculino , Espectrometría de Masas , Estudios ProspectivosRESUMEN
BACKGROUND AND AIM: Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS: Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS: Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3-ANCA was 0.79, significantly greater than for MPO-ANCA (0.58; P < 0.001). Using a cut-off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3-ANCA showed significantly greater sensitivity (64.9%) than MPO-ANCA (cut-off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). CONCLUSIONS: In Japanese children and adolescents, PR3-ANCA performed better as a serologic marker for diagnosis of UC than MPO-ANCA. To our knowledge, this is the first report of such a comparison.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Colitis Ulcerosa/diagnóstico , Mieloblastina/inmunología , Adolescente , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Peroxidasa/inmunología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Congenital chloride diarrhea (CCD) is characterized by persistent chloride (Cl)-rich diarrhea evident from birth. CCD is a rare autosomal recessive disorder caused by defects in the solute carrier family 26 member 3 (SLC26A3) gene, which encodes an intestinal Cl- /HCO3- , Na+ -independent exchanger. Various mutations of SLC26A3 have been described in CCD. However, no de novo mutations have been found to be responsible for CCD. Here we report the first such occurrence. METHODS: Clinical and laboratory findings during the perinatal period were obtained retrospectively from medical records. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: The male infant reported here was delivered at 29 weeks of gestation. Just after birth, he had watery diarrhea without meconium passage. High chloride concentrations in the diarrhea led to a diagnosis of CCD. Direct sequencing of all coding exons in SLC26A3 including exon-intron boundaries disclosed 2 compound heterozygous mutations: c.382G>A, p.G128S and c.2063-1g>t. The c. 2063-1g>t mutation was confirmed in his mother's DNA, but c.382G>A, p.G128S was absent in both mother and father. CONCLUSION: We concluded that c.382G>A, p.G128S represented a de novo mutation of SLC26A3, a very rare event in autosomal recessive disorders. To our knowledge, this is the first CCD case involving a de novo novel mutation of SLC26A3.
Asunto(s)
Antiportadores de Cloruro-Bicarbonato/genética , Diarrea/congénito , Errores Innatos del Metabolismo/genética , Mutación , Transportadores de Sulfato/genética , Diarrea/genética , Diarrea/patología , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/patologíaRESUMEN
Few reports describe oxysterols in healthy children or in children with liver disease. We aimed to determine whether developmental changes in urinary and serum oxysterols occur during childhood, and to assess whether oxysterols might be biomarkers for pediatric liver disease. Healthy children enrolled as subjects (36 and 35 for urine and serum analysis, respectively) included neonates, infants, preschoolers, and school-age children, studied along with 14 healthy adults and 8 children with liver disease. We quantitated 7 oxysterols including 4ß-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol using liquid chromatography/electrospray ionization-tandem mass spectrometry. Urinary total oxysterols were significantly greater in neonates than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.001), or adults (P < 0.001), declining with age. Serum total oxysterols in neonates were significantly lower than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.05), or adults (P < 0.01). Compared with healthy children, total oxysterols and 24(S)-hydroxycholesterol in liver disease were significantly increased in both urine (P < 0.001 and P < 0.001, respectively) and serum (P < 0.001 and P < 0.05, respectively). Oxysterols in liver disease, particularly 24(S)-hydroxycholesterol, were greater in urine than serum. Oxysterols change developmentally and might serve as a biomarker for pediatric liver disease. To our knowledge, this is the first such report.
Asunto(s)
Atresia Biliar/diagnóstico , Quiste del Colédoco/diagnóstico , Colestasis Intrahepática/diagnóstico , Hepatitis Autoinmune/diagnóstico , Fallo Hepático Agudo/diagnóstico , Oxiesteroles , Adolescente , Adulto , Factores de Edad , Atresia Biliar/sangre , Atresia Biliar/patología , Atresia Biliar/orina , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Niño , Preescolar , Quiste del Colédoco/sangre , Quiste del Colédoco/patología , Quiste del Colédoco/orina , Colestasis Intrahepática/sangre , Colestasis Intrahepática/patología , Colestasis Intrahepática/orina , Femenino , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/patología , Hepatitis Autoinmune/orina , Humanos , Lactante , Recién Nacido , Hígado/metabolismo , Hígado/patología , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/orina , Masculino , Persona de Mediana Edad , Oxiesteroles/sangre , Oxiesteroles/orina , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
BACKGROUND: Various serologic markers such as anti-glycoprotein 2 antibodies and anti-Saccharomyces cerevisiae antibodies have been reported to be diagnostically useful in Crohn's disease. Mitsuyama et al. reported that antibodies to Crohn's disease peptide 353, a newly proposed serologic marker, were more useful in Japanese adults than anti-Saccharomyces. We addressed the same issue in Japanese children and adolescents. METHODS: Prospectively enrolled subjects under 17 years old assessed and treated at 12 pediatric centers in Japan included groups with Crohn's disease, ulcerative colitis, other intestinal diseases, or good health. The 3 serum markers were analyzed by enzyme-linked immunosorbent assays. RESULTS: Enrolled subjects, numbering 367, included 120 with Crohn's disease, 148 with ulcerative colitis, 56 with other intestinal diseases, and 43 healthy subjects. In Crohn's disease, anti-Crohn's disease peptide 353, anti-glycoprotein 2, and anti-Saccharomyces concentrations (median, 2.25, 3.0, and 8.9 U/mL) were significantly greater than in ulcerative colitis (1.1, 1.9, and 3.4; all P < 0.001), other intestinal diseases (1.1, 1.85, and 2.95; all P < 0.001), and healthy controls (1.1, 1.7, and 2.8; all P < 0.001), respectively. At 95% specificity, sensitivity of anti-Crohn's disease peptide (45.0%) was significantly higher than for anti-glycoprotein 2 (30.8%; P < 0.05) or anti-Saccharomyces (26.7%; P < 0.01). CONCLUSIONS: Anti-Crohn's disease peptide 353 proved more useful for diagnosis of Crohn's disease in Japanese children than the other 2 markers. To our knowledge, this is the first pediatric report to that effect.
Asunto(s)
Anticuerpos/inmunología , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Péptidos/inmunología , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Japón , Masculino , Estudios Prospectivos , Saccharomyces cerevisiae/inmunología , Sensibilidad y EspecificidadRESUMEN
PURPOSE: This study aimed to investigate whether intra-tracheal administration of basic fibroblast growth factor (b-FGF) promotes the growth of tracheal cartilage. METHODS: Trachea of 4-week old mice were intubated and 2.5 µg b-FGF administered (Group 4) for periods from 1 to 5 days. Cervical tracheal outer diameter and tracheal ring length were compared in Group 1 (no intervention), Group 2 (tracheal intubation), Group 3 (intra-tracheal administration of distilled water) and Group 4, at 8 weeks of age. Outer diameter and tracheal ring length in Group 4 were also compared with that in Group 1 at 12 and 16 weeks of age. RESULTS: At 8 weeks of age, tracheal ring length with b-FGF administration for more than 4 days in Group 4 was significantly increased over that following 1-day administration. At 8 weeks of age, mean outer diameter and the mean tracheal ring length in Group 4 were significantly greater than in the other groups. Mean outer diameter and mean tracheal ring length were significantly greater in Group 4 than in Group 1 at 12 and 16 weeks of age. CONCLUSION: This study has shown that intra-tracheal administration of b-FGF enlarges the tracheal lumen.
Asunto(s)
Cartílago/crecimiento & desarrollo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Tráquea/crecimiento & desarrollo , Animales , Cartílago/efectos de los fármacos , Cartílago/patología , Ratones , Tráquea/efectos de los fármacos , Tráquea/patologíaRESUMEN
OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.
Asunto(s)
Antiportadores de Cloruro-Bicarbonato/genética , ADN/genética , Diarrea/congénito , Predicción , Errores Innatos del Metabolismo/genética , Mutación , Vigilancia de la Población , Transportadores de Sulfato/genética , Antiportadores de Cloruro-Bicarbonato/metabolismo , Análisis Mutacional de ADN , Diarrea/epidemiología , Diarrea/genética , Diarrea/metabolismo , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Incidencia , Recién Nacido , Japón/epidemiología , Masculino , Errores Innatos del Metabolismo/epidemiología , Errores Innatos del Metabolismo/metabolismo , Estudios Retrospectivos , Transportadores de Sulfato/metabolismo , Tasa de Supervivencia/tendencias , Factores de TranscripciónAsunto(s)
Colitis Ulcerosa/diagnóstico , Neuritis Óptica/diagnóstico , Dolor Abdominal/etiología , Adolescente , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Diagnóstico Diferencial , Diarrea/etiología , Esquema de Medicación , Femenino , Humanos , Imagen por Resonancia Magnética , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Glicoproteína Mielina-Oligodendrócito/sangre , Neuritis Óptica/complicaciones , Neuritis Óptica/diagnóstico por imagen , Neuritis Óptica/tratamiento farmacológicoRESUMEN
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare, genetically heterogeneous disorder that manifests oculocutaneous albinism together with bleeding diatheses that reflect a platelet storage pool deficiency. Ten genetic subtypes of this autosomal recessive condition have been described to date. Some patients with Hermansky-Pudlak syndrome type 1, 4, or 6 develop Crohn's-like inflammatory bowel disease at any age including early childhood, but most often in adolescence or young adulthood. Here we report infantile-onset of inflammatory bowel disease in a patient with Hermansky-Pudlak syndrome type 1 who responded to infliximab. CASE PRESENTATION: A Japanese boy, the second child of non-consanguineous healthy parents, was born with chalky white skin, silvery-white hair, and gray eyes, representing oculocutaneous albinism. He developed frequent diarrhea and fever accompanied by weight loss at 6 months, and was diagnosed with Crohn's-like inflammatory bowel disease based on the endoscopic finding of longitudinal ulcerations in the colon and the histopathologic finding of nonspecific chronic inflammation without granulomas at the age of 11 months. Treatment with an elemental diet, salazosulfapyridine, and corticosteroids failed to improve clinical or laboratory abnormalities, and the diarrhea became bloody. At 13 months he began treatment with infliximab, which produced marked improvement followed by clinical remission. Endoscopy at 20 months demonstrated healing of the colonic mucosa. At 22 months he is in sustained clinical remission receiving only infliximab. Because albinism with inflammatory bowel disease suggested Hermansky-Pudlak syndrome, we performed genetic screening using next-generation sequencing in a targeted gene panel analysis for primary immunodeficiency disease and/or inflammatory bowel disease. The patient proved to have a compound heterozygous mutation of the HPS1 gene resulting in Hermansky-Pudlak syndrome type 1. CONCLUSIONS: We consider this report to be the first account of type 1 Hermansky-Pudlak syndrome with infantile-onset of inflammatory bowel disease. Early administration of infliximab was effective. We recommend next-generation sequencing for patients with very early-onset inflammatory bowel disease suspected to be monogenic.
Asunto(s)
Síndrome de Hermanski-Pudlak/complicaciones , Síndrome de Hermanski-Pudlak/diagnóstico , Enfermedades Inflamatorias del Intestino/complicaciones , Edad de Inicio , Fármacos Gastrointestinales/uso terapéutico , Síndrome de Hermanski-Pudlak/genética , Heterocigoto , Humanos , Lactante , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Infliximab/uso terapéutico , Masculino , Proteínas de la Membrana/genética , Mutación , Inducción de RemisiónRESUMEN
BACKGROUND: Early definitive diagnosis of necrotizing enterocolitis (NEC) based on Bell's staging criteria is difficult because there are few observable changes on abdominal imaging and blood chemistry tests at the onset of the disease. PURPOSE: To investigate whether prostaglandin E-2 major urinary metabolite (PGE-MUM) can be a useful surrogate marker reflecting the disease state and severity of NEC in infants. METHODS: Infants were enrolled in this study between January 2014 and December 2016. NEC diagnosis was based on Bell's staging criteria > Stage II or necrotic bowel observed at surgery. After diagnosis, PGE-MUM level was measured and compared with that of the other disease and healthy infant groups. RESULTS: Median PGE-MUM value was highest in the NEC group (576 [65-3672] µg/gâ¢Cre/BSAâ¯×â¯1000), followed by the other disease group (94 [57-296] µg/gâ¢Cre/BSAâ¯×â¯1000) and the healthy infant group (19 [10-44] µg/gâ¢Cre/BSAâ¯×â¯1000) (sensitivity: 92.3%, specificity: 81.5%, accuracy: 85.0%; pâ¯<â¯0.01). PGE-MUM level correlated with improved status of NEC, length of necrotic intestine, and Bell's staging criteria. CONCLUSIONS: PGE-MUM level may be a useful surrogate biomarker reflecting the disease state of NEC. The method of urine sample collection is also advantageous, being noninvasive for infants. This is the first study reporting PGE-MUM level in NEC. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: LEVEL II.
Asunto(s)
Enterocolitis Necrotizante/orina , Prostaglandinas E/orina , Biomarcadores/orina , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Intratracheal injection of basic fibroblast growth factor (b-FGF) has been shown to enlarge the tracheal lumen 4â¯weeks after treatment. The objective of this study was to investigate the long-term effect of tracheal cartilage growth promotion by intratracheal injection of b-FGF. MATERIALS AND METHODS: New Zealand white rabbits were classified into four groups to receive either distilled water alone (Group 1; nâ¯=â¯16; control), 40⯵g (Group 2; nâ¯=â¯10), 100⯵g (Group 3; nâ¯=â¯13), or 200⯵g (Group 4; nâ¯=â¯16) of b-FGF dissolved in water. The treatment was injected into the posterior wall of the cervical trachea using a tracheoscope. The animals were sacrificed 4 or 12â¯weeks later. RESULTS: Four weeks after treatment, the mean luminal areas of tracheas for Groups 1, 2, 3, and 4 were 27.2, 25.6, 32.2, and 36.2â¯mm2, respectively. At 12â¯weeks, these were 29.3, 37.9, 42.5, and 56.0â¯mm2, respectively. The levels of glycosaminoglycan at 12â¯weeks were 93.9, 152.5, 123.2, and 210.6⯵g/mg, respectively. At 12â¯weeks, the levels of type II collagen were 77.2, 133.1, 99.2, and 148.9⯵g/mg, respectively. CONCLUSION: Twelve weeks after a single injection of b-FGF, the mean luminal area of the trachea continued to increase.
Asunto(s)
Cartílago/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Tráquea/efectos de los fármacos , Animales , Cartílago/crecimiento & desarrollo , Colágeno Tipo II/metabolismo , Femenino , Estudios de Seguimiento , Glicosaminoglicanos/metabolismo , Conejos , Tráquea/metabolismoRESUMEN
BACKGROUND: A gelatin sponge with slowly releasing basic fibroblast growth factor (b-FGF) enhances chondrogenesis. This study investigated the optimal amount of b-FGF in gelatin sponges to fabricate engineered cartilage. MATERIALS AND METHODS: b-FGF (0, 10, 100, 500, 1000, and 2000 µg/cm(3))-impregnated gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) were produced. Chondrocytes were isolated from the auricular cartilage of C57B6J mice and expanded. The expanded auricular chondrocytes (10×10(6) cells/cm(3)) were seeded onto the gelatin sponges, which served as scaffolds. The construct assembly was implanted in the subcutaneous space of mice through a syngeneic fashion. Thereafter, constructs were retrieved at 2, 4, or 6 weeks. RESULTS: (1) Morphology: The size of implanted constructs was larger than the size of the scaffold with 500, 1000, and 2000 µg/cm(3) b-FGF-impregnated gelatin sponges incorporating ß-TCP at 4 and 6 weeks after implantation. (2) The weight of the constructs increased roughly proportional to the increase in volume of the b-FGF-impregnated scaffold at 2, 4, and 6 weeks after implantation, except in the 2000 µg/cm(3) b-FGF-impregnated constructs group. (3) Histological examination: Extracellular matrix in the center of the constructs was observed in gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF at 4 weeks after implantation. The areas of cells with an abundant extracellular matrix were positive for cartilage-specific marker type 2 collagen in the constructs. (4) Protein assay: Glycosaminoglycan and collagen type 2 expression were significantly increased at 4 and 6 weeks on implantation of gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF. At 6 weeks after implantation, the ratio of type 2 collagen to type 1 collagen in constructs impregnated with 100 µg/cm(3) or more b-FGF was higher than that in mice auricular cartilage. CONCLUSION: Gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF incorporating ß-TCP with chondrocytes (10×10(6) cells/cm(3)) can fabricate engineered cartilage at 4 weeks after implantation.
Asunto(s)
Cartílago Articular/crecimiento & desarrollo , Condrocitos/citología , Preparaciones de Acción Retardada/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Esponja de Gelatina Absorbible/química , Andamios del Tejido , Materiales Biocompatibles/síntesis química , Fosfatos de Calcio/química , Cartílago Articular/citología , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/fisiología , Condrogénesis/efectos de los fármacos , Condrogénesis/fisiología , Preparaciones de Acción Retardada/química , Relación Dosis-Respuesta a Droga , Diseño de Equipo , Análisis de Falla de Equipo , Factor 2 de Crecimiento de Fibroblastos/química , Humanos , Ensayo de Materiales , Impresión Tridimensional , Ingeniería de Tejidos/instrumentaciónRESUMEN
AIM: This study aimed to develop new devices for translumenal endoscopic esophageal anastomosis-a stent and a ligating device-and to confirm the feasibility of our novel procedure using those devices. MATERIALS AND METHODS: We designed a ligating device as an overtube whose tip worked like the EVL device (Sumitomo Bakelite Co. Ltd., Tokyo, Japan). The newly developed procedure for anastomosis is as follows: a silicone elastic band, which was released from the device located at the upper esophagus, and a custom-made expandable stent, which was expanded by the balloon catheter in the lower esophagus, tightened the upper and lower esophageal walls. After producing the devices, we performed the anastomosis procedure in porcine models. RESULTS: A ligating device and an expandable stent were developed for this study. An ex vivo feasibility study was performed in three porcine models. Endoscopic visualization revealed that all steps in this procedure were technically successful. The median time needed to perform this procedure was 24 (range, 19-25) minutes. Patency of the anastomosis was confirmed in all specimens. CONCLUSIONS: Translumenal esophagoesophageal anastomosis using the new devices was feasible. The procedure time was sufficiently short for clinical use. An in vivo survival study is needed to confirm the safety and reliability of this procedure.