RESUMEN
OBJECTIVES: Congenital knee dislocation (CKD) is a rare condition, affecting 1 in 100 000 newborns. Its prenatal diagnosis is challenging and not well described in the literature, especially when it appears isolated and not as part of a complex malformation or syndromic pattern. The purpose of this study was to provide a comprehensive review of the available literature on the prenatal diagnosis and postnatal outcome of CKD and to summarize the current evidence on this topic. METHODS: A systematic review of the literature on the prenatal diagnosis of CKD was performed in PubMed, Scopus and EMBASE. A predefined combination of specific keywords was used, focusing on intrauterine manifestations, diagnostic methods, prenatal behavior, postnatal treatment and neonatal outcome as well as long-term outcome in terms of ambulation, motion and joint stability. The quality of studies was assessed using the National Institutes of Health tool for quality assessment of case series. A summary of results was carried out providing proportions and rates of diagnostic and prognostic features associated with this rare condition. RESULTS: In total, 20 cases were retrieved for analysis, of which 19 were obtained from the identified eligible studies (n = 16) and one was an unpublished case from our center. The median gestational age at prenatal diagnosis, which was made using ultrasound in most cases, was 20 weeks (range, 14-38 weeks). Bilaterality was observed in 11/20 (55%) cases. The condition was isolated in 7/20 (35%) cases and associated with other anomalies in 13/20 (65%) cases. An association was observed with oligohydramnios (4/20 (20%)), and an invasive procedure was performed in 13/20 (65%) cases, including 11 cases with an invasive procedure performed for diagnostic purposes. Genetic testing was normal in all isolated cases for which information was available (4/7), while a genetic syndrome was present in 10/13 (77%) non-isolated cases (Larsen, Noonan, Grebe, Desbuquois or Escobar syndrome). There were seven terminations of pregnancy, of which six were performed in cases with associated anomalies and one in an isolated case, 11 cases of postnatal survival, one case of intrauterine death and one of neonatal death. The fetal and neonatal deaths occurred in cases with associated anomalies or abnormal genetic findings. Postnatal treatment was mostly conservative, with only two reports (18% of the 11 surviving neonates) of surgical intervention, both in cases with associated anomalies. Postnatal follow-up was up to 1 year in most cases, and motor outlook appeared normal in all isolated cases. CONCLUSIONS: CKD is a rare fetal anomaly with a prenatal diagnosis achievable from the early second trimester, for which a favorable outcome can be expected when no associated anomalies are present. Prenatal diagnosis should include detailed ultrasound assessment and amniocentesis for extensive genetic studies, particularly in non-isolated cases. Early postnatal treatment achieves success in most cases without surgical intervention and leads to a normal motor outlook. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Insuficiencia Renal Crónica , Ultrasonografía Prenatal , Femenino , Humanos , Recién Nacido , Embarazo , Feto , Pruebas Genéticas , Diagnóstico Prenatal/métodos , Estudios Retrospectivos , Ultrasonografía Prenatal/métodosRESUMEN
PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.
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Enanismo , Maduración Sexual , Masculino , Femenino , Humanos , Ubiquitina-Proteína Ligasas/genética , Mutación , Proteínas de la Membrana/genética , Fenotipo , Proteínas de Unión al Calcio/genéticaRESUMEN
BACKGROUND AND AIMS: Subclinical inflammation is a central component of cardiometabolic disease risk in obese subjects. The aim of the study was to evaluate whether the white blood cell count (WBCc) may help to identify an abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children. METHODS AND RESULTS: A cross-sectional sample of 2835 Ow/Ob children and adolescents (age 6-18 years) was recruited from 10 Italian centers for the care of obesity. Anthropometric and biochemical variables were assessed in the overall sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315 children, respectively. Insulin resistance and whole body insulin sensitivity index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and Matsuda's test. Groups divided in quartiles of WBCc significantly differed for body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and relative wall thickness. Children with high WBCc (≥8700 cell/mm(3)) showed a 1.3-2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT, or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender, pubertal status, BMI and centers. CONCLUSIONS: This study shows that WBCc is associated with early derangements of glucose metabolism and preclinical signs of liver, vascular and cardiac damage. The WBCc may be an effective and low-cost tool for identifying Ow and Ob children at the greatest risk of potential complications.
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Enfermedades Cardiovasculares/sangre , Hepatopatías/sangre , Síndrome Metabólico/sangre , Obesidad Infantil/sangre , Adolescente , Factores de Edad , Alanina Transaminasa/sangre , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Grosor Intima-Media Carotídeo , Niño , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Recuento de Leucocitos , Hepatopatías/diagnóstico , Hepatopatías/epidemiología , Hepatopatías/fisiopatología , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Síndrome Metabólico/fisiopatología , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Obesidad Infantil/fisiopatología , Fenotipo , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
BACKGROUND AND AIMS: Lipid ratios to estimate atherosclerotic disease risk in overweight/obese children are receiving great attention. We aimed to compare the performance of non-high-density lipoprotein-cholesterol (HDL-C) versus triglycerides-to-HDL-C ratio (Tg/HDL-C) in identifying cardiometabolic risk factors (CMRFs) or preclinical signs of organ damage in outpatient Italian overweight/obese children. METHODS AND RESULTS: In this retrospective, cross-sectional study, 5505 children (age 5-18 years) were recruited from 10 Italian centers for the care of obesity, of which 4417 (78%) showed obesity or morbid obesity. Anthropometric, biochemical, and blood pressure variables were analyzed in all children. Liver ultrasound scan, carotid artery ultrasound, and echocardiography were performed in 1257, 601, and 252 children, respectively. The entire cohort was divided based on the 75th percentile of non-HDL-C (≥130 mg/dl) or Tg/HDL-C ratio (≥2.2). The odds ratio for insulin resistance, high blood pressure, metabolic syndrome, presence of liver steatosis, increased levels of carotid intima-media thickness (cIMT) and concentric left ventricular hypertrophy (cLVH) was higher in children with high levels of Tg/HDL-C with respect to children with high levels of non-HDL-C. CONCLUSIONS: In an outpatient setting of overweight/obese children, Tg/HDL-C ratio discriminated better than non-HDL-C children with CMRFs or preclinical signs of liver steatosis, and increased cIMT and cLVH.
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Enfermedades Cardiovasculares/etiología , HDL-Colesterol/sangre , Colesterol/sangre , Síndrome Metabólico/etiología , Sobrepeso/fisiopatología , Obesidad Infantil/fisiopatología , Triglicéridos/sangre , Adolescente , Algoritmos , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Italia/epidemiología , Hígado/diagnóstico por imagen , Hígado/fisiopatología , Masculino , Síndrome Metabólico/epidemiología , Sobrepeso/sangre , Obesidad Infantil/sangre , Estudios Retrospectivos , Factores de Riesgo , UltrasonografíaRESUMEN
Nephritis characterized by IgA mesangial depositions has been described both in Henoch-Schoenlein purpura (HSP) and in Berger's disease (BD), but common genetic traits are still uncertain. We report here the case of two brothers, the first affected by HSP with persistent nephritis and the second by BD, accidentally discovered as silent microhematuria 1 year after HSP onset in the first brother. HLA genotyping demonstrated the presence of HLA-B35 in both patients. Our findings reinforce the need to screen for urinary abnormalities in family members of patients affected by HSP nephritis to identify a silent IgA nephropathy.
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Glomerulonefritis por IGA/genética , Antígeno HLA-B35/genética , Nefritis/genética , Adolescente , Niño , Femenino , Genotipo , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/patología , Humanos , Vasculitis por IgA/complicaciones , Vasculitis por IgA/genética , Vasculitis por IgA/patología , Masculino , Persona de Mediana Edad , Nefritis/complicaciones , Nefritis/patología , FenotipoAsunto(s)
Artritis Juvenil/complicaciones , Articulación Atlantoaxoidea/patología , Luxaciones Articulares/etiología , Antirreumáticos/administración & dosificación , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/patología , Niño , Femenino , Glucocorticoides/administración & dosificación , Humanos , Luxaciones Articulares/diagnóstico , Luxaciones Articulares/tratamiento farmacológico , Imagen por Resonancia Magnética , Quimioterapia por Pulso , Tortícolis/etiología , Resultado del Tratamiento , Uveítis/etiologíaRESUMEN
The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies. The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1ß maturation and secretion by macrophages. Little is currently known about a possible role for the NLRP3 inflammasome in atherosclerosis progression in vivo. We generated ApoE-/- Nlrp3-/-, ApoE-/- Asc-/- and ApoE-/- caspase-1-/- double-deficient mice, fed them a high-fat diet for 11 weeks and subsequently assessed atherosclerosis progression and plaque phenotype. No differences in atherosclerosis progression, infiltration of plaques by macrophages, nor plaque stability and phenotype across the genotypes studied were found. Our results demonstrate that the NLRP3 inflammasome is not critically implicated in atherosclerosis progression in the ApoE mouse model.
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Apolipoproteínas E/deficiencia , Aterosclerosis/inmunología , Aterosclerosis/patología , Proteínas Portadoras/inmunología , Inflamasomas/inmunología , Animales , Apolipoproteínas E/genética , Apolipoproteínas E/inmunología , Aterosclerosis/genética , Proteínas Portadoras/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Inflamasomas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLRRESUMEN
This study reviews the data regarding clinical and ultrasound (US) examinations, collected during an 11-year period, in a DDH dedicated outpatient clinic. The material was analysed in order to verify the importance of US hip examination and Ortolani's test for early DDH diagnosis, to select dysplastic, unstable hips, to identify the role of the labrum in DDH, and to analyse the treatment strategy. Of the 21709 newborns (43418 hips) examined with US and Ortolani's manoeuvre for DDH diagnosis, 431 patients (356 F; 75 M; average age 42+/-33 days) had 574 unstable, dysplastic hips (1.32%). The hips identified according to Graf's classification were: 298 type D, 252 type IIIa, 4 type IIIb, 20 type IV. In 73.09% of the patients, no risk factors were identified; 18.56% had positive family history for DDH, 5.57% had breech presentation, 2.78% had both risk factors. Only 10.63% had a positive Ortolani's test. The diagnosis was made in 21.5% of cases by the 2nd week of life, in 52.9% between the 2nd-8th week, and in 25.5% after the 8th week. Unstable dislocated hips were treated, after reduction with or without sedation, by applying a cast; dysplastic hips were treated using a Gekeler splint. No open reductions or reconstruction surgery were needed. The labrum was always positioned on top of the femoral head, never inverted, and it was not an obstacle to closed reduction. Neither the Ortolani's sign, nor the risk factors are sure signs for the early diagnosis of DDH and its instability. Only US examination permits an early diagnosis of dysplasia and instability of the hip.
RESUMEN
UNLABELLED: Minimally invasive subtalar screw-arthroereisis has gained interest in the correction of flat feet in children. Between 1990 and 2004, this technique was used on 152 children, 74 bilaterally, for a total of 226 feet. There were 82 boys and 70 girls, with an average age of 10.6+/-1.9 years. The results were good in 95.4% of cases, whilst there were complications in 4.6%. For well corrected feet, 55 screws have now been removed, on average 2.9 years after implantation. The indications for such treatment are: talipes calcaneovalgus, which develops into a flat foot (spontaneous correction can be expected to 10-11 years), juvenile flat foot with medial protrusion of the talar head and complete absence of the longitudinal arch, symptomatic talipes calcaneovalgus with pain on the insertion of the tibialis posterior tendon, a minimum age of 6 years if a correction with conservative treatment does not show any improvement; a maximum age of 12-13 years considering that there always has to be a manual reducibility of the deformity. CONTRAINDICATIONS: posttraumatic flat foot, congenital flat foot, stiff flat foot, age over 13 years.
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Tornillos Óseos , Pie Plano/cirugía , Procedimientos Ortopédicos , Adolescente , Factores de Edad , Artrodesis , Calcáneo/cirugía , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Osteotomía/métodos , Complicaciones Posoperatorias , Factores de Tiempo , Resultado del TratamientoRESUMEN
Elastin is the main protein of elastic fibers and confers the property of elastic recoil to the tissues such as arteries, lung, elastic cartilage,... Elastin synthesis goes through several steps: gene transcription, alternative splicing of pre-mRNA, mRNA translation, hydroxylation of some proline residues of the newly synthesized protein-tropoelastin-, association of with a 67 kDa chaperone protein, secretion of tropoelastin molecules in the extracellular space, and their deposition on the microfibrillar scaffold which contains fibrillin 1, fibrillin 2, MAGP 1 and MAGP 2,.... After the synthesis of cross-links-lysinonorleucine, desmosine, isodesmosine-, elastin becomes insoluble and elastic. The elastogenic pathway is regulated at many levels. The most recently described regulatory mechanism of elastin synthesis is the control of elastin mRNA stability. Elastogenesis is well controlled during development and aging but remains responsive to external factors such as soluble compounds-cytokines, vitamins, hormones,...- and hemodynamic stress. In order to ensure its function, both quantity and quality of elastin should be and should remain optimal in elastic tissues.
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Elastina/biosíntesis , Proteínas de la Matriz Extracelular , Empalme Alternativo , Elementos Alu , Animales , Bovinos , Proteínas Contráctiles/metabolismo , Tejido Elástico/metabolismo , Elasticidad , Elastina/química , Elastina/genética , Matriz Extracelular/metabolismo , Fibrilina-1 , Fibrilina-2 , Fibrilinas , Regulación de la Expresión Génica , Genes , Sustancias de Crecimiento/fisiología , Hemodinámica , Humanos , Proteínas de Microfilamentos/metabolismo , Chaperonas Moleculares/fisiología , Polimorfismo Genético , Regiones Promotoras Genéticas , Conformación Proteica , Pliegue de Proteína , Procesamiento Proteico-Postraduccional , Precursores del ARN/genética , Factores de Empalme de ARN , ARN Mensajero/genética , Homología de Secuencia de Ácido Nucleico , Solubilidad , Relación Estructura-Actividad , Transcripción Genética , Tropoelastina/metabolismoRESUMEN
We have previously reported an adaptation of arterial wall elasticity in spontaneously hypertensive rats (SHR) that involves an increase in both fibronectin/alpha5beta1-integrin complexes and smooth-muscle elastic lamellae connections. We examined the mechanical strength (MS) of the carotid artery in relation to its elastic properties, its elastin/collagen content, and the structure of the internal elastic lamina. MS was defined as the in vitro intraluminal pressure and wall stress that produces rupture of the vascular wall. Intact carotid arteries from 3-month-old normotensive rats (Wistar-Kyoto, WKY) and SHR were cannulated on a specially designed device and adjusted to their in situ length. A slowly increasing static pressure was applied until wall rupture occurred to determine the static mechanical behavior and MS. Static elasticity was similar in SHR and WKY, as were the rupture pressure (2740+/-90 versus 2740+/-40 mm Hg) and wall stress at rupture (11.5+/-1.0 versus 12.8+/-0.4 MPa), indicating equivalent MS in both groups. Histological examination showed several wall ruptures and dissociation of lamellar units that did not differ significantly between the 2 groups. Confocal microscopy showed that the size of fenestrations of the internal elastic lamina and the fraction of area occupied by them were reduced 3-fold in SHR. We have demonstrated that static elasticity of the arterial wall and mechanical strength are similar in carotid arteries from SHR and WKY.
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Arterias Carótidas/fisiopatología , Hipertensión/fisiopatología , Animales , Arterias Carótidas/química , Arterias Carótidas/patología , Colágeno/análisis , Fuerza Compresiva , Técnicas de Cultivo , Elasticidad , Elastina/análisis , Hipertensión/metabolismo , Hipertensión/patología , Masculino , Microscopía Confocal , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
PURPOSE: Intimal hyperplasia is one of the main responses of the vascular wall to injury. In the current study, we tested the hypothesis that endoluminal seeding of host syngeneic vascular cells could limit intimal hyperplasia induced by either mechanical deendothelialization or chronic allograft rejection in rat aorta. METHODS: An experimental model of in situ seeding of syngeneic endothelial cells, smooth muscle cells (SMCs), and fibroblasts (FIBs) was used in mechanically deendothelialized and allografted aortas. In a preliminary study, the ability of the three cell types (n = 5 per group) to seed on the deendothelialized luminal surface of the aortic wall was evaluated after 2 days, with the use of fluorescent PKH as marker. In the first model, the abdominal aorta of Lewis rats was deendothelialized (n = 6) or deendothelialized and seeded with either SMCs (n = 6) or FIBs (n = 6) before flow was restored. In the allograft model, aortas were harvested from dark agouti rats and orthotopically grafted in Lewis receivers, directly (n = 6) or after deendothelialization. Deendothelialization was performed alone (n = 6) or associated with the seeding of similar host (Lewis) syngeneic SMCs (n = 6) or FIBs (n = 6). Results were evaluated at 2 months with histologic and morphometric methods. RESULTS: SMCs and FIBs were able to adhere in situ to the deendothelialized aortic wall, whereas endothelial cells were not. In mechanically deendothelialized aortas, the seeding of syngeneic SMCs led to a significant reduction in intimal thickness compared with deendothelialized aortas or FIB-seeded aortas (26.9 +/- 1.7 microm vs 55.5 +/- 1.7 and 56.7 +/- 1.7 microm, respectively), and a lower nuclear content (382.2 +/- 35.7 microm(2) vs 779.6 +/- 65.9 and 529.6 +/- 24.3 microm(2), respectively) of neointima. After SMC seeding, intimal hyperplasia was richer in elastin, whereas after FIB seeding it was richer in collagen. In allografts, the seeding of syngeneic SMC led to a significant reduction in intimal thickness compared with control aortas, deendothelialized aortas, or FIB-seeded aortas (31.6 +/- 1.1 microm vs 88.55 +/- 2.8, 74.6 +/- 2.9, and 85.7 +/- 2.6 microm, respectively), and a reduced nuclear content of the neointima (444.9 +/- 23.4 microm(2) vs 1529.1 +/- 116, 972.3 +/- 50, and 645.2 +/- 32.4 microm(2), respectively). Differences observed in the extracellular matrix composition were equivalent to those observed in the mechanically deendothelialized model. CONCLUSIONS: Our results suggest that endoluminal seeding of syngeneic SMCs can be effective in reducing intimal hyperplasia both in a deendothelialization model and in arterial allografts. SMC and FIB endoluminal seeding led to a significatively different accumulation of extracellular matrix in the intima.
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Aorta Abdominal/lesiones , Aorta Abdominal/patología , Modelos Animales de Enfermedad , Fibroblastos/trasplante , Músculo Liso Vascular/citología , Túnica Íntima/lesiones , Túnica Íntima/patología , Análisis de Varianza , Animales , Adhesión Celular , División Celular/fisiología , Movimiento Celular , Enfermedad Crónica , Colágeno/análisis , Elastina/análisis , Rechazo de Injerto/patología , Hiperplasia , Inflamación , Masculino , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas , Factores de Tiempo , Trasplante Homólogo , Trasplante Isogénico , Túnica Íntima/química , Cicatrización de Heridas/fisiologíaRESUMEN
Our aim was to determine the structural factors that determine the mechanical adaptation of the carotid arterial wall in stroke-prone hypertensive rats (SHRSP). Distensibility-pressure and elastic modulus-stress curves assessed by in vivo echo-tracking measurements indicated a reduction in arterial stiffness in 13-week-old SHRSP compared with Wistar-Kyoto rats (WKY). Elastin and collagen contents determined biochemically were not different between SHRSP and WKY. Confocal microscopy showed that the mean area of fenestrations and fraction of area occupied by fenestrations of the internal elastic lamina (IEL) were smaller in SHRSP than in WKY, which indicated a reduction in stress-concentration effects within the IEL. Immunohistologic staining of EIIIA fibronectin isoform and total fibronectin (also as determined by Western blot) was greater in SHRSP, which suggested increased cell-matrix interactions. We suggest that these structural modifications of the vascular wall play a synergistic role in the mechanical adaptation to a high level of stress in SHRSP.
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Arterias Carótidas/patología , Arterias Carótidas/fisiopatología , Hipertensión/patología , Hipertensión/fisiopatología , Accidente Cerebrovascular/etiología , Animales , Western Blotting , Arterias Carótidas/metabolismo , Colágeno/metabolismo , Elasticidad , Elastina/metabolismo , Fibronectinas/metabolismo , Hipertensión/metabolismo , Técnicas para Inmunoenzimas , Microscopía Confocal , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Estrés MecánicoRESUMEN
McCune-Albright syndrome (MAS) is a sporadic disease characterized by fibrous bone dysplasia, café-au-lait spots and hyperfunctional endocrinopathies. We report a 2.5-year-old child with MAS with an early and nonclassic onset. He was admitted to our attention for frequent fractures without clinical signs of endocrinopathies, found to have asymptomatic, nonautoimmune hyperthyroidism. The diagnosis of MAS was based on RX and MR imaging associated with hyperthyroidism. It is not clear if there was a correlation between the severity of bone disease and the presence of thyroid disorder. At the moment no standard treatment exists for bone fibrous dysplasia and hyperthyroidism in children before the age of 6 years.
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Displasia Fibrosa Poliostótica/complicaciones , Displasia Fibrosa Poliostótica/diagnóstico , Fracturas Óseas/etiología , Hipertiroidismo/etiología , Preescolar , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , RadiografíaRESUMEN
BACKGROUND AND PURPOSE: Under certain conditions, the Brown Norway (BN) rat is susceptible to intracerebral hemorrhagic vascular (ICV) lesions within the cerebral cortex, whereas the Long-Evans (LE) rat is prone to develop aneurysms in the circle of Willis. The incidence of these 2 pathological phenotypes was studied in progeny of different BNXLE crosses to determine their heritability in these new rat models. In addition, a possible link between ICV lesion occurrence and either the susceptibility to spontaneous rupture of the arterial internal elastic lamina (IEL) or basal plasma angiotensin-converting enzyme (ACE) activity was also studied in back-cross (BC) F1XBN rats, the only second-generation group with a high incidence of ICV lesions. METHODS: To induce cerebrovascular lesions, rats were submitted to experimental hypertension associated with ligation of 1 carotid artery. After death, the brain was examined for cerebral lesions. Numbers of arterial IEL ruptures were determined microscopically with the use of en face preparations. Plasma ACE activity was determined before the induction of hypertension. RESULTS: In general, groups that developed ICV lesions presented a low incidence of aneurysms. ICV lesion incidence was similar in F1 hybrids and BC(F1XBN) and greatly decreased in F2 and BC(F1XLE) rats compared with BN rats. No cerebral aneurysms developed in F1 rats. Aneurysmal incidence was 24% (20% ruptured) in LE, 42% (59% ruptured) in F2, and 50% (75% ruptured) in BC(F1XLE) rats. In BC(F1XBN) rats, neither the incidence of IEL rupture nor the plasma ACE activity was higher in the rats with ICV lesions. However, the mean blood pressure level was higher in these rats, and peak blood pressure was higher in rats with the most severe grades of ICV lesions. CONCLUSIONS: These data suggest a polygenic and dominant mode of inheritance of ICV pathology. The formation of aneurysms in the circle of Willis tended to be favored, and their rupture was clearly increased by the presence of BN rat alleles within the LE rat genome. These data may provide the basis for future studies to determine, in new rat models, which genes are involved in these pathologies.
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Hemorragia Cerebral/genética , Modelos Animales de Enfermedad , Aneurisma Intracraneal/genética , Animales , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/patología , Hemorragia Cerebral/patología , Círculo Arterial Cerebral/patología , Cruzamientos Genéticos , Aneurisma Intracraneal/patología , Masculino , Ratas/genética , Ratas Long-Evans/genéticaRESUMEN
The developing hip in children with osteochondrodysplasias has not been well-described because of delayed ossification and limitations of conventional radiologic techniques. Twenty-four children with various osteochondrodysplasias were evaluated by ultrasonography. Variation in the configuration of the acetabulum included a horizontal acetabular roof owing to delayed iliac development and a notched acetabular roof with lateral bone deficiency. All children had thickened acetabular cartilage except for one child with osteogenesis imperfecta. Coxa vara was a common finding. All neonates displayed a very small beta angle (mean, 42 degrees) because the labrum lay more vertically, secondary to deep engagement of the femoral head in the acetabulum. Proximal femoral ossification was delayed in most children, which allows use of ultrasonography at a later age than is possible in the normal pediatric population. Hip ultrasonography in children with skeletal dysplasias can aid in early diagnosis and is useful in assessing hip morphology and development.
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Articulación de la Cadera/diagnóstico por imagen , Osteocondrodisplasias/diagnóstico por imagen , Acondroplasia/diagnóstico por imagen , Factores de Edad , Preescolar , Displasia Cleidocraneal/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Articulación de la Cadera/anomalías , Humanos , Lactante , Recién Nacido , Inestabilidad de la Articulación/diagnóstico por imagen , Masculino , Osteogénesis Imperfecta/diagnóstico por imagen , Radiografía , Factores Sexuales , UltrasonografíaRESUMEN
The elastin content in the thoracic aorta of male Brown-Norway (BN) rats is 31.4+/-1.2% (dry weight), whereas that of male LOU rats is 37.2+/-1.0%. A similar difference in the elastin content of the thoracic aorta is also observed in female animals. Furthermore, in the thoracic aorta of young, growing rats as well as in cultured aortic smooth muscle cells, the steady-state level of elastin mRNA is significantly lower in the BN than in the LOU strain. These results suggested that 1 or more genes control the elastin mRNA level and the elastin content in the aortas of BN and LOU rats. A possible relationship between a polymorphism in the elastin gene and the elastin content of the aorta was tested. For this purpose, the aortic elastin content was measured in F(1) and F(2) generations bred from LOU and BN rats and was compared with that of the F(0) (parental) generation. A polymorphic marker located in intron 25 of the elastin gene has been used to genotype the F(2) rats. The degree of genetic determination of aortic elastin content was estimated to be 73% in the F(2) cohort, but the elastin locus accounts for only 3. 9% of the total variance in aortic elastin content. Other genes are thus responsible for the major part of the observed interstrain difference by regulating the transcription of the gene, the stability of elastin mRNA, and/or posttranslational events.
Asunto(s)
Aorta Torácica/química , Elastina/genética , Músculo Liso Vascular/química , Polimorfismo Genético , Alelos , Animales , Aorta Torácica/citología , Presión Sanguínea , Northern Blotting , Células Cultivadas , Colágeno/análisis , Elastina/análisis , Femenino , Expresión Génica/fisiología , Genotipo , Masculino , Músculo Liso Vascular/citología , ARN Mensajero/análisis , Ratas , Ratas Endogámicas , Especificidad de la EspecieRESUMEN
Spontaneous rupture of the internal elastic lamina (IEL) occurs in some arteries of the rat during growth and aging. Inbred, normotensive, Brown Norway (BN) rats are particularly susceptible to rupture of the IEL, especially in the abdominal aorta (AA). Preliminary experiments showed that different angiotensin-converting enzyme (ACE) inhibitors protect against rupture of the IEL in the BN rat to a greater extent than hydralazine, suggesting a role of the renin-angiotensin system (RAS) in this phenomenon. To explore this possibility, we have treated male BN rats from 4.5 to 14 weeks of age with either enalapril or losartan (both at 1, 3, and 10 mg x kg(-1) x d(-1)) or with the calcium antagonists mibefradil (at 3, 10, 30, and 45 mg x kg(-1) x d(-1)) and amlodipine (at 30 mg x kg(-1) x d(-1)). Systolic blood pressure (SBP) was measured weekly, and at the end of treatment we (1) recorded body and heart weights, (2) measured various parameters of the RAS in plasma, (3) quantified interruptions in the IEL on "en face" preparations of AA, and (4) quantified elastin, collagen, and cell proteins in the media of the thoracic aorta. Results showed that enalapril and losartan similarly decrease SBP and rupture of the IEL in the AA, suggesting that enalapril inhibits the latter via a decrease in the production of angiotensin II (Ang II) and not via another effect on ACE. The decrease in IEL rupture and in SBP, as well as the modifications in the parameters of the RAS, were all dose dependent. Mibefradil had little effect on the RAS and, at the highest doses, decreased SBP to an extent similar to that for enalapril at 3 mg x kg(-1) x d(-1) but did not significantly inhibit IEL rupture. Amlodipine decreased SBP, increased plasma renin concentration, and was without effect on IEL rupture. All treatments at the highest doses had a hypotrophic effect on the aortic media but differed in their effects on the heart, with enalapril and losartan decreasing and mibefradil and amlodipine increasing heart weight, suggesting that the inhibition of IEL rupture may be related to a cardiac hypotrophic effect. All these results, taken together, suggest that Ang II plays a role in the rupture of the IEL that is, in part, independent of SBP.