RESUMO
BACKGROUND: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy. OBJECTIVES: We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms. METHODS: The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11-17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time. RESULTS: Lifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months. CONCLUSIONS: Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.
Assuntos
Peso Corporal , Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tiazóis/uso terapêutico , Adolescente , Antropometria , Glicemia/efeitos dos fármacos , Criança , Diabetes Mellitus Tipo 2/fisiopatologia , Combinação de Medicamentos , Feminino , Humanos , Estilo de Vida , Masculino , Fatores de Risco , Resultado do TratamentoRESUMO
The most common sex chromosome aneuploidy, Klinefelter syndrome (KS), is associated with primary gonadal failure and increased morbidity and mortality from cardiometabolic disorders in adulthood. Children with KS also have a high prevalence of metabolic syndrome (MetS) features. To assess the relationship of gonadal and cardiometabolic function in children with KS, we evaluated serum hormones [gonadotropins, inhibin B (INHB), anti-mullerian hormone (AMH), total testosterone (TT)], and features of MetS (waist circumference, fasting lipid panel, fasting blood glucose (FBG), and blood pressure) in 93 pre-pubertal boys with KS age 4-12 years (mean 7.7 ± 2.5 years). The cohort was grouped by age and tanner stage, and biomarkers were compared to normal ranges. A total of 80% of this pre-pubertal cohort had ≥1 feature of metabolic syndrome (MetS) and 11% had ≥3 features of MetS. Risk of MetS was independent of age and body mass index. Sertoli cell dysfunction was common with 18% having an INHB below the normal range. A low INHB was associated with higher FBG, triglycerides, LDL, and lower HDL (p < 0.05). An INHB <50 ng/dL yielded a sensitivity of 83% and a specificity of 79% for having ≥3 features of MetS. INHB and AMH positively correlated with each other (p < 0.001), and high AMH was protective of MetS. TT was below the lower limit of normal in 49% of subjects, with mean values significantly lower than expected (3.3 ng/dL vs. 4.9 ng/dL, p < 0.0001), however, no convincing relationship between TT and MetS was seen. In conclusion, gonadal and cardiometabolic dysfunction are prevalent in pre-pubertal boys with KS. Although the relationship of testosterone deficiency and MetS is well-known, this study is the first to report an association between impaired Sertoli cell function and cardiometabolic risk.
Assuntos
Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Hipogonadismo/fisiopatologia , Síndrome de Klinefelter/fisiopatologia , Testosterona/sangue , Circunferência da Cintura/fisiologia , Hormônio Antimülleriano/sangue , Criança , Pré-Escolar , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Inibinas/sangue , Síndrome de Klinefelter/sangue , Hormônio Luteinizante/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Células de Sertoli/metabolismo , Triglicerídeos/sangueRESUMO
We present four children, three of them boys, affected with an identical clinical pattern consisting of early-onset ataxia, delayed dentition, hypomyelination and cerebellar atrophy. Dental radiographs showed variable absence of succedaneous teeth. Proton MR spectroscopy in one child showed elevated white matter myo-inositol. As the clinical and radiological picture in these patients is identical to that of four cases described earlier, we suggest that this disorder with ataxia, delayed dentition and hypomyelination (ADDH) represents a new entity. With the characteristic tooth abnormalities it should be straightforward to identify new patients in order to facilitate the search for the underlying genetic defect.
Assuntos
Ataxia/complicações , Encefalopatias/complicações , Encefalopatias/diagnóstico , Bainha de Mielina/fisiologia , Anormalidades Dentárias/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group clinical trial designed to test the hypothesis that aggressive reduction in insulin resistance early in the course of T2DM is beneficial for prolongation of glycemic control, as well as improvement in associated abnormalities and risk factors. Specifically, the trial compares treatment with metformin with two alternate approaches, one pharmacologic (combining metformin treatment with rosiglitazone) and one combining metformin with an intensive lifestyle intervention program. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10-17 yr of age, within 2 yr of diagnosis of diabetes at the time of randomization, lack evidence of autoimmunity, and have sustained C-peptide secretion. The primary outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for 6 consecutive months. Secondary outcomes include the effect of the alternative treatments on insulin secretion and resistance, body composition, nutrition, physical activity and fitness, cardiovascular risk monitoring, microvascular complications, quality of life, depression, eating pathology, and resource utilization. TODAY is the first large-scale, systematic study of treatment effectiveness for T2DM in youth. When successfully completed, this study will provide critical new information regarding the natural history of T2DM in youth, the benefits of initiating early aggressive treatment in these patients, and the efficacy of delivering an intensive and sustained lifestyle intervention to children with T2DM.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Comportamentos Relacionados com a Saúde , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Adolescente , Criança , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Estilo de Vida , Masculino , Rosiglitazona , Resultado do TratamentoRESUMO
Although GHRH has previously been shown to regulate proliferation of breast cancer cells and prevent apoptosis, the intracellular pathways mediating this effect have not been clarified. Exogenous GHRH stimulated a dose-dependent proliferative response within 24 h in MDA-231, as well as in T47D cells and in MCF-7 cells transfected with the GHRH receptor. The proliferation of MDA-MB-231 (MDA-231) cells was associated with an increase in tritiated thymidine uptake. In addition, phosphorylation of MAPK was rapidly stimulated by GHRH. The phosphorylation of MAPK by GHRH was prevented by transfection of the cells with dominant-negative Ras or Raf or by pretreatment of cells with Raf kinase 1 inhibitor. The inhibition of Ras and Raf, as well as the inhibition of MAPK phosphorylation by PD98059, also prevented GHRH-induced cell proliferation. Finally, pretreatment of cells with the somatostatin analog, BIM23014, also prevented GHRH-induced MAPK phosphorylation and cell proliferation. These results indicate that GHRH stimulates dose-dependent cell proliferation of MDA-231 breast cancer cells through a pathway that requires Ras, Raf, and MAPK phosphorylation. The results also provide support for a possible autocrine/paracrine antagonism between GHRH and somatostatin in the regulation of MDA-231 cell population maintenance. Taken together, the studies provide further insight into the possible role of GHRH as a growth factor in breast cancer.
Assuntos
Comunicação Autócrina/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Comunicação Parácrina/efeitos dos fármacos , Quinases raf/metabolismo , Proteínas ras/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo , Quinases raf/antagonistas & inibidores , Proteínas ras/antagonistas & inibidoresRESUMO
AIMS: To investigate whether degrading proteases can be found in patent calvarial sutures. Sutural growth and fusion means replacement of the sutural connective tissue, rich in fibronectin and collagen type V, by expanding calvarial bone. Proliferation of one tissue into the border area of another implies the presence of enzymes able to degrade extracellular matrix (ECM). An important family of proteases is the matrix metalloproteinases (MMPs), as is the plasminogen/plasmin system. METHODS AND RESULTS: Expression of two MMPs with substrate specifity for fibronectin and collagen type V and of the plasminogen activator system was studied by immunohistochemistry in samples of human fetal calvariae (age range weeks 19-35 of gestation). In all cases, intense staining for MMPs, urokinase, and urokinase receptor was found in the sutural connective tissue and along the outer and inner borders of calvarial bone. CONCLUSIONS: Our findings suggest that degradation of sutural connective tissue takes place during sutural growth. This might facilitate proliferation of calvarial bone. Recently, it was shown that an important regulatory mechanism of sutural growth is apoptosis of osteoblasts in the osteogenic front. Intact fibronectin is known to prevent apoptosis of proliferating osteoblasts while fibronectin degradation induces their apoptosis.
Assuntos
Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Receptores de Superfície Celular/metabolismo , Crânio/embriologia , Matriz Extracelular/metabolismo , Fibrinolisina/metabolismo , Humanos , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/imunologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/imunologia , Receptores de Superfície Celular/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Crânio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
In cranial sutural samples derived from five children with premature cranial suture fusion we have performed immunostaining for the urokinase plasminogen activator (uPA) and urokinase receptor (uPAR). We have found a strong reactivity for cell- or matrix-bound uPA and uPAR in the sutural connective tissue and associated with the osteoblasts and osteocytes lining the calvarial bone. The sutural tissue itself showed a banding with different intensity of urokinase and uPAR staining concerning connective tissue. It is proposed that the components of the plasminogen activating system are involved in tissue turnover of sutural tissue and in sutural growth.
Assuntos
Suturas Cranianas/enzimologia , Craniossinostoses/enzimologia , Ativadores de Plasminogênio/metabolismo , Receptores de Superfície Celular/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Tecido Conjuntivo/enzimologia , Humanos , Imuno-Histoquímica , Lactente , Osteocalcina/análise , Ativadores de Plasminogênio/análise , Receptores de Superfície Celular/análise , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Ativador de Plasminogênio Tipo Uroquinase/análiseRESUMO
Severe type I plasminogen deficiency has been recently linked to ligneous conjunctivitis, a rare and uncommon form of chronic conjunctivitis. In this study, eight unrelated ligneous conjunctivitis patients living in different parts of the world were examined. All affected subjects from which plasma was available displayed absent or markedly reduced plasminogen antigen and plasminogen functional activity. Molecular genetic studies of seven patients identified a Lys19-->Glu mutation in two boys in a homozygous state, and in two girls in a compound-heterozygous state in which the second plasminogen gene carried a missense (Arg134-->Lys) and a nonsense mutation (Cys133--> Stop), respectively. A fifth patient was shown to be homozygous for a frameshift mutation in plasminogen exon 14 (Gly565ins-G). In two unrelated subjects with ligneous conjunctivitis no mutations in the plasminogen gene were identified. Our results suggest that the Lys19-->Glu mutation is the most prevalent mutation in the plasminogen gene of patients with ligneous conjunctivitis.
Assuntos
Conjuntivite/etiologia , Plasminogênio/deficiência , Plasminogênio/genética , Adolescente , Criança , Pré-Escolar , Conjuntivite/enzimologia , Análise Mutacional de DNA , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Heterozigoto , Homozigoto , Humanos , Masculino , Mutação/genética , Núcleo FamiliarRESUMO
In a prospective study, clotting parameters of 37 children and adolescents with insulin-dependent diabetes mellitus (type 1 diabetes) were compared with those of a healthy control group. In a longitudinal follow-up over two years we found no statistical difference for most of the coagulation parameters investigated, including single factor analysis and coagulation inhibitors. The duration of type 1 diabetes was of no influence on these parameters. The only difference we found between patients and healthy controls was an elevation of PAI-1 in diabetics: median for PAI-1: 2.12 IU/ml in diabetics (range 0.50-8.40 IU/ml) and 0.84 IU/ml in normal controls (range 0.50-1.78 IU/ml). This difference was of statistic significance (p < 0.002) and also found in newly diagnosed patients. During observation time, none of our patients developed thrombosis or signs of vascular disease. In conclusion, we could not confirm the development of a hyper-coagulable state in pediatric diabetics, as it is described for adults with type 1 diabetes mellitus.
Assuntos
Coagulação Sanguínea , Diabetes Mellitus Tipo 1/sangue , Adolescente , Antitrombina III/análise , Criança , Pré-Escolar , Fibrinogênio/análise , Humanos , Lactente , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Inibidor 1 de Ativador de Plasminogênio/sangue , Estudos Prospectivos , Proteína C/análise , Proteína S/análise , Protrombina/análise , Tempo de ProtrombinaAssuntos
Osteoporose/diagnóstico , Absorciometria de Fóton/métodos , Adolescente , Adulto , Fatores Etários , Densidade Óssea/fisiologia , Desenvolvimento Ósseo/fisiologia , Calcitonina/uso terapêutico , Criança , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Programas de Rastreamento , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Grupos Raciais , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Aim of this study was to evaluate the postnatal growth pattern of the sphenoid sinus. PATIENTS: 83 cerebral MRI examinations of infants and children aged 5 months to 14 years were retrospectively reviewed for pneumatization and growth of sphenoid sinus. RESULTS: A continuous increase of pneumatization and growth of the sphenoid sinus was demonstrated between infancy and adolescence including considerable individual variations. Even in children less than two years old remarkable spatial extends of this sinus could be found in some cases. CONCLUSION: Diagnosis of an acute or chronical sinusitis in pediatric patients should alert the clinician to the possibility of a sphenoidal participation.
Assuntos
Imageamento por Ressonância Magnética , Seio Esfenoidal/crescimento & desenvolvimento , Adolescente , Cefalometria , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valores de Referência , Estudos Retrospectivos , Seio Esfenoidal/anatomia & histologiaRESUMO
BACKGROUND: Ligneous conjunctivitis is a rare form of chronic recurrent pseudomembranous disease and may be associated with systemic membranous pathological changes. Recently ligneous conjunctivitis has been linked to severe type I plasminogen deficiency. We report on a patient with plasminogen deficiency and severe bilateral ligneous conjunctivitis. A new treatment approach and its outcome in this patient are described. CASE REPORT: We present the case of a 9-month-old Turkish girl with massive swelling of the eyelids and hard white pseudomembranes on both lids. The conjunctival smear was positive for Streptococcus pneumoniae. The clinical diagnosis was: ligneous conjunctivitis with superinfection. Histological investigation showed fibrin as major component of the pseudomembranes. The coagulation analyses revealed decreased plasminogen activity (<5%; normal 80-120%) and decreased plasminogen antigen (<0.4 mg/dl; normal 6-25 mg/dl). The failure of surgical therapy led to the attempt at treatment with intravenous lys-plasminogen. A significant improvement of the ocular symptoms occurred; stabilization with no recurrent pseudomembranes could be achieved for 6 months after treatment. DISCUSSION: The initial amelioration of symptoms in our patient after systemic replacement therapy confirms the etiological importance of plasminogen deficiency in the development of ligneous conjunctivitis. Curative treatment of ligneous conjunctivitis is still not available. However, intravenous application of plasminogen offers new possibilities in therapy, although long-term treatment seems necessary.
Assuntos
Túnica Conjuntiva/patologia , Conjuntivite/genética , Plasminogênio/deficiência , Túnica Conjuntiva/microbiologia , Conjuntivite/complicações , Conjuntivite/diagnóstico , Conjuntivite/tratamento farmacológico , Conjuntivite Bacteriana/complicações , Conjuntivite Bacteriana/diagnóstico , Conjuntivite Bacteriana/microbiologia , Diagnóstico Diferencial , Infecções Oculares Bacterianas/complicações , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Feminino , Humanos , Lactente , Infusões Intravenosas , Fragmentos de Peptídeos/administração & dosagem , Plasminogênio/administração & dosagem , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Prognóstico , Streptococcus pneumoniae/isolamento & purificação , Superinfecção/complicações , Superinfecção/diagnóstico , Superinfecção/microbiologiaRESUMO
BACKGROUND: Although high-dose inhaled glucocorticoids (GCs) with or without chronically administered oral GCs are often used in children with severe persistent asthma, the adverse effects associated with their use have not been well-described in this patient population. OBJECTIVE: We sought to determine the GC-induced adverse effects profile of older children with severe persistent asthma. METHODS: A chart review of 163 consecutive children 9 years of age or older admitted to National Jewish for difficult to control asthma was done. RESULTS: The population studied consisted mostly of adolescents (mean +/- SD age, 14.4 +/- 2.1 years) with severe asthma receiving high-dose inhaled GC therapy (1675 +/- 94 microg/d) and averaging 6 systemic GC bursts per year. 50% required chronic oral GC therapy. GC-associated adverse effects were common and included hypertension (88%), cushingoid features (66%), adrenal suppression (56%), myopathy (50%), osteopenia (46%), growth suppression (39%), obesity and hypercholesterolemia (30%), and cataracts (14%). Height standard deviation scores of -0.44, -1.22, and -0.93 for those receiving intermittent, alternate day, and daily oral GCs, respectively, were smaller (less suppressed) than published values from the same institution before inhaled GC therapy (standard deviation scores of -1.26, -1.91, and -1.95, respectively). Osteopenia was strongly associated with growth suppression (odds ratio, 5.6; confidence interval, 2.7-11.8; P <.0001) and was found to be more common in female than male subjects, even after correcting for short stature (42% vs 18%, P <.006). CONCLUSIONS: GC-associated adverse effects are still unacceptably common among children with severe asthma, even in those not receiving chronically administered oral GC therapy yet receiving high-dose inhaled GCs. Therefore close monitoring and proper intervention are warranted, especially in female subjects, who appear to be at greater risk for osteopenia. There is clearly a need to consider alternative therapy or earlier intervention. The magnitude of growth suppression, while still a problem, appeared to be less severe with the addition of inhaled GC therapy. This observation suggests that high-dose inhaled GC therapy, by affording better asthma control and allowing less use of systemic therapy, has attenuated the growth-suppressive effects of poorly controlled asthma.
Assuntos
Asma/induzido quimicamente , Asma/epidemiologia , Glucocorticoides/efeitos adversos , Adolescente , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/fisiologia , Criança , Síndrome de Cushing/induzido quimicamente , Diabetes Mellitus Tipo 1/induzido quimicamente , Feminino , Crescimento/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Masculino , Fatores de RiscoRESUMO
Growth hormone-releasing hormone (GHRH) is an important regulator of somatotroph development and function. However, GHRH signaling is still not completely understood. Signaling through the mitogen-activated protein kinase (MAPK) pathway has been observed in a wide variety of cell types but has not been explored as a mediator of GHRH action. In this study, we examined the phosphorylation of MAPK pathway intermediates in response to GHRH. After treatment of the GH4 rat somatotroph cell line with rGHRH (10(7) M) for 2.5 min, there was robust phosphorylation of MAPK not seen in vehicle-treated cells. Treatment of HeLa cells with GHRH resulted in no activation of MAPK, but activation was conferred by transfection with the GHRH receptor cDNA. MAPK activation by GHRH was dose dependent from 1 to 100 nM, was evident at 2.5 min, peaked at 5 min, and returned to baseline by 20 min. Pretreatment of GH4 cells with somatostatin analog BIM23014 or the MEK1 inhibitor PD98095 prevented the activation of MAPK. Finally, treatment with GHRH increased GH4 proliferation in culture, and this response was prevented by pretreatment with BIM23014 and PD98095. These results indicate that GHRH activates the MAPK pathway. Furthermore, activation of MAPK may mediate, at least in part, the effects of GHRH on somatotroph cell line proliferation. The findings support the concept that multiple pathways mediate the effects of GHRH.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/fisiologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Hipófise/enzimologia , Animais , Western Blotting , Divisão Celular , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Células HeLa , Humanos , Cinética , MAP Quinase Quinase 1 , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação , Hipófise/citologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ratos , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Somatostatina/farmacologia , TransfecçãoRESUMO
OBJECTIVE: We discuss the recently increased epidemic of type 2 diabetes among children and adolescents in preventive terms and argue that this epidemic represents a failure of primary and secondary interventions. METHODS: We review the current literature regarding the characteristics of adolescents with type 2 diabetes. RESULTS: The common denominator in patients who develop adolescent-onset type 2 diabetes was extreme obesity with body mass index of 35-38 kg/m(2), accompanied by family obesity, a diet rich in fat and sedentary lifestyle. CONCLUSIONS: The current epidemic of type 2 diabetes among adolescents demonstrates that failure to prevent obesity at primary and secondary opportunities for intervention leads to the development of associated diseases with significant morbidity and potential mortality. Family education programs are needed to institute gradual, permanent changes in diet and activity.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Estilo de Vida , Obesidade/epidemiologia , Obesidade/prevenção & controle , Adolescente , Índice de Massa Corporal , Criança , Colorado/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Educação em Saúde , Humanos , Masculino , Obesidade/diagnóstico , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Distribuição por SexoRESUMO
Factor XII deficiency can be associated with a thrombotic and VWF deficiency with a haemorrhagic clinical course. To study the potential influence of factor XII deficiency on bleeding tendency in patients suffering from VWD we retrospectively compared the clinical outcome of children with either an isolated factor XII deficiency, an isolated VWD, or a combination of both. Patients with the combined coagulation defect showed significantly fewer bleeding events when compared to patients with isolated VWD, although ristocetin cofactor activities were reduced to a comparable degree. As far as aPTT values are concerned, there were no significant differences among the three groups. Whether this combination of thrombophilic and haemorrhagic coagulation disorders is only coincidental or the result of an active modulation of one of the two counteracting coagulation factors is not known at present.
Assuntos
Deficiência do Fator XII/complicações , Deficiência do Fator XII/diagnóstico , Hemorragia/etiologia , Doenças de von Willebrand/complicações , Doenças de von Willebrand/diagnóstico , Adolescente , Distribuição por Idade , Tempo de Sangramento , Criança , Pré-Escolar , Deficiência do Fator XII/fisiopatologia , Feminino , Hemorragia/fisiopatologia , Humanos , Incidência , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não Paramétricas , Doenças de von Willebrand/fisiopatologiaRESUMO
OBJECTIVE: To identify physical, behavioral, and environmental features of adolescents (aged 11-17 years) with type 2 diabetes mellitus and their families to define the involvement of known risk factors and to define a profile of at-risk individuals. DESIGN AND METHODS: A total of 42 subjects from 11 families with an adolescent in whom type 2 diabetes was previously diagnosed participated. All subjects underwent anthropometric measurement and completed food frequency and eating disorder questionnaires, and were classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In addition, laboratory tests to determine levels of hemoglobin A1c, fasting glucose, C peptide, insulin, and proinsulin were performed. RESULTS: Type 2 diabetes had been diagnosed in 5 of 11 mothers and 4 of 11 fathers before the study. Type 2 diabetes was diagnosed in 3 of the remaining 7 fathers during the study. In 3 families, both parents were affected with type 2 diabetes. As a group, participants were obese, with a body mass index higher than the 95th percentile for probands and fathers, and higher than the 85th percentile for mothers and siblings. The sum of skin fold measurements was above the 95th percentile for the probands, their siblings, and the parents. All groups had high fat intake and low fiber intake. None of the subjects participated in a structured or routine exercise program, and most reported no regular physical activity. Three of the probands met the criteria for binge-eating disorder, and 6 additional patients had notable characteristics of the disorder. Mothers affected with type 2 diabetes had markedly abnormal hemoglobin A1c levels, indicating poor control. There were no group differences in fasting concentrations of insulin, proinsulin, or C peptide. However, a third of the mothers with type 2 diabetes, and all but 1 of the siblings, had evidence of insulin resistance. CONCLUSIONS: Adolescents in whom type 2 diabetes has been diagnosed, as well as their first-degree family members, are obese. In addition, the incidence of diagnosed and undiagnosed type 2 diabetes or of insulin resistance in the families of adolescents with type 2 diabetes is striking. Probands and other family members have lifestyles characterized by high fat intake, minimal physical activity, and a high incidence of binge eating. These findings indicate that the families of adolescents with type 2 diabetes share many anthropometric and lifestyle risk factors. The design of treatment programs for adolescents with type 2 diabetes will need to address the lifestyle and health habits of the entire family.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Saúde da Família , Estilo de Vida , Adolescente , Adulto , Idade de Início , Análise de Variância , Antropometria , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Exercício Físico , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Ohio/epidemiologia , Fatores de RiscoAssuntos
Hiperfagia/fisiopatologia , Doenças Hipotalâmicas/fisiopatologia , Obesidade/fisiopatologia , Animais , Criança , Modelos Animais de Doenças , Hormônios/uso terapêutico , Humanos , Hiperfagia/tratamento farmacológico , Doenças Hipotalâmicas/tratamento farmacológico , Obesidade/tratamento farmacológico , Octreotida/uso terapêutico , RatosRESUMO
Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.