RESUMO
A cell-extraction protocol yielding an esophagus acellular matrix (EAM) scaffold for use in tissue engineering of an esophagus, including hypotonic lysis, multiple detergent cell extraction steps, and nucleic acid digestion, was developed in a rat model. Histological techniques, burst pressure studies, in vitro esophageal epithelial cell seeding, and in vivo implantation were used to assess cell extraction, extracellular matrix (ECM) preservation, and biocompatibility. Microscopy demonstrated that cell extraction protocols using sodium dodecyl sulfate (SDS) (0.5%, wt/vol) as a detergent resulted in cell-free EAM with retained ECM protein collagen, elastin, laminin, and fibronectin. Burst pressure studies indicated a loss of tensile strength in EAMs, but at intraluminal pressures that were unlikely to affect in vivo application. In vitro cell seeding studies exhibited epithelial cell proliferation with stratification similar to native esophagi after 11 days, and subcutaneously implanted EAMs displayed neovascularization and a minimal inflammatory response after 30 days of implantation. This study presents an esophagus acellular matrix tissue scaffold with preserved ECM proteins, biomechanical properties, and the ability to support esophageal cell proliferation to serve as the foundation for a tissue-engineered esophagus.
Assuntos
Esôfago/química , Matriz Extracelular/metabolismo , Implantes Experimentais , Animais , Materiais Biocompatíveis , Fenômenos Biomecânicos , Colágeno/metabolismo , Colágeno/ultraestrutura , Epitélio/efeitos dos fármacos , Epitélio/ultraestrutura , Esôfago/ultraestrutura , Matriz Extracelular/ultraestrutura , Fibronectinas/metabolismo , Fibronectinas/ultraestrutura , Técnica Indireta de Fluorescência para Anticorpo , Corantes Fluorescentes , Histocitoquímica , Indóis , Laminina/metabolismo , Laminina/ultraestrutura , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Engenharia Tecidual/métodos , Transplante HeterotópicoRESUMO
BACKGROUND: While there is information in the literature describing the poor nutritional intake of food-insecure youth, eating behaviours among food-insecure children - particularly, obese children are less well-described. We conducted focus groups with family members of low-income children who were initiating care in a paediatric obesity clinic. Food hiding emerged as a theme, and generated the motivation for this analysis. METHODS: Between April 2012 and December 2013, a total of 7 focus groups were conducted (4 food-insecure groups and 3 food-secure). Based on recruitment from 37 index patients, the focus groups were attended by a total of 47 participants. Participant responses about eating behaviours were evaluated using a combination of inductive codes derived from the data and deductive codes informed by criteria for diagnosis of disordered eating. RESULTS: While participants from food-secure and food-insecure households all had anecdotes about their children overeating, respondents in two of the food-insecure groups described episodes that resemble binge eating. The topic of hiding food emerged in the food-insecure groups, though was not endorsed in the food-secure groups despite probing. Night-time eating arose spontaneously in two of the food-insecure groups, but not in the food-secure groups. CONCLUSION: This study highlights the presence of food hiding, binge eating, and night-time eating in food-insecure children with obesity. These factors would further compound their health burden, and the relationship between disordered eating and food insecurity in children with obesity warrants further study.
Assuntos
Bulimia/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Abastecimento de Alimentos , Obesidade Infantil/psicologia , Pobreza/psicologia , Bulimia/complicações , Celulas Principais Gástricas , Criança , Estudos Transversais , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Grupos Focais , Humanos , Masculino , Motivação , Obesidade Infantil/complicaçõesRESUMO
BACKGROUND: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. METHODS: We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. RESULTS: Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. CONCLUSIONS: Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.
Assuntos
Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pentamidina/administração & dosagem , Pneumonia por Pneumocystis/prevenção & controle , Administração Intravenosa , Antifúngicos/efeitos adversos , Quimioprevenção/efeitos adversos , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pentamidina/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study was designed to evaluate the quality of life (QOL) of children living with HIV at an institutional care home in Bangalore, India. The Sneha Care Home is a unique residence that provides educational and community support with a focus on physical, nutritional, medical, and psychological care for orphans and vulnerable children. Cross-sectional health measures and interview data were collected from 97 residents including 52 boys and 45 girls between 5 and 12 years of age (mean age = 9). QOL was measured with the Pediatric Quality of Life 4.0 (PedsQL) Inventory. Caregivers perceived children to have an overall higher QOL than was self-reported by children (total score 83 vs. 78). Our findings indicated self-reported QOL decreased with age of the child, while caregiver-reported QOL increased with age, suggesting a need to ensure greater psychological support for older children. Physical measures showed the children's clinical severity of disease remained well controlled living in this residential, values-based care home.
Assuntos
Cognição/efeitos dos fármacos , Demência/induzido quimicamente , Guias como Assunto , Inibidores de Hidroximetilglutaril-CoA Redutases/normas , Hipercolesterolemia/tratamento farmacológico , Pravastatina/normas , Sinvastatina/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pravastatina/efeitos adversos , Pravastatina/uso terapêutico , Sinvastatina/efeitos adversos , Sinvastatina/uso terapêutico , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVE: Asians have a reduced risk for cerebral palsy (CP) compared with whites. We examined whether individual Asian subgroups have a reduced risk of CP and whether differences in sociodemographic factors explain disparities in CP prevalence. METHODS: In a retrospective cohort of 629 542 Asian and 2 109 550 white births in California from 1991 to 2001, we identified all children who qualified for services from the California Department of Health Services on the basis of CP. Asians were categorized as East Asian (Chinese, Japanese, Koreans), Filipino, Indian, Pacific Islander (Guamanians, Hawaiians, and Pacific Islanders), Samoan, or Southeast Asian (Cambodian, Laotian, Thai, Vietnamese). RESULTS: Overall, CP prevalence was lower in Asians than whites (1.09 vs 1.36 per 1000; relative risk = 0.80, 95% confidence interval [CI] = 0.74-0.87) and ranged from 0.61/1000 in Thai children to 2.08/1000 in Samoan children. Several Asian subgroups had low risk profiles with respect to maternal age, educational attainment, and birth weight. However, after we adjusted for maternal age and education, infant gender, and birth weight, the adjusted risk of CP remained lower in East Asians (odds ratio [OR] = 0.75, 95% CI = 0.65-0.87), Filipinos (OR = 0.87, 95% CI = 0.75-0.99), Indians (OR = 0.59, 95% CI = 0.44-0.80), Pacific Islanders (OR = 0.62, 95% CI = 0.40-0.97), and Southeast Asians (OR = 0.68, 95% CI = 0.57-0.82) compared with whites. CONCLUSIONS: Most Asian national origin subgroups have a lower rate of CP than whites, and this disparity is unexplained. Additional studies that focus on the cause of ethnic disparities in CP may provide new insights into pathogenesis and prevention.
Assuntos
Povo Asiático , Paralisia Cerebral/etnologia , Medição de Risco/métodos , Adolescente , Adulto , California/epidemiologia , Intervalos de Confiança , Feminino , Humanos , Recém-Nascido , Masculino , Razão de Chances , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential.
Assuntos
Doenças por Armazenamento dos Lisossomos/diagnóstico , Doenças por Armazenamento dos Lisossomos/terapia , Aborto Habitual/epidemiologia , Algoritmos , Doenças Cardiovasculares/etiologia , Diagnóstico Diferencial , Oftalmopatias/etiologia , Doença de Gaucher/diagnóstico , Humanos , Hidropisia Fetal/etiologia , Recém-Nascido , Doenças por Armazenamento dos Lisossomos/complicações , Doenças por Armazenamento dos Lisossomos/fisiopatologia , Insuficiência Respiratória/etiologia , Convulsões/etiologia , EsplenomegaliaRESUMO
PURPOSE: To assess the ultrastructural and fluid flow characteristics of cultured trabecular meshwork (TM) cells derived from fetal sources. METHODS: Fetal eyes were carefully dissected to isolate the developing TM tissue for culture. Immunostaining was used to assess the expression of the junction-associated proteins zonula occludens-1 (ZO-1) and occludin. Fetal and adult TM cells were grown to confluence on permeable membranes for both flow and ultrastructural studies. Fluid flow resistance was measured by permeation of horseradish peroxidase (hrp) activity and hydraulic conductivity (HC) experiments. The effects of dexamethasone (Dex) on permeability and HC were also evaluated. RESULTS: ZO-1 and occludin are expressed in the TM region of tissue sections and at cell borders in cultured fetal and adult TM cells. Transmission electron microscopy demonstrated that cultured TM cells possessed numerous mitochondria, electron-dense bodies, surface microvilli, and adherens and gap junctions. The permeation of hrp across fetal TM cell monolayers (0.030 +/- 0.010) and of adult TM cells (0.031 +/- 0.010) had similar values for absorbance at 470 nm (p = 0.83, 95% CI: -0.004, 0.005). Dex treatment significantly reduced the permeability to 0.022 +/- 0.008 (p = 0.002) and 0.018 +/- 0.009 (p = 0.004) for fetal and adult TM cells, respectively. The average HC (microl/min/mmHg/cm(2)) of fetal cells (2.78 +/- 1.03) and of the adult cells (2.15 +/- 1.31) was not significantly different (p = 0.24, 95% CI: -1.01, 0.26). Dex treatment significantly reduced HC in both fetal (1.24 +/- 0.72, p = 0.0004) and adult (1.29 +/- 0.29, p = 0.00001) TM. CONCLUSIONS: Cultured fetal TM cells exhibited similar expression of junctional proteins and ultrastructural features as their adult counterparts. The permeability and HC of the fetal cells were similar to their older adult counterparts. Dex treatment induced increased fluid flow resistance in both cell types. These cells may serve as a source for in vitro studies of meshwork physiology.