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Abstract Introduction Benign paroxysmal positional vertigo (BPPV) is one of the common disorders of the peripheral vestibular system. The prevalence of BPPV is found to be higher among middle-aged women. Objectives To estimate the serum levels of calcium and vitamin D in patients with BPPV, and to study their association. Methods The present is a hospital-based prospective case-control study. Venous blood samples of the 49 patients with BPPV and an equal number of age- and gender-matched individuals were recruited and submitted to an analysis of the serum levels of calcium and vitamin D. Results Among the cases, 67.3% were found to be females, and 32.7% were males. Most of the 30 cases (61.3%) were aged >40 years. The mean age of the cases was 44.39 years. The mean serum level of vitamin D in the cases was of 21.26 ng/ml compared with 17.59 ng/ml in the controls. The mean serum level of calcium was of 9.33 mg/dl in the cases, compared with 8.95 mg/dl in the controls. There was no significant difference in the serum levels of vitamin D and calcium between cases and controls. Conclusion We could not establish any correlation between the serum levels of calcium and vitamin D with BPPV. However, a negative relationship was found between the serum levels of vitamin D and the number of episodes of BPPV (p = 0.012).
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Introduction Benign paroxysmal positional vertigo (BPPV) is one of the common disorders of the peripheral vestibular system. The prevalence of BPPV is found to be higher among middle-aged women. Objectives To estimate the serum levels of calcium and vitamin D in patients with BPPV, and to study their association. Methods The present is a hospital-based prospective case-control study. Venous blood samples of the 49 patients with BPPV and an equal number of age- and gender-matched individuals were recruited and submitted to an analysis of the serum levels of calcium and vitamin D. Results Among the cases, 67.3% were found to be females, and 32.7% were males. Most of the 30 cases (61.3%) were aged > 40 years. The mean age of the cases was 44.39 years. The mean serum level of vitamin D in the cases was of 21.26 ng/ml compared with 17.59 ng/ml in the controls. The mean serum level of calcium was of 9.33 mg/dl in the cases, compared with 8.95 mg/dl in the controls. There was no significant difference in the serum levels of vitamin D and calcium between cases and controls. Conclusion We could not establish any correlation between the serum levels of calcium and vitamin D with BPPV. However, a negative relationship was found between the serum levels of vitamin D and the number of episodes of BPPV ( p = 0.012).
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The safety, efficacy, and cost-effectiveness of Infliximab biosimilar agents in the management of inflammatory bowel disease in adults have been shown. These agents have been recommended for pediatric inflammatory bowel disease, and although institutions are initiating therapy with the biosimilar agents (IFX-B), few are switching maintenance therapy from the originator (IFX-O). The aim was to compare biochemical markers of disease activity of children with inflammatory bowel disease on maintenance therapy with IFX-B to their previous markers on IFX-O. Methods: Single-center, retrospective chart review of 25 children with inflammatory bowel disease who transitioned from Remicade (IFX-O) to the biosimilar agent Inflectra (IFX-B) for maintenance therapy. Analysis included demographics and various biochemical markers of disease control. The nonparametric-related samples Wilcoxon signed-rank test was used to compare mean ranks of these markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, platelet count, albumin, body mass index z score) between the last 12 months on IFX-O and the first 12 months on IFX-B. Results: Between March 2018 and June 2018, the majority of patients with pediatric inflammatory bowel disease on maintenance therapy with IFX-O at our institution were transitioned to maintenance therapy with IFX-B. Of the 25 children included, 17 were diagnosed with Crohn disease and 8 with ulcerative colitis. The results of all, except albumin value, supported retention of the null hypothesis that there would not be a statistically significant difference in the biochemical markers of disease activity between the 2 medications. Conclusions: IFX-B is as effective as IFX-O for maintenance therapy in pediatric inflammatory bowel disease when comparing biochemical markers of disease activity.
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Our study aims to assess improvement with symptomatic treatment of pain-related functional gastrointestinal disorders (FGIDs) in a biopsychosocial construct and evaluate validity of Rome III criteria. Children with chronic abdominal pain diagnosed with an FGID or organic disease were followed for 1 year: 256/334 were diagnosed with an FGID and 78/334 were diagnosed with a possible organic disease due to alarm signs or not meeting Rome III criteria. After 1 year, 251 had true FGID and 46 had organic diseases. Ninety percent of FGID patients improved with symptomatic treatment over an average of 5.4 months. With a 95% confidence interval, Rome criteria predicted FGIDs with sensitivity 0.89, specificity 0.90, positive predictive value 0.98, and negative predictive value 0.59. We conclude that symptomatic treatment of pain-related FGIDs results in clinical improvement and could reduce invasive/expensive testing. Rome III criteria's high specificity and positive predictive value suggest they can rule in a diagnosis of FGID.
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Dor Abdominal/terapia , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Dor Abdominal/etiologia , Dor Abdominal/psicologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Empatia , Feminino , Gastroenteropatias/complicações , Humanos , Masculino , Negociação/psicologia , Educação de Pacientes como Assunto/métodos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
ABSTRACT: The influence of family history on children with irritable bowel syndrome (IBS) is unknown. We conducted a retrospective study to compare the clinical profile and management differences between children with a family history of IBS (FH-IBS) versus without. A total of 251 children were included in the study, 75 (30%) had FH-IBS and 176 (70%) did not. No significant differences were observed between the 2 groups in sex composition, age at initial visit, age of IBS diagnosis, dietary modifications, supplements, laxatives, antispasmodics, antidiarrheals, and cyproheptadine use. Children with FH-IBS were, however, more like to have psychological comorbidities (41% vs 23%, Pâ=â0.003), and were more likely to receive psychological counseling (49% vs 23%, Pâ<â0.001) and antidepressant treatment (36% vs 15%, Pâ<â0.001) versus children without. We concluded that children with FH-IBS are more likely to have underlying psychological disorders and receive psychological interventions.
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Síndrome do Intestino Irritável , Antidiarreicos/uso terapêutico , Criança , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/tratamento farmacológico , Laxantes/uso terapêutico , Parassimpatolíticos/uso terapêutico , Estudos RetrospectivosRESUMO
Cleft alveolus, a common birth defect of the maxillary bone, affects one in 700 live births every year. This defect is traditionally restored by autogenous bone grafts or allografts, which may possibly cause complications. Cell-based therapies using the mesenchymal stem cells (MSCs) derived from human gingiva (gingiva-derived mesenchymal stem cells [GMSCs]) is attracting the research interest due to their highly proliferative and multilineage differentiation capacity. Undifferentiated GMSCs expressed high level of MSC-distinctive surface antigens, including CD73, CD105, CD90, and CD166. Importantly, GMSCs induced with osteogenic medium for a week increased the surface markers of osteogenic phenotypes, such as CD10, CD92, and CD140b, indicating their osteogenic potential. The objective of this study was to assess the bone regenerative efficacy of predifferentiated GMSCs (dGMSCs) toward an osteogenic lineage in combination with a self-assembling hydrogel scaffold PuraMatrix™ (PM) and/or bone morphogenetic protein 2 (BMP2), on a rodent model of maxillary alveolar bone defect. A critical size maxillary alveolar defect of 7 mm × 1 mm × 1 mm was surgically created in athymic nude rats. The defect was filled with either PM/BMP2 or PM/dGMSCs or the combination of three (PM/dGMSCs/BMP2) and the bone regeneration was evaluated at 4 and 8 weeks postsurgery. New bone formation was evaluated by microcomputed tomography and histology using Hematoxylin and Eosin staining. The results demonstrated the absence of spontaneous bone healing, either at 4 or 8 weeks postsurgery in the defect group. However, the PM/dGMSCs/BMP2 group showed significant enhancement in bone regeneration at 4 and 8 weeks postsurgery, compared with the transplantation of individual material/cells alone. Apart from developing the smallest critical size defect, results showed that PM/dGMSCs/BMP2 could serve as a promising option for the regeneration of bone in the cranio/maxillofacial region in humans.
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Gengiva , Células-Tronco Mesenquimais , Animais , Regeneração Óssea , Diferenciação Celular , Osteogênese , Ratos , Células-Tronco , Microtomografia por Raio-XRESUMO
BACKGROUND: Rectal prolapse is a protrusion of rectal mucosa through the anal sphincter. Although uncommon, it is seen more often in children, younger than 4 years of age. The last data analysis of rectal prolapse and its clinical characteristics in children was performed over 30 years ago. Since that time, many medical advances have occurred that may alter our workup and management of this disease in children. We performed a chart review to reassess the clinical characteristics of rectal prolapse and its management. METHODS: This was a retrospective descriptive analysis study, assessing children less than 18 years of age that were diagnosed with rectal prolapse from 1999 to 2014 at a single tertiary care center. The onset of presentation, demographics, etiology, clinical characteristics, and management were analyzed. RESULTS: A total of 158 patients were diagnosed with rectal prolapse, with mean age of onset being 3 years. Constipation was the leading cause, with straining being the most common complaint. Stool consistencies with constipation varied. Many patients diagnosed with idiopathic recurrent rectal prolapse had either a social stressor or were described as having unusual behaviors associated with prolapse. Cystic fibrosis was only diagnosed in 4 patients. Thirty-four patients (22%) required surgical correction. CONCLUSIONS: Constipation remains the main cause of rectal prolapse. Cystic fibrosis is no longer a common etiology for rectal prolapse, because of the implementation of newborn screening. Patients with social stressors or atypical behavior may be at risk for recurrent rectal prolapse.
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Prolapso Retal , Canal Anal , Criança , Pré-Escolar , Constipação Intestinal/etiologia , Humanos , Recém-Nascido , Prolapso Retal/diagnóstico , Prolapso Retal/etiologia , Prolapso Retal/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.
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5'-Nucleotidase/imunologia , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Ligante 4-1BB/imunologia , Proteínas Ligadas por GPI/imunologia , Humanos , Células K562 , Células Matadoras Naturais/patologia , Linfócitos do Interstício Tumoral/patologia , Neoplasias/patologiaRESUMO
OBJECTIVES: Functional dyspepsia (FD) is a functional abdominal pain disorder. There is paucity of data on the economic impact of FD in children. Primary aim of our study was to estimate annual evaluation cost ("diagnosis and visit" cost) and secondary aim was to identify potential prognostic factors of FD in children. METHODS: Out of the 136 patients 86 met inclusion criteria and were divided into 2 clinical groups: Complete Improvement Group (CIG-30 patients) and Partial/No Improvement Group (PIG/NIG-56 patients). Medications used were noted descriptively. Annual evaluation cost was calculated using 2017 Medicare reimbursement rates. RESULTS: Annual evaluation cost in all patients was $724.874â±â$180.075 ($544.799â±â$87.995 in CIG and $904.949â±â79.083 in PIG/NIG). An extrapolated annual cost of evaluation in children with FD would be approximately $5.79 billion. Average number of clinic visits (3.1â±â1.2 in CIG vs 4.40â±â3.1 in PIG/NIG), duration of follow-up in months (9.2â±â6.6 in CIG vs 17.1â±â13.6 in PIG/NIG), use of imaging studies (7 patients in CIG [23.3%] vs 29 in PIG/NIG [51.8%]) and endoscopic procedures (17 in CIG [56.7%] vs 46 in PIG/NIG [82.1%]) were significantly higher in PIG/NIG (Pâ<â0.005). PIG/NIG required multiple medications for control of symptoms compared to CIG (4 patients in CIG [13.5%] vs 30 in PIG [53.6%], P value <0.001]. For every $500.00 decrease in total evaluation cost the odds of having a complete response was 0.998 (Pâ=â0.027). No prognostic factors were identified in children with FD. CONCLUSIONS: FD in children has a significant economic impact on health care expenditure. Patients with FD who have partial/no response to treatment incur greater financial cost potentially adding to health care expenditure.
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Dispepsia , Dor Abdominal , Idoso , Criança , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Humanos , Medicare , Prognóstico , Estados UnidosRESUMO
Upward lightning studies took place in Rapid City, South Dakota, USA and S. Paulo, Brazil during the summer thunderstorm seasons from 2011 to 2016. One of the main objectives of these campaigns was to evaluate and characterize the triggering of upward positive leaders from tall objects due to preceding nearby flash activity. 110 upward flashes were observed with a combination of high- and standard-speed video and digital still cameras, electric field meters, fast electric-field antenna systems, and for two seasons, a Lightning Mapping Array. These data were analyzed, along with correlated lightning location system data, to determine the triggering flash type responsible for the initiation of upward leaders from towers. In this paper, we describe the various processes during flash activity that can trigger upward leaders from tall objects in the USA and in Brazil. We conclude that the most effective triggering component is the propagation of the in-cloud negative leader during the continuing current that follows a positive return stroke.
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OBJECTIVES: There has been limited investigation of pediatric patients with inflammatory bowel disease (IBD) who have been treated with biologic agents and undergo operative management. Postoperative complications in the adult setting have been mixed and in the pediatric population the data have been limited. This study compares children with IBD treated with biologic agents to patients treated with nonbiologic therapy before bowel resection. METHODS: This is a single-center, retrospective chart review study of 62 children with IBD who underwent bowel resection between 2001 and 2017. Analysis included patient demographics, medications used before surgery, incidence of postoperative complications, indication for surgery, type of operation, and additional surgeries required. Postoperative complications were defined as superficial skin infection, leak at anastomotic site, intra-abdominal abscess, wound dehiscence, and so on. Complications were compared based on medical therapy. RESULTS: Of the 62 children reviewed, 21 carried the diagnosis of ulcerative colitis, 40 had Crohn disease, and 1 had IBD-unspecified. Thirty-seven of the patients were treated with infliximab, adalimumab, or vedolizumab before their bowel resection. There were 4 complications documented within 30 days of the operation, with an overall complication rate of 6.45%. There were 2 complications in each of the cohorts, including intra-abdominal abscess (2), abdominal wall abscess (1), and pouchitis (1). CONCLUSION: The number of complications was the same between those who did and did not receive a preoperative biologic agent. This study suggests that biologics may be safe to use in patients undergoing bowel resection.
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Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Fatores Biológicos/administração & dosagem , Doenças Inflamatórias Intestinais , Infliximab/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Adalimumab/efeitos adversos , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Fatores Biológicos/efeitos adversos , Produtos Biológicos , Estudos de Casos e Controles , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Infliximab/efeitos adversos , Masculino , Período Pré-Operatório , Estudos RetrospectivosRESUMO
AIM: To evaluate predictors of morbidity and mortality in pediatric patients with pulmonary hypertension (PH), laboratory and echocardiographic measures of PH were analyzed. METHODS: A retrospective review of all infants and children < 2 years of age with PH from January 2011 to August 2016 was conducted. Correlations were determined using Spearman's rank correlation coefficients. Differences in characteristics between survivors and nonsurvivors were analyzed and Kaplan-Meier survival curves were generated. RESULTS: Of 56 patients, the majority were extremely premature; of African American ethnicity; and had bronchopulmonary dysplasia. Patients who died were more likely to have underlying congenital heart disease; have a higher increase in the concentration of carbon dioxide in the blood (pCO2 ) with a corresponding greater mean percentage decrease in pH and percentage rise in NT-pro BNP during PH exacerbations; more likely to have been on medications for pulmonary hypertension; and have a higher RVSP/SBP (%) ratio and S/D ratio. There were positive correlations between percentage rise in NT-pro BNP and pCO2 ; NT-pro BNP and RVSP/SBP (%) ratio; and RVSP/SBP (%) ratio and S/D ratio. CONCLUSIONS: Infants and young children with pulmonary hypertension have increased morbidity and mortality. NT-pro BNP is a useful biomarker for both respiratory exacerbations and mortality, and RVSP/SBP (%) ratio and S/D ratio are echocardiographic identifiers for increased mortality.
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Hipertensão Pulmonar/sangue , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Respiratória/sangue , Biomarcadores/sangue , Pré-Escolar , Progressão da Doença , Ecocardiografia , Feminino , Mortalidade Hospitalar/tendências , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/epidemiologia , Lactente , Masculino , Morbidade/tendências , Precursores de Proteínas , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Some theorize that prolonged use of proton pump inhibitors (PPIs) may increase the risk of small intestinal bacterial overgrowth (SIBO). Chronic acid suppression and resultant hypochlorhydria may lead to an altered intraluminal environment, which, in turn, may promote the growth of bacteria in the small intestine. A handful of studies measured the risk of SIBO in adults taking PPIs and obtained mixed results; however, this risk has not been exclusively measured in children. AIM: This study aimed to measure the risk of SIBO in children taking PPI versus those not taking PPI. PATIENTS AND METHODS: This was a prospective cohort study. Evaluation of SIBO was performed using the glucose hydrogen breath test. Patients younger than 18 years of age taking a PPI longer than 6 months were compared with healthy control participants. After ingestion of glucose substrate, breath samples were obtained every 15 min for 2 h. An increase in breath hydrogen or methane above 12 ppm was considered diagnostic of SIBO. RESULTS: Overall, 83 participants were tested, of whom 56 were taking PPIs. SIBO was detected in five (8.9%) of the 56 participants taking PPI versus one (3.7%) of the 27 participants in the control group (P=0.359), with a relative risk of 2.4 (95% confidence interval: 0.29-19.6). CONCLUSION: To our knowledge, this is the first study in the English literature measuring the risk of SIBO in children taking PPIs. Our results indicate a potential risk of SIBO in chronic PPI users; however, this is not statistically significant. This is an important finding as PPIs are readily prescribed for children and are often taken longer than 6 months' duration.
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Síndrome da Alça Cega/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Síndrome da Alça Cega/diagnóstico , Testes Respiratórios/métodos , Estudos de Casos e Controles , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Masculino , Estudos Prospectivos , Inibidores da Bomba de Prótons/administração & dosagem , Medição de Risco/métodosRESUMO
OBJECTIVES: To evaluate the effect of oral sucrose on skin blood flow (SBF; perfusion units; PU) measured by Laser Doppler Imager (LDI) in term newborns and pain response (Neonatal Infant Pain Scale score; NIPS score) during heel lance; (2) determine SBF changes during heel lance; and (3) the relationship between SBF and NIPS. MATERIALS AND METHODS: Term infants ≤7 days old (n=56) undergoing routine heel lance were randomized to pretreatment with 2.0 mL oral 24% sucrose (n=29) or sterile water (n=27) in a double-blinded, placebo-controlled trial. SBF was assessed by LDI scans and NIPS scores at 10 minutes before lance, immediately after lancing, and 5 minutes after blood extraction. Mean SBF and median NIPS scores were compared between groups using General Linear Model or Kruskal-Wallis. Regressions examined the relationship between SBF immediately after heel lance and NIPS score. RESULTS: Mean SBF and median NIPS scores immediately after heel lance were lower in sucrose-treated infants (167.9±15.5 vs. 205.4±16.0 PU, P=0.09; NIPS 1 [interquartile range 0 to 4] vs. NIPS 3 [interquartile range 0 to 6], P=0.02), although no significant difference in mean SBF. During heel lance NIPS score was predictive of SBF. An increase of 1 in NIPS score was associated with 11 PU increase in SBF (R=0.21; P=0.09) for sucrose, and 16 PU increase for placebo-treated infants (R=0.20; P=0.014). CONCLUSIONS: Increased SBF assessed by LDI is a pain response among term neonates after routine heel lance, which was not completely attenuated by oral sucrose administration. Increased SBF is associated with NIPS scores. Sucrose analgesic efficacy evidenced by decreased NIPS scores for the sucrose group. Association of SBF with NIPS scores suggests that LDI is potentially useful for assessing newborn procedural pain.
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Analgésicos/administração & dosagem , Calcanhar/inervação , Dor/etiologia , Dor/prevenção & controle , Pele/irrigação sanguínea , Sacarose/administração & dosagem , Pressão Sanguínea , Método Duplo-Cego , Feminino , Frequência Cardíaca , Humanos , Recém-Nascido , Fluxometria por Laser-Doppler , Modelos Lineares , Masculino , Manejo da Dor , Medição da DorRESUMO
OBJECTIVES: Pentavalent rotavirus vaccine (RV5) has been shown to be well-tolerated and efficacious in preventing rotavirus gastroenteritis in healthy infants. Safety and immunogenicity of RV5 in infants with surgical gastrointestinal disease have not been studied. The aim of the present study was to evaluate the safety and immunogenicity of RV5 in infants with a history of congenital or acquired intestinal disease requiring resection compared with healthy infants. METHODS: Infants with intestinal resection were matched by gestational age and chronological age to healthy infants (controls). Dose 1 of RV5 was given at 10 to 12 weeks of chronological age. Doses 2 and 3 were given at intervals of 4 to 10 weeks, with all 3 doses given by 32 weeks. All infants were monitored for adverse events (AEs) by telephone calls, clinic visits, and parental written reports during the first 42 days after each dose and monthly thereafter by telephone for 12 months. Serum anti-rotavirus immunoglobulin A (IgA) titers were measured prevaccination and 2 weeks after dose 3. RESULTS: A total of 5 infants with surgical gastrointestinal disease and 3 control subjects were enrolled. All participants (100%) mounted a 3-fold increase in serum anti-rotavirus IgA geometric mean titer postvaccination. RV5 administration to surgical infants was well tolerated with a majority of AEs being attributed to the underlying medical condition. CONCLUSIONS: Postvaccination serum anti-rotavirus IgA levels indicate that RV5 is immunogenic in infants with a history of bowel resection, despite varying lengths of residual bowel. RV5 was well tolerated with few vaccine-related AEs.
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Anticorpos Antivirais/sangue , Gastroenterite/virologia , Infecções por Rotavirus/imunologia , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Esquemas de Imunização , Imunoglobulina A/sangue , Lactente , Enteropatias/cirurgia , Masculino , Projetos Piloto , Estudos Prospectivos , Vacinas contra Rotavirus/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologiaRESUMO
The Eph and Ephrin proteins, which constitute the largest family of receptor tyrosine kinases, are involved in normal tissue development and cancer progression. Here, we examined the expression and role of the B-type Eph receptor EphB2 in breast cancers. By immunohistochemistry using a progression tissue microarray of human clinical samples, we found EphB2 to be expressed in benign tissues, but strongly increased in cancers particularly in invasive and metastatic carcinomas. Subsequently, we found evidence that EphB2, whose expression varies in established cell breast lines, possesses multiple functions. First, the use of a DOX-inducible system to restore EphB2 function to low expressers resulted in decreased tumor growth in vitro and in vivo, while its siRNA-mediated silencing in high expressers increased growth. This function involves the onset of apoptotic death paralleled by caspases 3 and 9 activation. Second, EphB2 was also found to induce autophagy, as assessed by immunofluorescence and/or immunoblotting examination of the LC3, ATG5 and ATG12 markers. Third, EphB2 also has a pro-invasive function in breast cancer cells that involves the regulation of MMP2 and MMP9 metalloproteases and can be blocked by treatment with respective neutralizing antibodies. Furthermore, EphB2-induced invasion is kinase-dependent and is impeded in cells expressing a kinase-dead mutant EphB2. In summary, we identified a mechanism involving a triple role for EphB2 in breast cancer progression, whereby it regulates apoptosis, autophagy, and invasion.
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Apoptose/genética , Autofagia/genética , Neoplasias da Mama/patologia , Receptor EphB2/fisiologia , Animais , Neoplasias da Mama/genética , Células Cultivadas , Progressão da Doença , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Invasividade Neoplásica , Receptor EphB2/genética , Células Tumorais CultivadasRESUMO
EHD3 [Eps15 homology (EH) domain-containing protein 3] is a protein that resides in tubular and vesicular membrane structures and participates in endocytic recycling, although all its functions are unknown. Since Ehd3 is most abundantly expressed in brain tissues, we examined its role in brain cancer progression. Using immunohistochemistry, we report loss of EHD3 expression in gliomas, including low-grade astrocytomas, suggesting that this is an early event in gliomagenesis. EHD3 expression is also very low in most of glioma cell lines tested. In two cell lines, a bisulfite sequencing method identifies promoter hypermethylation as a mechanism of Ehd3 silencing, and its expression was restored by the demethylating agent 5-Azacytidine. Doxycycline-inducible restoration of EHD3 expression to glioma cells decreases their growth and invasiveness and induces cell cycle arrest and apoptosis. Furthermore, shRNA-mediated Ehd3 silencing increases cell growth. Using a xenograft model, we demonstrate Ehd3 growth inhibitory functions in glioma cells in vivo. We suggest that Ehd3 functions as a tumor suppressor gene and loss of its expression is a very common event in gliomas. This is the first study to highlight the importance of a member of the C-terminal EHD proteins in cancer and to link their functions to the cell cycle and apoptosis.
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Apoptose/genética , Neoplasias Encefálicas/genética , Proteínas de Transporte/genética , Ciclo Celular/genética , Genes Supressores de Tumor , Glioma/genética , Sequência de Bases , Neoplasias Encefálicas/patologia , Divisão Celular , Linhagem Celular Tumoral , Metilação de DNA , Primers do DNA , Inativação Gênica , Glioma/patologia , Humanos , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Análise Serial de TecidosRESUMO
BACKGROUND: Postnatal indomethacin is reportedly associated with an increased incidence of necrotizing enterocolitis (NEC) in preterm infants. Because indomethacin readily crosses the placenta, we hypothesized that antenatal indomethacin (AI) would increase the risk for NEC in preterm infants. OBJECTIVE: The goal of this study was to explore the association between AI and NEC in preterm infants. METHODS: Medical records of preterm infants, 23 to 32 weeks' gestational age, without major congenital anomalies, were reviewed. Maternal and neonatal data were abstracted. Association of AI within 15 days before delivery (predictor variable) and classification of NEC according to modified Bell's stage 2a or higher in the first 15 days after delivery (early NEC [primary outcome variable]) was explored by using bivariate analyses, multivariate logistic regression, and propensity score analysis. RESULTS: Of 628 eligible infants, 63 received AI and 28 developed early NEC. AI exposure was significantly associated with multiple gestation, race, antenatal corticosteroids and magnesium sulfate, lower birth weight and gestational age, umbilical arterial catheter placement, respiratory distress syndrome, postnatal vasopressors and antibiotics, patent ductus arteriosus, sepsis, NEC, intraventricular hemorrhage, and mortality. On multivariate logistic regression controlling for covariates, AI was significantly associated with early NEC (adjusted odds ratio: 7.193 [95% confidence interval: 2.514-20.575]; number needed to harm: 5). The results remained significant when analyses were repeated using AI exposure within 5 days before delivery as a predictor variable; on analyses stratified according to gestational age; and on propensity score analysis. CONCLUSIONS: AI was associated with NEC in preterm infants in the first 15 days of life in this study, as were multiple other clinical factors.
Assuntos
Enterocolite Necrosante/induzido quimicamente , Indometacina/efeitos adversos , Doenças do Prematuro/induzido quimicamente , Tocólise/efeitos adversos , Tocolíticos/efeitos adversos , Estudos de Coortes , Enterocolite Necrosante/epidemiologia , Feminino , Humanos , Recém-Nascido , Doenças do Prematuro/epidemiologia , Masculino , Análise Multivariada , Gravidez , Fatores de RiscoRESUMO
OBJECTIVES: The purpose of this study is to determine pharmacists' perceived knowledge and expertise required to make recommendations regarding selected pediatric topics. METHODS: A questionnaire was distributed to 400 pharmacists practicing in community, hospital, and home care settings. This instrument explored their perceived knowledge, expertise, and comfort in providing recommendations related to 38 pediatric topics. The impact of responder demographics on differences in perceived knowledge and expertise for each topic were evaluated. RESULTS: Ninety-five of 400 (24%) questionnaires were returned completed or partially completed. Forty-seven and 36 of responders practiced in the community or inpatient hospital setting, respectively. Seventy percent of responders reported that ≤ 40% of their patients were children. In general, responders believed they had the knowledge and expertise to make recommendations for the frequently occurring conditions or topics but not for the less familiar. Formal pediatric training was the most influential responder characteristic with a larger proportion having training that they believed enables them to have knowledge and expertise to make recommendations. Although less impressive, experience of more than 5 years and a community-based practice were also important factors. CONCLUSION: Additional training is beneficial in increasing the perceived knowledge and comfort of pharmacists making recommendations regarding pediatric patients.