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BACKGROUND: We performed a cross-sectional study in Indonesia to evaluate the performance of a single-visit approach of cervical cancer screening, using visual inspection with acetic acid (VIA), histology and cryotherapy in low-resource settings. METHODS: Women having limited access to health-care facilities were screened by trained doctors using VIA. If the test was positive, biopsies were taken and when eligible, women were directly treated with cryotherapy. Follow-up was performed with VIA and cytology after 6 months. When cervical cancer was suspected or diagnosed, women were referred. The positivity rate, positive predictive value (PPV) and approximate specificity of the VIA test were calculated. The detection rate for cervical lesions was given. RESULTS: Screening results were completed in 22 040 women, of whom 92.7% had never been screened. Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The approximate specificity was 98.1%, and the detection rate for CIN I or greater was 2.6%. CONCLUSION: The single-visit approach cervical cancer screening performed well, showing See and Treat is a promising way to reduce cervical cancer in Indonesia.
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Crioterapia/métodos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Adulto , Estudios Transversales , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Indonesia , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/métodosRESUMEN
BACKGROUND: Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-ßRI inhibitor) seeking to overcome GB treatment resistance. METHODS: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. RESULTS: Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-ß-dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. CONCLUSION: This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells.
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Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Metilasas de Modificación del ADN/antagonistas & inhibidores , Enzimas Reparadoras del ADN/antagonistas & inhibidores , Glioblastoma/tratamiento farmacológico , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Temozolomida/farmacología , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Aminopiridinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Astrocitos/efectos de los fármacos , Bencimidazoles/farmacología , Neoplasias Encefálicas/enzimología , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ciclina D/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular , Glioblastoma/enzimología , Guanina/análogos & derivados , Guanina/farmacología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Neuronas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Pirazoles/farmacología , Quinolinas/farmacología , Proteínas Smad/efectos de los fármacosRESUMEN
PURPOSE: N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive behavior. Current therapies in the treatment of high-grade meningioma are lacking with limited success. This study aims to validate the effect of NDRG2-targeted therapy using structurally related bioactive triterpene compounds derived from the edible mushroom Ganoderma lucidum (ganoderic acid A:GA-A/ganoderic acid DM:GA-DM) in human AM in relevant pre-clinical models. METHODS: Tissue samples from the AM tumor regions of three human patients and control non-tumor samples were used to analyze the expression pattern of NDRG2. In vitro cell culture and in vivo cell-line-derived orthotopic xenograft animal models of AM were utilized to assess efficacy of treatment with GA-A/DM. RESULTS: Downregulation of NDRG2 expression was observed in surgically resected high-grade meningiomas compared to normal brain. These results prompt us to use NDRG2-targeting agents GA-A/DM. In vitro results showed that 72-h treatments of 25 µM GA-A/DM induced AM cell death, upregulate NDRG2 protein expression, downregulate NDRG2 promoter methylation in meningioma cells as compared to azacitidine and decitabine, the most commonly used demethylating agents. Our results also demonstrated that GA-A/DM does not have any detrimental effect on normal human neurons and arachnoid cells. GA-A/DM promoted apoptotic factors (Bax) while suppressing MMP-9, p-P13K, p-AKT, p-mTOR, and Wnt-2 protein expression. RNAi-mediated knockdown of NDRG2 protein expression increased tumor proliferation, while forced expression of wt-NDRG2 decreased proliferation in an in vitro model. Magnetic resonance (MR) imaging and Hematoxylin (H&E) staining demonstrated gross reduction of tumor volume in GA-A/DM treated mice at 5 weeks when compared with saline-treated orthotopic AM xenografted controls. There was an overall decrease in tumor cell proliferation with increased survival in GA-A/DM-treated animals. Enzyme assays showed that GA-A/DM did not negatively impact hepatic function. CONCLUSION: GA-A/DM may be a promising natural therapeutic reagent in the treatment of AM by suppressing growth via NDRG2 modulation and altering of intracellular signal pathways. We have shown it could potentially be an effective treatment for AM with decreased cellular proliferation in vitro, decreased tumor volume and increased survival in vivo.
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Ácidos Heptanoicos/farmacología , Lanosterol/análogos & derivados , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Triterpenos/farmacología , Proteínas Supresoras de Tumor/efectos de los fármacos , Anciano , Anaplasia , Animales , Antimetabolitos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Azacitidina/farmacología , Muerte Celular/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Decitabina/farmacología , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Técnicas In Vitro , Lanosterol/farmacología , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias Meníngeas/patología , Meningioma/patología , Ratones , Ratones SCID , Persona de Mediana Edad , Terapia Molecular Dirigida , Clasificación del Tumor , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteína wnt2/efectos de los fármacos , Proteína wnt2/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates. METHODS: This retrospective analysis compared 3 patient groups-those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction. RESULTS: Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 +/- 0.7, IL-2RA induction 2.0 +/- 1.0, and thymoglobulin induction 1.9 +/- 1.2; P = .47) were similar between all groups. CONCLUSION: The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.
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Anticuerpos Monoclonales/uso terapéutico , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Subunidad alfa del Receptor de Interleucina-2/inmunología , Trasplante de Riñón/inmunología , Receptores de Interleucina-2/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Suero Antilinfocítico , Basiliximab , Creatinina/metabolismo , Daclizumab , Femenino , Humanos , Terapia de Inmunosupresión/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF.
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Anticarcinógenos/uso terapéutico , Arándanos Azules (Planta)/química , Neoplasias del Colon/prevención & control , Frutas , Lythraceae/química , Lesiones Precancerosas/prevención & control , Animales , Anticarcinógenos/farmacología , Azoximetano/toxicidad , Neoplasias del Colon/inducido químicamente , Frutas/química , Glutatión Transferasa/metabolismo , Hígado/enzimología , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Lesiones Precancerosas/inducido químicamente , Distribución Aleatoria , Ratas , Ratas Endogámicas F344RESUMEN
In image-free total knee arthroplasty (TKA) navigation, infra-red markers are attached to bony landmarks to provide kinematic data intra-operatively, with the aim of improving the precision of implant placement. In non-invasive navigation, infra-red markers are attached to the skin surface, with recent evidence suggesting that this can give repeatable measurements of lower limb mechanical alignment. The aim of our study was to evaluate the use of a non-invasive navigation system in the assessment of mechanical alignment with applied coronal force through the range of flexion. A previously validated non-invasive system (Physiopilot™) was tested on 23 volunteers with healthy knees. Two users performed two registrations of the software workflow on each participant's right and left knees. A force was manually applied to the end-point of varus and valgus knee laxity and the measured change in mechanical alignment was recorded. Force was applied with the knee positioned in increments of flexion from 0 to 90°. In keeping with previous studies, satisfactory values of coefficient of repeatability (CR) of 1.55 and 1.33 were found for intra-observer repeatability in measurement of supine mechanical femoro-tibial angle (MFTA) in extension, with a good inter-observer correlation of intraclass correlation coefficient (ICC) .72. However, when flexion was introduced, intra-observer and inter-observer reliability fell out with acceptable limits. Therefore, the trial did not support use of the Physiopilot™ system as a measure of MFTA when flexion is introduced. It was felt that learning-curve, soft tissue artefacts and lack of force standardisation equipment may have accounted for significant levels of error, with further studies required to address these issues.
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Artrometría Articular/instrumentación , Interpretación de Imagen Asistida por Computador/instrumentación , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiología , Examen Físico/métodos , Estimulación Física/instrumentación , Rango del Movimiento Articular/fisiología , Artrometría Articular/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Estimulación Física/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estrés MecánicoRESUMEN
PURPOSE: To test if active breath control during cone-beam computed tomography (CBCT) could improve planning target volume during accelerated partial breast radiotherapy for breast cancer. METHODS: Patients who were more than 40 years old, underwent breast-conserving dissection and planned for accelerated partial breast irradiation, and with postoperative staging limited to T1-2 N0 M0, or postoperative staging T2 lesion no larger than 3cm with a negative surgical margin greater than 2mm were enrolled. Patients with lobular carcinoma or extensive ductal carcinoma in situ were excluded. CBCT images were obtained pre-correction, post-correction and post-treatment. Set-up errors were recorded at left-right, anterior-posterior and superior-inferior directions. The differences between these CBCT images, as well as calculated radiation doses, were compared between patients with active breath control or free breathing. RESULTS: Forty patients were enrolled, among them 25 had active breath control. A total of 836 CBCT images were obtained for analysis. CBCT significantly reduced planning target volume. However, active breath control did not show significant benefit in decreasing planning target volume margin and the doses of organ-at-risk when compared to free breathing. CONCLUSION: CBCT, but not active breath control, could reduce planning target volume during accelerated partial breast irradiation.
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Neoplasias de la Mama/radioterapia , Tomografía Computarizada de Haz Cónico/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Respiración , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
One hundred thirty-two children who attended a research day-care center were studied to determine whether passive tobacco smoke exposure was associated with an increased rate of otitis media with effusion or with an increased number of days with otitis media with effusion during the first 3 years of life. Based on preliminary studies, a serum cotinine concentration of greater than or equal to 2.5 ng/mL was considered indicative of exposure to tobacco smoke. Otitis media with effusion was diagnosed using pneumatic otoscopy by nurse practitioners and pediatricians who reviewed the children's health status each weekday. The 87 children with serum cotinine concentrations greater than or equal to 2.5 ng/mL had a 38% higher rate of new episodes of otitis media with effusion during the first 3 years of life than the 45 children with lower or undetectable serum cotinine concentrations (incidence density ratio = 1.38, 95% confidence interval 1.21 to 1.56). The average duration of an episode of otitis media with effusion was 28 days in the children with elevated cotinine concentrations and 19 days in the children with lower cotinine concentrations (P less than .01). It is estimated that 8% of the cases of otitis media with effusion in this population and 17.6% of the days with otitis media with effusion may be attributable to exposure to tobacco smoke.
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Otitis Media con Derrame/complicaciones , Contaminación por Humo de Tabaco/efectos adversos , Factores de Edad , Niño , Guarderías Infantiles , Preescolar , Factores de Confusión Epidemiológicos , Cotinina/sangre , Femenino , Humanos , Incidencia , Lactante , Masculino , Análisis de Regresión , Infecciones del Sistema Respiratorio/complicaciones , Factores de Riesgo , Factores de Tiempo , Contaminación por Humo de Tabaco/análisisRESUMEN
The etiology and epidemiology of croup were studied in a pediatric group practice over an 11-year period, 1964 to 1975. Croup was diagnosed in 951 instances in 6,165 cases of lower respiratory tract infection (LRI) studied. As census figures of the practice clientele were available, attack rates were calculated. The incidence of total LRI was highest in the first year of life. In contrast, the attack rate for croup was highest in the second year of life; the rate declined gradually after that age. Croup was not diagnosed in the first month of life. Boys were 1.43 times more likely to develop croup than were girls. Three hundred sixty agents were isolated from the 951 croup cases. The parainfluenza viruses accounted for 74.2% of all isolates; 65% of the parainfluenza isolates were classified as parainfluenza virus type 1. Respiratory syncytial virus, influenza viruses A and B, and Mycoplasma pneumoniae were the only other agents isolated in appreciable numbers. The propensity of various agents to produce croup symptoms in children with LRI due to specific microorganisms was 58% for parainfluenzae type 1,60% for parainfluenzae type 2, and 29% for parainfluenzae type 3; similar figures for the other agents varied from 5% to 16%. The role of the various agents in the etiology of croup varied with patient age and depended on the propensity of the agent to produce the croup syndrome and the frequency of isolation of the agent at that age. The parainfluenza viruses were the most important croup agents at all ages; respiratory syncytial virus caused croup in children less than 5 years of age whereas the influenza viruses and M pneumoniae were significant causes of croup only in children more than 5 to 6 years old. Croup occurred predominately in late fall and early winter, times when the parainfluenza viruses, especially type 1, occurred most frequently. The epidemiology of croup differs from that of bronchiolitis, pneumonia, and tracheobronchitis; knowledge of this should be helpful to the clinician caring for children with LRI.
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Crup/epidemiología , Laringitis/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Respirovirus/epidemiología , Factores de Edad , Niño , Preescolar , Crup/microbiología , Femenino , Humanos , Lactante , Masculino , Infecciones por Paramyxoviridae/microbiología , Virus Sincitiales Respiratorios/aislamiento & purificación , Respirovirus/aislamiento & purificación , Infecciones por Respirovirus/microbiología , Estaciones del Año , Factores SexualesRESUMEN
The relationship between the occurrence of otitis media with effusion during the first 3 years of life and subsequent verbal and academic performance was examined in 61 socioeconomically disadvantaged children who attended a research day-care program. Study children were participants in a longitudinal study of child development in which the number of episodes of otitis media and duration of each otitis episode were reported prospectively from infancy. The incidence of otitis media was highest during the first 2 years of life. Bilateral otitis media accounted for 66% of the days with otitis media with effusion. Standardized tests of intelligence and academic performance were administered to the children when they were 3 1/2 to 6 years of age. No evidence of associations between measures of early childhood otitis media experience and these measures of verbal or academic functioning was found in this study population.
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Evaluación Educacional , Otitis Media con Derrame/psicología , Aprendizaje Verbal , Logro , Población Negra , Desarrollo Infantil , Preescolar , Cognición , Femenino , Humanos , Lactante , Pruebas de Inteligencia , Masculino , Estudios Prospectivos , Riesgo , Factores SocioeconómicosRESUMEN
The relationship between the occurrence of otitis media during the first 3 years of life and cognitive, academic, and classroom performance during the third year of elementary school was evaluated in 44 socioeconomically disadvantaged children. The children attended a research day-care program where their otitis media experience and psychoeducational development were documented prospectively from birth. No significant relationship was found between otitis media in early childhood and performance on tests of verbal intelligence or academic achievement in the third year of school. The number of days of otitis media before 3 years of age was significantly correlated with teachers' ratings of children's attentional behavior in the classroom, however. Children with more early otitis media tended to be rated as less task oriented and less able to work independently than children with less otitis media. This was an exploratory study of a small number of children. Further study of the potential association is needed.
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Conducta Infantil , Cognición , Aprendizaje , Otitis Media con Derrame/psicología , Niño , Humanos , Inteligencia , Pruebas de Inteligencia , Estudios ProspectivosRESUMEN
OBJECTIVE: To examine the relationship between otitis media with effusion (OME) and associated hearing loss between 6 and 24 months of age and children's language and cognitive development at 2 years of age. STUDY DESIGN: A prospective cohort design in which 86 African-American infants who attended group child-care centers were recruited between 6 and 12 months of age. Between 6 and 24 months, assessments included serial ear examinations using otoscopy and tympanometry, serial hearing tests, two ratings of the childrearing environment at home and in child care, and language and cognitive outcomes at 2 years. RESULTS: Children experienced either unilateral or bilateral OME an average of 63% and reduced hearing sensitivity an average of 44% of the time between 6 and 24 months of age. Although proportion of time with OME or with hearing loss was modestly correlated with measures of language and cognitive skills, these relationships were no longer significant when the ratings of the home and child-care environments were also considered. Children with more OME or hearing loss tended to live in less responsive caregiving environments, and these environments were linked to lower performance in expressive language and vocabulary acquisition at 2 years. CONCLUSIONS: Both OME and hearing loss were more strongly related to the quality of home and child-care environments than to children's language and cognitive development. Study results might be explained either by suggesting that children in less responsive caregiving environments experience conditions that make them more likely to experience OME and/or by suggesting that it may be more difficult for caregivers to be responsive and stimulating with children with more OME.
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Población Negra , Trastornos del Conocimiento/diagnóstico , Pérdida Auditiva Conductiva/diagnóstico , Trastornos del Desarrollo del Lenguaje/diagnóstico , Otitis Media con Derrame/diagnóstico , Medio Social , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Prospectivos , VocabularioRESUMEN
The effects of primycin, a potent ionophore in biological membranes, have been studied at the neuromuscular junction of the garter snake. Primycin in concentrations greater than 2 X 10(-7)M produced a time- and concentration-dependent depolarization of twitch muscle fibres. Primycin (10(-7)-5 X 10(-7)M) produced an increased rate of quantal release of acetylcholine, which was not maintained, and a slight reduction in quantal size. Time to onset and to peak effect of primycin were concentration-dependent whereas maximum frequency was not. Absence of extracellular Ca2+ produced a significant delay in the time to onset and to peak effect of primycin, but did not affect the peak miniature endplate potential (m.e.p.p.) frequency. Following 60 min exposure to primycin (5 X 10(-7)M), introduction of a high concentration of potassium (20 mM) produced no further increase in spontaneous release. In cut muscle preparations, exposure to primycin (10(-7)-5 X 10(-7)M) reduced peak endplate current (e.p.c.) amplitude until nerve stimulation resulted in failures or the release of one or two quanta. E.p.c. amplitude was not restored with prolonged washing. The effects of primycin on the nerve terminal are considered to be consistent with its ability to increase the permeability of membranes to calcium ions resulting in an influx of extracellular calcium, an efflux of mitochondrial calcium and eventual depletion of synaptic vesicles.
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Antibacterianos , Macrólidos , Unión Neuromuscular/efectos de los fármacos , Neurotransmisores/metabolismo , Animales , Calcio/fisiología , Dimetilsulfóxido/farmacología , Técnicas In Vitro , Lactonas/farmacología , Potenciales de la Membrana/efectos de los fármacos , Placa Motora/efectos de los fármacos , Potasio/farmacología , Serpientes , Factores de TiempoRESUMEN
To characterize patterns of herpes simplex virus type 1 infection, illness and transmission among children in group day care, the data for 115 children who had been followed longitudinally from early infancy in a research day care center were examined. By 5 years of age 37% of study children had evidence of herpes simplex virus type 1 infection as demonstrated by virus isolation and/or seroconversion. The incidence of infection was highest among children 1 to 2 years old. Four small clusters of primary infections were observed over the 12-year study period but no cluster involved more than 6 children. Fifty-five percent of primary infections occurred during these small outbreaks; the remainder were sporadic. Gingivostomatitis was observed in 26% of children with primary culture-proved infections; no child with infection identified solely by serologic means had a history of gingivostomatitis. The occurrence of gingivostomatitis did not appear to be associated with increased transmission of herpes simplex virus type 1 infection in this day-care setting.
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Guarderías Infantiles , Herpes Simple/epidemiología , Simplexvirus/aislamiento & purificación , Estomatitis Herpética/epidemiología , Anticuerpos Antivirales/sangre , Niño , Preescolar , Análisis por Conglomerados , Ensayo de Inmunoadsorción Enzimática , Femenino , Herpes Simple/microbiología , Herpes Simple/transmisión , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Recurrencia , Simplexvirus/inmunología , Estomatitis Herpética/microbiología , Estomatitis Herpética/transmisión , Estados UnidosRESUMEN
BACKGROUND: Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age. METHODS: This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms for < or = 36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication). FINDINGS: A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P < 0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B. CONCLUSIONS: Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.
Asunto(s)
Antivirales/uso terapéutico , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Ácidos Siálicos/uso terapéutico , Administración por Inhalación , Antivirales/administración & dosificación , Antivirales/efectos adversos , Niño , Preescolar , Método Doble Ciego , Femenino , Guanidinas , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Gripe Humana/virología , Masculino , Cooperación del Paciente/estadística & datos numéricos , Piranos , Ácidos Siálicos/administración & dosificación , Ácidos Siálicos/efectos adversos , Resultado del Tratamiento , ZanamivirRESUMEN
OBJECTIVE: To improve intraoperative observation of unexposed anatomic features and to verify surgical correction, a mobile computed tomographic (CT) scanner has been introduced into the operating room. To date, intraoperative CT scanning has been used predominantly for intracranial procedures. We report on the expanded use of intraoperative CT scanning for spinal surgery, because CT scanning provides excellent observation of osseous pathological features. We report on our first 17 cases, which involved complex craniocervical operations and spinal tumor resections. METHODS: The Tomoscan M CT scanner (Philips Medical Systems, Eindhoven, The Netherlands) is mobile and consists of a translatable gantry, a translatable table, and an operator's workstation. In the operating room, the patient is placed on the CT table and prepared in the usual manner. The aperture of the gantry is covered with sterile plastic drapes. The gantry is docked to the table for intraoperative CT scanning as needed for navigation and verification during surgery. Each series of scans requires approximately 15 to 20 minutes. RESULTS: Our initial experience with neurosurgical spinal cases demonstrated that the use of intraoperative CT scanning changed the course of surgery in 6 of 17 cases. CT scanning was beneficial in facilitating adequate ventral clival and craniocervical decompressions, promoting more complete tumor resections, and verifying correct graft and instrument placement before surgical closing. Other settings in which we have found the mobile CT scanner useful include the neurointerventional suite and the intensive care unit; it is also useful for radiotherapy planning. CONCLUSION: On the basis of findings for our first 17 spinal surgery cases, we conclude that intraoperative CT scanning of the spine is both feasible and beneficial for select complex spinal procedures from the craniocervical junction to the sacrum.
Asunto(s)
Encéfalo/cirugía , Cuello/cirugía , Neoplasias de la Columna Vertebral/cirugía , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Equipos y Suministros , Estudios de Factibilidad , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada por Rayos X/instrumentaciónRESUMEN
OBJECT: Hypertrophy of the superior facet of the inferior vertebra, resulting in a compression of the nerve root at the lateral foraminal exit, is a recognized cause of radicular symptoms, particularly in patients in whom previous lumbar spine surgery has failed. The lesion-specific presenting symptoms, imaging findings, and surgical treatment of this lesion, however, have received little attention. The authors prospectively studied a series of eight consecutive patients, in whom a diagnosis of lumbar stenosis at the lateral foraminal exit had been made, to elucidate the common presenting signs and symptoms of this disorder, as well as to evaluate the success of the operative treatment. METHODS: The eight patients were selected from a group of 250 consecutive patients who presented to a tertiary-care hospital and in whom a diagnosis of long-standing lumbar radiculopathy had been made. In all cases the diagnosis was confirmed by imaging studies and by intraoperative findings. The authors performed decompressive procedures on the nerve root via a medial facet-sparing approach. CONCLUSIONS: The authors conclude that this lesion presents with characteristic physical findings and on imaging studies that distinguish it from other causes of radiculopathy, and they propose a lesion-specific, facet-sparing surgical technique that has yielded excellent results.
Asunto(s)
Dolor de la Región Lumbar/etiología , Vértebras Lumbares/patología , Vértebras Lumbares/cirugía , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/cirugía , Raíces Nerviosas Espinales/patología , Raíces Nerviosas Espinales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Constricción Patológica/complicaciones , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/cirugía , Femenino , Humanos , Hipertrofia/complicaciones , Hipertrofia/diagnóstico por imagen , Hipertrofia/cirugía , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Enfermedades del Sistema Nervioso Periférico/patología , Estudios Prospectivos , Raíces Nerviosas Espinales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECT: Tarlov or perineurial cysts are lesions of the nerve root most often found in the sacral region. Although there is agreement that asymptomatic Tarlov cysts should be followed, it is still debated whether patients with symptomatic Tarlov cysts should be treated surgically. The authors assessed the outcome and efficacy of cyst wall resection in 10 patients with symptomatic Tarlov cysts. The medical literature is reviewed, theories of origin are evaluated, and suggestions as to their cause and pathogenesis are offered. METHODS: Ten consecutive patients harboring symptomatic Tarlov cysts were treated by the senior author between 1989 and 1999. All patients were assessed for neurological deficits and pain by neurological examination and visual analog scale, respectively. Computerized tomography myelography was performed in all patients to diagnose delayed filling of the cysts. A sacral laminectomy with resection of the sacral cyst or cysts was performed in all patients. Resected material from eight of 10 patients was submitted for histopathological evaluation. Seven (70%) of 10 patients obtained complete or substantial resolution of their symptoms, with an average follow up of 31.7 months. All of these patients had Tarlov cysts larger than 1.5 cm in diameter, producing radicular pain or bladder and bowel dysfunction. Three (30%) of 10 patients experienced no significant improvement. All three patients harbored Tarlov cysts smaller than 1.5 cm in diameter, producing nonradicular pain. Histopathological examination was performed on specimens from eight of 10 patients, which demonstrated nerve fibers in 75% of cases, ganglion cells in 25% of cases, and evidence of old hemorrhage in half. CONCLUSIONS: Large cysts (> 1.5 cm) and the presence of associated radicular symptoms strongly correlate with excellent outcome. Tarlov cysts may result from increased hydrostatic pressure and trauma.
Asunto(s)
Radiculopatía/cirugía , Quistes de Tarlov/cirugía , Adulto , Femenino , Humanos , Laminectomía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Neurológico , Radiculopatía/diagnóstico , Radiculopatía/patología , Sacro/patología , Sacro/cirugía , Quistes de Tarlov/diagnóstico , Quistes de Tarlov/patologíaRESUMEN
The authors present the case of a 15-year-old Jehovah's Witness with a hematocrit level of 19% who was 4 months pregnant and had a two-level spondyloptotic cervical spine fracture. The patient was transferred to Georgetown University Medical Center with C-5 quadriplegia 3 weeks after having been injured in an automobile collision. The neurosurgical issues in this case included addressing a rare cervical spine injury, assessing and treating a vertebral artery injury, and performing surgery on a pregnant minor with severe anemia who held strong Jehovah's Witness beliefs. An ethics consultation was convened to determine the validity of a pregnant minor's refusal to undergo transfusion on the grounds of her religious beliefs. This case illustrates the potential benefits of thorough technical and ethical evaluations and reveals how they may contribute to the delivery of care in complex neurosurgical cases. To the authors' knowledge, this is the first two-level spondyloptotic cervical spine fracture dislocation to be reported in the literature. The added complexities of the case, given that the patient was an anemic, adolescent, pregnant Jehovah's Witness who refused blood transfusion, also appear to be unprecedented.
Asunto(s)
Accidentes de Tránsito , Anemia Hipocrómica/complicaciones , Vértebras Cervicales/lesiones , Cristianismo , Ética Médica , Defensa del Paciente , Complicaciones Hematológicas del Embarazo , Complicaciones del Embarazo/cirugía , Embarazo en Adolescencia , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Adolescente , Femenino , Humanos , EmbarazoRESUMEN
Drug stocks in an animal unit were rationalized by discarding out-of-date or unwanted items and drawing up an approved stock list. A computerized system of stock control which enables a regular and accurate inventory of pharmaceuticals to be made was then established. In addition, the paperwork required for reordering drugs is produced automatically. Pharmaceuticals to a total value of 1650 pounds were discarded during the rationalization phase. The value of drugs stocked in the animal unit then stabilized at about one-third of previous levels. In the first 6 months of operation of the new system drug expenditure fell by about 40% in comparison with the same period 1 year previously. The drug stock control system has proved economical to operate and accurate, and can be run by persons without computer expertise. Valuable savings in both cost and labour have resulted. Effective management of drug expenditure by the animal unit is now possible.