RESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is diagnosed through polysomnography (PSG) testing and commonly treated with positive airway pressure (PAP). The initial recommended treatment for pediatric OSA is adenotonsillectomy, but when this is contraindicated or ineffective, PAP is the next option. Children followed in our pediatric sleep disorders center who are diagnosed with OSA and meet criteria for therapy are empirically prescribed a PAP device, usually auto-titrating PAP (APAP), to avoid delays in therapy. Titration PSG is performed later to assess adequacy of settings. The aims of this study were to determine how often PSG titration results in changes to empirically prescribed PAP and to assess adherence to therapy before and after PSG titration. METHODS: A retrospective medical records review was completed for children diagnosed with OSA, prescribed PAP, and had a titration PSG within a 5-y consecutive period of 2008-2012. Demographic data, type of device, pressure settings, and adherence downloads were reviewed. Adherence was assessed before and after titration overall and compared for those who did and did not have therapy changes following titration. RESULTS: The study included 121 participants. Median age at the time of the diagnostic PSG was 11 (interquartile range [IQR] 8-14) y. Most (106, 88%) were initially prescribed APAP. Median length of time between initial and follow-up PSG was 6.4 (IQR 4.4-10.1) months. The majority (94, 78%) had therapy changes following titration. Overall, adherence percentage > 4 h per night was not significantly increased post titration (P = .47). There were no statistically significant differences in adherence between those who had therapy changes and those who did not (P = .26). CONCLUSIONS: Titration studies resulted in therapy modifications for most children. Adherence was not increased following the titration PSG. Changes in therapy did not result in increased adherence. Titration PSGs may optimize empirically prescribed settings.
Assuntos
Apneia Obstrutiva do Sono , Criança , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Polissonografia , Estudos Retrospectivos , SonoRESUMO
Advances in medicine and technology have led to improved survival rates of children with chronic respiratory disease such as cystic fibrosis, neuromuscular disease, and ventilator dependence. Survival into adulthood has created the need for adult specialists for conditions originating in childhood. Transition from pediatric to adult health care is a process that requires advanced planning and preparation and is not a one-time transfer event. Transition should be standard practice, but many children with special health care do not experience successful transition outcomes. Barriers to successful transition include lack of a standardized process, inadequate planning, and poor communication. Adverse outcomes have occurred in cases of abrupt or haphazard transfers. A successful transition process includes early introduction and ongoing discussion that engages the adolescent to plan and prepare for the eventual transfer of care. Care responsibilities should be gradually shifted from the parent to the adolescent in a manner appropriate for the adolescent's age and developmental status. Good communication and collaboration between pediatric and adult care teams is crucial to ensure a smooth transfer of care. Incorporating the 6 core elements of transition can be helpful in developing a successful transition program. This narrative review summarizes the literature for health care transition from pediatric to adult care including the rationale, barriers, factors associated with successful transition, and special considerations. The intent of this review is to increase clinician awareness of health care transitions and the components necessary for an effective transfer of young adults with chronic respiratory disease. Understanding the transition process is an important consideration for both pediatric and adult clinicians, including respiratory therapists.
Assuntos
Fibrose Cística , Transtornos Respiratórios , Adulto , Doença Crônica , Fibrose Cística/terapia , Humanos , Pais , Transferência de Pacientes , Transição para Assistência do Adulto , Adulto JovemRESUMO
BACKGROUND: The transition from an ICU ventilator to a portable home ventilator (PHV) for children requiring long-term mechanical ventilation is a crucial step in preparing for discharge home and may not be successful on the first attempt. A review of this process at our institution revealed that some children required multiple trials before they were able to tolerate a PHV. A protocol was developed to standardize the transition process and reduce the number of failed attempts. Key features of the protocol included a transition readiness assessment and criteria for changing to the PHV. METHODS: A retrospective chart review was completed to evaluate the process of changing to a PHV before and after the protocol was in place during the time period of 2011-2018. Primary outcome measures included the number of transition attempts and the length of time to achieve successful transition. A successful transition attempt was defined as the ability to tolerate a PHV for 14 d. RESULTS: The study included 56 children ≤ 3 y old with a tracheostomy who required long-term ventilator support. The majority of subjects were from the neonatal ICU and had a diagnosis of bronchopulmonary dysplasia. There was a significant decrease in the number of attempts (P = .005) and in the length of time (P = .01) to successfully transition to a PHV for those who underwent the protocol. CONCLUSIONS: The process of changing from an ICU ventilator to a PHV in children requiring long-term mechanical ventilation was improved through the use of a standardized protocol. Both the number of failed attempts and the length of time to achieve successful transition were reduced when the protocol was applied. Further study is needed to evaluate other medical and nonmedical factors that may affect successful transition to a PHV.
Assuntos
Serviços de Assistência Domiciliar , Ventiladores Mecânicos , Criança , Humanos , Unidades de Terapia Intensiva , Respiração Artificial , Estudos Retrospectivos , Desmame do RespiradorRESUMO
Cystic fibrosis (CF) is a chronic disease requiring patients to have frequent specialty healthcare visits to delay progression of lung disease, prevent and treat failure to thrive and initiate early interventions to prevent acute illness and complications. The CF Foundation recommends that patients have visits with the CF care team at least every 3 months. During participation in the CF Foundation Learning and Leadership Collaborative IV, the CF team at Arkansas Children's Hospital initiated quality improvement work with the aim to increase the percentage of patients attending clinic four or more times a year from 35% in 2004 and 56% in 2005 (CF Foundation Registry data) to 90% or greater. We redesigned our scheduling system, rescheduled missed patient appointments in a timely fashion and created a process to monitor attendance. This quality improvement work led to a sustained increase in the percentage of patients attending clinic visits four or more times a year reaching our goal of 90% in 2012. Improvements were also noted in the number of patients with body mass index/weight-for-length centile of 25 or greater, which could be related to more frequent clinic attendance.
Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Assistência Ambulatorial/estatística & dados numéricos , Agendamento de Consultas , Fibrose Cística/terapia , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Assistência Ambulatorial/normas , Criança , Pré-Escolar , Fibrose Cística/epidemiologia , Feminino , Fidelidade a Diretrizes , Humanos , Incidência , Masculino , Assistência ao Paciente/normas , Equipe de Assistência ao Paciente/organização & administração , Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Estados UnidosRESUMO
OBJETIVOS: Evaluamos una estrategia para la prevención de la tuberculosis en las comunidades más afectadas por esta enfermedad. MÉTODOS: En 1996, trazamos un mapa de los casos de tuberculosis notificados (1985-1995) y de las personas con reacción positiva a la prueba de la tuberculina (1993-1995) en el condado de Smith, Texas, Estados Unidos de América. Definimos los dos conglomerados de mayor tamaño y densidad, identificando los dos vecindarios con mayor incidencia (180 manzanas y 3 153 residentes). Tras una preparación intensiva de la comunidad, personal sanitario capacitado ofreció a todos los residentes, de vivienda en vivienda, la posibilidad de hacerse la prueba de la tuberculina, a menos que estuviera contraindicado. A las personas con resultados positivos en esta prueba se las acompañó a un consultorio móvil para realizarles ahí radiografías, una evaluación clínica y, según fuera pertinente, proceder con el tratamiento preventivo con isoniazida. Para evaluar las repercusiones a largo plazo, trazamos un mapa de todos los casos de tuberculosis que se registraron en el condado de Smith durante el período equivalente después del proyecto. RESULTADOS: De las 2 258 personas que cumplían los requisitos para participar, 1 291 (57,1%) se sometieron a la prueba de la tuberculina, 229 (17,7%) presentaron resultados positivos en dicha prueba y 147 fueron tratadas. De 1996 al 2006, no se registró ningún caso de tuberculosis en ninguno de los vecindarios del proyecto, a diferencia de lo ocurrido en el decenio anterior a la intervención y en el resto del condado de Smith, donde aparecieron continuamente casos de tuberculosis. CONCLUSIONES: Dirigirse a los vecindarios con una incidencia alta para realizar el tamizaje activo en la comunidad y aplicar tratamiento preventivo con isoniazida puede acelerar la eliminación de la tuberculosis en los Estados Unidos.
OBJECTIVES: We evaluated a strategy for preventing tuberculosis (TB) in communities most affected by it. METHODS: In 1996, we mapped reported TB cases (1985-1995) and positive tuberculin skin test (TST) reactors (1993-1995) in Smith County, Texas. We delineated the 2 largest, densest clusters, identifying 2 highest-incidence neighborhoods (180 square blocks, 3153 residents). After extensive community preparation, trained health care workers went door-to-door offering TST to all residents unless contraindicated. TST-positive individuals were escorted to a mobile clinic for radiography, clinical evaluation, and isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we mapped all TB cases in Smith County during the equivalent time period after the project. RESULTS: Of 2258 eligible individuals, 1291 (57.1%) were tested, 229 (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no TB cases in either project neighborhood, in contrast with the preintervention decade and the continued occurrence of TB in the rest of Smith County. CONCLUSIONS: Targeting high-incidence neighborhoods for active, community-based screening and IPT may hasten TB elimination in the United States.
Assuntos
Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Tuberculose/transmissãoRESUMO
OBJECTIVES: We evaluated a strategy for preventing tuberculosis (TB) in communities most affected by it. METHODS: In 1996, we mapped reported TB cases (1985-1995) and positive tuberculin skin test (TST) reactors (1993-1995) in Smith County, Texas. We delineated the 2 largest, densest clusters, identifying 2 highest-incidence neighborhoods (180 square blocks, 3153 residents). After extensive community preparation, trained health care workers went door-to-door offering TST to all residents unless contraindicated. TST-positive individuals were escorted to a mobile clinic for radiography, clinical evaluation, and isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we mapped all TB cases in Smith County during the equivalent time period after the project. RESULTS: Of 2258 eligible individuals, 1291 (57.1%) were tested, 229 (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no TB cases in either project neighborhood, in contrast with the preintervention decade and the continued occurrence of TB in the rest of Smith County. CONCLUSIONS: Targeting high-incidence neighborhoods for active, community-based screening and IPT may hasten TB elimination in the United States.
Assuntos
Erradicação de Doenças/métodos , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/prevenção & controle , Adolescente , Adulto , Negro ou Afro-Americano , Antituberculosos/uso terapêutico , Criança , Feminino , Mapeamento Geográfico , Hispânico ou Latino , Humanos , Incidência , Isoniazida/uso terapêutico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Radiografia Torácica/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Fatores de Risco , Texas/epidemiologia , Teste Tuberculínico/estatística & dados numéricos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , População Branca , Adulto JovemRESUMO
A new actinomycete strain designated MITKK-103 was isolated from the soil of a flowerpot using a humic acid agar medium. The newly isolated strain was able to produce a large amount of actinomycin X2 even under nonoptimized growing conditions and serves as a promising source of this antibiotic. Actinomycin X2 has higher cytotoxicity toward cultured human leukemia (HL-60) cells than does actinomycin D, and it induces cell death via apoptosis. A nearly complete 16S ribosomal DNA (rDNA) sequence from the isolate was determined and found to have high identity (98.5-100%) with Streptomyces galbus, Streptomyces griseofuscus, and Streptomyces padanus, indicating that MITKK-103 belongs to the genus Streptomyces. The isolate clustered with species belonging to the S. padanus clade in a 16S-rDNA-based phylogenetic tree and showed 75% overall homology to S. padanus ATCC 25646 in DNA-DNA relatedness analysis. Although the growth of the isolate was somewhat different from the three species mentioned, the strain MITKK-103 most closely resembles S. padanus on the basis of the morphological and phenotypic characteristics, phylogenetic analysis, and genotypic data. As such, this is the first report of a strain of S. padanus capable of producing actinomycins.
Assuntos
Dactinomicina/análogos & derivados , Microbiologia do Solo , Streptomyces/metabolismo , Técnicas de Tipagem Bacteriana , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dactinomicina/biossíntese , Dactinomicina/toxicidade , Células HL-60 , Humanos , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Filogenia , Pigmentos Biológicos/biossíntese , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Streptomyces/classificação , Streptomyces/isolamento & purificação , Streptomyces/ultraestruturaRESUMO
Histopathologic features of breast cancer such as tumour size, grade and axillary lymph node (LN) status variably reflect tumour biology and time. Recent evidence suggests that the biological character of breast cancer is established at an early stage and has a major impact on clinical course. The aim of this study was to distinguish the impact of biology on breast cancer histopathology by comparing features of breast cancers diagnosed following population mammographic screening with prevalent vs incident detection and screening interval. Central histopathology review data from 1147 cases of ductal in situ and/or invasive breast cancer were examined. Size, grade and LN status of invasive cancers were positively correlated (P < 0.001). Prevalent invasive cancers were larger (P < 0.001) and more likely to be LN positive (P = 0.02) than incident cases, but grade was not associated with screening episode (P = 0.7). Screening interval for incident cancers was positively associated with invasive cancer size (P = 0.05) and LN status (P = 0.002) but not grade (P = 0.1). Together, these data indicate that biology and time both impact on size and LN status of invasive breast cancer, but grade reflects biology alone. In view of the clinical importance of breast cancer biology, grade as its most direct indicator assumes particular significance.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Programas de Rastreamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática/patologia , Mamografia , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Trophic factors have been found to play a significant role both in long-term survival processes and in more rapid and dynamic processes in the brain and spinal cord. However, little is known regarding the regulation of expression of growth factors, and how these proteins interact on a cell-to-cell basis. We have studied protein levels of one growth factor known to affect the noradrenergic innervation of the hippocampal formation, namely brain-derived neurotrophic factor (BDNF). The purpose of the present study was to determine if appropriate innervation or contact between the LC noradrenergic neurons and their target, the hippocampus, affects expression of this growth factor in either brain region. Fetal brain stem tissue, containing the LC, and hippocampal formation were dissected from embryonic day 17 rat fetuses and transplanted together or alone into the anterior chamber of the eye of adult Fisher 344 rats. The tissue was grown together for 6 weeks, after which the animals were sacrificed and ELISAs for BDNF were undertaken. Transplantation to the anterior chamber of the eye increased the expression of BDNF in the hippocampal but not the brain stem tissue, compared with levels observed in fetal and adult rats in vivo. In addition, double grafting with hippocampal tissue more than tripled BDNF levels in brain stem grafts and doubled BDNF levels in the hippocampal portion of double grafts compared with hippocampal single grafts. Triple grafts containing basal forebrain, hippocampus, and brain stem LC tissue increased brain stem and hippocampal BDNF levels even further. Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels to levels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.
Assuntos
Câmara Anterior/cirurgia , Transplante de Tecido Encefálico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transplante de Tecido Fetal , Sistema Nervoso/embriologia , Animais , Colchicina/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/transplante , Locus Cerúleo/citologia , Locus Cerúleo/metabolismo , Locus Cerúleo/transplante , Sistema Nervoso/metabolismo , Gravidez , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Septo do Cérebro/metabolismo , Septo do Cérebro/transplanteRESUMO
Trophic factors have been found to play a significant role both in long-term survival processes and in more rapid and dynamic processes in the brain and spinal cord. However, little is known regarding the regulation of expression of growth factors, and how these proteins interact on a cell-to-cell basis. We have studied protein levels of one growth factor known to affect the noradrenergic innervation of the hippocampal formation, namely brain-derived neurotrophic factor (BDNF). The purpose of the present study was to determine if appropriate innervation or contact between the LC noradrenergic neurons and their target, the hippocampus, affects expression of this growth factor in either brain region. Fetal brain stem tissue, containing the LC, and hippocampal formation were dissected from embryonic day 17 rat fetuses and transplanted together or alone into the anterior chamber of the eye of adult Fisher 344 rats. The tissue was grown together for 6 weeks, after which the animals were sacrificed and ELISAs for BDNF were undertaken. Transplantation to the anterior chamber of the eye increased the expression of BDNF in the hippocampal but not the brain stem tissue, compared with levels observed in fetal and adult rats in vivo. In addition, double grafting with hippocampal tissue more than tripled BDNF levels in brain stem grafts and doubled BDNF levels in the hippocampal portion of double grafts compared with hippocampal single grafts. Triple grafts containing basal forebrain, hippocampus, and brain stem LC tissue increased brain stem and hippocampal BDNF levels even further. Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels to levels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.
RESUMO
With rising numbers of single-parent families, a phenomenon becoming increasingly prevalent is the child orphaned by cancer. We sought to examine issues related to custody planning addressed prior to the patient's death. Ten deceased patients with minor children were identified. The contact person was administered a brief questionnaire regarding the minor children and custody issues. The study involved twenty children, ages ranging from 3-20, mean age 9.8. Only five of the ten families developed custody plans that were ultimately successful. One-half of the families reported the patient had suffered with this issue and almost one-half of the children were not aware of the custody plans that had been arranged for them. In 40% of the cases, the children ultimately went to people to whom the deceased parents were opposed. It is our belief that if we can improve these statistics, we might improve the quality of life of these families.
Assuntos
Assistência de Custódia , Neoplasias/tratamento farmacológico , Pais Solteiros/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Twenty-eight laboratories evaluated a new fluorescence in situ hybridization (FISH) strategy for chronic myeloid leukemia. In a three-part study, bcr/abl1 D-FISH probes were used to study bone marrow specimens. First, laboratories familiarized themselves with the strategy by applying it to known normal and abnormal specimens. Then, collectively the laboratories studied 20 normal and 20 abnormal specimens blindly and measured workload. Finally, each laboratory and two experts studied six serial dilutions with 98-0% abnormal nuclei. Using the reported normal cutoff of < 1% abnormal nuclei, participants reported no false-negative cases and 15 false-positive cases (1-6.6% abnormal nuclei). Results provided by participants for serial dilutions approximated the expected percentages of abnormal nuclei, but those from the experts exhibited greater precision. The clinical sensitivity, precision, nomenclature, workload, recommendations for training, and quality assurance in methods using D-FISH in clinical practice are discussed.
Assuntos
Técnicas de Laboratório Clínico/normas , Proteínas de Fusão bcr-abl/genética , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Medula Óssea/patologia , Corantes Fluorescentes , Humanos , Hibridização in Situ Fluorescente/instrumentação , Hibridização in Situ Fluorescente/métodos , Hibridização in Situ Fluorescente/normas , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Controle de Qualidade , Sensibilidade e Especificidade , Carga de TrabalhoRESUMO
Defined insertion mutations have been constructed in the Rhizobium (Sinorhizobium) meliloti phbC gene, which encodes poly-beta-hydroxybutyrate (PHB) synthase. The locus was isolated and subcloned from a genomic library of R. meliloti Rm1021 by complementation of phbC mutation of Alcaligenes eutrophus. PHB production was detected in wild-type R. meliloti under nutrient-limited conditions but not in rich medium. No PHB production was detected in the R. meliloti phbC mutants. The DNA sequence of the R. meliloti phbC gene was determined. The deduced polypeptide sequence is homologous to previously identified PhbCs from other bacteria. The R. meliloti phbC locus maps to pRmeSU47a, the smaller of the two megaplasmids in this strain.
Assuntos
Aciltransferases/genética , Dopamina beta-Hidroxilase/metabolismo , Sinorhizobium meliloti/genética , Acetonitrilas/metabolismo , Aciltransferases/metabolismo , Alcaligenes/enzimologia , Alcaligenes/genética , Sequência de Bases , Clonagem Molecular , Dopamina beta-Hidroxilase/genética , Genes Bacterianos/genética , Hidroxibutiratos/metabolismo , Dados de Sequência Molecular , Mutagênese Insercional , Fases de Leitura Aberta , Poliésteres/metabolismo , Sinorhizobium meliloti/classificação , Sinorhizobium meliloti/enzimologiaRESUMO
A visually pleasing chin is an important component of facial harmony. This study was undertaken to introduce a practical classification of chin dysmorphology, which can be used to guide the surgeon toward the appropriate surgical approach to chin repair. Analysis of life-size photography, based on standard anthropometric measurements, was completed on 2,879 patients from 1981 to 1991. Six hundred eighty-four patients were noted to have normal occlusion with some form of chin deformity. Analysis of this group of patients identified seven categories of chin dysmorphism: Class I, macrogenia (n = 170, 24.9%); Class II, microgenia (n = 435, 63.6%); Class III, combination of macrogenia in one direction and microgenia in the other direction (n = 54, 7.9%); Class IV, asymmetry (n = 4, 0.6%); Class V, soft tissue ptosis ("witch's chin") (n = 13, 1.9%); Class VI, pseudomacrogenia (normal skeletal symphysis menti with excess soft tissue covering) (n = 5, 0.73%); and Class VII, pseudomicrogenia (long-face deformity producing clockwise rotation of the normal mandible) (n = 3, 0.4%). Having diagnosed the dysmorphism, logical surgical recommendations for lower face improvement were postulated. Only patients with Class II chin deformity can be corrected with augmentation. Classes I, III, and IV require an osteotomy of the chin. Classes V and VI benefit from soft tissue correction. Class VII deformity can be corrected with a maxillary osteotomy.
Assuntos
Cefalometria/classificação , Queixo/anormalidades , Adolescente , Adulto , Idoso , Queixo/cirurgia , Estética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Fotogrametria , Cirurgia PlásticaRESUMO
I-131 is used to image patients diagnosed with papillary or follicular carcinoma of the thyroid after thyroidectomy to observe for metastatic disease or residual thyroid tissue. I-131 is excreted in gastric mucosa and is seen in the esophagus after the swallowing of saliva. The authors describe a patient in whom radiopharmaceutical activity in the mediastinum was subsequently shown to be due to a hiatal hernia.
Assuntos
Carcinoma Papilar/diagnóstico por imagem , Hérnia Hiatal/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Radioisótopos do Iodo , Mediastino/diagnóstico por imagem , Cintilografia , Pertecnetato Tc 99m de Sódio , TireoidectomiaRESUMO
Attenuated mutants of Venezuelan equine encephalitis virus (VEE) were isolated by selection for rapid penetration of cultured cells (R. E. Johnston and J. F. Smith, 1988, Virology 162, 437-443). Sequence analysis of these mutants identified candidate attenuating mutations at four loci in the VEE E2 glycoprotein gene: a double mutation at E2 codons 3 and 4, and single substitutions at E2 76, 120, and 209. Each candidate mutation was reproduced in an isogenic recombinant VEE strain using site-directed mutagenesis of a full-length cDNA clone of VEE. Characterization of these molecularly cloned mutant viruses showed that mutation at each of the four loci in the E2 gene was sufficient to confer both the accelerated penetration and attenuation phenotypes. Inoculation of the molecularly cloned viruses into rodent models that differ in their response to VEE suggested that individual mutations affected different aspects of VEE pathogenesis. Full-length clones containing multiple mutations were produced by combining independently attenuating mutations. Molecularly cloned viruses carrying two or three mutations were more attenuated in sensitive animal models than viruses which contained any single mutation alone. However, these highly attenuated strains still retained the ability to induce an immune response sufficient to protect against a high dose challenge with virulent VEE. These results indicate that production of a molecularly cloned live virus vaccine for VEE is feasible.
Assuntos
DNA Viral/genética , Genes Virais , Proteínas do Envelope Viral/genética , Proteínas Estruturais Virais/genética , Animais , Anticorpos Antivirais/biossíntese , Antígenos Virais/imunologia , Clonagem Molecular , Cricetinae , Cricetulus , Camundongos , Mutagênese Sítio-Dirigida , Vacinas Atenuadas , Virulência/genéticaRESUMO
One hundred and fifteen previously untreated adults aged over 60 years were referred to St Bartholomew's Hospital between 1978 and 1986 for management of acute myeloid leukemia (AML). Twenty-seven patients received symptomatic or palliative treatment only because combination chemotherapy was considered inappropriate. Eighty-eight patients received intensive chemotherapy with curative intent. There was a 48 per cent 'early death' rate and a 24 per cent incidence of resistant disease; complete remission (CR) was achieved in 25/88 patients (28 per cent). By multivariate analysis, a blast count less than 50 x 10(9)/l at presentation was the only factor predictive for achievement of CR whilst the latter and a presentation blast count less than 50 x 10(9)/l predicted for superior survival. Treatment was often curtailed on account of unacceptable toxicity; only 2/88 patients received the planned six cycles of treatment. Two patients died in CR. Four patients are alive in first CR at 3-9 years from treatment; one is alive in second CR following meningeal relapse. Overall survival was significantly worse than that of a contemporaneous group of adults aged 15-59 years treated at this hospital, but duration of CR was comparable. There are great difficulties involved in the intensive treatment of AML in elderly adults, but the major survival benefit gained by achieving CR should stimulate the search for better tolerated but still curative regimens.