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1.
Artigo em Inglês | MEDLINE | ID: mdl-38093136

RESUMO

PURPOSE: In the Netherlands, approximately 70% of severely injured patients (ISS ≥ 16) are transported directly to a Level I trauma center. This study compared the time needed to return to normal vital parameters and normal acid-base status in severely injured patients and some in-hospital processes in Level I versus Level II trauma centers. METHODS: This retrospective cohort study included all adult severely injured patients or adult trauma patients admitted to the intensive care unit between 2015 and 2020 in a Dutch trauma region. The primary endpoint was time until normal vital parameters and acid-base status. Secondary endpoints were complication rate, hospital length of stay, emergency department length of stay, and time until a computed tomography (CT) scan. RESULTS: A total of 2345 patients were included. Patients admitted to a Level I trauma center had a significantly higher rate of normalization of vital parameters over time (HR 1.51). There was no significant difference in normalization rate of the acid-base status over time (HR 1.10). In Level I trauma centers, time spent at the emergency department and time until the CT scan was significantly shorter (respectively, ß - 38 min and ß - 77 min), and the complication rate was significantly lower (OR 0.35). CONCLUSION: Severely injured patients admitted to a Level I trauma center require less time to normalize their vital functions. Level I centers are better equipped, resulting in better in-hospital processes with shorter time at the emergency department and shorter time until a CT scan.

2.
Injury ; 54(7): 110734, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37137737

RESUMO

BACKGROUND: Intraoperative 3D fluoroscopy (3DRX) is increasingly used in fracture management instead of conventional fluoroscopy (RX), but its effect on the treatment and outcome of tibial plateau fractures (TFs) is not well known. This study aims to evaluate whether the use of 3DRX in the treatment of tibial plateau fractures reduces the number of revision surgeries. METHODS: This retrospective cohort study includes all patients who underwent surgical treatment for TF in a single center from 2014 to 2018. Patient-, fracture-, and treatment characteristics were compared between the 3DRX and RX subgroups. The primary endpoint was the number of patients requiring revision surgery. Secondary endpoints were surgery duration, hospital length of stay, radiation exposure, postoperative complications, and secondary total knee arthroplasty. RESULTS: Eighty-seven patients were included, of which 36 were treated with 3DRX. Three patients in the RX group required revision surgery, while no revision surgery was performed in the 3DRX group (p = 0.265). The use of 3DRX resulted in significantly more intraoperative adjustments (25% versus 6%; p = 0.024) and an increase in surgery duration (by average of 28 min, p = 0.001), without a significant increase in postoperative wound infections (12% versus 19%; p = 0.374) or fracture-related infections (2% versus 2.8%; p = 0.802). The 3DRX group had an average radiation exposure of 7,985 mGy versus 1,273 mGy in the RX group (p<0.001). The hospital length of stay was 1 day shorter in the 3DRX group (5 days versus 4 days; p = 0.058). CONCLUSIONS: Implementing 3DRX in treating TFs improves the assessment of fracture alignment and implant position perioperatively, resulting in more intraoperative corrections and no revision surgeries within 6 weeks postoperatively. However, using 3DRX significantly increases perioperative radiation exposure and surgery duration without a significant rise in postoperative infections and a shorter hospital length of stay.


Assuntos
Exposição à Radiação , Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fluoroscopia/métodos , Hospitalização , Resultado do Tratamento
3.
Value Health ; 26(8): 1235-1241, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36878312

RESUMO

INTRODUCTION: Patient-Reported Outcomes Measurement Information System (PROMIS) enables the use of computer adaptive testing (CAT). The aim of this prospective cohort study was to compare the most commonly used disease-specific instruments with PROMIS CAT questionnaires in patients with trauma. METHODS: All patients with trauma (ages 18-75) who underwent an operative intervention for an extremity fracture between June 1, 2018, and June 30, 2019, were included. The disease-specific instruments were the Quick Disabilities of the Arm, Shoulder, and Hand for upper extremity fractures and the Lower Extremity Functional Scale (LEFS) for lower extremity fractures. Pearson's correlation (r) between the disease-specific instruments and the PROMIS CAT questionnaires (PROMIS Physical Function, PROMIS Pain Interference, and PROMIS Ability to Participate in Social Roles and Activities) was calculated at week 2, week 6, month 3, and month 6. Construct validity and responsiveness were calculated. RESULTS: A total of 151 patients with an upper extremity fracture and 109 patients with a lower extremity fracture were included. At month 3 and month 6, the correlation was strong between the LEFS and PROMIS Physical Function (r = 0.88 and r = 0.90, respectively), and at month 3, the correlation was strong between the LEFS and PROMIS Social Roles and Activities (r = 0.72). At week 6, month 3, and month 6, there was a strong correlation between the Quick Disabilities of the Arm, Shoulder, and Hand and PROMIS Physical Function (r = 0.74, r = 0.70, and r = 0.76, respectively). CONCLUSIONS: The PROMIS CAT measures are acceptably related to existing non-CAT instruments and may be a useful tool during follow-up after operative interventions for extremity fractures.


Assuntos
Fraturas Ósseas , Medidas de Resultados Relatados pelo Paciente , Humanos , Estudos Prospectivos , Extremidade Superior/cirurgia , Extremidade Superior/lesões , Computadores , Fraturas Ósseas/cirurgia , Sistemas de Informação
4.
PLoS One ; 16(6): e0252673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34086788

RESUMO

BACKGROUND: Through improvements in trauma care there has been a decline in injury mortality, as more people survive severe trauma. Patients who survive severe trauma are at risk of long-term disabilities which may place a high economic burden on society. The purpose of this study was to estimate the health care and productivity costs of severe trauma patients up to 24 months after sustaining the injury. Furthermore, we investigated the impact of injury severity level on health care utilization and costs and determined predictors for health care and productivity costs. METHODS: This prospective cohort study included adult trauma patients with severe injury (ISS≥16). Data on in-hospital health care use, 24-month post-hospital health care use and productivity loss were obtained from hospital registry data and collected with the iMTA Medical Consumption and Productivity Cost Questionnaire. The questionnaires were completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to investigate the drivers of health care and productivity costs. RESULTS: In total, 174 severe injury patients were included in this study. The median age of participants was 55 years and the majority were male (66.1%). The mean hospital stay was 14.2 (SD = 13.5) days. Patients with paid employment returned to work 21 weeks after injury. In total, the mean costs per patient were €24,760 with in-hospital costs of €11,930, post-hospital costs of €7,770 and productivity costs of €8,800. Having an ISS ≥25 and lower health status were predictors of high health care costs and male sex was associated with higher productivity costs. CONCLUSIONS: Both health care and productivity costs increased with injury severity, although large differences were observed between patients. It is important for decision-makers to consider not only in-hospital health care utilization but also the long-term consequences and associated costs related to rehabilitation and productivity loss.


Assuntos
Efeitos Psicossociais da Doença , Ferimentos e Lesões/economia , Adolescente , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/economia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Retorno ao Trabalho/economia , Ferimentos e Lesões/patologia , Adulto Jovem
5.
BMJ Open ; 11(1): e038707, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408198

RESUMO

OBJECTIVES: To determine prognostic factors for health status and recovery patterns during the first 2 years after injury in the clinical trauma population. DESIGN: A prospective longitudinal cohort study. SETTING: Ten participating hospitals in Brabant, the Netherlands. PARTICIPANTS: Injured adult patients admitted to a hospital between August 2015 and November 2016 were followed: 4883 (50%) patients participated. MAIN OUTCOME MEASURES: Primary outcome was health status, measured with the EuroQol-5-dimensions-3-levels (EQ-5D), including a cognition item and the EuroQol Visual Analogue Scale. Health status was collected at 1 week, 1, 3, 6, 12 and 24 months after injury. Potential prognostic factors were based on literature and clinical experience (eg, age, sex, pre-injury frailty (Groningen Frailty Index), pre-injury EQ-5D). RESULTS: Health status increased mainly during the first 6 months after injury with a mean EQ-5D utility score at 1 week of 0.49 and 0.79 at 24 months. The dimensions mobility, pain/discomfort and usual activities improved up to 2 years after injury. Lower pre-injury health status, frailty and longer length of stay at the hospital were important prognostic factors for poor recovery. Spine injury, lower and upper extremity injury showed to be prognostic factors for problems after injury. Traumatic brain injury was a prognostic factor for cognitive problems. CONCLUSION: This study contributes to the increase in knowledge of health recovery after injury. It could be a starting point to develop prediction models for specific injury classifications and implementation of personalised medicine. TRIAL REGISTRATION NUMBER: NCT02508675.


Assuntos
Nível de Saúde , Qualidade de Vida , Adulto , Estudos de Coortes , Humanos , Estudos Longitudinais , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos
6.
Injury ; 51(12): 2953-2961, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33008635

RESUMO

BACKGROUND: With the improved survival rates after trauma, the population of patients with disabilities increased. The knowledge about functional outcome and the relationship between health status and functional outcome is limited. The aim of the present prospective cohort study was to describe the functional outcome and health status over time, and the relationship between both. METHODS: Adult severely injured patients (ISS≥16) were included if hospitalised in Noord-Brabant within 48 h after injury between August 2015 and December 2016. The functional outcome (Glasgow Outcome Scale Extended - GOSE) and health status (EQ-5D) were measured at 1, 3, 6, 12 and 24 months after injury. Logistic and linear mixed models were used to examine functional outcome and health status over time. Measurements were divided into short- (1-3 months), mid- (6-12 months) and long-term (24 months). RESULTS: In total 239 severely injured patients were included. Functional outcome and health status improved over time. Prognostic factors during two years were a longer hospital length of stay, female gender and Glasgow Coma Scale. Besides age was a prognostic factor for health status and education level for functional outcome. A higher ASA classification was a long-term prognostic factor for a lower functional outcome and a lower health status. The patients with a good functional recovery showed a significant higher EQ-5D utility score and patients with a poor functional recovery reported significant more problems in the EQ-5 domains. CONCLUSION: There is a good relationship between the functional outcome and the health status during two years after a severe injury. It appears reliable to use functional outcome in terms of physical impairments in daily clinic to determine patients at risk for both a lower functional outcome and a lower health status over time.


Assuntos
Pessoas com Deficiência , Qualidade de Vida , Adulto , Feminino , Escala de Resultado de Glasgow , Nível de Saúde , Humanos , Estudos Prospectivos
7.
Injury ; 50(10): 1678-1683, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31337494

RESUMO

BACKGROUND: The implementation of trauma systems has led to a significant reduction in mortality and length of hospital stay. In our level I trauma centre, 24/7 in-hospital coverage was implemented, and a renovation of the trauma room took place to improve the trauma care. The aim of the present study was to examine the effect of the optimised in-hospital infrastructure in terms of mortality, processes and clinical outcomes. METHODS: We performed a retrospective cohort study of prospectively collected data. All adult trauma patients admitted to our trauma centre directly during two time periods (2010-2012 and 2014-2016) were included. Any patients below the age of 18 years and patients who underwent primary trauma screening in another hospital were excluded. Logistic and linear regression were used and adjusted for demographics and characteristics of trauma. The primary endpoint was mortality. The secondary endpoints were subgroups of earlier mortality rates and severely injured patients, processes and clinical outcomes. RESULTS: In period I, 1290 patients were included, and in period II, 2421. The adjusted mortality in the trauma room (odds ratio (OR): 0.18; CI: 0.05-0.63) and the total in-hospital mortality (OR: 0.63 CI: 0.42-0.95) showed a significant reduction in period II. The trauma room (TR) time decreased by 30 min (p < 0.001), and the time until CT decreased by 22 min (p < 0.001). The number of delayed diagnoses and complications were significantly lower in the second period, with an OR of 0.2 (CI: 0.1-0.2) and 0.4 (CI: 0.3-0.6), respectively. The hospital length of stay and ICU length of stay decreased significantly, -1.5 day (p = 0.010) and -1.8 days (p = 0.022) respectively. CONCLUSIONS: Optimisation of the in-hospital infrastructure related to trauma care resulted in improved survival rates in both severely injured patients as well as in the whole trauma population. Moreover, the processes and clinical outcomes improved, showing a shorter hospital length of stay, shorter TR time, fewer complications and fewer delayed diagnoses.


Assuntos
Cuidados Críticos/organização & administração , Recursos em Saúde/organização & administração , Centros de Traumatologia/organização & administração , Ferimentos e Lesões/terapia , Adulto , Cuidados Críticos/normas , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Taxa de Sobrevida , Tomógrafos Computadorizados/provisão & distribuição , Ferimentos e Lesões/mortalidade
8.
Methods Inf Med ; 46(1): 70-3, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17224985

RESUMO

OBJECTIVES: To determine whether self-directed learning about (electronic) patient records during a PBL (problem-based learning) block, dealing with the content of disciplines concerned with the diagnosis and therapy of diseases of the abdomen, increased the knowledge of the students with respect to the patient records. METHODS: At the beginning and at the end of the ten-week block the same questionnaire was offered to the students (180). Cohen's d for effect size was used to determine the increase in knowledge. RESULTS: For those students that answered the questionnaire twice (53), a Cohen's d of 0.94 was obtained. CONCLUSIONS: The knowledge of the students concerning the advantages and limitations of (electronic) patient records increased significantly. The corresponding effect size was large.


Assuntos
Educação de Graduação em Medicina/métodos , Informática Médica/educação , Sistemas Computadorizados de Registros Médicos , Aprendizagem Baseada em Problemas , Avaliação de Programas e Projetos de Saúde , Abdome/patologia , Currículo , Sistemas de Apoio a Decisões Clínicas , Avaliação Educacional , Humanos , Países Baixos , Faculdades de Medicina , Inquéritos e Questionários
9.
J Neurol ; 253(3): 372-6, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16283101

RESUMO

INTRODUCTION: We developed structured descriptions of signs and symptoms for specific seizure types (called Diagnostic Reference Frames-DRFs-by us) that can serve as a frame of reference in the process of classifying patients with epileptic seizures. In this study the validity of the DRFs for clinical use is evaluated and described. MATERIAL AND METHODS: In this study we use a decision support system based on the DRFs and using Bayes's rule for the validation of the DRFs. Patient's manifestations are entered in the decision support system and by successively applying Bayes's rule posterior probabilities are calculated. The DRFs with the highest posterior probability gives an indication of the classification of the seizure. The validation of the DRFs was performed by comparing the seizure type with the highest posterior probability with the classification of experienced epileptologists on a series of test cases with known epileptic seizures. In this way we assessed the accuracy of the DRFs in classifying patients with epileptic seizures. RESULTS: We included sixty-six patients in this efficacy study. The patients and/or their relatives described the manifestations occurring during a seizure. Sixty cases (91%) were correctly classified using the decision support system. DISCUSSION: The accuracy of 91 % indicates that the knowledge encoded in the DRFs for the included seizure types is valid. The next step is to test the DRFs in a clinical setting to evaluate the applicability in daily practice.


Assuntos
Convulsões/classificação , Convulsões/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Diagnóstico Diferencial , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes
10.
Med Phys ; 26(2): 310-8, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10076990

RESUMO

Motion and deformation of the cardiac wall may be measured by following the positions of implanted radiopaque markers in three dimensions, using two x-ray cameras simultaneously. Regularly, calibration of the position measurement system is obtained by registration of the images of a calibration object, containing 10-20 radiopaque markers at known positions. Unfortunately, an accidental change of the position of a camera after calibration requires complete recalibration. Alternatively, redundant information in the measured image positions of stereo pairs can be used for calibration. Thus, a separate calibration procedure can be avoided. In the current study a model is developed that describes the geometry of the camera setup by five dimensionless parameters. Maximum Likelihood (ML) estimates of these parameters were obtained in an error analysis. It is shown that the ML estimates can be found by application of a nonlinear least squares procedure. Compared to the standard unweighted least squares procedure, the ML method resulted in more accurate estimates without noticeable bias. The accuracy of the ML method was investigated in relation to the object aperture. The reconstruction problem appeared well conditioned as long as the object aperture is larger than 0.1 rad. The angle between the two viewing directions appeared to be the parameter that was most likely to cause major inaccuracies in the reconstruction of the 3-D positions of the markers. Hence, attempts to improve the robustness of the method should primarily focus on reduction of the error in this parameter.


Assuntos
Coração/diagnóstico por imagem , Coração/fisiologia , Processamento de Imagem Assistida por Computador , Fenômenos Biomecânicos , Calibragem , Simulação por Computador , Humanos , Funções Verossimilhança , Radiografia
11.
J Biomech ; 30(1): 95-8, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8970931

RESUMO

Motion and deformation of an object may be quantified by following attached markers in video or cine frame sequences. When recording cardiac motion by video (256 x 256 pixels, 50 Hz), generally no more than approximately 20 markers can be followed due to difficulties in proper identification of marker images. In the present study we developed the lower rank (LR) tracking method which can automatically follow considerably more than 20 markers. The performance of the method was evaluated in computer simulations of naturally moving myocardial markers observed in a sequence of 60 video frames. White noise was added to the marker coordinates. Realistic loss of data due to detection failure was simulated by deleting a generated marker image when the distance to another marker image was below a given minimum value. In a test, realistic values were substituted for the noise level sigma (0.5 pixel) and the minimum marker distance dm (4 pixels). For numbers of markers ranging from 50 to 100, 95-90% of the detected marker images was correctly tracked. Less than 0.7% was part of a false track, i.e. a track containing images of different markers. Under less favourable conditions (sigma = 1 pixel; dm = 8 pixels) the method was robust: for 75 markers with 40% of the marker images missing, still 70% of the detected images was correctly tracked, while the fraction in false tracks did not increase. The LR tracking method appears reliable for automatic tracking of large amounts of moving markers in a sequence of video or cine frames.


Assuntos
Coração/fisiologia , Processamento de Imagem Assistida por Computador , Algoritmos , Fenômenos Biomecânicos , Cinerradiografia , Simulação por Computador , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Modelos Cardiovasculares , Movimento (Física) , Função Ventricular , Gravação em Vídeo
12.
Int J Biomed Comput ; 33(3-4): 219-39, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8307654

RESUMO

Motion and deformation of an object such as the heart may be measured by tracking optical or radiopaque markers. In the experimental situation markers may fail to be detected due to occlusion or lack of contrast. As a result a continuous marker track is observed in separated parts, which often cannot be directly identified as corresponding to one marker. This paper presents a method of extrapolating a partly known track by using information provided by the known track part and the available complete tracks of other markers. The extrapolations are obtained by iteratively fitting a lower rank matrix to the set of noisy, incomplete marker tracks. The performance is evaluated with computer-simulated data and data obtained in an animal experiment. In both cases 43% of the available complete tracks were made incomplete by removal of track parts varying in length from 3% up to 44%. For the simulated data comparison of the extrapolations with true signal values results in a root mean square (RMS) error about equal to the noise level. For the animal experiment, when comparing the extrapolations with the measured values, in images of 256 x 256 pixels, the RMS error was found to be +/- 0.5 pixel, which is quite small relative to the total excursion of a marker (20 pixels). Estimation of the missing data by applying BMDPAM (BMDP Statistical Software Inc.) to the same data results in RMS errors which are about twice as high.


Assuntos
Coração/diagnóstico por imagem , Coração/fisiologia , Processamento de Imagem Assistida por Computador , Interpretação de Imagem Radiográfica Assistida por Computador , Processamento de Sinais Assistido por Computador , Algoritmos , Animais , Cinerradiografia , Simulação por Computador , Cães , Modelos Estatísticos , Contração Miocárdica , Gravação de Videoteipe
13.
Vaccine ; 11(6): 675-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8322492

RESUMO

Coinfection of a cell with two different types of enveloped virus can result in the generation of infectious virus particle pseudotypes having the internal proteins of one virus and the envelope proteins of the other virus. Vaccinia virus recombinants expressing either non-infectious virus-like particles of simian immunodeficiency virus (SIV) or the gD2 glycoprotein of herpes simplex virus were used to coinfect cells to determine if virus-like particle pseudotypes would be formed. Sucrose gradient sedimentation analysis and immunoprecipitation with a monoclonal antibody provided independent evidence of virus-like particle pseudotype formation. Preparations of such particles were immunogenic in mice. Recombinant-expressed virus-like particles thus represent a novel vaccine approach to presenting envelope glycoprotein antigens in a non-infectious state that mimics natural infection.


Assuntos
Anticorpos Antivirais/biossíntese , Vírus da Imunodeficiência Símia/imunologia , Vacinas Sintéticas/imunologia , Vaccinia virus/genética , Proteínas do Envelope Viral/imunologia , Vírion/imunologia , Animais , Linhagem Celular , Produtos do Gene gag/imunologia , Produtos do Gene pol/imunologia , Camundongos , Plasmídeos , Testes de Precipitina , Vaccinia virus/imunologia
14.
Vaccine ; 11(1): 43-53, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8427036

RESUMO

A simple yet powerful selection system was developed for the insertion of foreign genes in vaccinia virus. The selection system utilizes the vaccinia virus K1L (29K) host range gene which is located in HindIII M. This gene is necessary for growth in RK-13 cells but not in BSC40 or CV-1 cells. A vaccinia mutant (vAbT33) unable to grow on RK-13 cells was constructed having sequences at the 3' end of the K1L gene and the adjacent M2L gene deleted and replaced with the beta-galactosidase gene regulated by the BamHI F (F7L) promoter. A recombination plasmid containing the hepatitis B surface (HBs) antigen gene regulated by the M2L promoter and the complete sequence of the K1L gene was used to insert the HBs gene into vAbT33. The M2L negative K1L positive recombinant was easily isolated in two rounds of plaque purification by plating the virus on RK-13 cell monolayers. The K1L gene selection system allows the isolation of recombinants arising at frequencies as low as 1/100,000. It was noted that recombinants containing vaccinia sequence duplications (promoters) resulted in intragenomic recombinations that eliminated all sequences between the duplications. A second recombination plasmid was constructed that allowed insertion into the vaccinia genome without the loss of vaccinia coding sequences. This was achieved by insertion of the pseudorabies virus GIII gene regulated by the vaccinia H5R (40K) promoter between the translation and transcription stop signals at the 3' end of the K1L gene. The K1L gene transcription stop signal thus became the stop signal for the inserted GIII gene and an upstream transcription stop signal present in the H5R promoter fragment provided the stop signal for the K1L gene. This manipulation of the vaccinia genome had no effect on the accumulation or 5' end of the M2L gene transcripts. Although the insertion lengthened the 3' end and lowered the accumulation of K1L transcripts it altered neither the virulence nor the immunogenicity of the recombinant.


Assuntos
Vaccinia virus/genética , Vaccinia virus/imunologia , Sequência de Bases , DNA Viral/genética , Genes Virais , Vetores Genéticos , Dados de Sequência Molecular , Família Multigênica , Mutagênese Insercional , Plasmídeos , Recombinação Genética , Vacinas Sintéticas/isolamento & purificação , Vaccinia virus/patogenicidade , Vacinas Virais/isolamento & purificação , Virulência/genética
15.
J Virol ; 66(5): 2617-30, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1560521

RESUMO

These studies demonstrated that the inbred BALB/c mouse strain can be optimized for the assessment of vaccinia virus virulence, growth, and spread from the site of inoculation and immune protection from a lethal vaccinia virus challenge. The studies established that manipulation of the vaccinia virus genome generated mutants exhibiting a wide range of attenuated phenotypes. The nine NYCBH vaccinia virus mutants had intracranial 50% lethal doses that ranged from 2 to greater than 7 log10 units. The decreased neurovirulence was due to decreased replication in brain tissue. Three mutants had a decreased ability to disseminate to the lungs, brains, livers, and spleens of mice after intranasal infection. One mutant had a decreased transmission from mice infected by tail scarification to naive cage mates. Although the mutants, with one exception, grew to wild-type titers in cell culture, they showed a growth potential on the scarified skin of mice that was dramatically different from that of the wild-type virus. Consequently, all of the mutants had significantly compromised immunogenicities at low virus immunization doses compared with that of the wild-type virus. Conversely, at high immunization doses most mutants could induce an immune response similar to that of the wild-type virus. Three Wyeth vaccine strain mutants were also studied. Whereas the thymidine kinase, ribonucleotide reductase, and hemagglutinin mutants had a reduced virulence (50% lethal dose), only the thymidine kinase mutant retained its immunogenicity.


Assuntos
Vaccinia virus/genética , Vaccinia virus/patogenicidade , Vacínia/genética , Administração Intranasal , Animais , Anticorpos Antivirais , Encéfalo/microbiologia , Células Cultivadas , Modelos Animais de Doenças , Hemaglutininas/genética , Interações Hospedeiro-Parasita , Imunidade Ativa , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Endogâmicos BALB C , Mutagênese , Especificidade de Órgãos , Peptídeos/genética , Ribonucleotídeo Redutases/genética , Timidina Quinase/genética , Vacínia/imunologia , Vacínia/transmissão , Vaccinia virus/imunologia , Virulência
16.
Comput Biomed Res ; 25(2): 101-16, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1582188

RESUMO

An interactive Fortran program, MUCRA, is presented. The program can perform randomization analysis of a completely randomized or randomized-blocks design extended to growth and response curves. A single-step Scheffé-type procedure as well as the Peritz's closed step-down procedure have been implemented which control the familywise type I error-rate. In general, MUCRA is suitable as a computer tool for a distribution-free analysis of variance with repeated measures. The use of MUCRA is demonstrated by analyzing the effects oxprenolol and atenolol have on exercise heart rate. Oxprenolol is a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system. Atenolol is a beta 1-selective blocker without ISA. A randomized placebo-controlled crossover design was used to compare the effects of the beta 1-blockers on heart rate during a progressive maximal exercise test on a bicycle ergometer. Application of the Scheffé-type procedure showed that the two drugs significantly (alpha = .05) reduce the heart rate during the exercise test at the three prechosen times (2, 5, and 24 hr) after intake. The reduction from atenolol is more pronounced than from oxprenolol Oros at 2 and 5 hr.


Assuntos
Distribuição Aleatória , Software , Adulto , Atenolol/farmacologia , Exercício Físico/fisiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Oxprenolol/farmacologia , Design de Software
17.
Genetics ; 130(4): 771-90, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1582558

RESUMO

Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4; par-2 double mutant suggests that par-4 and par-2 gene products interact in this system.


Assuntos
Caenorhabditis/embriologia , Citoplasma/fisiologia , Genes Letais/genética , Animais , Caenorhabditis/genética , Diferenciação Celular/genética , Divisão Celular/genética , Genes Letais/fisiologia , Teste de Complementação Genética , Temperatura Alta , Mutação/genética , Oogênese/genética , Fenótipo
18.
Mol Gen Genet ; 221(1): 72-80, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2325632

RESUMO

The product of the maternally acting gene zyg-11 is required for early embryogenesis of Caenorhabditis elegans. One-cell embryos that lack a functional zyg-11 gene product exhibit an arrest of meiosis at metaphase II, a delay in the formation of pronuclei, unusually vigorous movements of cytoplasm, the formation of multiple pronuclei, incorrect segregation of P granules, and incorrect placement of the first cleavage furrow. We have isolated and sequenced a molecular clone of zyg-11, and shown that microinjection of the cloned DNA can rescue zyg-11 mutations. A transcriptional analysis shows that transcription of the gene is not limited to the female germ-line, despite the strict maternal-effect phenotype of zyg-11 mutations.


Assuntos
Caenorhabditis/genética , Genes , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Caenorhabditis/embriologia , Clonagem Molecular , DNA/genética , DNA/isolamento & purificação , Feminino , Meiose/genética , Microinjeções , Dados de Sequência Molecular , Mutação , Fenótipo , Mapeamento por Restrição , Transcrição Gênica
19.
Am J Physiol ; 258(2 Pt 2): H599-605, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2309920

RESUMO

Deformation of the cardiac wall is measured by using optical or radiopaque markers attached to the wall. When digitized images are used, the accuracy of the measurement of a marker position is limited by pixel resolution and the size of the marker. The spatial accuracy is improved by singular value decomposition (SVD) filtering. This filtering procedure is based on the assumption that displacements of markers are mutually related because they are embedded in a common continuum. In a computer stimulation with 48 markers in 51 video frames, the accuracy of the measurement of a marker position improved from 0.14 to 0.045 (SD) pixel. In an open-chest animal experiment, with markers on the surface of the heart, the deformation patterns were extracted more clearly using SVD filtering, while mutually related high-frequency components were not suppressed. In a 50-frame sequence of 256 X 256 video images of a 45 mm X 35 mm deforming surface with 50 markers of 8 pixels in diameter, the marker position resolution improves from 0.1 to 0.03 (SD) pixel (6 microns). Strain is determined with an accuracy of 0.002 over a distance of 30 pixels (6 mm).


Assuntos
Modelos Cardiovasculares , Animais , Simulação por Computador , Eletricidade , Matemática
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