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1.
Tijdschr Psychiatr ; 65(3): 202-204, 2023.
Artigo em Holandês | MEDLINE | ID: mdl-36951780

RESUMO

BACKGROUND: Hearing loss means a reduced access to a spoken language, depending on the severity and the possibility of hearing support. A sign language is on the other hand fully accessible. AIM: To describe the impact of hearing loss on mental health related to language ability. METHOD: From the literature a general picture will be presented of the impact of hearing loss on mental health. This is followed by a discussion of the influence of hearing loss on the prevalence and influence of diverse psychiatric conditions (schizophrenia, autism, depression/anxiety disorders). RESULTS: A relationship between mental health problems and hearing loss is evidenced. The use of a sign language seems to reduce the risk of a mental health problem in deaf individuals. CONCLUSION: The results have to be interpreted alongside the fact that research is based on relatively few countries. It is therefore not possible to generalize the results; cultural differences possibly exist. The relationship between language choice and language ability has not been studied in enough depth. More research and comparative research across countries is essential with full information on language choice/language ability.


Assuntos
Surdez , Perda Auditiva , Esquizofrenia , Humanos , Perda Auditiva/epidemiologia , Idioma , Língua de Sinais
2.
J Psychiatr Ment Health Nurs ; 20(5): 442-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22812505

RESUMO

This paper examines consumer or service user beliefs about the causes of mental illness. It presents a qualitative, participatory action research study involving semi-structured in-depth interviews with 16 people who had been diagnosed with a mental illness and attended a community mental health centre in metropolitan South Australia. Inductive thematic analysis was undertaken, with a range of beliefs about the possible cause of mental illness identified. Findings are organized within two key areas: social or environmental factors and physical or biological factors. The social or environmental category included varied situations, clustered under the subcategories of: stress during childhood, events in adulthood and religious beliefs. Physical or biological factors included beliefs that mental illness was inherited, caused by brain malfunction or chemical imbalance. Of note, one-third of consumer participants who discussed possible causes of mental illness identified multiple potential causes. Implications for service delivery, specifically related to therapeutic trust and engagement, are also considered.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Austrália do Sul
3.
Intern Med J ; 43(3): 308-16, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23176226

RESUMO

BACKGROUND: Warfarin-related intracerebral haemorrhage (WRICH) has high mortality. Haematoma expansion is prolonged in WRICH and independently predicts worse outcomes. Guidelines recommend prompt reversal of the warfarin coagulopathy, but evidence of benefit is lacking. AIMS: To determine whether the introduction of a WRICH reversal protocol (late 2008), which includes prothrombin complex concentrates (PCC), improves outcomes METHODS: All patients presenting with WRICH between January 2004 and July 2010 were included. Retrospective case note and radiology review was performed, collecting data on intracerebral haemorrhage (ICH) severity, degree and timeliness of reversal, and patient outcomes. Cox's proportional hazards analysis was used to compare outcomes associated with and without PCC after controlling for ICH severity. RESULTS: Eighty-eight patients were included (27 treated palliatively). Mean international normalised ratio was 2.9. Vitamin K, PCC and fresh frozen plasma were given alone or in combination to 68, 23 and 44 patients, and mean time from computed tomography scanning to administration was 2.2, 3.3 and 3.1 h respectively. Four patients received PCC pre-protocol (none before 2007), two during development and seventeen patients post-protocol. Those who received PCC had improved survival (P < 0.001). After controlling for ICH score, hazard ratio for death was 0.27 (P < 0.01) for use of PCC. Survival tended to be greater with earlier administration of PCC (P = 0.053). Despite improved survival, discharge domicile and function were not significantly worse. CONCLUSIONS: PCC reversal was associated with improved survival without worsened disability. Delays in administration may have reduced the potential benefits.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Resultado do Tratamento
4.
Appl Radiat Isot ; 71 Suppl: 23-4, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22484137

RESUMO

A monoenergetic X-ray syncrotron source was used to determine the energy response of a diamond detector in the range 5-25 keV, clarifying the elemental composition of the detector. The response is shown to be influenced by the detector housing and electrical contacts. A model for the energy response of the detector is determined that is valid in the 5 keV-15 MeV with an accuracy of 5% and therefore can be used to correct the dosimeter response to low-energy and scattered radiation.


Assuntos
Diamante , Radiometria/métodos , Dosimetria Termoluminescente/instrumentação , Radiometria/instrumentação , Síncrotrons , Raios X
5.
Proc Natl Acad Sci U S A ; 106(47): 20045-50, 2009 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-19897723

RESUMO

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that the vPFC is part of a circuit involved in non-spatial auditory processing and that the vPFC plays a functional role in non-spatial auditory cognition.


Assuntos
Percepção Auditiva/fisiologia , Cognição/fisiologia , Córtex Pré-Frontal , Estimulação Acústica , Animais , Vias Auditivas/fisiologia , Comportamento Animal/fisiologia , Eletrofisiologia , Humanos , Macaca mulatta , Masculino , Neurônios/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Vocalização Animal/fisiologia
6.
Appl Radiat Isot ; 67(3): 433-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18692398

RESUMO

Microdosimetry is useful in mixed-field radiation treatment strategies but relies on an understanding of electron physics at sub-micron dimensions. Monochromatic synchrotron light will be valuable in the development of Monte Carlo models of radiation transport at this length scale. In addition, synchrotron light offers new treatment strategies benefiting from high degrees of brightness and coherence including binary therapies such as photoactivation therapy (PAT) utilising photoelectric enhancement occurring in the kilovoltage range. Microdosimetric spectra for monoenergetic beams have been obtained in the range 15-33 keV with a tissue-equivalent proportional counter (TEPC) and have been compared to Monte Carlo calculations based on atomic models initially. Transport of electrons in molecular systems can also be considered where fundamental interaction data are also obtainable in synchrotron beams via photon scattering experiments utilising the optical model. In the absence of data from liquid water systems, MOSFET and silica-based optical fibre TLD are emerging contenders for experimental verification of microdosimetric spectra in the solid-state and glassy-state phases, respectively.


Assuntos
Síncrotrons , Raios X , Método de Monte Carlo , Radiografia
7.
Virology ; 320(2): 218-28, 2004 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15016545

RESUMO

In its native host species, the Rhesus Macaque, simian virus 40 (SV40) forms a persistent infection in the kidneys with no apparent harmful side effects. We show that SV40 infection of growth-arrested monkey kidney epithelial cells results in the specific disruption of certain Rb-E2F family complexes. Throughout the course of infection, p130-E2F and p107-E2F complexes are disrupted, but surprisingly pRb-E2F complexes remain intact. This suggests that the presence of some pRb-E2F complexes is not inhibitory to productive infection. Additionally, while a decrease of p130 steady state levels is observed during the later time points of infection, early during infection, p130 is readily detectable. This suggests SV40 infection overrides p130-mediated growth arrest through a mechanism(s) in addition to the well-documented T antigen-mediated degradation of p130. Finally, infection induces a dramatic relocalization of E2F4 from the nucleus to the cytoplasm. The implications of these observations to the life cycle of the virus are addressed.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Fosfoproteínas/metabolismo , Proteínas , Proteína do Retinoblastoma/metabolismo , Vírus 40 dos Símios/patogenicidade , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Fatores de Transcrição E2F , Rim/citologia , Proteínas Nucleares/metabolismo , Proteína p130 Retinoblastoma-Like , Vírus 40 dos Símios/metabolismo
8.
Vet Rec ; 153(1): 31-2, 2003 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-12877222
9.
J Agric Saf Health ; 7(2): 89-99, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11465388

RESUMO

In order to increase farm safety awareness and teach children good safety habits, farm safety day camp programs have been initiated in many communities. For the most part, the effectiveness of the programs is unknown because few evaluations have been performed. The purpose of this project was to qualitatively assess the overall strengths and weaknesses of farm safety day camp programs and to generate recommendations for future programs. Interviews, a literature search, and observations were used to identify strengths and weaknesses of the farm safety day camp programs. Major strengths of the programs are that: 1) positive attention is given to agriculture and agricultural safety; 2) programs are hands-on, interactive, and fun; 3) children gain knowledge about farm safety; 4) programs bring a community together to work toward a common goal; and 5) children talk to parents about safety. Key weaknesses of farm safety day camp programs are that: 1) there is a lack of parental involvement in many of the programs; 2) it is hard to change patterns of behavior in one day; 3) programs are expensive and time consuming; 4) curricula may include content that is inaccurate or inappropriate for the age of participants; and 5) evaluation is difficult. When done well, farm safety day camp programs can teach children about safety and influence safety practices affecting children on the farm. Recommendations for future farm safety day camp programs are: 1) ensure that child-development principles are applied to all aspects of program activities and curricula; 2) provide session leaders with accurate and relevant content; 3) increase parental involvement; and 4) address safety issues throughout the year.


Assuntos
Prevenção de Acidentes , Agricultura/educação , Educação em Saúde/normas , Avaliação de Programas e Projetos de Saúde , Segurança , Acampamento , Criança , Creches , Currículo , Educação em Saúde/métodos , Humanos , População Rural , Estados Unidos
10.
Pediatrics ; 107(6): E90, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11389288

RESUMO

OBJECTIVE: To determine whether the change from an all oral poliovirus vaccine (OPV) schedule to an inactivated poliovirus vaccine (IPV)-containing schedule has adversely affected the immunization status of young children in the United States. METHODS: Immunization data were abstracted from the medical records of children 8 to 35 months old seen consecutively for any reason in the offices of practicing pediatricians who are members of the Pediatric Research in Office Settings network of the American Academy of Pediatrics or the National Medical Association. Data on up to 120 eligible children were collected in each practice between March 1998 and January 2000. Patients were classified as fully immunized at 8 months old if they had received 3 diphtheria-tetanus-pertussis, 2 Haemophilus influenzae type b, 2 hepatitis B, and 2 poliovirus vaccines. Study children who were >/=12 months of age at the time that data were collected were categorized as being fully immunized at 12 months if they had received the same vaccines before their first birthday. To assess the effect of type of poliovirus vaccines on these outcomes, study patients were classified as being in an IPV or OPV group based on the initial type of vaccine received. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for IPV as a predictor of being fully immunized at 8 and 12 months of age, after adjusting for race/ethnicity of the patient, maternal education level, year of birth, and method of payment for vaccines. In addition, the effect of clustering of children within practices was accounted for by the use of generalized estimation equation techniques. RESULTS: Data were analyzed on 13 520 children from 177 practices in 42 states; 79.4% of patients were fully immunized at 8 months of age, and 88.7% of those eligible were fully immunized at 12 months of age. A total of 6910 patients (51.1%) were classified as OPV recipients, wheras 5282 (39.1%) received IPV. In addition, 1328 children (9.8%) were documented as having received poliovirus vaccine, but the particular type could not be determined. Compared with OPV recipients and after controlling for the confounding variables and the effect of clustering within practices, children in the IPV group were as likely as were OPV recipients to be fully immunized at 8 months of age (OR: 1.04; 95% CI: 0.88,1.23). At 12 months of age, the OR for IPV as a predictor of being fully immunized was 1.08 (95% CI: 0.90,1.30). When compared with OPV recipients, adjusted ORs for children in the undetermined poliovirus vaccine type group being fully immunized at 8 and 12 months of age were 0.84 (95% CI: 0.68,1.04) and 0.84 (95% CI: 0.67,1.07), respectively. CONCLUSIONS: The results of this national study indicate that the implementation of an IPV-containing poliovirus vaccine schedule has not had an adverse effect on the immunization status of young children who were vaccinated in the offices of practicing pediatricians.


Assuntos
Esquemas de Imunização , Vacina Antipólio de Vírus Inativado/imunologia , Pré-Escolar , Feminino , Política de Saúde , Humanos , Lactente , Masculino , Prontuários Médicos/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/imunologia , Padrões de Prática Médica , Estados Unidos/epidemiologia
11.
Endocrine ; 12(1): 81-8, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10855695

RESUMO

Estrogen deficiency following ovariectomy or menopause results in bone loss. Although evidence strongly suggests that the immune system is involved in the pathogenesis of estrogen-deficient osteoporosis, it is not clear what role, if any, the T-lymphocyte plays in this process. Therefore, we examined the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley rats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surgery into six groups to receive the following treatments: (A) sham/placebo; (B) sham/low-dose E2; (C) sham/high-dose E2; (D) Ovx/placebo; (E) Ovx/low-dose E2; (F) Ovx/high-dose E2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononuclear cells were isolated from the thymus, peripheral blood, spleen, lymph node and bone marrow, and were labeled for flow cytometric analysis using mouse anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigenic markers. In the thymus, ovariectomy caused a dramatic increase and E2 treatment caused a dose-dependent decrease in weight that was proportional to the number of thymocytes. In the bone marrow, ovariectomy caused a significant reduction in the percentage of all T-cell subsets examined and this effect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E2 treatment caused an increase in T-cell subsets in both the sham and Ovx groups, an effect that was more pronounced at d 14 compared with d 28. Although the percentages of some T-cell subsets in the other lymphoid organs/tissues were altered by ovariectomy or E2 treatment at d 0 and 14, all these changes had normalized by d 28 except for CD5 and CD4 cells in peripheral blood. In summary, with the exception of T-lymphocytes in the bone marrow, the effects of varying estrogenic states on T-cells were variable and transient. The influence of estrogen status on bone marrow T-lymphocytes suggests that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional role of T-cells in the bone marrow compartment.


Assuntos
Estradiol/farmacologia , Estrogênios/deficiência , Estrogênios/fisiologia , Tecido Linfoide/citologia , Ovariectomia , Linfócitos T/fisiologia , Animais , Células da Medula Óssea , Antígenos CD4/análise , Antígenos CD5/análise , Antígenos CD8/análise , Separação Celular , Estradiol/administração & dosagem , Feminino , Citometria de Fluxo , Linfonodos/citologia , Contagem de Linfócitos , Placebos , Ratos , Ratos Sprague-Dawley , Baço/citologia , Linfócitos T/imunologia , Timo/citologia
12.
Arch Pediatr Adolesc Med ; 154(5): 499-506, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10807303

RESUMO

OBJECTIVES: To describe how physicians coordinate patient care for specialty referrals and to examine the effects of these activities on referring physicians' satisfaction with the specialty care their patients receive and referral completion. DESIGN AND METHODS: Prospective study of a consecutive sample of referrals (N = 963) made from the offices of 122 pediatricians in 85 practices in a national practice-based research network. Data sources included a physician survey completed when the referral was made (response rate, 99%) and a physician survey and medical record review conducted 3 months later (response rate, 85%). Referral completion was defined as receipt of written communication of referral results from the specialist. RESULTS: Pediatricians scheduled appointments with specialists for 39.3% and sent patient information to specialists for 50.8% of referrals. The adjusted odds of referral completion were increased 3-fold for those referrals for which the pediatrician scheduled the appointment and communicated with the specialist compared with those for which neither activity occurred. Referring physicians' satisfaction ratings were significantly increased by any type of specialist feedback and were highest for referrals involving specialist feedback by both telephone and letter. Elements of specialists' letters that significantly increased physician ratings of letter quality included presence of patient history, suggestions for future care, follow-up arrangements, and plans for comanaging care; only the inclusion of plans for comanaging patient care was significantly related to the referring physicians' overall satisfaction. CONCLUSIONS: Better coordination between referring physicians and specialists increases physician satisfaction with specialty care and enhances referral completion. Improvements in the referral process may be achieved through better communication and collaboration between primary care physicians and specialists.


Assuntos
Continuidade da Assistência ao Paciente , Relações Interprofissionais , Pediatria , Qualidade da Assistência à Saúde , Encaminhamento e Consulta , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Illinois , Lactente , Masculino , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Análise de Regressão
13.
Pediatrics ; 104(1 Pt 1): 28-34, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10390256

RESUMO

OBJECTIVE: In this study we examined how gatekeeping arrangements influence referrals to specialty care for children and adolescents in private and Medicaid insurance plans. DESIGN/PARTICIPANTS: We conducted a prospective study of office visits (n = 27 104) made to 142 pediatricians in 94 practices distributed throughout 36 states in a national primary care practice-based research network. During 10 practice-days, physicians and patients completed questionnaires on referred patients, while office staff kept logs of all visits. Physicians used medical records to complete questionnaires for a subset of patients 3 months after their referral was made. RESULTS: Gatekeeping arrangements were common among children and adolescents with private (57.8%) and Medicaid (43.3%) insurance. Patients in gatekeeping plans were more likely to be referred with private (3. 16% vs 1.85% visits referred) and Medicaid (5.39% vs 3.73%) financing. Increased parental requests for specialty care among gatekeeping patients did not explain the increased referral rate. Physicians' reasons for making the referral were similar between the two groups. Physicians were less likely to schedule an appointment or communicate with the specialist for referred patients in gatekeeping plans. However, rates of physician awareness that a specialist visit occurred and specialist communication back to pediatricians did not differ between the two groups 3 months after the referrals were made. CONCLUSIONS: Gatekeeping arrangements are common among insured children and adolescents in the United States. Our study suggests that gatekeeping arrangements increase referrals from pediatricians' offices to specialty care and compromise some aspects of coordination.


Assuntos
Seguro Saúde/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Razão de Chances , Padrões de Prática Médica/economia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Encaminhamento e Consulta/economia , Inquéritos e Questionários , Estados Unidos
14.
Arch Pediatr Adolesc Med ; 153(7): 705-14, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10401803

RESUMO

OBJECTIVE: To describe how pediatricians refer patients to specialists, including frequency of referral decisions, reasons for referral, and types of referrals. DESIGN: We conducted a prospective study of visits (N = 58 771) made to 142 pediatricians in a national primary care practice-based research network. During 20 consecutive practice days, physicians and parents completed questionnaires for referred patients, and office staff kept logs of all visits. Physicians used medical records to complete questionnaires 3 months after referrals were made. RESULTS: Pediatricians referred patients to specialists during 2.3% of office visits. Referrals made during telephone conversations with parents accounted for 27.5% of all referrals. The most common reason for referral was advice on diagnosis or treatment (74.3%). Referrals were made most commonly to surgical subspecialists (52.3%), followed by medical subspecialists (27.9%), nonphysicians (11.4%), and mental health practitioners (8.4%). Physicians requested a consultation or a referral with shared management in 75% of cases. Otitis media was the condition referred most often (9.2%). Fifty other conditions accounted for 84.3% of all referrals. CONCLUSIONS: About 1 in 40 pediatric visits result in referral. Getting advice from a specialist is the most common reason for referral. Pediatricians desire a collaborative relationship with specialists for most of their referred patients. Physician training to increase clinical competence may be most useful for the 50 most commonly referred conditions. Education concerning the referral process should focus on the respective roles of the referring physician and specialist, particularly as they pertain to successful approaches for comanaging referred patients.


Assuntos
Medicina , Pediatria/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Especialização , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Atenção Primária à Saúde , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos
15.
Pediatrics ; 102(6): 1350-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9832568

RESUMO

OBJECTIVES: To describe the establishment of a national pediatric primary care research network to improve children's health care-Pediatric Research in Office Settings (PROS), and to evaluate the network's progress toward achieving its objectives. SETTING: Pediatric practices in all 50 states and Puerto Rico. PARTICIPANTS: Approximately 1400 pediatric practitioners from more than 470 practices. RESULTS: Beginning in 1986, a core of volunteer pediatrician coordinators from participating American Academy of Pediatrics chapters were identified to oversee local PROS efforts, represent practitioners, and inform the development of proposed research studies. PROS subsequently recruited practitioners from around the country, building a research infrastructure and a system of collaboration between the practitioners, research staff at the AAP, and investigative teams at academic institutions. This PROS collaboration has developed and conducted 10 primary care research studies that have added to the knowledge base of pediatric primary care. CONCLUSIONS: PROS has accomplished two of its initial objectives-development of a structure and process for pediatric practice-based research and provision of research experience to practitioners. Successful and consistent achievement of a third objective-meaningful dissemination of study results to relevant audiences-will depend on meeting several challenges.


Assuntos
Serviços de Saúde da Criança/normas , Pediatria/normas , Atenção Primária à Saúde/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Criança , Serviços de Saúde da Criança/organização & administração , Humanos , Modelos Organizacionais , Programas Nacionais de Saúde , Pediatria/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Desenvolvimento de Programas , Pesquisa , Estados Unidos
16.
Am J Physiol ; 275(2): H476-83, 1998 08.
Artigo em Inglês | MEDLINE | ID: mdl-9683435

RESUMO

In the intact animal, it is difficult to discriminate between the independent effects of series and direct ventricular interaction (DI) or the individual contributions of the pericardium and septum to DI. Left ventricular (LV) venous return (LVVR) and right ventricular (RV) end-diastolic pressure (RVEDP) were varied independently in a right-heart bypass model. LV minor-axis diameters were measured, and the product of the two diameters was used as an index of LV volume (LVVI). At each RVEDP (0, 5, 10, and 15 mmHg), increased LVVR caused an increased LVVI. When RVEDP was increased, increased pump output was required to maintain a given LVVI. RV-to-LV pressure gain (DeltaLVEDP/DeltaRVEDP) reflects coupling and DI. With the pericardium closed, the gain was dependent on RVEDP; when RVEDP was increased from 0 to 5 mmHg, the gain was not statistically different from zero, indicating little or no DI. When RVEDP was increased from 10 to 15 mmHg, the gain was not statistically different from 1.0, indicating approximately 1:1 coupling of the ventricles. Opening the pericardium reduced the gain, but significant interaction remained. When the septal contribution was accounted for, the remaining interaction was eliminated. In conclusion, DI substantially affects LVEDP-volume relations. Considerable increases in RV output may be required to counterbalance increased constraint to LV filling. With the pericardium closed, RV-to-LV coupling is minimal when RVEDP is low and increases to 1:1 coupling when RVEDP is high. Opening the pericardium reduces DI, but significant septum-mediated interaction remains.


Assuntos
Pressão Sanguínea , Septos Cardíacos/fisiologia , Pericárdio/fisiologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Animais , Diástole , Cães , Modelos Cardiovasculares , Análise de Regressão
17.
Biochemistry ; 37(17): 5923-9, 1998 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-9558326

RESUMO

Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and Epstein-Barr virus (EBV). Each member of this family encodes a serine protease that is a potential target for antiviral therapeutic intervention. We recently reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella, A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid, S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165 and Arg166 residues are involved in stabilizing the oxyanion intermediate in human herpes protease catalyzed reactions through the backbone NH and side chain, respectively. In the current study, site-directed mutagenesis was carried out to probe the catalytic function of these two amino acid residues. Substitution of Arg166 with an alanine has led to ablation of enzymatic activity without detectable change in CMV protease conformation, supporting suggestions from the crystal structure that Arg166 side chain plays a major role in catalysis. The wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was shown previously to hold a water molecule that can act as a hydrogen-bond donor to the oxyanion and was thus proposed to stabilize the oxyanion intermediate. However, kinetic characterization of the mutant R165A only reveals a 2.7-fold lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/- 0.4 min-1. These results confirm that Arg165 side chain is not involved in the stabilization of the oxyanion. It is likely that Arg165 only utilizes the backbone NH for catalysis as suggested by the crystal structure.


Assuntos
Arginina/fisiologia , Citomegalovirus/enzimologia , Endopeptidases/metabolismo , Mutagênese Sítio-Dirigida , Serina Endopeptidases , Alanina/metabolismo , Arginina/genética , Catálise , Citomegalovirus/genética , Dimerização , Endopeptidases/química , Endopeptidases/genética , Humanos , Cinética , Modelos Moleculares , Dobramento de Proteína , Estrutura Secundária de Proteína
20.
J Immunol Methods ; 154(1): 37-45, 1992 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-1401942

RESUMO

BUB/BnJ mice were previously identified as having exceptionally potent complement activity, relative to common mouse strains, in the lysis of antibody-coated human tumor cells. We describe herein our investigation into the molecular and genetic basis for this difference between mouse strains, and also our results with wild mice and mouse strains recently derived from the wild, to determine whether low complement levels are characteristic of wild mice. BUB complement was compared with complement from BALB/c and C57BL/6 mice. BUB mice had higher levels of most individual classical pathway components, except for C1, than the other two strains, but the difference was generally only 2-3-fold, so insufficient to fully explain the difference observed with tumor target cells. CH50 titers on antibody-coated sheep erythrocytes also demonstrated only a 2-4-fold difference. However, CH50 titers on antibody-coated human erythrocyte target cells demonstrated a difference similar in magnitude to that seen with human tumor targets. These results suggest that the difference between mouse strains depends partly on the use of human, rather than sheep, target cells. In an assay for alternative complement pathway activity using neuraminidase-treated human erythrocytes as targets, complements of BALB/c and BUB mice were similar in activity, suggesting that the difference between mouse strains is manifested in the early steps of complement activation. Analysis of F1 and backcross mice suggested that the difference in complement level between BUB and BALB/c or C57BL/6 mice is controlled by semi-dominant genes, and cannot be attributed to a single gene. Wild mice and mice recently derived from the wild generally had low complement levels, similar to most laboratory mice. However, three strains of aboriginal mice, including Mus hortulanus (spicilegus) and Mus spretus, had complement levels higher than that of BUB mice, and as high as sera from the rabbit or rat, which are the most potent known complement sources for the lysis of human tumor cells. In comparison with BUB mouse sera, M. hortulanus sera had at least four-fold higher levels of C3, C6, C8 and C9, and some or all of these differences may explain its higher total complement activity. In the lysis of antibody-coated human erythrocytes, M. hortulanus serum was more potent than any other complement source tested, including sera of the guinea pig, rat, rabbit or human. These strains may be useful in investigating the role of complement in various pathological processes, and in investigating the genetic regulation of the complement system.


Assuntos
Proteínas do Sistema Complemento/biossíntese , Camundongos Endogâmicos/imunologia , Muridae/metabolismo , Animais , Ensaio de Atividade Hemolítica de Complemento , Via Alternativa do Complemento , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/imunologia , Cruzamentos Genéticos , Citotoxicidade Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
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