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1.
BMC Med Res Methodol ; 21(1): 73, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865324

RESUMO

BACKGROUND: Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these. METHODS: We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations. RESULTS: The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance. CONCLUSION: Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.


Assuntos
Consenso , Humanos , Recém-Nascido
2.
Br J Cancer ; 116(12): 1585-1594, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28510570

RESUMO

BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer. METHODS: A systematic review of published studies reporting BAG-1 (mRNA and/or protein) expression and clinical outcome in early breast cancer. The REporting Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were used as a template against which data were assessed. Meta-analyses were performed for studies that provided a hazard ratio and 95% confidence intervals for clinical outcomes including disease-free survival or breast cancer-specific survival from univariate analysis. RESULTS: Eighteen studies used differing methodologies and reported on differing outcomes. Meta-analyses were only possible on results from a subset of reported studies. Meta-analyses suggested improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by immunohistochemisty. CONCLUSIONS: Increased levels of BAG-1 are associated with better breast cancer outcomes.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/química , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , RNA Mensageiro/análise , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Taxa de Sobrevida
3.
J Theor Biol ; 435: 238-247, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-28939346

RESUMO

Cooperation in a public goods game has been studied extensively to find the conditions for sustaining the commons, yet the effect of asymmetry between agents has been explored very little. Here we study a game theoretic model of cooperation for pest control among farmers. In our simple model, each farmer has a paddy of the same size arranged adjacently on a line. A pest outbreak occurs at an abandoned paddy at one end of the line, directly threatening the frontier farmer adjacent to it. Each farmer pays a cost of his or her choice to an agricultural collective, and the total sum held by the collective is used for pest control, with success probability increasing with the sum. Because the farmers' incentives depend on their distance from the pest outbreak, our model is an asymmetric public goods game. We derive each farmer's cost strategy at the Nash equilibrium. We find that asymmetry among farmers leads to a few unexpected outcomes. The individual costs at the equilibrium do not necessarily increase with how much the future is valued but rather show threshold behavior. Moreover, an increase in the number of farmers can sometimes paradoxically undermine pest prevention. A comparison with a symmetric public goods game model reveals that the farmer at the greatest risk pays a disproportionate amount of cost in the asymmetric game, making the use of agricultural lands less sustainable.


Assuntos
Agricultura/economia , Comportamento Cooperativo , Teoria dos Jogos , Controle de Pragas/economia , Custos e Análise de Custo , Humanos , Modelos Teóricos , Probabilidade , Risco
4.
Allergy ; 71(4): 433-42, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26505989

RESUMO

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.


Assuntos
Asma/epidemiologia , Asma/etiologia , Dieta , Fatores Etários , Asma/prevenção & controle , Suplementos Nutricionais , Frutas , Humanos , Razão de Chances , Vigilância da População , Risco , Vitamina D/administração & dosagem
6.
Exp Neurol ; 336: 113527, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33188818

RESUMO

The hippocampus is vulnerable to traumatic brain injury (TBI), and hippocampal damage is associated with cognitive deficits that are often the hallmark of TBI. Recent studies have found that TBI induces enhanced neurogenesis in the dentate gyrus (DG) of the hippocampus, and this cellular response is related to innate cognitive recovery. However, cellular mechanisms of the role of DG neurogenesis in post-TBI recovery remain unclear. This study investigated changes in long-term potentiation (LTP) within the DG in relation to TBI-induced neurogenesis. Adult male rats received a moderate TBI or sham injury and were sacrificed for brain slice recordings at 30 or 60 days post-injury. Recordings were taken from the medial perforant path input to DG granule cells in the presence or absence of the GABAergic antagonist picrotoxin, reflecting activity of either all DG granule cells or predominately newborn granule cells, respectively. Measurements of LTP observed in the total granule cell population (with picrotoxin) showed a prolonged impairment which worsened between 30 and 60 days post-TBI. Under conditions which predominantly reflected the LTP elicited in newly born granule cells (no picrotoxin), a strikingly different pattern of post-TBI changes was observed, with a time-dependent cycle of functional impairment and recovery. At 30 days after injury this cell population showed little or no LTP, but by 60 days the capacity for LTP of the newly born granule cells was no different from that of sham controls. The time-frame of LTP improvements in the newborn cell population, comparable to that of behavioral recovery reported previously, suggests the unique functional properties of newborn granule cells enable them to contribute to restorative change following brain injury.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Hipocampo/patologia , Plasticidade Neuronal , Sinapses/patologia , Animais , Atrofia , Comportamento Animal , Lesões Encefálicas Traumáticas/psicologia , Grânulos Citoplasmáticos/patologia , Fenômenos Eletrofisiológicos , Antagonistas GABAérgicos/farmacologia , Potenciação de Longa Duração , Masculino , Picrotoxina/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica
7.
Protein Eng Des Sel ; 21(6): 405-12, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18434422

RESUMO

Rational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure.


Assuntos
Arildialquilfosfatase/metabolismo , Substâncias para a Guerra Química/metabolismo , Compostos Organotiofosforados/metabolismo , Arildialquilfosfatase/química , Catálise , Estabilidade Enzimática , Hidrólise , Modelos Moleculares , Conformação Proteica , Desnaturação Proteica
8.
Perioper Med (Lond) ; 7: 2, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29423173

RESUMO

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an exercise stress test with concomitant expired gas analysis that provides an objective, non-invasive measure of functional capacity under stress. CPET-derived variables predict postoperative morbidity and mortality after major abdominal and thoracic surgery. Two previous surveys have reported increasing utilisation of CPET preoperatively in England. We aimed to evaluate current CPET practice in the UK, to identify who performs CPET, how it is performed, how the data generated are used and the funding models. METHODS: All anaesthetic departments in trusts with adult elective surgery in the UK were contacted by telephone to obtain contacts for their pre-assessment and CPET service leads. An online survey was sent to all leads between November 2016 and March 2017. RESULTS: The response rate to the online survey was 73.1% (144/197) with 68.1% (98/144) reporting an established clinical service and 3.5% (5/144) setting up a service. Approximately 30,000 tests are performed a year with 93.0% (80/86) using cycle ergometry. Colorectal surgical patients are the most frequently tested (89.5%, 77/86). The majority of tests are performed and interpreted by anaesthetists. There is variability in the methods of interpretation and reporting of CPET and limited external validation of results. CONCLUSIONS: This survey has identified the continued expansion of perioperative CPET services in the UK which have doubled since 2011. The vast majority of CPET tests are performed and reported by anaesthetists. It has highlighted variation in practice and a lack of standardised reporting implying a need for practice guidelines and standardised training to ensure high-quality data to inform perioperative decision making.

10.
Oncogenesis ; 5: e215, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-27043661

RESUMO

Mammary MCF-10A cells seeded on reconstituted basement membrane form spherical structures with a hollow central lumen, termed acini, which are a physiologically relevant model of mammary morphogenesis. Bcl-2-associated athanogene 1 (Bag-1) is a multifunctional protein overexpressed in breast cancer and ductal carcinoma in situ. When present in the nucleus Bag-1 is predictive of clinical outcome in breast cancer. Bag-1 exists as three main isoforms, which are produced by alternative translation initiation from a single mRNA. The long isoform of Bag-1, Bag-1L, contains a nuclear localisation sequence not present in the other isoforms. When present in the nucleus Bag-1L, but not the other Bag-1 isoforms, can interact with and modulate the activities of estrogen-, androgen- and vitamin D-receptors. Overexpression of Bag-1 mRNA in MCF-10A is known to produce acini with luminal filling reminiscent of ductal carcinoma in situ. As this mRNA predominantly overexpresses the short isoform of Bag-1, Bag-1S, we set out to examine whether the nuclear Bag-1L isoform is sufficient to drive premalignant change by developing a Bag-1L-overexpressing MCF-10A model. Two clones differentially overexpressing Bag-1L were grown in two-dimensional (2D) and three-dimensional (3D) cultures and compared with an established model of HER2-driven transformation. In 2D cultures, Bag-1L overexpression reduced proliferation but did not affect growth factor responsiveness or clonogenicity. Acini formed by Bag-1L-overexpressing cells exhibited reduced luminal clearing when compared with controls. An abnormal branching morphology was also observed which correlated with the level of Bag-1L overexpression, suggesting further malignant change. Treatment with Thio-2, a small-molecule inhibitor of Bag-1, reduced the level of branching. In summary, 3D cultures of MCF-10A mammary epithelial cells overexpressing Bag-1L demonstrate a premalignant phenotype with features of ductal carcinoma in situ. Using this model to test the small-molecule Bag-1 inhibitor, Thio-2, reveals its potential to reverse the atypical branched morphology of acini that characterizes this premalignant change.

11.
J Am Coll Cardiol ; 5(6 Suppl): 167B-174B, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3889108

RESUMO

Angina is an important though relatively insensitive and nonspecific predictor of the presence of significant coronary occlusive disease. If angina is present, there is a high probability of significant coronary atherosclerosis. However, the lack of angina, even with vigorous exertion, does not imply absence of severe and potentially lethal amounts of coronary stenosis because a high percent of patients who have had sudden cardiac arrest or myocardial infarction have not had prior angina pectoris. In many studies that carefully and specifically examined the prognostic importance of angina in relation to other variables, neither the presence of angina nor its severity was of prognostic significance, although a few studies suggested that the unstable form of angina may have unfavorable prognostic significance independent of the state of left ventricular function or the severity of coronary atherosclerosis. Thus, it would not appear to be wise to base individual or national decisions aimed at reducing the likelihood of death from coronary disease primarily on the presence or absence of angina pectoris.


Assuntos
Angina Pectoris/fisiopatologia , Arteriosclerose/fisiopatologia , Doença das Coronárias/fisiopatologia , Morte Súbita/etiologia , Adulto , Idoso , Análise de Variância , Angina Pectoris/complicações , Angina Pectoris/etiologia , Arteriosclerose/complicações , Doença das Coronárias/complicações , Doença das Coronárias/etiologia , Europa (Continente) , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Distribuição Aleatória , Risco , Estados Unidos
12.
J Am Coll Cardiol ; 27(5): 1270-7, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8609355

RESUMO

OBJECTIVES: This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis. BACKGROUND: The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized. METHODS: We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement. RESULTS: Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 +/- 0.09 mm (reference diameter 2.87 +/- 0.06 mm, mean +/- SE) and increased to 2.82 +/- 0.05 mm (p < 0.001) after stent placement. The balloon-inflated stent diameter was 2.98 +/- 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 +/- 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 +/- 0.01 vs. 0.27 +/- 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 +/- 0.27 vs. 2.68 +/- 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 +/- 0.34 mm2) than nonstented atherosclerotic vessels (0.44 +/- 0.28 mm2, p = 0.033). CONCLUSIONS: Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.


Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/terapia , Stents , Túnica Íntima/patologia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Doença da Artéria Coronariana/patologia , Hiperplasia , Suínos
13.
J Psychiatr Ment Health Nurs ; 12(3): 341-6, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15876242

RESUMO

Current traditional methods of mental healthcare service delivery, based on 'specialists' providing 'outpatient appointments' for formal therapy, are often inappropriate for the needs of patients in primary care. The estimated numbers of adults with mental health problems are immense, and it is this, combined with Department of Health initiatives aimed at improving choice and access, which make it essential that new ways of delivering services are explored. This trial examines the use of an assisted self-help treatment package for mild to moderate stress/anxiety [Assisted Bibliotherapy (AB)] with an adult clinical population referred by their general practitioner. Assisted Bibliotherapy is a brief intervention (8 weeks), with limited therapist contact (20-min sessions). Non-parametric statistical testing of scores from the Zung Anxiety Scale and the Clinical Outcomes in Routine Evaluation (CORE) questionnaire indicated positive results. There was significant improvement at post-treatment, which was maintained at 3 month follow-up. The results from this trial and a previous trial of AB by Kupshik & Fisher in 1999, indicate that it is an effective treatment which could be used as part of a stepped care approach to managing and treating stress/anxiety in primary care.


Assuntos
Ansiedade/enfermagem , Biblioterapia , Comportamento de Escolha , Acessibilidade aos Serviços de Saúde , Estresse Psicológico/complicações , Adulto , Ansiedade/psicologia , Terapia Cognitivo-Comportamental , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente , Satisfação do Paciente , Inventário de Personalidade/estatística & dados numéricos , Atenção Primária à Saúde , Psicometria , Encaminhamento e Consulta , Autocuidado/psicologia
14.
Neuroscience ; 77(2): 431-44, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9472402

RESUMO

Among the pathological processes initiated by traumatic brain injury are excessive neuroexcitation and target cell deafferentation. The current study examines the contribution of these injury components, separately as well as their combined effect, on postinjury alterations in the capacity for long-term potentiation and the immunolocalization of N-methyl-D-aspartate receptors and GABA. Adult rats underwent central fluid percussion traumatic brain injury, electrolytic bilateral entorhinal cortex lesions, or a combined injury of both procedures separated by 24 h. At two or 15 days postinjury, the capacity for long-term potentiation of the Schaffer collateral-commissural input to CA1 was measured in acute electrophysiological recordings. Entorhinal cortical lesions resulted in time-dependent increases in the effectiveness of tetanic stimulation to elevate population postsynaptic potentials and population spike amplitudes. These lesions also resulted in a marked intensification in the density of N-methyl-D-aspartate receptors in the CA1 stratum lacunosum-moleculare. All injury conditions that included fluid percussion as a component (alone or in combined injuries) produced a persistent impairment in long-term potentiation of the evoked population postsynaptic potentials. Thus, in combined injuries, the presence of concussion-induced neuroexcitation attenuated deafferentation-induced response increases. Both N-methyl-D-aspartate receptor and GABA immunobinding following combined injuries were also reduced relative to those observed following entorhinal lesions alone. The present results suggest that a process of receptor plasticity, possibly involving reactive synaptogenesis, may contribute to postdeafferentation enhancements of long-term potentiation, and that a traumatic brain insult will attenuate these enhancements. This interaction of different injury components suggests that recovery of function following brain injury may be enhanced by pharmacological reduction of neuroexcitation during postinjury intervals of reactive receptor plasticity.


Assuntos
Lesões Encefálicas/fisiopatologia , Córtex Entorrinal/fisiopatologia , Potenciação de Longa Duração/fisiologia , Animais , Lesões Encefálicas/patologia , Estimulação Elétrica , Eletrodos Implantados , Eletrofisiologia , Córtex Entorrinal/patologia , Potenciais Evocados/fisiologia , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/fisiologia , Ácido gama-Aminobutírico/metabolismo
15.
J Neurotrauma ; 18(10): 993-1009, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11686499

RESUMO

Traumatic brain injury (TBI) is documented to have detrimental effects on CNS metabolism, including alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. Studies on mitochondrial metabolism have also provided evidence for reduced activity of the cytochrome oxidase complex of the electron transport chain (complex IV) after TBI and an immediate (lhr) reduction in mitochondrial state 3 respiratory rate, which can persist for up to 14 days postinjury. Using differential display methods to screen for differences in gene expression, we have found that cytochrome c oxidase II (COII), a mitochondrial encoded subunit of complex IV, is upregulated following TBI. Since COII carries a binding site for cytochrome c in the respiratory chain, and since it is required for the passage of chain electrons to molecular oxygen, driving the production of ATP, we hypothesized that metabolic dysfunction resulting from TBI alters COII gene expression directly, perhaps influencing the synaptic plasticity that occurs during postinjury recovery processes. To test this hypothesis, we documented COII mRNA expression and complex IV (cytochrome c oxidase) functional activity at 7 days postinjury, focusing on the long-term postinjury period most closely associated with synaptic reorganization. Both central fluid percussion TBI and combined TBI and bilateral entorhinal cortical lesion were examined. At 7 days survival, differential display, RT-PCR, and Northern blot analysis of hippocampal RNA from both TBI and combined insult models showed a significant induction of COII mRNA. This long-term elevation in COII gene expression was supported by increases in COII immunobinding. By contrast, cytochrome oxidase histochemical activity within tissue sections from injured brains suggested a reduction of complex IV activity within the TBI cases, but not within animals subjected to the combined insult. These differences in cytochrome c oxidase activity were supported by in vitro assay of complex IV using cerebral cortical and hippocampal tissues. Our present results support the hypothesis that COII is selectively vulnerable to TBI and that COII differences may indicate the degree of metabolic dysfunction induced by different pathologies. Taken together, such data will better define the role of metabolic function in long-term recovery after TBI.


Assuntos
Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Regulação Enzimológica da Expressão Gênica/genética , Mitocôndrias/enzimologia , Animais , Northern Blotting , Clonagem Molecular , Metabolismo Energético/fisiologia , Córtex Entorrinal/patologia , Imuno-Histoquímica , Masculino , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Behav Neurosci ; 101(2): 179-86, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3580120

RESUMO

Adult male rats were implanted with chronically indwelling recording electrodes in the dentate hilus of one hemisphere and bipolar stimulating electrodes in the contralateral entorhinal cortex (EC). Daily measurements were then made of the amplitude of responses, evoked through the crossed temporodentate (CTD) pathway, while the rats were unanesthetized and unrestrained. The implanted rats were also trained to alternate turns in a T-maze, with the use of a rewarded-alternation procedure. After reaching criterion performance in the alternation task, each rat was given a lesion of the EC ipsilateral to the recording electrode (n = 14) or a sham lesion (n = 5). Mean amplitudes of the evoked responses increased over Postlesion Days 4-11, probably due to reactive synaptogenesis in the CTD system, reaching a level that was significantly elevated above prelesion levels by Postlesion Day 6. Rats given EC lesions exhibited a transient impairment in alternation performance, with the mean alternation score significantly below prelesion levels on Postlesion Days 2-6. Although 2 EC-lesioned rats did not show a behavioral deficit, the electrophysiological increases and behavioral recovery were correlated in the remaining 12 cases (Pearson r = .73). These results are consistent with the interpretation that sprouting by the CTD system contributes to recovery of T-maze alternation performance following unilateral EC lesions.


Assuntos
Aprendizagem por Discriminação/fisiologia , Hipocampo/fisiologia , Regeneração Nervosa , Orientação/fisiologia , Animais , Potenciais Evocados , Masculino , Ratos , Ratos Endogâmicos , Sinapses/fisiologia
17.
Restor Neurol Neurosci ; 19(3-4): 213-35, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12082223

RESUMO

Hippocampal afferents terminate in well-defined laminae, with a morphological segregation of input which has facilitated the interpretation of structural and functional synaptic reorganization observed after deafferentiation. Historically, most studies have induced hippocampal plasticity using single deafferentiation paradigms, however recent evidence indicates that sequential lesions or models based on combined injuries alter the pattern of dendritic structural reorganization and axonal sprouting. A better understanding of the interaction between deafferentiation-induced structural remodeling and other pathological mechanisms, which commonly coexist in central nervous system trauma, will require the use of combined injury paradigms where such plasticity can be systematically manipulated. In the context of traumatic brain injury, we have developed an injury model that combines the excessive neuroexcitation of concussive brain insult with the targeted hippocampal deafferentation of entorhinal cortical lesion. This review discusses the role of such an approach in defining posttraumatic hippocampal vulnerability, out- lining the effects of combined pathology on hippocampal circuitry, and considers the greater clinical relevance inherent in the combined injury approach. Experimental evidence obtained with the combined concussive plus deafferentation model is presented, detailing the interaction of injury components and highlighting structural, behavioral and electrophysiological evidence for maladaptive hippocampal plasticity. Subsequent studies utilizing pharmacological methods to manipulate this maladaptive plasticity are described, first targeting glutamate, acetylcholine and dopamine receptor pathways, and then applying select drugs to explore how various molecular mechanisms underlying combined neuroexcitation and deafferentation pathology might affect regenerative plasticity. Evidence implicating postinjury neurotransmitter modulation of exeitatory/inhibitory homeostasis, metalloproteinase regulation of extracellular matrix, and mitochondrial metabolic vulnerability is presented. Finally, the effect of age on outcome after combined neuroexcitation plus deafferentation insult is considered, as well as how future studies in such combined injury models will better define the full range of postinjury hippocampal plasticity possible after brain trauma.


Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Plasticidade Neuronal/fisiologia , Animais
18.
Obstet Gynecol ; 75(4): 716-9, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2314793

RESUMO

Breast cancer affects one in ten women during their lifetime. Recognizing the importance of early detection in the prognosis of this condition, the American Board of Obstetrics and Gynecology has stated guidelines encouraging breast disease education in obstetrics and gynecology training programs. To fulfill this academic responsibility, we have organized a multidisciplinary Breast Disease Detection and Treatment Clinic where patients with abnormal mammograms or any breast-related complaints are evaluated and managed. In cooperation with the radiology department and general surgery service, a mammogram review conference has been instituted. Abnormal mammograms are reviewed with a radiologist. Our activities have been coordinated such that a general surgery staff member and resident are present during the breast clinic hours to review mammograms and to examine the patients with the gynecologist, providing immediate consultation. Needle aspiration of breast cysts, repeat imaging studies, and general surgery referrals for breast biopsies are performed as indicated. The patient receives integrated care of her breast problem in one visit, and our residents gain the experience of diagnosing and managing breast problems which, before establishment of this clinic, were referred to the general surgery department. This multidisciplinary approach developed in our institution helps us provide the most efficient care to our patients, while providing our residents with integrated teaching and training concerning the diagnosis and management of breast disease.


Assuntos
Doenças Mamárias , Ginecologia/educação , Internato e Residência , Obstetrícia/educação , Instituições de Assistência Ambulatorial , Doenças Mamárias/diagnóstico , Doenças Mamárias/terapia , Educação Médica Continuada , Feminino , Cirurgia Geral/educação , Humanos , Radiologia/educação
19.
Behav Brain Res ; 5(3): 245-59, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7115568

RESUMO

The present study had two primary aims. The first was to determine the extent of the visual field of the deprived eye of a monocularly deprived cat using visual perimetry techniques, since recent reports have been contrary to previous research. The second aim was to determine whether enucleation of the experienced eye of a monocularly deprived cat was associated with any increase in the extent of the visual field of the deprived eye compared to forced usage (reverse-suture). The results indicate that the extent of the visual field using the deprived eye is limited to the ipsilateral monocular visual field. Further, enucleation of the experienced eye leads to a rapid expansion of the visual field of the deprived eye to include the entire ipsilateral hemifield which does not occur following reverse-suture. Possible reasons for the conflicting reports in the literature are discussed.


Assuntos
Dominância Cerebral/fisiologia , Retina/fisiologia , Privação Sensorial/fisiologia , Campos Visuais , Animais , Gatos , Orientação/fisiologia , Testes de Campo Visual , Percepção Visual/fisiologia
20.
Ann Thorac Surg ; 24(4): 323-9, 1977 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-303080

RESUMO

The diagnosis of perioperative myocardial infarction (POMI) in patients undergoing coronary artery bypass is uncertain because the criteria of infarction are unclear. Fifty patients who underwent coronary artery bypass were evaluated preoperatively and postoperatively with serial ECGs, creatine phosphokinase (CPK), isoenzyme determinations, and technetium pyrophosphate myocardial scans. Clinical evaluation correlated with exercise testing and postoperative angiography supported the diagnosis in questionable cases. Thirty-five patients (70%) had no evidence of POMI by any criteria, and 2 patients (4%) had unequivocal evidence of infarction by all criteria. Our studies indicate the complexities of diagnosing POMI. We believe that the serially recorded ECG is the most useful diagnostic technique. CPK isoenzyme determinations may be useful but are difficult to interpret in the operative setting. Preoperative cardiac scans are necessary so as to avoid a high incidence of false-positive scans postoperatively. In doubtful cases, postoperative coronary arteriography and left ventricular angiography may provide the most definitive information.


Assuntos
Ponte de Artéria Coronária , Infarto do Miocárdio/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Angiografia Coronária , Creatina Quinase/sangue , Diagnóstico Diferencial , Eletrocardiografia , Teste de Esforço , Feminino , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/enzimologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico por imagem , Cintilografia
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