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1.
Breast Cancer Res Treat ; 188(2): 351-359, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33788134

RESUMO

PURPOSE: This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. METHODS: Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman's Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. RESULTS: Ninety-nine participants (median age = 50) were treated with adjuvant (N = 23), neoadjuvant (N = 21) or without chemotherapy (N = 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only "fair" (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p = 0.006, neoadjuvant: ∆ = 45min, p = 0.038) and lower in week 18 than in week 3 (∆ = 43min, p = 0.010). CONCLUSION: Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Exercício Físico , Feminino , Monitores de Aptidão Física , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Autorrelato
2.
J Viral Hepat ; 24(2): 102-110, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27790789

RESUMO

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Adolescente , Adulto , Idoso , Animais , Antivirais/efeitos adversos , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento , Adulto Jovem
3.
BJOG ; 124(3): 463-472, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27102365

RESUMO

OBJECTIVE: Placental abruption has a profound impact on perinatal mortality, but implications for neurodevelopment during childhood remain unknown. We examined the association between abruption and neurodevelopment at 8 months and 4 and 7 years and evaluated the extent to which these associations were mediated through preterm delivery. DESIGN: Secondary analysis of a multicenter prospective cohort study. SETTING: Multicenter US National Collaborative Perinatal Project (1959-76). POPULATION: Women that delivered singleton live births. METHODS: Analyses of IQ scores were based on marginal structural models (MSM) to account for losses to follow-up. We also carried out a causal mediation analysis to evaluate if the association between abruption and cognitive deficits was mediated through preterm delivery, and performed a sensitivity analysis for unobserved confounding. MAIN OUTCOME MEASURES: We evaluated cognitive development based on the Bayley scale at 8 months (Mental and Motor Scores), and intelligent quotient (IQ) based on the Stanford-Binet scale at 4 years and the Wechsler Intelligence Scale for Children at 7 years. RESULTS: The confounder and selection-bias adjusted risk ratio (RR) of abnormal 8-month Motor and Mental assessments were 2.35 (95%CI 1.39, 3.98) and 2.03 (95%CI 1.13, 3.64), respectively, in relation to abruption. The associations at 4 years were attenuated and resolved at 7 years. The proportion of children with abruption-associated neurological deficits mediated through preterm delivery ranged from 27 to 75%. Following adjustment for unobserved confounding the proportion mediated through preterm delivery was attenuated. CONCLUSION: The effect of abruption on neurodevelopmental outcomes appears restricted to an effect that is largely mediated through preterm delivery. TWEETABLE ABSTRACT: Increased risk of cognitive deficits in relation to abruption appears to be mediated through preterm delivery.


Assuntos
Descolamento Prematuro da Placenta/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Trabalho de Parto Prematuro/epidemiologia , Criança , Desenvolvimento Infantil , Pré-Escolar , Cognição , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Nascimento Prematuro , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
4.
Early Hum Dev ; 127: 6-14, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30218893

RESUMO

BACKGROUND: Extremely preterm infants represent one of the highest risk categories for impairments in social competence. Few studies have explored the impact of the neonatal intensive care unit (NICU) environment on social development. However, none have specifically analyzed the effects of the care structure the infant receives during hospitalization on later social competence indicators. OBJECTIVE: To identify associations between the care structures received by extremely preterm infants in the NICU and scores on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) post-discharge. PARTICIPANTS: 50 extremely preterm infants (mean gestational age: 25 weeks during hospitalization; mean chronological age during follow-up assessment: 2 years, 4 months). METHODS: A secondary analysis of BITSEA data was performed exploring its relation to care structure data we extracted from electronic medical records (i.e., how much time infants were engaged in human interaction during their first thirty days of hospitalization and what types of interaction they were exposed to). RESULTS: Extremely preterm infants spend a considerable amount of time alone during hospitalization (80%) with nursing care comprising the majority of human interaction. Infants who experienced greater human interaction scored significantly higher on the Social Competence (p = 0.01) and lower on the Dysregulation (p = 0.03) BITSEA subscales. CONCLUSION: Human interaction and isolation in the NICU is associated with social competence and dysregulation outcomes in extremely preterm infants. Further research is needed to understand how various NICU care structures including centralized nursing teams, parental skin-to-skin care, and early therapy may synergistically play a positive role in developing social competence.


Assuntos
Desenvolvimento Infantil/fisiologia , Emoções/fisiologia , Lactente Extremamente Prematuro/psicologia , Unidades de Terapia Intensiva Neonatal , Relações Interpessoais , Comportamento Social , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
5.
Oncogene ; 25(33): 4595-604, 2006 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-16786001

RESUMO

Cadherin cell-cell adhesion proteins play an important role in modulating the behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell invasion, and when tumor cells turn on the expression of a non-epithelial cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype of the cells. Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin. In addition, we show that this downregulation is owing to increased turnover of the endogenous cadherins via clathrin-dependent endocytosis. p120(ctn) binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120(ctn) may accomplish this is to serve as a rheostat to regulate the levels of cadherin. Here, we show that the degradation of E-cadherin in response to expression of R-cadherin is owing to competition for p120(ctn).


Assuntos
Caderinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Endocitose , Regulação Neoplásica da Expressão Gênica , Fosfoproteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Ligação Competitiva , Caderinas/biossíntese , Cateninas , Adesão Celular , Linhagem Celular Tumoral , Regulação para Baixo , Células Epiteliais/citologia , Humanos , Fenótipo , Estrutura Terciária de Proteína , delta Catenina
6.
Expert Opin Pharmacother ; 17(8): 1043-53, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27042990

RESUMO

OBJECTIVE: To explore the treatment response, tolerability and safety of once-monthly paliperidone palmitate (PP1M) in non-acute patients switched from oral antipsychotics, stratified by time since diagnosis as recently diagnosed (≤3 years) or chronic patients (>3 years). RESEARCH DESIGN AND METHODS: Post hoc analysis of a prospective, interventional, single-arm, multicentre, open-label, 6-month study performed in 233 recently diagnosed and 360 chronic patients. MAIN OUTCOME MEASURES: The proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to endpoint) and maintained efficacy (defined as non-inferiority in the change in PANSS total score at endpoint [Schuirmann's test]). RESULTS: 71.4% of recently diagnosed and 59.2% of chronic patients showed a ≥20% decrease in PANSS total score (p = 0.0028 between groups). Changes in PANSS Marder factors, PANSS subscales, and the proportion of patients with a Personal and Social Performance scale (PSP) total score of 71-100 were significantly greater in recently diagnosed compared with chronic patients. PP1M was well tolerated, presenting no unexpected safety findings. CONCLUSION: These data show that recently diagnosed patients treated with PP1M had a significantly higher treatment response and improved functioning, as assessed by the PSP total score, than chronic patients.


Assuntos
Antipsicóticos/uso terapêutico , Palmitato de Paliperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Doença Crônica , Esquema de Medicação , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
J Am Coll Cardiol ; 24(1): 177-84, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8006263

RESUMO

OBJECTIVES: The purpose of this study was to delineate retrograde His-Purkinje system conduction and reentry (V3 phenomenon) during left ventricular extrastimulation and compare them with right ventricular extrastimulation. BACKGROUND: The V3 phenomenon has been well described in the past during right ventricular extrastimulation; however, it has not been studied systematically during left ventricular extrastimulation. METHODS: Left and right ventricular pacing were performed in 13 patients. Retrograde and anterograde routes of impulse propagation were determined on the basis of the sequence of His (H) and right bundle (RB) potentials, H-RB intervals, as well as the QRS configuration and axis of V3 beats. RESULTS: During right ventricular pacing, retrograde conduction of V2, when discernible, occurred exclusively through the left bundle at all coupling intervals equal to or shorter than the His-Purkinje relative refractory period, with the exception of two isolated beats. During left ventricular extrastimulation, His bundle activation was through the left bundle in nine patients and through the right or left bundle in three other patients. In one patient, the route could not be determined. The V3 phenomena occurred in eight patients during right ventricular pacing. Seven patients had a left bundle branch block pattern QRS configuration, and one had a right bundle branch block pattern configuration. V3 beats occurred in five patients during left ventricular apex pacing: left bundle branch block pattern configuration in one patient and right bundle branch block pattern configuration in four. In three of these four patients, the reentry was interfascicular and limited to the left bundle branch system. CONCLUSIONS: The left-sided His-Purkinje system is the preferred retrograde route of impulse propagation during both left and right ventricular extrastimulation. Reentry within the His-Purkinje system elicited by right ventricular extrastimulation involves both bundle branches, whereas this reentry tends to occur within the left-sided His-Purkinje system during left ventricular pacing.


Assuntos
Fascículo Atrioventricular/fisiopatologia , Ramos Subendocárdicos/fisiopatologia , Função Ventricular Esquerda , Função Ventricular Direita , Adolescente , Adulto , Estimulação Cardíaca Artificial/métodos , Estimulação Cardíaca Artificial/estatística & dados numéricos , Ablação por Cateter , Eletrocardiografia/instrumentação , Eletrocardiografia/estatística & dados numéricos , Eletrodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia
8.
J Am Coll Cardiol ; 19(5): 1005-12, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1552087

RESUMO

Adenosine has been shown to inhibit anterograde and retrograde conduction through the atrioventricular (AV) node while having little or no effect on accessory pathway conduction. Its rapid onset of action and short half-life make it particularly suitable for repetitive measurements. In this study, the utility of adenosine was tested in assessing completeness of accessory pathway ablation. Sixteen patients with an accessory pathway were studied (eight surgical ablations, eight catheter ablations with radiofrequency energy). Before ablation, no accessory pathway was sensitive to adenosine. Twelve patients with pre-excitation showed high grade AV node block with maximal pre-excitation on the administration of adenosine during atrial pacing. Four patients with a concealed accessory pathway demonstrated high grade AV block without evidence of latent anterograde accessory pathway conduction. Preablation ventriculoatrial (VA) block was not observed in any of the 16 patients in response to adenosine during ventricular pacing. Immediately after accessory pathway ablation, all patients developed AV and VA block with the administration of adenosine during atrial and ventricular pacing, respectively. These findings were confirmed during follow-up study 1 week later. Atrioventricular block during atrial and ventricular pacing with adenosine affords a reliable and immediate assessment of successful pathway ablation.


Assuntos
Adenosina , Nó Atrioventricular/efeitos dos fármacos , Eletrocoagulação , Bloqueio Cardíaco/induzido quimicamente , Sistema de Condução Cardíaco/cirurgia , Adenosina/efeitos adversos , Adenosina/farmacologia , Adolescente , Adulto , Idoso , Fibrilação Atrial/cirurgia , Estimulação Cardíaca Artificial , Eletrocardiografia , Eletrocoagulação/métodos , Feminino , Seguimentos , Bloqueio Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Terapia por Radiofrequência , Taquicardia Supraventricular/cirurgia , Resultado do Tratamento
9.
J Psychopharmacol ; 29(8): 910-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25999398

RESUMO

PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults (n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (-7.5 to -10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements (p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Palmitato de Paliperidona/administração & dosagem , Palmitato de Paliperidona/farmacologia , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Palmitato de Paliperidona/efeitos adversos , Estudos Prospectivos , Risperidona/administração & dosagem , Risperidona/farmacologia , Índice de Gravidade de Doença
10.
Neuropharmacology ; 39(7): 1139-46, 2000 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-10760357

RESUMO

LY354740 is a potent and selective agonist at the group II metabotropic glutamate receptors and is shown to be an effective inhibitor of glutamate release with significant anxiolytic and drug withdrawal alleviating properties in certain animal models. Rats with chronic inhibition of GABA synthesis in the dorsomedial hypothalamus (DMH) are highly anxious and exhibit panic-like responses to peripheral lactate infusions similar to patients with panic disorder. Using these panic-prone rats, we tested the efficacy of LY354740 in preventing the lactate-induced panic-like response, comparing it to alprazolam, a clinically effective anti-panic drug. Rats were fitted with femoral arterial and venous catheters and implanted with Alzet pumps infusing the GABA synthesis inhibitor L-allylglycine into the DMH. After four days of recovery, they were confirmed to be panic-prone to lactate infusions as indicated by increases in heart rate, blood pressure, respiratory rate and "anxiety" measured in the social interaction test. Next, they were pretreated with either vehicle, LY354740 (0.3 and 0.6 mg/kg) or alprazolam (0.5 and 1.0 mg/kg) and re-challenged with lactate infusions. LY354740 treatment was equally efficacious as alprazolam in preventing lactate-induced panic attacks in this model. These data suggest that LY354740 could be a novel anti-panic drug, as effective as alprazolam in acute treatment.


Assuntos
Comportamento Animal/efeitos dos fármacos , Compostos Bicíclicos com Pontes/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Láctico/antagonistas & inibidores , Pânico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/agonistas , Alilglicina/farmacologia , Alprazolam/administração & dosagem , Alprazolam/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Compostos Bicíclicos com Pontes/administração & dosagem , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Moduladores GABAérgicos/administração & dosagem , Moduladores GABAérgicos/farmacologia , Glutamato Descarboxilase/antagonistas & inibidores , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo Médio/fisiologia , Infusões Intra-Arteriais , Relações Interpessoais , Ácido Láctico/administração & dosagem , Ácido Láctico/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória/efeitos dos fármacos
11.
J Nucl Med ; 32(5): 777-82, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2022980

RESUMO

Radionuclide ventriculography and contrast ventriculography were performed in two comparable projections on 50 patients with suspected coronary artery disease. The efficacy of conventional cine display and Fourier image analysis of the radionuclide ventriculogram was compared using contrast ventriculography as the gold standard. Of seven different combinations of Fourier images, the combination of left anterior oblique amplitude and phase and left posterior oblique amplitude and phase provided the highest sensitivity (87%), specificity (83%), accuracy (86%), and kappa coefficient (0.64). To increase statistical power, segment data were collapsed to global data in which a heart was considered normal if all segments were normal and abnormal if one or more segments were abnormal. Fourier images had higher sensitivity (Fourier 87%, cine 47%); lower specificity (Fourier 83%, cine 92%), higher accuracy (Fourier 86%, cine 58%), and higher kappa coefficient (Fourier 0.64, cine 0.25), and these differences were statistically significant (p less than 0.01).


Assuntos
Doença das Coronárias/diagnóstico por imagem , Análise de Fourier , Imagem do Acúmulo Cardíaco de Comporta , Filmes Cinematográficos , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Doença das Coronárias/fisiopatologia , Apresentação de Dados , Feminino , Humanos , Masculino
12.
Am J Cardiol ; 65(9): 590-3, 1990 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-2309628

RESUMO

The value of right-sided cardiac catheterization was assessed prospectively in 200 patients undergoing left-sided catheterization for evaluation of known or suspected coronary artery disease. Before catheterization, data from right-sided catheterization was not felt to be necessary for clinical management. There were 6 +/- 2 extra minutes of procedure time and 86 +/- 63 extra seconds of fluoroscopy time used. Abnormalities were detected in 69 (35%) patients. These findings were unexpected in 37 of these patients and in 3 patients, further evaluation was prompted. However, management was altered in only 3 (1.5%) patients as a result of data obtained by right-sided catheterization. In conclusion this additional procedure rarely adds clinically useful information about patients undergoing left-sided catheterization and angiography for coronary artery disease without a clinical indication for right-sided catheterization.


Assuntos
Cateterismo Cardíaco , Doença das Coronárias/diagnóstico , Cateterismo Cardíaco/economia , Custos e Análise de Custo , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
13.
Brain Res ; 739(1-2): 46-51, 1996 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-8955923

RESUMO

Experiments were conducted to test if blockade of GABAA receptors in the dorsomedial hypothalamic nucleus (DMH) of rats, which is known to elicit cardiovascular and anxiety responses, would also elicit changes in the plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone. Male Sprague-Dawley rats were anesthetized with pentobarbital, fitted with femoral arterial catheters and implanted with microinjection cannulae into the DMH or the sites anterior to the DMH (i.e., closer to the paraventricular nucleus (PVN) of the hypothalamus). The rats were then injected with either artificial cerebrospinal fluid (aCSF; 100 nl) or the GABAA antagonist, bicuculline methiodide (BMI; 50 pmol in 100 nl) and their plasma samples obtained at 5, 30, 60, and 120 min after microinjection. Plasma ACTH and corticosterone were measured by using a radioimmunoassay. Rats injected with BMI, but not aCSF, into the DMH showed significant increases in heart rate (HR, 110 +/- 16 beats/min), blood pressure (BP; 30 +/- 4 mmHg), and plasma levels of both ACTH (64 +/- 10 pg/ml) and corticosterone (170 +/- 25 ng/ml) from baseline. BMI injections into the anterior sites closer to the PVN did not elicit significant increases in HR, BP, or plasma levels of ACTH and corticosterone. These results suggest that a tonic GABAA receptor-mediated inhibition system regulates a coordinated physiological and neuroendocrine response in the DMH and that this neuroendocrine response is not due to diffusion of BMI to the PVN of rats.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Corticosterona/metabolismo , Antagonistas GABAérgicos/farmacologia , Antagonistas de Receptores de GABA-A , Hipotálamo Médio/efeitos dos fármacos , Análise de Variância , Animais , Núcleo Hipotalâmico Anterior/efeitos dos fármacos , Coração/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Taxa Secretória/efeitos dos fármacos , Estresse Fisiológico/fisiopatologia
14.
Brain Res ; 548(1-2): 55-62, 1991 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-1868348

RESUMO

Recent studies have demonstrated that intrahippocampal cholinergic septal grafts can ameliorate deficits in spatial memory function and hippocampal cholinergic neurochemical activity in animals with disruptions of the septohippocampal system. However, no study has determined if the restoration of spatial memory function is correlated to the restoration of cholinergic activity, as measured by high-affinity choline uptake (HACU). The present study was designed to determine if such a correlation between behavioral and neurochemical restoration exists. Male Sprague-Dawley rats received either sham lesions (SHAM), bilateral lesions of the septohippocampal pathway (LES), or bilateral lesions along with intrahippocampal septal grafts (SG). After 8 months, rats were tested for their ability to perform spatial reference, spatial navigation and working memory tasks. Upon completion of the behavioral testing, neurochemical activity of the hippocampus was measured by HACU. The results indicate that animals in the SG group had significantly higher behavioral scores and hippocampal HACU rates than animals in the LES group. Regression analysis indicates that a significant correlation exists between performance on each behavioral task and HACU rates. These results demonstrate that hippocampal cholinergic activity, as measured by HACU, correlates significantly with performance on tests of spatial memory function.


Assuntos
Transplante de Tecido Encefálico/fisiologia , Colina/metabolismo , Memória , Neurônios/transplante , Percepção Espacial , Animais , Feminino , Transplante de Tecido Fetal/fisiologia , Aprendizagem , Masculino , Neurônios/fisiologia , Gravidez , Ratos , Ratos Endogâmicos , Análise de Regressão
15.
Neurosci Lett ; 222(2): 135-7, 1997 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-9111747

RESUMO

Linopirdine, a putative cognition enhancing agent, increases neurotransmitter release and blocks M-current in rat brain. Its effects on long-term potentiation (LTP) in the Schaffer collateral/CA1 pathway were investigated using standard, extracellular recording techniques in rat hippocampal slice preparation. When using a half maximal stimulus intensity for tetanic stimulation, a 30 min exposure to 3 or 10 microM linopirdine exerted no significant effect on excitatory postsynaptic potential (EPSP) slope, post-tetanic potentiation or LTP. In contrast, when a weak stimulus was employed, linopirdine enhanced the incidence and amplitude of LTP in a dose-dependent manner. These results indicate that linopirdine reduced stimulus intensity threshold for induction of LTP, an effect which may be mediated by its ability to enhance presynaptic glutamate release and cause CA1 membrane depolarization.


Assuntos
Hipocampo/fisiologia , Indóis/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Piridinas/farmacologia , Animais , Eletrofisiologia , Hipocampo/efeitos dos fármacos , Masculino , Técnicas de Cultura de Órgãos , Ratos
16.
Resuscitation ; 51(3): 269-74, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11738777

RESUMO

OBJECTIVE: To determine the frequency of CPR certification amongst residents living within a predominantly elderly community and examine the perceived barriers to learning basic CPR and factors associated with intent to become certified. METHODS: A household survey was sent with a community newsletter to each home of a non-gated elderly community that requires one member of each household to be at least 55 years of age. The community consists of 2488 homes (approximately 4000 residents). Thirteen Yes/No questions were asked in a skip-pattern based upon the question: "Are you CPR certified?" Data analysis included univariate, bivariate, and logistic regression. RESULTS: 947 participants with a mean age of 69 completed and returned the survey. Forty-eight percent of the participants had received prior training in CPR. Eighty-four percent were not currently certified in CPR, and top reasons cited were: 'don't know why' (36%), 'lack of interest' (20%), 'concerned about health risks' (17%). Forty-six percent of those not certified desired certification. Increasing age was inversely associated with CPR certification status and the desire to be certified. CONCLUSION: Almost half of the residents in this predominantly elderly community had received prior training in CPR, although most were not currently certified and cite significant specific and non-specific reasons and obstacles. Improved survival requires targeted interventions to achieve higher proportions of CPR-competent individuals in such high-risk communities.


Assuntos
Reanimação Cardiopulmonar/educação , Serviços de Saúde Comunitária , Serviços de Saúde para Idosos , Idoso , Arizona , Coleta de Dados , Feminino , Humanos , Masculino
17.
Acad Emerg Med ; 6(11): 1141-6, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10569387

RESUMO

Emergency medicine (EM) program directors have expressed a desire for more evaluative data to be included in application materials. This is consistent with frustrations expressed by program directors of multiple specialties, but mostly by those in specialties with more competitive matches. Some of the concerns about traditional narrative letters of recommendation included lack of uniform information, lack of relative value given for interval grading, and a perception of ambiguity with regard to terminology. The Council of Emergency Medicine Residency Directors established a task force in 1995 that created a standardized letter of recommendation form. This form, to be completed by EM faculty, requests that objective, comparative, and narrative information be reported regarding the residency applicant.


Assuntos
Correspondência como Assunto , Medicina de Emergência/educação , Guias como Assunto , Internato e Residência , Candidatura a Emprego , Avaliação Educacional , Humanos , Estados Unidos
18.
Pharmacol Biochem Behav ; 55(2): 249-56, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8951961

RESUMO

Since impairing gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition in the dorsomedial hypothalamus (DMH) of rats elicits a panic-like response, experiments were conducted to test if rats with GABA dysfunction in the DMH would be vulnerable to precipitation of a panic-like response after intravenous sodium lactate infusions. Rats were implanted with unilateral infusion cannula into the DMH which were connected with Alzet minipumps that chronically infused (3.5 nmol/microliter /h) either a-CSF (vehicle), dl-(racemic), l-(active) or d-(inactive) isomers of allylglycine (AG), an inhibitor of GABA synthesis. Another group of rats had l-allylglycine pumps implanted in the paraventricular nucleus of the hypothalamus (PVN) as anatomical controls. Animals were tested in the social interaction (SI) test and given sodium lactate infusions (10 ml/kg/15 min) before Alzet pump implantations and on days 4, 7, and 14 after pump placement. Rats were also tested in the elevated plus-maze on treatment day 4. Chronic impairment of GABA function in the DMH and not PVN resulted in rats being more anxious in the SI test on treatment days 4, 7, and 14 and in the elevated plus-maze on day 4 compared to a-CSF and d-AG infusions. Further, rats with GABA dysfunction in the DMH, and not PVN, exhibited significant increases in heart rate and blood pressure following IV sodium lactate infusions. There were significant decreases in DMH glutamic acid decarboxylase activity and GABA content in rats receiving 7 days of dl-AG or l-AG infusions. These results indicate that chronic reduction of GABA function in the DMH leads to the development of panic-like disorder in this animal model.


Assuntos
Nível de Alerta/efeitos dos fármacos , Núcleo Hipotalâmico Dorsomedial/fisiologia , Ácido Láctico/farmacologia , Ácido gama-Aminobutírico/fisiologia , Alilglicina/administração & dosagem , Alilglicina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Antagonistas GABAérgicos/administração & dosagem , Antagonistas GABAérgicos/farmacologia , Glutamato Descarboxilase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Bombas de Infusão Implantáveis , Infusões Intravenosas , Ácido Láctico/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtorno de Pânico/induzido quimicamente , Transtorno de Pânico/psicologia , Ratos , Ratos Sprague-Dawley , Comportamento Social
19.
J Occup Environ Med ; 43(4): 317-24, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11322092

RESUMO

A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.


Assuntos
Neoplasias Encefálicas/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Indústrias , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Ocupações , Fatores de Risco
20.
Clin Cardiol ; 14(9): 772-4, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1742911

RESUMO

Accelerated idioventricular rhythm (AIVR) is found most commonly in the presence of underlying heart disease. It is characterized by acceleration of a latent pacemaker that normally depolarizes slowly. We describe a 30-year-old man who was found to have episodes of accelerated idioventricular rhythm (AIVR) on cardiac monitoring during elective orthopedic surgery. Noninvasive evaluation including two-dimensional echocardiography was unremarkable. No late potentials were detected on a signal-averaged electrocardiogram. During an exercise tolerance test, AIVR was suppressed as heart rate increased. A 24-h Holter monitor revealed that the AIVR rate was consistently 73-76 beats/min, which appeared whenever the sinus rate slowed to this level. The patient has been asymptomatic, and the rhythm has persisted at least through a 5-month follow-up period.


Assuntos
Ritmo Idioventricular Acelerado/diagnóstico , Ritmo Idioventricular Acelerado/fisiopatologia , Cotovelo/inervação , Eletrocardiografia , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/fisiopatologia , Síndromes de Compressão Nervosa/cirurgia , Adulto , Nó Atrioventricular/fisiopatologia , Eletrocardiografia Ambulatorial , Teste de Esforço , Humanos , Masculino
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