RESUMEN
This study examined multiple influences on cognitive function among African Americans, including education, literacy, poverty status, substance use, depressive symptoms, and cardiovascular disease (CVD) risk factors. Baseline data were analyzed from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants were 987 African Americans (mean age 48.5 years, SD = 9.17) who completed cognitive measures assessing verbal learning and memory, nonverbal memory, working memory, verbal fluency, perceptuo-motor speed, attention, and cognitive flexibility. Using preplanned hierarchical regression, cognitive performance was regressed on the following: (1) age, sex, education, poverty status; (2) literacy; (3) cigarette smoking, illicit substance use; (4) depressive symptoms; and (5) number of CVD risk factors. Results indicated that literacy eliminated the influence of education and poverty status in select instances, but added predictive utility in others. In fully adjusted models, results showed that literacy was the most important influence on cognitive performance across all cognitive domains (p < .001); however, education and poverty status were related to attention and cognitive flexibility. Depressive symptoms and substance use were significant predictors of multiple cognitive outcomes, and CVD risk factors were not associated with cognitive performance. Overall, findings underscore the need to develop cognitive supports for individuals with low literacy, educational attainment, and income, and the importance of treating depressive symptoms and thoroughly examining the role of substance use in this population.
Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Aprendizaje , Características de la Residencia/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adulto , Factores de Edad , Enfermedades Cardiovasculares/etnología , Disfunción Cognitiva/etnología , Estudios Transversales , Depresión/etnología , Femenino , Humanos , Alfabetización/etnología , Masculino , Persona de Mediana Edad , Fumadores , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/etnologíaRESUMEN
Vertebroplasty provides an effective means of treating painful vertebral lesions although the majority of the literature relates to vertebroplasty using PMMA cement. The purpose of this study is to assess the safety and efficacy of vertebroplasty using Cortoss, a recently developed bis-GMA resin. Our newly established vertebroplasty service exclusively uses Cortoss cement and has a patient database which is updated on a regular basis using the medical records. To date, there are 34 patients on this database, mean age 66, in whom a vertebroplasty has been performed on 42 vertebral lesions with a mean of 2.2 ml of Cortoss injected into each lesion. The mean duration of follow up was 9.5 months. Eighty-two per cent of patients reported an improvement in their symptoms, while 79% required less analgesia post vertebroplasty. A total of 88.2% experienced no significant complications. In 38% there was an asymptomatic leakage of Cortoss. Four patients (11.8%) experienced significant complications: one asymptomatic PE, one episode of transient radicular leg pain, one generalized rash and one patient suffered retropulsion of the Cortoss due to further vertebral malignancy. Cortoss vertebroplasty provides comparable efficacy and safety to the published literature for PMMA.
Asunto(s)
Bisfenol A Glicidil Metacrilato/uso terapéutico , Cementos para Huesos/uso terapéutico , Polimetil Metacrilato/uso terapéutico , Fracturas de la Columna Vertebral/cirugía , Vertebroplastia/métodos , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Resultado del TratamientoRESUMEN
To examine the influence of the putative satiety factor (GLP-1) on the hypothalamo-pituitary-gonadal axis, we used GT1-7 cells as a model of neuronal luteinizing hormone- releasing hormone (LHRH) release. GLP-1 caused a concentration-dependent increase in LHRH release from GT1-7 cells. Specific, saturable GLP-1 binding sites were demonstrated on these cells. The binding of [125I]GLP-1 was time-dependent and consistent with a single binding site (Kd = 0.07+/-0.016 nM; binding capacity = 160+/-11 fmol/mg protein). The specific GLP-1 receptor agonists, exendin-3 and exendin-4, also showed high affinity (Ki = 0.3+/-0.05 and 0.32+/-0.06 nM, respectively) as did the antagonist exendin-(9-39) (Ki = 0.98+/-0.24 nM). At concentrations that increased LHRH release, GLP-1 (0.5-10 nM) also caused an increase in intracellular cAMP in GT1-7 cells (10 nM GLP-1: 7.66+/-0.4 vs. control: 0.23+/-0.02 nmol/mg protein; P < 0.001). Intracerebroventricular injection of GLP-1 at a single concentration (10 microg) produced a prompt increase in the plasma luteinizing hormone concentration in male rats (GLP-1: 1.09+/-0.11 vs. saline: 0.69+/-0.06 ng/ml; P < 0.005). GLP-1 levels in the hypothalami of 48-h-fasted male rats showed a decrease, indicating a possible association of the satiety factor with the low luteinizing hormone levels in animals with a negative energy balance.
Asunto(s)
Glucagón/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Fragmentos de Péptidos/farmacología , Precursores de Proteínas/farmacología , Ponzoñas , Animales , Calcio/análisis , Calcio/metabolismo , AMP Cíclico/metabolismo , Citoplasma/metabolismo , Relación Dosis-Respuesta a Droga , Exenatida , Privación de Alimentos , Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón , Hipotálamo/citología , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Masculino , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/metabolismo , Péptidos/metabolismo , Péptidos/farmacología , Precursores de Proteínas/administración & dosificación , Ratas , Ratas Wistar , Receptores de Superficie Celular/metabolismo , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
While the past century has seen significant improvement in life expectancies in the developed world, it has also witnessed diseases like HIV/AIDS, malaria and tuberculosis ravage populations in the developing world. In some Sub-Saharan African countries, life expectancies have plummeted to less than 40 years--nearly half of those in developed countries. Unequal access to the benefits of science and technology, including medical advances, exacerbate this disparity. In order to address the challenge of global health inequities and strengthen the role of science and technology innovation in contributing to real solutions, the Canadian Program on Genomics and Global health (CPGGH), based at the University of Toronto, has identified three guiding questions: Which genomics-related technologies are most likely to improve the health of people in developing countries?; How can developing countries harness these technologies for health development?; and What can industrialized countries do to assist developing countries?
Asunto(s)
Países en Desarrollo , Genómica/tendencias , Necesidades y Demandas de Servicios de Salud/organización & administración , Tecnología , África , África del Sur del Sahara , Biotecnología/organización & administración , Salud Global , Humanos , Nanotecnología , Desarrollo de Programa , Transferencia de TecnologíaRESUMEN
The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and beta2-integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L-selectin on neutrophils binds PSGL-1. At relatively low shear rates (100-200 s(-1)) firm adhesion is mediated in equal measure by LFA-1 binding to ICAM-3, and Mac-1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM-1 (CD54) to examine the relative roles of LFA-1 and Mac-1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L-selectin nor its O-glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose-dependent manner as ICAM-1 was titrated with blocking mAb. A direct interaction between LFA-1 and ICAM-1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac-1. Activation with MnCl2 also favored participation of the constitutively expressed LFA-1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM-1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s(-1) in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s(-1). The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte-endothelial cell interactions on surfaces is discussed.
Asunto(s)
Antígenos CD18/fisiología , Molécula 1 de Adhesión Intercelular/fisiología , Neutrófilos/citología , Animales , Adhesión Celular , Agregación Celular/fisiología , Comunicación Celular , Cloruros/farmacología , Citometría de Flujo , Humanos , Selectina L/fisiología , Antígeno-1 Asociado a Función de Linfocito/fisiología , Antígeno de Macrófago-1/fisiología , Compuestos de Manganeso/farmacología , Melanoma Experimental/patología , Glicoproteínas de Membrana/fisiología , Ratones , Neutrófilos/metabolismo , Estrés Mecánico , Células Tumorales CultivadasRESUMEN
Our previous studies have demonstrated that lipocortin 1 (LC1, also called annexin 1) is an important mediator of glucocorticoid action in the neuroendocrine system, particularly with regard to the powerful inhibitory actions of the steroids on the secretion of ACTH and its hypothalamic releasing hormones. In the present study, we have used an antisense oligodeoxynucleotide (ODN) unique to LC1 to investigate further the role of this protein in the regulatory effects of dexamethasone on ACTH release in vitro from rat anterior pituitary cells. Pituitary cells dispersed with collagenase retained their functional and morphological integrity in vitro and sequestered ODNs in a time-dependent manner from the incubation medium. LC1 was readily detected in the cells by Western blot analysis or by immunoprecipitation/autoradiography after preloading with 35S-methionine/cysteine; the bulk of the protein was contained within an intracellular pool but a small amount was attached to the outer cell surface (pericellular). Dexamethasone (100 nm, 2.5 h) initiated de novo synthesis of LC1; it also increased the amount of LC1 in the pericellular pool detected by either method and caused a concomitant decrease in intracellular LC1. The responses to the steroid were prevented by the inclusion in the medium of an LC1 antisense ODN (50 nM, 3.5 h) but the corresponding sense and scrambled ODN sequences were inert. None of the ODN sequences tested influence the expression of annexin 5 in the pituitary tissue. CRH-41 (100 pM-1 mM), forskolin (1 nM-1 mM) and an L-Ca2+-channel opener BAY K8644 (100 pM-1 microM) initiated concentration dependent increases in immunoreactive- (ir-) ACTH release from the pituitary cells that were reduced (P < 0.01) by preincubation with dexamethasone (100 nM, 2.5 h). The inhibitory effects of the steroid were reversed by the LC1 antisense ODN (50 nM, P < 0.01), whereas the LC1 sense and scrambled control sequences (50 nM) were both ineffective in this respect (P > 0.05). The results add further support to the view that the acute inhibitory effects of glucocorticoids on the secretion of ACTH by the pituitary gland are dependent on the generation of lipocortin 1.
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Anexina A1/genética , Dexametasona/farmacología , Glucocorticoides/farmacología , Oligonucleótidos Antisentido/farmacología , Adenohipófisis/metabolismo , Tionucleótidos/farmacología , Animales , Western Blotting , Compartimento Celular , Células Cultivadas , ADN Complementario/metabolismo , Electroforesis en Gel de Poliacrilamida , Masculino , Microscopía Confocal , Adenohipófisis/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Lipocortin 1 (LC1) is an important mediator of glucocorticoid action in the anterior pituitary gland, where it appears to act via cell surface binding sites to suppress peptide release. We have exploited a combination of fluorescence-activated cell (FAC) analysis/sorting and electron microscopy to detect, characterize, and localize LC1-binding sites on the surface of dispersed rat anterior pituitary cells, using human recombinant LC1 (hu-r-LC1) as a probe. High affinity (Kd = 14 +/- 3 nM) hu-r-LC1-binding sites were detected on approximately 80% of anterior pituitary cells dispersed with collagenase. The binding characteristics of the ligand resembled those observed in leukocytes, in that it was saturable; concentration, Ca2+, and temperature dependent; and abolished by trypsin. Functional studies demonstrated an excellent correlation between the presence of the cell surface binding protein and the capacity of an anti-LC1 monoclonal antibody to abrogate the inhibitory actions of dexamethasone (10 nM) on the release of ACTH initiated in vitro by CRH-41 (1 nM). Morphological analysis of cells harvested by FAC sorting showed that 1) somatotrophs, corticotrophs, lactotrophs, thyrotrophs, and gonadotrophs were all included in the population expressing LC1 binding sites; and 2) the LC1-binding sites assume a punctate distribution across the cell surface. These data show that anterior pituitary cells express high affinity surface LC1-binding protein(s); they thus provide further evidence for a specific membrane mechanism of action of LC1 in regulating the endocrine function of the anterior pituitary.
Asunto(s)
Anexina A1/metabolismo , Adenohipófisis/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Animales , Sitios de Unión , Células Sanguíneas/metabolismo , Separación Celular , Citometría de Flujo , Humanos , Leucocitos/metabolismo , Masculino , Microscopía Electrónica , Adenohipófisis/citología , Ratas , Proteínas Recombinantes/metabolismo , Distribución TisularRESUMEN
Our previous studies have identified a role for annexin 1 (also called lipocortin 1) in the regulatory actions of glucocorticoids (GCs) on the release of PRL from the rat anterior pituitary gland. In the present study we used antisense and immunoneutralization strategies to extend this work. Exposure of rat anterior pituitary tissue to corticosterone (1 nM) or dexamethasone (100 nM) in vitro induced 1) de novo annexin 1 synthesis and 2) translocation of the protein from intracellular to pericellular sites. Both responses were prevented by the inclusion in the medium of an annexin 1 antisense oligodeoxynucleotide (ODN; 50 nM), but not by the corresponding sense and scrambled ODN sequences. Unlike the GCs, 17beta-estradiol, testosterone, and aldosterone (1 nM) had no effect on either the synthesis or the cellular disposition of annexin 1; moreover, none of the steroids or ODNs tested influenced the expression of annexin 5, a protein closely related to annexin 1. The increases in PRL release induced in vitro by drugs that signal via cAMP/protein kinase A [vasoactive intestinal polypeptide (10 nM), forskolin (100 microM), 8-bromo-cAMP (0.1 microM)] or phospholipase C (TRH, 10 nM) were attenuated by preincubation of the pituitary tissue with either corticosterone (1 nM) or dexamethasone (100 nM). The inhibitory actions of the steroids on the secretory responses to vasoactive intestinal polypeptide, forskolin, and 8-bromo-cAMP were specifically quenched by inclusion in the medium of the annexin 1 antisense ODN (50 nM) or a neutralizing antiannexin 1 monoclonal antibody (antiannexin 1 mAb, diluted 1:15,000). By contrast, the ability of the GCs to suppress the TRH-induced increase in PRL release was unaffected by both the annexin 1 antisense ODN and the antiannexin 1 mAb. In vivo, interleukin-1beta (10 ng, intracerebroventricularly) produced a significant increase in the serum PRL concentration (P < 0.01), which was prevented by pretreatment of the rats with corticosterone (100 microg/100 g BW, sc). The inhibitory actions of the steroid were specifically abrogated by peripheral administration of an antiannexin 1 antiserum (200 microl, sc); by contrast, when the antiserum was given centrally (3 microl, intracerebroventricularly), it was without effect. These results support our premise that annexin contributes to the regulatory actions of GCs on PRL secretion and suggest that it acts at point distal to the formation of cAMP.
Asunto(s)
Anexina A1/fisiología , AMP Cíclico/farmacología , Glucocorticoides/farmacología , Prolactina/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Animales , Anexina A1/análisis , Anexina A1/inmunología , Colforsina/farmacología , Corticosterona/farmacología , AMP Cíclico/antagonistas & inhibidores , Dexametasona/farmacología , Sueros Inmunes/farmacología , Interleucina-1/administración & dosificación , Interleucina-1/farmacología , Masculino , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Prolactina/sangre , Ratas , Ratas Sprague-Dawley , Tirotropina/sangre , Hormona Liberadora de Tirotropina/farmacología , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.
Asunto(s)
Angioplastia de Balón/instrumentación , Hipertensión Renovascular/terapia , Obstrucción de la Arteria Renal/terapia , Stents , Adulto , Anciano , Angiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Renovascular/diagnóstico por imagen , Hipertensión Renovascular/etiología , Masculino , Persona de Mediana Edad , Obstrucción de la Arteria Renal/diagnóstico por imagen , Obstrucción de la Arteria Renal/etiología , Resultado del TratamientoRESUMEN
This study was designed to assess the efficacy of bepridil in reducing regional myocardial ischemia and to compare its efficacy with that of verapamil. Forty-five anesthetized, open-chest dogs were subjected to three 5-minute occlusions of the left anterior descending coronary artery (LAD), each followed by 45 minutes of reperfusion. Eleven dogs (group 1) served as controls. In 10 dogs, bepridil, 5 mg/kg, was administered before the third occlusion (group 2). In 11 dogs, verapamil was administered before the third occlusion (group 3). In each dog, on-line intramyocardial hydrogen ion concentration and carbon dioxide tension were measured in the myocardial segment supplied by the LAD. Regional myocardial contractility was assessed in this area with 2 pairs of ultrasonic crystals inserted to determine percent segmental shortening. Regional myocardial blood flow was determined during each occlusion by washout of xenon-127. The increase in hydrogen ion concentration and carbon dioxide tension did not change from occlusion 2 to occlusion 3 in the control group. Both bepridil and verapamil elicited a significant reduction in the extent of regional ischemia, evidenced by a reduction in the accumulation of hydrogen ions, in occlusion 3 vs occlusion 2. Systolic bulging occurred during all occlusions and the periods of reperfusion were not sufficient to allow complete recovery of regional function. Bepridil and verapamil each caused a significant increase in percent segmental shortening (both p less than 0.025), and verapamil effected a significant improvement of function during occlusion 3 compared with occlusion 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/fisiopatología , Pirrolidinas/farmacología , Verapamilo/farmacología , Animales , Bepridil , Dióxido de Carbono/metabolismo , Perros , Concentración de Iones de Hidrógeno , Contracción Miocárdica/efectos de los fármacos , Miocardio/metabolismoRESUMEN
1. Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. 2. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3'5'-monophosphate (8-Br-cyclic AMP) and an L-Ca(2+) channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. 3. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. 4. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. 5. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca(2+) entry.
Asunto(s)
Anexina A1/fisiología , Anticuerpos Monoclonales/farmacología , ADN sin Sentido/farmacología , Glucocorticoides/farmacología , Hormona del Crecimiento/efectos de los fármacos , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Anexina A1/genética , Anexina A1/inmunología , Colforsina/farmacología , Corticosterona/farmacología , Dexametasona/farmacología , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Técnicas In Vitro , Masculino , Microscopía Electrónica , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Hipófisis/ultraestructura , Ratas , Ratas Sprague-DawleyRESUMEN
Glucocorticoids have been shown repeatedly to inhibit the secretion of TSH in experimental animals and in man but their site and mode of action are unknown. In the present study, we have used an in vitro model to examine the effects of dexamethasone on the resting and pharmacologically evoked secretion of TSH by the rat anterior pituitary gland, and to show how they are influenced by inhibitors of RNA/protein synthesis. In addition, we have investigated the potential role of lipocortin 1 (LC1), a protein shown previously to contribute to glucocorticoid action in several systems, as a mediator of the glucocorticoid-induced suppression of TSH release in our in vitro preparation. The significant (P < 0.01) increases in the release of immunoreactive (ir)TSH from rat anterior pituitary tissue initiated by submaximal concentrations of TRH (10 nmol/l), vasoactive intestinal polypeptide (VIP, 10 nmol/l) or the adenyl cyclase activator, forskolin (100 mumol/l) were reduced significantly (P < 0.05) by preincubation of the tissue with dexamethasone (0.1 mumol/l). In contrast, irTSH secretion evoked by a submaximal concentration of the L-Ca2+ channel opener BAY K8644 (10 mumol/l) was unaffected by the steroid, although readily antagonised (P < 0.01) by nifedipine (1-100 mumol/l). Inclusion of actinomycin D (1.78 mumol/l) or cycloheximide (0.8 mumol/l), inhibitors of RNA and protein synthesis respectively, in the medium effectively abrogated the inhibitory effects of dexamethasone (0.1 mumol/l) on the secretory responses to TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l). LC1 was readily detectable by Western blotting in protein extracts of freshly excised anterior pituitary tissue. A small proportion of the protein was found to be attached to the outer surface of the cells where it was retained by a Ca(2+)-dependent mechanism. Exposure of the tissue to dexamethasone (0.1 mumol/l) caused a pronounced increase in the amount of cellular LC1 attached to the outer surface of the cells and a concomitant decrease in the intracellular LC1 pool. Progesterone (0.1 mumol/l) and aldosterone (0.1 mumol/l) were also weakly active in this regard, but thyroxine and tri-iodothyronine (0.1 mumol/l) were not. Addition of an N-terminal LC1 fragment, LC1(1-188) (0.05-0.53 pmol/l) to the incubation medium reduced significantly (P < 0.01) the increases in irTSH release induced by TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l), but failed to influence (P < 0.05) those initiated by BAY K8644 (10 mumol/l). Furthermore, the inhibitory actions of dexamethasone (0.1 mumol/l) on the release of irTSH provoked by TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l) were substantially reversed (P < 0.01) by a specific monoclonal anti-LC1 antibody, while an isotype-matched control antibody was without effect. The results show clearly that dexamethasone, a semi-synthetic glucocorticoid, acts at the pituitary level to inhibit the neurochemically evoked release of irTSH. They also provide novel evidence that the inhibitory actions of the steroid are dependent upon de novo RNA/protein synthesis and that they involve an LC1 dependent mechanism.
Asunto(s)
Anexina A1/farmacología , Dexametasona/farmacología , Adenohipófisis/metabolismo , Biosíntesis de Proteínas , Tirotropina/metabolismo , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Colforsina/farmacología , Depresión Química , Técnicas In Vitro , Masculino , Adenohipófisis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Hormona Liberadora de Tirotropina/farmacología , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
The recent introduction of the determinations of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by radioimmunoassay provided a new tool to obtain knowledge of in vivo platelet activation. We evaluated the plasma level of PF4 and beta TG in 14 normal subjects (mean PF4 7.7 ng/ml; beta TG 28.8 ng/ml), in 29 patients with chronic stable cardiovascular disorders (mean PF4 9.8 ng/ml; beta TG 32.6 ng/ml) and in 15 diabetics with vascular disease (mean PF4 14.5 ng/ml; beta TG 41.8 ng/ml). The great majority had normal values and no statistical differences were noted among the three groups (p greater than 0.05). Fifteen days of treatment with 150 mg daily of dipyridamole produced a significant reduction in the levels of both proteins (p less than 0.01), in contrast of the daily administration of 650 mg of aspirin, which failed to produce any significant change (p greater than 0.5). The patients and the normal subjects were also administered 3,000 USP units intravenously of porcine heparin. The values of the heparin released-platelet factor 4 (HR-PF4), evaluated 5 minutes after the injection, showed a good correlation between platelet concentration and HR-PF4 levels (z = 2.37, p less than 0.02) in the patients. The determination of standard residual following linear regression analysis of HR-PF4 indicated the presence of two distinct patient populations. One group, including the vast majority of patients, did not differ from the control (patients mean HR-PF4 111.1 ng/ml; controls: mean HF-PF4 136 ng/ml). The other group, with severe cardiovascular disease, but with normal levels of PF4 and beta TG in almost all patients and similar platelet concentrations, showed a significantly higher HR-PF4 (219 ng/ml). Neither aspirin nor dipyridamole had any effect on the level of HR-PF4. This HR-PF4 could represent a possible marker of the interaction of platelets with a seriously damaged atherosclerotic vessel wall.
Asunto(s)
Factores de Coagulación Sanguínea/análisis , Enfermedades Cardiovasculares/sangre , Heparina/farmacología , Factor Plaquetario 4/análisis , Adulto , Anciano , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Dipiridamol/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , beta-Tromboglobulina/análisisRESUMEN
This study was based on a nationwide sample of 778 family practice residents in the mid-1980s and was conducted to determine the personality types that were most common among those residents. The results showed that the single most common personality type was that in which the individual prefers to see the world in terms of challenges and future possibilities and to make decisions based upon his or her subjective values. These results showed that the sample differed significantly in Myers-Briggs personality type from both the general practitioners of the 1950s and the early family practice residents of the 1970s, who preferred to see the world in terms of the immediate facts of experience and to make decisions objectively. There were also significant differences between the civilian and military family practice residents, but not between the community-based and university-based residents. Implications regarding future practice styles, physicians' personal values, and manpower needs are discussed.
Asunto(s)
Selección de Profesión , Medicina Familiar y Comunitaria , Internado y Residencia , Personalidad , Distribución de Chi-Cuadrado , Hospitales Militares , Humanos , Pruebas de Personalidad , Factores de TiempoRESUMEN
The double-contrast barium enema is an examination of high radiation exposure to the patient. As part of a departmental audit, our own fluoroscopic screening times were being recorded. A study was undertaken to see if a determined effort could reduce the screening time without having a detrimental effect on the quality of the examinations. Methods of screening time reduction were identified and then implemented by two radiologists. In the period before the study the average screening time for radiologists A and B was 2.6 min and 3.2 min, respectively (over 56 examinations). After implementation of the changes, the average screening time for both was 0.9 min (over 50 examinations). This is a statistically significant reduction (p less than 0.01). The examinations were assessed independently by a gastroradiologist. No difference in the quality of the examinations was identified. We conclude that a significant reduction of screening time for the double-contrast barium enema can be achieved without loss of examination quality.
Asunto(s)
Sulfato de Bario , Enema , Enfermedades Intestinales/diagnóstico por imagen , Intestino Grueso/diagnóstico por imagen , Auditoría Médica , Humanos , Dosis de Radiación , Radiografía , Factores de TiempoRESUMEN
The pathogenesis of idiopathic multifocal osteonecrosis is poorly understood. It is difficult to diagnose with conventional radiography or computed tomography and poses a great management challenge. A case of idiopathic multifocal osteonecrosis is presented in a young boy illustrating the difficulties in the management of such patients.
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Huesos del Pie/patología , Osteonecrosis , Niño , Humanos , Imagen por Resonancia Magnética , Masculino , Osteonecrosis/etiología , Osteonecrosis/patología , Osteonecrosis/terapiaRESUMEN
BACKGROUND AND OBJECTIVES: Family medicine has the highest percentage of unfilled budgeted faculty positions of all clinical and basic science departments. To successfully recruit and retain academic leaders, personal and professional issues need to be recognized and valued. This study reports the results of a national survey of chairs and an important, often overlooked factor in recruitment and retention--the spouse of the department chair. METHODS: Questionnaires were sent to 107 chairs of academic departments or divisions of family medicine and their spouses. RESULTS: There was a usable response rate of 86%, and data from 85 questionnaires (79%) were analyzed. The spouses' highest role priority was family, perhaps reflecting their relatively young mean age of 48.6 years. There was a statistically significant correlation between those who were "oriented" to the role of chair's spouse and a higher level of participation in departmental activities. Data are also reported on spouse role satisfaction, expectations, and factors in deciding to stay or leave their current location. CONCLUSIONS: The results suggest that with the increased competition for family physicians in a multitude of practice settings, search committees for family medicine department chairs need to be innovative and attentive to personal as well as professional factors in recruiting and retaining future and current department chairs. It would be prudent to acknowledge the role of the spouse in decisions concerning job selection and satisfaction.
Asunto(s)
Docentes Médicos/provisión & distribución , Medicina Familiar y Comunitaria/educación , Lealtad del Personal , Rol , Esposos/psicología , Adulto , Actitud , Femenino , Objetivos , Humanos , Masculino , Persona de Mediana Edad , Satisfacción Personal , Estados UnidosRESUMEN
This study describes the construction and calibration of a three-channel bandage pressure monitor and evaluates its in-service use. The monitor was constructed from a range of commercially available, relatively inexpensive components consisting of a pressure sensor, piezoresistive transducer, differential amplifier and liquid crystal display. The pressure sensors show a good ratio of thickness to surface area (< 10%) and are sufficiently robust and flexible to conform to most anatomical profiles. The transducers are internally calibrated and temperature-compensated to provide an accurate and stable measurement of gauge pressure relative to atmospheric pressure. During laboratory assessment and in-service use, the system has proved to be reliable, accurate (typically < +/- 0.5 mmHg) and reproducible over repeated calibration.
Asunto(s)
Vendajes , Manometría/instrumentación , Monitoreo Fisiológico/instrumentación , Procesamiento de Señales Asistido por Computador , Calibración , Diseño de Equipo , Humanos , Presión , Estudios Prospectivos , Reproducibilidad de los Resultados , TransductoresRESUMEN
Fourteen nurses with experience in the use of high-compression bandaging were asked to bandage the same limb with two different bandaging systems: the 'Charing Cross' four-layer regimen (System A), and a modified system incorporating two new bandages (System B). A sub-bandage pressure monitor was used to quantify the efficacy of the resulting bandaging for the two systems. The results indicated that there was no significant difference between site sub-bandage pressures achieved using the two bandaging systems. Sub-bandage pressure profiles, however, fluctuated with patient posture, the best profiles being obtained with System B and the patient in the sitting position.
Asunto(s)
Vendajes/normas , Úlcera de la Pierna/enfermería , Vendajes/efectos adversos , Vendajes/provisión & distribución , Humanos , Úlcera de la Pierna/fisiopatología , Postura , Presión , Reproducibilidad de los Resultados , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
The aim of this investigation was to determine the relationship between muscle performance and the myosin heavy chain (MHC) composition and the reliability of electrophoretically determined MHC compositions. A total of thirty-one male subjects participated in the experiments. Maximal voluntary isometric contractions (MVC) of the knee extensors were performed at an arbitrary knee angle of 90 degrees and the following variables were recorded: maximal isometric force, muscle fibre conduction velocity (MFCV), electromechanical delay (EMD), maximal rate of force development (MRFD), median frequency of EMG (MF) and iEMG. Static isometric contractions of the knee extensors were held at an angle of 90 degrees using contractile forces of 10%, 50% and 100% MVC, respectively. These tests were conducted on separate days. Muscle biopsy samples were obtained from the left m. vastus lateralis before MVC and static endurance tests. MHC protein isoform differences were determined through sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) followed by densitometric analysis. Type I-MHC compositions of the m. vastus lateralis ranged from 20-68% with a mean of 49 +/- 18%, mean type IIa-MHC and type IIb-MHC percentages were 35 +/- 16% and 16 +/- 10%, respectively. MHC compositions of duplicate biopsy samples were not significantly different from that of original samples. The coefficients of variation calculated for duplicate biopsy samples suggested reasonable reproducibility for MHC isoform differentiation for type I-MHC and type-II MHC composition (CV = 12.6%). Differentiation between type IIa-MHC and type IIb-MHC was not always clear using the densitometric traces. Subjects with higher percentages of type II-MHC displayed significantly faster MFCV (r = 0.67, P < 0.1), isometric force development (r = 0.68, P < 0.1) and shorter periods of EMD (r = -0.72, P < 0.05). There was also a tendency toward faster MRFD in these subjects although results did not reach significance. Endurance times for isometric contractions held at 10%, 50% and 100% MVC to exhaustion were not correlated with MHC composition. No relationships between II-MHC composition and MF or iEMG were observed. It was suggested that surface electromyographic recordings obtained during isometric MVC did not reflect underlying differences in muscle fibre composition.