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1.
Int J Gynaecol Obstet ; 87(2): 203-10, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15491581

RESUMEN

OBJECTIVES: Percentage of deliveries assisted by a skilled birth attendant (SBA) has become a proxy indicator for reducing maternal mortality in developing countries, but there is little data on SBA competence. Our objective was to evaluate the competence of health professionals who typically attend hospital and clinic-based births in Benin, Ecuador, Jamaica, and Rwanda. METHODS: We measured competence against World Health Organization's (WHO) Integrated Management of Pregnancy and Childbirth guidelines. To evaluate knowledge, we used a 49-question multiple-choice test covering seven clinical areas. To evaluate skill, we had participants perform five different procedures on anatomical models. The 166 participants came from facilities at all levels of care in their respective countries. RESULTS: On average, providers answered 55.8% of the knowledge questions correctly and performed 48.2% of the skills steps correctly. Scores differed somewhat by country, provider type, and subtopic. CONCLUSION: A wide gap exists between current evidence-based standards and current levels of provider competence.


Asunto(s)
Competencia Clínica , Servicios de Salud Materna/normas , Partería/normas , Evaluación de Resultado en la Atención de Salud , Benin/epidemiología , Ecuador/epidemiología , Femenino , Humanos , Recién Nacido , Jamaica/epidemiología , Partería/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones del Embarazo/mortalidad , Complicaciones del Embarazo/prevención & control , Rwanda/epidemiología , Organización Mundial de la Salud
2.
Gut ; 53(7): 1010-9, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15194653

RESUMEN

BACKGROUND AND AIMS: Hepatic concentrations of the powerful vasoconstrictor and fibrogen endothelin 1 (ET-1) and its receptors increase in human and experimental cirrhosis, suggesting a major role for ET-1 in the pathology of chronic liver disease. We investigated whether ET-1 receptor antagonism, after the development of fibrosis and cirrhosis, arrests/reverses the progression of chronic liver disease. METHODS: Chronic liver injury was induced in rats by carbon tetrachloride (CCl(4)) treatment (0.15 ml/kg intraperitoneally twice a week) in conjunction with phenobarbital in drinking water (0.4 g/l) for four (group 1: fibrosis) and eight (group 2: cirrhosis) weeks. Rat were then treated concurrently with the ET-1 receptor antagonist TAK-044 (10 mg/kg/day) and CCl(4)/phenobarbital for a further four weeks. RESULTS: Histopathological examination revealed significant arrest of progression to cirrhosis in group 1 and reversal of cirrhosis in group 2 rats. TAK-044 treatment caused significant amelioration of portal hypertension, systemic hypotension, and liver injury (reduced activities of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), and improved hepatic synthetic capacity (increased serum albumin concentration) in both groups of rats relative to vehicle treated rats. TAK-044 treatment reduced collagen synthesis, as evidenced by decreased hepatic hydroxyproline content, mRNA expression of collagen-alpha type I, and tissue inhibitors of matrix metalloproteinases 1 and 2, and mRNA and protein expression of a potent fibrogenic cytokine, transforming growth factor beta1. CONCLUSIONS: The results emphasise the role of ET-1 in the development of cirrhosis and strongly suggest that blockade of its actions can be a rational therapy for chronic liver disease and its complications.


Asunto(s)
Antagonistas de los Receptores de Endotelina , Cirrosis Hepática Experimental/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Animales , Tetracloruro de Carbono , Progresión de la Enfermedad , Endotelina-1/metabolismo , Endotelina-1/fisiología , Hipertensión Portal/tratamiento farmacológico , Hígado/metabolismo , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Endotelina/metabolismo
3.
Gut ; 53(6): 877-83, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15138217

RESUMEN

BACKGROUND AND AIMS: The liver is a major site for the synthesis and actions of platelet activating factor (PAF), a potent hepatic vasoconstrictor and systemic vasodilator. As PAF is implicated in portal hypertension and hyperdynamic circulation associated with liver cirrhosis, we characterised changes in the hepatic PAF system in experimental cirrhosis. METHODS: In rats made cirrhotic by carbon tetrachloride (CCl(4)) administration for eight weeks, we determined hepatic levels of PAF and its cognate receptor, and the effects of PAF and PAF antagonist (BN52021) on portal and arterial pressure. RESULTS: Compared with control rats, cirrhotic rats had higher hepatic PAF levels, higher apparent hepatic efflux of PAF, and higher PAF levels in arterial blood (p<0.01, p<0.01, p<0.05, respectively). Relative to controls, cirrhotic livers had elevated hepatic PAF receptors (by mRNA and protein levels and [(3)H]PAF binding), higher (p<0.01) baseline hepatic portal pressure, and an augmented (p = 0.03) portal pressure response to PAF infusion (1 microg/kg). Portal infusion of BN52021 (5 mg/kg) showed that elevated endogenous PAF was responsible for 23% of the cirrhotic portal pressure increase but made no contribution to systemic hypotension. Finally, increased PAF receptor density was observed in the contractile perisinusoidal stellate cells isolated from cirrhotic livers relative to those from control livers. CONCLUSIONS: In cirrhosis, increased hepatic release of PAF elevates systemic PAF; in combination with upregulated hepatic PAF receptors in stellate cells, this contributes to portal hypertension.


Asunto(s)
Tetracloruro de Carbono/toxicidad , Cirrosis Hepática Experimental/metabolismo , Factor de Activación Plaquetaria/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Diterpenos/farmacología , Ginkgólidos , Lactonas/farmacología , Cirrosis Hepática Experimental/inducido químicamente , Masculino , Presión Portal/efectos de los fármacos , Presión Portal/fisiología , Ratas , Ratas Sprague-Dawley , Ganglio Estrellado/metabolismo
4.
Biochem Biophys Res Commun ; 288(3): 558-63, 2001 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-11676479

RESUMEN

Down-regulation and recovery of endothelin (ET) receptors and of ET-dependent phosphoinositide-specific phospholipase C (PI-PLC) signaling was examined in cultured cardiomyocytes from neonatal rats. Three hours treatment with 5 nM ET-1 decreased surface receptors to 30%, and transduction to 19%, of their respective time-zero values. After extensive washing and a 3 h recovery period surface receptors returned to 74% of the time-zero value, with concomitant recovery of signal transduction to 75% of the time-zero value. The recovery of PI-PLC signaling in these cells is in contrast with a previous report, but consistent with recovery of the receptor complement.


Asunto(s)
Endotelina-1/metabolismo , Miocardio/metabolismo , Transducción de Señal/fisiología , Animales , Autacoides/metabolismo , Sitios de Unión , Células Cultivadas , Regulación hacia Abajo , Radioisótopos de Yodo , Fosfatidilinositol Diacilglicerol-Liasa , Fosfoinositido Fosfolipasa C , Ratas , Fosfolipasas de Tipo C/metabolismo
5.
Eur J Pharmacol ; 415(1): 13-8, 2001 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-11245846

RESUMEN

The Ca2+ ionophore A23187 is routinely used to illustrate the extracellular Ca2+-dependence of a variety of cellular reactions. We found that A23187-induced hydrolysis of phosphoinositides to various inositol phosphates in rat Kupffer cells was accompanied by their release from the cells. The synthesis and release of inositol phosphates was A23187 concentration-dependent (0.5-10 microM), and was apparent at the lowest concentration tested. A23187-induced release of inositol phosphates increased time-dependently, was apparent at 5 s of stimulation and maximal at 20 min. The effects of A23187 were reversed by EGTA. The integrity of the cells was not affected by A23187 treatment as indicated by their exclusion of trypan blue and the lack of release of lactate dehydrogenase. We propose that such effects should be considered while evaluating the Ca2+-dependence of biological processes based on the actions of A23187.


Asunto(s)
Calcimicina/farmacología , Fosfatos de Inositol/metabolismo , Ionóforos/farmacología , Macrófagos del Hígado/efectos de los fármacos , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Células Cultivadas , Quelantes/farmacología , Relación Dosis-Respuesta a Droga , Ácido Egtácico/farmacología , Macrófagos del Hígado/citología , Macrófagos del Hígado/metabolismo , Masculino , Factor de Activación Plaquetaria/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
6.
Med Ref Serv Q ; 20(4): 63-71, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11865764

RESUMEN

End-of-life care is a hot topic in many hospitals of late, in part due to an aging society, which is forcing health care professionals to address the issue. A culture that places enormous value on youth and avoids the topic of death also contributes to the discomfort many health care professionals feel discussing this topic with their patients and family members. Inpatient satisfaction survey scores at Thunderbird Samaritan Medical Center (TSMC) were very inconsistent on the question of how the institution was meeting the emotional and/or spiritual needs of patients. A staff survey and needs assessment was also conducted regarding end-of-life care, which pointed out communication issues among staff members. All of these factors led to the development of an inter-disciplinary team to examine the issue of end-of-life care at TSMC.


Asunto(s)
Actitud Frente a la Muerte , Hospitales Comunitarios/normas , Cuidado Pastoral/normas , Satisfacción del Paciente/estadística & datos numéricos , Cuidado Terminal/normas , Arizona , Comunicación , Humanos , Capacitación en Servicio , Bibliotecólogos , Bibliotecas de Hospitales , Participación en las Decisiones , Evaluación de Necesidades , Objetivos Organizacionales , Rol Profesional , Relaciones Profesional-Paciente , Cuidado Terminal/psicología
7.
J Biol Chem ; 275(24): 17937-45, 2000 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-10849432

RESUMEN

Bone morphogenetic proteins (BMPs) occupy important roles during development serving to direct cells through specific differentiation programs. While several BMPs are essential for embryonic viability, their significance in mediating intercellular communication in the context of adult organ systems remains largely unknown. In the adult rat we characterized the tissue- and cell-specific transcription and translation of BMP-9. Utilizing a ribonuclease protection assay, we determined that in the adult animal, BMP-9 expression occurs predominantly in the liver. Furthermore, we determined that the non-parenchymal cells of the liver, i.e. endothelial, Kupffer, and stellate cells, are the major sources of this message. Western analyses corroborate the ribonuclease protection assay results, confirming that LEC and KC contain an abundance of immunoreactive BMP-9. Using [(125)I]BMP-9, a receptor with specific binding affinity for BMP-9 was characterized in primary cultures of hepatic endothelial cells and Kupffer cells. BMP-9 binding to these cell types was observed to be fully reversible and highly specific for this ligand. Additionally, we demonstrate that BMP-9 is specifically internalized upon binding to its receptor. This may represent a novel BMP receptor and is the first to be characterized in primary cultures of mature liver non-parenchymal cells. Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system.


Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Hígado/metabolismo , Receptores de Factores de Crecimiento , Animales , Unión Competitiva , Receptores de Proteínas Morfogenéticas Óseas , Proteínas Morfogenéticas Óseas/biosíntesis , Células Cultivadas , Endotelio/metabolismo , Factor 2 de Diferenciación de Crecimiento , Macrófagos del Hígado/metabolismo , Peso Molecular , Ratas , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo , Temperatura
8.
J Dev Behav Pediatr ; 20(4): 211-5, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10475594

RESUMEN

Twelve children with fibromyalgia and complaints of chronic dizziness were evaluated with both clinical office maneuvers of vestibular function and laboratory tests composed of electronystagmography and sinusoidal harmonic acceleration rotary chair testing. All test results were normal for spontaneous nystagmus with or without visual fixation, oculocephalic reflex, dynamic visual acuity, head-shaking nystagmus, Quix test, and Dix-Hallpike maneuver. Electronystagmography test results were essentially normal for saccades, gaze, Dix-Hallpike, pendular tracking, and caloric evaluation. Rotary chair testing was normal in all 12 patients. These findings suggest that central (brainstem) and peripheral vestibular (inner ear) mechanisms do not account for the complaints of dizziness in the pediatric patient with fibromyalgia. The common musculoskeletal abnormalities of fibromyalgia may affect their proprioceptive orientation, therefore giving them a sense of imbalance.


Asunto(s)
Mareo/etiología , Fibromialgia/fisiopatología , Vestíbulo del Laberinto/fisiopatología , Adolescente , Tronco Encefálico/fisiología , Niño , Electronistagmografía , Femenino , Humanos , Masculino , Propiocepción/fisiología
9.
Otolaryngol Head Neck Surg ; 121(1): 18-22, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10388870

RESUMEN

The role of canal-wall-down (CWD) versus intact-canal-wall (ICW) mastoidectomy in the treatment of chronic otitis media with or without cholesteatoma remains a debated issue. Although past conventional wisdom has held that CWD mastoid surgery leads to a "safe" ear and is technically less demanding than the more controversial ICW mastoidectomy, this is often not the case. Although our preference is an ICW technique when possible, 47 of 109 (43%) mastoid procedures for chronic otitis media performed between January 1993 and June 1996 involved a CWD mastoid cavity. More than two thirds of these procedures (32 of 47) represented revision surgery, the most common indication being a poorly contoured, preexisting CWD mastoidectomy with persistent otorrhea. A dry, well-epithelialized ear was obtained in 90% of cases. Our preferred method of ossicular reconstruction (double cartilage block ossiculoplasty) is detailed, and hearing results according to American Academy of Otolaryngology Head and Neck Surgery guidelines are reported.


Asunto(s)
Apófisis Mastoides/cirugía , Otitis Media/cirugía , Procedimientos Quirúrgicos Otológicos/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Colesteatoma del Oído Medio/cirugía , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento
10.
Laryngoscope ; 109(6): 911-4, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10369281

RESUMEN

OBJECTIVES/HYPOTHESIS: Multiple techniques of ossicular reconstruction have been advocated for hearing rehabilitation in the setting of chronic otitis media No single method can adequately address the clinical spectrum of disease severity. In the situation of a severely diseased ear requiring a canal wall down (CWD) mastoidectomy in the presence of an intact stapes superstructure, the authors have employed a double cartilage block (DCB) ossiculoplasty. The technique and short-term results are reviewed. STUDY DESIGN: Retrospective chart review in a tertiary referral otologic practice. METHODS: Twenty-three patients underwent a CWD tympanomastoidectomy with DCB ossiculoplasty. Ages ranged from 6 to 85 years (mean, 36.1 y). The majority of ears were actively draining at the time of surgery (83%) and most procedures were revisions of prior mastoidectomies (74%). Audiometric data (mean postoperative follow-up, 19.5 mo) were calculated according to 1995 American Academy of Otolaryngology-Head and Neck Surgery guidelines. RESULTS: Audiometric results were available in 20 patients. The mean air-bone gap (ABG) was 23.8 dB after surgery. Closure of the ABG to within 20 dB was achieved in 10 of 20 patients (50%). No cases of DCB extrusion have occurred to date. CONCLUSIONS: The DCB represents an excellent alternative to biocompatible prostheses for ossicular reconstruction in the setting of severe chronic ear disease. As with all methods of ossiculoplasty, long-term follow-up will be necessary to determine if this technique remains stable in the hostile environment in which it has been employed.


Asunto(s)
Cartílago Auricular/cirugía , Osículos del Oído/cirugía , Pérdida Auditiva Conductiva/etiología , Pérdida Auditiva Conductiva/prevención & control , Otitis Media/cirugía , Procedimientos de Cirugía Plástica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Audiometría , Niño , Enfermedad Crónica , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Reemplazo Osicular , Estudios Retrospectivos , Resultado del Tratamiento
11.
Eur J Pharmacol ; 367(1): 7-11, 1999 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-10082258

RESUMEN

Release of nitric oxide occurs as a consequence of glutamate stimulation of NMDA receptors and is dependent upon calcium-calmodulin activation of the enzyme nitric oxide synthase. Since nitric oxide may serve as an intracellular messenger for NMDA glutamatergic neurons, it could be hypothesized that blockade of its synthesis may produce pharmacological effects similar to those of NMDA receptor antagonists. The purpose of the present study was to compare the effects of nitric oxide synthase inhibitors to those of the high affinity NMDA open channel blocker phencyclidine in drug discrimination, a pharmacologically selective procedure in which phencyclidine produces distinctive effects. Rats were trained to discriminate 2 mg/kg phencyclidine from saline in a standard two-lever discrimination task with food reward. Whereas phencyclidine dose-dependently substituted for itself, 7-nitroindazole, L-NAME (N(G)-nitro-L-arginine methyl ester), and L-NOARG (N(G)-nitro-L-arginine) failed to substitute for phencyclidine when administered intraperitoneally. L-NAME and 7-nitroindazole were tested up to doses that disrupted responding, providing evidence that a behaviorally-relevant dosage range was evaluated. Although these results conflict with those of a previous study which found that nitric oxide synthase inhibitors substituted for phencyclidine and produced phencyclidine-like catalepsy in pigeons, they are consistent with research showing that these drugs did not produce phencyclidine-like pharmacological effects in behavioral procedures in rats.


Asunto(s)
Discriminación en Psicología/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fenciclidina/farmacología , Cloruro de Sodio/farmacología , Animales , Aprendizaje Discriminativo , Relación Dosis-Respuesta a Droga , Indazoles/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Nitroarginina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
12.
Otolaryngol Head Neck Surg ; 120(1): 12-6, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9914543

RESUMEN

Intravenous lidocaine has been reported to alleviate vertigo in Meniere's disease and suggested as a possible antivertigo agent after unilateral labyrinthectomy in a study of cats. To further evaluate the effects of intravenous lidocaine on the acute phase of postural compensation, we subjected 13 pigmented guinea pigs to unilateral labyrinthectomy. Seven received intravenous lidocaine (4 mg/kg) immediately after labyrinthectomy. The other six served as controls and received an equivalent-volume injection of normal saline solution. Total body curvature, trunk curvature, yaw head tilt, and roll head tilt were measured at frequent intervals for up to 30 hours after surgery. Both groups had immediate difficulties with posturing that gradually improved. The lidocaine group tended to exhibit delayed postural compensation, but this was only statistically significant for roll head tilt. These results do not show improvement in postural compensation from unilateral labyrinthectomy after the administration of intravenous lidocaine. A species-specific effect on the vestibular pathways is suggested, and we conclude that further evaluation of lidocaine and the vestibular system is warranted.


Asunto(s)
Oído Interno/cirugía , Lidocaína/farmacología , Postura , Vestíbulo del Laberinto/efectos de los fármacos , Animales , Cobayas , Inyecciones Intravenosas , Lidocaína/administración & dosificación , Vértigo/prevención & control , Vestíbulo del Laberinto/fisiología
13.
Am J Cardiol ; 81(2): 219-24, 1998 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-9591907

RESUMEN

Exercise treadmill testing is frequently performed to screen for coronary artery disease (CAD) in asymptomatic individuals; however, its clinical value is unclear. We examined a consecutive cohort of asymptomatic adults undergoing exercise treadmill testing at the Cleveland Clinic Foundation between September 1990 and December 1993. End points included (1) identification of subjects with severe CAD and (2) performance of any second diagnostic study within 90 days of the index exercise treadmill test. Screening exercise treadmill testing was performed in 4,334 adults (median age 51, 89% men); only 34% had > or = 1 cardiac risk factor and 15% exhibited an abnormal response to exercise. A second test after treadmill testing was performed in 215 patients (in 110, coronary angiography; in 105, stress thallium scintigraphy, followed by coronary angiography in 16). The strongest predictor of referral for a second test was an ischemic ST-segment response (adjusted odds ratio [OR] 34, 95% confidence intervals [Cl] 24 to 47, p < 0.0001). The only clinical variable independently associated with referral for a second test was female gender (adjusted OR 0.35, 95% CI 0.21 to 0.60, p <0.0001). Of the 126 patients who underwent coronary angiography, severe CAD was identified in only 19 individuals (10.44% of the original cohort, 95% CI 0.26% to 0.62%); coronary artery bypass grafting was performed in 14 of these patients. The estimated cost of exercise treadmill testing to identify 1 case of severe CAD for which surgical revascularization may provide a survival benefit was $39,623. The estimated cost per year of life saved was at least $55,274. Thus, as used in actual practice in 1 center, screening exercise treadmill testing has a low yield and is costly. This is perhaps in part because of the low-risk population that was selected and the failure to incorporate pretest variables, increasing probability of disease into post-test clinical decision making.


Asunto(s)
Enfermedad Coronaria/diagnóstico , Prueba de Esfuerzo/economía , Adulto , Angioplastia de Balón , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/cirugía , Análisis Costo-Beneficio , Toma de Decisiones , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Tasa de Supervivencia
14.
Biochim Biophys Acta ; 1359(2): 153-64, 1997 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-9409812

RESUMEN

Endothelin is a potent vasoactive peptide whose concentration increases in a number of pathophysiological states. In the intact animal, the liver is known to sequester approximately 12% of an injected bolus of [125I]endothelin-1 ([125I]ET-1). Endothelial cells (ECs) isolated from rat liver were maintained in culture in order to examine their role in ET sequestration. LECs were shown to express predominantly ET(B) receptors both by association assays and by Northern blot analysis. In these cells the reaction between [125I]ET-1 and its receptor was essentially irreversible. Ligand binding experiments performed at 4 degrees C showed that LECs in early culture (approximately 3 h) had 4.3 +/- 0.8 fmol of ET receptors per 10(6) cells; this number fell progressively to < or = 1 fmol/10(6) cells during 24 h of culture. The decrease in receptor numbers could be blocked by maintaining the cells at 4 degrees C. Northern blot analysis showed that relative to freshly isolated cells, mRNA for the ET(B) receptor decreased 4-fold in early culture, and recovered somewhat at 24 h. At 37 degrees C [125I]ET-1 bound by the cells was rapidly internalized, with concomitant down-regulation of ET receptors. Recovery of down-regulated ET receptors was sensitive to cycloheximide, making short-term receptor recycling unlikely. Metabolism of [125I]ET-1 was low at short (< 4 h) exposure times, and at 24 h showed a concentration dependence similar to that of ligand association, suggesting that ET-1 metabolism primarily was intracellular. ET stimulation of Kupffer cells and other hepatic cell types is known to activate phosphoinositide signaling, but no such activation was seen in LECs. Moreover, ET did not appear to stimulate protein tyrosine kinase activity in LECs. While hepatic LECs may lack some of the ET-dependent responses seen in other cell types, they likely contribute substantially to the liver's previously reported ability to sequester systemically administered ET.


Asunto(s)
Endotelina-1/metabolismo , Hígado/metabolismo , Animales , Northern Blotting , Células Cultivadas , Cicloheximida/farmacología , Regulación hacia Abajo/fisiología , Endotelina-1/farmacología , Endotelio/citología , Endotelio/metabolismo , Radioisótopos de Yodo , Macrófagos del Hígado/metabolismo , Hígado/citología , Masculino , Fosfatidilinositoles/metabolismo , Unión Proteica , Proteínas Tirosina Quinasas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina B , Receptores de Endotelina/metabolismo , Transducción de Señal/fisiología , Factores de Tiempo
15.
Am Heart J ; 134(5 Pt 1): 807-13, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9398092

RESUMEN

Controversy exists as to whether a sex bias exists that affects the diagnostic approach to suspected coronary artery disease: previous studies have used coronary angiography, but not other noninvasive testing, as a primary end point. This investigation examined posttest sex differences in diagnostic evaluation after exercise treadmill testing according to a broader end point than just coronary angiography alone. The design was a cohort analytic study with a 90-day follow-up. The study was done at the Cleveland Clinic Foundation, an academic group practice. Patients included consecutive adults (1023 men and 579 women) with chest pain but no documented coronary disease who were referred for symptom-limited exercise treadmill testing without adjunctive imaging; none had undergone prior invasive cardiac procedures. Main outcome measures included (1) performance of any subsequent diagnostic study (invasive or noninvasive) and (2) performance of coronary angiography as the next diagnostic study. During follow-up, 89 (8.7%) men and 48 (8.3%) women underwent a second diagnostic study (odds ratio 0.95; 95% confidence interval 0.66 to 1.37; p > 0.8), whereas 64 (6.3%) men and 21 (3.6%) women went straight to coronary angiography (odds ratio 0.56; 95% confidence interval 0.34 to 0.93; p = 0.02). In multivariable logistic regression analyses, which considered baseline clinical characteristics, the ST-segment response, and other prognostically important exercise responses, women tended to be less likely than men to be referred to any second test (adjusted odds ratio 0.70; 95% confidence interval 0.42 to 1.19; p > 0.1) but were markedly and significantly less likely to be referred straight to coronary angiography (adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.65). After exercise treadmill testing, women were only slightly less likely than men to be referred for subsequent diagnostic testing; they were, however, much less likely to be referred straight to coronary angiography as opposed to another noninvasive study.


Asunto(s)
Enfermedad Coronaria/diagnóstico , Prueba de Esfuerzo , Centros Médicos Académicos , Adulto , Angiografía Coronaria , Toma de Decisiones , Femenino , Humanos , Modelos Logísticos , Masculino , Prejuicio , Derivación y Consulta , Factores Sexuales
16.
Laryngoscope ; 107(11 Pt 1): 1445-50, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9369388

RESUMEN

Although use of the laser for stapedectomy has become common in recent years, controversy remains regarding whether the CO2 or visible-spectrum lasers (argon and KTP) are best suited for this operation. The main concern has been the potential for thermal injury to the inner ear with the visible-spectrum lasers attributable to their absorption characteristics. To further investigate this issue, the author performed 20 laser stapedectomies on adult chinchillas. Following placement of a 0.127-mm-diameter copper/constantan thermocouple (sampling at 12 Hz) beneath the footplate on the medial wall of the vestibule via a distant fenestration site, thermal changes with a micromanipulator-based CO2 and fiberoptic KTP system were compared. This was the first live animal model comparison of these two lasers. There was no statistical difference in the mean temperature elevation between the two systems (P = 0.395).


Asunto(s)
Dióxido de Carbono , Rayos Láser , Cirugía del Estribo/métodos , Conductividad Térmica , Animales , Chinchilla , Terapia por Láser , Factores de Tiempo
17.
Laryngoscope ; 107(9): 1199-202, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9292603

RESUMEN

Proper healing after surgery of the external auditory canal and open-cavity mastoid depend on epithelialization of exposed surfaces. This may be retarded by the formation of abundant granulation tissue or cicatrix, which can be dealt with by the use of thin, split-thickness skin grafts. This technique, which has received little attention in the literature, is described in detail and nine cases treated for various disorders are illustrated. Patient ages ranged from 5 to 80 years and the mean follow-up was 17.2 years. Results, complications, and caveats for successful grafting are presented.


Asunto(s)
Conducto Auditivo Externo/cirugía , Enfermedades del Oído/cirugía , Apófisis Mastoides/cirugía , Trasplante de Piel/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/cirugía , Niño , Preescolar , Colesteatoma del Oído Medio/cirugía , Cicatriz/patología , Conducto Auditivo Externo/anomalías , Deformidades Adquiridas del Oído/etiología , Deformidades Adquiridas del Oído/cirugía , Neoplasias del Oído/cirugía , Granuloma Eosinófilo/cirugía , Epitelio/fisiología , Estudios de Seguimiento , Tejido de Granulación/patología , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Osteotomía/métodos , Recurrencia , Trasplante de Piel/efectos adversos , Resultado del Tratamiento , Timpanoplastia/efectos adversos , Cicatrización de Heridas
18.
J Am Coll Cardiol ; 30(3): 641-8, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9283520

RESUMEN

OBJECTIVES: We sought to determine the relative influence of estimated functional capacity and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) findings on prediction of short-term all-cause and cardiac-related mortality. BACKGROUND: Decreased functional capacity and abnormal Tl-201 SPECT findings are predictive of increased cardiovascular risk and mortality. However, the relative importance of these variables as predictors of all-cause mortality is not well established. METHODS: Analyses were based on 3,400 consecutive adults undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic Foundation between September 1990 and December 1993; none had previous invasive procedures, heart failure or valve disease. Estimated functional capacity, classified by age and gender, and thallium perfusion defects, expressed as a stress extent thallium score on a 12-segment scale, were analyzed to determine their relative prognostic importance during 2 years of follow-up. RESULTS: Of 3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as cardiac related. On univariable analysis, estimated functional capacity was a strong predictor of death, with 62 (57%) deaths occurring in patients achieving < 6 metabolic equivalents (METs) (log-rank chi-square 86, p < 0.0001). On multivariable analysis, the strongest independent predictors of all-cause mortality were fair or poor functional capacity (adjusted relative risk [RR] 3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p < 0.0001) and age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p < 0.0001). The presence of SPECT thallium perfusion defects was a less powerful predictor of death (for each two additional segments with defects, adjusted RR 1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59 to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003). CONCLUSIONS: In this clinically low risk group, estimated functional capacity was a strong and overwhelmingly important independent predictor of all-cause mortality among patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial perfusion defects was of comparable importance for the prediction of cardiac mortality.


Asunto(s)
Prueba de Esfuerzo , Tolerancia al Ejercicio , Mortalidad , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/fisiopatología , Femenino , Cardiopatías/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Radioisótopos de Talio
19.
Am J Physiol ; 272(6 Pt 1): E967-75, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9227439

RESUMEN

Osteogenesis is a complex process whereby growth factors and mediators from both local and systemic sources modulate the bone-forming activities of osteoblasts. In the present study we utilized primary cultures of fetal rat calvarial cells to characterize osteoblast responsiveness to the vascular mediator endothelin-1 (ET-1) and to investigate whether ET-1 responses are regulated by osteogenic protein-1 (OP-1). We found that a 1- to 2-day exposure to OP-1 diminished ET-1 receptor ligand binding and signal transduction by downregulating ET-1 receptor mRNA expression. ET-1-mediated calcium signaling and ligand binding were completely abolished by the ETA receptor antagonist BQ-123, suggesting that ET-1 effects are mediated by this receptor. Northern analysis of total RNA revealed that ETA mRNA expression was inhibited approximately 50% by OP-1 treatment, whereas ETB receptor mRNA was not detected by this method of analysis. In OP-1-treated cultures, the magnitude and duration of ET-1 calcium signals varied among individual cells. This finding may be related to a heterogeneous OP-1 response, indicated by alkaline phosphatase induction in only a subpopulation of cells. These results suggest that modulation of osteoblast function by ET-1 occurs during distinct periods of phenotypic development and imply that downregulation of ET-1 responsiveness may be necessary for optimal bone formation in vivo.


Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Regulación hacia Abajo/efectos de los fármacos , Endotelina-1/farmacología , Osteoblastos/metabolismo , Receptores de Endotelina/biosíntesis , Factor de Crecimiento Transformador beta , Fosfatasa Alcalina/metabolismo , Animales , Proteína Morfogenética Ósea 7 , Calcio/metabolismo , Células Cultivadas , Citosol/metabolismo , Antagonistas de los Receptores de Endotelina , Endotelina-1/metabolismo , Feto , Humanos , Cinética , Osteoblastos/efectos de los fármacos , Péptidos Cíclicos/farmacología , Fosfatidilinositol Diacilglicerol-Liasa , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A , Proteínas Recombinantes/farmacología , Cráneo , Fosfolipasas de Tipo C/metabolismo
20.
Am J Otol ; 18(2): 207-13, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9093678

RESUMEN

OBJECTIVE: The objective of this study was to determine the usefulness of the head impulse test (HIT) and head-shake nystagmus (HSN), two easily performed office maneuvers, in the evaluation of the dizzy patient with reference to caloric irrigation results. OBJECTIVE AND SETTING: This was a prospective double-blind trial conducted at an outpatient academic tertiary referral center. PATIENTS: The study population was composed of 105 patients (35 male, 70 female) who presented for evaluation of dizziness and ranged in age from 13 to 87 years (mean 52.1). INTERVENTION: The intervention was HIT and HSN evaluation followed by bithermal binaural air caloric irrigations. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, and predictive values of HIT and HSN evaluation (individually and in combination) in relation to caloric results. RESULTS: Sensitivity of the tests was equally low (35%), whereas specificity was high (HIT 95%, HSN 92%). The positive predictive value for the two tests in combination (80%) was greater than for each individually (HIT 64%, HSN 50%). Negative predictive values remained stable when considering each test individually (HIT 86%, HSN 86%) or in combination (88%). CONCLUSIONS: The low sensitivity renders both tests inadequate as a screening tool for peripheral vestibular disease based on caloric results. However, when HIT and HSN results are both abnormal, there is a high likelihood of a significant caloric deficit.


Asunto(s)
Pruebas Calóricas , Movimientos de la Cabeza , Nistagmo Fisiológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Electrooculografía , Femenino , Fijación Ocular , Humanos , Masculino , Persona de Mediana Edad , Nervios Periféricos/fisiopatología , Estudios Prospectivos , Estudios Retrospectivos , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/fisiopatología
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