RESUMEN
OBJECTIVES: to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care. DESIGN: prospective, randomised, controlled trial. SETTING: two residential continuing care hospitals. PARTICIPANTS: two hundred and twenty-five permanent patients. INTERVENTION: patients were randomised to either specialist geriatric input or regular input. The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel. Regular input consisted of review as required by a medical officer attached to each ward. Reassessment occurred after 6 months. RESULTS: one hundred and ten patients were randomised to specialist input and 115 to regular input. These were comparable for age, gender, dependency levels and cognition. After 6 months, the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group (P = 0.0364) and increased from 11.07 to 11.5 in the regular group (P = 0.094). There was no significant difference in mortality or frequency of acute hospital transfers (11 versus 6 in the specialist versus regular group, P = 0.213). CONCLUSION: specialist geriatric assessment and medication review in hospital continuing care resulted in a reduction in medication use, but at a significant cost. No benefits in hard clinical outcomes were demonstrated. However, qualitative benefits and lower costs may become evident over longer periods.
Asunto(s)
Continuidad de la Atención al Paciente/economía , Revisión de la Utilización de Medicamentos , Evaluación Geriátrica , Cuidados a Largo Plazo/economía , Grupo de Atención al Paciente/economía , Actividades Cotidianas , Anciano , Análisis Costo-Beneficio , Geriatría , Humanos , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Prospectivos , Instituciones ResidencialesRESUMEN
Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger the activation of large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca(2+)](i) release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca(2+)-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKalpha subunit was unchanged. The Ca(2+)-sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKbeta1 subunit confers Ca(2+)-sensitivity to BK channel complexes and both transcript and protein levels for BKbeta1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKbeta1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.
Asunto(s)
Calcio/fisiología , Diabetes Mellitus Experimental/metabolismo , Regulación hacia Abajo/fisiología , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/antagonistas & inhibidores , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/biosíntesis , Músculo Liso Vascular/metabolismo , Arteria Retiniana/metabolismo , Animales , Arteriolas/metabolismo , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Ratas , Transcripción GenéticaRESUMEN
PURPOSE: To assess the effects of advanced glycation endproduct (AGE) modification of vascular basement membrane (BM) on endothelin-1 (Et-1) induced intracellular [Ca2+] ([Ca2+]i) homeostasis and contraction in retinal microvascular pericytes (RMP). METHODS: RMPs were isolated from bovine retinal capillaries and propagated on AGE modified BM extract (AGE-BM) or non-modified native BM. Cytosolic Ca2+ was estimated using fura-2 microfluorimetry and cellular contraction determined by measurement of planimetric cell surface area. ETA receptor mRNA and protein expression was assessed by real time RT-PCR and western blotting, respectively. RESULTS: Exogenous endothelin-1 (Et-1) evoked rises in [Ca2+]i and contraction in RMPs were found to be mediated entirely through ETA receptor (ETAR) activation. Both peak and plateau phases of the Et-1 induced [Ca2+]i response and contraction were impaired in RMPs propagated on AGE modified BM. ETAR mRNA expression remained unchanged in RMPs exposed to native or AGE-BM, but protein expression for ETAR (66 kDa) was lower in the AGE exposed cells. CONCLUSIONS: These results suggest that substrate derived AGE crosslinks can influence RMP physiology by mechanisms which include disruption of ETA receptor signalling. AGE modification of vascular BMs may contribute to the retinal hemodynamic abnormalities observed during diabetes.