RESUMEN
BACKGROUND: Most patients with psoriasis have limited disease which can be managed effectively in primary care. There is a marked variation in the frequency of referrals between practices reflecting, in part, inadequate training of general practitioners (GPs) in the management of psoriasis. OBJECTIVES: To assess the effectiveness of guidelines and training sessions on the management of psoriasis in reducing inappropriate referrals from primary care. METHODS: Patients aged 18 years or over with psoriasis were eligible for the cluster-randomized, randomized controlled trial if they were referred by their GP between 9 September 2002 and 31 December 2003 to one of four hospital dermatology departments in Greater Manchester, North-West England. All GPs from 165 health centres were invited to a lecture by a local dermatologist on the diagnosis and management of psoriasis. Health centres in the intervention arm received guidelines on the management of psoriasis in primary care, developed by local dermatologists, supplemented by the offer of a practice-based nurse-led training session; those in the control arm received neither guidelines nor training sessions. RESULTS: Eighty-two health centres were randomized to the intervention arm and 83 to the control arm. Outcome data were available for 188 of the 196 eligible patients referred during the study period. Patients in the intervention arm were significantly more likely to be appropriately referred in comparison with patients in the control arm [difference = 19.1%; odds ratio (OR) 2.47; 95% confidence interval (CI) 1.31-4.68; intracluster correlation coefficient (ICC) = 0]. Only 25 (30%) health centres in the intervention arm took up the offer of training sessions. There was no significant difference in outcome between health centres in the intervention arm that received a training session and those that did not (OR 1.28, 95% CI 0.50-3.29, ICC = 0). CONCLUSIONS: Dissemination of guidelines on the management of psoriasis in primary care can significantly enhance the appropriateness of referral of patients to secondary care.
Asunto(s)
Competencia Clínica , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud/normas , Psoriasis/terapia , Derivación y Consulta/normas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Educación Médica Continua/métodos , Inglaterra , Medicina Familiar y Comunitaria/educación , Medicina Familiar y Comunitaria/normas , Femenino , Investigación sobre Servicios de Salud/métodos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Examen Físico/métodos , Examen Físico/normas , Psoriasis/diagnósticoRESUMEN
BACKGROUND: Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients. METHODS: Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink. RESULTS: The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores. CONCLUSIONS: Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders.
Asunto(s)
Cognición , Esquizofrenia/tratamiento farmacológico , Triptófano/metabolismo , Administración Oral , Adulto , Afecto , Aminoácidos/administración & dosificación , Barrera Hematoencefálica , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biosíntesis de Proteínas , Esquizofrenia/fisiopatología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Triptófano/sangreRESUMEN
Have the limits for suitable recipient candidates for heart transplantation been exceeded? Does the current legislation and policy instituted at all levels, from DHHS to individual transplant programs, critically address the use of a dangerously limited resource? These and other questions must be the focus of future discussions regarding equitable and efficient heart transplantation in this country. The past has shown that many individuals working cooperatively within committees at federal and organizational levels have already made great strides in making organ transplantation a successful reality. Many factors influence the broadening gap between supply and demand. Each level of the system can make contributions that bring positive and creative solutions to old and new problems. Each team and committee must continue to demand representation from diverse, yet attentive, members to ensure that the specific needs of the thoracic organ recipients are properly reviewed and addressed. UNOS and its membership must continue to work together to meet the challenges of the growing acceptance of organ transplantation and the limited supply of donor organs. Continued efforts of politicians, health care professionals, and the general public must seek newer and more creative ways to manage the critical organ shortage and the ever-growing population of patients who seek heart transplantation as the only viable treatment option for their disease process. OPOs must continue their efforts to educate and promote organ donation and continue to work diligently toward increasing the pool of acceptable organ donors through improved patient management and the development of improved preservation and transport techniques. The transplant community must take the initiative to modify current legislation and to author new legislation to serve as better representors for the transplant patient population that desperately needs it.
Asunto(s)
Trasplante de Corazón , Obtención de Tejidos y Órganos/organización & administración , Costos de la Atención en Salud/estadística & datos numéricos , Asignación de Recursos para la Atención de Salud/organización & administración , Trasplante de Corazón/economía , Trasplante de Corazón/legislación & jurisprudencia , Trasplante de Corazón/estadística & datos numéricos , Trasplante de Corazón/tendencias , Humanos , Selección de Paciente , Estados Unidos , Listas de EsperaRESUMEN
We have identified GR138950, a potent antagonist of the angiotensin II receptor with high oral bioavailability, as our second drug candidate to GR117289. Using GR117289, a compound with moderate bioavailability (20%) in man as a lead, we pursued a strategy aimed at enhancing bioavailability. The strategy was based on SAR established around the diacid GR117289, and from this, it was proposed that a monoacid, in particular a trifluoromethanesulfonamide, should be better absorbed after oral administration and have enhanced oral bioavailability. This led to the identification of GR138950, a potent antihypertensive agent in the renal hypertensive rat, causing sustained falls in blood pressure after oral administration. Oral bioavailability of GR138950 in rats and dogs is high, confirming that GR138950 is well absorbed after oral administration. Moreover, the low plasma clearance and long plasma half-life suggest that this compound will be suitable for once a day administration. Furthermore, the preliminary data indicate that the high bioavailability of GR138950 seen in rats and dogs translates to man. These results demonstrate clearly that GR138950 has the potential to be a clinically effective antihypertensive agent. Further studies are in progress to evaluate GR138950 in the treatment of hypertension.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Antihipertensivos/farmacología , Antihipertensivos/farmacocinética , Benzofuranos/farmacología , Benzofuranos/farmacocinética , Administración Oral , Secuencia de Aminoácidos , Animales , Antihipertensivos/metabolismo , Benzofuranos/metabolismo , Disponibilidad Biológica , Modelos Animales de Enfermedad , Perros , Hipertensión/tratamiento farmacológico , Técnicas In Vitro , Cinética , Datos de Secuencia Molecular , Conejos , Ratas , Receptores de Angiotensina/metabolismo , Relación Estructura-ActividadRESUMEN
To determine the effect of smoking cessation on the number and type of inflammatory cells in the walls of the small airways, we examined the lungs of 13 lifetime nonsmokers, 25 patients who had stopped smoking for at least 6 months, and 49 current smokers. We found that, compared to nonsmokers, both ex-smokers and current smokers had significantly increased numbers of total inflammatory cells and polymorphonuclear leukocytes in the walls of the membranous, but not the respiratory bronchioles. These differences were found even when there was no emphysema present in the gross lung specimen, and current and ex-smokers were matched with the nonsmokers for age. The current and ex-smokers had similar numbers and types of inflammatory cells in the airway wall, and in both current and ex-smokers there was no difference in inflammatory cell number or type when the groups were subdivided based on emphysema score less than or greater than 5. Analysis of peribronchiolar alveolar attachments showed an increase in percentage of alveoli destroyed associated with an increased interalveolar distance in both the current and ex-smokers, which did not change with the presence of emphysema. Pulmonary function was similar in the current and ex-smokers, and the group with emphysema showed greater functional abnormalities compared to the group with little or no emphysema. We conclude that the cigarette smoking habit induces a stereotypical inflammatory response in the small airways. This inflammatory response does not abate after smoking cessation, and in this cross-sectional study, appears to be independent of the presence or absence of emphysema, but related to destruction of the peribronchiolar alveolar attachments.
Asunto(s)
Bronquios/patología , Bronquitis/patología , Fumar/patología , Anciano , Bronquitis/etiología , Estudios Transversales , Enfisema/patología , Femenino , Humanos , Recuento de Leucocitos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/patología , Fumar/efectos adversosRESUMEN
This study was designed to investigate the relationship between the cellular components of lung lavage fluid and the presence of airways disease and emphysema in resected lung specimens, primarily from current and ex-smokers. Since standard bronchopulmonary lavage cannot be performed on these specimens, an intrapulmonary lavage technique was developed and compared to the results of bronchoalveolar lavage performed prior to surgery on the lung or lobe opposite to the one resected. The specimen lavage produced inflammatory cell differential counts similar to those obtained by bronchopulmonary lavage, and studies on postmortem lungs showed that the fluid washed alveoli, respiratory and membranous bronchioles, and small cartilaginous bronchi. The results show that the variation in peripheral airways inflammation and extent of lung destruction by emphysema did not correlate with the variation in cell content observed in the lavage fluid. Similarly, the differential counts performed in the lavage fluid did not correlate with the smoking habits of the patient. We conclude that the changes in cell content of the lavage fluid do not reflect the extent or severity of the inflammatory disease and lung destruction present in the lungs of this group of patients.
Asunto(s)
Líquidos Corporales/citología , Bronquitis/patología , Enfisema/patología , Pulmón/patología , Bronquios/patología , Femenino , Humanos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Fumar , Irrigación TerapéuticaRESUMEN
The activities of glutathione peroxidase, superoxide dismutase and catalase, enzymes which play a critical role in protection of the vascular endothelium from oxygen free-radical injury, were determined in large vessel endothelial cells obtained under three different growth conditions: from freshly isolated from bovine pulmonary arteries, in the first (primary) subculture and after six serial subcultures (6.5 population doublings). The endothelium was obtained by mechanically scraping the vascular lumen. Endothelial cell monolayers were detached mechanically from the substratum prior to passage. No proteolytic enzymes were used in either procedure. The activities of catalase, superoxide dismutase and glutathione peroxidase determined in freshly isolated endothelial cells were, respectively, 39.9 +/- 10.3, 2.2 +/- 0.8 and 3.0 +/- 0.5 X 10(2) units per mg protein. After primary culture there was no change in superoxide dismutase activity, but a significant decrease in glutathione peroxidase activity to 1.4 +/- 0.4 X 10(2) was observed, and catalase activity dropped significantly to 18.6 +/- 5.0 units per mg protein. After 6.5 population doublings, the activity of all three enzymes returned to values similar to those of the freshly isolated cells. A fourfold increase in the protein to DNA ratio occurred in cells in primary culture and was maintained in sixth-passage cells. This increase in endothelial cell size upon culture was reflected in the electron microscopic evidence of cellular hypertrophy. Measurement of the rate of transport of 5-hydroxytryptamine by endothelial cell monolayers revealed a substantial loss upon multiple passage. Transport in the sixth-passage cells was decreased to one-half the rate of primary cells.(ABSTRACT TRUNCATED AT 250 WORDS)