Synthetic smooth muscle cell phenotype is associated with increased nicotinamide adenine dinucleotide phosphate oxidase activity: Effect on collagen secretion

ObjectiveSmooth muscle cells (SMCs) from prosthetic vascular grafts secrete higher levels of collagen than aortic SMCs under basal conditions and during incubation with oxidized low-density lipoprotein. We postulated that reactive oxygen species (ROS) contributed to the observed difference. The objective of this study was to assess the effect of ROS on collagen secretion by aortic and graft SMCs and explore the mechanism involved.MethodsSMCs isolated from canine aorta or Dacron thoracoabdominal grafts were incubated with 6-anilinoquinoline-5,8-quinone (LY83583), an agent that induces superoxide production. Type I collagen in the conditioned medium was measured by enzyme-linked immunosorbent assay, and superoxide anion production was measured by lucigenin assay.ResultsLY83583 stimulated a rapid increase in collagen production by graft SMCs that paralleled the LY83583-induced increase in superoxide production. The increase in both collagen and superoxide was greater in graft SMCs than aortic SMCs. Collagen and superoxide production were inhibited by superoxide scavengers. Nicotinamide adenine dinucleotide phosphate (NADPH) induced significantly more superoxide production by graft SMCs than aortic SMCs, suggesting that the NADPH oxidase system was more active in graft SMCs. NADPH oxidase inhibitors blocked the superoxide and collagen production induced by LY83583.ConclusionIn SMCs, the synthetic phenotype is associated with increased NADPH oxidase activity and elevated superoxide production in response to an oxidative stress. Superoxide, in turn, leads to increased collagen production.Clinical RelevanceThe inflammatory process after prosthetic vascular graft implantation causes oxidative stress that can stimulate collagen production by graft SMCs, contributing to the progression of intimal hyperplasia. The exaggerated response of graft SMCs to oxidative stress offers a potential target for therapeutic interventions

Building, Reality, Caring: What Nurses in Three Australian Psychogeriatric Assessment Units Say about the Built Environment

Many people believe that ‘purpose-built’ facilities will diminish some of the challenging behaviours exhibited by older people with dementia or psychiatric conditions. This study aimed to explore and understand what hands-on nurses in psychogeriatric assessment units experience and think of the built environment as a part of their day to day work. Twenty-one unstructured interviews were conducted with nurses at three psychogeriatric assessment units. The units ranged in style from an ancient adapted building to a contemporary 'purpose-built' facility. A critical hermeneutics derived from Gadamer was used to explore the interviews. It found that nurses think of the built environment in relation to the care needs of their patients, and feel bureaucratic restrictions in using the built environment more keenly than the shortcomings of the built environment itself. Nurses saw themselves and their patients as 'outcasts' or victims of those with money and power. The study concludes with suggestions for challenging the status quo, but also considers that being regarded as 'outcasts' allows opportunities to avoid being overly impressed by technological marvels

Matige bloeddrukregulatie bij patienten met diabetes mellitus type 2 in de eerste en tweede lijn.

OBJECTIVE: To investigate the degree to which the goals for adequate blood-pressure control in patients with type-2 diabetes mellitus (DM) are met in Dutch specialists' practice and in the primary-care setting. DESIGN: Cross sectional. METHOD: Data were collected from all consecutive patients with DM type 2 visiting the outpatient clinic of two physicians specialised in diabetes care, in Zwolle, the Netherlands, in the period 1 November 1999-30 April 2000. The target value for blood pressure was < or = 150/85 mmHg. In addition, baseline data were collected on patients in the primary-care setting who participated in a transmural project in Zwolle in the period 1 February 1997-31 January 1998. In 1998, the target blood pressure in the primary-care setting was < or = 160/90 mmHg. Patients who met the goals for adequate blood-pressure control were compared with patients who did not. RESULTS: A total of 502 patients from specialists' practice and 1084 patients from the primary-care setting were included. The prevalence of hypertension in specialists' practice was 89% (n = 377); of these patients, 140 (37%) had a good regulation of their blood pressure. The patients who had an adequate blood-pressure control and those who did not were comparable. Both groups were prescribed an average of 2.2 kinds of antihypertensive agent per patient. The prevalence of hypertension in the primary care was 69% (n = 733). The goal for adequate blood-pressure control, i.e. a blood pressure of < or = 160/90 mmHg, was achieved in 44% (n = 324). In the primary-care setting, an average of 1.1 kinds of antihypertensive agent was prescribed, 1.6 in patients who achieved the target value and 0.8 in those who did not (p < 0.05). CONCLUSION: Regulation of blood pressure in patients with type 2 DM and hypertension was far from optimal: 37% of patients in specialists' practice and 44% of those in the primary-care setting achieved the target value

Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours

Survival of patients with disseminated midgut carcinoid tumours varies. We investigated which factors predict survival at referral and during follow-up, with emphasis on urinary 5-hydroxyindolacetic acid (5-HIAA) levels. Between 1992 and 2003, 76 patients were studied; urine was prospectively collected over a 24 h period every 3 months in order to measure 5-HIAA levels. Uni- and multivariate analyses were performed. Median follow-up was 55 months with a median survival of 54 months. Prognostic factors for poor survival were high age, high gamma-glutamyltransferase levels and greatly increased 5-HIAA levels (>20 mmol/mol creatinine) The Hazard Ratio (HR) of a greatly increased 5-HIAA level was 3.33 (95% confidence interval (CI) 1.66-6.66, p=0.001). In a multivariate survival analysis with the 5-HIAA level as time dependent covariable, the HR for the 5-HIAA level was 1.007 (95% CI 1.004-1.010, p=0.000). In conclusion, patients with persistent moderately increased urinary 5-HIAA levels ( 20 mmol/mol creatinine) have favourable outcom