Using a problem detection study (PDS) to identify and compare health care provider and consumer views of antihypertensive therapy

The objectives of this study were to ascertain consumer knowledge and behaviour about hypertension and treatment and to compare these with health care providers' perceptions (of 'most' consumers). The design for the study was a problem detection study (PDS): focus groups and then survey. Focus groups and survey participants were convenience samples of consumers, doctors, nurses and pharmacists. The main outcome measures were agreement on a 5-point Likert scale with statements about consumers' knowledge and behaviour about high blood pressure and medication. The survey identified areas of consensus and disagreement between consumers and health providers. While general knowledge and concordance with antihypertensive therapy among consumers was good, consequences such as eye and kidney disease, interactions with herbal medicines, and how to deal with missing a dose were less well known. Side effects were a problem for over one-quarter of participants, and cost was a problem in continuing therapy. Half the consumers had not received sufficient written information. Providers overall disagreed that most consumers have an adequate understanding of the condition. They agreed that most consumers adhere to therapy and can manage medicines; and about their own profession's role in information provision and condition management. Consumers confirmed positive provider behaviour, suggesting opportunities for greater communication between providers about actions taken with their consumers. In conclusion, the PDS methodology was useful in identifying consumer opinions. Differences between consumer and provider responses were marked, with consumers generally rating their knowledge and behaviour above providers' ratings of 'most' consumers. There are clear gaps to be targeted to improve the outcomes of hypertension therapy.

Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression

Objectives: To identify potential molecular genetic determinants of cardiovascular ischemic tolerance in wild-type and transgenic hearts overexpressing A(1) adenosine receptors (A(1)ARs). Methods: cDNA microarrays were used to explore expression of 1824 genes ill wild-type hearts and ischemia-tolerant mouse hearts overexpressing A(1)ARs. Results: Overexpression of A(1)ARs reduced post-ischemic contractile dysfunction, limited arrhythmogenesis, and reduced necrosis by similar to80% in hearts subjected to 30 min global ischemia 60 mill reperfusion. Cardioprotection was abrogated by acute A(1)AR antagonism, and only a small number (19) of genes were modified by A(1)AR overexpression in normoxic hearts. Ischemia-reperfusion significantly altered expression of 75 genes in wild-type hearts (14 induced, 61 down-regulated), including genes for metabolic enzymes, structural/motility proteins, cell signaling proteins, defense/growth proteins, and regulators of transcription and translation. A(1)AR overexpression reversed the majority of gene down-regulation whereas gene induction was generally unaltered. Additionally, genes involved in cell defence, signaling and gene expression were selectively modified by ischemia in transgenic hearts (33 induced, 10 down-regulated), possibly contributing to the protected phenotype. Real-time PCR verified changes in nine selected genes, revealing concordance with array data. Transcription of the A(1)AR gene was also modestly reduced post-ischemia, consistent with impaired functional sensitivity to A(1)AR stimulation Conclusions: Data are presented regarding the early post-ischemic gene profile of intact heart. Reduced A(1)AR transcription is observed which may contribute to poor outcome from ischemia. A(1)AR overexpression selectively modifies post-ischemic gene expression, potentially contributing to ischemic-tolerance. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Use of tissue Doppler imaging to facilitate the prediction of events in patients with abnormal left ventricular function dobutamine echocardiography

The extent of abnormality in patients with positive do-butamine echocardiography (DE) is predictive of risk, but the wall motion score (WMS) has low concordance among observers. We sought whether quantifying the extent of abnormal wall motion using tissue Doppler (TD) could guide risk assessment in patients with abnormal DE in 576 patients with known or suspected coronary artery disease; standard DE was combined with color TD imaging at peak dose. WMS was assessed by an expert observer and studies were identified as abnormal in the presence of 2:1 segments with resting or stress-induced wall motion abnormalities. Patients with abnormal DE had peak systolic velocity measured in each segment. Tissue tracking was used to measure myocardial displacement. Follow-up for death or infarction was per-formed after. 16 +/- 12 months. Of 251 patients with abnormal DE, 22 patients died (20 from cardiac causes) and 7 had nonfatal myocardial infarctionis. The average WMS in patients with events was 1.8 +/- 0.5, compared with 1.7 +/- 0.5 in patients without events (p = NS). The average systolic velocity in patients with events was 4.9 +/- 1.7 cm/s and 6.4 +/- 6.5 cm/s in the patients without events (p <0.001). The average tissue tracking in patients with events was 4.5 +/- 1.5 mm and was significant. (5.7 +/- 3.1 mm),in those,without events (p <0.001). Thus, TD is an alternative to WMS for quantifying the total extent of abnormal left ventricular function-at DE, and appears to be superior for predicting adverse outcomes. (C) 2004 by Excerpta Medica, Inc.

Diagnostic accuracy of and patient satisfaction with telemedicine for the follow-up of paediatric burns patients

Videoconferencing has become a routine technique for the post-acute burns care of children in Queensland. We compared the agreement between clinical assessments conducted via videoconference and assessments conducted in the conventional, face-to-face manner (FTF). A total of 35 children with a previous burn injury were studied. Twenty-five children received three consecutive assessments: first FTF by a consultant in the outpatient department, then by a second consultant who reviewed the patient via videoconference, and then by the second consultant in person. The second consultant also reviewed another 10 children twice. At each review, the following variables were measured: scar colour, scar thickening, contractures, range of motion, the patient's level of general activity, any breakdown of the graft site, and adequacy of the consultation. Agreement between the two consultants when seeing patients FTF was moderately high, with an overall concordance of 85%. When videoconferencing was used, the level of agreement was almost the same, at 84%. If one consultant reviewed patients FTF first and then via videoconference, the overall concordance was 98%; if the process was reversed, the overall concordance was 97%. This study confirms that the quality of information collected during a videoconference appointment is comparable to that collected during a traditional, FTF appointment for a follow-up burns consultation.

Validity of self-reported skin screening histories

Screening by whole-body clinical skin examination may improve early diagnosis of melanoma and reduce mortality, but objective scientific evidence of this is lacking. As part of a randomized controlled trial of population screening for melanoma in Queensland, Australia, the authors assessed the validity of self-reported history of whole-body skin examination and factors associated with accuracy of recall among 2,704 participants in 2001. Approximately half of the participants were known to have undergone whole-body skin examination within the past 3 years at skin screening clinics conducted as part of the randomized trial. All positive and negative self-reports were compared with screening clinic records. Where possible, reports of skin examinations conducted outside the clinics were compared with private medical records. The validity of self-reports of whole-body skin examination in the past 3 years was high: Concordance between self-reports and medical records was 93.7%, sensitivity was 92.0%, and specificity was 96.3%. Concordance was lower (74.3%) for self-reports of examinations conducted in the past 12 months, and there was evidence of telescoping in recall for this more recent time frame. In multivariate analysis, women and younger participants more accurately recalled their history of skin examinations. Participants with a history of melanoma did not differ from other participants in their accuracy of recall.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-fine mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n = 44) and non-TMBC grade III with no or low scores (n = 160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n = 17) and non-MBC grade III cases (n = 140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R = 2.29), MIB1 > 50 (R = 3.80), ERBB2 negativity (R = 2.24) and p53 positivity (RR = 1.45). Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

3-D magnetic resonance angiography versus conventional angiography in peripheral arterial disease: Pilot study

Angiography is usually performed as the preoperative road map for those requiring revascularization for lower extremity peripheral arterial disease (PAD). The alternative investigations are ultrasound, 3-D magnetic resonance angiography (3-D MRA) and computed tomography angiography. This pilot study aimed to assess whether 3-D MRA could replace the gold standard angiography in preoperative planning. Eight patients considered for aortoiliac or infrainguinal arterial bypass surgery were recruited. All underwent both imaging modalities within 7 days. A vascular surgeon and a radiologist each reported on the images from both the 3-D MRA and the angiography, with blinding to patient details and each others reports. Comparisons were made between the reports for the angiographic and the 3-D MRA images, and between the reports of the vascular surgeon and the radiologist. Compared to the gold standard angiogram, 3-D MRA had a sensitivity of 77% and specificity of 94% in detecting occlusion, and a sensitivity of 72% and specificity of 90% in differentiating high grade (> 50%) versus low grade (< 50%) stenoses. There was an overall concordance of 78% between the two investigations with a range of 62% in the peroneal artery to 94% in the aorta. 3-D MRA showed flow in 23% of cases where conventional angiography showed no flow. In the present pilot study, 3-D MRA had reasonable concordance with the gold standard angiography, depending on the level of the lesion. At times it showed vessel flow where occlusion was shown on conventional angiogram. 3-D MRA in peripheral vascular disease is challenging the gold standard, but is inconsistent at present.

Nur77 regulates lipolysis in skeletal muscle cells - Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of total body weight and 50% of energy expenditure and is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. Excessive caloric intake is sensed by the brain and induces beta-adrenergic receptor (beta-AR)- mediated adaptive thermogenesis. beta-AR null mice develop severe obesity on a high fat diet. However, the target gene(s), target tissues(s), and molecular mechanism involved remain obscure. We observed that 30 - 60 min of beta-AR agonist ( isoprenaline) treatment of C2C12 skeletal muscle cells strikingly activated (> 100-fold) the expression of the mRNA encoding the nuclear hormone receptor, Nur77. In contrast, the expression of other nuclear receptors that regulate lipid and carbohydrate metabolism was not induced. Stable transfection of Nur77-specific small interfering RNAs (siNur77) into skeletal muscle cells repressed endogenous Nur77 mRNA expression. Moreover, we observed attenuation of gene and protein expression associated with the regulation of energy expenditure and lipid homeostasis, for example AMP-activated protein kinase gamma 3, UCP3, CD36,adiponectin receptor 2, GLUT4, and caveolin-3. Attenuation of Nur77 expression resulted in decreased lipolysis. Finally, in concordance with the cell culture model, injection and electrotransfer of siNur77 into mouse tibialis cranialis muscle resulted in the repression of UCP3 mRNA expression. This study demonstrates regulatory cross-talk between the nuclear hormone receptor and beta-AR signaling pathways. Moreover, it suggests Nur77 modulates the expression of genes that are key regulators of skeletal muscle lipid and energy homeostasis. In conclusion, we speculate that Nur77 agonists would stimulate lipolysis and increase energy expenditure in skeletal muscle and suggest selective activators of Nur77 may have therapeutic utility in the treatment of obesity.