The evolution of the doctor-patient relationship.

The doctor-patient relationship has undergone a transition throughout the ages. Prior to the last two decades, the relationship was predominantly between a patient seeking help and a doctor whose decisions were silently complied with by the patient. In this paternalistic model of the doctor-patient relationship, the doctor utilises his skills to choose the necessary interventions and treatments most likely to restore the patient's health or ameliorate his pain. Any information given to the patient is selected to encourage them to consent to the doctor's decisions. This description of the asymmetrical or imbalanced interaction between doctor and patient [Parsons T. The social system. Free Press, New York, 1951.](1) has been challenged during the last 20 years. Critics have proposed a more active, autonomous and thus patient-centred role for the patient who advocates greater patient control, reduced physician dominance, and more mutual participation. This patient-centred approach has been described as one where "the physician tries to enter the patient's world, to see the illness through the patient's eyes" [McWhinney I. The need for a transformed clinical method. In: Stewart M, Roter D, Communicating with medical patients. London: Sage, 1989.](2), and has become the predominant model in clinical practice today.

Evaluation of the mechanisms of damage to flexible ureteroscopes and suggestions for ureteroscope preservation.

AIM: To investigate the causes and costs of flexible ureteroscope damage, and to develop recommendations to limit damage. METHODS: The authors analysed repair figures and possible causes of damage to 35 instruments sent for repair to a leading UK supplier over a 1-year period, and calculated cost figures for maintenance of the instruments as opposed to repair and replacement costs. RESULTS: All damages were handling-induced and therefore did not fall under the manufacturer's warranty: 28 % were damaged by misfiring of the laser inside the instrument; 72 %, mainly crushing and stripping of the ureteroscope shaft tube, were likely to have occurred during out-of-surgery handling, washing and disinfection. Seventeen (4 %) instruments were not repaired and consequently taken out of service due to the extensive costs involved. Eighteen (51 %) ureteroscopes were repaired at an average cost of 10 833 USD. CONCLUSION: Damages to flexible ureteroscopes bear considerable costs. Most damages occur during handling between surgical procedures. Thorough adherence to handling procedures, and courses for theater staff and surgeons on handling flexible instruments may help to reduce these damages and prove a cost-saving investment. The authors provide a list of recommended procedural measures that may help to prevent such damages.

Angiogenesis and the tumour hypoxia response in prostate cancer: a review.

The formation of new blood vessels, angiogenesis, is a highly-regulated active process that is critical for the development of the normal and malignant prostate. The vascular endothelial growth factor (VEGF) system assumes a critical role in the angiogenic process. Angiogenesis is a prerequisite for the expansion of solid tumours beyond 1-3 mm3 and is stimulated in response to a hypoxic environment. This review discusses the process of angiogenesis and the key angiogenic mediator, VEGF, and their role in tumour progression and metastasis. A better understanding of the mechanisms behind angiogenesis will ultimately lead to the development of new anti-angiogenic agents in the management of prostate cancer.

The risks and benefits of cyclo-oxygenase-2 inhibitors in prostate cancer: a review.

Cyclo-oxygenase (COX), also referred to as prostaglandin (PG) endoperoxidase synthase, is a key enzymatic mediator in the production of arachidonic acids to PGs and eicosanoids. Two isoforms of COX exist, namely COX-1 and COX-2, which have distinct physiological functions and tissue distribution. Epidemiological studies suggest that regular consumption of aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX, could notably reduce the risk of developing many cancers. COX-2 expression has been shown to increase in many cancers and cancer cell lines, including human prostate adenocarcinoma. COX-2 may also be upregulated in proliferative inflammatory atrophy (PIA) of the prostate, a pre-neoplastic lesion. The COX-2 pathway may therefore be a useful target for chemoprevention of prostate cancer, and there is much interest in exploring this with the use of COX-2 inhibitor drugs such as celecoxib. While there is concern regarding the cardiovascular toxicities of coxibs, there is no evidence that there is any increased risk with the use of celecoxib in the short-term neoadjuvant setting.

Why do orthopaedic surgeons ignore the medial patellofemoral ligament?

The medial patellofemoral ligament (MPFL) is a condensation of the medial capsule of the knee joint. In the past two decades dissection studies have shown that it extends from the superomedial border of the patella to the femoral epicondyle, at or immediately above the adductor tubercle. MRI and operative studies have revealed that it is almost invariably damaged by lateral patellofemoral dislocation. Current surgical management of such dislocations may involve imbricating the torn medial capsule and parapatellar retinaculum back onto the medial border of the patella. If the medial patellofemoral ligament is torn at or near the femoral attachment, as the latest MRI and operative studies demonstrate it frequently is, then this medial reefing procedure will not be successful in restoring normal anatomy and function. Here we review the anatomy and function of the MPFL, its role in patellar dislocation and as well as surgical treatment for patellar dislocation.

Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system.

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates synchronized contraction of the cardiac chambers, and contributing to co-ordination of activities between cells of the arterial wall. In common with other multicellular systems, cardiovascular tissues express multiple connexin isotypes that confer distinctive channel properties. This review highlights how state-of-the-art immunocytochemical and cellular imaging techniques, as part of a multidisciplinary approach in gap junction research, have advanced our understanding of connexin diversity in cardiovascular cell function in health and disease. In the heart, spatially defined patterns of expression of three connexin isotypes-connexin43, connexin40, and connexin45-underlie the precisely orchestrated patterns of current flow governing the normal cardiac rhythm. Derangement of gap junction organization and/or reduced expression of connexin43 are associated with arrhythmic tendency in the diseased human ventricle, and high levels of connexin40 in the atrium are associated with increased risk of developing atrial fibrillation after coronary by-pass surgery. In the major arteries, endothelial gap junctions may simultaneously express three connexin isotypes, connexin40, connexin37, and connexin43; underlying medial smooth muscle, by contrast, predominantly expresses connexin43, with connexin45 additionally expressed at restricted sites. In normal arterial smooth muscle, the abundance of connexin43 gap junctions varies according to vascular site, and shows an inverse relationship with desmin expression and positive correlation with the quantity of extracellular matrix. Increased connexin43 expression between smooth muscle cells is closely linked to phenotypic transformation in early human coronary atherosclerosis and in the response of the arterial wall to injury. Current evidence thus suggests that gap junctions in both their guises, as pathways for cell-to-cell signaling in the vessel wall and as pathways for impulse conduction in the heart, contribute to the initial pathogenesis and eventual clinical manifestation of human cardiovascular disease.

Altered connexin expression in human congestive heart failure.

Congestive heart failure is associated with a high risk of life-threatening ventricular re-entrant arrhythmias. Down-regulation of the principal gap-junctional protein of the ventricular myocytes, connexin43, has previously been implicated in arrhythmia in ischaemic heart disease, but it is not known whether connexin43 is similarly reduced in heart failure due to idiopathic dilated cardiomyopathy, whether disease-related connexin43 down-regulation occurs at the level of transcription or translation, or whether the expression of other connexin isotypes is altered in congestive heart failure. We therefore investigated the expression of the four connexins expressed in the heart-connexins 43, 40, 45 and 37-at the mRNA and protein levels in explanted hearts from transplant patients with end-stage heart failure (NYHA class 4) by immunoconfocal analysis, and northern and western blotting. Connexin43 mRNA and protein were markedly downregulated in the left ventricle in end-stage heart failure due both to ischaemic cardiomyopathy and idiopathic dilated cardiomyopathy. Connexin43 content was spatially heterogeneous in the diseased ventricle. Connexin40 mRNA was increased in the ischaemic group, more so in the left ventricle than the right. This correlated with an increased depth of connexin40 protein expression in myocytes at the endocardial surface. Connexin45 mRNA and protein, present only in very low quantities, followed a similar trend to connexin43, while connexin37 (exclusively expressed in endothelium) showed no change. Our findings show that congestive heart failure is associated with significantly reduced levels of the principal gap junction protein, connexin43, in the left ventricle, potentially contributing to enhanced arrhythmogenicity and contractile dysfunction. This down-regulation is due predominantly to a reduced transcript steady-state level. Elevated connexin40 may represent a compensatory response that improves the spread of depolarization in the otherwise compromised ischaemic ventricle.

Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts.

The mouse is currently widely used as a model organism in the analysis of gene function but how developmentally regulated patterns of connexin gene expression in the mouse compare with those in the human is unclear. Here we compare the patterns of connexin expression in the heart during the development of the mouse (from embryonic day 12.5 to 6 weeks postpartum) and the human (at 9 weeks gestation and adult stage). The extent of connexin43 expression in the ventricles progressively increased during development of the mouse heart. The developmental pattern of expression for connexins 40 and 45 in the mouse heart was similar, but not identical, and in the ventricles showed a progressive and preferential expression in the conduction system. In general, these dynamic changes of connexins 43, 40 and 45 during mouse cardiac development appear to be mirrored in the human.

Differential expression of connexin43 and desmin defines two subpopulations of medial smooth muscle cells in the human internal mammary artery.

Upregulation of connexin43-gap junctions is associated with transition of contractile vascular smooth muscle cells (SMCs) to the synthetic state. To determine whether phenotypically distinct subpopulations of medial SMCs differentially express connexin43, we investigated the human distal internal mammary artery, a structurally heterogeneous vessel with features ranging from elastic to elastomuscular to muscular. Immunoconfocal microscopy combined with quantitative analysis and complemented by in situ hybridization showed that SMCs in the elastic medial regions expressed high levels of connexin43 but low levels of desmin, whereas those of muscular medial regions expressed low levels of connexin43 but high levels of desmin. Ultrastructurally, SMCs of both regions were of the contractile phenotype, but the former cells were irregular in shape with relatively prominent synthetic organelles whereas the latter were spindle shaped with fewer synthetic organelles. Vimentin, smooth muscle alpha-actin, calponin, h-caldesmon, and myosin heavy chains (SM1 and SM2) were equally highly expressed by most cells in both subpopulations. The connexin43/desmin expression pattern of SMCs in regions of intimal thickening resembled those of elastic medial regions. These findings refine the view suggested from previous studies that high levels of connexin43 expression are associated with SMCs of a less contractile/more synthetic phenotype. In the internal mammary artery, the 2 subpopulations of SMCs with markedly different connexin43 expression levels both represent a differentiated contractile phenotype, but the subpopulation showing high levels of connexin43-gap junctions is characterized by low levels of desmin and structural features that reflect a more synthetic tendency.