Barriers in psychiatrists' mind to active smoking cessation promotion in severe psychiatric disorders.

BACKGROUND: Promoting the cessation of smoking in mental healthcare is a priority of international health organizations as it is the most cost-effective intervention in psychiatry. AIM: To explore the representations of psychiatrists on their role in active smoking cessation prevention in severe psychiatric disorders. METHODS: Psychiatrists and residents in psychiatry were recruited at a national level by professional mailings. RESULTS: One thousand four hundred and sixty participants were included in the study, and only 46% reported actively promoting smoking cessation. In multivariate analyses, participants aged<35years were more likely to promote cessation of tobacco smoking, as well as the two thirds who believe that psychiatry is a systemic discipline with complex interactions between brain, body and mind. Almost two thirds of those promoting tobacco cessation reported lacking time to combine psychiatric and physical examination during one session. The psychiatrists who reported not promoting tobacco smoking cessation also reported never dealing with physical health in case of the absence of a general practitioner and thinking that physical examination may have a negative impact on the therapeutic relationship. Almost all (96%) reported promoting the need for a general practitioner for their patients. We found no significant difference between the public and private sectors (P>0.05). INTERPRETATION: Young psychiatrists are more prone than their elders to promote smoking cessation but report lacking time to include it in their daily practice. Promotion of tobacco smoking cessation should be included in the components for quality evaluation for mental health services and specific sessions dedicated to this intervention.

Non-invasive measurement of renal perfusion and oxygen metabolism to predict postoperative acute kidney injury in neonates and infants after cardiopulmonary bypass surgery.

BACKGROUND: The pathophysiology of acute kidney injury (AKI) after cardiopulmonary bypass surgery for congenital heart disease is not completely understood. The aim of this study was to carry out a prospective analysis of the diagnostic value of non-invasive monitoring of renal oxygenation and microcirculation by combining laser Doppler flowmetry and tissue spectrometry. METHODS: In 50 neonates and infants who underwent repair (n = 31) or neonatal palliation (n = 19) of congenital heart disease with cardiopulmonary bypass, renal oxygenation, and microcirculatory flow, the approximate renal metabolic rate of oxygen and Doppler-based renal resistive index were determined after surgery. Correlations between these parameters and the occurrence of AKI according to the Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease criteria were investigated. RESULTS: Acute kidney injury occurred in 45% of patients after repair and in 32% after palliation. Renal oxygenation was significantly lower and the approximate renal metabolic rate of oxygen significantly higher in patients with AKI (P < 0.05). The microcirculatory flow was significantly higher in patients with AKI after neonatal palliation (P < 0.05), whereas renal resistive index was significantly higher in patients with AKI after repair (P < 0.05). The sensitivity of renal oxygenation, metabolic rate of oxygen, microcirculation, and resistive index in predicting AKI was 78-80, 73-78, 64-83, and 71-74%, respectively, with a specificity of 63-65, 54-75, 64-78, and 46-74% (area under the curve: 0.73-0.75, 0.68-0.83, 0.52-0.68, and 0.60-0.75), respectively. CONCLUSIONS: Monitoring of renal oxygen metabolism allows early prediction of AKI in infants after cardiac surgery. In contrast, renal resistive index does not allow prediction of AKI after neonatal palliation with aortopulmonary shunt establishment.

Infrainguinal bypass for peripheral arterial occlusive disease: when arms save legs.

OBJECTIVES: Determine if arm veins are good conduits for infrainguinal revascularisation and should be used when good quality saphenous vein is not available. DESIGN: Retrospective study. MATERIALS AND METHODS: We evaluated a consecutive series of infrainguinal bypass (IB) using arm vein conduits from March 2001 to December 2006.We selected arm vein by preoperative ultrasound mapping to identify suitable veins. We measured vein diameter and assessed vein wall quality. We followed patients with systematic duplex imaging at 1 week, 1, 3, 6 and 12 months, and annually thereafter. We treated significative stenoses found during the follow-up. RESULTS: We performed 56 infrainguinal revascularisation using arm vein conduits in 56 patients. Primary patency rates at 1, 2 and 3 years were 65%, 51% and 47%. Primary assisted patencies at 1, 2 and 3 years were 96%, 96% and 82%. Secondary patency rates at 1, 2 and 3 years were 92%, 88% and 88%. The three-year limb salvage rate was 88%. CONCLUSIONS: We conclude that infrainguinal bypass using arm vein for conduits gives good patency rates, if selected by a preoperative US mapping to use the best autogenous conduit available.

Clinical results of autologous infrainguinal revascularization using grafts originating distal to the femoral bifurcation in patients with mild inflow disease.

AIM: Chronic critical limb ischemia (CLI) often requires venous bypass grafting to distal arterial segments. However, graft patency is influenced by the length and quality of the graft and occasionally patients may have limited suitable veins. We investigated short distal bypass grafting from the superficial femoral or popliteal artery to the infrapopliteal, ankle or foot arteries, despite angiographic alterations of inflow vessels, providing that invasive pressure measurement at the site of the planned proximal anastomosis revealed an inflow-brachial pressure difference of

[New treatments in vascular diseases]. / Nouveautés en chirurgie vasculaire.

In superficial venous insufficiency, surgery remains the treatment of choice. Endovenous therapies are a minimal invasive alternative, whose long-term results are not demonstrated yet. In the treatment of abdominal aortic aneurysm, endovascular repair (EVAR) and laparoscopic approach are comparatively studied with open repair, to define their precise indications. In occlusive arterial disease, endovascular treatment offers inferior results in term of durability and patency, however with a decrease in morbidity and mortality.

[Quality of life after superficial femoral vein harvest for infra-inguinal reconstructions]. / Evaluation de la qualité de vie après prélèvement de la veine fémorale superficielle lors de reconstructions infra-inguinales.

BACKGROUND: The superficial femoral vein (SFV) is a well-established alternative conduit for infra-inguinal reconstructivenous hypertension after SFV harvest may however result in significant morbidity. This study reports the efficiency of SFV as conduit for infra-inguinal reconstructions and characterize the anatomic and physiologic changes in harvest limbs and their relationship to the development of venous complications. METHODS: From May 1999 through November 2003, 23 SFV were harvested from 21 patients undergoing infra-inguinal reconstructions. Bypasses were controlled by regular duplex-ultrasound. The venous morbidity was assessed by measurements of leg circumferences, strain-gauge plethysmography and quality of life, investigated by the VEINES-QOL scale. RESULTS: At a mean follow-up of 10.4 months (range 1-56), primary, secondary patency and limb salvage rates of infra-inguinal bypasses using SFV are 71.4%, 76.2% and 85.7% respectively. No patient had major venous claudication. Oedema was significantly present in nine patients. Strain-gauge plethysmography showed outflow obstruction in all patients. The VEINES-QOL assessment showed no limitation in social and domestic activity, moderate complain about leg heaviness despite presence of oedema. CONCLUSION: The SFV harvest is a reliable conduit for infra-inguinal reconstructions and results in moderate venous morbidity in terms of functional consequences and quality of life.

Contrast-induced nephrotoxicity: clinical landscape.

Over 80 million doses of iodinated intravascular contrast media (CM) were administered in the most recent tabulations of 2003, corresponding to approximately 8 million liters, making it one of the highest volume medical drugs used compared to any other pharmaceutical. The evolution of CM has focused on minimizing adverse events by eliminating ionicity, increasing hydrophilicity, lowering osmolality and increasing the number of iodine atoms per molecule. Contrast media are classified into three general categories based on their osmolality relative to blood: high osmolar (5 times or greater than blood), low osmolar (2-3 times blood) and iso-osmolar (the same as blood). All imaging modalities that employ CM, especially computerized tomography (CT), have shown rapid growth. In the last two decades, the use of CT scanning has increased by 800%. From 1979 to 2002, the number of cardiac catheterization procedures in the USA increased by 390% and in Europe from 1992 to 1999 by 112%. There is a general consensus that renal insufficiency and diabetes are major risk factors for contrast-induced nephropathy (CIN), particularly when co-existing. The US Renal Data System documents a 'relentless' increase in kidney failure, projecting a 90% increase by 2010. Diabetes affects 194 million people worldwide and the number is anticipated to increase by 75% by 2025. The unavoidable conclusion is that patient exposure and prevalence of risk factors for CIN will continue to increase.

[Management of critical limb ischemia]. / Prise en charge de l'ischémie critique des membres inférieurs.

Critical limb ischemia (CLI) is the leading cause of major leg amputation. Diabetes, smoking and end stage renal disease are the main risk factors for CLI. Despite their reduced survival rate, most CLI patients should be treated by surgical or endovascular arterial reconstruction, since amputation rate with conservative treatment alone is as high as 95% at 1 year in surviving patients with tissue loss, and can be reduced to 25% with successful reconstruction. When arterial reconstruction is impossible or fails, spinal cord stimulation also allows to avoid major amputation in up to 75% of precisely selected patients. Timely management and multidisciplinary approach are advised to reduce the risk of major amputation.

Vacuum-assisted conservative treatment for the management and salvage of exposed prosthetic hemodialysis access.

Recurrent puncture of dialysis grafts can cause erosion and ulcer formation in the skin over the prosthetic material. Contamination of the wound can lead to infection of the graft, and the necessity to remove it. We describe four cases where agressive treatment with debridement, intravenous antibiotics and negative pressure therapy allowed prosthesis salvage without discontinuation of hemodialysis.

[Lung volume reduction surgery for emphysema: a unilateral or bilateral approach?]. / Chirurgie de réduction de volume pulmonaire pour emphysème: approche uni- ou bilatérale?

INTRODUCTION: Lung Volume reduction surgery (LVRS) is a recognized therapeutic option for patients presenting with severe and disabling pulmonary emphysema. Case selection is based upon clinical, morphological and functional criteria. STATE OF THE ART: LVRS has shown promising results, with improvements in exercise capacity, pulmonary function and quality of life, in selected patients with severe and disabling emphysema. A variety of surgical techniques have been described. The procedure may be unilateral or bilateral, through a sternotomy or by a video-assisted thoracoscopic (VATS) technique. The controversial aspects of the surgical technique will be analysed and discussed in the following review. PERSPECTIVES: A bilateral approach clearly offers a better functional improvement when compared to a unilateral procedure, however, the postoperative functional decline appears greater and more rapid after a bilateral procedure. A unilateral approach, with often less postoperative morbidity, allows the option to perform a future contra-lateral procedure in the event of further clinical or functional deterioration. CONCLUSIONS: In selected cases LVRS is an effective treatment for severe pulmonary emphysema. Different surgical techniques have been described. Nowadays VATS is considered to be the technique of choice, with the option to carry out a future unilateral or bilateral procedure.

[Intestinal barotrauma after diving--mechanical ileus in incarceration of the last loop of the small intestine between a mobile cecum and sigmoid]. / Barotraumatisme intestinal après plongée sous-marine--iléus mécanique sur incarcération de la dernière anse du grêle entre un caecum mobile et le sigmoïde.

A few hours after a self-contained underwater breathing apparatus (SCUBA) dive at 30 meters depth, a 49 years-old man complained of diffuse abdominal pain with nausea and vomitus. A laparotomy was performed 36 hours after a conservative treatment because of persistent mechanical small bowel obstruction. The last ileal loop was strangulated between a mobile ceacum and a long sigmoid loop. The man never had previous abdominal surgery. In absence of intestinal necrosis, a caecopexy was done and there was no post-operative complications. The gas distension during the ascension following the Boyle-Mariotte law and its distribution induced in this man with a special anatomy a mechanical small bowel obstruction. The treatment of mobile caecum and the literature of abdominal barotrauma is reviewed.

Thymus medulla consisting of epithelial islets each derived from a single progenitor.

The thymus is organized into medullary and cortical zones that support distinct stages of T-cell development. The formation of medulla and cortex compartments is thought to occur through invagination of an endodermal epithelial sheet into an ectodermal one at the third pharyngeal pouch and cleft, respectively. Epithelial stem/progenitor cells have been proposed to be involved in thymus development, but evidence for their existence has been elusive. We have constructed chimaeric mice by injecting embryonic stem (ES) cells into blastocysts using ES cells and blastocysts differing in their major histocompatibility complex (MHC) type. Here we show that the MHC class-II-positive medullary epithelium in these chimaeras is composed of cell clusters, most of which derive from either embryonic stem cell or blastocyst, but not mixed, origin. Thus, the medulla comprises individual epithelial 'islets' each arising from a single progenitor. One thymic lobe has about 300 medullary areas that originate from as few as 900 progenitors. Islet formation can be recapitulated after implantation of 'reaggregated fetal thymic organs' into mice, which shows that medullary 'stem' cells retain their potential until at least day 16.5 in fetal development. Thus, medulla-cortex compartmentalization is established by formation of medullary islets from single progenitors.

Essential requirement for c-kit and common gamma chain in thymocyte development cannot be overruled by enforced expression of Bcl-2.

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and gamma(c) single or double mutant mice. A bcl-2 transgene (E(mu)-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and gamma(c) wild-type (c-kit+gamma(c)+bcl+), (b) c-kit-deficient (c-kit(-)gamma(c)+bcl+), (c) gamma(c)-deficient (c-kit+gamma(c)-bcl+), or (d) c-kit and gamma(c) double-deficient mice (c-kit-gamma(c)-bcl+). The bcl-2 transgene was functionally active in wild-type and c-kit or gamma(c) single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or gamma(c) single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.

Influence of intercellular junctions on endothelin secretion of human umbilical vein endothelial cells in vitro.

The endothelium plays a pivotal role in the rheological regulation of blood flow by the secretion of vasoactive factors. The interaction between shear forces and the endothelium is determined by the mechanical properties of the endothelial cell layer which are associated with intercellular junctions. Cell-cell contacts could therefore modulate the secretion of vasocative factors in response to rheological stimuli. We investigated the relationship between intercellular junctions and the secretion of the vasoconstrictor peptide endothelin and the coagulation co-factor von Willebrand factor (vWF). Human umbilical vein endothelial cells (HUVECs) were used as in vitro endothelial model system. Intercellular junctions were reversibly disrupted by calcium chelation or hypertonic stress; alternatively, the formation of intercellular junctions was inhibited by culturing the cells in suspension or by plating them in the presence of an inhibitory anti-VE-cadherin antibody. The opening of intercellular junctions was verified by assessing transmonolayer electrical resistance (TMR) and immunofluorescence morphology. The concentration of endothelin and vWF was measured in the cell culture supernatants using specific ELISAs. The secretion of endothelin was inhibited by EGTA (5 mM) and stimulated by incubation with tumor necrosis factor alpha (TNFalpha, 40 ng/ml). Treatment with hypertonic medium (glycerol, 1,200 mosmol/l) for 10 minutes opened intercellular junctions and markedly reduced the secretion of endothelin. HUVECs in suspension culture did not secrete endothelin and failed to respond to TNFalpha, but readily resumed these functions upon forming a new monolayer on plastic. The reconstitution of intercellular junctions after suspension culture could be inhibited using a specific anti-VE-cadherin antibody. This antibody, but not a non-specific anti-human-IgG antibody reduced endothelin secretion. The secretion of von Willebrand Factor was less dependent on intercellular junctions. The opening of intercellular junctions did not induce cell death, since the cells continued to exclude trypan blue. The results of this study suggest a novel and potentially pathophysiologically/clinically relevant correlation between intercellular junctions and the secretion of endothelin in endothelial cells.

Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice.

Thymocytes and thymic dendritic cell (DC) lineages develop simultaneously and may originate from a common intrathymic progenitor. Mice deficient for two growth factor receptor molecules [c-kit and the common cytokine receptor gamma chain (gamma(c))] lack all thymocytes including T cell progenitors. Despite this lack of pro-T cells, thymic DC compartments were identified in c-kit(-)gamma(c)(-) mice. Thus, c-kit- and gamma(c)-mediated signals are not essential to generate thymic DCs. In addition, pro-T cells do not appear to be obligatory progenitors of thymic DCs, because DC development is dissociated from the generation of thymocytes in these mice. Thymic DCs in c-kit(-)gamma(c)(-) mice are phenotypically and functionally normal. In contrast to wild-type mice, however, thymic DCs in c-kit(-)gamma(c)(-) and, notably, in RAG-2-deficient mice are CD8alpha(neg/low), indicating that CD8alpha expression on thymic DCs is not independent of thymocytes developing beyond the "RAG-block."

Cell-cell contacts in the human cell line ECV304 exhibit both endothelial and epithelial characteristics.

Endothelial cells separate the intra- and extravascular space and regulate transport processes between these compartments. Since intercellular junctions are required for these specific cell functions, the cell-cell contacts in the permanent cell line ECV304 were systematically analyzed and compared with human umbilical vein endothelial cells (HUVECs) in primary culture and with the epithelial Madin Darby Canine Kidney (MDCK) cell line. Filter-grown ECV304 cells generate a distinct electrical resistance and a permeability barrier between cell culture compartments. Electron microscopy of ECV304 cells revealed lateral membrane interdigitations, typically found in endothelial cells in vivo, with direct membrane contact sites, which prevented the diffusion of lanthanum. By immunoblot and immunofluorescence analysis, the expression and cellular localization of the tight junction and adherens-type junction proteins occludin, ZO-1, symplekin, beta-catenin, and plakoglobin were analyzed. ECV304 cells display further characteristics of endothelial cells, including the expresssion of thrombomodulin and of the vitronectin receptor CD51, as well as the secretion of plasminogen activator inhibitor 1 (PAI-1) and endothelin. However, ECV304 cells also express proteins characteristically found in epithelial cells, including E-cadherin and the desmosomal proteins desmoplakin, desmocollin, and desmoglein; occasionally desmosomal structures can be identified by electron microscopy. In conclusion, ECV304 cells express many endothelial markers and form specialized intercellular junctions that display some epithelial features. Thus this reportedly endothelial-derived permanent human cell line may be dedifferentiated toward an epithelial phenotype.

[Cell polarity in the cardiovascular system]. / Zellpolarität im Herz-Kreislauf-System.

The importance of cell polarity as a fundamental biological principle is increasingly recognized in the cardiovascular system. Polar cell mechanisms underlie not only the development of the heart and blood vessels, but also play a major role in the adult organism for polarized endothelial functions such as the separation of the intra- and extravascular compartment and the vectorial exchange of substances between these compartments. Endothelial cells are connected through intercellular junctions which separate the functionally and structurally distinct luminal and abluminal cell surfaces. The luminal plasma membrane is in contact with the blood and takes part in the regulation of hemostasis. The abluminal cell membrane connects the endothelial cell with the basement membrane and modulates blood flow through the release of vasoactive substances. Results from epithelial model systems have shown that the polarized cell phenotype is generated by specific protein sorting and regulated protein trafficking between the trans-Golgi network and the cell surface. The polarized distribution of cell membrane proteins is maintained by anchorage with the cytoskeleton and limitation of lateral diffusion by tight junctions. Disturbances of cell polarity may contribute to the pathogenesis of disease states, including ischemic and radiocontrast-induced acute renal failure and carcinomas. Recent results have demonstrated the importance of cholesterol for protein traffic from the trans-Golgi network to the apical cell membrane. This novel intracellular function of cholesterol could point to a connection between cell polarity and the pathogenesis of arteriosclerosis. The polarity of the endothelium also has to be taken into account when developing gene-therapeutic strategies, since therapeutic success will not only depend on the efficient expression of the desired gene product, but also on its correct cellular location or secretion into the correct extracellular compartment. These examples demonstrate the biological and potentially clinical relevance of cell polarity in the cardiovascular system.

Antigen-receptor junctional diversity in growth-factor-receptor mutant mice.

Precursor lymphocytes undergo expansion prior to immunoglobulin (Ig) or T cell receptor (TCR) rearrangements. Development of thymocytes, but not B cells, is entirely blocked in mice lacking both the receptor-tyrosine-kinase c-kit and the common cytokine receptor gamma chain (gamma c). In c-kit-gamma c-mice, TCR beta rearrangements are limited to mono- or oligoclonal DJ junctions. Here, effects of lack of c-kit or gamma c, or both, on the junctional diversity of TCR gamma and delta, and Ig VH(DH)JH loci were analyzed. All rearrangements were present in wildtype and mutant mice. However, sequencing of the junctions revealed monoclonal TCR gamma (V gamma 2 J gamma 1) and TCR delta (V delta 1(D delta)J delta 2) joints in c-kit-gamma c-, but not c-kit+ gamma c- or wildtype thymocytes. In contrast to TCR beta, gamma and delta loci, VHDHJH junctions were more diverse in c-kit-gamma c-mice. Thus, the two analyzed growth factor receptors mediate signaling pathways required for progenitor expansion and generation of junctional diversity at TCR loci, but have less influence on the diversity of IgH junctions.

Immunological and functional analyses of the extracellular domain of human tissue factor.

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation via formation of an enzymatic complex with coagulation factor VII/VIIa (FVII/VIIa). Although FVII is the only known ligand for TF, several reports in recent years have shown that the function of TF may not be limited to serving as a trigger of coagulation but that TF could also play a role in cellular signaling, metastasis, adhesion and embryogenesis. To explore the loci of the extracellular domain of TF important for its function, we analyzed the functional and immunological epitopes of TF1-219 by the use of both E. coli expressed TF variants encompassing various portions of the extracellular domain of TF and different anti-TF monoclonal antibodies (mAbs). N- and C-terminally truncated TF variants were analyzed for their VIIa-dependent procoagulant activity (PCA). The results obtained are in agreement with previously performed mutant and structural analyses of the interaction of FVII/FVIIa with the extracellular domain of TF. In addition, we observed that combination of two TF variants, Ec-TF1-122 and Ec-TF120-219, yields a soluble and active two-chain TF molecule with remarkable PCA. The reaction patterns of anti-TF mAbs with truncated TF variants and synthetic TF-derived peptides demonstrated that at least three distinct conformation-dependent epitope areas of TF (residues 1-25, 175-202, and 181 -214, respectively) are detected by these mAbs raised against native TF. In fact, mAbs, which are directed to the same epitope area of TF, behave very similar in various applications including immunohistochemistry and clotting tests. Since mAbs directed to the C-terminal epitope area of TF (residues 181-214) influence TF activity independent of FVIIa-binding, this region may be involved in functions of TF distinct from haemostasis.

Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers.

OBJECTIVE: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of radiocontrast agents on polarized tubular cells in vitro. METHODS: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. RESULTS: The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. CONCLUSIONS: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of radiocontrast-induced nephropathy.