Pascal Meier

Rethinking the Triggering Inflammatory Processes of Chronic Periaortitis

Chronic periaortitis (CP) is an uncommon inflammatory disease which primarily involves the infrarenal portion of the abdominal aorta. However, CP should be regarded as a generalized disease with three different pathophysiological entities, namely idiopathic retroperitoneal fibrosis (RPF), inflammatory abdominal aortic aneurysm and perianeurysmal RPF. These entities share similar histopathological characteristics and finally will lead to fibrosis of the retroperitoneal space. Beside fibrosis, an infiltrate with variable chronic inflammatory cell is present. The majority of these cells are lymphocytes and macrophages as well as vascular endothelial cells, most of which are HLA-DR-positive. B and T cells are present with a majority of T cells of the T-helper phenotype. Cytokine gene expression analysis shows the presence of interleukin (IL)-1α, IL-2, IL-4, interferon-γ and IL-2 receptors. Adhesion molecules such as E-selectin, intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were also found in aortic tissue, and may play a significant role in CP pathophysiology. Although CP pathogenesis remains unknown, an exaggeratedinflammatory response to advanced atherosclerosis (ATS) has been postulatedto be the main process. Autoimmunity has also beenproposed as a contributing factor based on immunohistochemical studies. The suspected allergen may be a component of ceroid, which is elaborated within the atheroma. We review the pathogenesis and the pathophysiology of CP, and its potential links with ATS. Clinically relevant issues are summarized in each section with regard to the current working hypothesis of this complex inflammatory disease.

The Future of Angiotensin II Inhibition in Cardiovascular Medicine

Drugs, which interfere with the renin-angiotensin-aldosterone cascade such as angiotensin converting enzyme (ACE) inhibitors, have been available to clinicians for more than 20 years. They are now recognized as a very effective approach to treat patients with hypertension, heart failure, diabetic and non-diabetic chronic renal failure or patients with a high cardiovascular risk. The recent development of angiotensin II (Ang II) receptor antagonist has enabled to improve significantly the tolerability profile of this group of drugs while maintaining a high clinical efficacy. Yet, with the availability of Ang II receptor antagonists, new questions have arisen. Is it still possible to gain in efficacy with newer agents? What is the future of drugs such as neutral endopeptidase (NEP)/ACE inhibitors or renin inhibitors? The first objective of this review is to discuss the clinical implications of several large clinical trials that have been published recently with ACE inhibitors and Ang II receptor antagonists such as ALLHAT, LIFE, OPTIMAAL, Val-Heft, SCOPE, and more recently, CHARM, VALIANT and VALUE. With these trials, we can now define more precisely the role of these blockers of the renin-angiotensin system in the management of patients with cardiovascular complications. The second part of this review is devoted to new drugs interfering with the renin-angiotensin system. We discuss the recent results obtained with NEP/ACE inhibitors also named vasopeptidase inhibitors. Several compounds were or are in development but the experience with omapatrilat has blunted the enthusiasms for these compounds. Yet, vasopeptidase inhibitors remain very effective antihypertensive drugs and there is a great therapeutic potential for these agents provided one can define more accurately the risk/benefit ratio and the clinical indications. Finally, we present the recent data obtained with SPP 100, a new renin inhibitor that is actually under clinical development. SPP 100 has a sufficient bioavailability to induce a sustained blockade of the renin-angiotensin system when given orally to normal subjects. Recent studies have shown that SPP 100 lowers blood pressure in hypertensive patients as effectively as an Ang II receptor antagonist.

Imaging medullary cystic kidney disease with magnetic resonance

Medullary cystic kidney disease is characterized by multiple renal cysts at the corticomedullary boundary area, by autosomal dominant inheritance, and by onset of chronic renal failure in the third decade of life. Its clinical manifestations are often insignificant and nonspecific. Furthermore, its diagnosis may be difficult in sporadic forms where genetic linkage analysis cannot be performed. The authors report the case of a patient presenting with a sporadic form of medullary cystic kidney disease whose diagnosis was confirmed using computerized tomography with 3-dimensional reconstruction at the nephrography-excretion time and magnetic resonance imaging (MRI) with magnetic resonance angiography and urography after the injection of gadolinium, a nonnephrotoxic compound. Both imaging techniques showed normal-sized, normal-shaped kidneys containing multiple cysts from 1 to 30 mm in diameter in the medulla and at the corticomedullary junction. A characteristic medullary nephrogram appeared after injection of iodinated contrast medium or gadolinium corresponding to contrast-filled dilated collecting ducts. This report shows that MRI with gadolinium injection can substitute for computerized tomography in azotemic patients. MRI seems particularly promising for the diagnosis of cystic diseases of the kidney and must also be considered when investigating a patient with chronic renal failure of unknown origin.

Retroperitoneale Fibrose, Morbus Ormond, chronische Periaortitis,...?

Die retroperitoneale Fibrose oder Morbus Ormond ist eine seltene Krankheit charakterisiert durch eine entzundliche Fibrose des Retroperitoneums und der abdominalen Aorta, welche sich haufig bis in die iliacae communes Arterien erstreckt. Die abdominale Aorta kann aneurysmatisch verandert sein, weshalb die retroperitoneale Fibrose in solche mit oder ohne Aneurysma der Aorta abdominalis aufgeteilt werden kann. Typischerweise weisst die idiopathische retroperitoneale Fibrose keine aneurysmatische Erweiterung der Baucharterie auf. Die klinische Prasentation ist nicht spezifisch und beinhaltet unklare Abdomen-, Flanken- oder Ruckenschmerzen sowie Allgemeinsymptome wie Mudigkeit, Fieber und Gewichtsverlust. Die Ursache und die pathophysiologischen Mechanismen sind nicht klar, jedoch deuten viele Faktoren auf autoimmune Mechanismen hin. Die wichtigste Komplikation der retroperitonealen Fibrose ist die Harnleiterstauung mit Hydronephrose, welche ein- oder beidseitig auftreten kann und entlastet werden muss. Da di...