Topology of protease activities reflects atherothrombotic plaque complexity

The pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications, through plaque rupture. Here, we investigated the release of active proteases by human carotid plaques in relation to (1) the degree of lesion complexity and (2) their compartmentalization between cap, core and media. Eighty human carotid endarterectomy specimens were dissected into culprit stenosing (CPs) and adjacent non-complicated/non-stenosing plaques (NPs). Thirty-five additional CPs were microdissected into cap, core and media. All specimens were compared to control non-atherosclerotic endarteries for the release of components of the plasminogen/plasmin system and matrix metalloproteinases (MMPs). Results show a greater release of the plasminogen activators (PAs), plasmin and active MMPs by CPs compared to NPs, whereas healthy arteries released even lower levels. Furthermore, we highlight a functional interaction between these proteases in human atherosclerotic tissues and more importantly, we demonstrate that the core constitutes the main source of protease activities within CPs. Together, these results suggest that CPs generate plasmin, mainly in the core, which could in turn participate in MMP activation and the onset of complications.     

Renal granulomatoses: a retrospective study of 40 cases and review of the literature

Renal granulomatoses represent 0.5%-0.9% of nephropathies examined by renal biopsies. Granulomas can be isolated to the kidney or associated with other tissue involvement. We describe 40 consecutive patients with renal granulomatoses, associated with pauci-immune crescentic glomerulonephritis in 2 patients and with vasculitis in another, seen in northeastern Paris hospitals between January 1991 and February 2004. The criterion for inclusion was the presence of 1 or more epithelioid granulomas in the renal interstitium. Our population of 25 men and 15 women had a median age of 53 years. All patients suffered from renal insufficiency with median creatininemia of 236.8 micromol/L (range, 124-805 micromol/L), associated with hypertension (25%), median proteinuria of 0.6 g/24 h (range, 0.08-3.00 g/24 h), microscopic hematuria (15%) and leukocyturia (22.5%). Histologic examination of extrarenal specimens detected granulomas in 82.4% of the bronchial biopsies taken, and in 100% of the 2 skin biopsies, the 2 lymph-node biopsies, and the liver and colon biopsies. The following etiologies were retained: sarcoidosis for 20 (50%) patients, drug-induced for 7 (17.5%), tuberculosis for 3 (7.5%), Wegener granulomatosis for 2 (5%), and leprosy, Mycobacterium avium infection, and Crohn disease for 1 (2.5%) patient each. No etiology could be identified for 5 (12.5%) patients. Treatment must be adapted to the etiology of each case. The renal outcome after treatment was generally favorable, with the estimated median creatinine clearance increasing from 26 mL/min (range, 5.4-80.0 mL/min) to 46.5 mL/min (range, 0-118 mL/min) after a median follow-up of 35.5 months (range, 3-158 mo). Nonetheless, 32 patients had persistent renal insufficiency; 1 required hemodialysis and another underwent renal transplantation. Sarcoidosis and medications are the most common causes of renal granulomatosis. Idiopathic and drug-induced forms do not relapse after treatment discontinuation, and remission persists at long-term follow-up.     

Intermediate coronary care units: rationale, infrastructure, equipment, and referral criteria

The Spanish Working Group on Coronary Artery Disease of Spanish Society of Cardiology has considered to be necessary the development of this document on the need, structure and organization of Intermediate Cardiac Care Units (ICCU). Acute coronary syndrome registries show that an important percentage of patients receive a suboptimal care, due to an inadequate management of health resources or absence of them. Intermediate cardiac care units arise to solve these challenges and to manage in an efficient way these expensive and limited resources. Their aims are: a) to provide each patient the level of care required; b) to optimize the structural, technical and human resources, and c) to make easier continuous care and care gradient. As a result, ICCU should be established as an essential part of the cardiology department aim to cardiac patients requiring monitoring and medical care superior to those available in a regular cardiac ward but whose risk does not justify the technical and human costs of a Coronary Unit. This document describes the structure (equipment, human resources, management) required to reach the goals previously reported and includes recommendations about indications of admission in a ICCU. These indications include: a) patients with NSTE-ACS with intermediate or high risk but hemodynamically stable, and b) low risk STEAMI or high risk STEAMI stabilized after an initial admission at the Coronary Unit. The admission of some patients undergoing invasive procedures or suffering non-coronary acute cardiac diseases, is also considered.     

Plasma cell growth fraction using Ki-67 antigen expression identifies a subgroup of multiple myeloma patients displaying short survival within the ISS stage I

The current most powerful prognostic model in Multiple Myeloma (MM) combines beta-2 microglobulin (b2m) with albumin, corresponding to the International Staging System (ISS). However, the prognosis of patients within the ISS stage I (high albumin and low b2m) may vary. Ki-67 is a nuclear protein associated with cell proliferation. We retrospectively evaluated the percentage of bone marrow plasma cells expressing Ki-67 antigen (Ki-67 index) in a series of 174 untreated MM patients at diagnosis. Median survival was 51, 41 and 20 months respectively, and median Ki-67 index was 3.0%, 6.1% and 6.5% in ISS stages I, II, and III respectively. Independently of ISS, Ki-67 index > or =4% was highly predictive of adverse prognosis. Ki-67 index correlated with markers of intrinsic malignancy and with markers of tumour burden. Within ISS stage I, median survival was of 31 months (RR of death 2.65) in patients with Ki-67 index > or =4%. Eventually, the combination of Ki-67 with b2m produced an efficient prognostic model, which appeared most effective in our series when compared with b2m and KI-67 with chromosome 13 deletion models. In this series, we demonstrated that a proliferation marker provides clear-cut additional survival prognostic information to b2m into the ISS model.     

Prevalence of Toscana virus antibodies in volunteer blood donors and patients with central nervous system infections in southeastern France

Toscana virus (TOSV) is a sandfly-borne phlebovirus causing meningitis and encephalitis during the summer period. A significant proportion of infection results in asymptomatic or pauci-symptomatic forms. Although seroprevalence studies had been conducted in Italy, Spain, Greece, and Cyprus, no data were available from France at the outset of this study. We present here results of seroprevalence studies conducted in volunteer blood donors and in patients presenting with central nervous system (CNS) infections. Twelve percent of sera from blood donors and 18.9% of sera from patients hospitalized for CNS infection contained immunoglobulin G (IgG) reacting against TOSV or TOSV-related phleboviruses. This study confirms that TOSV and possibly TOSV-related phleboviruses actively circulates in southeastern France and demonstrates that a significant proportion of healthy blood donors and patients with CNS infections have a history of TOSV or TOSV-related phlebovirus infection.