Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.

OBJECTIVES: This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. METHODS: Patients (n=1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. RESULTS: The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 micromol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). CONCLUSIONS: Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Sub-acute intoxication by Senna occidentalis seeds in rats.

Senna occidentalis (So) is a weed that grows in pastures along fences and in fields cultivated with cereals such as corn and soybean, and many reports have been showing intoxication with this plant in different animal species. It is also used in many medicinal purposes. The objective of the present study was to better evaluate the toxic effects of prolonged administration of So seeds to rats. Forty male Wistar rats were divided into four groups of 10 animals each, three of them respectively fed rations containing 1%, 2% and 4% So seeds, and the last one (control) fed commercial ration for a period of 2 weeks. Fourteen rats were also used in a pair-feeding (PF) experiment. The rats of the experimental groups showed lethargy, weakness, recumbency, depression and emaciation. Two rats of the 4% group and two of the PF group died during the experiment. Histopathological study showed fiber degenerations in the skeletal (Tibial, pectoral and diaphragm) and cardiac muscles. In the liver parenchyma, was observed vacuolar degeneration and, in the kidney, mild nefrosis in the proximal convoluted tubules. All of these alterations occurred in a dose-dependent fashion. Moderate to severe degeneration and spongiosis in the central nervous system, especially in cerebellum. Electron microscopy revealed mitochondrial lesions in all analyzed tissues.     

Quality assurance, efficiency indicators and cost-utility of the evaluation workup for liver transplantation.

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost-analysis. A single-center, pre-LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre-LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre-LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre-LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre-LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost-utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of 4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre-LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from 4,710.8 to 4,165.4).     

Séquelles fonctionnelles de la chirurgie carcinologique du rectum

The development of therapeutic options for rectal cancer strives to reach the ultimate goals of improved local control and overall survival. However, preserving continence, as well as genitourinary and sexual function, remains elusive in some patients. Loss of bowel control may be the most unsettling factor in terms of quality of life. Patients must be accurately informed about the surgery’s possible adverse effects, and surgeons must offer the best options (e.g. colostomy bag or sphincteroplasty) in order to minimize these complaints.     

Bacterial DNA in patients with cirrhosis and sterile ascites. Its role as a marker of bacterial translocation and prognostic tool]

During the last decade, we have witnessed an increase in the amount of data related with the presence of bacterial translocation in experimental models of cirrhosis. However, clinical studies have been limited by the lack of non-invasive methods to study this phenomenon. Over the past years, the research developed in our laboratory has been focused on the detection of bacterial DNA in serum and ascitic fluid of patients with cirrhosis and sterile ascites, the clinical and immunological implications of such finding. Initially, by means of a polymerase chain reaction (PCR)-based method and automated nucleotide sequencing, we were able to detect and identify the presence of fragments of bacterial DNA in the mentioned patients with culture-negative, non-neutrocytic ascites. Since then, we have accumulated a core of data suggesting that the presence of bacterial DNA may have an important role not only as a marker of bacterial translocation, but also as a short-term prognostic factor. Here, we discuss the past, present and future of this line of investigation.     

Thrombin Inhibits the Migration of Human Liver Myofibroblasts

Scarring of the cornea, the transparent tissue at the front of the eyeball, is an important cause of visual impairment. A major chemokine upregulated in tear fluid after corneal injury is platelet‐derived growth factor (PDGF), which induces the stromal cells of the cornea (keratocytes) to assume a fibroblastic phenotype. We have investigated the role of PDGF in matrix contraction by human corneal fibroblasts (HCF) using the standard three‐dimensional (3D) fibroblast‐populated collagen matrix model (FPCM).
When stimulated with PDGF, HCF in monolayer (2D) display circular ruffles (CR) on their dorsal surface. Using immunolabeling, we found that CR contain proteins of the Arp2/3 complex, which is required for the assembly of filamentous actin during protrusive activity. This PDGF‐mediated ruffling ability is altered by antibodies or blocking peptides that specifically interfere with the Arp2/3‐mediated pathway of actin polymerization, as well as by the myosin light chain kinase inhibitor, ML9. Preincubation with anti‐PDGF‐BB antibody or with the tyrosine kinase inhibitor, AG1295, also inhibits CR. While PDGF efficiently stimulates HCF‐mediated cell protrusive activity and macroscopic collagen gel contraction in the 3D model, this effect is directly inhibited by all the substances which inhibit CR in 2D, demonstrating a direct involvement of the PDGF‐mediated CR pathway in tissue contraction. Thus, 3D PDGF‐induced matrix contraction by HCF involves the same players as CR, a phenomenon observed in 2D cell cultures: PDGF‐BB receptor, receptor tyrosine kinase, the machinery for filamentous actin assembly (Arp 2/3 complex, Scar and Wasp proteins), and myosin. The functional role of circular ruffling or its equivalent in three‐dimensional fibroblast‐populated collagen matrices seems to be a rapid reorganization of the actin cytoskeleton in preparation for cell‐matrix interaction.     

Ecological association between indoor radon concentration and childhood leukaemia incidence in France, 1990-1998.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.     

Functional prognosis of stroke in countries in the process of development: Senegal]

OBJECTIVE: To evaluate the functional outcome in patients followed in the department of neurology of Dakar for stroke. MATERIALS AND METHOD: Prospective longitudinal observational study from August 2003 to May 2005 included inpatients or outpatients with stroke one month or less from entry confirmed by computed tomography scan. Patients were followed monthly for 12 months. At each visit, data on functional autonomy measured by the Barthel index and the treatments received were collected. RESULTS: One hundred and seventy patients aged 25 to 90 years (mean 61+/-13 years) were evaluated. The sex ratio was 0.68. A total of 64.7% of strokes involved ischemic cerebral vascular accidents and 35.3% hemorrhagic vascular accidents. Right hemiplegia was present in 55.9%, left hemiplegia in 42.9% and bilateral paresis in 1.2% of patients. A total of 28.8% of patients died between d0 and d30, 50.6% within one year. At entry, the Barthel score was greater than 60 in only 4.7% of patients. After one-year follow-up, 58.3% of the patients had a Barthel score greater than 60, 19.1% had a score between 20 and 40 and 22.6% a score between 40 and 60. Only 53.5% received rehabilitation care. The parameters significantly associated with a functional recovery were age less than 55 years (P<0.05), hemorrhagic vascular accident as opposed to ischemic vascular accident (P<0.05), and earlier rehabilitation care under qualified personnel (P<0.01). DISCUSSION: Our study shows an important rate of mortality during the first year following stroke and the rather young age of our population. The parameters associated with a better functional recovery are comparable to most of the data in the literature. The results of our study suggest that it is possible to improve functional prognosis after stroke by setting measures of prevention of the risk factors and rehabilitation in the early management of hemiplegia.