Management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH): study design and baseline data

BACKGROUND: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. METHODS: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. RESULTS: Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. CONCLUSION: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.     

Entomofauna of buried bodies in northern France

Autopsies of exhumed cadavers can reveal important evidence for clarification of medical insurance and social issues. This study concerns insects sampled on 22 exhumed cadavers in the Lille area. For each corpse, the species and the stages of development were noted, as well as the time elapsed after burial, the location of the cemetery, the stage of decay and possible preservation treatment. A total of eight Diptera and two Coleoptera species were sampled on the corpses. The relationships between entomofauna and conditions of burial are discussed. Three species were regularly found because of their preference for underground environments or closed environments: Conicera tibialis, typically associated with buried bodies, Leptocera caenosa which is known to be associated with human faeces, water closets, caves and cracked soil pipes, and Ophyra capensis, sometimes found on human bodies kept indoors for several months, where blowflies have not had access. Triphleba hyalinata, which is associated with human bodies in wooden coffins, was found only twice.     

Perception of dynamic action in patients with schizophrenia

Neuropsychological studies have revealed that schizophrenic (SZ) patients have severe impairments in the cognitive integration of static and moving perceptual stimuli. Research on knowledge structures has shown that sequences of continuous actions are represented in memory as clusters of goal-directed events in a hierarchical manner. In the present study, we investigated the ability to segment familiar sequences of dynamic goal-directed actions into small and large meaningful units in a group of patients with schizophrenia (N = 16) and a group of healthy control subjects (N = 17). While viewing two videotaped movies, participants were requested to detect the transitions between component events at both low and high levels of the action categorical structure. Both groups detected significantly more events under the small-oriented condition as compared to the large-oriented condition. Differently from normal controls, patients recalled the event scenes in a detailed and fragmentary manner and showed considerable difficulties in detecting large action units. Moreover, low performance on action boundary detection significantly correlated with higher levels of disorganisation symptoms in patients with schizophrenia. A defective conceptual organisation of perceptive action knowledge would help to explain the severe everyday difficulties of these patients both in monitoring their own actions and in understanding others' intentions.     

Skin sensitivity to rocuronium and vecuronium: a randomized controlled prick-testing study in healthy volunteers

Prick tests are frequently used for the authentication of neuromuscular blocking drugs (NMBDs) as causative drugs for anaphylactic reactions during anesthesia. Unfortunately, the actual threshold concentration for skin testing remains debatable for most NMBDs. We studied the flare and wheal responses to prick tests with rocuronium and vecuronium. Thirty healthy, nonatopic, anesthesia-naive male and female volunteers (14 men and 16 women) from 18 to 40 yr of age were assigned randomly to receive a total of 10 prick tests-4 ascending dilutions (1:1000, 1:100, 1:10, and 1) of rocuronium and vecuronium and 2 controls-on both forearms. An assessor blinded to the assignment monitored systemic and skin responses to NMBDs and measured wheal and flare surfaces immediately after and 15 min after prick tests. None of the volunteers experienced any immediate systemic or cutaneous responses to rocuronium or vecuronium. Although a dilution of 1:1000 of both NMBDs failed to promote any skin response at 15 min, 50% and 40% of the subjects had a positive skin reaction to undiluted rocuronium and vecuronium, respectively. We demonstrated a sex effect related to smaller threshold concentration-induced cutaneous reactions in female volunteers to both muscle relaxants. Our observation questions the reliability of prick testing with undiluted solutions of rocuronium and vecuronium for the diagnosis of allergy. IMPLICATIONS: Building concentration-skin response curves to prick tests with rocuronium and vecuronium in healthy, nonatopic, anesthesia-naive male and female volunteers demonstrated that the nonreactive concentration for both muscle relaxants is the 1:1000 dilution of the stock solutions. Our observation calls into question the past practice of prick-testing skin for sensitivity to neuromuscular blocking drugs by using undiluted solutions.     

Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis

OBJECTIVE: To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury. SUMMARY BACKGROUND DATA: VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms. METHODS: Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed. RESULTS: Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls. CONCLUSIONS: VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.     

Three-dimensional virtual cholangioscopy: a reliable tool for the diagnosis of common bile duct stones

OBJECTIVE: Our goal was to evaluate the clinical reliability of a new software system employing 3-dimensional (3D) virtual anatomic reconstruction and intraluminal virtual exploration for detection of choledocholithiasis and preoperative visualization of the biliary anatomy. SUMMARY BACKGROUND DATA: Virtual reality systems have been proposed for gastroscopy, bronchoscopy, and colonoscopy, as well as for the 3D reconstruction of liver anatomy and hepatic lesions. The impact of these systems in preoperative diagnostics has not been established due to the lack of large clinical series evaluating their reliability. METHODS: From November 2000 to July 2002, all patients presenting to our Institute with suspected choledocholithiasis were prospectively included in the study. All patients underwent conventional magnetic resonance cholangiopancreatography (MRCP) and either intraoperative cholangiogram (IOC) or endoscopic retrograde cholangiopancreatography (ERCP). The digital data from MRCP were incorporated into an original virtual reality software system to generate a 3D reconstruction. All 3D reconstructions were evaluated by a surgeon and a computer software engineer who were blind to the results of the IOC or ERCP. Sensitivity and specificity were then calculated based on the results of either the IOC or ERCP. RESULTS: Sixty-five patients were enrolled in the study. The average time required to reconstruct the images into navigable virtual reality was 7.5 minutes (range, 4-13.5). The 3D virtual cholangioscopy had sensitivity and specificity rates of 71% and 91%, respectively, compared with 61% and 86% of the standard MRCP. CONCLUSION:: The 3D virtual cholangioscopy provides detailed preoperative reconstruction of biliary anatomy and reliable identification of choledocholithiasis with acceptable sensitivity and specificity in a clinical setting. Newer software developments may further enhance its accuracy, so that virtual cholangioscopy might challenge or replace more invasive diagnostic measures in the near future.