Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study

BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. METHODS: Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. RESULTS: In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.     

Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia

In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. An expansion of cells with lesions on one copy of chromosome 2 was evident in 20-25% of treated mice at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hypermutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer.     

Cloning, expression and sequence analysis of the SphI restriction-modification system

SphI, a type II restriction-modification (R-M) system from the bacterium Streptomyces phaeochromogenes, recognizes the sequence 5'-GCATGC. The SphI methyltransferase (MTase)-encoding gene, sphIM, was cloned into Escherichia coli using MTase selection to isolate the clone. However, none of these clones contained the restriction endonuclease (ENase) gene. Repeated attempts to clone the complete ENase gene along with sphIM in one step failed, presumably due to expression of SphI ENase gene, sphIR, in the presence of inadequate expression of sphIM. The complete sphIR was finally cloned using a two-step process. PCR was used to isolate the 3' end of sphIR from a library. The intact sphIR, reconstructed under control of an inducible promoter, was introduced into an E. coli strain containing a plasmid with the NlaIII MTase-encoding gene (nlaIIIM). The nucleotide sequence of the SphI system was determined, analyzed and compared to previously sequenced R-M systems. The sequence was also examined for features which would help explain why sphIR unlike other actinomycete ENase genes seemed to be expressed in E. coli.     

Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China

Esophageal transit scintigraphy seems to be a valid methodology to assess impaired esophageal motility in early stages of disease. The purpose of this study was to discriminate patients with primary Raynaud's phenomenon (RP) and patients with systemic sclerosis (SSc) from healthy subjects by esophageal scintigraphy with a semisolid meal. METHODS: We studied 32 patients with primary RP, 18 with SSc and 13 healthy subjects. Dysphagia, acid regurgitation and heartburn were scored. After an overnight fast, all subjects underwent esophageal scintigraphy, using a semisolid orally ingested bolus (10 mL apple puree) labeled with 99mTc-sulfur colloid. Esophageal transit and emptying time and integral value were evaluated with the subjects in the upright (sitting) and supine positions. Transit time was defined as the time from the entry of 50% of radioactivity into the upper esophagus until the clearance of 50% of the bolus from the whole esophagus. Emptying time was defined as the time from the entry of 50% of radioactivity into the upper esophagus, until the clearance of 100% of the bolus from the whole esophagus. Integral value was defined as the total counts under the time-activity curve normalized to the maximum. RESULTS: Esophageal transit and emptying time and integral value, evaluated in both positions, were significantly higher in patients with SSc than in healthy subjects and than in patients with RP. Moreover, patients with RP had all three parameters, assessed in supine position, significantly longer compared to healthy subjects. Clinical scores regarding dysphagia, acid regurgitation and heartburn were not significantly different between patients with RP and SSc. CONCLUSION: Esophageal transit and emptying time and integral value appear to be able to discriminate patients with primary RP from patients with SSc and patients with RP from healthy subjects, suggesting an early mild esophageal dysfunction in RP.     

Stenosis of the tubular neck: a possible mechanism for progressive renal failure

OBJECTIVE: To study the influence of continuous administration of heparin on platelet function in intensive care patients. DESIGN: Prospective, serial investigation. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. PATIENTS: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. INTERVENTIONS: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). MEASUREMENTS AND RESULTS: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 mumol/l), collagen (10 micrograms/ml), and epinephrine (25 mumol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4-10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e.g., epinephrine-induced maximum platelet aggregation:-45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e.g., ADP-induced maximum platelet aggregation: +42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. CONCLUSIONS: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.     

Toward wide-scale all-optical transparent networking: the ACTSoptical pan-European network (OPEN) project

The European ACTS project optical pan-European network (OPEN) aims at assessing the feasibility of an optical pan-European overlay network, interconnecting major European cities by means of a mesh of high-capacity optical fiber links, cross-connected through transparent photonic nodes. Both the transmission links and the routing network elements rely on wavelength division multiplexing (WDM) all-optical technologies, such as wavelength translation. This paper presents results obtained in the following domains covered within the project: network topology considerations (optimization and dimensioning); network physical layer simulation; fabrications of packaged functional modules based on advanced optoelectronic devices; laboratory demonstrations of N×10 Gb/s transmission and routing; feasibility of an optical time division multiplexing/WDM (OTDM/WDM) interface; and the field implementation of a 4×4 multiwavelength crossconnect prototype, featuring all-optical space and wavelength routing. This implementation was realized in two cross-border field trials, one conducted between Norway and Denmark and the other between France and Belgium. The final results of the Norway to Denmark field trials are presented, featuring the successful cascade of three wavelength-translating optical crossconnects (OXCs), along with the transmission over 1000 km of a mix of standard/submarine cable links for four channels at 2.5 Gb/s     

Microbial resistance: what is to be done? Information from the panel of experts

This document represents the recommendations of a panel of Spanish experts on antibiotic use and resistance. In a Task Force, under the auspices of the Spanish Ministry of Health and Consumer Affairs that took place in 1994 in Madrid, the members were gravely concerned about the national increase in antibiotic resistance. They analysed the development, evolution and spread of antibiotic resistance among community-acquired human bacterial pathogens in Spain, its relation with antibiotic consumption, and they proposed future surveillance strategies for monitoring the patterns of antibiotic use and consumption. Success will require a collective action among the producers (pharmaceutical industry), prescribers (doctors, veterinarians), dispensers (pharmacists), and consumers (patients). Two similar documents have been recently published by the American Society of Microbiology and the World Health Organization showing the global concern about this topic.