Thromboembolic events occur despite sinus rhythm maintenance in patients treated for atrial fibrillation: The Canadian Trial of Atrial Fibrillation experience

BACKGROUND: Anticoagulation reduces the risk of stroke in patients with atrial fibrillation. It is not clear whether patients who revert and are maintained in sinus rhythm should continue to receive warfarin. The recommendation is to anticoagulate these patients for a minimum of four weeks after cardioversion. Whether warfarin should be maintained for a longer period of time is unknown. METHODS AND RESULTS: To address this question, data from the Canadian Trial of Atrial Fibrillation were reviewed. Among the 403 patients, 81.9% had at least one risk factor for stroke, of whom only 60% were on warfarin. Nine thromboembolic events occurred in nine patients (2.2%): all had at least one risk factor for stroke. Six events occurred in patients who were either not anticoagulated (n=4) or for whom the international normalization ratio was subtherapeutic (n=2). Eight of the nine patients were in sinus rhythm at the last follow-up visit before and at the time of evaluation of the thromboembolic event. CONCLUSIONS: Anticoagulants are underused in atrial fibrillation patients at risk of stroke. Thromboembolic events are most often associated with suboptimal levels of anticoagulation and they occur despite the appearance of sinus rhythm maintenance.     

Rapid single-step FCGR3A genotyping based on SYBR Green I fluorescence in real-time multiplex allele-specific PCR

A polymorphism at position 559 in the cDNA of the FCGR3A gene encoding the FcgammaRIIIa generates two allotypes with either a valine (Val) or a phenylalanine (Phe) at amino acid position 158. This polymorphism is of major importance in immunopathology and in pharmacogenetics, especially monoclonal antibody treatments. In this study, we report a single-step and single-tube method for FCGR3A-158V/F genotyping by real-time multiplex allele-specific PCR and melting curve analysis in the presence of SYBR Green I fluorescent dye. Results obtained from 113 samples showed 100% accuracy compared to those obtained with a conventional PCR-based allele-specific restriction assay. Although this method requires expensive equipment, it is inexpensive in terms of consumables. It is also very rapid, reliable and suitable for large-scale analysis.     

Is angiotensin II a proliferative factor of cardiac fibroblasts?

Angiotensin II has been implicated as an important factor in cardiac remodeling, particularly in the development of pathological left ventricular hypertrophy. It is generally assumed that angiotensin II is able to alter the phenotype of cardiac myocytes and fibroblasts, and several experiments have suggested that this peptide can particularly affect the proliferation of cardiac fibroblasts. However, a review of the published results indicates that there is no evidence that angiotensin II can directly trigger mitogenesis through activation of the cyclin-dependent pathway. The observed proliferative effect might well be caused by stimulation of the synthesis of growth or inflammatory substances like platelet-derived growth factor and cytokines, by integrin activation due to secreted extracellular matrix proteins, or by a combination of these mechanisms. Angiotensin II thus appears to differentiate cardiac fibroblasts into a growth substance-secreting phenotype.     

Bladder involvement in scleroderma: report of 3 cases

Lower urinary tract involvement is the common manifestation of systemic sclerosis. It may represent a troublesome disturbance affecting the quality of life in systemic sclerosis patients. We report three patients with progressive systemic sclerosis who manifested pathologic abnormalities in the urinary bladder. The first patient manifested a recurrent macroscopic hematuria requiring transfusions. Both other patients developed functional and urodynamic abnormalities. With a review of the literature on this involvement of the bladder in systemic sclerosis we try to more understand urinary symptoms and urodynamics features of vesical involvement in systemic sclerosis patients.     

Critical clinicopathologic analysis of 23 cases of fine-needle breast sampling initially recorded as false-positive. The 44-year experience of the Institut Curie

BACKGROUND: Because false-positive cytologic diagnoses in breast tumors are rare, few cases have been reported, although their consequences may be highly detrimental to the patient. The authors report the Institut Curie's experience, by using a multidisciplinary approach. METHODS: Of 9334 benign breast tumors examined preoperatively for cytologic diagnosis by fine-needle sampling (FNS), the 23 (0.25%) FNS cases considered to be false-positive were retrospectively reviewed and analyzed. RESULTS: Tumors were situated close to the nipple in 7 cases and away from the nipple in 16 cases. Tumor stage was T0 for 1 case, T1 for 18 cases, and T2 for 4 cases. Radiologically, six tumors were classified as malignant, seven as indeterminate or suspicious, and nine as benign. Three of six tumors studied by flow cytometry were DNA aneuploid. Based on a multidisciplinary clinicopathologic review, 20 FNS cases were finally classified as false-positive, and the remaining 3 tumors with malignant FNS and subsequent benign histology were classified as true-positive, because local and/or metastatic progression was observed in the short term. CONCLUSIONS: The authors' review suggests two categories of false-positive cases: the first in which cytologic benign patterns are overdiagnosed, and the second in which atypical morphologic criteria were present. Nevertheless, as shown by the malignant course in three cases, patients with malignant preoperative FNS and corresponding benign histology always require close clinical follow-up. Finally, surgical overtreatment rate could be decreased if all radiologically benign tumors with positive/suspicious FNS were subject to intraoperative frozen section examination.     

Downregulation of endothelial nitric oxide synthase in rat aorta after prolonged hypoxia in vivo

The goal of this study was to determine whether hypoxia alters expression of endothelial nitric oxide synthase (eNOS) in the systemic circulation. Rats breathed either air or 10% oxygen for 12 hours, 48 hours, or 7 days. Thoracic aortas were excised and either mounted in organ bath myographs or frozen in liquid nitrogen for later extraction of protein and RNA. eNOS protein (Western blotting) was decreased (20% of normoxic control) after 12 hours, 48 hours, and 7 days of hypoxia. eNOS mRNA (ribonuclease protection assay) was similarly reduced. Acetylcholine (10(-4) mol/L) reversed phenylephrine (10(-5) mol/L) preconstriction by 53.3+/-5.6% in aortic rings from normoxic rats and 26.1+/-4.8% in rings from rats exposed to hypoxia for 48 hours (P<0.05), with comparable impairment of relaxation by the calcium ionophore A23187 (10(-5) mol/L). Responses to diethylamine nitric oxide and 8-bromo-cGMP were unaffected. Aortic cGMP levels after incubation with acetylcholine (10(-6) mol/L) averaged 14.0+/-1.8 fmol/mg in rings from normoxic rats compared with 8.7+/-1.0 fmol/mg in rings from hypoxic rats (P<0. 05). Similarly, nitrate concentration (by capillary electrophoresis) in the media in which the rings were incubated was reduced in the hypoxic group (5.6+/-0.23 micromol/L for hypoxic rats and 7.8+/-0.7 micromol/L for normoxic rats). Impaired endothelial NO release may handicap the vascular responses that defend vital organ function during hypoxia.