Non-fatal major bleeding during treatment with vitamin K antagonists: influence of soluble thrombomodulin and mutations in the propeptide of coagulation factor IX.

BACKGROUND AND OBJECTIVES: The key complication of treatment with vitamin K antagonists (VKAs) is bleeding. The major determinant of VKA-induced bleeding is the intensity of anticoagulation. Individual patient characteristics may also influence bleeding risk. In addition, soluble thrombomodulin (s-TM) levels and mutations in the propeptide of factor (F)IX are important candidate risk factors in this respect. PATIENTS AND METHODS: A matched case-control study was designed to search for risk factors that predict bleeding during VKA treatment. We selected cases that had experienced major bleeding during treatment with VKA and matched controls without bleeding complications from the databases of two Thrombosis Services. The controls were matched for indication of treatment, age, gender, type of anticoagulant used and whether or not treatment with VKA was stopped. DNA and plasma were stored of all cases and controls. RESULTS AND CONCLUSIONS: In total 110 patients and 220 controls consented to participate. The results indicate that s-TM levels, measured by ELISA, may be a risk indicator for bleeding [crude odds ratio 3.25 for the highest quartile vs. the lowest quartile (95% confidence interval 1.40, 7.51)]. Three novel mutations, determined by direct sequencing, in the gene portion encoding the propeptide of FIX were identified that do not seem to play an important role in bleeding risk during treatment with VKAs.     

Gender Differences in the Amount of Gingival Display During Smiling Using Two Intraoral Dental Biometric Measurements

Purpose: The aims of this study were to compare gender differences in the width and length of the maxillary right central incisor and the horizontal and vertical overlap of the anterior teeth and to determine the relationships of these two intraoral dental biometric measurements with the amount of gingival display during smiling. Materials and Methods: A total of 61 men and 66 women were included in this study. For each participant, the gingival tissue display during smiling was judged to be either visible or not, and the maximum mesiodistal and incisogingival dimensions of the maxillary right central incisor were measured, along with the amount of horizontal and vertical overlap of anterior teeth using a digital caliper. Gender differences in these parameters and the relationship between subjects showing gingival display when smiling and the two intraoral dental biometric measurements were determined. Statistical analyses of data were performed using SPSS (V11) software. The mean scores for gender were calculated, and a Student's t‐test was used to identify significant differences between both groups. Significance level was set to 0.05. Results: The age of the participants ranged between 23 and 52, with a mean of 33.47 ± 9.07 years. A relatively small percentage of the subjects (22.05%) displayed gingiva when smiling. More women displayed gingiva when smiling than men, with a 2:1 female:male ratio. Men exhibited significantly (p < 0.05) wider (8.76 ± 0.66 mm) and longer (10.28 ± 0.88 mm) central incisors compared to women (7.92 ± 0.72 mm; 9.27 ± 0.93 mm width and length, respectively). No gender differences were found in the width‐to‐length ratio. Subjects with gingival display had significantly more horizontal (4.28 ± 1.21 mm; p < 0.001), and vertical (3.52 ± 0.66 mm; p < 0.05) overlap of anterior teeth compared to those who did not display gingiva when smiling (2.40 ± 1.03 and 2.30 ± 0.93 mm, respectively). Conclusions: Significantly more women displayed gingiva in smiling. Men had significantly wider and longer central incisors. No differences were recorded between men and women relative to both the horizontal and vertical anterior tooth overlap. Subjects who displayed gingiva when smiling had more horizontal and vertical overlap of anterior teeth.     

Discoid lupus erythematosus

Discoid lupus erythematosus is a manifestation of chronic cutaneous lupus erythematosus with a small risk of systemic involvement. In this review article, the role of predisposing factors such as haplotype, hormones, antibodies and sunlight are discussed. The clinical features, including variants and associations, and management options are presented.     

Including emergency and acute care as a global health priority

The clinical findings of Takatsubo Cardiomyopathy and acute myocardial infarction can be very similar. While Takatsubo cardiomyopathy rarely leads to severe complications, acute myocardial infarction can be life threatening. Treatment of both these conditions is different and so it is imperative for clinicians to have a high index of suspicion for either. Several EKG differences between the two entities have been proposed. This article summarizes the EKG changes most likely seen in Takatsubo cardiomyopathy and compares them to those seen in Acute Myocardial infarction.     

Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner

Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression. We are unique in reporting that asTF, but not flTF, strongly associates with both tumor size and grade, and induces BrCa cell proliferation by binding to β1 integrins. asTF promotes oncogenic gene expression, anchorage-independent growth, and strongly up-regulates tumor expansion in a luminal BrCa model. In basal BrCa cells that constitutively express both TF isoforms, asTF blockade reduces tumor growth and proliferation in vivo. We propose that asTF plays a major role in BrCa progression acting as an autocrine factor that promotes tumor progression. Targeting asTF may comprise a previously unexplored therapeutic strategy in BrCa that stems tumor growth, yet does not impair normal hemostasis.     

The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P- selectin protein. All P-selectin polymorphisms as well as a common E- selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.      

Symptomatic and asymptomatic abnormalities in patients with lumbosacral radicular syndrome: Clinical examination compared with MRI

OBJECTIVE: To determine the frequency of symptomatic and asymptomatic herniated discs and root compression in patients with lumbosacral radicular syndrome (LRS) and to correlate clinical localization with MRI findings. METHODS: Fifty-seven patients with unilateral LRS were included in the study. Using the visual analogue scale, two physicians independently localized the most likely lumbar level of complaints. These clinical predictions of localizations were correlated with the MRI findings. RESULTS: MRI showed abnormalities on the symptomatic side in 42 of 57 patients (74%). In 30% of the patients, MRI confirmed an abnormality at the exact same level as determined after clinical examination. On the asymptomatic side, MRI showed abnormalities in 19 of 57 patients (33%), 13 (23%) of these patients had asymptomatic root compression. CONCLUSIONS: In more than two-thirds of the patients with unilateral LRS there was no exact match between the level predicted by clinical examination and MRI findings. These discrepancies complicate the decision whether or not to operate.