Comparison of Intravenous versus Topical Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Study

The purpose of this study was to compare the efficacy of topical Tranexamic Acid (TXA) versus Intravenous (IV) Tranexamic Acid for reduction of blood loss following primary total knee arthroplasty (TKA). This prospective randomized study involved 89 patients comparing topical administration of 2.0 g TXA, versus IV administration of 10 mg/kg. There were no differences between the two groups with regard to patient demographics or perioperative function. The primary outcome measure, perioperative change in hemoglobin level, showed a decrease of 3.06 ± 1.02 in the IV group and 3.42 ± 1.07 in the topical group (P = 0.108). There were no statistical differences between the groups in preoperative hemoglobin level, lowest postoperative hemoglobin level, or total drain output. One patient in the topical group required blood transfusion (P = 0.342). Based on our study, topical Tranexamic Acid has similar efficacy to IV Tranexamic Acid for TKA patients.     

Comparative in vitro activity of three fluoroquinolones against clinical isolates by E test

The in vitro susceptibility of levofloxacin, ciprofloxacin and moxifloxacin against several gram-positive and gram-negative clinical isolates was tested by E test. We found that the MIC(50) and MIC(90) values against all members of the Enterobacteriaceae family except Serratia were <0.5 mg/l for ciprofloxacin and levofloxacin (MIC range 0.006-32 mg/l) based on the in vitro susceptibility data. The susceptibility rates for ciprofloxacin and levofloxacin were more than 85% for Escherichia coli, citrobacter, enterobacter cloacae, enterobacter aerogenes and Klebsiella pneumoniae, although Serratia and Acinetobacter exhibited more or less similar susceptibility rates (about 80%). Pseudomonas aeruginosa demonstrated significant resistance to fluoroquinolones (MIC(90) >32 mg/l) and decreased bactericidal rates (<65%) to levofloxacin and ciprofloxacin. Respiratory pathogens such as Streptococcus pneumoniae and Haemophilus influenzae were highly susceptible (100%) to levofloxacin and moxifloxacin. The ineffectiveness of fluoroquinolones for treating coagulase-positive Staphylococcus aureus was demonstrated by poor in vitro susceptibility rates with levofloxacin (52%) and moxifloxacin (57%). Coagulase-negative staphylococci demonstrated significantly decreased bactericidal rates to levofloxacin (21%), while the in vitro susceptibility to moxifloxacin was higher (66%) than that to levofloxacin. We propose that the beneficial effect of inclusion of any of these three fluoroquinolones in treating Enterococcus infections is marginal, as demonstrated by significantly reduced susceptibility rates (<32%). These data demonstrate the utility of fluoroquinoles to treat several gram-negative bacterial infections (with the exception of Acinetobacter and P. aeruginosa), as well as S. pneumoniae and H. influenzae.     

Urokinase-type plasminogen activator is a preferred substrate of the human epithelium serine protease tryptase epsilon/PRSS22

Tryptase epsilon is a member of the chromosome 16p13.3 family of human serine proteases that is preferentially expressed by epithelial cells. Recombinant pro-tryptase epsilon was generated to understand how the exocytosed zymogen might be activated outside of the epithelial cell, as well as to address its possible role in normal and diseased states. Using expression/site-directed mutagenesis approaches, we now show that Lys20, Cys90, and Asp92 in the protease's substrate-binding cleft regulate its enzymatic activity. We also show that Arg(-1) in the propeptide domain controls its ability to autoactivate. In vitro studies revealed that recombinant tryptase epsilon possesses a restricted substrate specificity. Once activated, tryptase epsilon cannot be inhibited effectively by the diverse array of protease inhibitors present in normal human plasma. Moreover, this epithelium protease is not highly susceptible to alpha1-antitrypsin or secretory leukocyte protease inhibitor, which are present in the lung. Recombinant tryptase epsilon could not cleave fibronectin, vitronectin, laminin, single-chain tissue-type plasminogen activator, plasminogen, or any prominent serum protein. Nevertheless, tryptase epsilon readily converted single-chain pro-urokinase-type plasminogen activator (pro-uPA/scuPA) into its mature, enzymatically active protease. Tryptase epsilon also was able to induce pro-uPA-expressing smooth muscle cells to increase their migration through a basement membrane-like extracellular matrix. The ability to activate uPA in the presence of varied protease inhibitors suggests that tryptase epsilon plays a prominent role in fibrinolysis and other uPA-dependent reactions in the lung.     

Immunogenicity and safety study of Indirab: A Vero cell based chromatographically purified human rabies vaccine

A chromatographically purified Vero cell rabies vaccine, Indirab manufactured by Bharat Biotech International Limited, Hyderabad, India was subjected to safety and immunogenicity studies by both intramuscular and intradermal routes of administration in parallel with a reference vaccine, Verorab. A Pre-exposure study was undertaken in 239 subjects by intramuscular (IM) route (Study I), Post-exposure study in 188 patients by intramuscular route (Study II) and Simulated post-exposure study in 134 subjects by intradermal (ID) route (Study III). All subjects in these studies were administered with either the test or the reference vaccine as per WHO approved intramuscular and intradermal regimens. The blood samples were collected on days 0, 14 and 35 in case of Study 1, and days 0, 14, 28 and 90 in case of studies II and III. In all studies both vaccine groups had adequate antibody titers (>0.5 IU/mL) on all days tested post-vaccination and there was no significant difference in the titers observed (p > 0.05). Some side effects like pain, induration, itching and fever were noted in both vaccine groups in all studies. Both vaccines were well tolerated. Hence it can be concluded that Indirab is as safe and immunogenic as Verorab when administered by both intramuscular and intradermal routes.     

Vitamin D in esophageal cancer: Is there a role for chemoprevention?

Vitamin D has emerged as a promising anti-cancer agent due to its diverse biological effects on tumor differentiation, apoptosis and suppression of cellular proliferation. Current evidence suggests a protective role of vitamin D in colon cancer. The effect of vitamin D on esophageal cancer remains controversial. Multiple studies investigated the association between vitamin D and esophageal cancer, employing different modes of assessment of vitamin D status such as serum 25-hydroxyvitamin D levels, vitamin D dietary intake or exposure to ultraviolet B (UVB) radiation. Genetic variations of the vitamin D receptor (VDR) gene and VDR expression in esophageal specimens have also been investigated. Ecological studies evaluating exposure to UVB radiation yielded an inverse correlation with esophageal cancer. When vitamin D dietary intake was assessed, direct association with esophageal cancer was observed. However, circulating 25-hydroxyvitamin D concentrations showed inconsistent results. In this review article, we present a detailed summary of the current data on the effects of vitamin D on various histological subtypes of esophageal cancer and their precursor lesions. Well-powered prospective studies with accurate measurement of vitamin D status are needed before chemoprevention with vitamin D is recommended, as current evidence does not support a chemopreventive role of vitamin D against esophageal cancer. Future studies looking at the incidence of esophageal cancer in patients with pre-cancerous lesions (Barrett's esophagus and squamous cell dysplasia) receiving vitamin D supplementation are needed.