Effect of retinoids on the induction of colon cancer in F344 rats by N-methyl-N-nitrosourea or by 1,2-dimethyihydrazine

The possible modifying effect of synthetic and natural retinoidson the incidence of colon cancer in rats induced by 2 intrarectaldoses of 2.5 mg of N-methyl-N-nitrosourea (MNU) given once aweek for 2 successive weeks or a single 150 mg/kg body weightdose of 1,2-dime-thylhydrazine (DMH), s.c. was investigated.Emphasis was on the effect of the development of early tumorsas visualized by endoscopy. With the retinoids N-ethyl-retinamide,N-2-hydroxyethylretinamide, N-(4-hydro- xyphenyl)-all-trans-retinamide(RAHA), and retinyl acetate (RA) administered orally after thecarcinogens, significant differences in early developing tumorswere not found. At histopathological examination of the tumorsthe RAHA + DMH group had significantly fewer adenomas per animal.The percentage of adenoma bearing rats was significantly lowerin groups receiving RAHA + DMH or RA + DMH. However, food consumptionwas lower in rats consuming either RAHA or RA. Retinyl palmitate(RP) and RAHA was administered intrarectally to MNU-inducedrats either before or after the carcinogen. When administeredbefore MNU, RP caused a significant increase in the percentageof tumor bearing animals and the average number of tumors peranimal as visualized endos copically. At histopathological examination,all retinoid groups except RAHA given after the carcinogen,produced significantly more adenomas per animal and a significantlygreater adenoma incidence than did the control groups. Thus,in two systems, the oral administration of retinoids did notclearly inhibit the early or later stages of colon tumor development.Inirarectal infusion of two retinoids had no effect on colonicmor phology but at histopathological examination of later stagetumors there was an enhanced adenoma response.     

Diagnosis and management of hemorrhagic complications of percutaneous transhepatic biliary drainage: a primer for residents

Hemorrhagic complications are uncommon after percutaneous transhepatic biliary drainage. The presenting features include bleeding through or around the drainage catheter, hematemesis or melena. Diagnosis requires cholangiography, CT angiography or conventional angiography. Minor venous hemorrhage is managed by catheter repositioning, clamping or upgrading to a larger bore catheter. Major vascular injuries require percutaneous or endovascular procedures like embolization or stenting. A complete knowledge of these complications will direct the interventional radiologist to take adequate precautions to reduce their incidence and necessary steps in their management. This review presents and discusses various hemorrhagic complications occurring after percutaneous transhepatic biliary drainage along with their treatment options and suggests a detailed algorithm.     

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.     

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.     

Risk of comorbidities and outcomes in patients with lower gastrointestinal bleeding-a nationwide study

Background

The impact of comorbidities on outcomes of patients with lower gastrointestinal bleeding (LGIB) remains unknown.

Objective

Investigate the prevalence of comorbidities and impact on outcomes of patients with LGIB.

Methods

The Nationwide Inpatient Sample 2010 was used to identify patients who had a primary discharge diagnosis of LGIB based on International Classification of Diseases, the 9th revision, clinical modification codes. The presence of comorbid illness was assessed using the Elixhauser index. Logistic regression models were used to assess the contributions of the individual Elixhauser comorbidities to predict in-hospital mortality.

Results

A total of 58,296 discharges with LGIB were identified. The overall mortality was 2.3 %. Among the patients who underwent colonoscopy, 17.3 % of patients had therapeutic intervention. As the number of comorbidities increased (i.e., 0, 1, 2, or >3), mortality increased (1.7, 2.0, 2.4, and 2.4 %, respectively). The mortality rate was highest in patients >65 years of age (2.7 %). Patients >65 years of age with two or more comorbidities had a mortality rate of 5 % as compared to 2.6 % in those with less than two comorbidities. Congestive heart failure (odds ratio, 1.67 [95 % confidence interval, 1.48–1.95]), liver disease (2.64 [1.83–3.80]), renal failure (1.99 [1.70–2.33]), and weight loss (2.66 [2.27–3.12]) were associated with a significant increase in mortality rate. Comorbidities increased hospital stay and costs.

Conclusions

Comorbidities were associated with increased the risk of mortality and health care utilization in patients with LGIB. Identification of comorbidities and development of risk-adjustment tools may improve the outcome of patients with LGIB.