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Human factor VIIa is a vitamin K-dependent glycoprotein consisting of 406 amino acids having a molecular weight of 50 kDa (1). Factor VIIa is the initiating factor in the conversion of prothrombin to thrombin via the extrinsic pathway (1). Specifically, factor VIIa forms a complex with tissue factor that activates factor X and factor IX, which in turn forms a multimolecular complex with factor V, which then converts prothrombin to thrombin on the surface of platelets with the resultant production of fibrin monomers. The resultant fibrin undergoes self-polymerization until a critical size is achieved and the protein becomes insoluble as the hemostatic plug or clot. Recently, recombinant human factor VIIa (rhFVIIa) has become commercially available for the treatment of hemophiliacs with antibodies to factor VIII or factor IX and individuals who are congenitally factor VIIdeficient (1). Even more recently, rhFVIIa has been used to control bleeding in cases of trauma in both hemophiliacs as well as nonhemophiliac patients (2–9). This use of rhFVIIa in surgical and trauma units has raised the possibility that rhFVIIa might also be clinically useful in other medical situations. Herein, we report a case of a 68-year-old man with a severe coagulopathy due to alcohol-associated cirrhosis, who experienced a spontaneous acute intracranial hemorrhage and was treated with rhFVIIa with cessation of the intracranial bleeding with clinical and radiological stabilization of his intracranial injury.

8-oxoguanine glycosylase (OGG1) is primarily involved in base excision repair (BER) by excising 8-oxoguanine, a mutagenic by-product of reactive oxygen species exposure. Increased markers of DNA damage/repair have been identified in atherosclerotic plaques, however their effects on plaque stability

DNA damage and repair activity is increasingly recognized in atherogenesis. By facilitating DNA strand joining by catalyzing phosphodiestere bond formation, DNA ligase is crucial in single/double stranded DNA break repair. We aimed to identify differential DNA ligase activity as well as a

Background Prophylaxis against hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) includes lifelong hepatitis B immunoglobulin (HBIG) and oral antiviral agent(s). In the presence of high-genetic-barrier nucleos(t)ide analogues, the need for lifelong HBIG is questioned. We evaluated the safety and cost-effectiveness of a limited HBIG course. Methods OLT from 2006 to 2013 were reviewed. Patients with pre-OLT hepatitis B virus surface antigen who received HBV prophylaxis with 2 HBIG doses (anhepatic and first post-operative day; 10,000 units/dose) and potent nucleos(t)ide analogues were included. The primary end point was HBV recurrence (HBV-DNA detection). Results Thirteen patients (primary transplants) were included, median Model for End-Stage Liver Disease score was 18, and there was no fulminant failure; HBV-DNA was detected in 4 patients at OLT. After OLT, 10 patients received entecavir and/or tenofovir. Median follow-up was 23 months. One recurrence occurred (7.7%) at month 13 (HBV-DNA: 14 IU/mL); the graft maintained excellent function. This minimal viremic expression is related to hepatocellular carcinoma recurrence with neoplastic replication carrying integrated HBV-DNA; thus, there is no defined HBV viral recurrence. No graft loss or patient death was related to HBV recurrence. The 1-year patient and graft survival rate was 84.6%. Cost-savings in the first year was $178,100 per patient when compared with Food and Drug Administration–approved HBIG dosing. Conclusions In the era of potent oral nucleos(t)ide analogues, a limited HBIG course appears to be cost-effective in preventing HBV recurrence.

Collagens, the most abundant proteins in animals, also occur in some recently described nucleocytoplasmic large DNA viruses such as Mimiviridae , which replicate in amoebae. To clarify the impact of viral collagens on the immune response of animals exposed to Mimiviridae , we have investigated the localization of collagens in Acanthamoeba polyphaga mimivirus particles and the response of mice to immunization with mimivirus particles. Using protein biotinylation, we have first shown that viral collagen encoded by open reading frame L71 is present at the surface of mimivirus particles. Exposure to mimivirus collagens elicited the production of anti-collagen antibodies in DBA/1 mice immunized intradermally with mimivirus protein extracts. This antibody response also targeted mouse collagen type II and was accompanied by T-cell reactivity to collagen and joint inflammation, as observed in collagen-induced arthritis following immunization of mice with bovine collagen type II. The broad distribution of nucleocytoplasmic large DNA viruses in the environment suggests that humans are constantly exposed to such large virus particles. A survey of blood sera from healthy human subjects and from rheumatoid arthritis patients indeed demonstrated that 30% of healthy-subject and 36% of rheumatoid arthritis sera recognized the major mimivirus capsid protein L425. Moreover, whereas 6% of healthy-subject sera recognized the mimivirus collagen protein L71, 22% of rheumatoid arthritis sera were positive for mimivirus L71. Accordingly, our study shows that environmental exposure to mimivirus represents a risk factor in triggering autoimmunity to collagens.

Liver biopsy continues to play a critical role in the evaluation and management of patients with liver disease. Although history, physical examination, and serological markers often obviate the need for a diagnostic liver biopsy, it is still considered the criterion standard, especially when the etiology of liver disease remains obscure. Even with a thorough history and laboratory workup, significant fibrosis and/or cirrhosis can be missed in as many as 32% of patients without a liver biopsy. 1 In fact, results of a liver biopsy have been shown to alter diagnosis in as many as 14% of patients with chronically elevated liver enzymes and significantly affect patient management in as many as 18% of such patients. 1,2 Moreover, current noninvasive imaging and serological markers of hepatic fibrosis remain investigational and have not been shown to be as accurate as liver biopsy. EUS has an established and integral role in the diagnosis, management, and treatment of several GI, liver, and pancreaticobiliary diseases. New indications and techniques for EUS continue to emerge as experience grows with this technology. Although there are reports of EUSguided FNA of the liver for evaluation of discrete hepatic lesions, there is only limited information on the role of EUS in assisting with diagnostic liver biopsy. Only 1 study to date has evaluated the histological adequacy of liver tissue obtained with EUS guidance; this particular study used the 19-gauge Tru-Cut core biopsy needle. 3 There are no data regarding histological adequacy when EUS-guided liver biopsy is performed by using a 19-gauge FNA needle. It is presumed that use of such a needle may limit the histological adequacy of the specimen obtained. 4 It remains uncertain whether EUS-guided liver biopsy by using a 19-gauge aspiration needle can acquire an adequate tissue specimen to provide a histological diagnosis. Therefore, the primary aim of this study was to evaluate the histological adequacy of liver tissue specimens obtained using a 19-gauge aspiration needle via a EUSguided approach. Specifically, we analyzed the length of the biopsy specimen, the number of complete portal tracts (CPTs), and the ability of the pathologist to make a diagnosis with the obtained specimen.

Niacin (Vitamin B3) is a naturally occurring human nutrient found in abundance in meat, yeast, vegetables, and seeds. Deficiencies of this vitamin lead to pellagra and it has also been found to be useful in the treatment of hypercholesterolemia. As the use of niacin has increased, several cases of hepatotoxicity have been reported resulting in the recommendation to initiate treatment with a lower dose and to monitor liver function test. We report two cases of hepatotoxicty in young adults who attempted to pass a drug screening test based on faulty internet advice to use niacin.

Despite advances in therapeutic strategies, atherosclerotic coronary artery disease (CAD) remains the commonest worldwide cause of morbidity and mortality. DNA damage and repair have been identified as important in atherogenesis. DNA ligase is crucial in single/double stranded DNA break repair by

Introduction Conventional risk stratification fails to identify many individuals presenting with major adverse cardiovascular events (MACE). Coronary artery calcification (CAC) is a powerful independent predictor of MACE however its use is limited by radiation and expense. MicroRNAs are non-coding RNAs that regulate transcription and their differential expression is acknowledged to be a hallmark of a number of diseases. We aim to determine if a peripheral blood-based microRNA profile is predictive of the presence and extent of CAC in humans. Methods Study patients met the following inclusion criteria: attendance for elective cardiac computed tomography; age 18–65 years; no history of coronary artery disease, cardiomyopathy or tachyarrhythmia; normal renal function; no history of diabetes mellitus; no autoimmune disease; no infection; no malignancy. Peripheral venesection was performed and an Agatston score was derived using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System and stored at –80 o C until Toray’s microarray analysis was undertaken. Results 24 participants were recruited (mean age 54 years; 67% male) and divided into the following categories: [CAC score 0] n = 6; [CAC score 1–10] n = 6; [CAC score 11–100] n = 6; [CAC score > 100] n = 6. Groups were matched according to their baseline characteristics; Table 1. The Student’s t-test was performed between groups. MiR-1181 was significantly down-regulated in all case groups compared to controls: [CAC 1–10] effect size (ES) = 1.76, p = 0.012; [CAC 11–100] ES = 1.74, p = 0.013; [CAC > 100] ES = 3.86, p 100 compared to controls (ES = 3, p Conclusions Human blood-based miRNA-1181 appears to predict the presence and extent of CAC. Likewise miRNAs miR-138-2-3p, miR-6816-3p and miR-8059 are differentially expressed in patients with high CAC scores. We plan to validate these findings using quantitative real-time PCR and to test these results in a prospective cohort. Ultimately miRNAs could act as a biomarker for MACE and identifying their associated molecular pathways may explain the mechanisms underpinning CAC.

Several studies suggest veterans have a higher prevalence of hepatitis C virus infection than nonveterans, possibly because of military exposures. The purpose of this study was to estimate the prevalence of anti-hepatitis C antibody and evaluate factors associated with infection among users of Department of Veterans Affairs medical centers. Using a two-staged cluster sample, 1288 of 3863 randomly selected veterans completed a survey and underwent home-based phlebotomy for serological testing. Administrative and clinical data were used to correct the prevalence estimate for nonparticipation. The prevalence of antihepatitis C antibody among serology participants was 4.0% (95% CI, 2.6%-5.5%). The estimated prevalence in the population of Veterans Affairs medical center users was 5.4% (95% CI, 3.3%-7.5%) after correction for sociodemographic and clinical differences between participants and nonparticipants. Significant predictors of seropositivity included demographic factors, period of military service (e.g., Vietnam era), prior diagnoses, health care use, and lifestyle factors. At least one traditional risk factor (transfusion or intravenous drug use) was reported by 30.2% of all subjects. Among those testing positive for hepatitis C antibody, 78% either had a transfusion or had used injection drugs. Adjusting for injection drug use and nonparticipation, seropositivity was associated with tattoos and incarceration. Military-related exposures were not found to be associated with infection in the adjusted analysis. In conclusion, the prevalence of hepatitis C in these subjects exceeds the estimate from the general US population by more than 2-fold, likely reflecting more exposure to traditional risk factors among these veterans.

We report on the case of a 40-year-old patient with coagulopathic alcoholic cirrhosis who underwent ultrasound-directed pericardiocentesis and fine-needle aspiration biopsy of the pancreas after receiving recombinant human factor VIIa (rhFVIIa). The infusion of rhFVIIa rapidly corrected her coagulopathy and made it possible to perform both procedures. The marked changes produced in the prothrombin time and international normalized ratio as a result of the infusion of rhFVIIa are presented. As a result of these changes in coagulation status, both procedures were performed safely, and the patient's clinical management and subsequent care plan were defined.

A 29-year-old woman with cystic fibrosis presented with abdominal pain, which had worsened over 3 days, together with low-grade fever and chills. The pain, which radiated from the central to the lower abdomen, increased with movement and had been present since bilateral lung transplantation 4months earlier. She had occasional nausea and nonbilious vomiting. The medical history included laparotomy for postoperative small bowel obstruction, diabetes mellitus, and osteoporosis. Medications included metoclopramide, lactulose, prednisone, tacrolimus, azathioprine, valacyclovir, itraconazole, cotrimoxazole, alendronate, lansoprazole, pancreatic enzymes, insulin, calcium, folate, and a multivitamin. Examination was normal except for mild periumbilical tenderness. Laboratory tests revealed mild anemia and a slight nonanion gap acidosis. Two small duodenal ulcers were discovered at EGD. Biopsy specimens revealed mild duodenitis with superficial ulceration. At

Purpose: Monotherapy with interferon alpha (IFN) thrice a week for hepatitis C (HCV) is associated with an end of treatment virologic response rate (ETR) of less than 25% and a sustained virologic response rate of less than 15%. Patients with genotype 1 respond poorly than those infected with other genotypes. We examined the effect of high dose (5 MU daily) and longer duration (18 months) of IFN monotherapy in HCV patients with genotype 1.

malignancy. High grade dysplasia (OR 6.66 [95% CI, 1.52-29.08]) and ductal dilatation (OR 10.96 [95% CI, 2.25-53.42]) were independently associated with malignancy in multivariate analysis. Fourteen (56%) of 25 patients with high grade dysplasia on endoscopic biopsy were revealed as carcinoma after resection. Conclusions The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Adenoma with high grade dysplasia and ductal dilatation are significant predictors of malignancy in the ampullary adenoma.

High dose interferon alpha monotherapy in patients with chronic hepatitis C and normal alanine aminotransferase level

Eosinophilic pneumonitis secondary to pegylated interferon alpha-2b and/or ribavirin therapy

Pegylated interferon and ribavirin treatment in patients with hepatitis C virus associated vasculitis

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

• To determine whether the frequency of chronic hepatitis B in homosexual men reflects the high rate of acute hepatitis B or an altered response to hepatitis B, 236 homosexual men were prospectively followed up after entry into the placebo group of a hepatitis B vaccine trial. Sixty-six participants (28.0%) developed hepatitis B ten to 18 months after entering the study. Only four (6.1%) of the 66 had persistence of hepatitis B beyond six months, similar to reports in nonhomosexual subjects. This study suggests that the high rate of acute hepatitis B is the major factor contributing to the high prevalence of chronic hepatitis B in homosexual men, rather than an altered host response. Clinical features of the acute illness could not be used to identify patients who developed chronic hepatitis B. (Arch Intern Med1985;145:881-882)