Impact of beta-blocker therapy on functional capacity criteria for heart transplant listing.

BACKGROUND: Peak exercise oxygen consumption is a widely used parameter to determine the need for transplant listing in patients with severe heart failure. Currently, beta-blocker therapy is known to benefit patients with severe heart failure, although it has minimal or no effects on peak exercise oxygen consumption. This raises the hypothesis that peak exercise oxygen consumption transplant-listing criteria are not valid for patients with heart failure who receive beta-blocker therapy. METHODS: We compared outcomes in patients with chronic heart failure who underwent heart transplant evaluation with peak exercise oxygen consumption 相似文献   

Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist.

Vicriviroc (SCH 417690), a CCR5 receptor antagonist, is currently under investigation for the treatment of human immunodeficiency virus infection. The objective of this study was to identify human liver cytochrome P450 enzyme(s) responsible for the metabolism of vicriviroc. Human liver microsomes metabolized vicriviroc via N-oxidation (M2/M3), O-demethylation (M15), N,N-dealkylation (M16), N-dealkylation (M41), and oxidation to a carboxylic acid metabolite (M35b/M37a). Recombinant human CYP3A4 catalyzed the formation of all these metabolites, whereas CYP3A5 catalyzed the formation of M2/M3 and M41. CYP2C9 only catalyzed the formation of M15. There was a high correlation between the rates of formation of M2/M3, M15, and M41, which was determined using 10 human liver microsomal samples and testosterone 6beta-hydroxylation catalyzed by CYP3A4/5 (r > or = 0.91). Ketoconazole and azamulin (inhibitors of CYP3A4) were potent inhibitors of the formation of M2/M3, M15, M41, and M35b/M37a from human liver microsomes. A CYP3A4/5-specific monoclonal antibody (1 microg/microg of protein) inhibited the formation of all metabolites from human liver microsomes by 86 to 100%. The results of this study suggest that formation of the major vicriviroc metabolites in human liver microsomes is primarily mediated via CYP3A4. CYP2C9 and CYP3A5 most likely play a minor role in the biotransformation of this compound. These enzymology data will provide guidance to design clinical studies to address any potential drug-drug interactions.     

Primary nasal Tuberculosis — A case report

During the past two decades, Tuberculosis — both pulmonary and extrapulmonary have re-emerged as a major health problem worldwide. Nasal tuberculosis may be primary, or secondary to pulmonary tuberculosis or facial lupus. However all of them are rare entities. Nasal tuberculosis should be considered in the differential diagnosis of chronic nasal granulomas. We report a case of primary nasal tuberculosis in an adult female who presented with a polypoidal lesion in the nasal cavity. The diagnosis was based upon smear study, histopathology, culture & polymerase chain reaction. The patient successfully responded to antituberculous therapy and is presently disease free. Given the resurgence of tuberculosis in recent times, it is important that otolaryngologists remain aware of this rare clinical entity.     

CD10 immunohistochemical staining in urothelial neoplasms

CD10, or common acute lymphoblastic leukemia antigen, is a cell surface neutral endopeptidase that inactivates various bioactive peptides. It is expressed by hematopoietic cells and their neoplasms and in a variety of nonhematopoietic tissues and neoplasms. CD10 has been suggested as a useful marker for urothelial carcinoma, but the few studies of CD10 in urothelial tissues have shown varying results; a comparative study of the CD10 immunoprofile in a range of urothelial tumors has not been performed. We report the CD10 immunoprofile of 70 cases representing urothelial lesions as defined by the World Health Organization Classification (2004) of urothelial neoplasia. We demonstrated moderate to strong CD10 immunohistochemical staining in 67% (40/60) of urothelial neoplasms, with a predominantly cytoplasmic staining pattern. We found a statistically significant difference in staining intensity (scale, 0-3) between high-grade neoplasms (mean, 2.5), dysplasia (mean, 1.7), and low-grade lesions (mean, 1.3), with the high-grade group showing a propensity for a more diffuse staining distribution than the low-grade group. Larger studies incorporating molecular genetic techniques should help better define the role of CD10 in urothelial tumorigenesis.     

Comparative efficacy and safety evaluation of cefaclor VS amoxycillin + calvulanate in children with Acute Otitis Media (AOM)

Acute Otitis Media (AOM) is the most frequent respiratory tract infection of infancy and childhood that is treated with antimicrobial agents. The most common causative pathogens includeStreptococcus pneumoniae, Hemophilus influenzae andMoxarella catarrhalis, and therefore antibacterial management should target against these isolates. Cefactor, a congener of cephalexin monohydrate, is a semisynthetic cephalosporin antibiotic. It is an orally active cephalosporin which has demonstrated activity against a wide range of organismsin vitro. Present study is designed as a multicentric prospective trial to study and compare the efficacy and safety of cefaclor versus amoxicillin+clav in children with acute otitis media. One hundred and sixty seven patients were evaluated for efficacy endpoints in the cefaclor arm comprised of 104 males and 63 females with a mean age of 5.74±2.80 years and 185 patients in the amoxy-clav group comprised of 118 males and 67 females with a mean age of 4.93±2.92 years. Both cefaclor and amoxy-clav caused a significant improvement in all the signs and symptoms after a 10-day treatment period. However, between-the-group comparisons showed that the reduction i nmost of the symptoms was significantly more in cefaclor arm as compared to amoxicillin-clav arm. The clinical success (clinical cure + improvement) at the end of therapy was significantly more in cefaclor arm: 98% with cefaclor versus 85% with amoxicillin+clav, p<0.05 (Table 3). Failure cases were prescribed other antibiotics according to the culture sensitivity reports, as rescue medication. Bacterial eradication rates were largely consistent with clinical responses. Bacteriological eradication was seen in 95% of patients in cefaclor group and 78% of patients in amoxicillin+clav group. In conclusion, cefaclor is a well tolerated and effective antibacterial option for acute otitis media in children and it is superior to the combination of amoxicillin+clav in efficacy and tolerability in acute AOM. Moreover, its expanded spectrum of activity, ability to achieve adequate concentrations in tissues, suitability for twicedaily dosing, and proven tolerability suggest that it is a good alternative to agents traditionally used in acute otitis media.     

Screening asymptomatic diabetic patients for coronary artery disease prior to renal transplantation

BACKGROUND: Coronary artery disease (CAD) is a significant contributor to excess mortality in renal transplant candidates with diabetes mellitus (DM). Prior studies relating to risk stratification for significant CAD in diabetics are confined to Caucasian type 1 DM patients. METHODS: To assess the prevalence of clinically silent CAD and to identify variables that are associated with CAD, we retrospectively analyzed the cardiac catheterization data of 97 asymptomatic type 1 and 2 DM kidney and kidney-pancreas transplant candidates. RESULTS: Thirty-three percent of type 1 and 48% of type 2 DM patients had significant stenosis (> or = 70%) in 1 or more coronary arteries. On multivariate logistic regression analysis, body mass index (BMI) >25 was significantly associated with CAD (relative risk = 4.8, P = 0.002). The age of the patient (7% increase in risk/year, P = 0.01; or relative risk = 3.0 if age >47 years, P = 0.032) and smoking history (2% increase in risk/pack-year of smoking, P = 0.10) were also associated with CAD. African American patients, who comprised 30% of the sample, had a 71% lower risk compared with Caucasian patients (P = 0.03). Factors that were not significantly associated with CAD included gender, type of diabetes, and whether dialyzed for >6 months prior to catheterization. CONCLUSIONS: We conclude that a notable proportion (approximately one-third to one-half) of asymptomatic type 1 and type 2 diabetic renal transplant candidates have significant CAD. Additionally, young African American DM patients with no smoking history and a BMI 相似文献   

Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome

OBJECTIVE: To evaluate the effects of surgical weight loss on fatty liver disease in severely obese patients. SUMMARY BACKGROUND DATA: Nonalcoholic fatty liver disease (NAFLD), a spectrum that extends to liver fibrosis and cirrhosis, is rising at an alarming rate. This increase is occurring in conjunction with the rise of severe obesity and is probably mediated in part by metabolic syndrome (MS). Surgical weight loss operations, probably by reversing MS, have been shown to result in improvement in liver histology. METHODS: Patients who underwent laparoscopic surgical weight loss operations from March 1999 through August 2004, and who agreed to have an intraoperative liver biopsy followed by at least one postoperative liver biopsy, were included. RESULTS: There were 70 patients who were eligible. All patients underwent laparoscopic operations, the majority being laparoscopic Roux-en-Y gastric bypass. The mean excess body weight loss at time of second biopsy was 59% +/- 22% and the time interval between biopsies was 15 +/- 9 months. There was a reduction in prevalence of metabolic syndrome, from 70% to 14% (P < 0.001), and a marked improvement in liver steatosis (from 88% to 8%), inflammation (from 23% to 2%), and fibrosis (from 31% to 13%; all P < 0.001). Inflammation and fibrosis resolved in 37% and 20% of patients, respectively, corresponding to improvement of 82% (P < 0.001) in grade and 39% (P < 0.001) in stage of liver disease. CONCLUSION: Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome.