Dose-dependent pharmacokinetics of itraconazole after intravenous or oral administration to rats: intestinal first-pass effect

The dose-dependent pharmacokinetics of itraconazole after intravenous (10, 20, or 30 mg/kg) and oral (10, 30, or 50 mg/kg) administration and the first-pass effects of itraconazole after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 10 mg/kg were evaluated in rats. After intravenous administration at a dose of 30 mg/kg, the area under the plasma concentration-time curve from time zero to infinity (AUC(0- infinity )) was significantly greater than those at 10 and 20 mg/kg (1,090, 1,270, and 1,760 micro g. min/ml for 10, 20, and 30 mg/kg, dose-normalized at 10 mg/kg). After oral administration, the AUC(0- infinity ) was significantly different for three oral doses (380, 687, and 934 micro g. min/ml for 10, 30, and 50 mg/kg, respectively, dose-normalized at 10 mg/kg). The extent of absolute oral bioavailability (F) was 34.9% after an oral dose at 10 mg/kg. The AUC(0- infinity ) (or AUC(0-8 h)) values were comparable between intravenous and intraportal administration and between intragastric and intraduodenal administration, suggesting that the hepatic and gastric first-pass effects were almost negligible in rats. However, the AUC(0-8 h) values after intraduodenal and intragastric administration were significantly smaller than that after intraportal administration, approximately 30%, suggesting that the intestinal first-pass effect was approximately 70% of that of an oral dose of 10 mg/kg. The low F after oral administration of itraconazole at a dose of 10 mg/kg could be mainly due to the considerable intestinal first-pass effect.     

Twin AV node and induced supraventricular tachycardia in Fontan palliation patients

INTRODUCTION: The coexistence of two distinct atrioventricular (AV) nodes has been described in congenital heart disease requiring Fontan type palliation. The purpose of this study was to evaluate the occurrence of twin AV node according to anatomical subgroups, and to determine its relation to tachycardia. METHODS: From 2001 to 2003, we performed an electrophysiologic (EP) study upon 52 consecutive patients who had undergone cardiac catheterization after Fontan completion. Atrial pacing was performed at three or more different atrial sites. RESULTS: In 10/52 patients, two different QRS complexes were recorded at different pacing sites, suggesting twin AV node (9/20 in right isomerism, 1/8 discordance AV connections, 0/24 other complex anomalies). AV reciprocating tachycardia (AVRT), presumably involving two AV nodes and a connecting sling, was induced in 6 of 10 patients who had twin AV node (4/6 used posterior AV node as an antegrade limb, 2/6 used an anterior AV node as an antegrade limb). Heterotaxy syndrome (P < 0.001) and complete AV septal defect (P = 0.002) were found to be risk factors for twin AV node. Junctional tachycardia (JT; HR > 150/min) with either VA dissociation (7/9) or second degree VA block (2/9) were induced by pacing or isoproterenol infusion in 9/52 patients. CONCLUSION: JT induction was associated with a twin AV node (P = 0.04), or a history of early postoperative junctional ectopic tachycardia (P = 0.02). A complicated AV node conduction system such as twin AV node was frequent in heterotaxy syndrome. Both AVRT and JT with VA block may be important causes of tachyarrhythmia in this patient group.     

Effect of atorvastatin monotherapy and low-dose atorvastatin/ezetimibe combination on fasting and postprandial triglycerides in combined hyperlipedemia

Postprandial triglyceride (TG) levels are easy to measure and are associated with future cardiovascular risk. The aim of this study was to compare the effects of statin monotherapy and low-dose statin/ezetimibe on lipid parameters including fasting and postprandial TG. After a 4-week dietary run-in period, 78 patients with combined hyperlipidemia were randomized into 1 of 2 treatment groups for 8 weeks: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. An oral fat load test was performed before and after the drug-treatment period. The low-dose combination had a tendency to decrease fasting TG more than atorvastatin monotherapy. The combination regimen showed a greater reduction in postprandial TG (-13% ± 42% and -34% ± 30%, in the atorvastatin and combination groups, respectively, P = .03) and total cholesterol (TC; P = .03). The changes in low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were not different between the 2 groups. The reduction in apo B/A1 was greater in the combination group (-32% ± 19% and -42% ± 13%, in the atorvastatin and combination groups, respectively, P = .02). In conclusion, these results demonstrated a potential beneficial effect of low-dose atorvastatin/ezetimibe combination treatment on postprandial TG control after comparable LDL-C lowering in patients with combined hyperlipidemia.     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

Hemobilia caused by liver abscess due to intrahepatic duct stones

Hemobilia occurs when injury or disease causes communication between intrahepatic blood vessels and the biliary tract. Causes of hemobilia include trauma; gallstones; inflammatory diseases; and vascular disorders such as aneurysm, tumor, and coagulopathy. Recently, with the increasing use of invasive diagnostic and therapeutic procedures involving the hepatobiliary tract, an increasing proportion of the causes of hemobilia have been of iatrogenic origin. Hemobilia may also be associated with liver abscess, but this condition is very rare. Our review of the English-language literature disclosed few cases of liver abscess associated with hemobilia. Here, we present a case of hemobilia caused by liver abscess due to intrahepatic duct stones. Liver abscess should be considered in the causes of hemobilia, especially in areas where hepatobiliary parasitic infection is endemic.     

Evaluation of lung function and clinical features of interlaminar cervical epidural steroid injections: a randomized controlled trial

ObjectiveInterlaminar cervical epidural steroid injections (ICESIs) are commonly used to treat axial neck pain and cervical radicular pain. However, local anesthetics can spread to and block the phrenic nerve and upper segments of the thoracic spinal cord where the sympathetic innervation of the lungs emerges. Therefore, changes in lung function may occur following ICESIs.MethodsThe primary outcome measure was the pulmonary function test (PFT) result 30 minutes before and after ICESI with ropivacaine (0.1875% or 0.25%). The secondary outcome measure was the comparison of the pain scores and functional disability between the two concentrations of ropivacaine 4 weeks after the ICESIs.ResultsFifty patients were randomly assigned to either the R1 (0.1875% ropivacaine) or R2 (0.25% ropivacaine) group. No significant difference was observed between the pre-ICESI and 30-minute post-ICESI PFT results within each group, and no difference was observed between the two groups. After 4 weeks of treatment, both groups showed a significant decrease in pain scores and functional disability; however, no significant differences were observed between the two groups.ConclusionsThis study showed no significant change in lung function after ICESIs in either group and no local anesthetic concentration-based difference in the clinical efficacy of the ICESIs.     

Microtubule- and dynein-mediated movement of Orientia tsutsugamushi to the microtubule organizing center

The host cell microfilaments and microtubules (MTs) are known to play a critical role in the life cycles of several pathogenic intracellular microbes by providing for successful invasion and promoting movement of the pathogen once inside the host cell cytoplasm. Orientia tsutsugamushi, an obligate intracellular bacterium, enters host cells by induced phagocytosis, escapes to the cytosol, and then replicates in the cytosol. ECV304 cells infected with O. tsutsugamushi revealed the colocalization of the MT organizing center (MTOC) and cytosolic orientiae by indirect immunofluorescence assay. Using immunofluorescence microscopy in the presence and absence of MT-depolymerizing agents (colchicine and nocodazole), it was shown that the cytosolic oriential movement was mediated by MTs. By transfection study (overexpression of dynamitin [also called p50], which is known to associate with dynein-dependent movement), the movement of O. tsutsugamushi to the MTOC was also mediated by dynein, the minus-end-directed MT-related motor. Although the significance of this movement in the life cycle of O. tsutsugamushi was not proven, we propose that the cytosolic O. tsutsugamushi bacteria use MTs and dyneins to propel themselves from the cell periphery to the MTOC.     

Association of vitamin D receptor and estrogen receptor gene polymorphisms with bone mass in postmenopausal Korean women

OBJECTIVE: To examine the relationship between vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphism and bone mineral density (BMD). DESIGN: Polymorphisms at the VDR FokI and ER PvuII and XbaI gene sites, serum bone-specific alkaline phosphatase, urinary N-telopeptide of type I collagen, and BMD at the lumbar spine and proximal femur were analyzed in 229 postmenopausal Korean women. RESULTS: The distribution of ER PvuII and XbaI and VDR FokI restriction fragment length polymorphisms was as follows: pp 39.3%, Pp 46.3%, PP 14.4%, xx 34.1%, Xx 61.1%, XX 4.8%. ff 17.0%, Ff 43.7%, and FF 39.3%, respectively (upper-case letters signify the absence, and lower-case letters signify the presence of the restriction site). After adjusting for potential confounding factors such as age, body mass index, and menopause duration, ER PvuII was independently associated with BMD at the lumbar spine and XbaI polymorphism BMD at the femoral neck. The lumbar spine BMD in the pp genotype was 7.5% lower than in the PP genotype, and the femoral neck BMD was 4.8% lower in the Xx genotype than in the xx genotype. By itself, the VDR FokI polymorphism was not related to BMD, but by combining the FokI genotype (FF) with ER genotypes, such as ppxx and the PpXx, the difference in the BMD at the Ward's triangle became significant. There were no significant differences in the levels of biochemical markers between the genotypes of three polymorphisms. CONCLUSION: ER polymorphisms, singly and in relation to VDR FokI polymorphism, influence bone mass in Korean women.