We cannot be sure as to why our results differ selleck chemical Ixazomib so markedly from the other studies. It is possible that a small part of the effect is due to memory effects, but it cannot in any simple way account for most of the differences. It could be something about the questions asked. Our questions identified a small group who reported having not smoked for sometime before deciding to quit. This possibility does not seem to have been allowed in the other studies. Both our study and those before us focused on the delay between deciding to make a quit attempt and it��s implementation. However, the measure that is used in the other studies conflates this delay with planning. But being committed with a delay does not mean that the delay will be used for planning.

Choosing a quit day in advance is not necessary for there to be planning nor does it guarantee that there will be planning. There can be conditional planning either before or after any commitment to act. This all said, we have no clear explanation as to why conflating planning and any delay between the decision to quit and its implementation would lead to the higher rate of success associated with unplanned attempts. We have now included more detailed questions on the extent of planning activity in the ITC survey, so we will eventually be able to address these issues empirically. This area of research has huge potential implications for smoking cessation practice, which encourages planning. Research on behavioral interventions that typically include elements of planning are demonstrably effective (e.g.

, Stead, Perera, & Lancaster, 2009), and while their benefits may be independent of any planning component, we know of no randomized control trials in which the control group is not also subject to a period of delay. However, both West and Sohal (2006) and Ferguson et al. (2009) warn against making the conclusion that planning per se leads to failure, arguing that it indicates some unresolved internal conflict, and it is this that makes abstinence less likely. We agree with Hughes and Carpenter (2006) that research is urgently needed to resolve these issues. Conclusion Those who implemented a quit attempt on the day they decided to quit and those who delayed for a week or more had comparable rates of success. This suggests that delaying per se does not predict failure.

We found some evidence of an association between delaying for 1�C6 days and failing at a quit attempt, but this was confounded by other factors determining failure. Importantly, our study adds to the growing body of evidence (Ferguson et al., 2009; Larabie, 2005; Murray et al., 2009; West & Sohal, 2006) suggesting that smokers who Brefeldin_A are motivated to quit should not be discouraged from implementing a quit attempt as soon as the decision is made. Research is needed on optimizing postimplementation evidence-based cessation support.

Significant relevance of overexpression of Pyk2 and disease-free survival was first demonstrated in the current clinical expression study. Consistent with the poor prognosis, patients with higher levels of Pyk2 showed aggressive new product tumour progression, advanced tumour staging and more invasiveness. Positive correlation between Pyk2 and FAK was also found in our study. In addition to the detection of Pyk2 and FAK in the liver tumour and non-tumour tissues, the gene expression levels of ezrin and fibronectin, two potential metastatic genes, were also investigated according to patients’ different expression levels of Pyk2. Ezrin, as a key determinant of tumour metastasis, has been implicated as a conduit for signals between metastasis-associated cell surface molecules and signal transduction components (Hunter, 2004; Khanna et al, 2004).

Furthermore, recent study demonstrated the co-operative effect of ezrin and c-Src, which also correlated with Pyk2, in cancer cells, in cancer cell metastases (Elliott et al, 2004). In this study, higher expression levels of ezrin were found to be consistent with overexpression of Pyk2. Similarly, another gene, fibronectin, which plays important roles in the promotion of cancer cell survival, progression and metastasis, presented higher expression levels in patients with overexpression of Pyk2 (Thant et al, 2000; Fornaro et al, 2003; Han et al, 2006). The association of fibronectin and pyk2 has been reported previously (Loeser et al, 2003). The similar expression trend of the genes Pyk2 and FAK with ezrin and fibronectin might also suggest the potential role of Pyk2 in liver cancer metastasis/recurrence.

To confirm our findings in clinical samples, we further conducted in vitro functional studies and an in vivo animal study in an orthotopic liver tumour model with highly local (intrahepatic) and distant (lung) metastatic potential. Our animal study also first demonstrated that overexpression of Pyk2 was found in infiltrative liver tumour cells (local metastasis) and lung metastatic nodules. This in vivo animal study further confirmed the significant correlation of Pyk2 with HCC invasiveness. In addition to animal study, our primary function study also indicated that Pyk2 played important role in HCC cell proliferation and invasion.

However, Entinostat the distinct cell signalling pathways under the regulation of Pyk2 related to cell invasion and migration should be investigated to elucidate the exact molecular mechanism in addition to the phenomenon demonstrated in our clinical and animal studies. In summary, overexpression of Pyk2 and FAK was found in nearly 60% of HCC patients and was significantly correlated with poor prognosis. The significance of Pyk2 in HCC invasiveness was also demonstrated by our orthotopic liver cancer animal model with higher metastatic potential.

The new TNM staging and Edmonson staging of these patients was based on the clinical and pathological diagnosis (Ng et al, 2006). The study protocol was approved by the Institutional www.selleckchem.com/products/AZD2281(Olaparib).html Review Board of the University of Hong Kong. Informed consent was obtained from each patient before operation. Protein expression of Pyk2 and FAK in tumour and adjacent non-tumour liver tissues by immunostaining and Western blot The paraffin sections of the tissue samples were immunochemically stained for Pyk2 and FAK using Dako EnVision? system (Dako, Glostrup, Denmark). In brief, after de-paraffinisation, endogenous peroxidase activity was quenched by immersing the sections for 30min in absolute methanol containing 0.3% H2O2. The sections were processed to unmask the antigens by conventional microwave oven heating in 10mM citric acid buffer (pH 6.

0) for 12min. The sections were then treated with 10% normal goat serum for 30min to reduce the background staining, followed by treatment of appropriate primary antibodies (Pyk2: cytoplasm staining �C H-109, Santa Cruz Biotechnology Inc., 2145 Delaware Avenue, Santa Cruz, CA, USA; Nuclear staining �C Upstate Biotechnology, Charlottesville, VA, USA; FAK: Upstate Biotechnology) at 4��C overnight. After washing, the sections were incubated with EnVision? secondary antibody for 30min at room temperature and then visualised with chromogenic substrate solution for 2min. The slides were examined under light microscope by two independent investigators with the experience of liver pathology.

According to the intensity and area of the staining signalling, the intracellular protein expression of Pyk2 and FAK was classified into higher expression (over 50% of tumour section) and lower expression (less than 50% of tumour section) groups, respectively by an integrated imaging system (MetaMorph Imaging system version 3.0; Universal Imaging Corp, West Chester, PA, USA). Western blot assay was modified from the method described previously (Liang et al, 2003). Proteins from liver tissues were prepared by using urea buffer (8M urea, pH 8.0). Protein extracts were separated by 12% SDS�CPAGE and transferred to PDMF membrane (Millipore, Billerica, MA, USA) according to the standard protocol. After blocking with 5% non-fat milk for 1h, antibody with proper dilution was hybridised with the membrane at 4��C overnight.

The membrane was washed three times with tris buffered saline with tween 20 (TBS/T) each for 10min and incubated with secondary antibody for 1h at room temperature. Protein signal was detected by ECL Plus system (Amersham Biosciences, Piscataway, NJ, USA). The signals were quantified by scanning densitometry (Syngene, Cambridge, UK). Gene expression of Pyk2, FAK, ezrin and fibronectin in tumour tissues by real-time quantitative RT�CPCR Tissue samples were stored Batimastat at ?80��C until total RNA extraction.

Notably, we found a high prevalence of regular snus use regardless of initial reactions, especially among men. Our findings also highlight age at first snus use as a relevant predictor of future snus use among women, who selleck chemicals had a higher predicted probability of being snus users if they experimented with snus as adults. Dizziness and pleasurable buzz were the strongest predictors of smoking in this study, consistent with prior reports. Haberstick et al. (2011) examined retrospective responses to the ESE among 2,482 young adult twins and found that individual differences in initial reactions to cigarettes are best explained by heritable and environmental influences on dizziness. The authors suggest that dizziness may represent the most genetically informative subjective experience and therefore could be used clinically to identify individuals at risk of regular use (Haberstick et al.

, 2011). In a study comparing retrospective responses to the ESE with prospective responses to a Nicotine Spray Effects questionnaire among 58 young adult non-smokers with modest lifetime exposure to cigarettes, Perkins, Lerman, Coddington, and Karelitz (2008) found that reporting dizziness on the ESE was associated with greater prospective ratings of ��feel the effects�� and ��want more�� when comparing nicotine spray to placebo. This may indicate that the ESE item of dizziness predicts greater sensitivity to the reinforcing effects of nicotine (Perkins et al., 2008). Furthermore, the results of a factor analysis of reactions to initial cigarette use identified a ��pleasant�� dimension, an ��unpleasant�� dimension, and a ��buzz�� dimension that consisted of dizziness and pleasurable buzz.

The ��buzz�� factor was significantly associated with increased odds of progressing to regular smoking, and this effect was especially strong among individuals who did not experience any pleasant reactions (Richardson et al., 2010). Finally, among 8,373 youths who ever smoked a whole cigarette, Hu, Davies, and Kandel (2006) found that dizziness was significantly associated with 18% increased odds of ever daily smoking after adjustment for important potential confounders such as depressive symptoms, self-esteem, and having friends who smoke. To our knowledge, this is the first study to describe initial reactions to snus and their impact on future regular snus use.

Our finding that 79% of men and 54% of women who exclusively tried snus became Carfilzomib users is striking and suggests that, particularly for men, snus use is easily adopted after trying regardless of initial reactions. The tolerability of snus may be greater than cigarettes due to route of administration as nicotine is absorbed through the digestive system rather than inhaling, or to social acceptability as there is no secondhand smoke or public restrictions on its use. For women, it was notable that a later age at first snus use predicted future use.

Like an R2 value for least squares regression, higher AUC-ROC values reflect better prediction and are interpreted as the probability of correctly identifying an individual as DS (vs. ITS) based upon dependence score. Thus, AUC-ROC ranges from 0.5 (random guessing) to 1.0 (perfect prediction; Hanley & McNeil, 1982). Dependence selleck chemicals Dorsomorphin and Smoking Behavior Within ITS, we assessed the relationship between dependence and smoking behaviors by running separate least square regression models for each dependence measure, examining linear and quadratic effects of smoking behavior on each dependence measure. All analyses controlled for history of daily smoking (CITS or NITS); models that did not control for smoking history yielded virtually identical results.

Results Differences in Dependence Between ITS and DS ITS were significantly less dependent than DS on every measure of dependence (Table 1). The differences were very large, as seen in the steep slopes of the logistic functions in Figure 1. Three measures (NDSS, FTND, and WISDM Primary) yielded AUC-ROC values greater than or equal to .90��that is, the measures correctly differentiated ITS from DS more than 90% of the time. When scored dichotomously, the HONC classified all DS and 93% of ITS as dependent, yielding the lowest AUC-ROC value (0.54). However, the continuous HONC achieved an AUC-ROC of 0.81. Table 1. Differences in Dependence Between Daily Smokers (DS) and Intermittent Smokers (ITS) and Also Within ITS Figure 1.

Differences in dependence measures Fagerstr?m Test for Nicotine Dependence (FTND), time to first cigarette (TTFC), Nicotine Dependence Syndrome Scale (NDSS), Wisconsin Inventory of Smoking Dependence Motives (WISDM) Primary, WISDM Secondary, Hooked … On every measure except TTFC, CITS were more dependent than NITS but the effects were more modest, with AUC-ROC values in the .60�C.70 range (Table 1) and as illustrated by the less-steep curves in Figure 1. The HONC classified 87% of NITS and 97% of CITS as dependent, yielding a modest AUC-ROC of 0.56, but was the most discriminating measure (AUC-ROC = 0.70) when scored continuously. Relationship Between Dependence Measures and Smoking Behavior Among ITS All the dependence measures showed some variation within ITS (Table 1). Continuous HONC scores spanned the entire range of the scale, and WISDM scores nearly did so as well.

TTFC ranged from 0 min (smoking Carfilzomib immediately upon waking) to 20 hr. When ITS�� NDSS scores are considered as z-scores and evaluated as percentiles against the published normative sample (Shiffman et al., 2004), ITS�� scores ranged from the 0.1th to the 94th percentile. There was also substantial variation in ITS smoking behavior as recorded in EMA. Mean CPD (on days smoked) averaged 3.48 (SD = 2.36) cigarettes, but ranged from 1 to 17.5 CPD. The maximum CPD averaged 7.69 (SD = 5.61), ranging from 1 to 32 CPD. These two metrics were highly correlated, r = .86.

However, such work is beyond the scope of this study. Taken together, these novel data demonstrate that the LXA4 counter-regulatory signal in renal fibrosis may be mediated, in part by let-7c induction and that downregulation of let-7c miRNA by TGF-��1 is important in driving newsletter subscribe fibrotic responses. Future work will investigate the specific role of let-7c in human renal fibrosis. Concise Methods Cell Culture A full list of abbreviations used in the manuscript is detailed in Supplemental Table 4. Immortalized human kidney epithelial cells (HK-2; ECACC, Porton Down, UK) were cultured at 37��C in a humidified atmosphere of 95% air/5% CO2, and maintained in DMEM-F12 (Sigma-Aldrich, Steinheim, Germany) supplemented with 2 mM l-glutamine, 100 U/ml penicillin, 100 ��g/ml streptomycin, 10 ng/ml endothelial growth factor, 36 ng/ml hydrocortisone, 3 pg/ml triiodothyronine, and 5 ��g/ml insulin, 5 ��g/ml transferrin, and 5 ng/ml selenium (ITS) solution (Sigma-Aldrich).

Primary human mesangial cells (Clonetics, Basel, Switzerland) were maintained in MCDB-131 medium (Gibco, Carlsbad, CA), supplemented with 10% (v/v) heat-inactivated FBS, 2 mM l-glutamine, 100 U/ml penicillin, and 100 ��g/ml streptomycin. Normal rat kidney fibroblasts (NRK-49F cells) were maintained in DMEM, supplemented with 10% (v/v) heat-inactivated FBS, 100 U/ml penicillin, and 100 ��g/ml streptomycin. After serum-starvation for 24 hours, cells were stimulated with vehicle (0.1% ethanol) or LXA4 (1.0��10?9 M; Merck, Calbiochem, Nottingham, UK) for 30 minutes and media was removed and replaced with media with or without TGF-��1 (10 ng/ml; PromoCell GmbH, Heidelberg, Germany) for 30 minutes to 48 hours.

HK-2 cells were incubated with pertussis toxin (50 ng/ml; List Biologic Laboratories Inc, Campbell, CA) for 16 hours before LXA4 or TGF-��1 stimulation. For all cell stimulations, three independent experiments were performed. Real-Time qPCR RNA extraction from HK-2 cells was performed using an RNeasy RNA extraction kit according to the manufacturer��s protocol (Qiagen, Crawley, UK). RNA quality was assessed using a Bioanalyzer 2100 (Agilent Technologies, Berkshire, UK). Real-time TaqMan PCR was used to quantify relative gene expression levels of CDH1, CDH2, JAG1, TGF��R1, TGF��R2, COL1A1, COL1A2, THBS1, HES1, and FN1 using preoptimized gene expression assays (Applied Biosystems, Foster City, CA). 18s rRNA was used as an endogenous control for normalization. miRNA-enriched RNA was extracted AV-951 from HK-2 cells using a miRNeasy RNA extraction kit (Qiagen). Real-time TaqMan PCR of miRNAs was used to validate let-7c, let-7a, and miR-192 expression using miRNA expression assays (Applied Biosystems). RNU48 expression was selected as an endogenous control for normalization of target miRNAs.

Measures of PSE The primary dependent variable in this study was the child’s exposure to PSE from all persons who smoked in the child’s environment. Parents provided information about their child’s PSE in response to a 15-item PSE Questionnaire that included questions these about the number of smokers in the home, parent/family smoking patterns and exposure, as well as home smoking rules. Specifically, parents were asked, ��How many cigarettes did you smoke in your home and to how many was your child exposed?�� They were also asked this question for each smoker living in or visiting the home and were similarly asked to report smoking and exposure occurring in the car. Exposure was defined as the number of cigarettes smoked in the same room or car as the child.

Parents were required to record a specific number of cigarettes smoked and exposed along a continuum ranging from yesterday through 7 days ago. However, the number of cigarettes smoked and the number of cigarettes to which the child was exposed over the previous 72 hr (3 days) was of primary interest for this study, as this timeframe was used to validate against measures of cotinine whose half-life falls within this window (Collier, Goldstein, Shrewsbury, Zhang, & Williams, 1990). Smoking parents participating in the study were asked to report on the number of cigarettes smoked and exposed from himself/herself and all other smokers living in the home and from those who visited. Nonsmoking parents were asked to report on the number of cigarettes smoked and the number of cigarettes to which the child was exposed from the smoking spouse/partner and all other smokers living in the home or visiting.

Responses were used to calculate the parents�� and all sources�� average daily smoking and the child’s average daily exposure to the cigarettes smoked in the home or car. Urine collection For toilet-trained children, urine samples were obtained in the clinic using standard urine collection methods. Children urinated into standard urine collection cups, and urine was transferred to plastic test tubes for freezing and analyses. For non�Ctoilet-trained children (n=15), samples were collected using a sterile pediatric urine collection bag (Pediabag; n=14) or via cotton rolls placed in the diaper (n=1). Obtained urine was expressed into a collection cup.

Obtained samples were split and frozen in a standard freezer with tubes labeled with a randomly assigned identification number for laboratory use. Twenty-one (16.9%) subjects were unable to provide sufficient urine to split (<10 ml of urine in a single void). Batched samples were packed in dry ice and shipped to the Mass Spectrometry laboratories at San Diego State University, San Diego, Batimastat CA, for analyses of cotinine levels. All samples were assayed by a high-performance liquid chromatography and tandem mass spectrometry method (Bernert et al., 1997). Statistical analyses Cotinine values below detection were set to 0.

Serum Ca 19.9 levels The sensitivity, specificity, positive and negative predictive figure 2 values of abnormal Ca 19.9 levels for the diagnosis of pancreatic cancer were 91, 87, 91 and 87%, respectively (Table 1). Serum Ca 19.9 levels were normal or non interpretable due to cholestasis in 26 patients. Among them, 14 (54%) patients had serum KRAS2 mutations. Combination of both tests increased sensitivity to 98% with a negative predictive value of 96% for the diagnosis of pancreatic cancer (Table 1). Table 1 Accuracy of serum KRAS2 mutation detection, serum Ca19.9 levels, and both for the diagnosis of pancreatic cancer DISCUSSION In the present study, only the most frequent KRAS2 gene mutation G12D (aspartic acid) observed in pancreatic cancer (Iguchi et al, 1996; Tada et al, 1998; Castells et al, 1999; Watanabe et al, 1999) was analysed in the serum of patients and controls, in order to limit the cost of such test and to validate it in clinical practice.

Our study underlines the high feasibility of KRAS2 mutations analysis, as circulating DNA was obtained in sufficient quantities in all patients. Mean serum DNA concentration were 730ngml?1, which is comparable to that observed in the series of Mulcahy et al (1998). In the present study, detection of KRAS2 mutations in circulating DNA had a low sensitivity but a high specificity for the diagnosis of pancreatic cancer. The sensitivity (47%) was in agreement with previous studies (27 to 81%) (Mulcahy et al, 1998; Yamada et al, 1998; Castells et al, 1999; Porta et al, 1999; Theodor et al, 2000; Zambon et al, 2000), although the search for five other possible KRAS2 mutations in codon 12 was not performed.

Higher KRAS2 mutation prevalences have been reported in pancreatic or duodenal juice (63 to 87%), due probably to higher DNA tumour content in pancreatic juice as compared to plasma (Wilentz et al, 1998; van Laethem et al, 1998; Watanabe et al, 1999). Use of samples of pancreatic juice however requires invasive procedures (fine-needle aspiration during endoscopic ultrasonography Drug_discovery or endoscopic retrograde pancreatography). Three studies have reported a higher specificity of serum KRAS2 mutations compared to the current study (100 vs 87%), but their control groups included few patients and essentially healthy subjects (Mulcahy et al, 1998; Porta et al, 1999; Theodor et al, 2000). Since KRAS2 mutations have been reported in pancreatic tissue or juice from 6�C42% of patients with chronic pancreatitis (Furuya et al, 1997; Mulligan et al, 1999; L��ttges et al, 2000; Ha et al, 2001), and knowing that a part of this mutated DNA can be released into circulation (Yamada et al, 1998), the control group should include patients with chronic pancreatitis.

There is a dynamic and complex regulation pattern of the activity of meprin-�� in colorectal cancer. Increased zymogen activation contributes to higher proteolytic activity in primary else tumors stages I to IV (Fig. 5A), and the inhibitory activity against meprin-�� is reduced in the blood in colorectal cancer patients (Fig. 5B). The inefficient activation in liver metastases is in accordance with the previous observation that the uPA-system, a meprin-�� activator, is inactive in liver metastases, due to the lack of uPA activation and the over-expression of plasminogen activator inhibitor [27], [28]. Even though many matrix metalloproteases (MMPs) are known to be increased in invasive primary tumors in colorectal cancer [29], there are few analyses that include liver metastases.

In one such study, MMP-9 was shown to be increased in primary tumors but not liver metastases [30]. That study and our data point to significant differences between protease networks in primary tumors and liver metastases, which is relevant for therapeutic approaches using protease inhibitors. We studied cell migration in MDCK cells expressing meprin-�� at the cell surface bound in heterodimeric protein complexes with transmembrane meprin-�� [31]. Meprin-expressing cells migrated significantly faster on laminin-1 coated dishes in the presence of plasminogen and HGF. Meprin-�� might be activated at the cell surface by plasmin, generated from plasminogen through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor (u-PAR), which both are known to be up-regulated by HGF in MDCK cells [32].

This system most probably also contributes to the activation of meprin-�� in tumors in vivo, as u-PA and u-PAR are up-regulated in colorectal cancer [33], [34], [35], [36]. In our migration assay, the pro-migratory effect is indeed due to meprin-��, as plasmin activates meprin-�� but not meprin-�� [7] and because actinonin, which reverses the pro-migratory effect, does inhibit meprin-�� with approximately 100-fold higher potency (Ki 2*10?8 M) than meprin-�� (Ki 2*10?6 M) GSK-3 [10]. Both laminin-1 and laminin-5 are cleaved by meprin-�� in vitro [37], and we speculate that meprin-�� might expose cryptic pro-migratory epitopes in a similar fashion as has been previously shown with laminin-5 and laminin-1 for MT1-MMP [38] and elastase [39], respectively. The uPA-plasminogen system is also crucially important in angiogenesis [23], [40], and plasmin in turn might activate meprin-�� as a downstream angiogenic effector in colorectal cancer. In line with our data, a pro-angiogenic effect of meprin-�� has also been observed in a morpholino knockdown in zebrafish [14].

As a result, the outcomes of patients with acute and chronic HBV related liver diseases undergoing kinase inhibitor 17-AAG LT are now similar to or better than those with non-HBV related liver transplantation [13], [14]. While the prophylactic therapies in the management of HBV in transplant recipients represent a significant step in LT, there remain controversies and challenges that have not been adequately resolved. Long-term prophylaxis with HBIG is expensive and has been associated with the development of surface antigen mutations. Similarly, emergence of drug resistance caused by tyrosine-methionine-aspartate-aspartate (YMDD) motif mutants occurs with prolonged LAM therapy. The choice of antiviral drugs or drug combinations and duration of prophylaxis are still being debated in the literature.

It has been suggested that short-term rather than life-long HBIG could be used with or without combination of oral nucleos(t)ide analogs in low risk patients [15], [16], [17]. This strategy emphasized the need to identify risk factors capable of predicting hepatitis B relapse after LT for optimal prophylaxis. While several studies have identified clinical predictors such as high viral loads [18], [19], cumulative corticosteroid dose for immunosuppression [20], recurrence of HCC post LT [21], [22], HBIG monoprophylaxis (12) [12] and prolonged LAM therapy [19], [23], none has assessed the predictive roles of the histopathological characteristics in liver explants as well as the genotypic features of the viruses in pre-LT serum samples.

The aim of this study, therefore, was to evaluate the predictive value of all the aforementioned clinicopathological and genotypic virological factors in hepatitis B relapse after LT in patients receiving combination treatment of short-term HBIG and life-long LAM. Methods Ethics statement This study was conducted under the approval of the Institutional Review Board, Chang Gung Memorial Hospital, Taiwan. Written informed consent was obtained from all patients included. Patients Between September 2002 and August 2009, 150 consecutive HBsAg positive patients undergoing LT in Chang Gung Memorial Hospital Linko medical center were included under informed consent. The indications for LT in this group of patients included HCC, decompensated liver diseases and fulminant hepatic failure. All patients were alive more than 3 months after LT and were followed up monthly in the outpatient clinic. This study was approved by the institutional review board at Chang Gung Memorial Hospital. Entinostat HBV prophylaxis protocol Prior to transplantation, LAM (Zeffix, GlaxoSmithKline, Middlesex, UK) (100 mg/day orally) was commenced in 79 patients. Among them, 39 patients received the prophylactic therapy for more than one month.