While approximately 80% of health care providers that treat HIV-i

While approximately 80% of health care providers that treat HIV-infected patients believe that smoking is a major health issue affecting HIV-infected scientific study individuals, less than half report that they frequently prescribe nicotine replacement therapy (NRT), varenicline, or bupropion (Shuter, Salmo, Shuter, Nivasch, Fazzari, & Moadal, 2011). Also, there have been few studies that have examined the efficacy of tobacco dependence treatment pharmacotherapy in this population, and the studies that have been reported have used NRT and not other treatments such as varenicline (Lloyd-Richardson et al., 2009; Vidrine, Arduino, Lazev, & Gritz, 2006; Wewers, Neidig, & Kihm, 2000). Varenicline is an effective tobacco dependence treatment pharmacotherapy among healthy smokers (Cahill, Stead, & Lancaster, 2011; Fiore et al.

, 2008) and smokers with cardiovascular disease (Rigotti, Pipe, Benowitz, Arteaga, Garza, & Tonstad, 2010). However, a recent meta-analysis suggests that varenicline increases the risk of adverse cardiovascular events (Singh, Loke, Spangler, & Furberg, 2011). Further, a Food and Drug Administration (FDA) warning was issued in 2009, advising health care professionals about the risks of serious psychiatric symptoms in patients taking varenicline (FDA, 2009). Thus, the safety of this pharmacotherapy among HIV-infected smokers could be a concern given the increased risk of both cardiovascular disease and psychiatric problems in the HIV-infected population. In this paper, we report the safety of varenicline and NRT among HIV-infected individuals enrolled in a tobacco dependence treatment protocol as part of a prospective study.

Preliminary information regarding the effectiveness of varenicline in this population is also provided. Methods Participants The participants were recruited from one site of the Lung HIV study, a multisite study funded by the National Heart, Lung, and Blood Institute (R01HL090313-01). The overall objective of the Lung HIV study is to characterize HIV-associated lung infections and complications in the era of combination antiretroviral therapy (ART). The eight sites conduct independent projects as well as collaborative projects (Crothers et al., 2011). Our site is focused on examining longitudinal changes in lung function among HIV-infected smokers who quit, as compared with those who continue to smoke.

As such, study participants AV-951 were exposed to intensive tobacco dependence treatment in order to obtain the maximum number of abstinent individuals. Randomization was not used to assign participants to treatment, since our goal was to deliver the most efficacious therapy available based on the Clinical Practice Guideline (Fiore et al., 2008). To be eligible for this study, an individual had to be an adult infected with HIV, a daily smoker of five or more cigarettes, and interested in quitting smoking in the next 30 days.

In addition, patients under octreotide treatment tended to have l

In addition, patients under octreotide treatment tended to have lower MELD scores than patients undergoing other treatment modalities although there was no overall difference in MELD score between the various groups. In summary, this retrospective Carfilzomib PR-171 analysis of survival of BCLC stage-matched patients with HCC showed that octreotide treatment produces a similar survival benefit as TACE or multimodal therapy as compared to no active treatment. Given the few side effects of long-acting octreotide [Sandostatin LAR] this treatment seems to be a therapeutic option for patients with HCC and needs further randomised controlled studies in BCLC stage-matched patients. Competing interests The authors declare that they have no competing interests. Authors’ contributions JK performed chemoembolization.

MPR recruited patients. MSH and CM were equally involved in the design of the study, patient recruitment, management of the patients, statistical analysis and drafted the manuscript. All authors read an approved the final manuscript.
The mechanisms by which organs undergo repair following injury is of increasing therapeutic interest because targeting either dysregulated or failed repair mechanisms is an attractive alternative to targeting injury mechanisms. Proof of principle that targeting such repair mechanisms can augment normal repair has been established (1). However, there is a paucity of knowledge about normal repair and dysregulation of normal repair in chronic inflammatory diseases.

Working toward this aim, we have recently described a key role for epithelial cell phagocytosis in repair and remodeling of the functional units of the kidney, the nephrons, following severe ischemic injury, a model for acute tubular necrosis in humans (2). In addition to this role for epithelial cells in repair and regeneration, there is now an established literature indicating that in certain circumstances macrophages (Ms) perform crucial roles in repair, not only by engaging in scavenger and debris-clearing functions, but also through paracrine signaling to parenchymal cells that support tissue regeneration (3,�C7). To identify genes that may play roles in repair rather than in injury we performed representational difference analysis of normal rat kidney and kidney subjected to ischemia reperfusion injury (IRI) during the phase of organ repair (8).

This analysis revealed that the gene encoding the transmembrane protein Kim1 (also known as Tim1; see ref. 9) was highly up-regulated during repair. Subsequent analysis indicated that Kim1 functions in repair, at least in part, by functioning as a scavenger receptor on injured epithelial cells (2). In addition to the Kim1 gene, this analysis identified that the Entinostat gene encoding glycoprotein nonmetastatic melanoma B (Gpnmb) was also markedly up-regulated following injury.

��2 tests were applied to test for association of single nucleoti

��2 tests were applied to test for association of single nucleotide polymorphisms (SNPs) with disease, and the presence of MAP DNA. RESULTS: SLC11A1 Dasatinib manufacturer 1730G>A and SLC11A 1469+14G>C were not associated with CD, UC, or IBD. The SLC11A1 1730A minor allele was over-represented in patients who did not require immunomodulator therapy (P = 0.002, OR: 0.29, 95% CI: 0.13-0.66). The frequency of the SLC11A1 469+14C allele was higher in the subset of study participants who tested positive for MAP DNA (P = 0.02, OR: 1.56, 95% CI: 1.06-2.29). No association of SLC11A1 1730G>A with MAP was observed. CONCLUSION: Although SLC11A1 was not associated with IBD, association with MAP suggests that SLC11A1 is important in determining susceptibility to bacteria implicated in the etiology of CD.

Keywords: NRAMP1, Crohn��s disease, Ulcerative colitis, IS900 polymerase chain reaction INTRODUCTION The solute carrier family 11 (SLC11A1) gene (also known as natural resistance associated macrophage protein 1, NRAMP1)[1] has been associated with susceptibility to intracellular pathogens since its initial identification in mice[2]. SLC11A1 encodes a divalent cation transporter that is located in endosome and phagosome membranes[3] of macrophages and monocytes within the liver, spleen and lungs[2,4]. This transporter plays a key role in mounting an effective immune response against intracellular pathogens[1,5] through its involvement in the acidification of the phagosomes[6], as well as the regulation of nitric oxide, interleukin-10[7] and vacuolar iron concentrations[8].

Given the pivotal roles that SLC11A1 plays in innate immunity, it is not surprising that the relationship between polymorphisms in SLC11A1 and a number of autoimmune and mycobacterial diseases has been explored. Associations have been found with leprosy[9], tuberculosis[10], rheumatoid arthritis[11], visceral leishmaniasis[12], multiple sclerosis[13], type 1 diabetes mellitus[14], and inflammatory bowel disease (IBD)[15-18]. Most of these disease associations have been with a promoter dinucleotide microsatellite (GTn) that is known to affect SLC11A1 expression levels[19]. However, SLC11A1 also contains a number of single nucleotide polymorphisms (SNPs), including SLC11A1 1730G>A (rs17235409; D543N) and SLC11A1 469+14G>C (rs3731865; INT4G>C).

The non-synonymous SNP 1730G>A is thought to alter Drug_discovery the protein function[18], whereas the intronic SNP 469+14G>C has no known functional effect, but has been suggested to be in linkage disequilibrium with functional promoter polymorphisms[12]. SLC11A1 1730G>A and SLC11A1 469+14G>C have been tested for association with Crohn��s disease (CD) in two European cohorts. Although the smaller of the two studies found no association with CD, Gazouli et al[18] have reported a significant association of both SNPs with disease (SLC11A1 1730G>A Pgenotypic = 0.

Dr MJC was supported

Dr. MJC was supported inhibitor Pfizer by a Career Development Award from National Institute on Drug Abuse (K23 DA020482). Declaration of Interests None declared. Acknowledgments The authors wish to thank Drs Jane G. Zapka and Elizabeth Garrett-Mayer for their comments on an earlier version of this manuscript.
Smoking experimentation may represent normative adolescent risk taking or mark the onset of chronic smoking (Chassin, Presson, & Sherman, 1989). Family processes are theorized to discriminate transient from persistent pathways (Graber & Brooks-Gunn, 1999; Schulenberg, Maggs, & Hurrelman, 1997). Empirically based methods that enable this distinction are critical for the development of effective targeted intervention (Dierker, Avenevoli, Goldberg, & Glantz, 2004).

Parental behavior (parenting and smoking status) is particularly influential in determining whether experimentation escalates to regular smoking (Bricker et al., 2007; Darling & Cumsille, 2003). Recently, ��smoking-specific socialization�� (e.g., discussion, punishment, and consequences) has demonstrated incremental utility in prediction of youths�� smoking trajectories (Chassin et al., 2005; Middlecamp-Kodl & Mermelstein, 2004). However, the direction of effects is inconsistent, perhaps due to variations in measurement and moderation by parental smoking status. For example, positive effects of frequency and quality of communication are greater when parents are nonsmokers, whereas punishment has positive effects when parents are nonsmokers and negative effects when parents are smokers (Chassin et al.

, 2005; Harakeh, Scholte, de Vries, & Engels, 2005). In addition, more frequent parent�Cteen communications about smoking are associated with increased risk of smoking; however, longitudinal findings suggest that higher frequency may be a reaction to experimentation rather than a risk factor (Ennett, Baumann, Foshee, Pemberton, & Hicks, 2001; Harakeh et al., 2005). Questionnaire measures of qualitative aspects of smoking-specific communications (e.g. responsive, constructive) also exert a protective effect on youth smoking (Engels & Willemsen, 2004; Harakeh et al., 2005). Thus, deepening understanding of individual differences in smoking-specific communication patterns is promising for specifying mechanisms by which varying family processes exert their influence.

Standardized direct observations methods have unique potential to advance this line of inquiry. Observation methods generate a nuanced characterization of the communication processes by which messages and attitudes about smoking are transmitted and Brefeldin_A responded to within families. While parental smoking-specific socialization is a critical aspect of smoking-related family processes, it occurs within a dynamic conversational context (Ary, James, & Biglan, 1999).

2004), overexpressed LTBP-1 could participate in maintaining high

2004), overexpressed LTBP-1 could participate in maintaining high levels of TGF-�� in the fibrotic nodule, a location from which it could be eventually activated. Although the expression of TGF-�� and LTBP-1 at the mRNA and protein considering levels should be coordinated, there is some controversy on this issue. Whereas erythroleukaemia, foreskin fibroblast and breast cancer human cell lines express TGF-�� and LTBP-1 coordinately after treatment with exogenous TGF-��, certain osteoblast-like cell lines regulate TGF-�� and LTBP-1 expression in an independent manner. Furthermore, a human glioblastoma cell line has been described that secretes active TGF-�� in the absence of LTBP (Miyazono et al. 1991; Olofsson et al. 1992; Dallas et al. 1994; Koli & Keski-Oja 1995).

In this regard, exogenous TGF-�� treatment increased LTBP-1 mRNA in AhR wild-type MEFs, but neither exogenous TGF-�� nor the addition of TGF-�� antibodies had any effect on LTBP-1 mRNA in AhR-null MEFs. The role of the AhR as a negative regulator of LTBP-1 expression in MEF cells could be also extrapolated in vivo to the periportal areas of the liver. Because the expression of the fibroblast marker protein ��-actin was coincident with fibrosis and with LTBP-1 overexpression in the periportal areas of AhR?/? liver, it could be suggested that the fibroblast cells present in such area, in the absence of AhR, could produce higher levels of LTBP-1 and TGF-��, thus leading to collagen deposition and fibrosis. In agreement with these data, recent results have suggested that biliary fibrosis could result from a transdifferentiation process involving portal fibroblasts and hepatic stellate cells (Wells et al.

2004). Although LTBP-1 has been traditionally considered as a localization protein for TGF-��, it has also been lately considered as a component of the ECM (Koli et al. 2001). Elevated levels of LTBP-1 in the ECM have also been reported in several fibrotic conditions, such as allograft arteriosclerosis and tuberculous pleurisy (Maeda et al. 1993; Waltenberger et al. 1993a, 1993b) and in patients suffering from chronic hepatitis C (Kinnman et al. 2000). According to this, AhR-null MEFs, grown post confluently, had an excess of LTBP-1 deposition in their ECM (Santiago-Josefat et al. 2004) that could be similar to that observed in the periportal ECM of the fibrotic areas of AhR-null livers.

All these data suggest not only that LTBP-1 has an important role in TGF-��-mediated fibrosis, but also that the AhR is an important regulator of both LTBP-1 and TGF-�� activities. A relevant issue is the mechanism by which the AhR modulates LTBP-1 expression. GSK-3 It is possible that the AhR, as a transcription factor, could regulate LTBP-1 expression by direct binding to its promoter. To address this possibility, gene reporter studies are underway to identify putative regulatory elements for AhR binding on the mouse LTBP-1 gene.

We have tested for the effect of LPS alone, which had no effect o

We have tested for the effect of LPS alone, which had no effect on the viability of the Bosutinib molecular weight colon tumor cells (supplemental Figure S1 at http://ajp.amjpathol.org) using the MTT and the cytotoxicity assays. The apoptosis in tumor cells was assessed after 24 to 72 hours of incubation with the macrophage-conditioned media by Annexin-V-FITC staining and after 48 hours by caspase-3/7 activity assays. There was a significant apoptosis induction (2.5-fold) in tumor cells treated with actM supernatants, starting early at 24 hours (6.37% to 15.87%) and continuing until 72 hours compared with untreated HCT116 tumor cells (Figure 1A). In contrast, diffM supernatants induced only an early increase in the percentage of apoptotic HCT116 tumor cells at 24 hours (6.37% to 17.87%), but cell death diminished at later time points (Figure 1A).

Considering the 48 hours time point, these findings were in accordance with caspase activity data, showing threefold up-regulation in caspase 3/7 activity in HCT116 tumor cells treated with actM supernatants (Figure 1B). Thus, our data suggest that actM may release a soluble factor into the media, which might be responsible for apoptosis induction in HCT116 tumor cells. To investigate whether DAPK is involved in the observed apoptosis induction, we examined DAPK mRNA and protein expression. Real-time RT-PCR revealed that the steady state level of DAPK mRNA remained unchanged during the whole experimental setup (data not shown). However, there was an increase in the DAPK protein level even after 6 hours of incubation with supernatants from diffM and actM (Figure 1C).

While the DAPK protein level was found to be increased only slightly at later time points after incubation with diffM supernatants, the DAPK protein level continued to increase markedly after incubation with actM supernatants, similar to the time course of apoptosis induction (Figure 1C). These data suggest that macrophage-mediated secretion of cytotoxic factors by actM might induce DAPK protein accumulation without affecting its gene transcription. Figure 1 Macrophage-induced cell death in HCT116 cells is accompanied by DAPK up-regulation. A: Annexin-V measurements of HCT116 cells (ctrl) and HCT116 cells subjected to diffM supernatant (sup.) or actM supernatant. B: HCT116 subjected to diffM supernatant or … Similar results were obtained using freshly isolated PBMCs treated with 10 ng/ml LPS for 4 hours.

The supernatants were given to HCT116 tumor cells. Indeed, we observed an up-regulation of DAPK after 6 hours and a further reinforcement after 24 hours (Figure 1D). Simultaneously, after 6 hours and 24 hours cleaved fragments of caspase 3 could be detected as signs of apoptosis induction (Figure 1D). Increase in TNF�� and IFN�� Release on Macrophage Activation Earlier studies showed that TNF�� and IFN�� promote DAPK-dependent apoptosis.2,1 These cytokines might be the cytotoxic Cilengitide factors secreted by actM in our experimental setting.

All samples were diagnosed as colon or rectal cancer by hematoxyl

All samples were diagnosed as colon or rectal cancer by hematoxylin and eosin stain. All tissues were primary CRC tissue surgically removed prior to other clinical treatments. Tissues were sliced to an approximate size of 1.0 cm2 �� 10 ��m by microtome. The sliced section samples used for this citation study were not performed by manual microdissection (MMD). No further information including demographic and clinical data were requested for these samples. The study has been reviewed and approved by the Institutional Review Board of the University of Chicago. AMDS AMDS is a fully automated genetic analytical system based on a DNA-chip which has 23 reaction wells containing reagents for PCR and Invader? assays (Figure 1A and 1B).

When a user adds a sample (whole blood, purified DNA or tissue homogenate) to the DNA purification cartridge and starts the attached software, AMDS performs DNA extraction, transfers the DNA to the chip, performs PCR and the Invader? assay, reads the results, and displays judging result in about 70 minutes. Assay flow of mutation detection is shown in Figure 1C. In step 1, DNA is extracted and purified by the DNA purification cartridge; in step 2, the purified DNA fluid sample is transferred to the DNA-Chip; in step 3, InvaderPlus? (PCR and Invader? reaction continuously in the same tube) is conducted; in the last step, AMDS reports a genotyping result of the sample. InvaderPlus? was performed under the following conditions: denature for 2 min at 93��C, followed by 30 or 35 cycles of 31 seconds at 93��C and 16 seconds at 66��C, and Taq polymerase deactivation for 2 minutes at 97��C, followed by 10 minutes of signal detection at 61��C.

Fluorescence signal of FAM (Fluorescence aminohexyl) was monitored in channel F1 at 520 nm with excitation of 490 nm, and fluorescence signal of RED (Redmond Red) was monitored in channel F2 at 595 nm with excitation of 580 nm. Figure 1 AMDS mutation detection system. DNA-chip and DNA Purification Cartridge All DNA chips and DNA purification cartridges were manufactured in a clean room at the level of ISO class 8. Required reagents mixture (1.99 ��l) for a DNA chip containing 0.1 ��l of 1 M MOPS buffer (pH 7.7) (DOJINDO LABORATORIES, Kumamoto, Japan), 0.05 ��l of 10 mM each deoxyribonucleoside triphosphate (Roche, CA, USA), 0.96 ��l of 1 M trehalose (Hayashibara, Okayama, Japan) aqueous solution, 0.

60 ��l of 20 �� oligo mix, 0.22 ��l of 5.0 U/��l Hawk Taq polymerase (Roche, CA, USA), 0.04 ��l of 15,000 U/��l Cleavase (Hologic, WI, USA) were dispensed and dried Drug_discovery in wells of a DNA chip. 20 �� oligo mixture was prepared with 0.06 ��l of 100 ��M forward primer, 0.06 ��l of 100 ��M reverse primer, 0.06 ��l of 50 ��M of FAM-FRET (Fluorescence resonance energy transfer) cassette (Hologic, WI, USA), 0.

A variety of substrates that include extracellular matrix protein

A variety of substrates that include extracellular matrix proteins, growth factors, and cytokines [23], [24], [25], [26], [27], [28] are cleaved by meprins www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html whose biological function however is still poorly understood. The location and the proteolytic activity of meprins are evidence of functions at the interface of the host and the luminal environment. Meprin �� knock-out mice were more susceptible to DSS-induced experimental colitis and underwent greater colon damage and inflammation than wild-type mice [17], [29]. Meprins may act as a mucosal defence mechanism that protects the intestinal epithelium against potential toxic peptides and also against enteric commensal and pathogenic bacteria by modulating the interaction between microbes and the host mucosa.

The aims of the present study were to investigate meprin mRNA expression in ileal biopsies of CD patients since AIEC bacteria show a tropism for ileal colonization in CD patients and to analyse the role of meprins in the interaction of CD-associated E. coli and intestinal epithelial cells. Results Intestinal expression of meprins �� and �� Meprin expression was analysed by quantitative RT-PCR. The level of meprin �� mRNA expression was not significantly lower in the ileal biopsies of UC or CD patients than that of healthy controls (Fig. 1A). In contrast the level of meprin �� mRNA expression was significantly reduced in ileal biopsies of CD patients, compared to that of healthy controls (Fig. 1B, P=0.0067 Mann-Whitney U test).

Interestingly, this was independent of macroscopic inflammation, as uninvolved ileal CD biopsies alone also showed significantly less meprin �� mRNA expression than did controls (Fig. 1B, P=0.0387 after Bonferroni correction for multiple testing). Ileal biopsies from UC patients showed equally high meprin �� mRNA expression as healthy controls. Of note, among non-IBD controls two patients had diverticulitis and presented expression levels for meprin �� (1.6 and 2.4) and �� (2.7 and 3.9) close to the median, and one patient had pouchitis but the pouchitis-derived biopsy showed a rather low level for meprin �� (0.8) and almost average meprin �� expression (2.2). Figure 1 Intestinal meprin �� and meprin �� mRNA. Meprin expression was also analyzed in an adherent-invasive Entinostat E. coli (AIEC)-induced colitis model in C57BL/6J mice. We observed that both meprin �� and �� were highly expressed at the mRNA level in the ileum compared to the colon (Fig. 1C and D). No significant modified expression of both meprins was observed following AIEC reference strain LF82 infection.

Then, the RR using PA and PP are identical (2 0); however, the DI

Then, the RR using PA and PP are identical (2.0); however, the DIFF is 5% using PA but is 15% using PP. Moderators of the relationship of PA versus PP Given www.selleckchem.com/products/nutlin-3a.html that PA almost always decreases over time and PP usually increases over time (Hughes et al., 2003), we anticipated that the relationship of PA and PP would change with different follow-up durations; however, we did not find that whether follow-ups were at 6 months versus longer influenced our results. This may be because relapse and recycling of new quit attempts are rare after 6 months (Hughes, Peters, & Naud, 2008). We believe that the relationship of PA and PP for follow-ups of less than 6 months may differ from those reported herein, but this hypothesis requires testing.

Another likely influence on the relationship of PA to PP is how soon after a quit date successful abstinence begins (Hughes et al., 2003). For example, most PA measures require abstinence to begin within the first month after a quit date. Almost no PP measures do so. Thus, if long-term abstinence is due to a ��late quit,�� this would not be a PA-defined success but would be a PP-defined success. Although late quits have thought to be unusual, recent experience with nicotine blocking agents such as varenicline suggest that they can induce late quit successes (Fagerstrom & Hughes, 2008). However, in our analyses, we did not find that the relationship of PP to PA differed between varenicline and other medication conditions. One possible explanation for this is that other study medications (in our case this was NRT and bupropion) also induce later quits or prevent a lapse from becoming relapse.

For example, clinical studies have found that NRT (Shiffman et al., 2006) and bupropion (West, Baker, Cappelleri, & Bushmakin, 2008) also are nicotine blockers and thus can also result in delayed quitting. Assets and limitations The major assets of our analyses include our use of (a) within-study rather than between-study comparisons of PA versus PP, (b) a larger more comprehensive sample of studies, (c) meta-analytic techniques that allowed derivation of equations for estimating PA from PP and vice versa, and (d) direct tests whether PA and PP produce similar effect sizes for treatment outcomes. One important liability of our analyses is that we only examined studies testing a pharmacological treatment.

It is reasonable to hypothesize that the therapeutic effects of psychosocial treatments take longer to take effect than do pharmacological treatments. If this is the case (and we cannot find empirical verification Drug_discovery of this assumption), then psychosocial treatments might especially produce late quitters, and thus, the relationship of PA to PP might differ for psychosocial versus medication trials. A second liability is that many of the articles were not clear on the exact sample sizes used for PA and PP measures nor on whether biochemical verification was required for both PA and PP or for only one of the two.

BIOLOGIC AGENTS Infliximab Infliximab (Remicade? Centocor, Malver

BIOLOGIC AGENTS Infliximab Infliximab (Remicade? Centocor, Malvern PA) is a chimeric (75% mouse/25% human) anti-TNF�� monoclonal antibody; TNF�� mediates multiple newsletter subscribe pro-inflammatory processes central to the pathogenesis of IBD. The first study that defined efficacy of infliximab in the treatment of active CD randomized patients with moderate-severe, medically-refractory, disease to receive a single infusion of placebo or 5, 10 or 20 mg/kg of infliximab. Seventeen percent, 81%, 50% and 64% of patients respectively had a response (CDAI decrease �� 70 points) at wk 4 (P < 0.001 for all infliximab patients vs placebo). Overall, 33% of all infliximab patients compared to 4% of placebo achieved remission at wk 4 (P = 0.005). While significantly more infliximab patients maintained a response at 12 wk, 37% had relapsed, suggesting that a single dose was insufficient[95].

Those patients who had an initial response to the single infusion were subsequently randomized to receive continued dosing with 10 mg/kg every 8 wk or placebo. After 44 wk, 53% of the infliximab group were in remission compared to 20% of the placebo group (P = 0.013)[96]. The ACCENT I study expanded on the potential maintenance benefits of infliximab after an initial response. In the trial, 573 patients received a 5 mg/kg intravenous (IV) infusion of infliximab at wk 0, after which they were assessed for clinical response by CDAI (decrease in score �� 70 and a 25% reduction in total score).

Three hundred and thirty five patients (58%) met this criterion and were randomized to one of three treatment groups: placebo at wk 2 and 6 and then every 8 wk (group I ), infliximab 5 mg/kg on the same schedule (group II) or 5 mg/kg at wk 2 and 6 followed by 10 mg/kg every 8 wk (group III). Treatment was continued for 46 wk. At wk 14 or later, patients in all groups who initially had response and then worsened were allowed GSK-3 to cross over to active episodic retreatment (infliximab 5, 10 or 15 mg respectively for groups I , II, and III given on an ��as needed�� basis). At wk 30, 21% of patients in groupI, 39% in group II (P = 0.003) and 45% in group III (P = 0.0002) respectively were in remission, while median time to loss of response was reported as 19, 38 (P = 0.002) and more than 54 wk (P = 0.0002) respectively. Significantly more patients in groups II and III combined (29%) compared with group I (9%) had discontinued steroids at wk 54, and fewer hospitalizations and surgeries related to CD occurred in the maintenance therapy groups. There were no differences in serious adverse events between the three groups[97].