for extending our interpretations and natu- measurements with fatigue severity and blood rally agree that bile duct loss, rather than manganese levels. Gut 2004;53:587–92.
2 Taylor-Robinson SD, Oatridge A, Hajnal JV, et al.
liver fibrosis, governs the severity of choles- MR imaging of the basal ganglia in chronic liver magnetisation transfer contrast measurements purposes of this study, we chose to examine with liver dysfunction and neuropsychiatric status.
patients with stage I–II disease to remove the clarify some of the points in response to the possibility of hepatic encephalopathy or cirr- 3 Krieger D, Krieger S, Jansen O, et al. Manganese recent leading article (Gut 2004;53:475–7) hosis as a cause for the MTR findings. We and chronic hepatic encephalopathy. Lancet1995;346:270–4.
believe that both this patient selection and 4 Rose C, Butterworth RF, Zayed J, et al.
globus pallidus (GP) magnetisation ratios the demonstration of normal cerebral mag- Manganese deposition in basal ganglia structures (MTRs) in patients with fatigue and primary netic resonance spectroscopy (MRS) in these results from both portal-systemic shunting and patients, compared with healthy volunteers, As we stated in the paper, fatigue in PBC is does indeed achieve this. We found reduced a subjective multidimensional symptom with GP MTRs in patients with stage I–II disease, 5 Maeda H, Sato M, Yoshikawa A, et al. Brain MR many potential determinants, including sleep imaging in patients with hepatic cirrhosis: disturbance, depression, and personality, in relationship between high intensity signal in basalganglia on T1-weighted images and elemental addition to a potential central neurological studied four patients with stage III–IV dis- cause.1 We therefore wholeheartedly concur ease and, as a group, there were no signifi- cant differences in GP MTR indices compared 6 Taylor-Robinson SD, Sargentoni J, Marcus CD, et they state that brain manganese (Mn) deposi- with stage I–II patients. Although this may be al. Regional variations in cerebral proton tion is certainly not the cause of fatigue in all spectroscopy in patients with chronic hepatic patients with PBC. We certainly do not believe studied, the lack of clear distinction between that we drew this conclusion. However, we do stage I–II and stage III–IV disease may believe that our findings of reduced GP MTRs also reflect a process that adversely affects 7 Taylor-Robinson SD, Sargentoni J, Oatridge A, et in patients with stage I–II disease, which were al. MR imaging and spectroscopy of the basalganglia in chronic liver disease: correlation of T1- cirrhosis, owing to early bile duct loss.
measured fatigue, do open up a novel avenue The commentators point out that the value abnormalities in proton and phosphorus-31 MR of research into a poorly understood symptom of liver biopsy staging of PBC is limited owing spectra. Metab Brain Dis 1996;11:249–68.
In order to control for inter-examination system variability, it is necessary to normalise stage I–II and III–IV groups. We accept the the raw MTRs against an internal region of possibility of sampling error but, in our view, interest (ROI). Although it might initially liver biopsy still remains the gold standard appear easier to analyse the raw MTR data, for diagnosing cirrhosis. We disagree with the normalisation to an internal standard allows A 54 year old man was treated with pegylated external sources of variation, unrelated to the been useful in supporting the histological diagnoses as cerebral MRS abnormalities are ribavirin 1000 mg daily for chronic hepatitis viously published protocols to calculate GP C genotype 3a (.56105 IU/ml). There was no indices, normalised to the putamen and to Child-Pugh A cirrhosis.6 7 We did not assume history of gastrointestinal disease or morbid- the frontal white matter,2 3 and these were that MRS would be abnormal in stage III–IV used to test associations with fatigue and patients; in fact, there were no significant differences between these patients and stage chain reaction (HCV-PCR) was negative and alanine aminotransferase (ALT) and aspar- Fatigue in PBC merits further research. We tate aminotransferase (AST) levels remained chose two rather than one internal control hope that we will be able to take further elevated at 2–3 times above the upper limit.
ROI because, contrary to the assertion in the ‘‘steps in the right direction’’.
Continuation of this well tolerated therapy editorial, there is evidence for Mn accumula- tion in brain structures, other than the GP, in However, at week 14, the patient reported a patients with cirrhosis.4 5 Rose et al reported Liver Unit, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College London, London, UK significantly elevated Mn concentrations in bloody diarrhoea. Colonoscopy showed con- the frontal and occipital cortex, pallidum, N Patel, A Oatridge, G Hamilton, J V Hajnal tinuous pancolitis, macroscopically sugges- Robert Steiner MR Unit, MRC Clinical Sciences Centre, tive of inflammatory bowel disease (IBD).
Hammersmith Hospital Campus, Imperial College Histology revealed a severe highly active GP, putamen, and frontal white matter.5 In pancolitis with basal plasmocytosis, crypt both series, the highest Mn concentration was abscesses, and crypt distortion, as seen in in the GP. Our choice of two standard ROIs was made to maximise the interpretation of the raw data although we accept that the a priori assumption that pathology is absent M Prince, J Goldblatt, M Bassendine, D E J Jones (5-ASA) was initiated. Steroids were tapered from these regions in this and all relevant Centre for Liver Research, University of Newcastle, magnetic resonance studies to date, which with clinical remission. 5-ASA was continued have used internal controls, may be false. This at a dose of 3 g daily for eight weeks followed Correspondence to: D M Forton, Hepatology Section, may explain the unexpected trend towards a Faculty of Medicine, Imperial College London at St positive association between blood Mn and the Mary’s Hospital, 10th floor QEQM Building, South putaminal index normalised to white matter.
daily) there was complete clinical and endo- scopic remission. Histology showed a mild expressed concern about an apparent auto- residual increase in mononuclear inflamma- correlation in our data that did not equal 1.
Conflict of interest: None declared.
tory cells. PCR revealed a virological relapse Table 2 in our paper1 shows the correlation coefficients between individual MTR indices an unchanged twofold elevation in ALT and and blood Mn level. We did not compare the normalised putamen index against the nor- 1 Forton DM, Patel N, Prince M, et al. Fatigue and We suspect that the ulcerative colitis-like primary biliary cirrhosis: association of globus severe pancolitis in this patient with no history of IBD was probably an adverse effect beta has been used in a pilot study investi- 8 Tilg H, Vogelsang H, Ludwiczek O, et al. A of the antiviral treatment with interferon/ randomized placebo controlled trial of pegylated ribavirin rather than a concomitant disease.
refractory active UC.6 In this study, a high interferon alpha in active ulcerative colitis. Gut2003;52:1728–33.
others.1–3 To our knowledge, the present case is the fourth reported in the literature.
Another IFN beta study in ulcerative colitis Interferon has immune stimulating proper- has been presented recently.7 In this small, ties4 and may trigger autoimmune diseases placebo controlled, randomised, dose escalat- ing study, clinical improvement was observed in 50% of IFN beta treated patients compared interferon treatment in active ulcerative with 14% in the placebo group. We recently colitis (Gut 2003;52:1728–33) seems interest- presented data on the first placebo controlled use of IFN alpha in the treatment of active UC in patients with or without corticosteroid observed no significant advantage of any IFN It is with great interest that we read the paper group over placebo but did not observe wor- Correspondence to: Dr R Sprenger, Bahnhofstr 6c, 2004;53:987–92) in which they describe a sening of disease in any IFN treated patient.
The mechanisms of action of IFN alpha are novel association of the toll-like receptor 4(TLR4) +896 A.G polymorphism with both Conflict of interest: None declared.
probably multiple but the possible interac-tions of IFN alpha with the cytokine cascade Crohn’s disease (CD) and ulcerative colitis and immune system are usually not consid- (UC), supporting the genetic influence of ered. Favouring Th1 responses and suppres- pattern recognition receptors (PRRs) in trig- sing Th2 type immune responses could imply gering inflammatory bowel disease (IBD).
1 Awakawa T, Hirohashi S, Hasegawa K, et al. A case of acute phase ulcerative colitis like colitis molecular patterns of microorganisms in the developed by the interferon-beta therapy for diseases such as ulcerative colitis or allergic intestinal flora. Independently, we performed chronic hepatitis C. Nippon Shokakibyo Gakkai disorders. We agree with the authors that IFN alpha might have the potential to enhance a similar study. However, special attention to 2 Mavrogiannis C, Papanikolaou IS, Elefsiniotis IS, inflammatory reactions and alloreactivity in the presence of anti-Saccharomyces cerevisiae et al. Ulcerative colitis associated with interferon certain situations but are also convinced that treatment for chronic hepatitis C. J Hepatol colleagues1 have recently reported that the inflammatory properties. Larger controlled S cerevisiae mannan-LBP complex is recog- 3 Niki T, Nishida K, Honsako Y, et al. A case of nised by CD14 on monocytes and signalling ulcerative colitis along with characteristic features trials with IFN alpha in ulcerative colitis are on computed tomography (CT), developed by the treatment with interferon for chronic hepatitis C.
Nippon Shokakibyo Gakkay Zasshi similar to that induced by lipopolysaccharide Department of Medicine, University Hospital 4 Tilg H. New insights into the mechanisms of Patients and controls were recruited from interferon alfa: An immunoregulatory and anti- enterology, VU University Medical Centre, Department of Gastroenterology, University Hospital 5 Baid S, Tolkoff-Rubin N, Saidman S, et al. Acute humoral rejection in hepatitis C-infected renaltransplant recipients receiving antiviral therapy.
Correspondence to: Dr H Tilg, Internal Medicine 3, Diagnosis of disease was based on clinical, Department of Medicine, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; histopathological, and endoscopic findings.
CD patients were categorised using the Vienna classification (general patient char- As interferon alpha (IFN alpha) suppresses Conflict of interest: None declared.
acteristics are described elsewhere2). ASCA the synthesis of proinflammatory cytokines and induces various anti-inflammatory cyto- described previously.3 Genotyping for the 1 Fuss IJ, Heller F, Boirivant M, et al. Nonclassical Crohn’s disease, lamina propria cells manifest CD1d- restricted NK T cells that produce IL-13 formed as described previously by our group.4 The CD14-260 and TLR4+896 genotypes, allele, ulcerative colitis lamina propria cells and ulcerative colitis. J Clin Invest 2004;113:1490–7.
natural killer T cells demonstrate increased 2 Fuss IJ, Neurath MF, Boirivant M, et al. Disparate between the different clinical patient groups secretion of the Th2 cytokines interleukin 5 CD4+ lamina propria (LP) lymphokine secretion and controls. In addition, synergism between profiles in inflammatory bowel disease. Crohn’s CD14 and TLR4 genotypes and alleles (carrier LP cells manifest increased secretion of IFN- trait analyses) was studied. Vienna classifica- gamma, whereas ulcerative colitis LP cells potently suppress synthesis of both IL-5 and tion and ASCA status were included in the manifest increased secretion of IL-5. J Immunol attractive agent for the treatment of ulcera- 3 Gasche C, Reinisch W, Vogelsang H, et al.
tive colitis. IFN alpha therapy showed no Prospective evaluation of interferon-alpha in frequency of the G allele of TLR4+896 was benefit in patients with Crohn’s disease.3 This treatment of chronic active Crohn’s diseases. Dig significantly increased in CD patients com- may be explained by the fact that Crohn’s pared with controls (19% v 10%; p = 0.049; disease is thought to be a Th1 linked disease.
4 Sumer N, Palabiyikoglu M. Induction of remission odds ratio (OR) 2.1 (95% confidence interval IFN alpha therapy seems to be more success- by interferon-alpha in patients with chronic active ulcerative colitis. Eur J Gastroenterol Hepatol ful in chronic active ulcerative colitis, a more assessed in patients using the Vienna classi- Th2 linked disorder. Sumer and Palabiyikoglu fication. Carriage of TLR4 +896*G signifi- Madsen SM, Schlichting P, Davidsen B, et al. An reported that more than 80% of patients with active ulcerative colitis responded to high systemic interferon-alpha-2A and prednisolone localisation of CD compared with non-colonic dose IFN alpha therapy within two weeks of enemas in the treatment of left-sided ulcerative localisation (43% v 12%; p = 0.0017; OR 5.5 treatment and were in complete clinical and colitis. Am J Gastroenterol 2001;96:1807–15.
(95% CI 1.9–15.4)). There was a clear trend 6 Musch E, Andus T, Malek M. Induction and (test for trend: x2: 16, p,0.0001) when we therapy.4 Madsen et al recently presented a maintenance of clinical remission by interferon compared the increasing frequency of the G study comparing systemic IFN alpha therapy beta in patients with steroid-refractory active allele of TLR4 +896 in controls (10%) to CD ulcerative colitis: an open long-term pilot trial.
and prednisolone enemas in the treatment of Aliment Pharmacol Ther 2002;16:1233–9.
left sided ulcerative colitis.5 Ulcerative colitis 7 Nikolaus S, Rutgeerts P, Fedorak R, et al.
Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study.
correlated with carriage of the TLR4 G allele.
suppresses IL-5 synthesis in leucocytes. IFN 6 Braat H, Dijkgraaf M, Curvers W, et al. A Table 1 CD142260 and TLR4+896 genotype distribution in Crohn’s disease functional single polymorphism of the TLR4 gene is correlated with Crohn’s disease but not withulceratice colitis. Gastroenterology2004;124:A367.
7 Arnott IDR, Nimmo ER, Drummond HE, et al.
Scottish and Irish Crohn’s disease patients: evidence for genetic heterogeneity within Europe? England. Genes Immun 2004;5:417–25.
8 von Aulock S, Schro¨der NWJ, Gueinzius K, et al.
Heterozygous toll-like receptor 4 polymorphism does not influence lipopolysaccharide-induced cytokine release in human whole blood. United States. J Infect Dis 2003;188:938–43.
9 Erridge C, Stewart J, Poxton IR. Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the toll-like receptor 4 Gene show no deficit in lipopolysaccharide signalling. UnitedStates. J Exp Med 16-6-, 2003;197:1787–91.
*TLR4*G was more frequent in CD patients compared with HC (19% v 10%; p = 0.0489; odds ratio (OR) 2.076 (95% confidence interval (CI) 1.041–4.142)).
ÀTLR4*G was significantly associated with colonic localisation compared with non-colonic localisation(43% v 12%, p = 0.0017; OR 5.455 (95% CI 1.931–15.410)).
Vienna Classification: (age) A1: age ,40 years; A2: age .40 years; (behaviour) B1: non-stricturing, Just as the weakest link in a chain deter- non-penetrating; B2: stricturing; B3: penetrating; (localisation) L1: ileal; L2: colonic; L3: ileocolonic; L4: mines how much weight the chain will hold, the weakest link in the data used by Fioricaet al will determine how much weight we asreaders should give to their findings and TLR4 G allele carriage in ASCA positive and ASCA negative patients (23% v 14%; p = 0.33) interesting to know whether Franchimont et (data not shown) and there was no difference al tested for ASCA in their CD patients and noma (Gut 2004;53:925–30). Clearly, the whether or not an association between ASCA weakest link in their data is the material by colonic localisation (40% v 46%; p = 1.00) while the frequency of G allele carriage was et al, a careful assessment of the reliability identical to that of CD patients with colonic A A van Bodegraven, C J J Mulder, R Linskens, of the Walsh data is imperative.1 Well known localisation (43%) without correcting for criticisms of the Walsh trial include the lack Laboratory of Immunogenetics and Department of Gastroenterology, VU University Medical Centre, De graphy scanning that led to five patients TLR4+896 A.G and CD14–260 C.T in CD.
undergoing surgery alone for stage 4 disease, Klein et al have described a German popula- the exclusion of a number of patients in the neoadjuvant arm for ‘‘protocol violations’’ Correspondence to: Dr S A Morre´, VU University when in fact several had evidence of pro- Medical Centre, Faculty of Medicine, Laboratory of gressive disease and should have been con- Immunogenetics, Section Immunogenetics of Infectious healthy controls.5 This association could not sidered treatment failures, and the lack of a Diseases, Room J396, Van der Boechorststraat 7, be confirmed in our population. Preliminary uniform surgical technique that led to five data by Braat et al demonstrated an increased different types of operations being performed Conflict of interest: None declared.
reported in the literature. However, these colleagues (Gut 2004;53:987–92) corrobo- rated the results of Braat et al. In contrast greater problem in the Walsh trial related to internal inconsistencies in the survival data.
1 Tada H, Nemoto E, Shimauchi H, et al.
association between the G allele of TLR4+896 Saccharomyces cerevisiae-and Candida albicans- and disease phenotype (colonic localisation).
derived mannan induced production of tumor reveals that the survival data in the text of In contrast with the aforementioned studies necrosis factor alpha by human monocytes in a the report does not match the data in the Kaplan-Meier survival curves, but interest- demonstrate an association between suscept- ingly the discrepancy is only for the neoadju- ibility to CD and the TLR4 and CD14 SNPs in a vant arm.1 In all cases the survival data for 2 Linskens RK, Mallant-Hent RC, Murillo LS, et al.
the surgery alone arm matches up precisely.
Genetic and serological markers to identify For example, in the text of the manuscript, phenotypic subgroups in a Dutch Crohn’s disease survival by intention to treat at three years in the neoadjuvant arm is reported as 32%, yet intention to treat in the neoadjuvant arm is agonists, and as heterozygous carriership of serological markers to differentiate between approximately 48%.1 Similar discrepancies the TLR4 +896 A.G does not seem to impair ulcerative colitis and Crohn’s disease: pANCA, occur at essentially every data point for both LPS signalling,8 9 further agonist identifica- ASCA and agglutinating antibodies to anaerobic tion to elucidate the microorganisms involved coccoid rods. England. Eur J Gastroenterol actually received graphs, but only for the in CD and especially in colonic localisation is essential to obtain insight into both the Koning MHMT, et al. No evidence for involvement the data in the text. Importantly, the statis- aspects of CD. This insight may be helpful of the toll-like receptor 4 (TLR4) A896G and tics for survival are calculated from the CD14 C-260T polymorphisms in the susceptibility in developing strategies for the prevention Kaplan-Meier curves, raising concern that to ankylosing spondylitis. Ann Rheum Dis 2005 the difference in survival between groups is in fact not significant. This alarming discre- TLR4 and CD is most likely not strongly based polymorphism in the CD14 gene is associated pancy has never been adequately addressed despite a letter to the New England Journal of Scand J Gastroenterol 2002;37:189–91.
Medicine and a subsequent reply by Dr Walsh.2 The response by Walsh was that the graphs first day of treatment. This therapy was given 4 Peck CC, Wood JD. Brain-gut interactions in were mislabelled, but even with a different label the data points continue to be incon- Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharges In light of this, I would like to know how Prednisolone was tapered without exacerba- Fiorica et al handled the data from the Walsh tion of colitis during this treatment, and the trial. Did they use data from the Kaplan- 6 Chaplan SR, Bach FW, Shafer SL, et al. Prolonged Meier survival curves or from the text and Clinical reports by Kemler and colleagues,3 alleviation of tactile allodynia by intravenous tables in the manuscript? Were they aware of who reported on a patient with ulcerative lidocaine in neuropathic rats. Anesthesiology the discrepancy and if so why did they not colitis exacerbated by spinal cord stimulation, 7 Sinnot CJ, Garfield JM, Strichartz GR. Differential specify how they dealt with it in their meta- complete remission of a patient with ulcera- efficacy of intravenous lidocaine in alleviatingipsilateral versus contralateral neuropathic pain in analysis? In light of these concerns, as well as tive colitis after spinal cord injury, support other issues regarding this trial, is it appro- the involvement of neural control in ulcera- 8 Ramus GV, Cesano L, Barbalonga A. Different priate to even include it in a meta-analysis tive colitis. Systemic lidocaine, which has concentrations of local anaesthetics have different modes of action on human lymphocytes. Agents reviewed and the statistics validated? This is ectopic discharges without blocking nerve an especially important issue as the Walsh study is the only trial that included just central and/or peripheral nerve function.
patients with adenocarcinoma, and as stated Thus, in this case, the effectiveness of these in the manuscript by Fiorica et al, robust drugs could be attributed to modulation of analysis showed that exclusion of the Walsh Currently available binding resins used for trial would lead to loss of statistical signifi- using a 2% gel (400 mg lidocaine), maximum cance for overall mortality (Gut 2004;53:925– plasma levels were 0.5–1.9 mg/l in patients generally poorly tolerated because of unpal- 30). This would leave us where we started, with proctitis two hours after application of atability and associated gastrointestinal side lacking any significant evidence that neoad- effects. We suggest that there is now a viable juvant therapy improves survival for patients concentrations of 1.2–2.1 mg/l of lidocaine has been shown to be effective for neuro- pathic pain.6 7 Therefore, it is possible that in ulcerative colitis, lidocaine administered per A 30 year old man presented with steator- Correspondence to: Dr S R DeMeester, University of effects after being absorbed into blood and Southern California, Keck School of Medicine, Los has an effect on central and/or peripheral right hemicolectomy following a road traffic nerves. Another possibility is direct anti- Physical examination, relevant blood tests, Conflict of interest: None declared.
whether systemic administration of lidocaine microscopic examination of colonic biopsies can achieve adequate concentrations in colo- were normal. A trial of cholestyramine in nic tissue to have a direct anti-inflammatory preference to a SeCHAT scan caused cessation 1 Walsh TN, Noonan N, Hollywood D, et al. A of diarrhoea on one sachet per day. However, comparison of multimodal therapy and surgery his abdominal bloating continued unabated for esophageal adenocarcinoma. N Engl J Med and he found the treatment unpalatable.
colesevelam 2.5 g/3.75 g on alternate days.
multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1999;341:384.
This was well tolerated, with complete cessa- ulcerative colitis which was assessed by sig- tion of his steatorrhoea and lethargy, and no side effects. In addition, he rapidly gained eters (data not shown), suggesting that pain or pain inducing substances could be a cause of exacerbation of ulcerative colitis as well as symptomatic bile salt malabsorption resistant to antidiarrhoeal agents and intolerant of Lidocaine and mexiletine therapy could be useful for the treatment of the subgroup of ulcerative colitis has been shown.1 In clinical menced on colesevelam (table 1). In all of patients with ulcerative colitis that are settings, local anaesthetics such as lidocaine these cases colesevelam was well tolerated refractory to conventional medical treat- and ropivacaine were used, administered per ments. While we do not know how to select rectum, for the treatment of distal ulcerative Colesevelam is a non-absorbed water insol- responders to this treatment, pain could be colitis with a response rate of 83% after long uble polymer which sequesters bile.1 It has treatment periods (6–34 weeks) for procto- been approved for usage by the US FDA, and sigmoiditis (n = 49).2 We report a patient has been received as a valuable alternative for with total ulcerative colitis that was amelio- lowering cholesterol.2 Colesevelam has high rated by continuous intravenous administra- affinity for dihydroxy and trihydroxy bile Correspondence to: Dr Y Yokoyama, Kochi Medical acids in the intestine which causes increased administration of mexiletine (a congener of faecal bile acid secretion, reducing the enter- ohepatic circulation of bile acids.2 This allows 7-hydroxylase, the rate limiting enzyme in bation of ulcerative colitis was admitted to bile acid synthesis, to increase the conversion our hospital. Total ulcerative colitis had been of hepatic cholesterol to bile acids.2 It has not Conflict of interest: None declared.
abstract suggests that colesevelam may be study to reveal a total type of colitis.
beneficial for patients with diarrhoea who Conventional medical therapies, including 1 Neunlist M, Aubert P, Toquet C, et al. Changes in Crohn’s disease.3 There are no other pub- pulse therapy), 5-aminosalicylate, and leuco- lished data to support its role in bile salt cytapheresis were not effective. Abdominal ulcerative colitis. Gut 2003;52:84–90.
induced diarrhoea. Colesevelam is reported to 2 Bjo¨rck S, Dahlstrom A, Ahlman H. Treatment of be 4–6 times as potent as traditional bile salt distal colitis with local anaesthetic agents.
severe at night. We administered continuous sequestrants, possibly due to its greater systemic lidocaine (1 mg/min on the first day 3 Kemler MA, Barendse GAM, Van Kleef M.
binding affinity for glycocholic acid.4 It is and 1.3 mg/min on subsequent days) only at Relapsing ulcerative colitis associated with spinal administered in tablet form, and in one study night, resulting in complete disappearance of abdominal pain and bloody diarrhoea on the Table 1 Characteristics of four patients with markedly symptomatic bile salt malabsorption resistant to antidiarrhoeal agentsand intolerant of cholestyramine given colesevelam structure enables greater tolerability with less Any researchers interested in applying for potential drug interactions than with resins.1 hydrochloride: a novel bile acid-binding resin.
national register should contact Dr Helen 3 Knox JF, Rose D, Emmons J, et al. Colesevalam clinical trial to date include flatulence, Harris (Register Co-ordinator) or Ms Shirley for the treatment of bile acid diarrhea induced dyspepsia, and diarrhoea although the inci- diarrhea in Crohn’s disease: patients intolerant of dence of adverse events does differ signifi- cantly from that observed with placebo, and is lower than with cholestyramine.2 It is 4 Steinmetz KL. Colesevelam hydrochloride.
rarely associated with constipation, unlike Am J Health Syst Pharm 2002;59:932–9.
5 Heller DP, Burke SK, Davidson DM, et al.
Friday) or ext. 7906 (Monday to Friday); fax: Absorption of colesevelam hydrochloride in absorbed and is excreted entirely via the +44 (0)20 8200 7868; email: helen.harris@ gastrointestinal tract, preventing systemic or
side effects.5 Furthermore, there is little No data will be released that could identify 6 Donovan JM, Stypinski D, Stiles MR, et al. Drug evidence for clinically significant interactions interactions with colesevelam hydrochloride, a individual patients directly or via linkage to novel, potent lipid-lowering agent. Cardiovasc other data. Any study proposals should then be submitted to the register co-ordinator for clinically significant effects of absorption of There is a theoretical risk of fat soluble vitamin deficiency following such efficientbile acid sequestration. None of our patients developed any significant change in fasting triglycerides or fat soluble vitamin levels to This symposium is co-sponsored by the Office of Continuing Medical Education, University Each film coated tablet contains coleseve- lam 625 mg (active ingredient).2 The recom- Gastrointestinal Disorders (IFFGD). It will hypercholesteraemia is 3.75 g once a day or take place on 7–10 April 2005 in Milwaukee, 1.875 g twice per day, although the optimal Wisconsin, USA, at The Pfister Hotel, 424 E.
dose is 4.375 g in adults.2 The optimal dose for bile salt malabsorption is not clear but an effective dose has varied between two and six In 1998, a national register of hepatitis C tel: +1 800 558 8222; fax: +1 414 273 5025; tablets/day in our series. Colesevelam was virus (HCV) infections with a known date of email:; web: http:// acquisition was established. The register was set up to help inform the natural history of binding resin in tablet form that maintains the benefits of cholestyramine, yet is palat- largest cohorts of individuals with known effects, and has greater potency. It provides date HCV infections, with over 1120 regis- a very attractive alternative therapy for tered patients. The majority of infections in patients with bile salt malabsorption and the register are those that were acquired following transfusion of HCV infected blood that was issued before the introduction of Department of Medicine and Therapeutics, Imperial routine screening of the blood supply for College Faculty of Medicine, Chelsea and Westminster In reference 38 of the paper by C Gasche and In order to get maximum benefit from this P Grundtner, published in the January issue Correspondence to: Dr H J N Andreyev, Department national resource, the register steering group (Genotypes and phenotypes in Crohn’s dis- of Medicine and Therapeutics, Imperial College would like to invite clinical and epidemio- ease: do they help in clinical management? Faculty of Medicine, Chelsea and Westminster logical researchers to submit proposals to Gut 2005;54:162–7), the page span is incor- Hospital, 369 Fulham Rd, London SW10 9NH, UK; envisaged that a variety of studies might benefit from linkage with or access to the In the paper by Sheu et al in the July 2003 register, and proposals from all specialties issue of Gut (B-S Sheu, S-M Sheu, H-B Yang, Conflict of interest: None declared.
and institutions are welcomed. Such studies A-H Huang, and J-J Wu. Host gastric Lewis are urgently needed to help determine the expression determines the bacterial density of Helicobacter pylori in babA2 genopositive infec- disease on healthcare services, and to assess tion. Gut 2003;52:927–932), the B and C 1 Bays H, Dujovne C. Colesevelam HCl: a non- the impact of currently available treatments slides of figure 1 have been transposed and systemic lipid-altering drug. Expert Opin as well as those that may become available in the arrow on D should be labelled LeX not


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Administrative Appeals Tribunal DECISION AND REASONS FOR DECISION [2008] AATA 639 ADMINISTRATIVE APPEALS TRIBUNAL No NT2005/7, NT2005/56 to 65 TAXATION APPEALS DIVISION ROCHE PRODUCTS PTY LIMITED Applicant COMMISSIONER OF TAXATION Respondent DECISION Tribunal Place Sydney Decision The decision of the Commissioner of Taxation is


Gender matters V A N I T A N A Y A K M U K H E R J E E ‘The empowerment and autonomy of women and the improvement of their political, social, economic and health status is a highly important end in itself. In addition, it is essential for the achievement of sustainable development. The full participation and partnership of both women and men is required in productive and reproductive life,

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