bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic polymorphisms of tumour necrosis factor receptor superfamily 1A and 1B affect responses to infliximab in Japanese patients with Crohn’s disease
Authors: MATSUKURA H. , IKEDA S. , YOSHIMURA N. , TAKAZOE M. , MURAMATSU M.
Published: July 2010

Background  Tumour necrosis factor alpha is the key inflammatory cytokine involved in the pathogenesis of Crohn’s disease. Infliximab, a chimaeric monoclonal antibody of tumour necrosis factor‐α is successfully used for the treatment of Crohn’s disease, although the response to infliximab therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness.

Aim  To investigate whether the polymorphisms in these genes are associated with the response to infliximab treatment as tumour necrosis factor‐α exerts its biological activity through TNF receptor superfamily 1A and 1B.

Methods  Eighty Crohn’s disease patients were enrolled in the study and classified into responder and nonresponder according to the efficacy of infliximab treatment. Single nucleotide polymorphisms of TNF receptor superfamily 1A (rs767455 and rs4149570) and TNF receptor superfamily 1B (rs1061622, rs1061624 and rs3397) were determined.

Results  The minor allele carrier of rs767455 showed a significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95% CI: 0.08–0.91). A TNF receptor superfamily 1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and nonresponder (P = 0.01).

Conclusion  These results suggest that tumour necrosis factor receptor genotypes may be involved in the different responses to infliximab in Japanese patients with Crohn’s disease.
Review article: gastroparesis
Authors: PATRICK A. , EPSTEIN O.
Published: July 2010

Background  Gastroparesis is a chronic disorder caused by stomach pump failure and characterized by profound nausea, vomiting and epigastric pain. Most often, the cause is unapparent and of the known associations, diabetes is the most common. Diagnosis is usually made using an isotope‐labelled test meal. Treatment is incremental and includes education, dietary support, prokinetic and antiemetic agents. There are novel approaches including gastric neurostimulation.

Aim  To review current concepts of gastric motor function, aetiology, investigation and treatment of gastroparesis.

Methods  A systematic web‐based review of the literature was undertaken using a lexicon of terms associated with gastroparesis.

Results  There are few controlled studies of this condition. Little is known about causation or underlying nerve, muscle or pacemaker pathology. Idiopathic gastroparesis occurs most commonly in women and gastric emptying is often abnormal in diabetes. Isotopic gastric scintigraphy remains the gold standard investigation, but alternative tests are being developed. Treatment is multimodal and includes education, and nutritional support. There are no adequately powered controlled trials to support a particular drug regimen. In intractable gastroparesis, gastric neurostimulation appears to offer benefit.

Conclusion  Despite a significant progress in the past decade, further controlled trials are required into the therapeutic options available for treating this intriguing condition.
Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug‐induced liver injury
Authors: GARCÍA‐CORTÉS M. , LUCENA M. I. , PACHKORIA K. , BORRAZ Y. , HIDALGO R. , ANDRADE R. J. ,   ON BEHALF OF THE SPANISH GROUP FOR THE STUDY OF DRUG‐INDUCED LIVER DISEASE (GRUPO DE ESTUDIO PARA LAS HEPATOPATÍAS ASOCIADAS A MEDICAMENTOS, GEHAM)
Published: July 2010

Background  Causality assessment in hepatotoxicity is challenging. The current standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug‐induced liver injury.

Aim  To compare the Naranjo method with the standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity.

Methods  Two hundred and twenty‐five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between‐observer and between‐scale differences using percentages of agreement and the weighted kappa (κw) test.

Results  A total of 249 ratings were generated. Between‐observer agreement was 45% with a κw value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, κw: 0.71). Concordance between the two scales was 24% (κw: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability.

Conclusion  The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.
Response rate and predictors of response in a short‐term empirical trial of high‐dose rabeprazole in patients with globus
Authors: SINN D. H. , KIM J. H. , KIM S. , SON H. J. , KIM J. J. , RHEE J. C. , RHEE P.‐L.
Published: July 2010

Background  Although the aetiology of globus (the sensation of a lump in the throat) remains unclear, gastro‐oesophageal reflux disease is associated with globus. A short‐term trial with a high‐dose proton pump inhibitor has been shown to be a sensitive tool for diagnosing gastro‐oesophageal reflux disease.

Aim  To see whether patients with globus symptom responded to short‐term high‐dose rabeprazole trial and assess predictors of symptom response.

Methods  Sixty‐four patients with globus symptom were analysed. Patients received rabeprazole 20 mg b.d. for 14 days. Patients completed a daily diary assessing the severity and frequency of globus.

Results  Forty‐one patients (64%) were diagnosed clinically with gastro‐oesophageal reflux disease. Based on the pH testing and endoscopy, the prevalence of gastro‐oesophageal reflux disease was 22% (14 of 64). The globus symptom score was significantly higher in patients with gastro‐oesophageal reflux disease compared with patients without gastro‐oesophageal reflux disease (P = 0.004). Two patients (3%) had complete resolution and 22 (34%) had more than a 50% improvement in the globus symptom score. Endoscopic findings (P = 0.714), pathological acid exposure on pH testing (P = 0.741) or baseline gastro‐oesophageal reflux disease symptoms (P = 0.606) were not associated with improvement of globus symptom.

Conclusion  While gastro‐oesophageal reflux disease may be an aggravating factor in patients with globus, it does not appear to be the sole cause of globus symptom.
Clinical trial: randomized study of clarithromycin versus placebo in active Crohn’s disease
Authors: LEIPER K. , MARTIN K. , ELLIS A. , WATSON A. J. M. , MORRIS A. I. , RHODES J. M.
Published: July 2010

Background  Crohn’s disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad‐spectrum antibiotic that has good penetration into macrophages.

Aim  To assess the efficacy of clarithromycin in active Crohn’s disease.

Methods  Patients with Crohn’s disease activity index > 200 and serum C‐reactive protein ≥ 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI ≤ 150) or response (fall in CDAI ≥ 70 from pre‐treatment level) at 3 months.

Results  The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn’s disease activity index was 35 (80) clarithromycin and −2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn’s disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01).

Conclusion  Clarithromycin 1 g for 3 months is ineffective in active Crohn’s disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance.
Stem cell mobilization and collection in patients with liver cirrhosis
Authors: LORENZINI S. , ISIDORI A. , CATANI L. , GRAMENZI A. , TALARICO S. , BONIFAZI F. , GIUDICE V. , CONTE R. , BACCARANI M. , BERNARDI M. , FORBES S. J. , LEMOLI R. M. , ANDREONE P.
Published: July 2010

Background  Bone marrow‐derived stem cells (BMSC) and granulocyte colony‐stimulating factor (G‐CSF) have been proved to contribute to tissue regeneration after liver injury.

Aims  To test the safety of G‐CSF and define the exact dose capable of mobilizing BMSC in the majority of patients with liver cirrhosis; and to assess the feasibility of leukapheresis to collect BMSC from peripheral blood.

Methods  In this study, we treated 18 patients affected by liver cirrhosis with increasing doses of G‐CSF to mobilize CD34+ and CD133+ BMSC into the peripheral blood.

Results  The dose‐finding phase demonstrated that 15 μg/kg/day of G‐CSF is the optimal dose to mobilize both CD34+ and CD133+ stem cells. Circulating BMSC were collected by a single step leukapheresis in three patients and the mean number of CD34+ and CD133+ cells cryopreserved was 1.3 ± 0.7 and 1.2 ± 0.5 × 106/kg, respectively. No severe adverse events were observed during the drug administration and stem cell collection. Noteworthy is, none of the patients showed a significant modification of liver function.

Conclusions  Our study demonstrates that G‐CSF administration and BMSC collection from the peripheral blood is possible and safe in patients with liver cirrhosis. The optimal dose to mobilize BMSC in cirrhotics is 15 μg/kg/day. At this dose, G‐CSF does not seem to modify the residual liver function in cirrhotic patients.
Time trends in first‐diagnosis rates of colorectal adenomas: a 24‐year population‐based study
Authors: COTTET V. , JOOSTE V. , BOUVIER A.‐M. , MICHIELS C. , FAIVRE J. , BONITHON‐KOPP C.
Published: July 2010

Background  Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population.

Aim  To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma‐bearing individuals detected over a 24‐year period.

Methods  A total of 11 027 patients were first‐diagnosed with colorectal adenomas among Côte‐d’Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma‐bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area.

Results  Standardized diagnosis rates were 89.6/100 000 men and 50.3/100 000 women. During the period 1976–1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994–1999. The estimated proportion of adenoma‐bearing individuals diagnosed during the 24‐year period was 20.0% in men and 16.0% in women.

Conclusion  Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma‐bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence.
Meta‐analysis: remission and response from control arms of randomized trials of biological therapies for active luminal Crohn’s disease
Authors: TINÈ F. , ROSSI F. , SFERRAZZA A. , ORLANDO A. , MOCCIARO F. , SCIMECA D. , OLIVO M. , COTTONE M.
Published: July 2010

Background  Remission and response are the main outcomes to evaluate the efficacy of new treatments for Crohn’s disease (CD).

Aim  To explain variation of remission and response rates in active luminal CD.

Methods  We studied control patients from trials of biological therapies through articles retrieved by MEDLINE search (from 1997 to 2007) and by bibliography review. Thousand nine hundred and thirteen control patients from 28 trials were identified; data were extracted by three independent observers and pooled by DerSimonian and Laird random effect model; factors influencing remission and clinical response were explored by metaregression for aggregated data.

Results  The pooled control rates of remission and response were 17% and 33%, respectively, both with significant heterogeneity among studies (P < 0.0001). At metaregression, the time of primary outcome evaluation was associated with remission, whereas the trial’s criteria for defining response and publication year were predictors of response. CDAI score, CRP levels or other clinical variables related with disease activity or concomitant medications were not significant factors.

Conclusions  Populations used as ‘add‐on’ treatment comparator in trials of biological therapies for active luminal CD are poorly characterized and outcomes are heterogeneous. Planning of future trials will require better description of patients and concomitant therapies, blinding of outcome assessors and homogeneous criteria of outcome definition.
Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti‐viral activity of clevudine for 12 weeks in patients with chronic hepatitis B
Authors: LIM S. G. , LEUNG N. , HANN H. W. L. , LAU G. K. K. , TREPO C. , MOMMEJA‐MARIN H. , MOXHAM C. , SORBEL J. , SNOW A. , BLUM M. R. , ROUSSEAU F. , MARCELLIN P.
Published: July 2010

Background  Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics.

Aim  To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor.

Methods  A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off‐treatment follow‐up. Patients had chronic HBV infection, were nucleoside‐naïve without co‐infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method.

Results  A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was −3.2, −3.7 and −4.2 log10 copies/mL (−0.64, −0.74 and −0.84 log10 IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half‐life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound.

Conclusion  Clevudine appears to be a potent and tolerable (over 12 weeks) anti‐viral and the optimal dosage appears to be 30 mg once daily.
Gastrointestinal side effects in chronic opioid users: results from a population‐based survey
Authors: COOK S. F. , LANZA L. , ZHOU X. , SWEENEY C. T. , GOSS D. , HOLLIS K. , MANGEL A. W. , FEHNEL S. E.
Published: July 2010

Background  Gastrointestinal side effects are commonly associated with opioid treatment for pain.

Aim  To understand gastrointestinal side effects associated with opioid treatment.

Methods  This study was a population‐based survey of adults in the US who use opioids to manage pain unrelated to cancer. Participants were recruited from an existing Web‐enabled panel and a supplemental panel of individuals who previously indicated an interest in participating in Web‐based surveys.

Results  Overall, 2055 individuals participated in the main phase of the survey. Fifty‐seven per cent of participants reported having had constipation that they associated with opioid treatment, and 49% reported constipation in the previous 4 weeks. Thirty‐six per cent of participants reported new or worsening constipation in the previous 4 weeks. Thirty‐three per cent of participants reported constipation as their most bothersome symptom associated with opioid treatment, 13% reported nausea, 11% abdominal pain and 10% gas. Seventy‐three per cent of the participants who reported any GI symptoms did not change the dosage level or frequency of use of opioids because of adverse events, which may be explained by the fact that 72% of participants used over‐the‐counter laxatives and 12% a prescription laxative.

Conclusion  Constipation is a frequent and significant event occurring with opioid use.
Systematic review: gastro‐oesophageal reflux disease and dental lesions
Authors: PACE F. , PALLOTTA S. , TONINI M. , VAKIL N. , BIANCHI PORRO G.
Published: July 2010

Background  Dental erosion (DE), which is the irreversible loss of tooth substance that does not involve bacteria ranging from a minimal loss of surface enamel to the partial or complete exposure of dentine by a chemical process, is acknowledged as an established extra‐oesophageal manifestation of gastro‐oesophageal reflux disease (GERD). However, the real impact of GERD in the genesis of this lesion remains unclear.

Aim  To review the existing literature to assess the relationship between DE and GERD.

Methods  Studies that assessed the prevalence of DE in individuals with GERD or vice versa were identified in Medline and the Cochrane Controlled Trials Register via a systematic research strategy.

Results  Seventeen studies met the selection criteria. Studies, however, differed greatly as far as design, population methods of diagnosing GERD, duration of follow‐up and, consequently, findings. The median prevalence of DE in GERD patients was 24%, with a large range (5–47.5%), and the median prevalence of GERD in DE adults patients was 32.5% (range: 21–83%) and in paediatric population 17% (range: 14–87%). Children with GERD are found by a majority of studies at increased risk of developing DEs in comparison with healthy subjects, as are intellectually disabled people.

Conclusions  This systematic review shows that there is a strong association between GERD and DE. The severity of DEs seems to be correlated with the presence of GERD symptoms, and also, at least in adults, with the severity of proximal oesophageal or oral exposure to an acidic pH. The inspection of the oral cavity in search for DEs should become a routine manoeuvre in patients with GERD.
Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease
Authors: BUREAU C. , METIVIER S. , PERON J. M. , SELVES J. , ROBIC M. A. , GOURRAUD P. A. , ROUQUET O. , DUPUIS E. , ALRIC L. , VINEL J. P.
Published: July 2010

Background  Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS).

Aim  To assess the correlation between LS and HVPG and to investigate the performance of transient elastography for the diagnosis of significant portal hypertension (PHT).

Methods  Liver stiffness was measured by Fibroscan in 150 consecutive patients who underwent a liver biopsy with haemodynamic measurements. Usual clinical and biological data were collected. Significant PHT was defined as a HVPG ≥10 mmHg.

Results  Hepatic venous pressure gradient was found to be ≥10 mmHg in 76 patients. Cirrhosis was diagnosed in 89 patients. HVPG was found to be correlated with: LS (ρ = 0.858; P < 0.001) and inversely correlated with prothrombin index (ρ = −0.718; P < 0.001). Regarding significant PHT, AUROC for LS and prothrombin index were 0.945 [0.904–0.987] and 0.892 [0.837–0.947] respectively. The cut‐off value of 21 kPa accurately predicted significant PHT in 92% of the 144 patients for whom LS was successful.

Conclusion  Liver stiffness measurement is correlated with HVPG and transient elastography identifies patients with significant PHT.
Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alfa‐2a plus ribavirin
Authors: BAIN V. G. , LEE S. S. , PELTEKIAN K. , YOSHIDA E. M. , DESCHÊNES M. , SHERMAN M. , BAILEY R. , WITT‐SULLIVAN H. , BALSHAW R. , KRAJDEN M. ,   ON BEHALF OF THE CANADIAN PEGASYS STUDY GROUP
Published: July 2010

Background  The impact of reduced drug exposure on outcomes in patients with chronic hepatitis C has not been determined in routine clinical practice.

Aim  To examine the impact of exposure to peginterferon alfa‐2a and ribavirin on early virological response (EVR) and sustained virological response (SVR) in treatment‐naïve patients with HCV genotype 1 infection enrolled in a large expanded access programme.

Methods  Eight hundred and ninety‐one patients treated for 48 weeks with an initial ribavirin dose of 800 or 1000/1200 mg/day were evaluated. Ribavirin 1000 mg/day (<75 kg) or 1200 mg/day (≥75 kg) and peginterferon alfa‐2a 180 μg/week were considered optimal. The impact of reduced drug exposure (expressed as a percentage of optimal) on EVR and SVR was evaluated.

Results  Mean ribavirin exposure in week 0–12 was 70% and 96% in patients assigned to ribavirin 800 and 1000/1200 mg/day, respectively. EVR and SVR rates were lower in patients assigned to ribavirin 800 than 1000/1200 mg/day (EVR, 75% vs. 84%, respectively, P < 0.001; SVR, 45% vs. 54%, respectively, P = 0.011). Furthermore, there was a strong correlation between achievement of EVR and SVR and ribavirin dose over the first 12 weeks expressed either as absolute dose or proportion of optimal dose received (P < 0.001 for both).

Conclusions  Ribavirin exposure to week 12 is significantly associated with EVR and SVR in genotype 1 patients. Maintenance of an optimal ribavirin dose is the most important modifiable factor during combination therapy for chronic hepatitis C.
Changes of gastric histology in patients with erosive oesophagitis receiving long‐term lansoprazole maintenance therapy
Authors: Haber M. M. , Hunt B. , Freston J. W. , Peura D. A. , Kovacs T. O. , Atkinson S. , Hisada M.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 83–96

Background  Changes in gastric histology associated with long‐term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described.

Aim  To evaluate the effect on gastric histology of long‐term dose‐titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis.

Methods  Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status.

Results  Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long‐term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori‐positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori‐negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori‐positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori‐negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow‐up period.

Conclusions  Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated.
Lymphogranuloma venereum proctitis masquerading as inflammatory bowel disease in 12 homosexual men
Authors: Soni S. , Srirajaskanthan R. , Lucas S. B. , Alexander S. , Wong T. , White J. A.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 59–65

Background  Lymphogranuloma venereum (LGV) is a recognized cause of proctitis. Symptoms, endoscopy and histology findings are similar in IBD and LGV proctitis.

Aims  To characterize the clinical, endoscopic and histological features seen in men diagnosed initially with IBD and subsequently with LGV proctitis, and to attempt isolation of Chlamydia trachomatis DNA from the stored rectal biopsy specimens of these patients using real‐time PCR.

Methods  Clinical data were collated from confirmed or suspected cases of LGV proctitis where endoscopy and biopsy had been performed as part of the investigation of clinical symptoms. LGV was confirmed by the detection of LGV‐specific DNA from rectal swab specimens, with supportive evidence from Chlamydial serology. Stored histological specimens from rectal biopsies were analysed retrospectively for LGV‐specific DNA with molecular techniques.

Results  Rectal biopsies had been obtained from twelve cases of LGV proctitis. Mucosal ulcers, cryptitis, crypt abscesses and granulomas were common histological findings. Extraction of LGV‐specific DNA from rectal biopsy specimens enabled confirmation of three suspected cases.

Conclusions  During the recent LGV proctitis epidemic among UK men who have sex with men, it has become apparent that this infection may closely resemble IBD. Gastroenterologists should remain alert to LGV as a cause of proctitis in this group.
Meta‐analysis: the effects of placebo treatment on gastro‐oesophageal reflux disease
Authors: Cremonini F. , Ziogas D. C. , Chang H. Y. , Kokkotou E. , Kelley J. M. , Conboy L. , Kaptchuk T. J. , Lembo A. J.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 29–42

Background  There appears to be a significant placebo response rate in clinical trials for gastro‐oesophageal reflux disease. Little is known about the determinants and the circumstances associated with placebo response in the treatment of gastro‐oesophageal reflux disease (GERD).

Aims  To estimate the magnitude of the placebo response rate in randomized controlled trials for GERD and to identify factors that influence this response.

Methods  A meta‐analysis of randomized, double‐blind, placebo‐controlled trials, published in English language, which included >20 patients with GERD, treated with either a proton pump inhibitor or H2‐receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched, considering only studies that reported a global response for ‘heartburn’.

Results  A total of 24 studies included 9989 patients with GERD. The pooled odds ratio (OR) for response to active treatment vs. placebo was 3.71 (95% CI: 2.78–4.96). The pooled estimate of the overall placebo response was 18.85% (range 2.94%–47.06%). Patients with erosive oesophagitis had a non‐significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; P = 0.246). Placebo response was significantly lower in studies of PPI therapy vs. studies of H2 RAs (14.51% vs. 24.69%, respectively; P = 0.05).

Conclusions  The placebo response rate in randomized controlled trials for GERD is substantial. A lower placebo response was associated with the testing of PPIs, but not the presence of erosive oesophagitis.
Determination of pig apolipoprotein B genotype by gene amplification and restriction fragment length polymorphism analysis
Authors: Kaiser M. E. , Sturley S. L. , Attie A. D. , Nevin D. N. , Purtell C.
Published: July 2010

Summary

Sequence differences within the pig apoB gene can be used to identify rapidly four of eight known pig apoB alleles, designated LPB1‐LPB8. We describe the use of gene amplification, followed by endonuclease digestion and agarose gel electrophoresis, to discern size and restriction site differences. LPB5, a common allele associated with reduced low density lipoprotein clearance and hypercholesterolaemia in pigs, is identified by a 283‐bp insertion in intron 28. LPB3 and LPB7 are distinguished by a unique HindIII site; LPB8 shares a unique HincII site with LPB5. This method facilitates identification of the apoB genotype of pigs used in lipoprotein research and allows for further investigation into the association of particular apoB alleles with lipoprotein metabolism abnormalities.
Lack of acetylcholine nicotine alpha 7 receptor suppresses development of collagen-induced arthritis and adaptive immunity
Authors: Westman M , Saha S , Morshed M , Lampa J
Published: July 2010

Activation of the alpha7 receptor (α7nAChR) has been shown to be important in inflammation and immune regulation, and is also essential in the neural cholinergic anti-inflammatory pathway. The aim of this study was to investigate the role of α7nAChR in the development of experimental arthritis and immune activation. Mice lacking the α7nAChR were immunized with collagen II and the development of arthritis was assessed. Another group of α7nAChR-deficient mice was immunized with ovalbumin, spleen and lymph node cells were isolated and the proliferative responses to restimulation with ovalbumin or concanavalin A were investigated. We could demonstrate significantly milder arthritis and less cartilage destruction, together with a decrease of T cell content in lymph nodes in mice lacking the α7nAChR compared to wild-type controls. In addition, mice lacking the α7nAChR had a deficient proliferative response to concanavalin A, whereas antigen presentation-dependent proliferation was not affected. These results indicate important roles for α7nAChR in arthritis development as well as in regulation of T cell-dependent immunological mechanisms. In addition, the data implicate α7nAChR as a therapeutic target for modulation of adaptive immune responses.
The effect of paternal diet‐induced obesity on sperm function and fertilization in a mouse model
Authors: Bakos H. W. , Mitchell M. , Setchell B. P. , Lane M.
Published: July 2010

Although obvious effects of obesity on female reproduction and oocytes are emerging, the effects on male fertility and sperm quality are less clear with studies reporting conflicting results. We hypothesize that male obesity affects sperm function and physiology probably as a result of elevated oxidative stress in spermatozoa and therefore elevated levels of sperm DNA damage and loss of function. Six‐week‐old C57/Bl6 male mice (n = 36) were randomly allocated to two groups: group 1 (n = 18) received a control diet, whereas group 2 (n = 18) received a high‐fat diet (HFD). At the completion of a 9‐week period, mice were sacrificed and spermatozoa were obtained. Sperm motility, concentration, intracellular reactive oxygen species (ROS) production and sperm DNA damage were measured. The ability of the sperm to undergo capacitation, acrosome reaction, sperm binding and ability to fertilize an oocyte were also assessed. The percentage of motile spermatozoa was decreased in the HFD group compared with controls (36 ± 2% vs. 44 ± 4%; p < 0.05). Intracellular ROS was elevated (692 ± 83 vs. 409 ± 22 units; p < 0.01) in the HFD group compared with controls. Sperm DNA damage was also increased (1.64 ± 0.6% vs. 0.17 ± 0.06%; p < 0.05) in the HFD group compared with the control group. Furthermore, the percentage of non‐capacitated sperm was significantly lower compared with controls (12.34% vs. 21.06%; p < 0.01). The number of sperm bound to each oocyte was significantly lower (41.14 ± 2.5 vs. 58.39 ± 2.4; p < 0.01) in the HFD group compared with that in controls and resulted in significantly lower fertilization rates (25.9% vs. 43.9%; p < 0.01). This report provides evidence that obesity may induce oxidative stress and sperm DNA damage as well as decreased fertilizing ability. This is important as DNA damage in the sperm as a result of oxidative stress has been linked to poor reproductive outcomes.
Erotomanic delusions in mentally handicapped patients: two case reports
Authors: COLLACOTT R. A.
Published: July 2010

ABSTRACT. Two cases of mentally handicapped patients, who developed delusions of passion, are described. The relationship of these cases to de Clerambault's Syndrome, and their pathogenetic features, are discussed.
Folate metabolism and problem behaviour in mentally handicapped epileptics
Authors: DEB S. , COWIE V. A. , RICHENS A.
Published: July 2010

ABSTRACT. Two groups of mentally handicapped residents were studied consisting of 32 epileptics on anti‐epileptic medication and 32 non‐epileptic controls. The epileptic group showed a significantly low serum folate level compared with the non‐epileptic control group. Serum vitamin B12 and behaviour rating did not show any significant difference between two groups. Comparison of patients receiving phenytoin and those who were not showed significantly lower serum folate in the sub‐group receiving phenytoin, but there was no significant difference between the sub‐groups with respect to vitamin B12 or behaviour problem rating.
Psycho‐social assessment of 36 de Lange patients
Authors: BECK B.
Published: July 2010

ABSTRACT. Thirty‐six de Lange patients aged 5–47 years with a median age of 16 years were tested by the Vineland Social Maturity Scale. Significant physical handicaps affecting the scoring were found in six patients. The social quotients varied from 2.2–99.5. Eighty‐one per cent of the patients scored less than 52. Specific retardation was found in verbal communication. Other cognitive skills also showed low scoring, while the patients showed relatively high scores in self‐help items. Fifteen patients lived in large institutions for the mentally retarded, three patients lived in hostels or boarding‐schools, and one patient lived in her own home. Only two patients, both severely retarded, did not attend any regular daily activity. It is concluded that de Lange patients will not be able to live without support in the community, that they are particularly retarded in verbal communication but that they function relatively well in everyday self‐help skills.
Mortality and survival of the Down's syndrome population in Western Australia
Authors: MALONE Q.
Published: July 2010

ABSTRACT. From 1976 to 1984, there were 149 Down's syndrome live births in Western Australia. Where previously the coexistence of congenital heart disease was a major determinant of early mortality, current survival rates do not reflect this. Survival rates have significantly increased over the last decade: particularly so for those with coexistent congenital heart disease. Projected frequencies for Down's syndrome persons in Western Australia are expected to significantly increase. This rise in prevalence will have major economic effects on the planning and delivery of health care for this population.
The Aberrant Behaviour Checklist: a British replication and extension of its psychometric properties
Authors: NEWTON J. T. , STURMEY P.
Published: July 2010

ABSTRACT. The Abberrant Behaviour Checklist was administered to 209 British mentally handicapped adults in two large residential facilities. This sample included a substantial proportion (45%) of non‐ambulant people not included in previous studies. The five‐factor solution originally reported by Aman et al. (1985a) was replicated using both four‐point ratings and dichotomously recoded rating. For both methods of scoring, the five scales derived from Aman et al.'s original factor analysis remained highly internally consistent. Dichotomously coded ratings may offer the advantage over four‐point ratings of retaining the same factor structure with better reliability.
Short‐term memory difficulties and Down's syndrome
Authors: MARCELL M. M. , WEEKS S. L.
Published: July 2010

ABSTRACT. Nonretarded (NR) individuals typically show better short‐term memory for brief sequences of auditory than visual information (the modality effect). The present study attempted to determine whether the failure of Down's syndrome (DS) individuals to show the modality effect is due to the verbal‐expressive demands of oral responding in memory tasks. DS, NR and MR (non‐DS mentally retarded) subjects listened to or looked at increasingly long sequences of digits and attempted to recall them either orally or manually (through placement of items). Analyses suggested the following: (1) manual responding failed to enhance auditory recall in either DS or any other subjects; and (2) difficulty in recalling auditory stimuli was greatest for DS mentally retarded subjects. An additional assessment of DS, MR and NR subjects on a standardized auditory short‐term memory test requiring a nonverbal pointing response replicated the above findings.
Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects
Authors: FRANCESCHI C. , CHIRICOLO M. , LICASTRO F. , ZANNOTTI M. , MASI M. , MOCCHEGIANI E. , FABRIS N.
Published: July 2010

Eighteen non‐institutionalized Down's syndrome (DS) children (mean age: 7.0±10/12 years) with a history of respiratory tract, auditory and skin infections, low pi a sin.i levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc‐unbound STF molten les, and reduced absolute number of circulating T‐lymphocytes, were given an oral non‐pharmacological supplementation of zinc sulphate (1 mg Zn ++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologicalty before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T‐lymphocytes was significantly increased by zinc treatment, The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school utiendance after zinc supplementation wore recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness in phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio‐availability and/or in the utilization of zinc in DS, This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.
Transdermal scopolamine in drooling
Authors: BRODTKORB E. , WYZOCKA‐BAKOWSKA M. M. , LILLEVOLD P. E. , SANDVIK L. , SAUNTE C. , HESTNES A.
Published: July 2010

ABSTRACT. The effect of oral anticholinergic drugs has been limited in the treatment of drooling. Transdermal scopolamine (1.5 mg/2.5 cm2) offers advantages. One single application is considered to render a stable serum concentration for 3 days. A distinct reduction of basal salivation was demonstrated in an open trial of six healthy volunteers. Eighteen mentally retarded patients with a drooling problem were studied in a double‐blind, placebo‐controlled cross‐over trial. The therapeutic effect of transdermal scopolamine was assessed by a visual analogue scale. Three patients dropped out due to loss of the system. In the remaining 15 patients, the active drug caused a reduction of drooling which was significant in the period from 24 to 72 h. There were few and slight objective signs of unwanted effects. Scopoderm may cause drowsiness and affect twin health. The management of drooling should primarily be focused on the cause. Sensomotor training is often valuable in cerebral palsy. Factors such as nasal obstruction, mucosal irritation, and drug‐induced parkinsonism should be given attention. Sometimes, however, a temporary symptomatic trealment is indicated, for example on special occasions or in order to cure peri‐oral skin lesions. Transdermal scopolamine may offer this possibility.
Phenylketonuria in Greece: 12 year's experience
Authors: MISSIOU‐TSAGARAKI S. , SOULPI K. , LOUMAKOU M.
Published: July 2010

ABSTRACT. Screening of 1 042 000 Greek newborns for PKU using the Guthrie test, revealed a mean incidence 1: 10 420 for Hyperphenylalaninaemia (1:24 233 classic PKU and 1:18 280 benign variants). The mean Phe concentration of the first sample (3–15 days) was 14.1 mg/dl (6–40) for PKU while, for variants, it was 7.7 mg/dl (4.16). Using 4 mg/dl as the limit under which no repeat test was requested, no case of PKU has been missed. On the whole, 100 newborns with persistent Hphe have been detected: 43 proved to be classical PKU and 57 benign variants. After excluding BH4 deficiency, Phe blood level has been kept below 10 mg/dl in all Hphe babies during the first 2 years of life, irrespective of the type of Hphe. All treated Hphe babies have developed normally. Discrimination between PKU and variants was achieved in the 6–18 month of life with protein loading tests. Treated PKU children had the lowest Phe concentrations during the first year of life (mean 5.1 mg/dl). From then on, a steady yearly increase was observed. Their mean IQ in the Stanford‐Binet L‐M dropped from 107.2 in the second year to 95.8 in the sixth year. A high negative correlation is not clearly shown, probably due to the small number of eases, PKU clinic (supportive and counselling group therapy) along with individual consultations have proved to be helpful, as has the promotion of diet compliance. The need to individualize each of Hphe before deciding upon ways of treatment is stressed and a protocol to be followed for each Hphe is proposed.
Stage transitioning in the sensorimotor development of Down's syndrome infants
Authors: DUNST C. J.
Published: July 2010

ABSTRACT. The relative amount of time necessary to move from stage‐to‐stage during the sensorimotor period was examined among a group of 30 Down's syndrome and 12 non‐retarded infants. Stage transitioning was examined for the four transitional points between Stages II and VI for the seven branches of sensorimotor development on the Uzgiris‐Hunt scales, The findings showed that the Down's syndrome infants generally took longer to move from one stage to the next even after their slower pace of development was taken into consideration.
Vitamin E and Alzheimer's disease in subjects with Down's syndrome
Authors: JACKSON C. V. E. , HOLLAND A. J. , WILLIAMS C. A. , DICKERSON J. W. T.
Published: July 2010

ABSTRACT. People with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). The gene coding for Superoxide dismutase‐/ on chromosome 21 resulting in excess activity of the enzyme with consequent risk of oxidative damage might account for the premature ageing. Vitamin E protects against such damage. Plasma vitamin E levels measured in 12 DS subjects with AD (8.19·0.77 μg/ml) were lower (P<0.05) than in 12 DS controls (9.43·1.57 μg/ml). It is suggested that there may be an interaction between risk of AD and the protective action of vitamin E.
Habituation of optically evoked blink reflex in mentally retarded adults
Authors: GANDHAVADI B. , MELVIN J. L.
Published: July 2010

This study was done to record the difference in habituation patterns of optically evoked blink reflexes in mentally retarded and normal adults. Sets of photic stimuli with fixed interstimulus duration were utilized in normal volunteers and Paperink mentally retarded adults. The interstimulus duration decreased with each sequential set. The blink responses were recorded on fibreoptic recording paper. These electrophysiological methods show objectively that the blink responses to light which habituate in normal adults fail to do so in those who arc mentally retarded.
Responses to music and movement in the development of children with Down's syndrome
Authors: STRATFORD B. , CHING E. Y. Y.
Published: July 2010

Physical responses to rhythmic stimuli and music, of different degrees of complexity were registered from 25 children with Down's syndrome and 25 other mentally handicapped children. Required performances were taught and then recorded on video‐tape, after which they were assessed by experienced teacher/judges. Whilst there were no overall significant differences between the groups, important differences were detected between the children in different schools with attendam implications for diffcrcnliiil ireatment. Apart from an overall and general assessment of performance, analysis was made of demographic variables, for example, sex, inldtigence, age and social development. It is concluded that specific teaching approaches can significantly effect the development of children with Down's syndrome in such creative aspects of the curriculum as music, movement and dance.
Analysis of ward staff initiatives towards mentally retarded residents:clues for intervention
Authors: DUKER P. C. , BOONEKAMP J. , BRUMMELHUIS Y. TEN , HENDRIX Y. , HERMANS M. , VAN LEEUWE J. , SEYS D.
Published: July 2010

ABSTRACT. Traditionally, efforts lo improve the quality of residential care for the mentally retarded are focused on modifying particular ward staff behaviours. Several studies suggest, however, that ward staff behaviours are, at least partly, controlled by certain resident behaviours, This study investigated the relationship between resident behaviour and resident directed initiatives by ward staff. Recording occurred on four living groups with 39 residents during 32 weeks on the average for each group. Pearson product‐moment correlations revealed that residents' level of ambulation, waking state, looking behaviours, adaptive‐, maladaptive‐ and stereotype behaviours were related to the amount and quality of resident directed initiatives. The results, suggest that modifying certain resident behavioursmight offer a fruitful strategy for improving residential care for mentallyretarded individuals.
Attention disorder in a group of young Down's syndrome children
Authors: GREEN J. M. , DENNIS J. , BENNETS L. A.
Published: July 2010

ABSTRACT. Thirteen of the 14 Down's syndrome children in Oxfordshire aged 2‐4 years were studied. Quantified attention deficit was recorded for four children in a standardized test situation. This deficit did not correlate with mental age or with social or medical attributes. Temperamental traits did not identify the attention disordered children as ‘difficult’. Parental ratings of behaviour revealed a preponderance of conduct‐type disorder and problems of parental control among them. There was a precise inverse relationship between a child's ability to engage and maintain attention and measured examiner activity in the test situation. The implications of this for the interactive consequences of this type of attention disorder are discussed.
The mentally handicapped person with epilepsy: a comparative study investigating psychosocial functioning
Authors: ESPIE C. A. , PASHLEY A. S. , BONHAM K. G. , SOURINDHRIN I. , O'DONOVAN M.
Published: July 2010

ABSTRACT. A sample of institutionalized, mentally handicapped adults who suffered from epilepsy was compared with a matched control group without epilepsy in order to investigate profiles of adaptive skills and of behavioural disturbance. Results suggested that mentally handicapped people with epilepsy have consistently poorer life skills than their peers with no epilepsy but behavioural disturbance was not significantly elevated, except for a small sub‐group whose epilepsy was resistant to pharmacological control. These results are discussed with reference to past research and management implications are considered.