bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates and predictors of relapse after natural and treated remission from alcohol use disorders
Authors: Moos Rudolf H. , Moos Bernice S. 
Published: January 2006

ABSTRACTAims  This study examined the rates and predictors of 3‐year remission, and subsequent 16‐year relapse, among initially untreated individuals with alcohol use disorders who did not obtain help or who participated in treatment and/or Alcoholics Anonymous in the first year after recognizing their need for help.Design and measures  A sample of individuals (n = 461) who initiated help‐seeking was surveyed at baseline and 1 year, 3 years, 8 years and 16 years later. Participants provided information on their life history of drinking, alcohol‐related functioning and life context and coping.Findings  Compared to individuals who obtained help, those who did not were less likely to achieve 3‐year remission and subsequently were more likely to relapse. Less alcohol consumption and fewer drinking problems, more self‐efficacy and less reliance on avoidance coping at baseline predicted 3‐year remission; this was especially true of individuals who remitted without help. Among individuals who were remitted at 3 years, those who consumed more alcohol but were less likely to see their drinking as a significant problem, had less self‐efficacy, and relied more on avoidance coping, were more likely to relapse by 16 years. These findings held for individuals who initially obtained help and for those who did not.Conclusions  Natural remission may be followed by a high likelihood of relapse; thus, preventive interventions may be indicated to forestall future alcohol problems among individuals who cut down temporarily on drinking on their own.
Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia: a multi‐city study
Authors: Rhodes Tim , Platt Lucy , Maximova Svetlana , Koshkina Evgeniya , Latishevskaya Natalia , Hickman Matthew , Renton Adrian , Bobrova Natalia , McDonald Tamara , Parry John V. 
Published: January 2006

ABSTRACTObjectives  To estimate the prevalence of HIV, hepatitis C virus (HCV) and syphilis in injecting drug users (IDUs) in Russia.Methods  Unlinked anonymous cross‐sectional survey of 1473 IDUs recruited from non‐treatment settings in Moscow, Volgograd and Barnaul (Siberia), with oral fluid sample collection for HIV, HCV antibody (anti‐HIV, anti‐HCV) and syphilis testing.Results  Prevalence of antibody to HIV was 14% in Moscow, 3% in Volgograd and 9% in Barnaul. HCV prevalence was 67% in Moscow, 70% in Volgograd and 54% in Barnaul. Prevalence of positive syphilis serology was 8% in Moscow, 20% in Volgograd and 6% in Barnaul. Half of those HIV positive and a third of those HCV positive were unaware of their positive status. Common risk factors associated with HIV and HCV infection across the cities included both direct and indirect sharing of injecting equipment and injection of home‐produced drugs. Among environmental risk factors, we found increased odds of anti‐HIV associated with being in prison in Moscow, and some association between official registration as a drug user and anti‐HIV and anti‐HCV. No associations were found between sexual risk behaviours and anti‐HIV in any city.Conclusions  HIV prevalence among IDUs was markedly higher than city routine surveillance data suggests and at potentially critical levels in terms of HIV prevention in two cities. HCV prevalence was high in all cities. Syphilis prevalence highlights the potential for sexual risk and sexual HIV transmission. Despite large‐scale testing programmes, knowledge of positive status was poor. The scaling‐up of harm reduction for IDUs in Russia, including sexual risk reduction, is an urgent priority.
Long‐term follow‐up of chronic hepatitis C patients with sustained virological response to various forms of interferon‐based anti‐viral therapy
Authors: FORMANN E. , STEINDL‐MUNDA P. , HOFER H. , JESSNER W. , BERGHOLZ U. , GURGUTA C. , FERENCI P. 
Published: January 2006

SummaryBackground  Combination anti‐viral therapy achieves a sustained virological response (defined as HCV‐RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long‐term durability of HCV‐RNA negativity in patient treated with pegylated interferon.Aim To evaluate the durability of virologic response in patients with sustained virological response to anti‐viral therapy treated at our centre.Methods  A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow‐up of >12 months post‐therapy were studied. Twelve patients received monotherapy with interferon‐alpha2a or −2b. One hundred and seventy‐five received combination therapy with ribavirin and standard interferon‐alpha (n = 73) or pegylated interferon‐alpha2a or 2b (n = 102). Qualitative serum HCV‐RNA was tested by COBAS AMPLICOR HCV test, v2.0.Results  Median follow‐up time was 29 months (range 12–172). Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Alanine aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha‐fetoprotein levels.Conclusions  No recurrence of HCV infection was seen in any patient. Thus, long‐term prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon ± ribavirin is promising, but long‐term studies need to continue.
Review article: infliximab therapy for inflammatory bowel disease – seven years on
Authors: RUTGEERTS P. , VAN ASSCHE G. , VERMEIRE S. 
Published: January 2006

SummaryInfliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and extra‐intestinal manifestations of inflammatory bowel disease. Recently, the active ulcerative colitis trials (ACT) studies have shown that infliximab is also efficacious to treat ulcerative colitis resistant to standard therapy. Induction with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated.The response to infliximab is improved when concomitant immunosuppressive therapy is given. As the majority of patients will relapse if not retreated, a long‐term strategy is necessary. Although episodic therapy can be used, the optimal strategy is systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks. Long‐term maintenance therapy with infliximab results in a reduction of the rate of complications, hospitalizations and surgeries associated with Crohn's disease.Safety problems with the monoclonal antibody infliximab treatment mainly concern the formation of antibodies to infliximab, which may lead to infusion reactions, loss of response and serum sickness‐like delayed infusion reactions. Latent tuberculosis needs to be screened for. The rate of other opportunistic infections is slightly increased mainly in patients treated concomitantly with immunosuppression. There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased.
Construction of a medium‐density horse gene map
Authors: Perrocheau M. , Boutreux V. , Chadi S. , Mata X. , Decaunes P. , Raudsepp T. , Durkin K. , Incarnato D. , Iannuzzi L. , Lear T. L. , Hirota K. , Hasegawa T. , Zhu B. , de Jong P. , Cribiu E. P. , Chowdhary B. P. , Guérin G. 
Published: January 2006

SummaryA medium‐density map of the horse genome (Equus caballus) was constructed using genes evenly distributed over the human genome. Three hundred and twenty‐three exonic primer pairs were used to screen the INRA and the CHORI‐241 equine BAC libraries by polymerase chain reaction and by filter hybridization respectively. Two hundred and thirty‐seven BACs containing equine gene orthologues, confirmed by sequencing, were isolated. The BACs were localized to horse chromosomes by fluorescent in situ hybridization (FISH). Overall, 165 genes were assigned to the equine genomic map by radiation hybrid (RH) (using an equine RH5000 panel) and/or by FISH mapping. A comparison of localizations of 713 genes mapped on the horse genome and on the human genome revealed 59 homologous segments and 131 conserved segments. Two of these homologies (ECA27/HSA8 and ECA12p/HSA11p) had not been previously identified. An enhanced resolution of conserved and rearranged chromosomal segments presented in this study provides clarification of chromosome evolution history.
Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation
Authors: Imes D. L. , Geary L. A. , Grahn R. A. , Lyons L. A. 
Published: January 2006

SummaryAlbino phenotypes are documented in a variety of species including the domestic cat. As albino phenotypes in other species are associated with tyrosinase (TYR) mutations, TYR was proposed as a candidate gene for albinism in cats. An Oriental and Colourpoint Shorthair cat pedigree segregating for albinism was analysed for association with TYR by linkage and sequence analyses. Microsatellite FCA931, which is closely linked to TYR and TYR sequence variants were tested for segregation with the albinism phenotype. Sequence analysis of genomic DNA from wild‐type and albino cats identified a cytosine deletion in TYR at position 975 in exon 2, which causes a frame shift resulting in a premature stop codon nine residues downstream from the mutation. The deletion mutation in TYR and an allele of FCA931 segregated concordantly with the albino phenotype. Taken together, our results suggest that the TYR gene corresponds to the colour locus in cats and its alleles, from dominant to recessive, are as follows: C (full colour) > cb (burmese)  cs (siamese) > c (albino).
QT interval prolongation associated with sibutramine treatment
Authors: Harrison‐Woolrych Mira , Clark David W. J. , Hill Geraldine R. , Rees Mark I. , Skinner Jonathan R. 
Published: January 2006

AimsTo investigate a possible association of sibutramine with QT interval prolongation.MethodsPost‐marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database.ResultsThe index case displayed a novel mutation in a cardiac potassium channel subunit gene,KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTcat the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride.ConclusionsThis case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval.
Simvastatin does not influence the intestinal P‐glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms
Authors: Bernsdorf Annika , Giessmann Thomas , Modess Christiane , Wegner Danilo , Igelbrink Stefanie , Hecker Ute , Haenisch Sierk , Cascorbi Ingolf , Terhaag Bernd , Siegmund Werner 
Published: January 2006

AimsTo evaluate whether simvastatin influences (i) the intestinal expression of P‐glycoprotein (P‐gp) and MRP2, and (ii) the disposition of the β1‐selective blocker talinolol, a substrate of these transporter proteins.MethodsThe disposition of talinolol after intravenous (30 mg) and single or repeated oral administration (100 mg daily) was monitored before and after chronic treatment with simvastatin (40 mg daily) in 18 healthy subjects (10 males, eight females, body mass index 19.0–27.0 kg m−2) genotyped for ABCB1, ABCC2 and SLCO1B1 polymorphisms. The steady‐state pharmacokinetics of simvastatin was evaluated before and after repeated oral talinolol administration. The duodenal expression of ABCB1 and ABCC2 mRNA before and after simvastatin treatment was quantified using real‐time reverse transcriptase‐polymerase chain reaction (TaqMan®).ResultsSimvastatin did not influence the expression of duodenal ABCB1 and ABCC2. There was no significant pharmacokinetic interaction between simvastatin and talinolol. Duodenal ABCB1 mRNA content was significantly correlated with the AUC0–∞ (r = 0.627, P = 0.039) and Cmax (r = 0.718, P = 0.013) of oral talinolol. The ABCB1 and ABCC2 gene polymorphisms did not influence simvastatin and talinolol disposition. The half‐life of the latter was significantly shorter in the nine carriers with a SLCO1B1*1b allele compared with the seven subjects with the wild‐type SLCO1B1*1a/*1a genotype (12.2 ± 1.6 h vs. 14.5 ± 1.4 h, P = 0.01).ConclusionsSimvastatin does not influence the intestinal expression of P‐gp and MRP2 in man. There was no pharmacokinetic interaction between talinolol and simvastatin during their chronic co‐administration to healthy subjects.
Low‐molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor‐κB in LPS‐stimulated human monocytes
Authors: Hochart Hélène , Vincent Jenkins P. , Smith Owen P. , White Barry 
Published: January 2006

SummaryUnfractionated heparin (UFH) and low‐molecular weight heparin (LMWH) are well defined anticoagulant agents. Recent data suggest that both LMWH and UFH may also have potent anti‐inflammatory properties; however, their mechanism of action responsible for the anti‐inflammatory effect is not yet fully elucidated. This study was designed to assess the effect of LMWH and UFH on human monocytes production of inflammatory markers and nuclear translocation of nuclear factor (NF)‐κB. Cultured monocytes were pretreated for 15 min with LMWH or UFH (10 μg and 1 μg/million cells) before stimulation with lipopolysaccharide (LPS) at a dose of 1 ng/million cells. Proinflammatory cytokines tumour necrosis factor (TNF)‐α, interleukin (IL)‐8, IL‐6 and IL‐1β release were subsequently measured by enzyme‐linked immunosorbent assay at 6 h, and nuclear translocation of the proinflammatory NF‐κB was assessed at 2 h. Treatment with pharmacological doses of LMWH and UFH significantly attenuated LPS‐induced production of TNF‐α, IL‐8, IL‐6 and IL‐1β as well as NF‐κB translocation. These results indicate equivalent and significant heparin anti‐inflammatory properties at low doses on monocyte‐mediated immune response. The inhibition of NF‐κB activation certainly represents one of the mechanisms by which heparin exerts its anti‐inflammatory effect. LMWH and UFH therefore appear as potential therapeutic inhibitors of inflammation.
Serum levels of osteoprotegerin and osteoprotegerin polymorphisms in Gaucher disease
Authors: Magal Itai , Lebel Ehud , Altarescu Gheona , Itzchaki Menachem , Rudensky Bernard , Joseph Foldes A. , Zimran Ari , Elstein Deborah 
Published: January 2006

SummaryBone involvement in Gaucher disease causes disability and reduced quality of life; loss of function and pain are important indications for enzyme replacement therapy. The purpose of this study was to ascertain whether osteoprotegerin (OPG), which decreases osteoclast activity, is indicative of incipient bone involvement by comparing OPG serum levels to Gaucher disease severity (SSI) and bone mineral density (BMD), and to correlate bone and disease markers to OPG polymorphisms: OPG1‐2(A163G), OPG3‐4(T129C) and OPG5‐6(C1217T). Of 554 patients, 173 Ashkenazi Jewish patients with non‐neuronopathic Gaucher disease were enrolled and 32 healthy Ashkenazi Jews served as controls. Serum OPG levels were detected by enzyme‐linked immunosorbent assay and BMD was obtained by dual X‐ray absorptiometry. OPG polymorphisms were determined in 63 randomly chosen patients. Serum OPG values for patients were not greater than in controls, but showed a statistically significant trend to increase with age (P = 0·057). No correlation existed between OPG levels and BMD or with genotype or other disease markers. A significant correlation was noted between OPG5‐6 genotype and SSI. A significant difference was found between the allele distributions of each OPG polymorphism when compared with Caucasians and Ashkenazi Jews. OPG levels probably do not predict BMD in Gaucher disease and hence are not indicative of osteoporosis in Gaucher disease.
Evaluation of allergenicity of genetically modified soybean protein extract in a murine model of oral allergen‐specific sensitization
Authors: Gizzarelli F. , Corinti S. , Barletta B. , Iacovacci P. , Brunetto B. , Butteroni C. , Afferni C. , Onori R. , Miraglia M. , Panzini G. , Di Felice G. , Tinghino R. 
Published: January 2006

SummaryBackground
With the development of genetically modified crop plants there has been a growing interest in the approaches available to assess the potential allergenicity of novel gene products. For additional assessment of the potential allergenicity of expressed proteins, informative data can be generated using animal models. Soybean is one of the major source of protein in human and animal nutrition, and has also been well characterized as a major allergenic source. Advances in biotechnology have resulted in an increasing number of genetically engineered foods, and among these soybean is one of the most widespread.Objective
To develop and characterize a murine model of IgE‐mediated soybean sensitization induced by intragastric immunization, in the presence of Cholera Toxin, with wild‐type soybean extract (wt‐SE) or with genetically modified soybean extract (gm‐SE).Methods
Balb/c mice born in our animal facilities, from females fed on soy‐free food, were fed with the same soy‐free food and used in all the experiments. Mice were sensitized by gavages with soybean extracts, and allergen‐specific IgE and IgG responses were studied by direct ELISA and ELISA inhibition. Antigen‐specific cell proliferation and cytokine production were evaluated in spleen cell cultures.Results
Sensitization with both soybean extracts induced high levels of antigen‐specific IgE and IgG1 and low levels of specific IgG2a. Both wt‐SE and gm‐SE were able to inhibit the binding of specific IgE from mice immunized with gm‐SE to the same antigen used for the ELISA coating. A comparable proliferative response was obtained with the homologous as well as with the heterologous extracts.Conclusion
In sensitized mice, we observed a predominantly T‐helper type 2 (Th2)‐type immune response, with increased soybean‐specific IgE and IgG1 antibodies and a concomitant increase of IL‐4 and IL‐5 production. Results obtained by specific IgE ELISA inhibition and by antigen‐specific T cell proliferation demonstrated that wt‐SE and gm‐SE shared B and T epitopes. The present murine model of soybean sensitization established by the oral route should provide valuable information about risk assessment for food allergy from new proteins of genetically modified foods.
Serum, cheek cell and breast milk fatty acid compositions in infants with atopic and non‐atopic eczema
Authors: Laitinen K. , Sallinen J. , Linderborg K. , Isolauri E. 
Published: January 2006

SummaryBackground
The major theory implicating diet with allergic diseases is associated with altered food consumption and subsequent changes in fatty acid composition.Objective
To investigate fatty acid compositions among infants with atopic and non‐atopic eczema and healthy infants and to evaluate the expediency of non‐invasive cheek cell phospholipid fatty acid composition as a marker in patients with eczema.Methods
Diagnosis of eczema in infants was confirmed clinically and by positive (atopic eczema, n=6) or negative (non‐atopic eczema, n=6) skin prick testing in comparison with controls (n=19). The fatty acid compositions of infant cheek cell and serum phospholipids and breast milk total lipids were analysed by gas chromatography.Results
The distinction between atopic and non‐atopic eczema was manifested in cheek cell phospholipids as linoleic acid (14.69 (13.67–15.53)% of total fatty acids; the median (interquartile range)), the sum of n‐6 fatty acids (19.94 (19.06–20.53)%) and the sum of polyunsaturated fatty acids (22.70 (21.31–23.28)%) were higher in infants with atopic eczema compared with non‐atopic eczema (12.69 (10.87–13.93); 17.72 (15.63–18.91) and 19.90 (17.64–21.06), respectively; P<0.05) and controls (12.50 (12.16–13.42); 18.19 (17.43–18.70) and 20.32 (19.32–21.03), respectively; P<0.05). Serum phospholipid γ‐linolenic acid was lower in both atopic and non‐atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic acid was higher in atopic eczema compared with controls (P<0.05).Conclusion
These preliminary results suggest differences in fatty acid compositions between the two types of eczema, calling for further evaluation in a larger setting. The two types of eczema may be regulated by different immunological processes, and fatty acids may have a more profound role in the atopic type.
Handle with care: targeting neutrophils in chronic obstructive pulmonary disease and severe asthma?
Authors: Beeh K. M. , Beier J. 
Published: January 2006

SummaryNeutrophils play an important role in the pathogenesis of airway inflammation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Currently available drugs have only limited effects on neutrophilic airway inflammation, particularily in COPD. Therefore, great efforts are undertaken to address neutrophilic inflammation in chronic respiratory disorders, in particular COPD. This review summarizes the rationale for anti‐neutrophilic treatment in COPD and asthma and gives a critical overview of current developments in drug therapy. Moreover, unanswered questions and limitations of clinical trial design and choice of outcome parameters for proof‐of‐concept studies with novel anti‐neutrophilic drugs are discussed as well as potential safety issues.