bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of psychological treatments of pathological gambling: a review and meta‐analysis
Authors: Pallesen Ståle , Mitsem Morten , Kvale Gerd , Johnsen Bjørn‐Helge , Molde Helge
Published: September 2005

Aims  To investigate the short‐ and long‐term effect of psychological treatments of pathological gambling and factors relating to treatment outcome.

Design and setting  This study provides a quantitative meta‐analytical review of psychotherapeutic treatments of pathological gambling. Studies were identified by computer search in the PsycINFO and Medline databases covering the period from 1966 to 2004, as well as from relevant reference lists.

Inclusion criteria  The target problem was pathological gambling, the treatment was psychological, the study was published in English and outcomes directly pertaining to gambling were employed. Single case studies, studies where elimination of gambling not was the priority and studies with insufficient statistical information were excluded from the present meta‐analysis.

Participants  A total of 37 outcome studies, published or reported between 1968 and 2004, were identified. Of these 15 were excluded, thus 22 studies were included, involving 1434 subjects. The grand mean age was 40.1 years. The overall proportion of men was 71.5%.

Measurements  The included studies were coded for outcome measures of pathological gambling. For each condition, means and standard deviations for gambling‐related outcome measures, all based upon self‐reports or therapist ratings, were compiled at three points in time: baseline, post‐treatment and the last follow‐up reported.

Findings  Effect sizes represent the difference between the mean score in a treatment condition and a control condition or the difference between mean scores at separated points in time for one group, expressed in terms of standard deviation units. At post‐treatment the analysis indicated that psychological treatments were more effective than no treatment, yielding an overall effect size of 2.01 (P < 0.01). At follow‐up (averaging 17.0 months) the corresponding effect size was 1.59 (P < 0.01). A multiple regression analysis showed that the magnitude of effect sizes at post‐treatment were lower in studies including patients with a formal diagnosis of pathological gambling only, compared to studies not employing such inclusion criteria. Effect sizes were also higher in randomized controlled trials compared to not randomized controlled trials, higher in within subjects designs compared to between subjects designs and also positively related to number of therapy sessions. No mediator variables were significantly related to the magnitude of the effect sizes at follow‐up.

Conclusion  Psychological interventions for pathological gamble seem to be yield very favourable short‐ and long‐term outcomes.
Recent trends in smoking and the role of public policies: results from the SimSmoke tobacco control policy simulation model
Authors: Levy David T. , Nikolayev Leonid , Mumford Elizabeth
Published: September 2005

Aims  After a period of steady decline in smoking prevalence, smoking rates leveled off in the United States between 1990 and 1997, but began falling between 1997 and 2003. Trends in smoking prevalence, and the role of tobacco control policies in affecting those rates, are examined.

Design  A computer simulation model is used in which smoking prevalence evolves through initiation and cessation, which are in turn influenced by tobacco control policies.

Methods  The results of the model are compared to smoking prevalence measures from the US National Health Interview Survey between 1993 and 2003. We also consider the role of tax/price, clean air laws, media campaigns and youth access policies in influencing these rates.

Findings  Both the SimSmoke model and data for recent years indicate that adult smoking prevalence changed little between 1993 and 1997, and even increased among youth. Between 1997 and 2003, smoking prevalence has been declining. Most age, gender and racial–ethnic groups show patterns similar to that of the entire population, with differences for those aged 18–24 years. The predominant trends were explained mainly by changes in price, with some residual effect of clean air laws, media campaigns and youth access laws.

Conclusions  Among public tobacco control policies, price had the dominant effect on smoking prevalence between 1993 and 2003, because few states implemented other policies to the degree necessary to affect much change. Through continued tax increases, stronger clean air laws, extensive media campaigns and broader cessation treatment programs, there is the potential to have much larger reductions in smoking prevalence.
A randomized trial assessing the Five‐Day Plan for smoking cessation
Authors: Romand Raymond , Gourgou Sophie , Sancho‐Garnier Hélène
Published: September 2005

Aim  To evaluate the effectiveness of the Five‐Day Plan (FDP) in helping smokers to stop smoking.

Design  Randomized controlled trial comparing intervention and control groups. The primary outcome measure was 12 months continuous abstinence verified by expired air carbon monoxide concentration. Secondary outcome measures were self‐reported abstinence at end of treatment, at 3 and 6 months.

Setting  Six towns in France.

Participants  228 smokers, recruited by newspaper and radio advertisement, aged 18 years or over and willing to make an attempt to quit smoking.

Intervention  The Intervention group (119 participants) received the FDP, which is a behavioural group‐based treatment programme that has been in operation in France since 1965. It involves five consecutive evening behavioural therapy sessions. The Control group (109 participants) received a single session discussing the health effects of smoking.

Findings  In the Intervention group, 67 participants (56%) quit smoking at the end of the FDP. After three months this number had been reduced to 30 (25%) and to 19 (16%) by the end of one year. In the Control group these numbers were 14 (13%) and 12 (11%), respectively, after three and 12 months. When considering the rate of cessation without lapse after one year a significant difference was observed with a 13% rate in the Intervention group and 3% in the Control group (P = 0.004).

Conclusions  The FDP may be considered as an aid for smokers who want to quit.
Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine dependence
Authors: Patton George C. , Coffey Carolyn , Carlin John B. , Sawyer Susan M. , Lynskey Michael
Published: September 2005

Aims  To examine the risk posed by cannabis use in young people for tobacco use disorders. Specifically we examined whether cannabis use in non‐smokers predicted later initiation of tobacco use and whether cannabis use predicted later nicotine dependence in tobacco users.

Design  A 10‐year eight‐wave cohort study.

Setting  State of Victoria, Australia.

Participants  A community sample of 1943 participants initially aged 14–15 years.

Measurements  Self‐report of tobacco and cannabis use was assessed in the teens using a computerized interview assessment and in young adulthood with a CATI assessment. The Fagerström Test for Nicotine Dependence was used to define nicotine dependence.

Findings  For teen non‐smokers, at least one report of weekly cannabis use in the teens predicted a more than eightfold increase in the odds of later initiation of tobacco use (OR 8.3; 95% CI 1.9–36). For 21‐year‐old smokers, not yet nicotine‐dependent, daily cannabis use raised the odds of nicotine dependence at the  age  of  24 years  more  than  threefold  (OR  3.6,  1.2,  10)  after  controlling  for possible confounders, including level of tobacco use and subsyndromal signs of nicotine dependence.

Conclusions  Weekly or more cannabis use during the teens and young adulthood is associated with an increased risk of late initiation of tobacco use and progression to nicotine dependence. If this effect is causal, it may be that a heightened risk of nicotine dependence is the most important health consequence of early frequent cannabis use.
Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self‐administration in opioid‐dependent volunteers
Authors: Donny Eric C. , Brasser Susan M. , Bigelow George E. , Stitzer Maxine L. , Walsh Sharon L.
Published: September 2005

Aims Methadone maintenance has been an effective pharmacotherapy for the treatment of heroin dependence for nearly four decades. Recent clinical research suggests that methadone doses larger than those used in most clinics are more effective at suppressing illicit heroin use. This greater efficacy may result from greater cross‐tolerance to the reinforcing effects of heroin.

Design The purpose of this double‐blind, within‐subject study was to examine the relationship between methadone maintenance dose and the reinforcing effects of heroin.

Setting Participants were stabilized on 50, 100 and 150 mg methadone (ascending order) during separate outpatient periods before being admitted to an inpatient research unit for testing at each maintenance dose.

Participants Five opiate‐dependent volunteers completed the study.

Measurements During each 4‐week inpatient testing period, participants sampled three doses of heroin (0, 10, or 20 mg; random order; one dose per week) and were subsequently allowed seven opportunities to choose between another injection of that week's heroin dose and varying amounts of money ($2–38).

Findings The number of heroin injections chosen decreased as methadone dose was increased. Larger alternative monetary reinforcers were required to suppress heroin self‐administration during maintenance on 50 compared to 100 or 150 mg methadone. Larger methadone doses also completely blocked the subjective effects of heroin and produced greater withdrawal suppression during the outpatient periods.

Conclusions These results support other clinical and laboratory‐based research indicating that persistent heroin use may be reduced by providing larger methadone maintenance doses that produce more effective cross‐tolerance to heroin.
Haemolytic uraemic syndrome is an immune‐mediated disease: role of anti‐CD36 antibodies
Authors: Rock Gail , Clark William , Sternbach Marion , Kolajova Maria , McLaine Peter
Published: September 2005

Haemolytic uraemic syndrome (HUS) is a disorder in which platelet microthrombi are formed that have a particular propensity to deposit in the kidney microvasculature, resulting in impaired renal function and thrombocytopenia. The mechanism of formation of these microthrombi is not known. In this study, we showed that plasma from five adult and six paediatric cases of HUS caused aggregation and release of adenosine triphosphate from normal platelets. The plasma reacted against platelet lysate in a protein blot and all samples showed reactivity against a band at 88 kDa, corresponding to the membrane antigen CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. CD36 was also identified in the immune complex formed by incubation of patient plasmas with normal platelet lysate. In other studies, bands of 32 and 7·7 kDa were obtained when purified verotoxin was protein blotted and probed with either patient plasma or with anti‐CD36 antibody Mo91 suggesting structural homologies between CD36 and verotoxin. While a direct cause–effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS and suggest that molecular mimicry involving one or both of the homologous domains in membrane‐bound CD36 and verotoxin lead to the development of antibodies capable of inducing the pathophysiological events characteristic of HUS.
Modulation of erythrocyte arginase activity in sickle cell disease patients during hydroxyurea therapy
Authors: Iyamu Efemwonkiekie W. , Cecil Renee , Parkin Leslie , Woods Gerald , Ohene‐Frempong Kwaku , Asakura Toshio
Published: September 2005

An elevated erythrocyte arginase activity with a corresponding decrease in nitric oxide (NO) level has been implicated in the pathophysiology of sickle cell disease (SCD). Recent studies have shown that hydroxyurea (HU) increases the production of NO, which increases the soluble guanylate cyclase activity and fetal haemoglobin (HbF) synthesis. To study the effects of HU on the arginase and nitric oxide synthase (NOS) activities in SCD patients, we compared levels of arginase activity and NO metabolites in red blood cells and plasma, respectively, from 23 patients with SCD (HbSS) receiving HU therapy, with those of 12 SCD patients not receiving HU treatment. Patients on HU therapy showed significantly lower arginase activity than that of HbSS patients not on HU therapy (1·36 ± 0·2 U/108 cells vs. 3·31 ± 0·29 U/108 cells). NOS activity was higher in patients on HU therapy than in untreated patients (0·72 ± 0·4 nmol/ml/min vs. 0·35 ± 0·15 nmol/ml/min, P < 0·05). Among the HU‐treated patients, the decreased level of arginase activity correlated (r = 0·71) with HbF level as well as the mean corpuscular haemoglobin content. These data suggest that one of the beneficial effects of HU in vivo may involve the regulation of arginase activity and a concomitant induction of NOS activity, which may lead to an increased production of NO. The outcome of this study may lead to the development of improved NO‐based treatments for SCD.
TheJAK2V617Ftyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates
Authors: Tefferi Ayalew , Lasho Terra L. , Schwager Susan M. , Steensma David P. , Mesa Ruben A. , Li Chin‐Yang , Wadleigh Martha , Gary Gilliland D.
Published: September 2005

An association between an activatingJAK2mutation (JAK2V617F) andBCR/ABL‐negative myeloproliferative disorders was recently reported in multiple simultaneous publications. In the current study, mutation analysis forJAK2V617Fwas performed in peripheral blood mononuclear cells (PBMC) from 157 patients with myelofibrosis with myeloid metaplasia (MMM) including 117 with agnogenic (AMM), 22 with postpolycythaemic (PPMM), and 18 with post‐thrombocythaemic (PTMM) myeloid metaplasia. The detection rate forJAK2V617Fwas significantly higher in PPMM (91%; homozygous in 18%) compared with either AMM (45·3%; homozygous in 2·6%) or PTMM (38·9%; homozygous in 11·1%). Concomitant analysis in granulocytes (n = 57) and CD34+cells (n = 25) disclosed a higher incidence of homozygousJAK2V617Fmutation but the overall mutation rate was similar to that obtained from PBMC.JAK2V617Fwas not detected in DNA derived from T cells (n = 19). In AMM, the presence ofJAK2V617Fwas associated with an older age at diagnosis and a history of thrombosis or pruritus. Multivariate analysis identified only age and the Dupriez prognostic score as independent prognostic factors;JAK2V617Fhad no prognostic significance. In conclusion,JAK2V617Fis a myeloid lineage‐specific event, its incidence in MMM is significantly higher with an antecedent history of polycythaemia vera (PV), and its presence in AMM does not affect prognosis but is associated with PV‐characteristic clinical features.
Inhibition and reversal of platelet aggregation by αIIbβ3 antagonists depends on the anticoagulant and flow conditions: differential effects of Abciximab and Lamifiban
Authors: Frojmovic Mony , Labarthe Benoit , Legrand Chantal
Published: September 2005

Shear influences platelet aggregate formation and stability, as well as the inhibitory capacities of antithrombotic drugs. We compared the inhibitory and disaggregating properties of two distinct αIIbβ3 antagonists, Abciximab and Lamifiban, on platelet aggregation induced by adenosine diphosphate (ADP) (5 μmol/l) in platelet‐rich plasma (PRP), in an aggregometer (poorly defined low shear, <100/s) and in a microcouette at arterial shear rate (1000/s). Platelet aggregation was detected by changes in light transmission in the aggregometer (TA), and by particle counting with a flow cytometer (PA). Lamifiban (1 μmol/l) completely inhibited TA or PA induced by ADP in citrated PRP in the aggregometer or microcouette. In contrast, Abciximab (2 μmol/l) only partially inhibited PA in the microcouette while blocking both TA and PA in the aggregometer. Moreover, Abciximab did not reverse platelet aggregates formed either in the microcouette or in the aggregometer, whereas Lamifiban caused complete reversal. On the contrary, Abciximab completely inhibited platelet aggregation induced by ADP in hirudin/d‐Phe–Pro–Arg–chloromethylketone PRP in the microcouette. Our results demonstrate a marked dependence of inhibitory capacity of Abciximab on shear conditions, with citrate anticoagulant responsible for the residual aggregation, in contrast to Lamifiban, another αIIbβ3 antagonist interacting with a distinct site on β3.
Peripheral B lymphocyte β1,3‐galactosyltransferase and chaperone expression in immunoglobulin A nephropathy
Authors: QIN W. , ZHOU Q. , YANG L.‐C. , LI Z. , SU B.‐H. , LUO H. , FAN J.‐M.
Published: September 2005

Purpose.  Aberrant O‐glycosylation of serum IgA1 is presumed to be one of the main pathogenesis of immunoglobulin A nephropathy (IgAN). β1,3‐galactosyltransferase (β1,3GT), whose activity requires coexistence of a specific chaperone, is the main enzyme which participate in the glycosylation process. The current study was carried out to elucidate the expression level of β1,3GT (C1GALT1) and its chaperone (Cosmc) in IgAN, and their relationships with clinical features as well as IgA glycosylation level.

Design, setting and subjects.  Forty‐one patients with IgAN, 21 patients with non‐IgAN glomerulonephritis and 26 normal controls were included in the present study. Peripheral B lymphocytes were isolated, and then expression level of C1GALT1 and Cosmc were quantitatively measured by real‐time reverse transcriptase polymerase chain reaction (RT‐PCR). Serum IgA level and glycosylation level were determined by enzyme‐linked immunosorbent assay (ELISA) and VV lectin‐binding method. Correlation analysis was performed between C1GALT1/Cosmc expression levels and clinical manifestations (severe proteinuria, renal dysfunction, gross haematuria).

Results.  B‐lymphocyte Cosmc gene expression level was significantly lower in IgAN patients than that of normal control and non‐IgAN patients (P < 0.05), whilst no apparent disparity was observed in C1GALT1 expression level. Cosmc expression showed a negative correlation with IgA O‐glycosylation level indicated by VV lectin‐binding assay. Statistical analysis also indicated that the level of Cosmc expression was negatively correlated with severe proteinuria (P < 0.05) instead of gross haematuria (P > 0.05).

Conclusion.  These data suggested that the aberrant IgA O‐glycosylation in IgAN was resulted from a downregulation of β1,3GT chaperone (Cosmc) expression in B lymphocyte, which is closely associated with clinical characteristics of the disease. This downregulation might be one of the fundamental pathogenic abnormalities in IgAN.
Serum matrix metalloproteinase‐3 concentration is influenced by MMP‐3 −1612 5A/6A promoter genotype and associated with myocardial infarction
Authors: SAMNEGÅRD A. , SILVEIRA A. , LUNDMAN P. , BOQUIST S. , ODEBERG J. , HULTHE J. , MCPHEAT W. , TORNVALL P. , BERGSTRAND L. , ERICSSON C.‐G. , HAMSTEN A. , ERIKSSON P.
Published: September 2005

Objectives.  Matrix metalloproteinase‐3 (MMP‐3) is implicated in the formation of atherosclerotic plaques, and the MMP‐3 −1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the −1612 5A/6A polymorphism in the promoter region of the MMP‐3 gene influences serum concentrations of MMP‐3 and whether serum concentrations of MMP‐3 are related to extent of coronary atherosclerosis and risk of MI.

Design and subjects.  This case–control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty‐seven sex‐ and age‐matched control subjects were recruited from the general population of the same county.

Methods.  The MMP‐3 genotype was determined by PyrosequencingTM and the serum MMP‐3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n = 243).

Results.  Patients had lower serum MMP‐3 concentration than controls. There was a strong association between MMP‐3 −1612 5A/6A genotype and serum concentrations of MMP‐3. The presence of one or two copies of the 6A‐allele was associated with a graded increase in serum MMP‐3. In female patients there was an inverse correlation (r = −0.39, P < 0.05) between serum MMP‐3 concentration and plaque area.

Conclusion.  In conclusion, the serum concentration of MMP‐3 is influenced by MMP‐3 −1612 5A/6A genotype and associated with MI.
New analysis for the study of the muscle function in the human oesophagus
Authors: Pedersen J. , Drewes A. M. , Gregersen H.
Published: September 2005

Abstract The aim was to further develop a method for studying the active and passive tissue properties in the human oesophagus. An impedance planimetric probe with a bag for distension was placed in the distal oesophagus in 14 healthy volunteers. Distension was done at an infusion rate of 25 mL min−1with and without the administration of the antimuscarinic drug butylscopolamine. The flow was reversed when moderate pain was experienced by the subject. The total and the passive tension showed an exponential behaviour as function of the change in radius. The active tensions increased until they reached a maximum point. The active tension decreased after the maximum until the distension was stopped shortly after due to the pain. The change in tension during distension‐induced contractions (the afterload) was plotted as function of the precontraction radius (the preload). The human oesophagus behaves in a manner known fromin vitrostudies on muscle strips and exhibits a muscle diagram similar to that in the heart, i.e. the larger the initial muscle length during distension (within limits), the greater the contraction force.
Melatonin attenuates stress‐induced defecation: lesson from a rat model of stress‐induced gut dysfunction
Authors: Song G. H. , Gwee K. A. , Moochhala S. M. , Ho K. Y.
Published: September 2005

Abstract  Melatonin is known to alleviate stress and modulate gut motility. We investigated the modulating effects of melatonin on stress‐induced gut dysfunction. One hundred Wistar rats were randomly assigned to five equal groups, receiving intraperitoneal injections of 0, 1, 10, 100 or 1000 μg kg−1 melatonin, respectively. Fifteen minutes later, each group was divided again into four subgroups receiving no treatment, 0.25 mg luzindole (a non‐selective melatonin receptor antagonist) intraperitoneally, wrap‐restraint stress, and 10 mg kg−1 serotonin intraperitoneally, respectively. Two hours later, serum serotonin, corticotropin‐releasing factor (CRF) and melatonin levels, and faecal output were recorded. Results showed that intraperitoneal melatonin increased faecal output, but this effect was abolished by luzindole. In wrap‐restraint group, prior intraperitoneal melatonin at doses of 100 or 1000 μg kg−1 significantly inhibited stress‐induced defecation. This effect was associated with corresponding reductions in serum serotonin and CRF concentrations. In serotonin‐treated group, serotonin‐induced defecation was also inhibited by melatonin. In conclusion, melatonin exhibited an excitatory effect on bowel output in rats placed under resting state, while attenuated defecation in those subjected to wrap‐restraint stress or serotonin treatment. The inhibitory effects of melatonin on stress‐induced defecation may stem from its antagonistic effect on stress‐induced enhancement of serotonin and CRF secretion.
Selective block of external anal sphincter activation during electrical stimulation of the sacral anterior roots in a canine model
Authors: Bhadra N. , Mortimer J. T.
Published: September 2005

Abstract  Our aim was to electrically activate small diameter parasympathetic fibres in the sacral anterior roots, without activating the larger somatic fibres to the external anal sphincter (EAS). Electrodes were implanted on selected roots in five adult dogs. Pressures were recorded from the rectum and EAS. Quasitrapezoidal (Qzt) pulses for selective activation of smaller axons and narrow rectangular (Rct) pulses to activate all fibres were applied. Sphincter block was defined as [(Pmax − Pmin)/Pmax] × 100%. Roots were also tested with 20 Hz trains. In three animals, evacuation of bowel contents was recorded with artificial fecal material. Stimulation with Qzt pulses showed decrease in sphincter recruitment with increasing pulse amplitudes, indicating propagation arrest in the large fibres. The average sphincter suppression was 94.1% in 16 roots implanted. With Qzt pulse trains, the average evoked sphincter pressure was significantly lower than Rct pulses. Evoked rectal pressures were not significantly different. The mean mass of expelled bowel contents of 51.1 g by Qzt trains was significantly higher than that of 14.8 g expelled by Rct trains. Our results demonstrate that this selective stimuli can activate small diameter fibres innervating the distal bowel and result in significant evacuation of rectal contents.
The effects of tegaserod, a 5‐HT4 receptor agonist, on gastric emptying in a murine model of diabetes mellitus
Authors: Crowell M. D. , Mathis C. , Schettler V. A. , Yunus T. , Lacy B. E.
Published: September 2005

Abstract  The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5‐HT4 receptor partial agonist, on gastric emptying.

Methods:  Gastric emptying rates of a 20% glucose test meal were determined in 12–20‐week‐old female db/db mice and control littermates. The effects of tegaserod (0.1–2.0 mg kg−1, i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5‐HT4antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying.

Results:  Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg−1) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod.

Conclusions:  Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5‐HT4 receptors. These findings suggest that 5‐HT4 receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.
Short‐term ursodeoxycholic acid treatment improves gallbladder bile turnover in gallstone patients: a randomized trial
Authors: Guarino M. P. , Carotti S. , Sarzano M. , Alloni R. , Vanni M. , Grosso M. , Sironi G. , Maffettone P. L. , Cicala M.
Published: September 2005

Abstract  Ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and reduces risk of biliary pain and complications in gallstone (GS) patients. These effects could be partially explained by the improved GB bile turnover.

Objectives:  To assess the effect of short‐term UDCA treatment on GB motility and bile turnover.

Methods:  Ultrasonographic (US) assessment of GB volumes was performed in 16 GS patients, in the postprandial phase, for 90 min with a time sampling of 1 min, before and after 30 days of UDCA (10 mg kg−1 die−1) or placebo, randomly assigned. US data were analysed with statistical tools and with computer fluido‐dynamic (CFD) software FluentTM to simulate GB bile flow.

Results:  After therapy, fasting volume (FV) increased from 21.6 ± 9 to 28.2 ± 12 mL (p < 0.001) while the ejection fraction (EF) remained unchanged (44.5 ± 17% vs 45.1 ± 20%; p: ns). Volumes before and after treatment were poorly correlated (0.02 < r < 0.35), unlike those in placebo patients (r > 0.6). The average GB volume was increased in 7 out of 10 patients following UDCA (range 7–67%). CFD analysis supports the finding of improved bile flow after treatment.

Conclusions:  Unlike results of conventional US parameters of GB motility, CFD analysis shows that UDCA improves GB bile turnover in GS patients.
Relationship between the mechanism of gastro‐oesophageal reflux and oesophageal acid exposure in patients with reflux disease
Authors: Scheffer R. C. H. , Wassenaar E. B. , van Herwaarden M. A. , Holloway R. H. , Samsom M. , Smout A. J. P. M. , Akkermans L. M. A.
Published: September 2005

Abstract  This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro‐oesophageal reflux disease (GORD). In 31 patients, 3‐hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24‐hour ambulatory manometry and pH recording. In the 3‐hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 ± 23 s and 41 ± 5 s, respectively, P < 0.001). In the 24‐hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.
Regional differences in gastrointestinal motility disturbances during acute necrotising pancreatitis
Authors: Seerden T. C. , De Winter B. Y. , Van Den Bossche R. M. , Herman A. G. , Pelckmans P. A. , De Man J. G.
Published: September 2005

Abstract  Patients with acute pancreatitis often suffer from intestinal motility disturbances but the mechanism of this dysfunction is largely unknown. We studied the effect of acute necrotising pancreatitis (ANP) on in vivo gastrointestinal motility and in vitro intestinal contractility in mice. ANP was induced non‐invasively by feeding young female mice a choline‐deficient ethionine‐supplemented (CDE) diet during 72 h. Gastric emptying and intestinal transit were measured in vivo 15 min after intragastric gavage of a semiliquid Evans blue bolus. Gastric and intestinal neuromuscular function was determined in vitro on isolated muscle strips. ANP significantly decreased gastric emptying from 61.2 ± 9.8 to 34.9 ± 7.1% and intestinal transit from 63.4 ± 5.6 to 32.5 ± 5.4%. ANP did not affect receptor‐dependent and receptor‐independent gastric muscle contractions except the contractions to substance P, which were slightly inhibited. In intestinal muscle strips, ANP significantly decreased contractions to EFS, carbachol, PGF2α, substance P and KCl. Our results show that ANP delays gastric emptying in vivo, associated with a specific reduction in substance P contractility in vitro. ANP also impairs intestinal transit in vivo, associated with a non‐specific reduction of intestinal contractility in vitro. We conclude that ANP impairs gastrointestinal motility in mice with underlying regional differences in the pathogenic mechanisms.
Indiscriminate loss of myenteric neurones in the TNBS‐inflamed guinea‐pig distal colon
Authors: Linden D. R. , Couvrette J. M. , Ciolino A. , Mcquoid C. , Blaszyk H. , Sharkey K. A. , Mawe G. M.
Published: September 2005

Abstract This investigation was conducted to establish whether guinea‐pig trinitrobenzene sulfonic acid (TNBS)‐colitis was associated with a change in the number of neurones of the myenteric plexus, and, if so, whether select subpopulations of neurones were affected. Total neurones were quantified with human (Hu) antiserum, and subpopulations were evaluated with antisera directed against choline acetyltransferase, nitric oxide synthase, calretinin, neuronal nuclear protein or vasoactive intestinal peptide (VIP). Colitis was associated with a loss of 20% of the myenteric neurones, most of which occurred during the first 12 h past‐TNBS administration. During this period, myenteric ganglia were infiltrated with neutrophils while lymphocytes appeared at a later time‐point. The neuronal loss persisted at a 56‐day time‐point, when inflammation had resolved. The decrease in myenteric neurones was not associated with a decrease in any given subpopulation of neurones, but the proportion of VIP‐immunoreactive neurones increased 6 days following TNBS administration and returned to the control range at the 56 days. These findings indicate that there is an indiscriminant loss of myenteric neurones that occurs during the onset of TNBS‐colitis, and the loss of neurones may be associated with the appearance of neutrophils in the region.
Laboratory wash resistance of long‐lasting insecticidal nets
Authors: Gimnig John E. , Lindblade Kim A. , Mount Dwight L. , Atieli Francis K. , Crawford Sara , Wolkon Adam , Hawley William A. , Dotson Ellen M.
Published: September 2005

Long‐lasting insecticidal nets (LLINs) may eliminate the need for retreatment of mosquito nets used for the control of malaria and other vector‐borne diseases. The efficacy of LLINs after repeated washing under laboratory conditions has been used to predict long‐lasting efficacy under field conditions. We evaluated under laboratory conditions the wash resistance of two LLINs (PermaNet® 1.0, Vestergaard‐Frandsen, Denmark; Olyset®, Sumitomo Chemical Co., Japan), two candidate LLINs (Dawa®, Siamdutch Mosquito Netting Co., Thailand; Insector, Athanor, France) and a net treated with a process designed to increase its wash resistance and compared them with conventionally treated nets (deltamethrin, 25 mg/m2). Nets of all six types were washed using a standard protocol and tested weekly using WHO cone bioassays with Anopheles gambiae (Kisumu strain). The PermaNet® 1.0 was the most wash resistant with >50% mosquito mortality in WHO cone bioassays after as many as 20 washes. The Dawa® net also retained some activity after repeated washing but exhibited wide variation in insecticide retention and biological activity. The remaining nets lost >90% of their biological activity after six washes as measured by 24‐h mortality of A. gambiae in WHO cone tests. After 20 washes, all nets lost >50% of their initial insecticide concentrations except for the Olyset® net. After 20 washes, nets were heated for 4 h at 60 °C to determine whether biological activity could be restored by heat‐assisted regeneration. Only the Olyset® net was regenerated by heating, with average mosquito mortality and knockdown in WHO cone tests rising to >90% after heating for 4 h at 60 °C. However, regeneration of the biological activity of Olyset® nets that had been washed three times did not occur at 30 °C or 35 °C after 12 weeks. The wash resistance of these LLINs corresponded well to their retention of biological activity observed in a field trial, suggesting that wash resistance may be a good predictor of the longevity of insecticidal activity of LLINs under field conditions.
Short communication: Impact of long‐term (14 years) bi‐annual ivermectin treatment on Wuchereria bancrofti microfilaraemia
Authors: Kyelem D. , Medlock J. , Sanou S. , Bonkoungou M. , Boatin B. , Molyneux D. H.
Published: September 2005

Ivermectin has been and continues to be extensively used to control onchocerciasis in areas of hyper and mesoendemicity within the African Programme of Onchocerciasis Control. As programmes to eliminate lymphatic filariasis (LF) caused by Wuchereria bancrofti expand, areas of coendemicity with onchocerciasis will be incorporated into LF programmes. This study reports that in villages which were hyperendemic for onchocerciasis after some 14 years of treatment with ivermectin, no W. bancrofti could be detected in a population of 1210 individuals whilst in adjacent villages a prevalence of around 3% was found. Despite the long period of ivermectin treatment Mansonella perstans did not appear to respond to ivermectin in this setting.
Epidemiology of drug‐resistant malaria in Republic of Congo: using molecular evidence for monitoring antimalarial drug resistance combined with assessment of antimalarial drug use
Authors: Nsimba Basile , Jafari‐Guemouri Sayeh , Malonga David A. , Mouata André M. , Kiori Jeannine , Louya Frédéric , Yocka Dominique , Malanda Maurice , Durand Rémy , Le Bras Jacques
Published: September 2005

In Congo, urgent efforts are needed to help with the revision of the national antimalarial drug policy. Despite its high resistance level, chloroquine (CQ) is still extensively used as the first‐line treatment for uncomplicated Plasmodium falciparum malaria. The study was conducted in children under 5 years with uncomplicated malaria in Pointe‐Noire and Brazzaville, the two largest cities that contain approximately 60% of the population of Congo. We investigated by polymerized chain reaction and sequencing methods the frequency distribution of molecular markers for antimalarial drug resistance, including mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene associated with CQ resistance and mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes conferring resistance to sulphadoxine/pyrimethamine (SP) among pre‐treatment P. falciparum isolates, as well as assessing antimalarial drug use in the community. pfcrt (K76T) mutation was present in most isolates (96.4%, n = 138) and high frequency (69.2%, n = 133) of triple‐mutant dhfr‐S108N, N51I, C59R was observed. The quintuple mutant (dhfr‐S108N, N51I, C59R and dhps‐A437G or S436A, K540E) considered as molecular marker for SP treatment failure was not found because dhps‐K540E mutation was absent in isolates tested; this is a clear evidence for the excellent efficacy of SP that we previously described in the same population. The complete absence of the dhps‐K540E mutation is a deterrent component for using this molecular marker as an early warning tool for SP resistance testing in that population. Poor compliance issues related to the antimalarial drug use including inappropriate manufacturing practices reported in this study require intensive attention and should be taken into account when implementing drug policy change. If Congo changes its treatment policy from CQ to SP monotherapy, this will not last long. The strategy of combining SP with other affordable and effective antimalarial drugs such as the artemisinin derivatives to improve efficacy and to delay the development of parasite resistance is essential.
Ten novel HLA‐DRB1 alleles and one novel DRB3 allele
Authors: Lazaro A. M. , Steiner N. K. , Moraes M. E. , Moraes J. R. , Ng J. , Hartzman R. J. , Hurley C. K.
Published: September 2005

Ten novel HLA‐DRB1 and one DRB3 alleles are described. Eight of the variants are single‐nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 and DRB3*020204). Two alleles differ by two nucleotide changes altering one (DRB1*1447 and *1361) amino acid and one allele alters three nucleotides and two amino acids.
Novel HLA‐Cw*06 allele, Cw*0612, identified by sequence‐based typing†
Authors: Hwang S.‐H. , Cha C.‐H. , Kwon O.‐J. , Heo Y.‐S. , Hur S.‐S. , Lee M.‐N. , Oh H.‐B.
Published: September 2005

In this report, we describe the identification of an human leucocyte antigen‐Cw*06 (HLA‐Cw*06) nucleotide sequence variant, a new HLA‐Cw*0612. The new allele was detected during routine HLA typing by high‐resolution sequence‐based typing. Allele Cw*0612 showed one nucleotide difference with Cw*0602 at codon 153 (GCG→ACG) resulting in an amino acid change from alanine to threonine.
HLA‐A*2626, a new allele identified through external proficiency‐testing exercise†
Authors: Longhi E. , Frison S. , Colombini I. , Malagoli A. , Crespiatico L. , Poli F.
Published: September 2005

A new allele, officially named HLA‐A*2626, has been detected in a blood sample belonging to a Caucasian subject human leucocyte antigen typed for Lombardy Region external proficiency‐testing exercise. The DNA sequences of exons 2, 3 and 4 of this new allele are identical to those of HLA‐A*2601 except at codon 259 of exon 4 (CCT→CTT). This variation modifies the encoded protein from proline to leucine.
Quantitative rules for lymphocyte regulation: the cellular calculus and decisions between tolerance and activation
Authors: Hodgkin P. D.
Published: September 2005

The innovation of fluorescent division‐tracking techniques has elevated our understanding of lymphocytes to a new level. These techniques applied in vitro have identified quantitative rules for lymphocyte differentiation, proliferation and survival that had previously been hidden. The many patterns of quantitative response revealed by these analyses provide a sharp contrast to the traditional idea that T cells must make a binary choice between tolerance and activation. Here, evidence for the classic dogma of two‐signal theory and T–T help is re‐examined in the light of the new quantitative view to show how logical difficulties can be resolved.
MHC‐F DNA sequences in bonobo, gorilla and orangutan
Authors: Rojo R. , Castro M. J. , Martinez‐Laso J. , Serrano‐Vela J. I. , Morales P. , Moscoso J. , Zamora J. , Arnaiz‐Villena A.
Published: September 2005

The major histocompatibility complex (MHC)‐F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)‐F orthologous DNA sequences in Pongidae in order to study the MHC‐F gene evolution and its products' function. HLA‐F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC‐F proteins show that MHC‐F may be a protein with a typical class I structure and that the key residues of the peptide‐binding region (PBR) are highly conserved in MHC‐F in all studied primates species. Thus, MHC‐F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC‐F protein could be involved, together with MHC‐G and MHC‐E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC‐G and MHC‐E orthologues. The evolutionary pathway of the six‐base‐pair deletion at exon 2 existing in some primates is put forward.
A first estimate of the amino acid requirement for milk production of the high‐producing female mink (Mustela vison)
Authors: Fink R. , Tauson A.‐H. , Chwalibog A. , Hansen N. E.
Published: September 2005

Thirty mink dams nursing litters of six kits were assigned to one of three dietary treatments [high protein (HP), medium protein (MP) and low protein (LP)], fed ad libitum for 4 week from parturition, to investigate the effects of protein supply on milk yield and milk composition in order to estimate the amino acid requirement of the lactating mink. Twelve dams were held in an intensive care unit and subjected to balance experiments and the kits were injected with deuterium oxide to determine water kinetics and milk yield. Eighteen dams were kept under normal farm conditions but with feed intake of dams and live weight gain of kits being determined and milk samples collected. The ME intake was higher (p < 0.05) in dams fed the LP and MP diets than in dams fed the HP diet, whereas the amino acid intake (g/day) was lowest (p < 0.05) in dams fed the LP diet. In the third and fourth weeks of lactation milk yield was higher (p < 0.05) in dams fed the LP and MP diets than in dams fed the HP diet. Chemical composition of milk was not affected (p > 0.05) by dietary treatment. However, protein content tended (p = 0.06) to be lower in dams fed the LP diet. Amino acid content (g/16 g N) of milk was higher (p < 0.05) in dams fed the LP and MP diets than in dams fed the HP diet. This resulted in the highest (p < 0.05) amino acid intake and highest (p < 0.001) live weights of kits nursed by dams fed the LP and MP diets, which may be explained by a combined effect of higher ME intake and reduced energetic costs for glucose production through less amino acids being used in gluconeogenesis. In conclusion, the improved performance of dams fed the LP diet suggested that their requirement of essential amino acids and non‐specific N were covered, and the requirement of digestible amino acids of lactating mink (kg0.75) was, thereby, estimated by use of a factorial approach including the amino acid excretion in milk of LP dams.
Long‐term effects of early‐life dietary L‐carnitine on lymphoid organs and immune responses in Leghorn‐type chickens
Authors: Deng K. , Wong C. W. , Nolan J. V.
Published: September 2005

The long‐term effects of supplementing Leghorn‐type chickens with dietary L‐carnitine after hatching for 4 weeks on growth, lymphoid organ weights, humoral and cell‐mediated immune responses were assessed in a 12‐week study. A commercial starter feed supplemented with 0 (control), 100 (LC) or 1000 (HC) mg L‐carnitine/kg was offered to day‐old ISA Brown cockerels for 4 weeks, then all birds were given a commercial pullet grower feed for another 8 weeks. No differences (p > 0.05) in growth rates, feed intake or feed utilisation efficiency existed among the dietary treatments throughout the study. Compared with control birds, HC‐fed birds had a lower (p < 0.05) thymus weight relative to bodyweight (BW) at Week 4, but a higher (p < 0.05) relative thymus weight at Week 12. A higher (p < 0.05) serum primary antibody response to sheep red blood cells (SRBC) in HC‐fed birds than in the other two groups was also detected at Week 12. Relative spleen or bursa weights and cutaneous responses of toe webs to phytohaemagglutimin (PHA) (an in vivo indicator of cell‐mediated immune responses) did not differ (p > 0.05) among dietary treatments at any time. It is concluded that a short‐term supply of dietary L‐carnitine to a conventional commercial feed after hatching enhanced subsequent humoral immunity in Leghorn‐type chickens. Further study is warranted to confirm such a long‐term effect.
Effects of level of feed intake and Fusarium toxin‐contaminated wheat on rumen fermentation as well as on blood and milk parameters in cows
Authors: Seeling K. , Lebzien P. , Dänicke S. , Spilke J. , Südekum K.‐H. , Flachowsky G.
Published: September 2005

The aims of this study were to examine the effects of and possible interactions between dry matter (DM) intake and feeding Fusarium toxin‐contaminated wheat on ruminal fermentation, serum chemical parameters and milk yield of dairy cows. Fourteen dairy cows equipped with ruminal and duodenal cannulas were analysed. All animals were fed the same ration, the daily feed amounts being adjusted to current performance. On DM basis, the ration consisted of 60% concentrate including 55% wheat [Fusarium‐contaminated wheat (mycotoxin period) or control wheat (control period)] and was completed with 40% maize and grass silage. Each cow was fed the contaminated wheat [deoxynivalenol (DON), 8.21 mg/kg DM and zearalenone (ZON), 0.09 mg/kg DM] and the control wheat (0.25 mg DON/kg DM and 51 μg ZON/kg DM). As expected, a higher organic matter (OM) intake decreased the amounts of fermented crude nutrients related to the respective intakes. An increased amount of crude protein degraded (p < 0.05) and a lower molar percentage of propionate in the rumen fluid were observed when feeding the Fusarium toxin‐contaminated wheat at increased OM intakes in comparison with the control wheat. The activities of serum aspartate aminotransferase (ASAT; p < 0.001), glutamate dehydrogenase (GLDH; p < 0.01) and gamma glutamyl transferase (γ‐GT; p < 0.01) increased with increasing OM intake and were not related to the mycotoxin contamination of the wheat.