bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface characteristics of implants influence their bone integration after simultaneous placement of implant and GBR membrane
Authors: Lima Luiz A. , Fuchs‐Wehrle Anita M. , Lang Niklaus P. , Hämmerle Christoph H.F. , Liberti Edson , Pompeu Eduardo , Todescan José H.
Published: November 2003

Abstract: The purpose of this study was to evaluate the influence of titanium surface characteristics on bone integration of implants, and to describe the pattern of peri‐implant tissue healing after simultaneous implant placement and guided bone regeneration. In four healthy mongrel dogs mandibular premolars were extracted. Two weeks following full mouth prophylaxis and 4 months after extractions, simultaneous membrane and implant surgeries were performed. Efforts were made to produce bony defects with dimensions of 7×7×7 mm. Into these, 24 standard ITI® implants (∅=4.1 mm; length=8 mm) with either a titanium plasma‐sprayed (TPS) or a machined surface (MS) were placed. Although implants were inserted 4 mm into cancellous bone, difficulties in achieving optimal primary stability were encountered. All dogs were maintained on a soft diet. Chlorhexidine rinses were performed three times a week. Full mouth prophylaxis was performed every 2 weeks. In the case of membrane exposure, the membranes were removed prematurely (4–6 or 14–15 weeks after surgery). Two dogs were sacrificed at 16 weeks and two at 24 weeks after surgery. Nondecalcified histologic sections were processed and histometric analyses were carried out. When membranes were removed after 4–6 weeks, a vertical bone growth (VB) of 45–61% of the original defect was noted. After membrane removal at 14–15 weeks, similar VB was observed. However, if membranes were left in situ for 24 weeks, VB was between 79% and 96%. In this group of sites, the VB was 66% at 16 weeks and 86% at 24 weeks. Osseointegration in the regenerated bone area ranged from 12% to 32% for the TPS and from 0.0% to 3.6% for the MS implants at 16 and 24 weeks combined. Osseointegration in the pristine host bone area ranged from 16% to 35% for the TPS and from 0.0% to 11% for the MS sites at 16 and 24 weeks. In conclusion, the fraction of implant‐bone integration was much higher in the pristine bone compared to that in the regenerated bone. TPS surfaces positively influenced the fraction of osseointegration in comparison to MS surfaces for both regenerated and pristine bone. Furthermore, early membrane removal negatively affected the fraction of bone defect fill.
Comparison of the diagnostic potential of direct digital and conventional intraoral radiography in the evaluation of peri‐implant conditions
Authors: Mörner‐Svalling Ann‐Catherine , Tronje Gunilla , Andersson Lars G. , Welander Ulf
Published: November 2003

Abstract: The aims of this study were to examine whether viewers agreed on details seen in direct (real time) digital and conventional film radiographs of implants, and whether there were differences in agreement between the systems. Intra‐oral radiographs of implants were exposed both as direct digital and conventional film radiographs. Fifty pairs of radiographs with similar projection and exposure were selected, showing 59 implants. Ten viewers assessed the radiographs separately and noted eight different details. The viewers showed very high agreement in their assessments of radiographs of each technique separately, and there were no statistically significant differences. However, there was a tendency to stronger agreement in the direct digital radiographs in four assessed points out of eight. The patients' experience of having radiographs exposed with the two methods was also studied by questionnaire. The patients' opinions on the two techniques did not differ statistically. This study shows that digital radiography has at least equal diagnostic yield compared to film radiography.
Effects of ivermectin and doramectin faecal residues on the invertebrate colonization of cattle dung
Authors: Suarez V. H. , Lifschitz A. L. , Sallovitz J. M. , Lanusse C. E.
Published: November 2003

Abstract: 
The effects of avermectin [ivermectin (IVM) and doramectin (DRM)] faecal residues on dung colonization and degradation by invertebrates were evaluated during late spring in the east of La Pampa province, Argentina. The study was conducted after collection of faecal material from animals (10 steers per group) allocated to the following groups: untreated control group (CG) and groups treated subcutaneously (200 μg/kg) with either DRM (DG) or a long‐acting formulation of IVM (IG). Fifty pats (550 g each) per group were collected, prepared and deposited on the field on days 3, 7, 16 and 29 post‐treatment (pt). Eight pats per group were recovered after 7, 14, 21, 42, 100 and 180 days post‐deposition (pd) on the field. The weight, percentage of dry matter, number of arthropods and nematodes from faeces were determined. The faecal concentrations of IVM and DRM were measured by high performance liquid chromatography (HPLC) throughout the trial period to correlate the pattern of drug degradation in dung with pd time. The total number of arthropods in dungs from CG was higher (P < 0.05) than those counted between days 3 and 29 pt in IG and DG. A decrease in the number of Coleoptera larvae (P < 0.05) between days 21 and 42 days pd was observed in both treated groups. Diptera larvae counts in CG pats were significantly higher (P < 0.05) than those obtained in treated groups in the 7‐ and 14‐day‐old pats. A lower number (P < 0.05) of Collembola, compared with pats from CG, was recovered from IG and DG pats deposited at days 3 and 7 pt and exposed from day 42. The counts of Acari in pats from treated animals were lower (P < 0.05) than those observed in CG pats at 3, 8 and 16 days pt. There were no differences neither in adult Scarabaeidae recovered nor in the proportions of dung buried and destroyed by great dung beetles. Dung specific nematodes were reduced (P < 0.05) in IG and DG pats from 3 and 7 days pt compared with those of CG pats. The comparative results shown here demonstrate that the negative effects of both IVM and DRM on dung colonization are similar. The pattern of drug degradation in the environment was very slow. High residual concentrations of both active parent compounds were recovered in dungs exposed in the field for up to 180 days pd. Concentrations as high as 13 ng/g (IVM) and 101 ng/g (DRM) were measured in faeces obtained from pats deposited on day 27 pt and exposed to the environment during 180 days. The results show a decrease in invertebrate colonization of dung recovered from IVM‐ and DRM‐treated cattle, which is in agreement with the large drug residual concentrations measured in faeces.
Internal Auditing and Risk Assessment in Large Italian Companies: an Empirical Survey
Authors: Allegrini Marco , D’Onza Giuseppe
Published: November 2003

This paper aims at achieving an overall view regarding the state of the art of internal auditing in large Italian companies. Mainly, it is focused on risk assessment practices and on the execution of a risk‐based approach in the audit process.

The research is based on a survey carried out on the ‘Top100’ companies listed at the Italian Stock Exchange.

Survey results reveal that practices vary significantly among three different models:

A few companies (25%) carry out mainly traditional compliance activities and they generally follow an audit‐cycle approach for the annual audit planning;

In most companies (67%), internal auditors adopt the COSO model and perform mainly operational auditing. Risk‐based approach is applied predominantly at macro level.

Finally, it is possible to identify a very few large companies (8%), in which auditors are applying a risk‐based approach both at macro and micro level.
The Role of Internal Auditors in Mergers, Acquisitions and Divestitures: An International Study
Authors: Selim Georges M. , Sudarsanam Sudi , Lavine Mike
Published: November 2003

This paper presents the results of a survey‐based study into the role played by internal auditors in Mergers, Acquisitions and Divestitures (M, A & D). The research, funded by the IIA‐ Research Foundation, was carried out during the years 2000 and 2001 and involved interviews in 22 organisations spanning 6 countries. The findings indicate that internal auditor's involvement in M, A and D can only be described as moderate. However, the study also shows that internal auditors see themselves capable of playing a larger role, a view supported by senior executives in other functions in these organisations. The study sets out the pre‐requisites for internal auditors expanded role and discusses the means of achieving this.
Detection and decay of theBtendotoxin in soil from a field trial with genetically modified maize
Authors: Hopkins D. W. , Gregorich E. G.
Published: November 2003

Genetically modified plants and their residues may have direct effects on ecosystem processes. We aimed to determine the amount in soil of the insecticidal δ‐endotoxin, originally from the bacteriumBacillus thuringiensis, introduced into soil by root exudates and residues from genetically modified maize, to compare the short‐term rates of decay ofBt‐maize and non‐Bt‐maize, and to determine the rate at which the toxin inBt‐maize leaves decomposes in soil. Intact soil, size fractions of soil, soluble fractions from soil and fractions of organic residues from a field whereBt‐maize had been cultivated for 4 years were analysed for theBtδ‐endotoxin. Traces of the δ‐endotoxin were detected in the whole (unfractionated) soil, the water‐soluble fractions, and some of the particle‐size fractions, but it was sufficiently concentrated only in the > 2000‐µm size fraction to be quantified. The δ‐endotoxin concentrations in this fraction ranged between 0.4 and 4.4 ng toxin g−1fraction, which equated to 70, 6 and 50 mg toxin m−2in the 0–15, 15–30 and 30–60 cm depths, respectively (or 126 mg toxin m−2over the 0–60 cm depth) in the field in June (early summer). The > 2000‐µm size fraction was a mixture of light‐ and dark‐coloured organic material and mineral material comprising sand grains and stable aggregates. For samples collected early in the growing season, most of the detected δ‐endotoxin was present in the light‐coloured organic material, which was comprised of primarily live roots. However, recognizable maize residues, probably from previous years' crops, also contained δ‐endotoxin. In a laboratory incubation study,Bt‐and non‐Bt‐maize residues were added to soil and incubated for 43 days. There was no detectable difference in the decomposition of plant material from the two lines of maize, as determined by CO2production. The quantity of δ‐endotoxin in the decomposing plant material and soil mixtures declined rapidly with time during the incubation, with none being detectable after 14 days. The rapid disappearance of the δ‐endotoxin occurred at a rate similar to that of the water‐soluble components of the maize residues. The results suggested that much of the δ‐endotoxin in crop residues is highly labile and quickly decomposes in soil, but that a small fraction may be protected from decay in relatively recalcitrant residues.
Bioavailability of hydrophobic organic contaminants in soils: fundamental concepts and techniques for analysis
Authors: Semple K. T. , Morriss A. W. J. , Paton G. I.
Published: November 2003

Soils represent a major sink for organic xenobiotic contaminants in the environment. The degree to which organic chemicals are retained within the soil is controlled by soil properties, such as organic matter, and the physico‐chemical properties of the contaminant. Chemicals which display hydrophobic and lipophilic characteristics, as well as a recalcitrant chemical structure, will be retained within the soil, and depending on the ‘strength’ of the association may persist for long periods of time. This review describes the behaviour of hydrophobic organic contaminants in soils, focusing on the mechanisms controlling interactions between soil and contaminants. The bioavailability of contaminants in soil is also discussed, particularly in relation to contact time with the soil. It considers the degradation of organic contaminants in soil and the mechanisms microbes use to access contaminants. Finally, the review discusses the ‘pros’ and ‘cons’ of chemical and biological techniques available for assessing bioavailability of hydrophobic organic chemicals in soils, highlighting the need to quantify bioavailability by chemical techniques. It concludes by highlighting the need for understanding the interactions between the soil, contaminants and biota which is crucial to understanding the bioavailability of contaminants in soils.
Exchange of greenhouse gases between soil and atmosphere: interactions of soil physical factors and biological processes
Authors: Smith K. A. , Ball T. , Conen F. , Dobbie K. E. , Massheder J. , Rey A.
Published: November 2003

This review examines the interactions between soil physical factors and the biological processes responsible for the production and consumption in soils of greenhouse gases. The release of CO2 by aerobic respiration is a non‐linear function of temperature over a wide range of soil water contents, but becomes a function of water content as a soil dries out. Some of the reported variation in the temperature response may be attributable simply to measurement procedures. Lowering the water table in organic soils by drainage increases the release of soil carbon as CO2 in some but not all environments, and reduces the quantity of CH4 emitted to the atmosphere. Ebullition and diffusion through the aerenchyma of rice and plants in natural wetlands both contribute substantially to the emission of CH4; the proportion of the emissions taking place by each pathway varies seasonally. Aerated soils are a sink for atmospheric CH4, through microbial oxidation. The main control on oxidation rate is gas diffusivity, and the temperature response is small. Nitrous oxide is the third greenhouse gas produced in soils, together with NO, a precursor of tropospheric ozone (a short‐lived greenhouse gas). Emission of N2O increases markedly with increasing temperature, and this is attributed to increases in the anaerobic volume fraction, brought about by an increased respiratory sink for O2. Increases in water‐filled pore space also result in increased anaerobic volume; again, the outcome is an exponential increase in N2O emission. The review draws substantially on sources from beyond the normal range of soil science literature, and is intended to promote integration of ideas, not only between soil biology and soil physics, but also over a wider range of interacting disciplines.
The influence of the root‐knot nematode Meloidogyne incognita, the nematicide aldicarb and the nematophagous fungus Pochonia chlamydosporia on heterotrophic bacteria in soil and the rhizosphere
Authors: O'Flaherty S. M. , Hirsch P. R. , Kerry B. R.
Published: November 2003

Plant‐pathogenic nematodes are a major cause of crop damage worldwide, the current chemical nematicides cause environmental damage, but alternatives such as biological control are less effective, so further understanding of the relationship between nematodes, nematicides, biological control agents and soil and rhizosphere microorganisms is needed.

Microbial populations from roots of cabbage and tomato plants infested with the root‐knot nematode Meloidogyne incognita were compared with those from plants where the nematode was controlled by the nematicide aldicarb, or a nematophagous fungus with biological control potential, Pochonia chlamydosporia. The total numbers of culturable bacteria and fungi in rhizosphere soil were similar in all three treatments for both plants, around 100‐fold more than in control soil in which there were no plants. However, there were clear differences in the catabolic diversity, assessed by Biolog EcoPlate™ carbon substrate utilization assays, between microbial populations from unplanted soil and the rhizosphere. In cabbage, a poor host for M. incognita, the rhizosphere population from P. chlamydosporia‐treated plants was distinct from the population from untreated and aldicarb‐treated plants. In tomato, a host susceptible to the nematode, the catabolic diversity of populations from aldicarb‐ and P. chlamydosporia‐treated plants was similar and differed from the untreated, nematode‐infested plants. The genetic diversity of the fast‐growing heterotrophic bacteria in the tomato rhizosphere, indicated by PCR fingerprinting with ERIC primers, was very different in the infested roots, whereas the profiles of isolates from both aldicarb‐ and P. chlamydosporia‐treated roots were similar. Evidently, nematodes have a greater impact on the rhizosphere population of a susceptible host, tomato, than a poor one, cabbage, and nematode‐infested roots are colonized by a different subpopulation of soil microbes from that on plants where infection is controlled, illustrating differences in root morphology and physiology.
Micro‐scale distribution of microorganisms and microbial enzyme activities in a soil with long‐term organic amendment
Authors: Poll C. , Thiede A. , Wermbter N. , Sessitsch A. , Kandeler E.
Published: November 2003

Microbial ecology is the key to understanding the function of biodiversity for organic matter cycling in the soil. We have investigated the impacts of farmyard manure added over 120 years on organic matter content, enzyme activities, total microbial biomass and structure of microbial populations in several particle‐size fractions of a Luvic Phaeozem a few kilometres northeast of Halle, Germany. We compared two treatments: no fertilization (control) and 12 t farmyard manure (FYM) ha−1 year−1 since 1878. The fine fractions contained most C and N, microbial biomass, total amount of phospholipid fatty acids (PLFAs) and greatest invertase activity. Xylanase activity as well as fungal biomass increased only gradually with diminishing particle size, whereas the relative abundance of fungi decreased with diminishing particle size. The least diversity of the soil microbial community, indicated by the smallest Shannon index based on the abundance and amount of different PLFAs and small number of terminal restriction fragments (T‐RFs) of 16S rRNA genes, was in the sand fractions. The results supported the hypothesis that this microhabitat is colonized by a less complex bacterial community than the silt and clay fractions. Addition of FYM had enhanced the amount of organic matter, total microbial biomass, and xylanase and invertase activity, and induced a shift of the microbial community towards a more bacteria‐dominated community in the coarse sand fraction. Microbial communities in finer fractions were less affected by addition of FYM.
Use of biomarkers for alcohol use disorders in clinical practice
Authors: Neumann Tim , Spies Claudia
Published: November 2003

Background  Biomedical markers may provide additive objective information in screening and confirmation of acute or recent consumption, intoxication, relapse, heavy drinking, hazardous/harmful use/abuse and dependence and alcohol use related organ dysfunction (alcohol use‐related disorders: AUDs).

Aims  To review the use of biomarkers in clinical practice to detect AUDs.

Findings  About one‐fifth of the patients seen in clinical practice have AUDs, which offer a variety of treatment options if diagnosed. The diagnosis of AUDs relies on clinical and alcohol‐related history, physical examination, questionnaires and laboratory values. No clinical available laboratory test [e.g. for acute abuse: alcohol in blood or breath; for chronic alcohol abuse: γ‐glutamyl transferase (GGT), mean corpuscular volume (MCV), carbohydrate‐deficient transferrin (CDT)] is reliable enough on its own to support a diagnosis of alcohol dependence, harmful use or abuse. Sensitivities, specificities and the predictive values may vary considerably according to patient and control group characteristics (e.g. gender, age or related comorbidity). In patient groups with limited cooperation markers may be helpful when considering treatment options.

Conclusions  More research is needed to determine the value of markers (single or combined, with questionnaires) in the context of clinical decision‐making algorithms in defined settings and with defined dichotomous outcome variables.
When absorptive capacity meets institutions and (e)learners: adopting, diffusing and exploiting e‐learning in organizations
Authors: Martin Graeme , Massy Jane , Clarke Thomas
Published: November 2003

E‐learning was thought to be one of the fastest growing industries on both sides of the Atlantic and has been frequently heralded as a transforming influence on global corporate training and higher education. Despite such rhetoric, the adoption, diffusion and exploitation have been slower than anticipated. In this paper we attempt to explain why this might have been the case in Europe by drawing on an increasingly influential body of management literature on the absorptive capacity (ACAP) of organizations to acquire, assimilate and use new technologies and ideas. We supplement this work on absorptive capacity with two other streams of literature on learners and on the business systems or institutionalist perspective, which focuses on the embeddedness of unique organizational forms, ideas and human resource development approaches in particular national business systems. We develop a model of absorptive capacity for e‐learning in organizations (ACAP for eL), which we argue has important theoretical implications for business and management academics in developing a model of technology transfer and diffusion, key lessons for HRD practitioners and politicians associated with furthering e‐learning developments in their organizations, and also for policy makers at government level wishing to spread the e‐learning message.
E‐learning: emerging uses, empirical results and future directions
Authors: Welsh Elizabeth T. , Wanberg Connie R. , Brown Kenneth G. , Simmering Marcia J.
Published: November 2003

The use of network technology to deliver training is the latest trend in the training and development industry and has been heralded as the ‘e‐learning revolution.’ In an effort to separate hype from reality, this paper reviews practitioner and research literature on e‐learning, incorporating unpublished information from interviews with managers and consultants directly involved in e‐learning initiatives. Specific attention is given to why organizations use e‐learning, what the potential drawbacks to e‐learning are, what we know from research about e‐learning and what the future of e‐learning may hold.
Nutritional support
Authors: Ofman J. , Koretz R. L.
Published: November 2003

Nutritional support currently accounts for about 1% of the total health care costs in the USA. Interestingly, most of the prospective randomized controlled trials to date have not been able to demonstrate that this therapeutic intervention alters morbidity or mortality. In fact, parenteral nutritional support may predispose the recipients to developing systemic infections. There have been a few areas in which nutritional support may be of benefit. Enteral supplements given to underweight women who suffer hip fractures reduce the hospital stay and, presumably, overall cost. Preoper‐ative parenteral nutritional support may produce a small absolute reduction in post‐operative morbidity, but its cost becomes prohibitive. Preoperative enteral nutritional support, especially if carried out in the home, may be of benefit (using the most optimistic interpretation of a small number of trials); if so, it is an economically defensible intervention. Particular nutrients or diets may have specific effects on certain disease processes. Indirect comparisons have suggested that elemental diets can be used to treat flares of Crohn's disease (perhaps because putative food antigens are removed). However, corticosteroid therapy is more efficacious. Furthermore, it is less expensive to employ 6‐mercaptopurine as the next modality in steroid failures. Branched‐chain amino acid infusions may have some effect on hepatic encephalopathy, but again, lactulose is less expensive. Nutritional support is one area of medicine in which there has been far more enthusiasm than the data justify. Disease‐associated malnutrition probably is a secondary phenomenon, not an important cause of morbidity. The widespread use of this modality cannot be justified in a cost‐constrained health care system.
Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta‐analysis of long‐term omeprazole trials
Authors: Carlsson R. , Galmiche J.‐P. , Dent J. , Lundell L. , Frison L.
Published: November 2003

Background:

This meta‐analysis investigated factors that may affect the risk of relapse of oesophagitis, and evaluated the predictive value of symptoms for the presence of relapse during long‐term treatment.

Methods:

Individual data from 1154 patients included in five independently conducted, randomized, long‐term clinical trials of the efficacy of different dosage regimens of omeprazole, standard ranitidine treatment and placebo for the prevention of relapse of oesophagitis were pooled for this meta‐analysis. The therapeutic regimens studied were omeprazole 20 mg o.m. (OME20) in 366 patients, omeprazole 10 mg o.m. (OME10) in 225 patients, omeprazole 20 mg weekends (OMEW) in 235 patients, ranitidine 150 mg b.d. (RAN) in 179 patients, or placebo (PLA) in 149 patients.

Results:

OME20 maintained 82.4% (95% CI: 78.2–86.6%) of patients in endoscopic remission over the 6‐month period compared to 71.9% (95% CI: 65.5–78.3%) for OME10, 52.3% (95% CI: 44.4–60.1%) for RAN, 42.7% (95% CI: 35.8–49.5%) for OMEW, and 10.6% (95% CI: 5.0–16.3%) for PLA. A Cox's regression analysis of time to recurrence of oesophagitis showed that four factors were associated with a higher relapse rate during placebo and active maintenance therapy: (a) pre‐treatment severity of oesophagitis (P<0.0001), (b) young age (P=0.01), (c) non‐smoking (P=0.02) and (d) moderate/severe regurgitation before entry into the trials (P=0.03). Asymptomatic relapse of oesophagitis was uncommon, being found in only 8.6% of the patients.

Conclusions:

Maintenance treatment with omeprazole 10 and 20 mg daily is superior to all other regimens tested, and is only marginally influenced by the pre‐treatment severity of oesophagitis. Age contributes to the factors that influence the outcome during long‐term treatment with omeprazole. Symptom relief is highly predictive for the maintenance of healing.
Cytoprotective effect of bismuth subsalicylate in indomethacin‐treated rats is associated with enhanced mucus bismuth concentration
Authors: Tanaka S. , Guth P. H. , Carryl O. R. , Kaunitz J. D.
Published: November 2003

Background:

Bismuth compounds prevent gastric injury from the short‐term administration of nonsteroidal anti‐inflammatory drugs. We studied the mechanisms underlying the gastroprotective actions of bismuth subsalicylate against indomethacin‐induced injury in rats.

Methods:

An in vivo microscopic technique was used in which acid output, surface cell intracellular pH (pHi), gastric mucus gel thickness and mucosal blood flow were measured simultaneously. Concentrations of bismuth in mucus were measured by atomic absorption.

Results:

Indomethacin (60 mg/kg) significantly thinned the mucus gel layer and augmented the decrease of pHi during luminal acid superfusion, consistent with a weakened gastric mucosal barrier to acid. Bismuth subsalicylate partially reversed this effect of indomethacin on pHi, consistent with gastroprotection. Neither a prostaglandin‐inhibiting but non‐injurious dose of indomethacin (5 mg/kg), bismuth subsalicylate, or their combination affected mucus gel thickness or pHi homeostasis. In separate experiments, indomethacin (60 mg/kg) significantly increased gastric mucus bismuth concentration in rats given bismuth subsalicylate.

Conclusion:

Bismuth accumulation in the gastric mucus during the evolution of mucosal injury may play an important role in the gastroprotective effect of bismuth subsalicylate against indomethacin injury.
Studies of water and electrolyte movement from oral rehydration solutions (rice‐ and glucose‐based) across a normal and secreting gut using a dual isotope tracer technique in a rat perfusion model
Authors: Wall C. R. , Bates M. S. , Cleghorn G. J. , Ward L.
Published: November 2003

Aims:

To establish a model to measure bidirectional flow of water from a glucose oral rehydration solution (G‐ORS) and a newly developed rice‐based oral rehydration solution (R‐ORS) using a dual isotope tracer technique in a rat perfusion model. To measure net water, sodium and potassium absorption from the ORS.

Method:

In vivosteady‐state perfusion studies were carried out in normal and secreting (induced by cholera toxin) rat small intestine (n=11 in each group). To determine bidirectional flow of water from the ORS the animals were initially labelled with tritium, and deuterium was added to the perfusion solution. Sequential perfusate and blood samples were collected after attainment of steady‐state conditions and analysed for water and electrolyte content.

Results:

There was a significant increase in net water absorption from the R‐ORS compared to the G‐ORS in both the normal (P<0.02) and secreting intestine (P<0.05). Water efflux was significantly reduced in the R‐ORS group compared to the G‐ORS group in both the normal (P<0.01) and the secreting intestine (P<0.01). There was an increase in sodium absorption in the R‐ORS group compared to the G‐ORS. The G‐ORS produced a significantly greater blood glucose level at 75 min compared to the R‐ORS (P<0.03) in the secreting intestine.

Conclusions:

This study demonstrates the improved water absorption from a rice‐based ORS in both the normal and secreting intestine. Evidence that the absorption of water may be influenced by the osmolality of the ORS was also demonstrated.
Maintenance therapy with cisapride after healing of erosive oesophagitis: a double‐blind placebo‐controlled trial
Authors: McDougall N. I. , Watson R. G. P. , Collins J. S. A. , McFarland R. J. , Love A. H. G.
Published: November 2003

Background:

There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing.

Aims:

To determine whether cisapride is more effective than placebo as maintenance therapy after healing of moderate erosive oesophagitis in two respects: first, in preventing symptomatic relapse and preserving quality of life; and, second, in improving oesophageal motor function.

Patients:

Forty‐two patients whose grade II–III oesophagitis had been healed with omeprazole were randomized to receive either cisapride 20 mg nocte or placebo for 6 months. Oesophageal pH monitoring and manometry were performed before starting maintenance therapy and after 4 weeks, and symptomatic status and quality of life were assessed at weeks 0, 4, 13 and 26.

Results:

After 4 weeks of maintenance therapy, lower oesophageal sphincter pressure improved in the cisapride group (16.4–21.9 mmHg, P = 0.01) but not in the placebo group (25.5–22.7 mmHg, P = 0.2). Oesophageal pH monitoring showed no significant changes in either group. Sixteen (76%) cisapride patients and 12 (57%) placebo patients withdrew within 4 weeks owing to symptomatic relapse (P = 0.2). After 26 weeks, 21 (100%) cisapride and 17 (81%) placebo patients had relapsed (log‐rank analysis of survival time P = 0.07). Quality of life parameters deteriorated in both treatment groups to a similar degree.

Conclusion:

Maintenance therapy with cisapride 20 mg nocte improves the lower oesophageal sphincter pressure in patients whose oesophagitis has been healed with omeprazole. However, cisapride is no better than placebo in preventing symptomatic relapse or deterioration in quality of life.
Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin‐dependent) diabetes mellitus
Authors: Annese V. , Lombardi G. , Frusciante V. , Germani U. , Andriulli A. , Bassotti G.
Published: November 2003

Background:

Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs.

Aims:

The purpose of the present study was to compare the effects of erythromycin (250 mg 60 min before meals) and cisapride (10 mg 30 min before meals) on gastric emptying of healthy subjects and insulin‐dependent diabetics.

Patients and methods:

Six type 1 diabetic patients with a previous scintigraphic demonstration of gastroparesis and five healthy subjects were recruited for the study. Gastric emptying was scintigraphically studied by labelling the solid component of a standard test meal. Three scintigraphic studies, spaced at least 3 days apart, were carried out on each subject, basally and after erythromycin or cisapride.

Results:

Cisapride significantly accelerated gastric emptying in both the healthy subjects and the diabetic patients without any significant effect on the lag‐time, whereas erythromycin in addition to a significant improvement of the overall gastric emptying also showed a pronounced effect on the lag‐time in both groups (controls 25 ± 5 vs. 37 ± 8 min, P≤0.04; diabetics 65 ± 11 vs. 112 ± 16 min, P<0.03).

Conclusions:

Erythromycin may represent an effective therapeutic alternative to more established forms of treatment in patients with diabetic gastroparesis, especially when other drugs have failed.
The long‐term management of patients with bleeding duodenal ulcers
Authors: McAlindon M. E. , Taylor J. S. W. , Ryder S. D.
Published: November 2003

Background:

Gastrointestinal haemorrhage is a common complication of duodenal ulcers. Patients who bleed are at substantial risk of recurrent bleeding.

Aim:

To determine whether appropriate therapeutic steps were taken to reduce the risk of recurrent haemorrhage in patients with a bleeding duodenal ulcer.

Methods:

The management of patients surviving a duodenal ulcer bleed in the University Hospital, Nottingham, was assessed by case‐note review before (1993) and after (1995–1996) institution of clinical guidelines. The following measures aimed at reducing the risk of recurrent haemorrhage were considered appropriate: stopping non‐steroidal anti‐inflammatory drugs (NSAIDs) when these were implicated in bleeding; successful eradication of Helicobacter pylori if present; and long‐term maintenance acid‐suppression therapy.

Results:

In 1993, appropriate steps were taken to reduce the risk of recurrent haemorrhage in only 48% of cases. Following the institution of guidelines, management improved significantly in 1995–1996 (appropriate in 83% of cases, P<0.001), was associated with increased referral to gastroenterologists (P<0.001), improved patient compliance with follow‐up (P<0.05), and more rigorous attempts to identify (P<0.001) and ensure clearance (P<0.001) of H.␣pylori.

Conclusion:

In this study, inadequate long‐term management of patients with a bleeding duodenal ulcer was common. This was due to a failure to adopt strategies aimed at reducing the risk of ulcer relapse and rebleeding. The quality of care improved significantly following the institution of guidelines and encouragement to refer to gastroenterologists.
Comparison of two dosing regimens of cisapride in the treatment of reflux oesophagitis
Authors: Schütze K. , Bigard M. A. , Waes L. van , Hinojosa J. , Bedogni G. , Hentschel E.
Published: November 2003

Aim:

In an international, multicentre, double‐blind trial, to document the therapeutic equivalence of two dosing regimens of cisapride on endoscopic healing and symptom improvement in patients with proven reflux oesophagitis grade I or II (Savary–Miller).

Methods:

Four hundred and seven patients were randomly allocated to treatment with either cisapride 10 mg q.d.s or cisapride 20 mg b.d. for 8–12 weeks depending on whether complete healing was found at endoscopy. The primary parameters of efficacy were cure of oesophagitis and improvement of the reflux symptom score.

Results:

The healing rates at endpoint were 73% in both treatment groups. The mean total reflux symptom score decreased from baseline to endpoint from 7.9–2.1 (cisapride 10 mg q.d.s.) and 7.9–2.5 (cisapride 20 mg b.d.). Each of the two treatment regimens was well tolerated. The most frequently (6.9%) reported adverse event (diarrhoea) was mild or moderate in most cases and can be explained by the pharmacological action of cisapride.

Conclusions:

The results of the study demonstrate that cisapride 10 mg q.d.s. and 20 mg b.d. are equivalent in terms of efficacy and safety in the treatment of reflux oesophagitis.
current practice and future perspectives in the management of gastro‐oesophageal reflux disease
Authors: LAMBERT R.
Published: November 2003

Gastro‐oesophageal reflux disease (GERD) is primarily due to incompetence of the lower oesophageal sphincter (LOS) and crural diaphragm, with transient LOS relaxation frequently accounting for daytime reflux. In the absence of drugs that adequately correct the motility defects of GERD, treatment is directed towards decreasing gastric acidity. Oesophageal healing is related to control of 24‐h intragastric acidity, the degree of acid suppression and duration of treatment.

H2‐receptor antagonists are generally less effective in GERD than in peptic ulcer disease. While providing symptomatic relief in non‐erosive GERD, they are often ineffective in healing erosive oesophagitis. Proton pump inhibitors provide more rapid and complete healing and symptom resolution. They are superior to H2‐receptor antagonists in the long‐term management of erosive oesophagitis and in reducing recurrence of oesophageal stricture following mechanical dilatation. In Barrett's oesophagus, high‐dose proton pump inhibitors in combination with laser/photodynamic ablation therapy can produce metaplastic regression, although this does not preclude future emergence of adenocarcinoma.

Surgical morbidity and mortality rates in GERD generally remain higher than those associated with long‐term pharmacotherapy. However, direct comparisons between laparascopic anti‐reflux surgery and proton pump inhibitor maintenance therapy remain to be performed.

Although there is no evidence that H. pylori infection worsens the severity of oesophagitis or that H. pylori is carcinogenic in the metaplastic oesophageal mucosa, it has been suggested that H. pylori‐positive patients requiring long‐term proton pump inhibitor therapy receive bacterial eradication therapy to reduce the risk of developing atrophic gastritis.
Twenty‐four‐hour intragastric acidity and plasma gastrin during 3‐month treatment with omeprazole in healthy subjects
Authors: DELCHIER J.‐C. , BENAMOUZIG R. , STANESCU L. , ROPERT A. , VALLOT T. , WIRQUIN V. , ROUDOT F. , LAMARQUE D. , HAMELIN B.
Published: November 2003

Background: Prolonged treatment with omeprazole 20 or 40 mg/day is sometimes required, especially for severe oesophagitis. However, information about long‐term effects on intragastric acidity and plasma gastrin response with such drug regimens is scarce.

Methods: Sixteen healthy subjects (11 men, 5 women, mean age 29 years) randomly received either 20 or 40 mg of omeprazole once daily (at 08.00 h) for 3 months. Gastric pH was recorded every 6 s for 24 h from noon to noon under standardized conditions, and blood samples were collected hourly in order to determine the 24‐h plasma gastrin response on day 0 (pre‐entry), day 7, day 28 and day 90.

Results: From day 0 to day 7, 24‐h median pH increased from 1.7 to 4.6 and mean percentage of time at pH < 4 decreased from 89% to 35% with omeprazole 20 mg. Respective values with omeprazole 40 mg were 1.9 to 4.3, and 89% to 34%. Inhibition of gastric acidity remained unchanged during the 3 months of treatment. Despite similar effects on the basis of 24‐h analysis, the decrease in daytime acidity was slightly higher with omeprazole 40 mg than with omeprazole 20 mg. Twenty‐four‐hour integrated plasma gastrin significantly increased with both drug regimens between day 0 and day 7 (P < 0.01), and between day 7 and day 28 (P < 0.01) with omeprazole 40 mg; there was no significant increase between day 28 and day 90 with either of the drug regimens.

Conclusion: Omeprazole 20 and 40 mg/day provides long‐term stable acid suppression with a progressive increase in gastrin response, stabilizing after 2 months of treatment.
Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis
Authors: GIONCHETTI P. , VENTURI A. , RIZZELLO F. , CORBELLI C. , FANTI S. , FERRETTI M. , BOSCHI S. , MIGLIOLI M. , CAMPIERI M.
Published: November 2003

Background: Rectal treatment with mesalazine enemas is the first‐line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5‐ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema.

Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc‐SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5‐ASA and Ac‐5‐ASA were measured for 6 h.

Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac‐5‐ASA was low.

Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.
Comparison of ranitidine and lansoprazole in short‐term low‐dose triple therapy for Helicobacter pylori infection
Authors: Kihira K. , Satoh K. , Saifuku K. , Taniguchi Y. , Takimoto T. , Yamamoto H. , Ido K. , Yoshida Y. , Kimura K.
Published: November 2003

Aim:

To evaluate the efficacy and safety of two 1‐week low‐dose triple‐therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection, 99␣patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole.

Methods:

The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended.

Results:

The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79–97%) and 92% in the RCM group (45 of 49; 95% CI = 84–99%). The incidence of adverse events was 16% and 18% for the two groups, respectively.

Conclusions:

No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2‐blocker is sufficient to achieve optimal H. pylori eradication.
Zamifenacin (UK‐76, 654), a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome
Authors: Houghton L. A. , Rogers J. , Whorwell P. J. , Campbell F. C. , Williams N. S. , Goka J.
Published: November 2003

Background:

Zamifenacin is a new potent gut M3 selective muscarinic antagonist developed for possible use in irritable bowel syndrome.

Methods:

In this multicentre, double‐blind, parallel group, placebo‐controlled study, the effect of a single dose of zamifenacin 10 mg or 40 mg on both fasting (30 min) and fed (60 min) colonic motor activity was assessed in 36 patients with irritable bowel syndrome (aged 25–68 years; 19 male). Colonic motility was recorded using a five‐channel solid‐state catheter introduced by colonoscopy to a depth of 35 cm in an unprepared colon.

Results:

Zamifenacin 40 mg profoundly reduced colonic motility, particularly after the meal (P < 0.05). This was reflected by a significant reduction in the mean amplitude of contractions, number of contractions, percentage duration of contractions, activity index and the motility index (P < 0.05). A smaller reduction in all the motility parameters was obtained with 10 mg zamifenacin, but these changes were not statistically significant. Three patients each on placebo and zamifenacin reported side‐effects, but these were mild and transient.

Conclusion:

A single 40 mg dose of zamifenacin significantly reduces colonic motility in irritable bowel syndrome patients without significant antimuscarinic effects. The results of this study confirm that the concept of developing selective antimuscarinic agents may be a promising approach to the treatment of irritable bowel syndrome. Not only would such compounds benefit from not having the usual side‐effects of anticho‐linergics but they might also offer much more in the way of dose flexibility.
Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease
Authors: JONES A. L. , JARVIE D. R. , SIMPSON D. , HAYES P. C. , PRESCOTT L. F.
Published: November 2003

Background: The threshold plasma paracetamol concentration at which N‐acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis.

Aim: The aim was to determine if the pharmacokinetics of NAC are altered by chronic liver disease.

Subjects and methods: NAC was given intravenously in a dose of 600 mg over 3 min to nine patients with biopsy‐proven cirrhosis (Child's grade; 1 A, 4 B, 4 C; aetiology: 7 alcohol‐related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg.

Results: The area under the serum concentration–time curve was increased (152.34 mg/L.h ± 50.38 s.d.) in cirrhotics compared with normal controls; (93.86 mg/L.h ± 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with chronic liver disease (4.52 L/h ± 1.87 s.d.) compared with controls (6.47 L/h ± 0.78; P < 0.01).

Conclusions: Increased vigilance for untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.