bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of Osmium Isotope Ratios as a New Tool to Determine the Provenance of Gold with Platinum‐Group Metal Inclusions*
Authors: Junk S. A. , Pernicka E.
Published: December 2004

The sudden increase in the amount of Celtic gold coins circulating in central Europe during the second century bc coincides with the appearance of platinum‐group mineral (PGM) inclusions in the Celtic gold. It has been proposed that large amounts of gold were introduced from the eastern Mediterranean by mercenaries following the conquest by Alexander the Great, but another hypothesis might be the discovery of entirely new gold sources in central Europe during this time. The presence of PGM inclusions in gold objects is usually taken as an indication for an origin from placer deposits (Hartmann 1970; Park 1986). Initially, it was hoped that those inclusions could be characteristic for a certain deposit, but Meeks and Tite (1980) have shown that the compositional variation within a single gold object can be as large as the total variation observed in all investigated gold artefacts. Therefore, the elemental composition of the PGMs in gold artefacts does not provide any reliable information on the provenance of the gold.

An alternative to chemical analysis of the inclusions is the determination of their osmium isotope ratios. Similarly to lead, osmium exhibits a variable isotopic composition due to the radioactive decay of 187Re and 190Pt. In order to investigate the potential of this new geochemical tool to determine the provenance of ancient gold, a quasi‐non‐destructive method for the determination of Os isotope ratios with LA–MC–ICP–MS has been developed.

The results show that different types of deposits can be distinguished by Os isotope patterns and their distributions when applying a simple descriptive statistical method. In contrast to lead isotope ratios, the variations of Os isotope abundances are rather large in many ore deposits. But, also contrary to lead, the heterogeneity of the Os isotope ratios of the deposits is preserved in the artefacts, because the analysed PGMs are not dissolved during melting of the gold. Therefore, it is feasible to distinguish between different types of gold sources and to define specific deposits provided that the artefact contains several PGMs. The application of this new technique to Celtic gold coins from southern Germany and coins from western Anatolia has been demonstrated in this study.
Insect Remains from the Collections in the Egyptian Museum of Turin
Authors: Panagiotakopulu E.
Published: December 2004

The identification of insects preserved in pharaonic antiquities stored in the Egyptian Museum of Turin provides new information on aspects of biogeography, storage and trade. The khapra beetle, Trogoderma granarium, the biscuit beetle, Stegobium paniceum, and the house fly, Musca domestica, were recovered from food offerings from tombs in Egypt, and Dermestes frischii was found embedded in resin from a cartonnage mask. The study produced some of the earliest records of pests of stored products, and the khapra beetle may indicate early contacts with the Indian subcontinent. The problems of differentiating modern and ancient infestation are discussed.
The nature, extent and causes of land degradation in South Africa: legacy of the past, lessons for the future?
Authors: Meadows M. E. , Hoffman M. T.
Published: December 2004

The aim of this paper is to reassess the land degradation and desertification problem in South Africa. The country has a wide range of interrelated environmental and development challenges existing in a socio–political context recently subject to substantial change. The paper outlines the fundamental environmental constraints and opportunities that underlie degradation phenomena and illustrates the nature, extent and geographical distribution of the major forms of soil and vegetation degradation in the country. The principal causes of degradation are identified and some important land use and land tenure questions that need to be addressed in the near future are posited.
Are Statistical Contributions to Medicine Undervalued?
Authors: Breslow Norman E.
Published: December 2004

Summary. Econometricians Daniel McFadden and James Heckman won the 2000 Nobel Prize in economics for their work on discrete choice models and selection bias. Statisticians and epidemiologists have made similar contributions to medicine with their work on case‐control studies, analysis of incomplete data, and causal inference. In spite of repeated nominations of such eminent figures as Bradford Hill and Richard Doll, however, the Nobel Prize in physiology and medicine has never been awarded for work in biostatistics or epidemiology. (The “exception who proves the rule” is Ronald Ross, who, in 1902, won the second medical Nobel for his discovery that the mosquito was the vector for malaria. Ross then went on to develop the mathematics of epidemic theory—which he considered his most important scientific contribution—and applied his insights to malaria control programs.) The low esteem accorded epidemiology and biostatistics in some medical circles, and increasingly among the public, correlates highly with the contradictory results from observational studies that are displayed so prominently in the lay press. In spite of its demonstrated efficacy in saving lives, the “black box” approach of risk factor epidemiology is not well respected. To correct these unfortunate perceptions, statisticians would do well to follow more closely their own teachings: conduct larger, fewer studies designed to test specific hypotheses, follow strict protocols for study design and analysis, better integrate statistical findings with those from the laboratory, and exercise greater caution in promoting apparently positive results.
Sequential Tests for Noninferiority and Superiority
Authors: Brannath W. , Bauer P. , Maurer W. , Posch M.
Published: December 2004

Summary.  The problem of simultaneous sequential tests for noninferiority and superiority of a treatment, as compared to an active control, is considered in terms of continuous hierarchical families of one‐sided null hypotheses, in the framework of group sequential and adaptive two‐stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows one to construct designs where, e.g., a rigid stopping criterion is chosen, rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to use monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide, at the interim analysis, whether he is satisfied with the noninferiority margin achieved at this stage, or wants to go for more at the second stage. In the case where he proceeds to the second stage, he may perform midtrial design modifications (e.g., reassess the sample size). The proposed approach allows one to “spend,” e.g., less of α for an early proof of noninferiority than for an early proof of superiority, and is illustrated by typical examples.
Effect of conjugated equine estrogen in combination with two different progestogens on the risk factors of coronary heart disease in postmenopausal Chinese women in Taiwan: a randomized one‐year study
Authors: Chang Ting‐Chen , Lien Yih‐Ron , Chen Ming , Cheng Shao‐Pei , Chen Ruey‐Jien , Chow Song‐Nan
Published: December 2004

Background.  To compare the effect of hormone replacement therapy (HRT) using estrogen plus dydrogesterone or estrogen plus medroxyprogesterone acetate (MPA) on the risk factors for coronary heart disease (CHD) in postmenopausal women.

Methods.  A randomized, prospective 1‐year clinical trial was designed. All of the postmenopausal women (n = 279) received sequential conjugated equine estrogen (CEE) at a dose of 0.625 mg/day for 25 days (days 1–25) of each month. These women were also randomly assigned to receive either dydrogesterone 10 mg/day (E + D group, n = 140) or MPA 5 mg/day (E + P group, n = 139) for 14 days (days 12–25) of each month. Serum biochemical markers, lipoproteins, plasma prothrombin time (PT), partial prothrombin time (PPT) and antithrombin III‐antigen (ATIII‐Ag) were analyzed at baseline, and after 6 and 12 months of treatment.

Results.  Liver function, renal function, PT and PPT did not change significantly during the 12‐month trial. The E + D group had a more pronounced increase in high density lipoprotein cholesterol (HDL‐C) than the E + P group (10.6% vs. 2.7%) after 12 months of treatment (p < 0.05). Both groups showed reduced concentrations of total cholesterol (T‐CHO), low density lipoprotein cholesterol (LDL‐C) and ATIII, whereas triglyceride (TG) was increased at the end of the trial (without intergroup difference).

Conclusions.  Our study demonstrated a favorable effect on lipoprotein profiles with both hormone replacement therapy regimens. Dydrogesterone appears to be superior to medroxyprogesterone acetate from the perspective of modification of coronary heart disease risk factors.
Pregnancy at high altitude: a hyperviscosity state
Authors: Kametas Nikos A. , Krampl Elisabeth , McAuliffe Fionnuala , Rampling Michael W. , Nicolaides Kypros H.
Published: December 2004

Background.  Pregnancy at high altitude has been associated with intrauterine growth restriction and preeclampsia. These conditions, at sea level, have been linked to increased hematocrit and blood viscosity. The aim of this study was to investigate the effect of high altitude on maternal hemorheology.

Methods.  This was a cross‐sectional study. We examined 94 pregnant women at 10–38 weeks of gestation resident at high altitude (4370 m above sea level) and 75 at sea level, and 24 and 17 nonpregnant women at each altitude, respectively. Blood and plasma viscosity, hematocrit, plasma fibrinogen, albumin and total protein concentrations were determined in blood samples obtained after an overnight period of fasting.

Results.  Pregnancy at high altitude, compared to sea level, is characterized by higher hematocrit, blood viscosity (at high shear rate), plasma viscosity, total protein and fibrinogen concentrations (25%, 38%, 7%, 13.3% and 25%, respectively) and 6% lower albumin concentration. Nonpregnant women at high altitude, compared to sea level, had higher hematocrits, blood viscosity, plasma viscosity, total protein and fibrinogen concentrations (25%, 55%, 18%, 26% and 98%, respectively) and 13% lower albumin concentration.

Conclusion.  Pregnancy at high altitude compared to sea level is characterized by increased blood viscosity as a result of increased hematocrit and plasma viscosity.
Urinary nitric oxide metabolite changes in spontaneous and induced onset active labor
Authors: Chen Da‐Chung , Ku Chih‐Hung , Huang Yi‐Chun , Chen Chi‐Huang , Wu Gwo‐Jang
Published: December 2004

Background.  The aim of this prospective, randomized study was to investigate the changes in urinary nitric oxide (NO) metabolite between the latent and the active phases of spontaneous and either prostaglandin E1 (PGE1) or prostaglandin E2 (PGE2)‐induced labors.

Methods.  Eighty‐eight singleton pregnant women at 36–41+ weeks' gestation without signs of fetal distress were enrolled. The first group consisted of 29 pregnant women in whom labor was induced by PGE1 applied intravaginally. The second group consisted of 29 pregnant women with labor induced by PGE2 applied intracervically. The third group consisted of 30 women, who had spontaneous active labor. Clinical data of the three groups were assessed as labor progressed.

Results.  Urinary nitric oxide/creatinine (U NO/Cr) decreased significantly after the onset of active labor in all three groups (p < 0.005), with the percentage decline of 42.2%, 28.6% and 10.1%, respectively. The magnitude of the difference in decline in U NO/Cr after active labor between the PGE1‐induced and the spontaneous labor group was significantly reduced (p = 0.0047) after adjustment for potential confounders using the generalized estimating equations test (GEE). The duration of the latent phase was significantly shortened in the PGE1‐induced group as compared with the spontaneous labor group (p < 0.01).

Conclusions.  Decreased U NO/Cr may facilitate transition from the latent to the active phase either in spontaneous or induced labors. Our results indicate that U NO/Cr can serve as an easily obtained marker for use in controlling myometrial contractility and cervical ripening at the onset of active labor. The nitric oxide system is present in the human uterus and may contribute to uterine quiescence during pregnancy and show down‐regulation in U NO/Cr at the initiation of active labor.
Sense of place and migration historiesIdiotopyandidiotope
Authors: Pascual‐de‐Sans Àngels
Published: December 2004

The aim of this article is to explore a methodological approach relevant to the study of population mobility. The approach considers not only the whole migratory process and the sequence of connected movements, but also what happens between each of them. The study of mobility is considered inseparable from the study of passage, permanence and settlement. This paper establishes the interest in elaborating concepts that express the interaction between people and places, and how these interactions contribute to an understanding of migratory processes and of ‘place histories’. In this sense, geographical identification (idiotopy) and place identification (idiotope) are put forward as useful concepts.
A new methodology for evaluating coastal scenery: fuzzy logic systems
Authors: Ergin A , Karaesmen E. , Micallef A , Williams A T
Published: December 2004

Coastal scenery evaluated by utilization of selected landscape components was subjected to a fuzzy logic systems approach. Twenty‐six top‐rated parameters were identified from a literature search/questionnaire surveys carried out in Malta, Turkey and the UK and coastal scenery investigated at 57 sites. A coastal scenic evaluation checklist system was finalized and consisted of assessment parameters based on a five‐point scale ranging from low to high attribute values. Coastal user parameter preferences and priorities for these parameters were obtained by a questionnaire perception study (n=270) given to both locals and visitors. Assessment parameter weights were calculated from this public perception survey via matrices relating to the selected landscape components. For each of the 26 parameters, a membership‐graded matrix was established to counteract potential errors in assigning grades to the parameters when one has to give a unique number to the attribute value. To overcome subjectivity and quantify uncertainty, fuzzy logic mathematical methodology was adopted to this checklist approach. This enabled an Evaluation Index (D) value to be calculated, establishing a 5‐class evaluation system. Class 1 scenery (extremely attractive natural site) had D values > 0.85; Class 2, between 0.85 and 0.65; Class 3, between 0.65 and 0.4; Class 4, between 0.4 and zero; Class 5 (very unattractive, intensively developed urban) below zero.
Articular calcified cartilage canals in the third metacarpal bone of 2‐year‐old thoroughbred racehorses
Authors: Boyde A. , Firth E. C.
Published: December 2004

We describe morphological aspects of the articular calcified cartilage mineralizing front ‘tidemark’ in the distal joint surface of the third metacarpal bone from 14 horses. Compositional backscattered electron scanning electron microscopy and confocal scanning light microscopy were conducted on polymethylmethacrylate (PMMA)‐embedded medio‐lateral slices. After maceration, scanning electron microscopy (SEM) was used to study the calcified cartilage surface in the ‘wedges’ intervening between the slices. An anatomically reproducible clustering of canals in the calcified cartilage was found at one site on the sagittal ridge in all the horses. The site is one that is relatively less loaded during joint function. These canals through calcified cartilage result from osteoclastic resorption (cutting cones) penetrating from bone through to the non‐mineralized hyaline articular cartilage. Their presence may indicate a pathway for connection between bone and cartilage extracellular fluid. In one horse, repair of such canals by plugging with new calcified cartilage was demonstrated. Differences in the degree of mineralization of regions of cartilage were seen in the combined compositional‐cum‐topographical backscattered SEM images of the macerated ‘tidemark’ front. More‐or‐less circular patches of lower mineralization density were frequently centred on (and may possibly originate from) canals. These microanatomical features should be searched for in other joints, at other ages and in other species to discover their frequency and significance.
The nucleolus and its modifications during oogenesis of Torpedo marmorata
Authors: Prisco M. , Ricchiari L. , Montella R. , Liguoro A. , Andreuccetti P.
Published: December 2004

The structural organisation of the nucleolar apparatus during oogenesis of the spotted ray Torpedo marmorata was investigated. The observations showed that unlike other cartilaginous fishes, in T. marmorata the nucleolar apparatus was always represented by one or two conspicuous nucleoli, whose organization significantly changed during oocyte development. In the smallest follicles (follicles <300 μm in diameter) the nucleolus was made up of granular and fibrillar components, and actively incorporated 3H uridine; later it becomes more and more electron‐dense so in follicles of 400 μm in diameter its components and 3H uridine incorporation were no longer evident. These results indicate that in T. marmorata the nucleolar apparatus significantly changes and undergoes a possible impairment in rRNA synthesis. After nucleolus inactivation, the synthesis of rRNA may be substained by granulosa.
Feeding ecology of central Baltic Sea herring and sprat
Authors: Möllmann C. , Kornilovs G. , Fetter M. , Köster F. W.
Published: December 2004

A unique dataset of stomach contents sampled between 1977 and 1999 in the central Baltic Sea was used to perform a comprehensive study of the feeding ecology of Central Baltic herring Clupea harengus and sprat Sprattus sprattus. Both fish species were mainly preying upon calanoid copepods with Pseudocalanus sp. dominating the diet of herring, whereas sprat generally preferred Temora longicornis. Sprat preyed upon older copepodite stages, indicating size‐selective particulate feeding, whereas herring additionally fed on smaller copepodite stages, indicating occasional low food supply inducing filter‐feeding. Additional food sources other than copepods were mysids in winter and autumn for medium to large herring, as well as cladocerans for sprat in spring and summer, determined by the seasonal occurrence of these plankton species. Seasonally the highest feeding activity of both fishes species occurred in spring and summer, the main reproductive periods of calanoid copepods. The most important food item for both predators in spring was Pseudocalanus sp. In summer sprat switched to T. longicornis and Acartia spp. Since the late 1970s, the total stomach fullness decreased and the fraction of empty stomachs increased. In parallel the amount of Pseudocalanus sp. in the diets of both fish species decreased. Further, a considerable dietary overlap between both species in spring indicated considerable competition for food resources, especially due to an enlarged sprat stock. The results of this study support the hypothesis that growth reductions observed in Baltic herring and sprat are due to combination of a change in food availability and an increase in density‐dependent competition.
Antipredator behaviour of 0+ year Perca fluviatilis: effect of vegetation density and turbidity
Authors: Snickars M. , Sandström A. , Mattila J.
Published: December 2004

In this study, the combined influence of vegetation density and water turbidity on habitat utilization of a prey fish, 0+ year perch Perca fluviatilis, under predation risk (pike, Esox lucius) was investigated. The vegetated habitat was overall preferred over the open habitat in the presence of a predator. The level of turbidity, and to a lesser extent vegetation density, however, influenced the response of 0+ year perch. The use of the vegetated habitat was lower in very turbid than in clear and turbid conditions, suggesting reduced antipredator behaviour in very turbid water. The effect of vegetation density on antipredator behaviour was only present in clear water, where the use of a structural refuge decreased with increasing vegetation density. No such effect was observed in turbid and very turbid water. The results showed that the structuring role of vegetation or habitat complexity may diminish with increased turbidity. The observed masking effect of turbidity suggests that predator‐prey interactions in vegetated habitats are more complex than what has generally been thought.
National Service Frameworks and UK general practitioners: street‐level bureaucrats at work?
Authors: Checkland Kath
Published: December 2004

This paper argues that the past decade has seen significant changes in the nature of medical work in general practice in the UK. Increasing pressure to use normative clinical guidelines and the move towards explicit quantitative measures of performance together have the potential to alter the way in which health care is delivered to patients. Whilst it is possible to view these developments from the well‐established sociological perspectives of deprofessionalisation and proletarianisation, this paper takes a view of general practice as work, and uses the ideas of Lipsky to analyse practice‐level responses to some of these changes.

In addition to evidence‐based clinical guidelines, National Service Frameworks, introduced by the UK government in 1997, also specify detailed models of service provision that health care providers are expected to follow. As part of a larger study examining the impact of National Service Frameworks in general practice, the response of three practices to the first four NSFs were explored. The failure of NSFs to make a significant impact is compared to the practices’ positive responses to purely clinical guidelines such as those developed by the British Hypertension Society. Lipsky's concept of public service workers as ‘street‐level bureaucrats’ is discussed and used as a framework within which to view these findings.
Helminths as therapeutic agents for inflammatory bowel disease
Authors: Hunter M. M. , Mckay D. M.
Published: December 2004

Over the last decade major advances have been made in our understanding of the mechanisms and mediators of inflammation that hold the promise of the development of new therapies for inflammatory disease. While much is to be gleaned from the application of new technologies, assessment of the age‐old host–parasite relationship may also provide insights on how to counter pathological inflammatory events. In the case of inflammatory bowel disease [particularly Crohn's disease, which is associated with T helper 1 (Th1) events] it is proposed that infection with parasitic helminths would be beneficial: the paradigm being that of immune deviation, where Th2 cytokines mobilized in response to the helminth will prevent or antagonize the disease‐promoting Th1 events in the gut. The situation is unlikely to be this simple. Here we review and critique the data in support of helminth therapy for inflammatory bowel disease, drawing attention to the gaps in knowledge and presenting a view on how the field may be advanced. While the concept of helminth therapy may be superficially unappealing, this review may convince the reader of the value of more extensive analyses of the impact of helminth infection on enteric inflammation.
Guidelines for the appropriate use of non‐steroidal anti‐inflammatory drugs, cyclo‐oxygenase‐2‐specific inhibitors and proton pump inhibitors in patients requiring chronic anti‐inflammatory therapy
Authors: Dubois R. W. , Melmed G. Y. , Henning J. M. , Laine L.
Published: December 2004

Aim : To rationalize decision making around the use of different non‐steroidal anti‐inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk.

Methods : The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community‐based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo‐oxygenase‐2‐specific inhibitors and proton pump inhibitor co‐therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as ‘appropriate’, ‘uncertain’ or ‘inappropriate’.

Results : In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as ‘appropriate’ for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo‐oxygenase‐2‐specific inhibitor + proton pump inhibitor as ‘inappropriate’. For patients aged > 65 years and at low risk, an NSAID or cyclo‐oxygenase‐2‐specific inhibitor alone was rated as ‘uncertain’. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as ‘inappropriate’, and either a cyclo‐oxygenase‐2‐specific inhibitor or an NSAID +proton pump inhibitor was rated as ‘appropriate’. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo‐oxygenase‐2‐specific inhibitor in conjunction with a proton pump inhibitor was rated as ‘appropriate’.

Conclusions : Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo‐oxygenase‐2‐specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.
Chemotherapy for pancreatic cancer
Authors: Shore S. , Raraty M. G. T. , Ghaneh P. , Neoptolemos J. P.
Published: December 2004

Pancreatic cancer is a common, highly lethal disease that is rising in incidence. Chemotherapy based on 5‐fluorouracil (5‐FU) has been shown to prolong survival in advanced pancreatic cancer. Gemcitabine improves major symptoms and survival outcomes compared with bolus 5‐FU. Many novel small molecules are being widely and actively researched. These compounds are based on classical mechanisms of action as well as biological therapies targeting novel cellular survival pathways, and include fluoropyrimidines, nucleoside cytidine analogues, platinum analogues, topoisomerase‐inhibitors, antimicrotubule agents, proteasome inhibitors, vitamin D analogues, arachidonic acid pathway inhibitors, histone deacytylator inhibitors, farnesyltransferase inhibitors and epidermal growth factor receptor therapies.

Adjuvant chemotherapy has also demonstrated the best survival outcomes following resection compared to other adjuvant or neo‐adjuvant strategies such as radiation‐based treatments. These benefits are superimposed on the dramatic increase in resectability rates and reduction in post‐operative mortality achieved by centralisation of treatment in high‐volume speciality centres.

Newer ‘small‐molecule’ drugs as well as the latest ‘large‐molecule’ biological agents hold considerable promise for the future. Real advances are anticipated over the next five years but are dependent on large randomised controlled trials for success.
Dyspeptic symptoms associated with Helicobacter pylori infection are influenced by strain and host specific factors
Authors: Treiber G. , Schwabe M. , Ammon S. , Walker S. , Klotz U. , Malfertheiner P.
Published: December 2004

Background : Dyspepsia can be associated with H. pylori infection.

Aim : To assess dyspeptic symptoms and potentially influencing factors before and up to 6 months following successful H. pylori eradication therapy.

Methods : Prospective cohort study involving H. pylori positive subjects from ambulatory or hospitalized care. Main outcome measures were symptoms during baseline and follow‐up, the proportion of symptom‐free patients, and symptom scores.

Results : After successful eradication, the summary score of all dyspeptic symptoms decreased and during follow‐up, the proportion of symptom‐free patients was higher in the group with peptic ulcers (69.4% vs. 40.9%, P < 0.0001) than with functional dyspepsia (FD).

Regardless of diagnosis, virulent strains of H. pylori were associated with a higher prevalence of epigastric pain before treatment: absolute risk‐difference (ARD) with Oip‐A: 18.2%, Odds Ratio (OR) 2.35 [1.3–4.2, 95%‐CI], P = 0.01; with Cag‐A: 24.6%, OR 2.81 [1.6–5], P = 0.01. Low‐dose aspirin in part was a major risk factor in FD for previous weight loss bdfore study entry. Post‐treatment, non‐ulcer patients were more likely to suffer from distention/bloating. Likewise, alcohol induced persistence of nausea and vomiting in this population.

Conclusions : Dyspeptic symptoms in H. pylori infected patients are more common with virulent strains. Symptoms are more likely to persist despite successful eradication if patients initially harboured virulent strains or concomitant aspirin or alcohol intake are present. In one‐third of peptic ulcer patients, symptoms will not be cured 3 months after therapy.
The acidity index: a simple approach to the measurement of gastric acidity
Authors: Tutuian R. , Castell D. O. , Xue S. , Katz P. O.
Published: December 2004

Background : The percentage of time intragastric pH < 4 is a major parameter in evaluating the efficiency of acid‐suppressive therapies. This parameter is easy to calculate, but does not identify the actual pH level. Recent studies have recommended the use of the integrated intragastric acidity as a more refined method of assessing intragastric acid control.

Aim : To describe a new parameter, the acidity index, based on the logarithmic aspect of pH calculation, which may overcome the limitations of the percentage of time intragastric pH < 4 and the integrated intragastric acidity.

Methods : The acidity index was calculated by obtaining the sum of 1000 × % time pH < 1, 100 × % time pH < 2 and ≥ 1, 10 × % time pH < 3 and ≥ 2 and % time pH < 4 and ≥ 3. The total percentage of time pH < 4 and the integrated intragastric acidity were calculated based on previous descriptions. The correlations between these parameters were analysed.

Results : The mean ± s.d. values were 60% ± 22% for the percentage of time pH < 4, 172 ± 178 for the acidity index and 1114 ± 1176 mmol/L.h for the integrated intragastric acidity. Both the integrated intragastric acidity (r = 0.63) and acidity index (r = 0.70) showed only fair correlation with the percentage of time pH < 4. In contrast, there was a strong positive correlation (r = 0.93) between the acidity index and integrated intragastric acidity.

Conclusion : The acidity index is easy to calculate, allows a more accurate assessment of the intragastric acidity than does the percentage of time pH < 4, and is comparable with the more complicated integrated gastric acidity in assessing intragastric pH control.
Mycophenolate mofetil for Crohn's disease: short‐term efficacy and long‐term outcome
Authors: Wenzl H. H. , Hinterleitner T. A. , Aichbichler B. W. , Fickert P. , Petritsch W.
Published: December 2004

Aim : To assess the long‐term efficacy of the antimetabolite agent mycophenolate mofetil in patients with Crohn's disease.

Methods : Twenty patients with complicated Crohn's disease were treated with mycophenolate mofetil, 1 g b.d., for up to 7 years. Twelve patients were intolerant to azathioprine, seven were resistant to azathioprine and one had a history of mesalazine‐induced pancreatitis. The response to mycophenolate mofetil was determined by calculation of the Harvey–Bradshaw index, the ability to taper steroids and the grading of fistula activity.

Results : After 6 months, 11 of the 20 patients had responded. Seven of the 11 responders relapsed after a median of 18 months, three have an ongoing response at month 17, 19 and 82, and one discontinued mycophenolate mofetil owing to toxicity. After initial treatment failure, mycophenolate mofetil was continued in 12 of 17 patients for a further 2–41 months without inducing a stable remission. Mycophenolate mofetil was of benefit in nine of the 12 patients intolerant to azathioprine and in two of the seven patients resistant to azathioprine. Perianal fistulas improved in seven of eight patients; five of the seven subsequently deteriorated, but only one due to reactivated perianal disease.

Conclusions : Mycophenolate mofetil was initially effective in a sizeable fraction of patients with complicated Crohn's disease, but relapse within 18 months was common. Nevertheless, mycophenolate mofetil could be a useful alternative in patients intolerant to azathioprine.
Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics
Authors: Tonini M. , Cipollina L. , Poluzzi E. , Crema F. , Corazza G. R. , De Ponti F.
Published: December 2004

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5‐hydroxytryptamine‐3 (5‐HT3) and 5‐HT4 receptors for metoclopramide; 5‐HT4 receptors for levosulpiride) and ability to permeate the blood–brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5‐HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti‐emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood–brain barrier, hyperprolactinaemia is a side‐effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood–brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
Cost‐effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re‐bleeding
Authors: Raines D. L. , Dupont A. W. , Arguedas M. R.
Published: December 2004

Background: Measurement of the hepatic venous pressure gradient may identify a sub‐optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost‐effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined.

Methods: A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta‐blockers alone, beta‐blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta‐blockers plus isosorbide mononitrate or beta‐blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non‐responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years.

Results: The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost‐effectiveness ratio of the latter strategy was $136 700 per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re‐bleeding were increased.

Conclusions: The cost‐effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re‐bleeding rates.
Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis
Authors: Malik A. H. , Kumar K. S. , Malet P. F. , Jain R. , Prasad P. , Ostapowicz G.
Published: December 2004

Background : Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature.

Aim : To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis.

Methods : One hundred and eighty‐six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages.

Results : The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III–IV) had more fragments than those with no or mild fibrosis (stages 0–II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis.

Conclusions : Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.
Improvement in serum pepsinogens and gastrin in long‐term monitoring after eradication of Helicobacter pylori: comparison with H. pylori‐negative patients
Authors: Ohkusa T. , Miwa H. , Nomura T. , Asaoka D. , Kurosawa A. , Sakamoto N. , Abe S. , Hojo M. , Terai T. , Ogihara T. , Sato N.
Published: December 2004

Background : A decrease in pepsinogen and gastrin levels 1–3 months after Helicobacter pylori eradication is well known. However, few data are available on the long‐term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori‐negative patients with dyspepsia.

Aim : We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori‐negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio.

Methods : We enrolled 172 H. pylori‐positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non‐treated H. pylori‐negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System.

Results : In the H. pylori‐negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 ± 20.8 ng/mL, 9.2 ± 4.2 ng/mL, 6.0 ± 1.7 and 53.5 ± 29.2 pg/mL, respectively. In H. pylori‐positive patients with long‐term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 ± 46.6 ng/mL, 25.9 ± 17.1 ng/mL, 3.4 ± 1.3 and 131.9 ± 130.8 pg/mL, respectively, before treatment. At 1–3 months after eradication, serum pepsinogen I and II levels in the H. pylori‐positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12–15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1–3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12–15 months.

Conclusion : The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long‐term follow‐up study.
Helicobacter pylori infection in two areas in Japan with different risks for gastric cancer
Authors: Nobuta A. , Asaka M. , Sugiyama T. , Kato M. , Hige S. , Takeda H. , Kato T. , Ogoshi K. , Keida Y. , Shinomura J.
Published: December 2004

Background : We evaluated the relationship between Helicobacter pylori and various factors associated with gastric cancer in two areas in Japan with different risks for mortality due to gastric cancer.

Methods : A total of 250 sera from Niigata and 209 from Okinawa were used. H. pylori antibody and CagA antibody were measured by antigen‐specific ELISAs. Serum gastrin and pepsinogen levels were determined by RIA.

Results : Although there was no significant difference in H. pylori prevalence among the persons in Niigata (50%) and Okinawa (42%), CagA prevalence in these populations was significantly different, at 41% and 26%, respectively (OR = 1.98, 95%CI: 1.33–2.95, P < 0.01). Serum gastrin levels in Niigata were significantly lower than those in Okinawa in H. pylori‐negative persons (P < 0.01). The serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in H. pylori positive persons (P < 0.01), whereas there was no significant difference in H. pylori‐negative persons. Among those positive for H. pylori, serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in CagA‐negative persons (P < 0.01), whereas no significant difference was observed in CagA‐positive persons.

Conclusions : These results suggest that the difference in the mortality ratio of gastric cancer between Niigata and Okinawa is mainly associated with the difference between areas in the prevalence of cagA‐positive strains rather than that of H. pylori itself.
Helicobacter pylori‐positive patients with pruritic skin diseases are at increased risk for gastric cancer
Authors: Shiotani A. , Sakurane M. , Furukawa F.
Published: December 2004

Background : Helicobacter pylori infection has been implicated as a possible cause of extraintestinal disorders such as skin diseases. A number of case reports describe patients with skin diseases, such as prurigo nodularis, that are associated with gastric cancer.

Aim : The aim of this study was to examine the prevalence of H. pylori infection and the incidence of gastric cancer in patients with pruritic skin diseases.

Methods : The patients were examined for circulating specific IgG antibodies against H. pylori in sera using ELISA. H. pylori‐positive patients who were more than 40 years old underwent endoscopic screening for gastric cancer.

Results : We examined 134 patients with pruritic skin diseases, including 55 cases of cutaneous pruritus, 21 cases of prurigo chronica multiforme, 15 cases of nummular dermatitis and 43 cases of chronic urticaria. Early gastric cancer was detected in 2/36 (5.6%) patients with cutaneous pruritus and 3/16 (18.8%) with prurigo chronica multiforme. The prevalence of early gastric cancer was 5.6%, which was much higher than that among patients undergoing general endoscopic screening for gastric cancer.

Conclusions : These results suggest that H. pylori‐positive patients with pruritic skin diseases may be at increased risk for development of gastric cancer, and endoscopic screening in such patients is recommended.
Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer
Authors: Shiotani A. , Iishi H. , Uedo N. , Higashino K. , Kumamoto M. , Nakae Y. , Tatsuta M.
Published: December 2004

Background : In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density.

Aim : The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer.

Methods : We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age‐matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA.

Results : Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded‐type group than in the depressed‐type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases.

Conclusions : Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.
Expression of leptin in two‐layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment
Authors: Nakamura M. , Takahashi T. , Matsumoto T. , Akiba Y. , Matsui H. , Tsuchimoto K. , Ishii H. , Yamada H.
Published: December 2004

Background : Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori‐infected human and Mongolian gerbil fundic mucosa.

Aim : The present study was undertaken to clarify the H. pylori–induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts.

Methods : GSM06 cells were incubated with an air− liquid interface on a collagen gel layer containing mouse fibroblast cell line L929. Medium containing H. pylori bacilli (ATCC43504) at 10–100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry. The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity.

Results : L929 cells in the control group showed a spindle shape with scarce cytoplasm. In the H. pylori‐treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity. In contrast, L929 cells incubated with H. pylori alone did not undergo this differentiation.

Conclusions : Attachment of H. pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts. We suggest that leptin plays a role in this transformation.