bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in woody vegetation cover in the Kruger National Park, South Africa, between 1940 and 1998
Authors: Eckhardt H. C. , van Wilgen B. W. , Biggs H. C.
Published: March 2003

Changes in the cover and density of shrubs and trees were assessed from aerial photographs (1940, 1974 and 1998) as well as from fixed‐point photographs taken in 1984 and 1996 in the Kruger National Park, South Africa. Woody cover (trees and shrubs combined) increased by 12% on granite substrates but decreased by 64% on basalt substrates over the past 58 years. Both these figures are expressed in terms of the initial values, respectively. The density of the large tree component of woody vegetation decreased on both substrates. Woody vegetation cover declined as fire return periods became shorter, but the relationship was weak. The increases in woody plant density and cover on granite are thought to be the result of decreased competition from grasses, which in turn is a result of overgrazing by wild herbivores whose numbers have been kept high through the provision of surface water. These effects were not seen on the relatively nutrient‐rich basalts, where grasses can recover rapidly even after heavy grazing. The decline in overall woody cover on basalts is interpreted as a result of regular, short‐interval prescribed burning over the past 40 years, while the universal decline in large trees seems to result from an interaction between regular, frequent fires and utilization by elephants. The implications for management are discussed.
Elephant utilization of Colophospermum mopane: possible benefits of hedging
Authors: Smallie J. J. , O'connor T. G.
Published: March 2003

The pattern of utilization of Colophospermum mopane by elephant was investigated in a semi‐arid savanna, the Venetia‐Limpopo Nature Reserve, South Africa, using an animal‐based approach. C. mopane is a staple food item in the diet of elephant, with most individual trees being utilized lightly (< 10% of biomass removed). Utilization of branch, foliage and main stems accounted for most of the utilization of trees < 4 m high whilst utilization of bark accounted for the majority of utilization of trees > 4 m high. The most preferred height of utilization of branches was < 1 m above ground level, reflecting the short stature of C. mopane in the study area. Elephant selected C. mopane trees < 2 m in height that had been previously utilized by them; specifically trees where the terminal part of the main stem had been previously broken and had been coppiced (hedging). The preferred size range of branches utilized by elephant was 0.946–1.718 cm in diameter; hedged C. mopane trees in the 1–2 m category had, on average, significantly more branches within this size range than non‐hedged trees. This hedging of C. mopane appears to have increased the availability of a preferred food item.
Resource availability and distribution patterns, indicators of competition between Macrotermes bellicosus and other macro‐detritivores in the Comoé National Park, Côte d'Ivoire
Authors: Korb Judith , Linsenmair Karl Eduard
Published: March 2003

Interspecific competition has rarely been demonstrated in field studies. For it to occur a resource must be in limited supply and potential competitors must be concurrently active in time and space. We studied the availability of plant litter during the course of the year and the activity and distribution of macro‐detritivores (termites, diplopods and earthworms) in two habitats in a Guinea savanna (Côte d'Ivoire), to test whether interspecific competition might be important. Plant litter was limited during the rainy season in the savanna, but was never limited in the gallery forest. The termite Macrotermes bellicosus, the dominant macro‐detritivore in this area, and other detritivorous termites (e.g. Microtermes spp., Ancistrotermes spp., Odontotermes spp.) were active all year round with a peak during the rainy season, when diplopods and earthworms were also active. In the savanna at the beginning of the rainy season when food became limiting, other detritivorous termite species were more active in the absence of M. bellicosus than in its presence. This complementary activity pattern of M. bellicosus and other termites indicates that interspecific competition among detritivorous termites may be occurring. However, the spatio‐temporal distribution of diplopods and earthworms suggests that interspecific competition with M. bellicosus is of minor importance.
COX‐2, prostanoids and colon cancer
Authors: Ota S. , Bamba H. , Kato A. , Kawamoto C. , Yoshida Y. , Fujiwara K.
Published: March 2003

Epidemiological, experimental, and clinical studies have demonstrated that colon carcinogenesis may be prevented by nonsteroidal anti‐inflammatory drugs (NSAIDs). Although controversy remains, recent studies, including ours, have revealed that NSAIDs suppress colon carcinogenesis at the adenoma stage where cyclooxygenase‐2 (COX‐2), a major molecular target in this action, is mainly expressed in interstitial cells but not in tumour cells. Therefore, it is unlikely that NSAIDs prevent colon cancer formation through modulating the functions of tumour cells. A more possible assumption is that NSAIDs suppress colon carcinogenesis through the inhibition of prostaglandin formation. However, the mechanisms by which prostanoids promote colon carcinogenesis have not been elucidated to date. A prostanoids act through both membrane receptors and nuclear receptors such as peroxisome proliferator receptor (PPAR) γ or δ, one focus in this area is to investigate their roles in colon carcinogenesis, including the induction of growth factors.
Review article: volume expansion in patients with cirrhosis
Authors: Henriksen J. H. , Kiszka‐Kanowitz M. , Bendtsen F. , Møller S.
Published: March 2003

Adequate size and distribution of the circulating medium are important for cardiovascular function, tissue oxygenation, and fluid homoeostasis. Patients with cirrhosis have cardiovascular dysfunction with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, vasodilation with low systemic vascular resistance, increased whole‐body vascular compliance, and increased arterial compliance. The effectiveness and temporal relations of plasma/blood volume expansion depend highly on the type of load (water, saline, oncotic material, red blood cells).

Patients with cirrhosis respond in some aspects differently from healthy subjects, owing to their disturbed circulatory function and neurohormonal activation. Thus the increase in cardiac output and suppression of the renin‐angiotensin‐aldosterone system and sympathetic nervous system during volume expansion may be somewhat blunted, and in advanced cirrhosis, especially the non‐central parts of the circulation, including the splanchnic blood volume, are expanded by a volume load. Infusion of oncotic material (preferably albumin) is important in the prevention of post‐paracentesis circulatory dysfunction.

In conclusion, volume expansion in advanced cirrhosis is qualitatively and quantitatively different from that of healthy subjects, and in those with early cirrhosis. Timely handling is essential, but difficult as it is a balance between the risks of excess extravascular volume loading and further circulatory dysfunction in these patients with a hyperdynamic, but hyporeactive, circulation.
Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results
Authors: Lauritsen K. , Devière J. , Bigard M.‐A. , Bayerdörffer E. , Mózsik G. , Murray F. , KristjánsdÓttir S. , Savarino V. , Vetvik K. , De Freitas D. , Orive V. , Rodrigo L. , Fried M. , Morris J. , Schneider H. , Eklund S. , Larkö A.
Published: March 2003

Introduction : Esomeprazole, the first proton pump inhibitor to be developed as an optical isomer, has demonstrated more effective healing vs. omeprazole and lansoprazole in patients with reflux oesophagitis (RO). However, RO recurs in a high proportion (∼80%) of these patients within 12 months of initial therapy, highlighting the importance of maintenance treatment. Previous studies have shown esomeprazole to be effective as maintenance therapy in healed RO patients.

Aim:  This study was conducted to compare esomeprazole 20 mg once daily (o.d.) with lansoprazole 15 mg o.d. for the prevention of recurrence of RO.

Methods:  1391 patients with endoscopically verified RO (LA classification) were enrolled in this randomized, double‐blind, parallel‐group, multicentre trial. During the initial healing phase of the study, all patients received 4–8 weeks' open treatment with esomeprazole 40 mg: 1236 healed (identified by endoscopy at 4 and 8 weeks) and symptom‐free (i.e. no heartburn or acid regurgitation) patients were randomized to 6 months' maintenance treatment with esomeprazole 20 mg o.d. or lansoprazole 15 mg o.d.. Time to relapse (relapse of RO and/or discontinuation due to symptom recurrence) was analysed using a log‐rank test.

Results:  Esomeprazole maintained a significantly higher proportion of patients in remission than lansoprazole over the 6‐month course of treatment (P < 0.0001, intention‐to‐treat analysis). After 6 months' treatment, 83% of esomeprazole recipients were in remission compared with 74% of lansoprazole recipients (life‐table estimates). Esomeprazole gave a longer time to relapse than lansoprazole irrespective of baseline LA Grade, significantly so for baseline LA Grades B, C and D (P < 0.05 for each comparison). Significantly more patients were free from heartburn in the esomeprazole group compared with the lansoprazole group at 1, 3 and 6 months (P < 0.05). Significant differences at 6 months between esomeprazole 20 mg o.d. and lansoprazole 15 mg o.d. were also observed for control of epigastric pain and acid regurgitation (P < 0.05 and P < 0.001, respectively). Both treatment regimens were well tolerated.

Conclusion:  Esomeprazole 20 mg o.d. is a more effective maintenance treatment than lansoprazole 15 mg o.d. for symptom‐free patients with healed RO.
Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease
Authors: Friend
Published: March 2003

Inflammatory bowel diseases are treated in some cases by local administration of anti‐inflammatory drugs. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side‐effect profiles and may improve patient compliance. This review covers a number of issues important in the design of oral delivery systems of glucocorticosteroids for local therapy of colonic inflammation. The choice of specific glucocorticosteroids is based on the drug’s physicochemical and pharmacological properties. The conditions under which an orally administered glucocorticosteroid (or other drug) must be delivered to treat ulcerative colitis are also discussed. These conditions include variations in local pH, transit throughout the gastrointestinal tract, the potential role of gut microflora, and drug dissolution in both the healthly and diseased large intestine. The effective delivery of topically‐active glucocorticosteroids in ulcerative colitis and Crohn’s colitis patients is complex, but if successful could improve their usefulness.
Amoxycillin resistance is one reason for failure of amoxycillin–omeprazole treatment of Helicobacter pylori infection
Authors: Dore  , Piana  , Carta  , Atzei  , Are  , Mura  , Massarelli  , Maida  , Sepulveda  , Graham  , Realdi
Published: March 2003

Background:

The efficacy of omeprazole and amoxycillin dual therapy to treat Helicobacter pylori infection has been inconsistent, suggesting the presence of host or bacterial factors influencing treatment success. The aim of this study was to assess the role of pre‐treatment amoxycillin resistance in the efficacy of omeprazole and amoxycillin dual therapy.

Methods:

We studied 43 consecutive dyspeptic patients with H. pylori infection. Pre‐treatment H. pylori infection was established by the combination of positive rapid urease test, culture and histology. Amoxycillin susceptibility testing was performed by an Epsilometer test (E‐test) method and amoxycillin resistance was defined as minimum inhibitory concentration greater than 8 μg/mL. Patients received 20 mg omeprazole twice daily for 28 days and amoxycillin 1000 mg twice daily for 2 weeks. Adverse effects were documented using a questionnaire. H. pylori status was reassessed 6–8 weeks after the end of treatment by rapid urease testing and histological examination of gastric biopsies.

Results:

Forty‐two dyspeptic patients completed the study, and one patient dropped out. H. pylori infection was cured in 23 of 42 patients (55%). The cure rate was higher in patients harbouring amoxycillin‐sensitive organisms than in those with resistant strains: 66% (19/29) vs. 31% (4/13), respectively (P = 0.049). No significant differences in cure rates were evident in relation to age, sex, smoking habits or compliance.

Conclusions:

The effectiveness of amoxycillin–omeprazole dual therapy was greatly reduced in the presence of pre‐treatment amoxycillin‐resistant H. pylori. The success rate in patients with amoxycillin‐sensitive H. pylori was only 66%, suggesting the presence of additional factors affecting the efficacy of this therapy.
Gastrointestinal pH profiles in patients with inflammatory bowel disease
Authors: Press  , Hauptmann  , Hauptmann  , Fuchs  , Fuchs  , Ewe  , Ramadori
Published: March 2003

Background:

5‐Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.

Aim:

To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5‐amino salicylic acid in the intestinal lumen.

Methods:

Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn’s disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease).

Results:

The median gastric pH values in the patient groups (Crohn’s disease 2.4, range 1.5–4.1; ulcerative colitis 1.95, range 1.55–4.4) were significantly higher than those observed in the controls (1.55, range 0.95–2.6). In the small bowel and colonic segments, all the pH values of Crohn’s disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission.

Conclusions:

The luminal release of 5‐amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.
Helicobacter pylori‐positive peptic ulcer patients do not adapt to aspirin
Authors: Konturek J. W. , Konturek S. J. , Stachura J. , Domschke W.
Published: March 2003

Background:

Recent studies indicate that eradication of Helicobacter pylori might prevent peptic ulcer formation in patients treated with non‐steroidal anti‐inflammatory drugs (NSAIDs). On the other hand, gastric adaptation after repeated exposures to aspirin (ASA) is well documented but the influence of H. pylori on this process remains to be elucidated.

Aim:

To compare gastric damage and adaptation following repeated exposures to ASA in a group of patients with H. pylori infection, before and after eradication of the bacterium, and in H. pylori‐negative controls.

Methods:

Eight healthy volunteers without H. pylori infection and eight patients with duodenal ulcer (DU) history and H. pylori infection before and after H. pylori eradication were given ASA 2 g/day for a period of 14 days. Mucosal damage was evaluated by endoscopy and histology of biopsy samples. Gastric microbleeding, DNA synthesis in the gastric mucosa and mucosal expression, as well as luminal content of transforming growth factor‐α (TGFα) were determined on days 0, 3, 7 and 14 of the ASA course.

Results:

In all patients aspirin‐induced gastric damage reached a maximum on day 3. In H. pylori‐positive patients, this damage was maintained at a similar level up to day 14, whereas in H. pylori‐negative controls and H. pylori‐eradicated patients this damage significantly lessened on day 14 and was accompanied by elevated DNA synthesis as well as increased mucosal expression and luminal release of TGFα.

Conclusions:

H. pylori‐positive DU patients do not adapt to continued administration of ASA but eradication of the bacterium restores adaptation. This phenomenon deserves further clinical evaluation.
Equipotent inhibition of gastric acid secretion by equal doses of oral or intravenous pantoprazole
Authors: Hartmann  , Ehrlich  , Fuder  , Lühmann  , Emeklibas  , Timmer  , Wurst  , Lücker
Published: March 2003

Background:

Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 system, and linear pharmacokinetics. The recommended oral dose for treatment of acid‐related diseases is 40 mg.

Methods:

Using a randomized, crossover study design we compared the ability of 40 mg oral and intravenous pantoprazole to elevate the intragastric pH in healthy volunteers (n = 20, ‘per protocol’), during two treatment phases. The duration of each phase was 5 days. Pantoprazole 40 mg was administered once daily either as a tablet or as an intravenous injection. A 24 h pH‐metry was used to record the intragastric pH on day 5 of each regimen; this was compared to the baseline curve obtained before each study period. The calculated 90% confidence intervals (90% CI) represent the mean difference in the intragastric pH, attained after intravenous or oral administration. The predefined equivalence range for the 90% CI was ± 20% for the percentage time at which the gastric pH was at least pH 3 or 4 and ± 1 unit for the median pH.

Results:

Pantoprazole was well tolerated during both treatment phases. The mean of the 24 h median pH was 3.3 and 3.1 for the intravenous and oral treatments, respectively; the corresponding differences were 0.2 (90% CI: – 0.03 to 0.44). For the mean percentage time at which the pH was 3 or above, the respective calculated values were 57% and 51%, with a difference between the two administration routes of only 5.7% (90% CI: 1.8 to 9.6). At an intragastric pH of 4 or above, the mean percentage time was 42% and 38% following intravenous and oral treatment, respectively, with a difference between the treatment routes of only 4.4% (90% CI: 0.6 to 8.3).

Conclusions:

These results imply that the two formulations of pantoprazole can be assumed to be equipotent. Hence, the intravenous formulation of pantoprazole could be considered as an alternative route of administration.
Review article: the management of inflammatory bowel disease during pregnancy
Authors: Subhani  , Hamiliton
Published: March 2003

The management of inflammatory bowel disease during pregnancy is a particular challenge because adequate disease control before and during gestation is essential for both maternal and foetal health. As a practical problem this situation arises frequently, because a quarter of patients conceive after the diagnosis of their disease.

Many of the clinical, biochemical, radiological and endoscopic investigations that are used to monitor and assess disease activity are difficult to use and interpret during pregnancy. Furthermore, patients and clinicians often have concerns about the safety of medical and surgical treatments for the foetus.

This review is designed for the practising clinician, to guide the management of patients with inflammatory bowel disease before and during pregnancy. The literature is at times conflicting and data on some issues are scanty, therefore recommendations are based on the balance of evidence including, if necessary, extrapolation from other conditions.
Review article: anthranoid laxatives and their potential carcinogenic effects
Authors: GORKOM B. A. P. VAN , VRIES E. G. E. DE , KARRENBELD  , KLEIBEUKER
Published: March 2003

Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short‐term use of these substances is generally safe, long‐term use cannot be recommended.
Prevention of post‐operative recurrence of Crohn’s disease requires adequate mucosal concentration of mesalazine
Authors: FRIERI  , PIMPO  , ANDREOLI  , ANNESE  , COMBERLATO  , CORRAO  , PALUMBO  , STURNIOLO  , TONELLI  , CAPRILLI  ,   GRUPPO ITALIANO PER LO STUDIO DEL COLON E DEL RETTO
Published: March 2003

Background

: Surgical resection of Crohn’s disease is followed by early recurrence in a high percentage of patients. Mesalazine has been shown to be effective in the prevention of post‐operative recurrence, but some 50% of patients under treatment recur at 3 years of follow‐up.

Aim

: To establish whether the mucosal concentration of mesalazine might affect the development of post‐operative recurrence.

Methods

: Colon‐ileoscopy was performed in 25 consecutive patients resected for Crohn’s disease. The mean time from surgery was 14 months. After the operation, all patients were taking oral mesalazine (Asacol, 2.4 g/day). Ten patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing of the lumen) in the neoterminal ileum, five of whom also showed juxta‐anastomotic colonic involvement. Fifteen patients were free of recurrence. At endoscopy, four biopsies were taken from the perianastomotic area (two specimens at the ileal site and two specimens at the colonic site of the anastomosis). The specimens were weighed and immediately frozen at −80 °C. Mesalazine concentration (ng/mg) was measured in tissue homogenates by high‐ performance liquid chromatography with electrochemical detection. Fisher’s exact test was used for the statistical analysis.

Results

: The mean value of mucosal mesalazine concentration, expressed as ng/mg of tissue, was significantly lower in patients with recurrence than in those without recurrence both in the ileum (mean ± s.d.: 21.6 ± 28.3 vs. 70.9 ± 47.4; P = 0.007) and in the colon (25.8 ± 26.4 vs. 60.3 ± 32.5; P = 0.010).

Conclusions

: The mucosal conentration of mesalazine in the juxta‐anastomatic area is significantly lower in patients with recurrence than in those free of recurrence. These data could suggest an association between mucosal mesalazine concentrations and the clinical effectiveness of the drug.
Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis
Authors: Venturi  , Gionchetti  , Rizzello  , Johansson  , Zucconi  , Brigidi  , Matteuzzi  , Campieri
Published: March 2003

Background

: Although 5‐aminosalicylic acid (5‐ASA) oral compounds are the standard maintenance treatment for ulcerative colitis in remission, some patients cannot use them because of side‐effects. Clinical and experimental observations have suggested the potential role of probiotics in inflammatory bowel disease therapy.

Aim

: To evaluate the effects on intestinal microflora and the clinical efficacy of a new probiotic preparation in patients with ulcerative colitis in remission.

Patients and methods

: Twenty patients with ulcerative colitis, intolerant or allergic to 5‐ASA, have been treated with a new probiotic preparation (VSL # 3, CSL, Milan, Italy) containing 5 × 1011 cells/g of 3 strains of bifidobacteria, 4 strains of lactobacilli and 1 strain of Streptococcus salivarius ssp. thermophilus. Two doses of 3 g were administered o.d. for 12 months. Faecal samples for stool culture were obtained from the patients at the beginning of the trial and after 10, 20, 40, 60, 75, 90 days, 12 months and at 15 days after the end of the treatment. The following bacterial groups have been evaluated in the faeces: total aerobic and anaerobic bacteria, enterococci, Streptococcus thermophilus, lactobacilli, bifidobacteria, Bacteroides, clostridia, coliforms. Patients were assessed clinically every two months, and assessed endoscopically at 6 and 12 months or in relapse.

Results

: Faecal concentrations of Streptococcus salivarius ssp. thermophilus, lactobacilli and bifidobacteria increased significantly in all patients, compared to their basal level, from the 20th day of treatment (P < 0.05) and remained stable throughout the study. Concentrations of Bacteroides, clostridia, coliforms, total aerobic and anaerobic bacteria did not change significantly during treatment (P = N.S.). Fifteen of 20 treated patients remained in remission during the study, one patient was lost to follow up, while the remaining relapsed. No significant side‐effects have been reported.

Conclusions

: These results show that this probiotic preparation is able to colonize the intestine, and suggest that it may be useful in maintaining the remission in ulcerative colitis patients intolerant or allergic to 5‐ASA. Controlled trials are warranted to confirm these preliminary results.
Seroprevalence of cytotoxin‐associated gene A positive Helicobacter pylori strains in Changle, an area with very high prevalence of gastric cancer in South China
Authors: Wong  , Lam  , Ching  , Hu  , Ong  , Chen  , Gao  , Chen  , Jiang  , Hou  , Lu  , Wang  , Ho  , Yuen  , Lai  , Kwok  , Hui  , Covacci  ,   THE CHINA GASTRIC CANCER STUDY GROUP
Published: March 2003

Background

: Helicobacter pylori, especially the CagA‐positive strains, are closely associated with peptic ulcers and gastric cancers. We performed a large scale gastric cancer screening project and examined the prevalence of H. pylori and CagA‐positive strains in Changle, China, an area with one of the World’s highest gastric cancer mortality. We also compared the prevalence with that in Hong Kong which has one‐tenth of the gastric cancer mortality of that in Changle.

Methods

: A total of 2424 subjects in Changle and 523 subjects in Hong Kong had endoscopic examination and venesection. Sera were tested for anti‐H. pylori antibody and anti‐CagA antibody and correlated with endoscopic findings.

Results

: In Changle, 80.9% of the subjects were H. pylori carriers. Out of 551 carriers, 408 (74%) were positive for anti‐CagA antibody. A total of 76% and 87% of the asymptomatic and gastric cancer patients were positive for anti‐CagA antibody, respectively (P > 0.05). Compared to Hong Kong, there was a significantly (P < 0.0001) higher prevalence of CagA‐positive strains in asymptomatic subjects in Changle (76%) than in Hong Kong (28%), but not in peptic ulcers or gastric cancers.

Conclusions

: Subjects in Changle had a high prevalence of H. pylori infection and a high prevalence of the CagA‐positive strains. The contrast in the prevalence of CagA‐positive strains, in asymptomatic subjects in two areas with differing gastric cancer mortality, supports the pathogenic role of CagA‐positive strains in gastric carcinogenesis.
Invasive and non‐invasive tests for Helicobacter pylori infection
Authors: Vaira D. , Holton J. , Menegatti M. , Ricci C. , Gatta L. , Geminiani A. , Miglioli M.
Published: March 2003

There are two general ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non‐invasive procedure. The invasive procedures involve an endoscopy and biopsy. A biopsy is essential because often the mucosa may appear macroscopically normal but nevertheless be inflamed. A biopsy is obtained by histological examination, culture, polymerase chain reaction or detection of the presence of urease activity in biopsy material.

The non‐invasive tests that can be used to diagnose the infection are serology, detection of labelled metabolic products of urea hydrolysis in the breath (13CO2, 14CO2), the urine or the blood, and detection of H, pylori antigen in a stool specimen. At present no single test can be relied upon to detect definitely colonization by H. pylori, and a combination of two is recommended if this is feasible. The choice of the test to be used is not straightforward and may vary according to the clinical condition and local expertise.
Review article: interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease
Authors: Corrigan  , Stevens
Published: March 2003

5‐Aminosalicylic acid (5‐ASA) has replaced sulphasalazine as first line therapy for mild to moderately active inflammatory bowel disease and is widely used. A number of reports have linked oral 5‐ASA therapy to chronic tubulo‐interstitial nephritis and this relationship is now well established. Despite increasing recognition of the potential for this serious adverse event, guidelines for monitoring renal function in patients prescribed 5‐ASA preparations are not widely employed. Whilst the incidence of this adverse event in the population of patients with inflammatory bowel disease treated with mesalazine is low, the morbidity in an affected individual is high with some cases progressing to end‐stage renal disease. Routine monitoring of renal function is simple and inexpensive and could prevent this outcome. Based on the available data, serum creatinine should be estimated prior to commencing treatment, monthly for the first 3 months, 3‐monthly for the next 9 months, 6‐monthly thereafter and annually after 5 years of treatment.
Comparison of lansoprazole‐based triple and dual therapy for treatment of Helicobacter pylori‐related duodenal ulcer: an Asian multicentre double‐blind randomized placebo controlled study
Authors: Wong  , Xiao  , Hu  , Qian  , Huang  , Li  , Hu  ,   DALDIYONO, Manan  , Lesmana  , Carpio  , Perez  , Fock  , Kachintorn  , Phornphutkul  , Kullavanijaya  , Ho  , Lam
Published: March 2003

Bakcground

: In Asian countries with limited resources, clarithromycin‐based triple therapy may not be readily available. There are also few direct comparisons of different regimens in Asia.

Aim

: To compare two lansoprazole‐based non‐clarithromycin triple therapies and one dual therapy in a prospective double‐blind placebo‐controlled study of Helicobacter pylori eradication and duodenal ulcer healing.

Methods

: Fourteen centres in Asia participated in this study. Patients with acute duodenal ulcer who were H. pylori‐positive were recruited. They were randomized to receive: (a) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and metronidazole 500 mg b.d. for 2 weeks (LAM‐2 W), or (b) LAM for 1 week and placebo (LAM‐1 W), or (c) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and placebo for 2 weeks (LA‐2 W). Upper endoscopy was repeated at week 6 to check for duodenal ulcer healing. Symptoms and side‐effects were recorded.

Results

: A total of 228 patients were recruited, and two patients took less than 50% of the drugs. H. pylori eradication rates (intention‐to‐treat) were 68 out of 82 (83%) with LAM‐2 W, 55 out of 71 (78%) with LAM‐1 W and 43 out of 75 (57%) with LA‐2 W. There were significant differences (P=0.001) in eradication rates when comparing either LAM‐2 W or LAM‐1 W with LA‐2 W. The eradication rate in patients with metronidazole resistant H. pylori strains were significantly lower than those with metronidazole sensitive strains (P=0.0001). The duodenal ulcer healing rates at week 6 were 85%, 85% and 72% in LAM‐2 W, LAM‐1 W and LA‐2 W, respectively (P=0.065). Side‐effects occurred in 13%, 11% and 9% in LAM‐2 W, LAM‐1 W and LA‐2 W, respectively. H. pylori eradication and initial ulcer size were factors affecting duodenal ulcer healing.

Conclusions

: This Asian multicentre study showed that 1‐week lansoprazole‐based triple therapy without clarithromycin has similar efficacy in H. pylori eradication and ulcer healing compared with a 2‐week regimen. Both triple therapies were significantly better than dual therapy in H. pylori eradication. Therefore, 1‐week lansoprazole‐based triple therapy is as safe and effective as 2‐week therapy in eradication of H. pylori infection and healing of duodenal ulcer in these Asian centres.
Cyclosporin in the treatment of adults with refractory coeliac disease—an open pilot study
Authors: Wahab  , Crusius  , Meijer  , Uil  , Mulder
Published: March 2003

Aim:

To evaluate the effect of cyclosporin treatment on clinical and histological parameters in adult patients with refractory coeliac disease.

Methods:

Thirteen patients were treated with oral cyclosporin for 2 months, aiming at serum levels of 100–200 ng/mL. Seven extended medication intake up to a maximum of 12 months. Before and after treatment, clinical parameters were monitored and small intestinal biopsies taken. Ten of 13 patients were typed for HLA‐DQA1 and ‐DQB1 alleles.

Results:

Eight of 13 patients responded histologically to cyclosporin treatment. Normalization of villi was demonstrated in five patients, three after prolonged treatment. Eight patients reported a clinical response, of whom six had concomitant histological improvement. No serious side‐effects of cyclosporin were noticed. Nine of 10 patients who were immunogenetically typed carried the coeliac disease associated serologic DQ2 markers, one carried neither DQ2 nor DQ8 markers.

Conclusion:

In our study group of 13 adult refractory coeliac disease patients, cyclosporin in therapeutic doses induced a histological improvement in eight patients (61%), in five of whom (38%) normalization of villi was demonstrated. Thus, we believe that cyclosporin is a therapeutic option in refractory coeliac disease, although we could not confirm earlier reports of unconditional successful treatment.
Interaction of Helicobacter pylori eradication and non‐steroidal anti‐inflammatory drugs on gastric epithelial apoptosis and proliferation: implications on ulcerogenesis
Authors: Leung  , To  , Chan  , Lee  , Chung  , Sung
Published: March 2003

Background:

Apoptosis is associated with loss of gastric mucosal integrity and may play an important role in ulcer development.

Aim:

To examine how Helicobacter pylori and NSAIDs interact to effect apoptosis and proliferation of the gastric mucosa.

Methods:

Patients presenting with musculoskeletal pain requiring NSAID treatment and without previous exposure to NSAID or pre‐existing ulcers were recruited. Patients were divided into three groups: (A) H. pylori‐infected; (B) H. pylori‐eradicated; and (C) non‐infected patients. They were given naproxen for 8 weeks. Patients with non‐ulcer dyspepsia and H. pylori infection who were given anti‐Helicobacter therapy were recruited as controls (D). Endoscopy was performed at baseline and 8‐weeks after receiving naproxen. Gastric antral biopsies were obtained to assess apoptosis by terminal uridine deoxynucleotidyl nick end‐labelling (TUNEL) and proliferation by Ki67 immunostaining.

Results:

A total of 55 patients were studied. H. pylori‐positive patients had a higher apoptosis and proliferation index at baseline than non‐infected patients (P < 0.0001), and eradication of H. pylori resulted in a significant reduction in these parameters. The NSAID induced apoptosis in non‐infected subjects (P=0.03) whilst apoptosis was reduced in H. pylori‐positive patients receiving NSAID (P=0.02). After 8 weeks of NSAID, post‐treatment apoptosis was significantly higher in patients with persistent H. pylori infection than in non‐infected patients (P=0.01).

Conclusions:

Eradication of H. pylori prior to NSAID therapy significantly reduces the level of apoptosis in the gastric mucosa, which may contribute to maintaining mucosa integrity and preventing ulcer development.
Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study
Authors: Seifert  , Schmitt  , Gültekin  , Caspary  , Wehrmann
Published: March 2003

Aim:

Adequate patient sedation is mandatory for most interventional endoscopic procedures. Recent anaesthesiologic studies indicates that propofol and midazolam act synergistically in combination and therefore may be superior to sedation with propofol alone in terms of sedation efficacy, recovery and costs (due to a presumed lower total dose of propofol needed).

Methods:

A total of 239 consecutive patients undergoing therapeutic EGD or ERCP (EGD/ERCP‐ratio, 1:1) randomly received either propofol alone (n=120, group A, loading dose 40–60 mg intravenously, followed by repeated doses of 20 mg) or propofol plus midazolam (n=119, group B, initial midazolam dose of 2.5–3.5 mg intravenously, followed by repeated doses of 20 mg of propofol) for sedation. Vital signs (heart rate, blood pressure, oxygen saturation, electrocardiogram) were continuously monitored. Procedure‐related parameters, the recovery time and quality (post‐anaesthesia recovery score) as well as the patient’s co‐operation and tolerance to the procedure (visual analogue scale) were prospectively assessed.

Results:

Patients of group A and B were well matched with respect to demographic and clinical data, endoscopic findings, and the type of associated procedures. In group A, a mean dose of 0.25 ± 0.13 mg·min/kg propofol was used compared to 0.20 ± 0.09 mg·min/kg of propofol in group B (P < 0.01, plus additional 2.9 ± 0.5 mg of midazolam). Clinically relevant changes in vital signs were observed at comparable frequencies with a lowering of the systolic blood pressure < 90 mmHg in six out of 119 patients in group B and one out of 120 patients in group A (P=0.07). The sedation efficacy was rated similarly in both groups, whereas the mean recovery time (group A, 19 ± 7 min vs. group B, 25 ± 8 min, P <  0.05) as well as the recovery score (post‐anaesthesia recovery score group A, 8.0 ± 1.1 vs. post‐anaesthesia recovery score group B, 7.3 ± 1.2, P <  0.001) were significantly better with propofol alone than with propofol plus midazolam.

Conclusion:

During therapeutic endoscopy, sedation with propofol and midazolam requires a lower total dose of propofol, but otherwise has no superior sedation efficacy and is associated with a slower post‐procedure recovery than sedation with propofol alone.
Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics for 1 week—a meta‐analysis of efficacy
Authors: Gisbert  , González  , Calvet  , Roqué  , Gabriel  , Pajares
Published: March 2003

Objective:

To compare the efficacy of proton pump inhibitor vs. ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication.

Methods:

Randomized trials comparing 1‐week regimens with (i) proton pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was confirmed by histology or 13C‐urea breath test at least 4 weeks after therapy. Data sources included PubMed database and abstracts from congresses until October 1999. Statistical analysis was by meta‐analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method).

Results:

Twelve studies met the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A, and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A, mean H. pylori eradication efficacy by intention‐to‐treat analysis (pooled data) was 76.6% (95% CI: 72–81%) and 73.7% (95% CI: 69–78%) with proton pump inhibitor, C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on H. pylori eradication was 1.15 (95% CI: 0.8–1.64%). Mean H. pylori eradication with RBC, C and N was 87.2% (95% CI: 83–91%), and 74.9% (95% CI: 74–84%) with proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95% CI: 1.08–2.85%).

Conclusion:

RBC and proton pump inhibitor have similar efficacy for H. pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co‐prescribed antibiotics.
Inhibition of platelet activation by 5‐aminosalicylic acid in inflammatory bowel disease
Authors: Carty  , Macey  , Rampton
Published: March 2003

Background:

Platelets play an important role in inflammation and are activated in inflammatory bowel disease. Micro‐vascular thrombosis in the gut wall leading to intestinal micro‐infarction may be a pathogenic feature of Crohn’s disease. 5‐Aminosalicylic acid is an effective treatment for patients with inflammatory bowel disease.

Aims:

To assess the effects of 5‐aminosalicylic acid on platelet activation, when taken orally and in vitro by patients with inflammatory bowel disease.

Methods:

Spontaneous and thrombin‐induced platelet activation were studied using fluorescent antibodies to the activated platelet surface glycoprotein P‐selectin and flow cytometry.

Results:

Baseline platelet activation in inflammatory bowel disease was significantly greater than that in controls (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex‐vivo platelet activation was 50% lower in patients with inflammatory bowel disease taking 5‐aminosalicylic acid orally than in those not on such treatment (P < 0.05). In vitro, 5‐aminosalicylic acid significantly reduced both spontaneous (P < 0.03 for ≥1 μM 5‐aminosalicylic acid) and thrombin‐induced platelet activation (P < 0.02 for ≥ 1 μM 5‐aminosalicylic acid).

Conclusions:

5‐Aminosalicylic acid given either orally or in vitro inhibits platelet activation. If this effect reflects an in vivo action in the gut, it could contribute to the beneficial actions of 5‐aminosalicylic acid in inflammatory bowel disease.
CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole
Authors: Adachi K. , Katsube T. , Kawamura A. , Takashima T. , Yuki M. , Amano K. , Ishihara S. , Fukuda R. , Watanabe M. , Kinoshita Y.
Published: March 2003

Background:

CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19‐mediated metabolism varies among the different proton pump inhibitors.

Aim:

To determine the effect of CYP2C19 genotype status on intragastric pH during dosing with lansoprazole or rabeprazole.

Subjects and methods:

The subjects were 20 male volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status was determined by a polymerase chain reaction‐restriction fragment length polymorphism method. Twenty‐four‐hour monitoring of intragastric acidity was performed three times: once without medication, once on the last day of a 7‐day course of rabeprazole, and once on the last day of a 7‐day course of lansoprazole.

Results:

Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (homo‐EMs, n=7), heterozygous extensive metabolizers (hetero‐EMs, n=9), and poor metabolizers (PMs, n=4). The median pH during rabeprazole administration was not influenced by CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole dosing was higher than in homo‐EMs and hetero‐EMs. The percentage of time with pH < 4.0 had a similar tendency to that of median pH.

Conclusion:

CYP2C19 genotype status influences gastric acid suppression by lansoprazole, but not by rabeprazole.
A new quadruple therapy for Helicobacter pylori using tripotassium dicitrato bismuthate, furazolidone, josamycin and famotidine
Authors: Liu Wen‐Zhong , Xiao Shu‐Dong , Hu Pin‐Jin , Lu Hong , Cui Yi , Tytgat Guido N. J.
Published: March 2003

Background:

In our previous study, a triple therapy using tripotassium dicitrato bismuthate (TDB), josamycin and furazolidone achieved a suboptimal cure rate of Helicobacter pylori infection.

Aim:

To investigate whether the addition of an antisecretory agent raises the cure rate using this regimen.

Methods:

One hundred and twenty H. pylori positive patients with peptic ulcer disease or functional dyspepsia were randomly assigned to receive 1‐week quadruple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d., josamycin 1000 mg b.d. and famotidine 20 mg b.d. (BFJF group), or triple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d. and clarithromycin 250 mg b.d. (BFC group). H. pylori status was assessed by histology and culture of gastric biopsy specimens before and at least 4 weeks after completion of therapy.

Results:

Seven patients (three in the BFJF group and four in the BFC group) dropped out. Eradication rates (intention‐to‐treat/per protocol) were 90%/95% in the BFJF group and 82%/88% in the BFC group, respectively (P > 0.05). Duodenal ulcer healing rates were 94% (16/17) in the BFJF group and 80% (20/25) in the BFC group, respectively (P > 0.05). Mild side‐effects occurred in 11 (18%) patients in the BFJF group and 10 (17%) in the BFC group (P > 0.05).

Conclusions:

One‐week quadruple therapy consisting of TDB, furazolidone, josamycin and famotidine achieves a high cure rate of H. pylori infection.
The use of 6‐mercaptopurine in patients with inflammatory bowel disease after failure of azathioprine therapy
Authors: Boulton‐Jones J. R. , Pritchard K. , Mahmoud A. A.
Published: March 2003

Introduction:

Azathioprine is a useful therapy in patients with inflammatory bowel disease that is difficult to control. However, 10% of patients are unable to tolerate azathioprine, and the best form of treatment for this group of patients is unknown. The azathioprine metabolite 6‐mercaptopurine may be a useful therapy for these patients.

Aim:

To review our clinical experience of the use of the 6‐mercaptopurine in inflammatory bowel disease patients who are intolerant of azathioprine.

Methods:

All patients who were prescribed 6‐mercaptopurine in a 2‐year period were identified from pharmacy records. The case notes were reviewed and those who had previously been intolerant of azathioprine were included.

Results:

A total of 19 with either ulcerative colitis and Crohn’s disease were included. The reasons for discontinuing azathioprine were side‐effects (13 patients), failure of efficacy (four patients) and leucopenia (two patients). Eleven of the 19 patients (68%) tolerated 6‐mercaptopurine, including seven out of 13 patients (54%) who discontinued azathioprine due to side‐effects. The length of follow‐up of patients on 6‐mercaptopurine was between 126 and 780 days (median 390 days).

Discussion:

6‐mercaptopurine should be considered in patients with inflammatory bowel disease who require continuing immunosuppressive therapy, but are intolerant of azathioprine.
Review article: agents affecting gall‐bladder motility – role in treatment and prevention of gallstones
Authors: Van Erpecum K. J. , Venneman N. G. , Portincasa P. , Vanberge‐Henegouwen G. P.
Published: March 2003

Various agents may either enhance or impair post‐prandial gall‐bladder motility, and they are identified in this review. When studying the impact of medication on gall‐bladder motility, the effects on interdigestive gall‐bladder and intestinal motility should also be taken into account. Patients at high risk of gallstone disease, and patients who are treated chronically with gall‐bladder motility inhibiting drugs, may benefit from improved gall‐bladder motility using a prokinetic agent. However, there are no long‐term studies to prove that such a strategy prevents gallstone formation.