bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal and hormonal responses to isotonic saline infusion after 3 days' head‐down tilt vs. supine and seated positions
Authors: Mauran P. , Sediame S. , Pavy‐Le Traon A. , Maillet A. , Carayon A. , Barthelemy C. , Weerts G. , Guell A. , Adnot S.
Published: March 2003

Aim:  The study aimed to determine whether prolonged exposure to simulated microgravity produces a level of thoracic volume receptor loading similar to that seen in the upright position or immediately after lying down.

Methods:  We used a cross‐over design to compare responses to a saline infusion in eight healthy subjects during a 4‐day, −6° head‐down tilt (HDT) and in the acute seated and acute supine positions.

Results:  The first 24 h of HDT were associated with greater urinary excretion of water and sodium (UV, UNaV) than seated and acute supine [cumulative UV, 3035 ± 219, 2311 ± 156 (P < 0.05), and 2448 ± 182 mL (P < 0.05), respectively; cumulative UNaV, 256 ± 19, 180 ± 11 (P < 0.05), and 189 ± 15 mmol (P < 0.05), respectively]. Haemoglobin and haematocrit were increased after 24 h and plasma volume decreased after 48 h of HDT (P < 0.05). With prolongation of HDT, UV and UNaV returned near the baseline values, and plasma atrial natriuretic factor (ANF) and renin values returned to acute seated levels; in acute supine, ANF values were higher and renin lower than in the two other positions. After a 30‐min infusion of 20 mL kg−1 isotonic saline on the fourth HDT day or during acute seated or acute supine, sodium excretion within 4 h was similar during HDT and acute seated (83 ± 6 and 84 ± 9 mmol, respectively) and greater during supine (104 ± 8 mmol, P < 0.05). The renin decrease was greater in HDT and seated than in supine. The plasma ANF increase was greater during HDT than during supine; during seated, plasma ANF was unchanged.

Conclusion:  These data suggest that, after 4 days of HDT, thoracic volume receptor loading returns to the same level as in the seated position, leading to blunted responses to volume expansion as compared with the acute supine position.
A leptin‐sympathetic‐leptin feedback loop: potential implications for regulation of arterial pressure and body fat
Authors: Mark A. L. , Rahmouni K. , Correia M. , Haynes W. G.
Published: March 2003

Aim:  This manuscript briefly reviews evidence and potential implications of a leptin‐sympathetic‐leptin feedback loop.

Results:  Leptin increases sympathetic nerve activity to brown adipose tissue, kidney and other tissues. This action has implications for regulation of arterial pressure. In turn, there is evidence that sympathoadrenal stimulation inhibits leptin mRNA expression and secretion from white adipose tissue through beta adrenergic mechanisms.

Conclusion:  This sympathetic modulation of leptin expression has potential implications for regulation of body fat.
Biomass density of wild and domestic herbivores and carrying capacity on a working ranch in Laikipia District, Kenya
Authors: Mizutani Fumi
Published: March 2003

This study of biomass densities of wild animals and domestic stock was carried out on the Lolldaiga Hills ranch in the Laikipia District, Kenya, between 1989 and 1995, as part of the study of the ecology of leopards and their impact on the working ranch. The ranch is set amongst the Lolldaiga Mountains, north‐west of Mount Kenya, and lies in ecological Zone IV. The vegetation in the area was classified as a scattered tree grassland. The weighted mean annual rainfall was 554 mm. The ranch carried 1543 kg km−2 of wild animals and 6512 kg km−2 of cattle and sheep. The ranch has produced beef, milk and wool since its foundation over 70 years ago, with a steadily maintained output and without any apparent degradation of the land. The milk production of normally over 450,000 kg per year was reduced, or ceased, in periods of drought and may represent a useful ‘safety valve’. The feasibility of multiple land use and conservation of wildlife are discussed.
The Systematic Reconnaissance Flight (SRF) as a tool in assessing the ecological impact of a rural development programme in an extensive area of the Lowveld of South Africa
Authors: Peel Michael John Stephen , Stalmans Marc
Published: March 2003

Land use cover and the current ecological condition of the natural resources of a 71,300 ha area were assessed quantitatively and qualitatively. The Systematic Reconnaissance Flight (SRF) was used to achieve the above within severe time constraints set by the terms of reference for the project. North–south grid lines, spaced 1 and 2 km apart, were flown using a helicopter. Changes in land use classes along flight transects were documented using a Global Positioning System. The co‐ordinates were transformed within a Geographic Information System into land cover values. The SRF with sampling intensities ranging from 5.13 to 9.89% yielded a difference of only 0.2% between the estimated cover of sugar cane compared to the known area under sugar cane. The other land cover classes were considered adequately quantified. The qualitative assessment shows the natural resources to be under severe strain, in particular within the riparian zone. Recommendations as to future agricultural expansion are made. The SRF was highly cost‐effective in achieving the stated objectives of the project.
Status of large mammals in the mountain sector of Kahuzi‐Biega National Park, Democratic Republic of Congo, in 1996
Authors: Inogwabini Bila‐Isia , Hall Jefferson S. , Vedder Amy , Curran Bryan , Yamagiwa Juichi , Basabose K.
Published: March 2003

Kahuzi‐Biega National Park, located in eastern Democratic Republic of Congo, harbours an abundance of endemic species and maintains important populations of Grauer's gorilla (Gorilla gorilla graueri) and elephants (Loxodonta africana). This paper reports on the status of large mammals within the mountain sector of the park in 1996, 2 years after the arrival of half a million Rwandan refugees in the area immediately adjacent to the sector. Large mammal surveys found that gorilla populations had remained stable and that elephants were concentrated within a subsector of the area. However, although chimpanzees (Pan troglodytes), blue monkeys (Cercopithecus mitis), and owl‐faced monkeys (C. hamlyni) were abundant and widespread, most terrestrial mammal species were found in very low densities and had been subjected to poaching. Nevertheless, important mammal populations remained and complemented the biodiversity conservation value of the park.
Ecological condition of encroached and non‐encroached rangelands in Borana, Ethiopia
Authors: Angassa Ayana , Baars Robert M. T.
Published: March 2003

The range condition was assessed in six communal grazing areas and one Government ranch in both areas encroached by bushes or shrubs and non‐encroached areas. In each area, three altitude zones were distinguished and in each altitude zone one transect, covering both encroached and non‐encroached rangeland, away from water sources, was selected. The assessment was based on botanical composition of the herbaceous layer, basal cover, litter cover, relative number of seedlings, age distribution of grasses and soil condition. A total of 41 grasses, four legumes, three sedges and 28 tree and/or shrub species were identified. The grasses Aristida adscensionis, Cenchrus ciliaris, Chrysopogon aucheri and Panicum coloratum were common or dominant in all sampled areas. Pennisetum mezianum and Pennisetum stramineum were typically found in the encroached vegetation. In general, the range condition was good. The encroached vegetation had a significantly lower score for range condition than the non‐encroached vegetation for most of the parameters as well as for the total score, although the differences were small. Differences based on altitude and distance of sample sites from water sources within transects were not significant, except for the relative number of seedlings. No signs of overgrazing were detected.
Widespread ‘hilltopping’ in Acraea butterflies and the origin of sex‐role‐reversed swarming in Acraea encedon and A. encedana
Authors: Jiggins Francis M.
Published: March 2003

In some populations of the butterflies Acraea encedon and A. encedana, most females are infected with a bacterium that kills their sons. The resulting shortage of males is associated with females adopting a sex‐role‐reversed mating system, in which females swarm at landmarks such as hilltops and compete for males. We have observed the mating behaviour of Acraea species that are not known to be infected with the male‐killer. In over half of these species, males were found to aggregate on hilltops. It is likely that this behaviour was ancestral to the sex‐role‐reversed swarms of Acraea encedon and A. encedana, and we discuss how the spread of the male‐killing infection may have converted this mating system into sex‐role‐reversed swarming.
Modelling the energy budget of a colonial bird of prey, the Ruppell's griffon vulture, and consequences for its breeding ecology
Authors: Ruxton G. D. , Houston D. C.
Published: March 2003

Colonial nesting is rare in birds of prey. In this study we develop further Pennycuick's (1979) model of energy balance to consider the implications of colonial nesting for the breeding ecology of Ruppell's griffon vultures. To achieve a realistic foraging range, and remain in energy balance, the birds need to do more than fill their crop once on each foraging trip. They must remain in the feeding area and digest some of this food and refill the crop to obtain sufficient energy to pay for the flight costs and have sufficient energy to satisfy their own requirements and that of the chick. Given the known distances that the birds have to travel to forage, it would be impossible for them to rear more than one chick. The low growth rate of griffon vulture chicks may be an adaptation to the low rate at which energy can be delivered by the parents. The optimal time for a bird to be away from the nest changes with the distance they have to travel. Assuming that one parent remains on the nest at all times to guard the chick, it is optimal for both parents to take turns to forage on the same day if the distance to a feeding area is under 150 km, but to switch to each parent being away for a whole day when the distance is greater than this. Soaring flight is essential for such a scavenger, because of the low energy expenditure. If a vulture relied on the more energetically demanding flapping flight its maximum foraging range would be under 40 km. Griffon vultures are known to be able to depress their basal metabolic rate, and this has major implications for their foraging range, which then becomes constrained by the flight speed rather than by the amount of food they need to obtain. Griffon vultures minimize energy expenditure on all activities, because even small increases in their energy demands have a large impact on the foraging range that the bird can use.
Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease
Authors: Tomita T. , Fukuda Y. , Tamura K. , Tanaka J. , Hida N. , Kosaka T. , Hori K. , Sakagami T. , Satomi M. , Shimoyama T.
Published: March 2003

Background:

The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long‐term outcome.

Aims:

To evaluate the relapse rate of peptic ulcer in the long‐term follow‐up of patients after H. pylori eradication therapy.

Patients and methods:

Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received `conventional treatment' including acid decreasing therapy with a histamine H2‐receptor antagonist or proton pump inhibitor (PPI). In group B, patients received `dual therapy' including one antibiotic plus acid‐decreasing therapy. In group C, patients received `triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years.

Results:

Intention‐to‐treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow‐up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred.

Conclusion:

Eradication of H. pylori infection changes the natural course of peptic ulcer.
A critical approach to new forms of treatment of Crohn's disease and ulcerative colitis
Authors: Seegers D. , Bouma G. , Peña A. S.
Published: March 2003

Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti‐TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long‐term complications are not yet known. The recent increase of tuberculosis in patients treated with anti‐TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine‐tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.
Overview: initial and long‐term management of gastro‐oesophageal reflux disease
Authors: Dent J. , Talley N. J.
Published: March 2003

Initial management of gastro‐oesophageal reflux disease aims to confirm a symptom‐based diagnosis, to relieve symptoms, to reassure the patient as to the treatable nature of reflux disease, and to initiate risk management and healing of oesophagitis. The aims of long‐term management include adequate control of symptoms, prevention of complications, and improvement of quality of life. Management options in terms of use of proton pump inhibitors are either daily therapy (maintenance), intermittent courses of therapy (for example, 4 weeks, then cease and observe), or on‐demand therapy. This overview discusses the advantages and disadvantages of these different strategies for the management of reflux disease.
Review article: pharmacology of esomeprazole and comparisons with omeprazole
Authors: Dent J.
Published: March 2003

Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the systemic circulation, compared with an equal dose of omeprazole. Also, this superior delivery has been shown to cause a more consistent and greater suppression of pentagastrin‐stimulated gastric acid secretion by esomeprazole, 20 mg, compared with omeprazole, 20 mg. The superior acid‐suppressant properties of esomeprazole have been revealed by extensive 24‐h intragastric pH‐monitoring studies. Compared with omeprazole, 20 mg, esomeprazole, 20 mg and 40 mg, has been shown to give superior outcomes on three key measures of antisecretory effect: (1) consistency amongst individuals; (2) duration over the 24‐h cycle; (3) overall impact on pH. As there is a substantial increment of acid control from esomeprazole, 20 mg, to esomeprazole, 40 mg, this latter dose is the most appropriate to investigate for modern initial therapy of reflux disease, with the aim of achieving the highest possible response rates in the shortest possible time.
Beclomethasone dipropionate enemas versus prednisolone sodium phosphate enemas in the treatment of distal ulcerative colitis
Authors: Campieri  , Cottone  , Miglio  , Manenti  , Astegiano  , D’arienzo  , Manguso  , D’albasio  , Bonanomi  , Galeazzi  , Orlando  , Castiglione  , Gionchetti
Published: March 2003

Aim:

To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60mL enema (PP) once daily in patients with active distal ulcerative colitis.

Methods:

One hundred and fifty‐seven patients were enrolled in a multicentre, 4‐week, randomized, double‐blind trial. Patients were assessed at baseline, 2 and 4 weeks.

Results:

Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic–pituitary–adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups.

Conclusions:

It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.
Low‐dose famotidine and effervescent cimetidine in healthy subjects: a placebo‐controlled overnight pH study
Authors: Reilly  , Grimley  , Usselmann  , Cottrell  , Mann  , Raskin  , Nwokolo
Published: March 2003

Background:

Amongst the low‐dose H2‐receptor antagonists available for the self‐medication of dyspepsia, both famotidine 10 mg and cimetidine 200 mg have been shown to raise intragastric pH, but there is a delay after ingestion before significant effects can be demonstrated. A new effervescent preparation of cimetidine 200 mg releases an acid buffer which has a more rapid effect on intragastric pH.

Aim:

To investigate the relative abilities of low‐dose famotidine and effervescent cimetidine to raise intragastric pH after a single postprandial evening dose.

Methods:

Twenty‐four healthy subjects (12 men, 12 women, median age 32 years) completed a three‐period crossover trial of famotidine 10 mg, effervescent cimetidine 200 mg and placebo. After a standard meal was given at 18.30 h to subjects fasted for 5.5 h, drug or placebo was given at 19.30 h. Intragastric pH was recorded with combined glass electrodes from 18.00 to 07.30 h by digital recorders.

Results:

Over the 12 h post‐dose period the mean area under the pH/time curve (AUC ) after famotidine 10 mg was 3.73, after cimetidine 200 mg effervescent 2.79, and after placebo 2.07. Over the same period the median pH and percentage of time that recordings were above pH 3 were 3.45 and 52.5 after famotidine 10 mg, 2.40 and 33.8 after cimetidine 200 mg effervescent, and 1.68 and 15.9 after placebo. Both active treatments were significantly different from placebo by each measure (P < 0.001), and famotidine 10 mg was significantly more effective than cimetidine 200 mg effervescent by each measure over the 0–12 h period (P < 0.001). Comparisons of mean AUCs for each 15 min period after dosing showed that decrease in acidity was significantly greater after cimetidine 200 mg effervescent than after famotidine 10 mg for the first 60 min. In the later post‐dose period only famotidine 10 mg raised pH for all time points to 12 h, whilst the effect of effervescent cimetidine 200 mg was detectable to ≈ 8 h.

Conclusions:

Inhibition of gastric acidity over the 12 h post‐dose period was significantly greater and endured longer after famotidine 10 mg than after effervescent cimetidine 200 mg, but for the 60 min period immediately after dosing the effect on intragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H2‐receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film‐coated tablets.
Review article: interferon and hepatitis C—factors predicting therapeutic outcome
Authors: Mabee  , Crippin  , Lee
Published: March 2003

Hepatitis C chronically infects ≈ 1.5% of Americans and is the most common clinical problem facing hepatologists. Since the virus was initially described in 1989, development of an effective therapy has been challenging. Although several different therapeutic agents have been used, no therapy has been shown to reliably eradicate the virus. Interferon‐alpha, a cytokine with immunostimulatory and anti‐viral properties, has become the therapy of choice for patients with chronic hepatitis C infection. Trials assessing the efficacy of interferon‐alpha have characterized host and viral factors predictive of responses to treatment. A thorough understanding of these predictive factors is requisite to providing cost‐effective therapeutic decisions for the patient with chronic hepatitis C infection.
Colchicine in chronic hepatitis B: a pilot study
Authors: Floreani  , Lobello  , Brunetto  , Aneloni  , Chiaramonte
Published: March 2003

Rationale:

Because of its antifibrotic and anti‐inflammatory effects, colchicine has been proposed as a treatment for liver disease. Early in vitro studies have demonstrated that colchicine blocks mitosis in the metaphase and inhibits DNA synthesis.

Aim:

A pilot study of hepatitis B virus (HBV)‐related/HBV‐DNA+ve chronic liver disease.

Patients:

Nine biopsy‐proven chronic hepatitis patients (three with cirrhosis) entered the study. Two of them were HBeAg+ve and seven were antiHBe+. All patients were HBV‐DNA+ve/antiHBc IgM+ve (index values of anti‐HBc IgM ranged from 0.370 to 1.200). All of them had a major contraindication to interferon therapy or refused antiviral treatment. The known persistence of positive HBsAg ranged from 2 to 21 years.

Methods:

After informed consent, the patients received 1 mg colchicine a day orally for 5 days‐a‐week over 6 months. Testing for liver enzymes and viral markers was performed at the baseline and after 3 and 6 months.

Results:

None of the patients experienced side‐effects during the treatment. The two HBeAg+ve patients seroconverted to anti‐HBe with a normalization of AST/ALT during therapy. Among the seven antiHBe+ve patients, four had a complete normalization of transaminases (one patient cleared the HBsAg with seroconversion to anti‐HBs). Six of the nine patients were HBV‐DNA‐ve at the end of therapy and were still negative after 12 months of follow‐up.

Conclusion:

These preliminary results suggest that colchicine might have an antiviral activity in HBV‐DNA+ve chronic liver disease, and it could be regarded as an alternative therapy to interferon.
A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg
Authors: Hoogstraten H. J. F. Van , Smet M. B. M. De , Renooij  , Breed  , Engels  , Ouden‐Muller J. W. Den , Rijk  , Smit  , Zwertbroek  , Hop  , Henegouwen G. P. Van Berge , Schalm  , Buuren H. R. Van ,   REPRESENTING THE DUTCH MULTICENTRE PBC STUDY GROUP
Published: March 2003

Background:

Ursodeoxycholic acid (UDCA) prolongs transplantation‐free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established.

Aim:

To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment.

Methods:

A 6‐month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3‐month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months.

Results:

Sixty‐one patients were enrolled. No side‐effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (− 8%; P = 0.003), aspartate aminotransferase (− 11%; P = 0.01), alanine aminotransferase (− 17%; P < 0.001), γ‐glutamyl transferase␣(− 34%; P < 0.001), immunoglobulin M (− 11%; P = 0.002) and cholesterol (− 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group.

Conclusions:

Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/day is a suboptimal dose for treating PBC.
Eradication ofHelicobacter pyloriwith lansoprazole, roxithromycin and metronidazole—an open pilot study
Authors: Pohle  , Stoll  , Kirchner  , Heep  , Lehn  , Bock  , Domschke
Published: March 2003

Background:

The most extensively studiedHelicobacter pylorieradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested.

Aim:

To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre out‐patient care in an open pilot study.

Methods:

163 patients with duodenal ulcer and provenH. pyloriinfection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily.H. pyloristatus was determined by urease quick test, histology, microbiology and13C‐urea breath test before starting and at least 4 weeks after completing treatment.

Results:

150 patients were available for evaluation;H. pyloriwas successfully eradicated in 84.7% (127/150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by13C‐urea breath test; and in 75.3% (113/150), at least two tests were negative. Side‐effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of theH. pyloriisolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%).

Conclusions:

ForH. pylorieradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole‐resistantH. pyloriis not rare in Germany and, in the present study, has strongly influenced treatment success.
Review article: gender‐related differences in functional gastrointestinal disorders
Authors: Mayer E.A. , Naliboff B. , Lee O. , Munakata J. , Chang L.
Published: March 2003

Many functional gastrointestinal disorders and other chronic visceral pain disorders such as interstitial cystitis and chronic pelvic pain are more common in women than in men. In irritable bowel syndrome (IBS) there is a 2 : 1 female to male ratio in prevalence of symptoms in community samples. Female irritable bowel syndrome patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms.

While animal studies have clearly demonstrated gender‐related differences in pain perception and antinociceptive mechanisms, unequivocal evidence for gender‐related differences in human pain perception or modulation has only been provided recently. Gender‐related differences may be related to constant differences in the physiology of pain perception, such as structural or functional differences in the visceral afferent pathways involved in pain transmission or modulation, and/or they may be related to fluctuations in female sex hormones.

Preliminary evidence suggests that female irritable bowel syndrome patients show specific perceptual alterations in regards to rectosigmoid balloon distension and that they show differences in regional brain activation measured by positron emission tomography. This preliminary evidence suggests that gender‐related differences in symptoms and in the perceptual responses to visceral stimuli exist in IBS patients and can be detected using specific stimulation paradigms and neuroimaging techniques.
Review article: the pharmacology of rabeprazole
Authors: Williams  , Pounder
Published: March 2003

Rabeprazole sodium is a new substituted benzimidazole proton pump inhibitor with several differences compared with existing proton pump inhibitors. In vitro and animal studies have demonstrated that rabeprazole is a more potent inhibitor of H+,K+‐ATPase and acid secretion than omeprazole, and is a more rapid inhibitor of proton pumps than omeprazole, lansoprazole, or pantoprazole. This probably reflects rabeprazole’s faster activation in the parietal cell canaliculus. In human studies, once‐daily doses of 5–40 mg of rabeprazole inhibit gastric acid secretion in a dose‐dependent fashion. A once‐daily dose of 20 mg has consistently achieved profound decreases in 24‐h intragastric acidity in single and repeat dosing studies, in healthy volunteers and patients with either peptic ulcer disease or gastro‐oesophageal reflux disease. Significantly greater decreases in intragastric acidity are achieved on day 1 of dosing with rabeprazole 20 mg than with omeprazole 20 mg. As with other proton pump inhibitors, rabeprazole has in vitro antibacterial activity against Helicobacter pylori, with greater activity against this organism than either lansoprazole or omeprazole. In addition to inhibiting bacterial urease activity, rabeprazole binds to several molecules on H. pylori. Clinical trials are needed to assess the clinical importance of these findings, as well as to assess whether the potential advantages of rabeprazole result in clinical benefit for patients with acid‐related diseases.
Combination therapy of pentoxifylline and TNFα monoclonal antibody in dextran sulphate‐induced mouse colitis
Authors: Murthy  , Cooper  , Yoshitake  , Meyer  , Meyer  , Murthy
Published: March 2003

Background:

Tumour necrosis factor‐alpha (TNFα) has been suspected of playing an important role in the pathogenesis of inflammatory bowel diseases, and has become a target for the treatment of these diseases. Open‐label, placebo controlled studies have shown that engineered CDP571 and chimeric anti‐TNF antibody (cA2) provide a significant benefit in Crohn’s disease. Since these antibodies have to be used repeatedly to maintain remission in inflammatory bowel disease, there is a concern that their use may compromise host defence and produce toxic side‐effects.

Methods:

We evaluated the combined use of mouse specific TNFα mab (25 μg/mouse, Endogen) and pentoxifylline (PF, 100 mg/kg/day, p.o., TNFα release inhibitor) in the DSS (3% dextran sulphate solution) model of mouse colitis. Colitis was induced by the feeding of 3% DSS for three cycles. The study groups were: Group I: single injection of rat anti‐mouse IgG, Group II: single injection of TNFα mab, Group III: daily PF for three cycles, Group IV: single injection of TNFα mab + PF for three cycles, Group V: TNFα mab at the beginning of each cycle (three injections) and Group VI: TNFα mab (three injections) + daily PF for three cycles. Daily disease activity (DAI) was measured throughout the study. At the end of each cycle, colon tissue was processed for histology, myeloperoxidase (MPO) and plasma TNFα.

Results:

Mice treated with a single injection of TNFα alone or TNFα mab + PF showed significantly lower DAI, inflammation scores and ulcer index compared with the IgG treated group. Mice treated with TNFα mab + PF had no ulcers. Multiple injections of TNFα mab or TNFα mab + PF showed greater inhibition in DAI and cytokines in the first two cycles. However, in the third cycle, multiple injections of TNFα mab showed adverse proinflammatory effects.

Conclusion:

The simultaneous administration of pentoxifylline and TNFα mab may enhance therapeutic outcomes in inflammatory bowel disease and reduce the side‐effects associated with the repeated use of TNFα mab.
Is routine histological evaluation an accurate test for Helicobacter pylori infection?
Authors: MACONI  , VAGO  , GALLETTA  , IMBESI  , SANGALETTI  , PARENTE  , CUCINO  , BONETTO  , PORRO G. BIANCHI
Published: March 2003

Aim

: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C‐urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago‐gastro‐duodenoscopy.

Materials and Methods

: One‐hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C‐urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori‐positive if two or more tests were positive.

Results

: Eighty‐one patients (70.4%) were found to be H. pylori positive. 13C‐urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re‐evaluation by an expert pathologist showed a high sensitivity (98.8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%.

Conclusion

: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre‐treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.
A new mesalazine gel enema in the treatment of left‐sided ulcerative colitis: a randomized controlled multicentre trial
Authors: GIONCHETTI  , ARDIZZONE  , BENVENUTI  , BIANCHI PORRO  , BIASCO  , CESARI  , D'ALBASIO  , DE FRANCHIS  , MONTELEONE  , PALLONE  , RANZI  , TRALLORI  , VALPIANI  , VECCHI  , CAMPIERI
Published: March 2003

Background

: A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis.

Aim

: To evaluate the efficacy, safety and patient tolerability of mesalazine gel enema compared with mesalazine foam enema in the treatment of patients with acute left‐sided ulcerative colitis.

Methods

: In a randomized multicentre investigator‐blind parallel group trial, 103 patients with mild to moderate left‐sided colitis or proctosigmoiditis were randomly allocated to mesalazine 2 g gel enema (n = 50 evaluable patients) and mesalazine 2 g foam enema (n = 53 evaluable patients) for 4 weeks. Clinical symptoms, endoscopic and histological findings were assessed at entry, 2 and 4 weeks. Patients' evaluation of treatment tolerability and acceptability was assessed at 2 and 4 weeks.

Results

: After 4 weeks of treatment, clinical remission was achieved by 76% of mesalazine gel enema‐treated patients and 69% of patients treated with mesalazine foam enema (P = 0.608). Endoscopic remission rates at week 4 were 51 and 52% for the mesalazine gel and foam enemas, respectively (P = 0.925). Histological remission was achieved by 30% of patients in both groups. Patients reported that the new mesalazine gel preparation was significantly better tolerated than the foam enema.

Patients in the foam group had significantly more difficulty in retention (25% vs. 6%, P < 0.05), abdominal bloating (50% vs. 26%, P < 0.005) and discomfort during administration (48% vs. 26%, P < 0.05).

Conclusion

: The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema.
Immunosuppressive therapy for ulcerative colitis: results of a nation‐wide survey among consultant physician members of the British Society of Gastroenterology
Authors: STACK  , WILLIAMS  , STEVENSON  , LOGAN
Published: March 2003

Background

: The role of immunosuppressive therapy in ulcerative colitis remains controversial. There is little information available on how frequently immunosuppressives are used, the circumstances, dose and duration of use and perceived benefit.

Methods

: A postal survey was sent to consultant gastroenterologist members of the British Society of Gastroenterology.

Results

: Questionnaires were returned by 81% of the 496 UK consultants approached. Azathioprine use was frequent, with 93% reporting previous use and 86% use within the past year. Although 95% usually prescribed a ≤ 2 mg/kg dose, only 39% were prepared to prescribe higher doses. There was marked variation in duration of use, with 46% using azathioprine for < 2 years and 17% continuing it for 4 years or longer. Consultants with more experience of azathioprine in ulcerative colitis used it at higher maintenance doses for longer periods, and in patients with less extensive disease. Cyclosporin use was reported by 47% of those caring for ulcerative colitis patients, with 36% having used it at least once in the past year. However, 65% of users estimated that fewer than 50% of patients subsequently avoided colectomy. On stopping cyclosporin only 21% always introduced an alternative immunosuppressive, while 23% never did so. Potentially serious side‐effects attributable to azathioprine and cyclosporin were reported by 36% and 45% of users of each drug, respectively.

Conclusions

: This survey reveals considerable variation in the amount and pattern of immunosuppressive use in ulcerative colitis, with serious side‐effects commonly seen. There is a pressing need for further randomized controlled trials to provide reliable evidence as to how immunosuppressive therapy should be used in ulcerative colitis.
A multicentre evaluation of the laser assisted ratio analyser (LARA): a novel device for measurement of 13CO2 in the 13C‐urea breath test for the detection of Helicobacter pylori infection
Authors: Cave D. R. , Veldhuyzen van Zanten S. , Carter E. , Halpern E. F. , Klein S. , Prather C. , Stolte M. , Laine L.
Published: March 2003

Background

: The laser assisted ratio analyser (LARA) was developed as a novel device to measure 13CO2 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2).

Methods

: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of 13C‐urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample.

Results

: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 ± 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 ± 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis.

Conclusions

: The LARA provides an accurate non‐invasive means of detecting 13CO2 in the 13C‐urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive ‘gold standard’ methods.
Review article: the management of Giardiasis
Authors: Vesy  , Peterson
Published: March 2003

Giardiasis is the intestinal infection resulting from infestation with the human parasite Giardia intestinalis, also called Giardia lamblia. The infection may be asymptomatic or present with a variety of symptoms such as diarrhoea, weight loss, abdominal cramps, and failure to thrive. Giardiasis is most often diagnosed after recent travel or in day care centres. The organism has two stages in its life cycle. It is usually ingested as a cyst with as few as 10–25 cysts being sufficient to cause infection. After excystation, the organism is a replicative trophozoite which may attach to the small bowel wall. Giardia intestinalis does not invade the bowel wall. Trophozoites may encyst and be shed in faeces for future ingestion by another host. Diagnosis of infection is by stool examination which may also eliminate other possible infectious agents. Small bowel biopsy may be necessary in difficult individual cases or to rule out non‐infectious illnesses, and stool ELISA may serve for large population screening examinations. The mainstay of treatment is metronidazole 250–400 mg three times per day by mouth for 5 days.
Evaluation of treatment regimens to cure Helicobacter pylori infection—a meta‐analysis
Authors: Laheij  , Rossum L. G. M. Van , Jansen  , Straatman  , Verbeek
Published: March 2003

Objective

: To assess effectiveness of treatment to cure Helicobacter pylori infection.

Data Synthesis

: Meta‐analysis of 666 manuscripts (full papers, abstracts, letters to the editor) identified through Medline and a manual search (1986 to January 1998). Data were overviewed by regression analysis with weighted random effects models.

Subjects

: 53 228 patients with H. pylori infection.

Interventions

: Patients were treated with 132 different medication combinations.

Main outcome measure

: Cure of H. pylori infection per protocol and intention‐to‐treat basis at least 28 days after treatment.

Results

The nationality of the patients and therapeutic regimen have a significant impact on the results, after correction for the heterogeneity in the precision of the cure rate caused by different study sizes and random effect for study. On the basis of the original sample size, cure rates of 80–85% were achieved using combinations of a proton‐pump inhibitor or ranitidine bismuth citrate with two antibiotics including clarithromycin, amoxycillin and metronidazole or tinidazole. Comparable cure rates were also achieved using a combination of a proton‐pump inhibitor or H2‐receptor antagonist with bismuth subcitrate or tripotassium dicitrato bismuthate, metronidazole and tetracycline. The dose of clarithromycin influenced cure rates. Treatment duration did not influence the outcome.

Conclusion

Several therapeutic regimens are eligible to cure H. pylori infection. However, none of the medication combinations were able to cure H. pylori infection in more than 85% of the patients assessed by intention‐to‐treat. The countries in which the studies were performed also had a significant impact on eradication rates.
The effects of oral rabeprazole on endocrine and gastric secretory function in healthy volunteers
Authors: Dammann  , Burkhardt  , Wolf
Published: March 2003

Aim

: To evaluate the short‐term effects of rabeprazole 20 mg on endocrine parameters, in particular serum testosterone and cortisol, and on 24 h intragastric pH, H+ activity and nocturnal gastric acid secretion.

Methods

: In this double‐blind, two‐period crossover study, 12 healthy young male volunteers were randomly given oral rabeprazole 20 mg o.m. or placebo for 14 days. There was a washout period of at least 1 week between the two studies. The effects of rabeprazole and placebo on cortisol and testosterone (primary criteria), and on tri‐iodothyronine, thyroxine, 17β‐oestradiol, thyroid‐stimulating hormone, thyroxine‐binding protein, parathyroid hormone, insulin, glucagon, rennin, aldosterone, follicle‐stimulating hormone, luteotrophic hormone, prolactin, somatotrophic hormone, dehydroepiandrosterone, cortisol‐binding globulin and urinary 6‐β hydroxycortisol were compared. Intragastric 24 h pH, 24 h H+ activity and nocturnal gastric acid secretion were determined by pH probe and gastric aspiration.

Results

: Rabeprazole produced no clinically relevant effects on endocrine function as assessed by measurement of serum testosterone, circadian serum cortisol levels, ACTH‐stimulated serum cortisol levels and 17 other endocrine function tests. Rabeprazole significantly increased the 24 h median pH values compared to placebo (on Days 7 and 14 median values ranged from 3.92 to 6.88 with rabeprazole and from 1.48 and 4.22 with placebo, P < 0.001) and significantly decreased the integrated 24 h H+ activity (AUC08–08) from 343 mmol/L/h with placebo to 44 mmol/L/h with rabeprazole (P < 0.001). Following cessation of dosing, intragastric pH levels decreased and H+ activity increased, but acid secretion did not recover completely during the next 72 h. The mean value for nocturnal gastric acid secretion on Days 7 and 8 was 36 mmol/6 h with placebo and 5.6 mmol/6 h with rabeprazole (P < 0.001). Rabeprazole was well tolerated.

Conclusion

: Rabeprazole did not influence endocrine function in healthy young male volunteers during short‐term dosing. Rabeprazole substantially increased intragastric pH over a 24 h period and significantly decreased intragastric acidity and nocturnal gastric acid secretion.