bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic fluctuations in the cardiac performance of the isolated Langendorff‐perfused mouse heart: pyruvate abolishes the fluctuations and has an anti‐ischaemic effect
Authors: Wang Q.‐D. , Tokuno S. , Valen G. , Sjöquist P.‐O. , Thorén P.
Published: March 2003

During the development of a Langendorff preparation of isolated mouse hearts, hitherto undescribed cyclic fluctuations in left ventricular pressure and coronary flow were independently observed in three laboratories. Isolated mouse hearts were perfused with crystalloid glucose‐containing Krebs–Hensleit buffer in a constant pressure model, and left ventricular pressures were measured via an intraventricular balloon catheter. After acquiring technical skill in preparing the mouse hearts, the perfusionists observed that fluctuations in cardiac performance with a cycle period lasting 5–10 min occurred shortly after initiation of perfusion. Each fluctuation cycle consisted of a phase of increase and a phase of decrease. Synchronized with the fluctuations in left ventricular pressure, increases and decreases in dP/dt max took place. Analogous fluctuations in coronary flow occurred, with onset 1–2 min later than changes in left ventricular systolic pressure. In some preparations a gradual ST‐segment elevation was seen on the electrocardiogram during the systolic pressure increase phase. The amplitude of the fluctuations could be augmented by increasing the perfusion pressure, and reduced, but not abolished, by lowering the pressure. Changes in buffer calcium, magnesium, or sodium concentration did not alter the fluctuations, nor did any change of anaesthetics, mouse strain, or left ventricular drainage. Altering the perfusion mode from constant pressure to constant flow did not prevent the occurrence of the cyclic fluctuations. The hearts became stable and the fluctuations disappeared when the buffer was supplemented with 2 mm pyruvate. In the present study, pyruvate given throughout stabilization and reperfusion also markedly attenuated the ischaemic insult, as evidenced by the delayed ischaemic contracture and a reduced magnitude of ischaemic contracture. A cardioprotective effect was only visible at early reperfusion, did not affect the final functional recovery. In conclusion, a phenomenon of cyclic fluctuations in left ventricular pressure followed by fluctuations in coronary flow was observed in isolated mouse hearts. These could be abolished by adding 2 mm pyruvate to the perfusion buffer. Pyruvate in the buffer also markedly attenuated the post‐ischaemic deterioration of cardiac performance seen in this mouse model.
Altered myosin isoform expression in rat skeletal muscles induced by a changed thyroid state
Authors: Wahrmann J. P. , Fulla Y. , Rieu M. , Kahn A. , Dinh‐Xuan A. T.
Published: March 2003

The aim of our study was to find out, which are the thyroid linked mechanisms responsible for the changes in myosin isoform composition which accompany endurance training (ET) in rodents. We studied the interaction between ET and altered sedentary group with no thyroid treatment or Se group. Six groups of rats were compared: (1) a trained group with no thyroid treatment or T group; (2) a thyroid state in rats; (3) a sedentary group rendered hypothyroid with 6‐n‐propyl thio uracil (H); (4) a sedentary group rendered hyperthyroid with T3 (150 μg kg−1 every other day for 4 weeks) (St); (5) trained rats rendered hyperthyroid with T3 (150 μg kg−1 every other day for 4 weeks) (Tt) and (6) a trained group kept euthyroid with T3 (150 ng kg−1 every other day for 4 weeks) (Te). In each group myosin isoform composition was determined in five muscles, three locomotor muscles: (1) extensor digitorum longus, (2) superficial lateral gastrocnemius, (3) deep medial gastrocnemius, (4) an antigravity muscle, the soleus and (5) a rhytmic respiratory muscle, the crural diaphragm. Different muscles responded in a specific way to variations of the thyroid state and training.
Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: influence of dietary sodium
Authors: DiBona G. F.
Published: March 2003

Aim:  Administration of angiotensin II (angII) into the cerebral ventricles or specific brain sites impairs arterial baroreflex regulation of renal sympathetic nerve activity (SNA). Further insight into this effect was derived from: (a) using specific non‐peptide angII receptor antagonists to assess the role of endogenous angII acting on angII receptor subtypes, (b) microinjection of angII receptor antagonists into brain sites behind an intact blood–brain barrier to assess the role of endogenous angII of brain origin and (c) alterations in dietary sodium intake, a known physiological regulator of activity of the renin–angiotensin system (RAS), to assess the ability to physiologically regulate the activity of the brain RAS.

Methods:  In rats in balance on low, normal or dietary sodium intake, losartan or candesartan was injected into the lateral cerebral ventricle or the rostral ventrolateral medulla (RVLM) and the effects on basal renal SNA and the arterial baroreflex sigmoidal relationship between renal SNA and arterial pressure were determined.

Results:  With both routes of administration, the effects were proportional to the activity of the RAS as indexed by plasma renin activity (PRA). The magnitude of both the decrease in basal renal SNA and the parallel resetting of arterial baroreflex regulation of renal SNA to a lower arterial pressure was greatest in low‐sodium rats with highest PRA and least in high‐sodium rats with lowest PRA. Disinhibition of the paraventricular nucleus (PVN) by injection of bicuculline causes pressor, tachycardic and renal sympathoexcitatory responses mediated via an angiotensinergic projection from PVN to RVLM. In comparison with responses in normal sodium rats, these responses were greatly diminished in high‐sodium rats and greatly enhanced in low‐sodium rats.

Conclusion:  Physiological changes in the activity of the RAS produced by alterations in dietary sodium intake regulate the contribution of endogenous angII of brain origin in the modulation of arterial baroreflex regulation of renal SNA.
Territoriality and spatial patterns of white rhinoceros in Matobo National Park, Zimbabwe
Authors: Rachlow Janet L. , Kie John G. , Berger Joel
Published: March 2003

Boundaries associated with reserves or conservation areas may alter spatial patterns of individuals, and may affect the sexes differently in species that exhibit sex‐specific patterns of space use. Because of poaching threats, most African rhinos today persist within sanctuaries or reserves with fenced perimeters. We examined spatial patterns of adult white rhinos (Ceratotherium simum) in Matobo National Park, Zimbabwe. Matobo Park contains a high‐density population of rhinos within a fenced reserve and a lower‐density group outside of the fenced area. Adult females in the lower‐density group used significantly larger home ranges than those in the high‐density group. Overlap among female home ranges was extensive in both groups. Adult male white rhinos establish territories that are exclusive of other males performing scent‐marking behaviours, and in Matobo Park, male territories were much larger than those observed in other populations of white rhinos. Additionally, few adult males in the high‐density reserve held territories that occupied most available space; two‐thirds of adult males were excluded from establishing territories, and followed a non‐territorial tactic. In the absence of dispersal opportunities, managers may need to regulate the number of males within smaller reserves. Monitoring of spatial patterns should be undertaken to permit management decisions to be made with an understanding of male behaviour and territorial status.
Fire survival of the Critically Endangered succulent, Euphorbia clivicola R.A. Dyer – fire‐avoider or fire‐tolerant?
Authors: Pfab M. F. , Witkowski E. T. F.
Published: March 2003

The hypothesized ultimate agent of decline for one of the only two known populations of Euphorbia clivicola R. A. Dyer, a Critically Endangered species endemic to the Northern Province of South Africa, is the unsuitable fire management practised within the Nature Reserve in which the population is protected. Management recommendations concerning the fire regime need to consider fire survival in this succulent species. Fire survival of succulents may be due to the avoidance of fire in refugia or due to fire tolerance by vegetative recovery. Subsequent to a fire, damage to E. clivicola plants was determined. New growth (post‐fire resprouting) and rock cover surrounding plants were assessed to determine whether plants tolerated fire through vegetative regrowth or survived fire through protection in refugia. Plants were found to be tolerant of fire, sustaining only mild damage with apparent fire mortality at 3% (2% of the plants were already dead prior to the fire). Fire damage stimulated vegetative regrowth, regrowth being more common in plants that had sustained higher levels of fire damage.
Feeding habits of the spotted hyaena in the Niokolo Koba National Park, Senegal
Authors: Di Silvestre Ilaria , Novelli Ottavio , Bogliani Giuseppe
Published: March 2003

The food habits of the spotted hyaena were studied during the dry season in relation to food availability in the Niokolo Koba National Park, Senegal. Frequency of occurrence of the different foods was quantified by means of scat analysis; species occurrence in the diet was compared with availability in the study area. Large and medium‐sized mammals, such as the buffalo, the hartebeest and the warthog, were eaten more often than expected.
Angulate and leopard tortoises in the Thicket Biome, Eastern Cape, South Africa: populations and biomass estimates
Authors: Mason Mervyn C. , Kerley Graham I. H. , Weathreby Craig A. , Branch William R.
Published: March 2003

The population parameters (morphometrics, population size and biomass) were determined for leopard and angulate tortoises in the Thicket Biome, Eastern Cape, South Africa. Leopard tortoises had a mean total length of 306.47mm (SD = 94.65mm, range 59–496mm,n = 89). Males were smaller (mean total length 277.31mm, SD = 71.85mm, range 73–377mm,n = 36) than females (mean total length = 332.33mm, SD = 97.64mm, range 59–496mm, n = 53). Angulate tortoises had a mean total length of 155.17mm (SD = 33.89mm, range 59–194mm, n = 18). Males were larger (mean total length = 186mm, SD = 8.40mm, range 174–194mm, n = 5) than females (mean total length = 143.31mm, SD = 32.48mm, range 59–178mm, n = 13). The estimated population density for leopard tortoises was 0.85 tortoises ha−1 with an estimated biomass of 6.02kg −1. Angulate tortoise population density was estimated at 0.12 tortoises ha−1 with a mean biomass of 0.06kg ha−1. The possible consequences of this high density and biomass are discussed.
Surveys of sympatric lemurs at Anjamena, north‐west Madagascar
Authors: Müller Pie , Velo Arsène , Raheliarisoa Evelyne‐Odette , Zaramody Alphonse , Curtis Deborah J.
Published: March 2003

In order to assess the status of lemurs along the lower reaches of the Mahavavy in north‐west Madagascar, we carried out transect line sampling at Anjamena between April and August 1995. These data were complemented by additional absence–presence surveys conducted in 1994 and 1995 in many of the remaining forested areas of the region. This is the first study of lemur population density estimates for the faunal subregion between the rivers Mahavavy and Betisboka. Six sympatric lemurs are found at Anjamena: Cheirogaleus medius, Eulemur fulvus rufus, E. mongoz, Lepilemur sp., Microcebus murinus and Propithecus verreauxi coronatus. Data suggest that in some parts of the region large numbers of lemurs may still be found (E. f. rufus 121 individuals per km2, E. mongoz (45), Lepilemur sp. (110), M. murinus (85) and P. v. coronatus (173)). No density data are provided for C. medius. In conclusion, as high lemur population densities may still be found and, in particular, P. v. coronatus is not known to exist in any protected area, Anjamena could serve as an important addition to the protected area system of north‐west Madagascar.
Endemicity of Afromontane grasshopper assemblages: implications for grassland conservation
Authors: Foord S. H. , Ferguson J. W. H. , Van Jaarsveld A. S.
Published: March 2003

The Drakensberg escarpment in southern Africa is extensively afforested with pine plantations. The Afromontane grasslands in this area have large numbers of endemic plant taxa, but very little is known of their invertebrate fauna. We report on the microgeographical and broad‐scale geographical characteristics of grasshoppers and their allies (Orthoptera) at the Groenvaly grassland fragmentation experiment site, South Africa. Pre‐fragmentation sampling indicates that control sites and experimental fragments were comparable at the start of the experiment. Of the surveyed species (total 31 species) 25% are endemic to this grassland with another 33% occurring more widely in montane grasslands of south‐eastern South Africa. The level of orthopteran endemicity is therefore similar to that of plants, emphasizing the conservation importance of this threatened habitat. There was a significant inverse relation between the degree of stenotopy of a species within the study site and its geographical range in southern Africa, with implications for interpreting the conservation importance of taxonomically and geographically unknown taxa such as the beetles (Coleoptera) in the Afromontane grassland. This information on endemicity of the Afromontane Orthoptera indicates that these grasslands harbour a diverse endemic fauna representing a significant part of southern African biodiversity.
Gastrin interferes with the differentiation of gastric pit cells and parietal cells
Authors: Nakajima T. , Konda Y. , Izumi Y. , Kanai M. , Takeuchi T. , Chiba T.
Published: March 2003

Background:

Gastrin is known to have stimulatory effects on gastric mucosa; however, long‐term effect of gastrin stimulation is not well known.

Aim and methods:

To investigate the long‐term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene‐expressing mice showed serum gastrin levels of more than 600 pg/mL.

Results:

Neither progastrin nor glycine‐extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30–35‐week‐old transgenic mice were 30–50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K‐ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo, specific gastrin binding sites were observed in the mid‐glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells.

Conclusions:

These results suggest that long‐term stimulation of gastrin increases the expression of CCK‐B/gastrin receptors in the less‐differentiated pit cells that are the main component of elongated gastric units, and lessens the well‐differentiated characteristics of parietal cells.
Analysis of Helicobacter pylori and nonsteroidal anti‐inflammatory drug‐induced gastric epithelial injury
Authors: Igarashi M. , Takagi A. , Jiang X. , Hasumi K. , Watanabe S. , Deguchi R. , Miwa T.
Published: March 2003

Background:

Helicobacter pylori and nonsteroidal anti‐inflammatory drugs (NSAIDs) are important factors in gastric mucosal injury. However, the relationship between H. pylori and NSAID‐related gastroduodenal mucosal injury has not been clarified.

Aim:

To determine the role of H. pylori in NSAID‐induced gastric mucosal injury and to examine the effects of H. pylori, indomethacin and sofalcone on gastric epithelial cells in culture, as a useful model to study gastric mucosal injury. In addition, we studied the effect of sofalcone, a gastric mucosal protection agent, on H. pylori and NSAID‐induced gastric mucosal injury.

Methods:

Cytotoxic and noncytotoxic strains of H. pylori were used, each with an inoculum of 107 cfu/mL. The effect on the growth of RGM–1 cells (a rat gastric epithelial cell line) was studied by MTT assay, and levels of prostaglandin E2 in culture supernatants were measured by EIA.

Results:

Both cytotoxic and noncytotoxic strains of H. pylori tended to induce cell injury in RGM‐1 cells at 48 h after inoculation. Indomethacin alone induced gastric epithelial injury in a dose‐dependent manner, but did not augment cell injury induced by H. pylori. In addition, sofalcone (10−5 mol/L) showed a suppressive effect on indomethacin‐induced gastric epithelial injury.

Conclusion:

These findings indicate that indomethacin induces gastric mucosal injury regardless of H. pylori infection, and suggests that sofalcone may be a useful drug in the treatment of NSAID‐induced mucosal injury.
Medical treatment of active Crohn's disease
Authors: Scribano M. L. , Prantera C.
Published: March 2003

Crohn's disease, a heterogenous inflammatory process that can affect various sites in the gut, presents an ongoing management challenge for the clinician. The treatment of active disease and complications is one of the main goals in the therapy of this disease. New therapies are aimed at delivering the active compounds to the diseased site, reduction or suppression of enteral flora and modulation of more focal targets within the immune response.

The use of antibiotics in the therapy of Crohn's disease is gaining popularity, on the grounds that intestinal bacteria may play a role in the pathogenesis of Crohn's disease lesions. Metronidazole is one of the most widely used antibiotics, especially in the treatment of perianal disease.

Corticosteroids are the mainstays of medical treatment in active Crohn's disease and induce the remission of symptoms in about 60–80% of patients.

The use of immunosuppressive agents, such as cyclosporine and methotrexate, in patients with active disease resistant to standard therapy has gained acceptance in recent years.

With new therapies the outlook for patients with Crohn's disease is more optimistic than it has been for a long time.
Crohn's disease – the role of nutritional therapy
Authors: Forbes A.
Published: March 2003

Maintenance of adequate nutrition is of obvious importance in the management of patients with Crohn's disease. Exclusive parenteral nutrition can achieve high rates of remission, but this is not usually necessary since exclusive elemental and polymeric enteral regimes can yield similarly good results. Comparison of exclusive enteral formula feeding with steroid treatment favours steroids only because compliance is less complete for the restrictive nutritional regimes, and formula feeds should always be the first choice in the growing child with active Crohn's disease. It is probable that the nature of the lipid provided in Crohn's diets is clinically important, and there is some evidence that the n‐3 fatty acids are beneficial. Continuation of nutritional supplements once remission has been obtained appears valuable even when malnutrition is not a major consideration.
Randomized comparison of 1‐hour topical method vs. amoxycillin plus omeprazole for eradication of Helicobacter pylori in duodenal ulcer patients
Authors: Przytulski  , Regula  , Dziurkowska‐Marek  , Kohut  , Hennig  , Marek  , Ostrowski  , Nowak  , Butruk
Published: March 2003

Background:

A novel 1‐h topical method eradicated Helicobacter pylori in 96% of dyspeptic patients. The eradication rate of amoxycillin/omeprazole therapy varies from 0 to 93%.

Aim:

To compare both methods in patients with endoscopically proven duodenal ulcer.

Methods:

Eighty patients (59 males, 21 females; median age 43 years) were randomized into two therapeutic groups. The first group (group A) was treated with a 6‐week course of ranitidine 300 mg/day, then omeprazole 20 mg b.d. with pronase 36 000 units/day for 2 days, followed by 1‐h topical therapy with a solution of bismuth, metronidazole, amoxycillin and pronase. The second group (group B) consisted of patients treated with omeprazole 20 mg b.d. and amoxycillin 2 g/day for 2 weeks, followed by a 4‐week course of ranitidine 300 mg/day. Eradication of H.␣pylori was assessed by urease test, histology, a polymerase chain reaction and a 13C‐urea breath test, all of which were performed 4 weeks after discontinuation of the antibacterial treatment.

Results:

Eradication rates in groups A and B were 2.5% and 35% in an intention‐to‐treat analysis, respectively. Side‐effects were encountered in 40.5% and 12.5% of subjects in groups A and B, respectively. Treatment tolerance was rated as poor by 54% of patients in group A and 2.5% of patients in group B.

Conclusions:

Both treatment regimens, the 1‐h topical method and amoxycillin with omeprazole, have low eradication rates in patients with duodenal ulcer. In addition, the topical treatment is characterized by a high rate of side‐effects and poor tolerance. Based on the results of our study, neither method can be recommended for eradication of H. pylori in patients with duodenal ulcer.
Antibiotic prophylaxis for ERCP: a comparison of oral ciprofloxacin with intravenous cephazolin in the prophylaxis of high‐risk patients
Authors: Davis  , Kolios  , Alveyn  , Robertson
Published: March 2003

Background:

Cholangitis and septicaemia are serious complications of endoscopic retrograde cholangiopancreatography (ERCP). They occur mainly following therapeutic ERCP in the setting of an obstructed biliary system. The optimum prophylactic antibiotic regimen in such patients is not yet defined but usually depends on intravenous agents.

Aim:

To compare the efficacy of oral ciprofloxacin with intravenous cephazolin.

Methods:

One hundred and fifty patients at high risk from septic complications were randomized prospectively to either oral ciprofloxacin (750 mg b.d.) or intravenous cephazolin (1 g b.d.), commenced at least 90 min prior to the ERCP and continued for 3 days. Bacteriological cultures were taken from bile during the procedure and from blood both immediately and at 24 h post‐procedure.

Results:

There were no significant differences between the two treatment groups in the pre‐ERCP clinical or radiological findings or in the types of procedure performed. One patient did not undergo an ERCP and was excluded from the final analysis. Of the 77 patients in the ciprofloxacin group there were no positive blood cultures and one positive culture from a nasobiliary drain. Two out of the 72 cephazolin patients had positive blood cultures immediately post‐ERCP; one of these two patients and one other cephazolin patient had positive bile cultures. There were no cases of cholangitis or septicaemia in the ciprofloxacin group and three cases in the cephazolin group. One patient from each treatment group died within the 7‐day study. Adverse drug reactions were minimal and none of the different clinical outcomes in the two groups reached statistical significance.

Conclusion:

Oral ciprofloxacin is a cost‐effective prophylactic agent for high‐risk ERCP.
Comparison of omeprazole and lansoprazole in short‐term triple therapy for Helicobacter pylori infection
Authors: Spinzi  , Bierti  , Bortoli  , Colombo  , Fertitta  , Lanzi  , Venturelli  , Minoli
Published: March 2003

Background:

Effective anti‐Helicobacter pylori therapies with few side‐effects are needed.

Aim:

To study the effectiveness of short‐term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body.

Results:

A total of 356 patients were randomized in this single‐blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention‐to‐treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side‐effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy).

Conclusions:

This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.
Ranitidine bismuth citrate plus clarithromycin 7‐day regimen is effective in eradicating Helicobacter pylori in patients with duodenal ulcer
Authors: Pozzato  , Zagari  , Cardelli  , Catalano  , Giglio  , Lami  , Pilotto  , Scarpulla  , Spadaccini  , Susi  , Tosatto  , Olivieri  , Bazzoli  , Roda
Published: March 2003

Background:

No clinical study has been performed to‐date to evaluate the efficacy of the dual therapy of ranitidine bismuth citrate (RBC) plus clarithromycin (C) 500 mg b.d. given for 7 days for the eradication of H. pylori.

Aim:

To assess the eradication rates achieved by treatment with RBC 400 mg b.d. for 28 days combined with clarithromycin 500 mg b.d. for 7 days in H. pylori‐positive duodenal ulcer patients. Methods: One hundred and twelve H. pylori‐positive patients with endoscopically proven active duodenal ulcer were included in a multicentre, open, randomized trial. H. pylori infection was initially detected by CLO‐test and histology on antral and corpus biopsies, and by 13C‐urea breath test (UBT). Patients were included if at least two of the tests were positive for H. pylori infection. Patients were randomized to receive RBC 400 mg b.d. for 4 weeks combined with clarithromycin 500 mg b.d. for the first 7 days (Group A) or 14 days (Group B). A second endoscopy was performed at least 28 days after the end of therapy for the assessment of ulcer healing and H. pylori infection. Eradication was assumed if all the tests (CLO‐test, histology and UBT) were negative for H. pylori.

Results:

Fifty patients in Group A and 55 in Group B were assessed for H. pylori eradication and ulcer healing. The eradication rates according to intention‐to‐treat analysis were 75% in Group A and 80% in Group B. Considering only those patients with evaluable data at least 28 days after the end of therapy, H. pylori eradication was achieved in 84% and 82% in Group A and B, respectively. No statistically significant difference in eradication was found between the two groups by Mantel–Haenszel test. Only one patient, in Group A, was withdrawn because of adverse events (epigastric pain and pruritus).

Conclusions:

Dual therapy with RBC plus clarithromycin for 7 days could be an effective regimen for H. pylori eradication.
Dialysis of the rectum for sampling drug concentrations in the luminal extracellular fluid of the gut: technique and precision
Authors: Egan  , Sandborn  , Mays  , Tremaine  , Lipsky
Published: March 2003

Background:

It is useful to measure the luminal concentration of drugs which act in the gut. Dialysis of the rectum has not previously been used or validated for this purpose.

Aim:

To determine the precision of rectal dialysis for measuring rectal drug concentrations.

Methods:

To establish the duration of dialysis required to approach equilibrium, the rate of methotrexate diffusion into dialysis bags was first determined in vitro. The precision of rectal dialysis for sampling the methotrexate concentration of colonic lumen extracellular fluid was determined in seven subjects who underwent two consecutive dialysis procedures. Subjects treated with subcutaneous methotrexate for refractory inflammatory bowel disease were studied.

Results:

Methotrexate crossed the dialysis membrane by a first‐order process, and after a 2 h in vitro dialysis, equilibration was 74 ± 2% (mean ± s.d.) complete. Rectal dialysis was well tolerated by all subjects. The mean ± s.e. methotrexate concentration of 3.6 ± 1.1 nmol/L in the first dialysate was not significantly different from 3.6 ± 0.9 nmol/L in the second dialysate, P = 0.99 (paired two‐tailed t‐test). Similar precision was obtained for an endogenous molecule, potassium, secreted by the rectal mucosa.

Conclusions:

Dialysis of the rectum is a well tolerated and precise technique for sampling the colonic lumen extracellular fluid for quantitative analyses of exogenous and endogenous substances.
Changes in Helicobacter pylori‐induced gastritis in the antrum and corpus during and after 12 months of treatment with ranitidine and lansoprazole in patients with duodenal ulcer disease
Authors: Meining  , Kiel  , Stolte
Published: March 2003

Background:

Several studies have shown that acid‐suppressing treatment leads to aggravation of Helicobacter pylori gastritis in the corpus. It remains unclear whether this augmentation of the inflammation reverts to baseline after termination of treatment.

Methods:

In 114 H. pylori‐infected duodenal ulcer patients we investigated the gastritis parameters in antral and corpus mucosa before treatment, after 6 and 12 months of therapy, and 6 months after termination of treatment with 15 mg lansoprazole or 150 mg ranitidine/day.

Results:

Lansoprazole and ranitidine led to a significant aggravation of gastritis in the corpus after 6 and 12 months of treatment. However, while there was no change in gastritis in the antrum with ranitidine, treatment with lansoprazole led to partial elimination of H. pylori with improvement of the inflammation in this part of the stomach. Following termination of therapy, the observed changes reverted to baseline. No increase in intestinal metaplasia and/or atrophy in the antrum or corpus was observed.

Conclusion:

Both substances are associated with an aggravation of H. pylori gastritis in the corpus. However, only lansoprazole leads to a partial elimination of H. pylori with improvement of the inflammation in the antrum. The changes provoked by acid‐suppressing treatment revert to baseline after termination of therapy.
Lansoprazole and omeprazole in the prevention of relapse of reflux oesophagitis: a long‐term comparative study
Authors: Carling  , Axelsson  , Forssell  , Stubberöd  , Kraglund  , Bonnevie  , Ekström
Published: March 2003

Background:

Proton pump inhibitors are superior to H2‐receptor antagonists in the prevention of relapse of oesophagitis, but few data directly compare the relative efficacies of lansoprazole and omeprazole in preventing oesophagitis relapse over a prolonged period.

Methods:

Patients with healed Grade II, III or IV oesophagitis were treated with lansoprazole 30 mg o.d. or omeprazole 20 mg o.d. for 48 weeks. Endoscopy and symptom assessment were performed after 12, 24 and 48 weeks of treatment and an additional symptom assessment 36 weeks after starting treatment.

Results:

Intention‐to‐treat analysis included 248 patients (lansoprazole n = 126, omeprazole n = 122). Comparison of time to endoscopic and/or symptomatic relapse revealed no difference between the treatments. There was no significant difference between treatments with respect to the proportion of patients in whom endoscopic and/or symptomatic relapse was reported (lansoprazole 12/126 (9.5%), omeprazole 11/122 (9.0%)). No difference between the treatments in either the number or severity of adverse events was reported.

Conclusions:

Continuous treatment with either lansoprazole 30 mg or omeprazole 20 mg is effective in preventing the relapse of oesophagitis over a 48‐week period in a majority of patients. Both treatments exhibit a similar side‐effect profile.
Review article: current practice and future perspectives in detection and diagnosis of pancreatic cancer
Authors: Haycox  , Lombard  , Neoptolemos  , Walley
Published: March 2003

Pancreatic cancer is the tenth most prevalent malignancy and the fifth most common cause of cancer death in the developed world. Less than 10% of patients survive for more than 1 year following diagnosis and the 5‐year survival rate (0.4%) is the lowest of any cancer. The poor prognosis associated with this diagnosis led in the past to therapeutic nihilism on the part of clinicians who were all too aware of the limitations of their available therapeutic strategies. Breaking this therapeutic impasse requires a significant expansion in the knowledge of clinicians concerning the pathogenesis and behaviour of pan‐ creatic cancer. Recent advances in the scientific understanding of the aetiology of pancreatic cancer has facilitated progress towards the development of promising and innovative approaches to the early detection and diagnosis of pancreatic cancer. While acknowledging that pancreatic cancer will continue to present significant challenges to both scientists and clinicians in the foreseeable future, it is becoming increasingly clear that recent advances in our scientific knowledge base holds the potential to significantly improve prognosis for patients. The challenge facing both scientists and clinicians is how best to translate such promising scientific advances into survival and quality of life benefits to patients.
Ranitidine bismuth citrate (RBC) based triple therapy for 7 days is more effective than RBC plus clarithromycin for 14 days in dyspeptic patients with Helicobacter pylori infection
Authors: Cestari
Published: March 2003

Background:

Ranitidine bismuth citrate (RBC) in co‐prescription with clarithromycin for 2 weeks has been shown to be effective for the eradication of Helicobacter pylori. Moreover, several studies have reported good H. pylori eradication rates with RBC plus two antibiotics for 1 week.

Aim:

To compare the H. pylori eradication rates and safety of two different RBC co‐prescription regimens.

Methods:

Patients undergoing endoscopy for upper gastrointestinal symptoms were randomized to open treatment with either RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 1 week (RbcCT) or RBC 400 mg b.d. plus clarithromycin 500 mg b.d. (RbcC) for 2 weeks. H. pylori infection was detected by CLO‐test on antral biopsy and confirmed by histology on antral and corpus biopsies and by 13C‐urea breath test (UBT). A further UBT was performed at least 4 weeks after the end of treatment to assess the H. pylori eradication. H. pylori eradication was calculated for an intention‐to‐treat (ITT) population (all H. pylori‐positive patients who received at least one treatment dose) and for an all‐patients‐treated (APT) population (patients of the ITT population assessed for H. pylori at least 4 weeks after the end of treatment).

Results

Two hundred and ninety‐five patients (142 males, 153 females, mean age 48 years) were recruited to the study. Of these, 239 had H. pylori infection confirmed by all three tests required by the protocol. The two treatment groups were similar with respect to all the demographic data. H. pylori ITT eradication rates were 85% (104/123) for RbcCT and 67% (78/116) for RbcC. APT eradication rates were 92% (104/113) for RbcCT and 76% (78/103) for RbcC. A significant statistical difference was found between the two treatments, irrespective of the population analysis (P = 0.001). Adverse events occurred in 7% of patients on RbcCT and in 13% on RbcC. No serious adverse events were reported.

Conclusions:

The 1‐week treatment with RBC plus clarithromycin and tinidazole yielded higher eradication rates than the 2‐week treatment with RBC plus clarithomycin. Both treatments were well tolerated.
Effects of two anticholinergic drugs, trospium chloride and biperiden, on motility and evoked potentials of the oesophagus
Authors: Pehl  , Wendl  , Kaess  , Pfeiffer
Published: March 2003

Background:

Anticholinergic drugs are known to impair the motor function of the oesophagus but their effects on the oesophageal afferent pathways are unknown.

Aim:

To determine the effects of a peripherally‐acting (trospium chloride) and a centrally‐acting (biperiden) anticholinergic drug on the motility and the evoked potentials of the oesophagus.

Methods:

Nine healthy volunteers were randomized to receive 1.2 mg trospium chloride (TC), 5 mg biperiden (BIP) or saline i.v. Primary peristalsis was elicited by swallowing a 5 mL water bolus and secondary peristalsis by insufflation of 20 mL air, 10 times each. Oesophageal potentials were evoked by electrical stimulation in the distal and proximal oesophagus (30 stimulations at 0.4 Hz, two runs).

Results:

Both anticholinergic drugs reduced by a similiar amount the contraction amplitudes (TC 17 mmHg, BIP 25 mmHg, saline 67 mmHg; P < 0.01) and the rate of secondary contractions (TC 60%, BIP 70%, saline 95%; P < 0.01). In contrast, only biperiden prolonged the latencies of the evoked potentials (N1 peak, distal oesophagus: BIP 191 ms, TC 102 ms, saline 101 ms; P < 0.01; P1 peak: BIP 322 ms, TC 161 ms, saline 144 ms; P < 0.01).

Conclusions:

Both anticholinergic drugs depress oesophageal motility, but only the centrally‐acting anticholinergic drug biperiden modifies the oesophageal evoked potentials, suggesting a central cholinergic transmission of the oesophageal afferent pathways.
Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin–tazobactam
Authors: Settle  , Wilcox  , Fawley  , Corrado  , Hawkey
Published: March 2003

Background

Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk.

Aim

To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin–tazobactam (PT).

Methods

A prospective, ward‐based, crossover study was carried out on two well‐matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad‐spectrum antibiotic treatment.

Results

There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P = 0.001) and diarrhoea (18/34 vs. 1/14, P = 0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment.

Conclusions

Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.
Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study
Authors: Mitsuyama  , Saiki  , Kanauchi  , Iwanaga  , Tomiyasu  , Nishiyama  , Tateishi  , Shirachi  , Ide  , Suzuki  , Noguchi  , Ikeda  , Toyonaga  , Sata
Published: March 2003

Background

Germinated barley foodstuff (GBF) has been shown to attenuate intestinal injury in animal models, largely by increasing luminal short‐chain fatty acid production.

Aim

To investigate the safety and efficacy of GBF in the treatment of ulcerative colitis (UC).

Methods

Ten patients with active UC received 30 g of GBF daily for 4 weeks in an open‐label treatment protocol while the baseline anti‐inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Pre‐ and post‐treatment stool concentrations of short‐chain fatty acids were measured by gas‐liquid chromatography.

Results

Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 6.9 ± 1.4 to 2.8 ± 1.5 (mean ± S.E.M., P < 0.05). The endoscopic index score fell from 6.1 ± 2.3 to 3.8 ± 2.3 (P < 0.0001). Patients showed an increase in stool butyrate concentrations after GBF treatment (P < 0.05). No side‐effects were observed.

Conclusions

Oral GBF therapy may have a place in management of ulcerative colitis, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.
Review article: drug interactions with agents used to treat acid‐related diseases
Authors: Humphries  , Merritt
Published: March 2003

Patients with acid‐related diseases often need to take multiple medications. Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)‐receptor antagonist or a proton pump (H+,K+‐ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials. Also, treatment for acid‐related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states. Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid‐related and many other diseases. Thus, it is important to understand the potential for clinically significant drug–drug interactions in this setting. H2‐receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance. Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g. warfarin, digoxin). In these cases, drug–drug interactions can result in significant toxicity and even death. There are marked differences among H2‐receptor antagonists and proton pump inhibitors in their potential for such interactions. The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs. The most recently developed H2‐receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications. These differences are important when choosing medications for the safe treatment of patients with acid‐related diseases.
Evaluation of omeprazole as a cost‐effective diagnostic test for gastro‐oesophageal reflux disease
Authors: BATE  , RILEY  , CHAPMAN  , DURNIN  , TAYLOR
Published: March 2003

Background

: There is a need for a simple, therapeutic test that is of diagnostic value and can also provide rapid symptom relief in patients who present with classic, mild symptoms suggestive of gastro‐oesophageal reflux disease (GERD), when the diagnosis is based on symptom assessment alone.

Aim

: To assess the diagnostic value of a therapeutic trial of omeprazole 40 mg in a dyspeptic population.

Methods

: A total of 90 patients with symptoms suggestive of GERD entered the study. Patients underwent endoscopy and ambulatory oesophageal pH monitoring for 18–24 h. Patients then received omeprazole 40 mg o.m. for 2 weeks.

Results

: There was a significant correlation between the diagnoses obtained from a trial of omeprazole and the diagnoses obtained from pH monitoring (P < 0.05). There was no significant correlation between the diagnoses obtained from endoscopy and those obtained from pH monitoring. Both omeprazole and endoscopy were compared to pH monitoring as the ‘gold standard’ for the diagnosis of GERD and the cost per correct diagnosis with omeprazole was £47 (95% CI: £40–£59) compared to £480 (95% CI: £396–£608) with endoscopy. There was a complete absence of acid‐related symptoms in the majority (59%) of patients after 3 days of omeprazole 40 mg therapy and, after 2 weeks, 82% of patients had experienced an improvement in overall symptoms ( 1 grade).

Conclusions

: We conclude that omeprazole can be used as a clinically effective tool in the initial management of GERD and that it is of diagnostic value in patients who present with typical symptoms, such as heartburn, when the diagnosis is based on symptom assessment alone.
Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms
Authors: PEUHKURI  , VAPAATALO  , NEVALA  , KORPELA
Published: March 2003

Background:

In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose.

Aim:

To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose‐induced symptoms.

Methods:

After an overnight fast, 18 lactose maldigesters were given, in a randomized double‐blind study design at 1‐week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded.

Results:

The propantheline‐induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0–12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow‐up) increased by 15% after metoclopra‐ mide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found.

Conclusions:

In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.
Review article:Helicobacter pyloriand gastro‐oesophageal reflux disease—clinical implications and management
Authors: O’connor
Published: March 2003

A significant proportion of patients with gastro‐oesophageal reflux disease (GERD) haveHelicobacter pyloriinfection, but it is unclear whether or notH. pylorishould be treated in this clinical setting. The aim of this review was to critically assess the relationship betweenH. pyloriand GERD and its potential implications for the management of GERD. Data for this review were gathered from the following sources up to April 1998—the biomedical database MEDLINE, a detailed review of medical journals, and a review of abstracts submitted to relevant international meetings.

On average, 40% of GERD patients carryH. pyloriinfection, with a reported infection prevalence ranging from 16% to 88%. To date, there has been no reported controlled trial of effectiveH. pyloritherapy in GERD. GERD has been reported to developde novofollowing the cure ofH. pyloriin peptic ulcer disease.

In the presence ofH. pylori, proton pump inhibitor therapy appears to accelerate the development of atrophic corpus gastritis, a potentially precancerous condition. Conversely, proton pump inhibitor therapy seems to become less effective after cure ofH. pylori. The mechanisms underlying these important contrasting phenomena are poorly understood.

The relationship betweenH. pyloriand GERD is complex, and it is difficult to give definitive guidelines on the management ofH. pyloriinfection in GERD. Controlled trials ofH. pyloritherapy in GERD are urgently needed, as well as further long‐term data on both the natural history of gastric histopathological changes in theH. pylori‐positive GERD patient treated with proton pump inhibitors, and the impact ofH. pyloristatus on the clinical efficacy of antisecretory therapy. Pending these data, it is perhaps advisable to advocate cure ofH. pyloriin young patients with proton pump inhibitor‐dependent GERD who, in the absence of anti‐reflux surgery, are faced with the likelihood of long‐term medical therapy.