bluuebunny/crossref_metadata_2025 huggingface dataset:
Eradication of Helicobacter pylori infection induces an increase in body mass index
Authors: Azuma T. , Suto H. , Ito Y. , Muramatsu A. , Ohtani M. , Dojo M. , Yamazaki Y. , Kuriyama M. , Kato T.
Published: March 2003

Background:

The relationship between H. pylori infection and body mass indices is controversial.

Aim:

To investigate the relationship between H. pylori infection and body indices, and to examine the effect of H. pylori eradication therapy on body indices.

Methods:

Nine‐hundred and thirty‐two employees of an industrial corporation were examined for H. pylori infection and body mass indices. Three hundred and two H. pylori‐positive cases diagnosed with chronic gastritis by upper gastrointestinal endoscopy or radiography underwent eradication therapy. Body mass indices, serum total cholesterol levels and symptom scores were obtained before and at 12 months after eradication therapy.

Results:

There was no significant difference in body weight, body mass index (BMI) or serum total cholesterol level between the H. pylori‐positive and H. pylori‐negative groups. However, body weight and BMI increased significantly 12 months after eradication of H. pylori infection. In contrast, there was no significant difference in body weight and BMI 12 months after eradication therapy in the non‐eradication group. Serum total cholesterol levels did not change after eradication therapy in either the eradication or non‐eradication groups.

Conclusion:

Eradication of H. pylori infection induced an increase in BMI in industrial workers with chronic gastritis in Japan.
Gastric cancer and Helicobacter pylori
Authors: Axon A.
Published: March 2003

Gastric cancer is the second commonest cause of death from malignancy in the world. Its pathogenesis is comparatively well understood and its aetiology multifactorial. Non‐cardia gastric cancer usually arises in a stomach that has been inflamed over a long period and where atrophy and intestinal metaplasia have supervened. The commonest cause of gastric inflammation is infection with Helicobacter pylori. Colonization with this organism increases the relative risk of developing this cancer by about six [Helicobacter and Cancer Collaborative Group. Gut 2001; 49: 347–53]. Its likelihood increases with the severity and extent of the gastritis. Severity is influenced by the virulence of the infecting organism, the genetics of the host, bile reflux, dietary factors and the presence of hypochlorhydria which influences the extent, as well as the severity, of the inflammation. The only predisposing factor which can easily be manipulated is H. pylori infection, which can be successfully treated in 80–90% of cases using a 1‐week therapeutic regimen.
Review article: albumin in the treatment of liver diseases—new features of a classical treatment
Authors: Arroyo V
Published: March 2003

Albumin was introduced initially in the treatment of patients with cirrhosis and ascites to increase serum albumin concentration due to its oncotic effect. Although its administration declined some years later, at present it constitutes an essential treatment in clinical hepatology. Several studies have clearly demonstrated its efficacy in the prevention and treatment of circulatory dysfunction and hepatorenal syndrome in patients with cirrhosis. These effects can be due not only to its properties as a plasma expander but also to its capacity to bind numerous substances such as bile acids, nitric oxide and cytokines. Based on this capacity an albumin dialysis system (MARS) has recently been developed. The usefulness of this system in the management of patients with acute and chronic liver failure is, at present, under evaluation.
The role of the gastroenterologist in the provision of artificial nutrition support
Authors: Stockdale  , Williams  , Pennington
Published: March 2003

Background:

Nutrition support is required for the prevention or treatment of malnutrition in patients with intestinal failure and those who are unable to eat.

Aims:

To determine the demands upon gastroenterologists for nutrition support, the available resources, and compliance with the British Society of Gastroenterology (BSG) guidelines.

Method:

A questionnaire was circulated to all 483 consultant physician members of the BSG.

Results:

There were 336 (70%) replies. Fifty‐three per cent of respondents reported malnutrition in 20% or more of their patients. Seventy‐nine per cent of consultants supervised patients on enteral feeding, and 64% supervised parenteral feeding. Feeding jejunostomy was used by 61% of Teaching Hospital (TH) consultants but only 38% of District General Hospital (DGH) consultants (P < 0.001). Twenty‐seven per cent of respondents headed, or were members of, a nutrition support team (NST). Forty‐five and 38% of respondents did not follow written protocols for peripheral and central parenteral nutrition, respectively. Fifty‐five per cent monitored catheter complications, of whom 44% reported catheter infections in 5% or more of their patients. Weights of inpatients were obtained by 76% of DGH consultants and 91% of TH consultants (P < 0.001). Fifty‐eight per cent of respondents did not arrange for nutritional screening. Ninety‐six per cent of consultants could access a dietitian, 55% had access to an NST and 36% had a nutrition nurse specialist (NNS). An NNS was available to 57% of TH consultants but only 23% of DGH consultants (P < 0.001).

Conclusions:

Gastroenterologists have a major role in nutrition support. Facilities are suboptimal. Observing guidelines may improve nutritional care. These findings have implications for resources and training.
Interferon alpha with ribavirin for the treatment of chronic hepatitis C in non‐responders or relapsers to interferon monotherapy
Authors: Moreno‐Monteagudo  , Fernández‐Bermejo  , García‐Buey  , Sanz  , Iacono  , García‐Monzón  , Borque  , Moreno‐Otero
Published: March 2003

Background:

A more effective therapy for chronic hepatitis C virus‐infected patients is needed.

Aim:

To evaluate the efficacy, tolerance and timing of response to interferon alpha plus ribavirin in 60 patients with no response or reactivation after interferon alpha alone.

Methods:

Sixty patients, 42 non‐responders and 18 relapsers, received 3 million units three times weekly of interferon alpha‐2b plus 1–1.2 g ribavirin daily, for 6 months. Basal biochemical and virological (HCV RNA and genotype) parameters were determined. Clinical examination, recording adverse effects, and laboratory tests, including viraemia, were carried out at 1, 2, 3 and 6 months.

Results:

A significant (P < 0.001) progressive decrease of HCV RNA and alanine transaminase (ALT) levels was observed during treatment. On finalizing the sixth month, 42 patients (70%) had normal ALT and 26 (43.3%) were HCV RNA negative. Of these 26 complete responders, in 20 the viraemia was undetectable by the third month, while a late clearance at the sixth month of treatment was observed in six patients. Response rates were higher in previous responders to interferon alone (P < 0.05). Mild adverse effects appeared in 46 patients (79.6%), but only three were withdrawn due to serious side‐effects. Significantly (P < 0.001), haemoglobin and leucocytes decreased, and bilirubin, ferritin and uric acid increased in the first month of treatment, with no changes thereafter.

Conclusions:

Interferon alpha plus ribavirin progressively decreased HCV RNA and ALT levels, achieving a complete response in the six months of treatment in 26 (43.3%) patients. This combined therapy was well tolerated.
Review article: targeting TNFα as a key cytokine in the inflammatory processes of Crohn’s disease — the mechanisms of action of infliximab
Authors: Van Deventer S.J.H.
Published: March 2003

Crohn’s disease is a chronic, debilitating gastrointestinal disorder in which a variety of cellular processes and pro‐inflammatory mediators influence the pathogenesis of the disease. Although the potential roles and functions of the pro‐inflammatory mediators continue to be debated, several mediators, specifically tumour necrosis factor‐alpha, have been clearly identified as having a pivotal role in the inflammation of the bowel mucosa of these patients. Therapies specifically focusing on the inflammatory process underlying Crohn’s disease have the potential for providing disease modification and prolonged remission. Infliximab, an antitumour necrosis factor‐alpha monoclonal antibody, has been demonstrated to neutralize tumour necrosis factor‐alpha and restore and reset the immunological dysbalance of the inflamed mucosa. Preliminary studies with infliximab suggested that treatment resulted in a rapid and almost complete inhibition of multiple inflammatory pathways. In clinical studies of infliximab, patients with Crohn’s disease achieved rapid reduction in clinical signs and symptoms, substantiated by both endoscopic and microscopic evaluation.
Indomethacin‐induced gastric antral damage in hamsters: are neutrophils involved?
Authors: Fitzpatrick  , Sakurai  , Le
Published: March 2003

Background:

A direct role for neutrophils in the pathophysiology of indomethacin‐induced gastric damage is controversial. Therefore, such damage was evaluated in hamsters.

Methods:

Gastric antral damage was evaluated 4 h after the oro‐gastric administration of indomethacin (30 mg/kg). Prior to indomethacin, hamsters were treated with various pharmacological agents: rebamipide, methotrexate or anti‐neutrophil serum (ANS). The number of circulating neutrophils was determined from Wright–Giemsa stained blood smears. Myeloperoxidase (MPO) activity was measured as a marker of gastric antral neutrophil infiltration.

Results:

Indomethacin caused primarily gastric antral damage. By histology, this damage did not penetrate the muscularis mucosa. A significant increase in gastric antral MPO activity was also found in indomethacin‐treated hamsters. Rebamipide decreased macroscopic gastric antral damage in a dose‐related fashion. Methotrexate treatment reduced the circulating blood neutrophil number by 38–44%, but did not affect gastric damage. ANS treatment resulted in near complete neutropenia, and also in a substantial reduction (84%) in gastric antral MPO activity. However, gastric antral damage was not significantly altered by ANS.

Conclusions:

Neutrophils are not directly involved in the pathophysiology of indomethacin‐induced damage to the hamster gastric antrum.
Failure of a 1‐day high‐dose quadruple therapy for cure of Helicobacter pylori infection
Authors: Wermeille  , Cunningham  , Armenian  , Zelger  , Buri  , Merki  , Hadengue
Published: March 2003

Background:

The optimal duration of treatment for eradication of Helicobacter pylori has still to be defined. A 1‐day high‐dose quadruple therapy with a combination of amoxycillin (or tetracycline), metronidazole, a bismuth salt and a proton pump inhibitor has led to eradication rates of 57–77%. In view of the high frequency of metronidazole‐resistant strains of H. pylori in Europe, we hypothesized that by using clarithromycin in place of metronidazole and by increasing the dose of proton pump inhibitor, the efficacy of a 1‐day high‐dose quadruple therapy could be improved.

Methods:

Patients were randomized to receive either amoxycillin 1000 mg b.d., clarithromycin 500 mg b.d. and lansoprazole 30 mg b.d. for 7 days, or amoxycillin 2000 mg q.d.s., clarithromycin 500 mg q.d.s., lansoprazole 30 mg t.d.s. and bismuth subcitrate 240 mg q.d.s. for 1 day.

Results:

It was originally intended to include 100 patients. The first planned interim analysis performed after follow‐up was completed for 30 patients revealed H. pylori eradication rates of 80% (12/15) in the 7‐day triple therapy group and 20% (3/15) in the 1‐day quadruple therapy group, the difference being highly significant (P = 0.003). Because the efficacy of the 1‐day treatment was so low, the study was stopped for ethical reasons. Eleven patients who failed with the 1‐day treatment were re‐treated with the 7‐day triple therapy: the eradication rate was 91% (10/11).

Conclusions:

One‐day high‐dose quadruple therapy with amoxycillin, clarithromycin, lansoprazole and bismuth subcitrate is dramatically less effective than the classic 7‐day triple therapy with the same antibiotics.
Review article: antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP)
Authors: Subhani  , Kibbler  , Dooley
Published: March 2003

This review examines the evidence for antibiotic prophylaxis in endoscopic retrograde cholangiopan‐creatography (ERCP), and provides detailed advice about suitable antibiotic regimens in appropriate high‐risk patients.

Ascending cholangitis and infective endocarditis are potential complications of endoscopic ERCP. The pathophysiology of these two complications is quite separate and different sub‐groups of patients require prophylaxis with appropriate antibiotic regimens.

Ascending cholangitis results from bacterial infection of an obstructed biliary system, usually from enteric Gram‐negative microorganisms, resulting in bacteraemia. There is incomplete drainage of the biliary system after ERCP in up to 10% of patients who require stenting. Antibiotics started in these patients will probably reduce the frequency of cholangitis by 80%. If antibiotics are restricted to this group, ≈90% of all patients having an ERCP will avoid antibiotics, but 80% of cholangitic episodes will be prevented.

Infective endocarditis may result from the bacteraemia caused at the time of the ERCP in patients with an abnormal heart valve. Antibiotic prophylaxis, in particular covering α‐haemolytic streptococci, should be started before the procedure in this defined high‐risk group.
Efficacy of omeprazole versus ranitidine for symptomatic treatment of poorly responsive acid reflux disease—a prospective, controlled trial
Authors: Maton P. N. , Orlando R. , Joelsson B.
Published: March 2003

Background

: H2‐receptor antagonists are widely used in patients with gastro‐oesophageal reflux disease (GERD) and are frequently continued when symptoms persist. Aim: To compare the efficacy of omeprazole 20 mg once daily with that of ranitidine 150 mg twice daily in relieving GERD symptoms, in patients who remained symptomatic following a 6‐week course of ranitidine therapy.

Methods

: Patients with heartburn on at least 4 days/week but who did not have endoscopy to assess oesophageal mucosa could participate. This two‐phase, prospective trial included a 6‐week open‐label phase (phase I), followed by an 8‐week double‐blind phase (phase II). Patients still symptomatic following treatment with ranitidine 150 mg twice daily (phase I) were randomized to double‐blind treatment (phase II) with either omeprazole 20 mg once daily or ranitidine 150 mg twice daily. The primary efficacy variable was the proportion of patients with heartburn resolution during weeks 4 and 8 of phase II.

Results

: Of the 533 patients with GERD who received ranitidine in phase I, 348 patients (65%) were still symptomatic. A total of 317 patients (59%) were randomized to double‐blind treatment (phase II). At week 8, a significantly (P < 0.0004) greater proportion of omeprazole‐treated patients (70%) experienced no more than mild heartburn compared with ranitidine‐treated patients (49%). Complete resolution of heartburn also occurred in a significantly (P < 0.00001) greater proportion of omeprazole‐treated patients (46% vs. 16% of the ranitidine group at week 8).

Conclusions

: After 6 weeks of ranitidine treatment, the majority of patients with GERD were still experiencing moderate to severe heartburn. Omeprazole was significantly more effective than ranitidine in resolving heartburn in this group of patients.
Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1‐week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer
Authors: Ducóns J. A. , Santolaria S. , Guirao R. , Ferrero M. , Montoro M. , Gomollón F.
Published: March 2003

Background

: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results.

Methods

: A prospective trial was designed to study the effectiveness of the 1‐week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre‐treatment and post‐treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E‐test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea‐breath test 2 months after treatment.

Results

: The eradication rate (intention‐to‐treat analysis) was 77% (95% CI: 69–86). No clinical factor was found to be different between eradicated and non‐eradicated patients. Clarithromycin‐resistant strains were found in 10 (10%; CI: 5–17) patients. The eradication rate was 20% (CI: 3–56) in these patients vs. 83% (CI: 75–91) in patients harbouring clarithromycin‐sensitive strains (P < 0.001). A logistic‐regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure.

Conclusions

: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor‐triple therapies are used.
Comparison of two 3‐day Helicobacter pylori eradication regimens with a standard 1‐week regimen
Authors: Grimley  , Penny  , O’sullivan  , Shebani  , Lismore  , Cross  , Illing  , Loft  , Nwokolo
Published: March 2003

Background

: The duration of Helicobacter pylori eradication regimens has decreased to 1 week with cure rates of over 90%. This can be attributed to the use of triple drug regimens including potent inhibitors of gastric acid secretion and clarithromycin. There is no theoretical reason why shorter regimens should not be possible.

Aim

: To compare two 3‐day, low‐dose, twice daily regimens with 1 week of omeprazole 20 mg b.d., clarithromycin 250 mg b.d., and metronidazole 400 mg b.d. (OCM)

Methods

: Outpatients referred for gastroscopy were screened by biopsy urease test. H. pylori‐positive patients were randomized to receive either lansoprazole 30 mg b.d., tri‐potassium dicitrato bismuthate one tablet b.d., clarithromycin 250 mg b.d., and amoxycillin 1 g b.d. for 3 days (LTdbCA), or ranitidine bismuth citrate 400 mg b.d., clarithromycin 250 mg b.d. and amoxycillin 1 g b.d. for 3 days (RbcCA) or omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. for 1 week (OCM). They were not pre‐treated with a gastric acid inhibitor. After 8 weeks, H. pylori status was assessed by 13C urea breath test.

Results

: 974 out of 1114 patients referred for gastroscopy were screened by biopsy urease test. 140 patients were not screened either because they were anticoagulated or for technical reasons. 334 patients were H. pylori‐positive: 154 were excluded mostly because of allergy to penicillin and personal reasons but 180 were randomized to treatment All regimens were well tolerated.

For LTdbCA (n=60), RbcCA (n=59), and OCM (n=61) the H. pylori cure rates (95% CI) were 23% (12–34), 14% (5–23) and 87% (79–95), respectively, using intention‐to‐treat analysis and 25% (14–36), 15% (6–24) and 88% (80–96), respectively, if analysed per protocol. OCM was significantly superior to LTdbCA and RbcCA (P < 0.001) but there was no significant difference between regimens LTdbCA and RbcCA.

Conclusions

: OCM is an extremely effective H. pylori eradication regimen. The 3‐day regimens tested both have poor cure rates. Pre‐treatment with a proton pump inhibitor, higher doses or more frequent dosing may be necessary to increase the cure rate of short duration regimens. However, this could make them less acceptable than the H. pylori eradication regimens currently available.
Efficacy of two different dosage regimens of omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection
Authors: Bayerdörffer  , Lonovics  , Dité  , Díete  , Domján  , Kisfalvi  , Mégraud  , Pap  , Sipponen  , Burman  , Zeijlon
Published: March 2003

Background:

While addition of metronidazole to the omeprazole–amoxycillin combination has been shown to be advantageous, the optimal dosage and drug distribution of the antimicrobials has not been sufficiently evaluated.

Aim:

To investigate the efficacy of two different regimens of omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

Methods:

Two hundred and fifty‐five patients with H. pylori associated duodenal ulcers were randomly treated with either a 1‐week regimen of omeprazole 20 mg b.d., amoxycillin 1000 mg b.d. and metronidazole 800 mg b.d. (OAM b.d.) or a combination of omeprazole 40 mg o.d., amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM t.d.s.). All patients subsequently received omeprazole 20 mg o.d. for an additional 3 weeks. H. pylori status was assessed by histology and 13C‐UBT prior to treatment and 8 weeks after randomization. Additional biopsies were obtained for H. pylori culture to determine primary and secondary resistance to metronidazole by agar dilution.

Results:

Two hundred and thirty‐seven patients were included in the intention‐to‐treat analysis and 198 patients in the per protocol analysis. With intention‐to‐treat analysis, the cure rate was 77% after treatment with OAM b.d. (95% CI, 69%–85%) and 76% after OAM t.d.s. therapy (95% CI, 67%–83%). Ulcer healing (intention‐to‐treat analysis) was documented in 95% of patients in the OAM b.d. group (n=122) and in 97% of patients in the OAM t.d.s. group (n=115). Adverse events were reported in 26 (20%) and in 18 (14%) patients in the OAM b.d. and OAM t.d.s. groups, respectively. None resulted in discontinuation of treatment. Overall primary resistance of H. pylori against metronidazole was found in 22 of 116 strains (19%).

Conclusions:

The combination of omeprazole, amoxycillin and metronidazole achieves about an 80% cure rate of H. pylori infection even in active ulcers. The total daily dose, and the choice of twice or three times daily dosing does not seem critical with this regimen.
Atrophic gastritis during long‐term omeprazole therapy affects serum vitamin B12 levels
Authors: Schenk  , Kuipers  , Klinkenberg‐Knol  , Bloemena  , Sandell  , Nelis  , Snel  , Festen  , Meuwissen
Published: March 2003

Background

: Omeprazole maintenance therapy for gastro‐oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori‐infected patients and with a decreased absorption of protein‐bound, but not of unbound cobalamin.

Aim

: To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy.

Methods

: Forty‐nine H. pylori‐positive GERD patients were treated with omeprazole for a mean (± s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow‐up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow‐up for histopathological scoring according to the updated Sydney classification.

Results

: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow‐up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow‐up. During follow‐up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136–716) vs. (T1) 341 (136–839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156–716) at latest follow‐up (P < 0.01).

Conclusions

: The development of atrophic gastritis during omeprazole treatment in H. pylori‐positive GERD patients is associated with a decrease of serum vitamin B12 levels.
Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis
Authors: Schepke  , Raab  , Hoppe  , Brensing  , Paar  , Potyka  , Sauerbruch
Published: March 2003

Background

: The haemodynamic effect of propranolol on portal pressure in patients with portal hypertension is highly variable and does not correlate with propranolol racemate plasma concentrations.

Aim

: To investigate the stereoselective metabolism of the propranolol enantiomers and its impact on portal haemodynamics in patients with liver cirrhosis since only S‐propranolol is haemodynamically active.

Methods

: Twenty patients with liver cirrhosis and portal hypertension received 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol stereoisomer plasma concentrations were determined.

Results

: During the 4 h examination period we observed a significant reduction in PBV (18.3 ± 2.2%, P < 0.0001) vs. baseline. The area under the curve (AUC) during the study period was significantly different for the two isomers (S‐propranolol 1217.0 ± 118.5 nmol.h/L; R‐propranolol 728.8 ± 103.8 nmol.h/L, P < 0.0001). Seven patients (35%) were portal haemodynamic non‐responders to propranolol. Propranolol stereoisomer AUC values were no different between responders (S‐propranolol 1133.3 ± 132.0 nmol.h/L; R‐propranolol 718.0 ± 129.7 nmol.h/L) and non‐responders (S‐propranolol 1371.8 ± 250.5 nmol.h/L; R‐propranolol 746.9 ± 200.3 nmol.h/L); neither was there a correlation between propranolol enantiomer plasma concentrations and the portal haemodynamic effect.

Conclusions

: Our data demonstrate a stereoselective metabolism of propranolol enantiomers in liver cirrhosis. However, following oral propranolol administration, stereoisomer plasma concentrations do not predict the portal haemodynamic effect.
Review article: pharmacological options in achalasia
Authors: Bassotti  , Annese
Published: March 2003

Achalasia is a common primary oesophageal motor disorder. Treatment has been based traditionally on a surgical approach; however, there is new evidence that some medical strategies may be of benefit. The purpose of the present article was to review the current medical management of achalasia. A Medline search identified original articles and reviews published in the English‐language literature between 1966 and 1998. This search has revealed that the pharmacological treatment of achalasia is limited to some subgroups of patients (for example, early stages of the disease and elderly patients), and that nitrates, nifedipine, and botulinum toxin are the best studied and most effective compounds.
Mesalazine‐induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era?
Authors: Bus  , Nagtegaal  , Verspaget  , Lamers  , Geldof  , Van Krieken  , Griffioen
Published: March 2003

Background

: It is an accepted fact that non‐steroidal anti‐inflammatory drugs (NSAIDs) are potent inhibitors of colorectal carcinogenesis. However, the major disadvantages of NSAIDs are gastrointestinal and renal toxicity. We conducted a prospective pilot study on the effects of the safe salicylic acid derivative, mesalazine, on apoptosis and proliferation of tumour cells and on normal tissue in colorectal cancer patients.

Methods

: Patients with colorectal cancer were asked to take mesalazine enemas for 14 days. Biopsies from malignant and normal tissue were taken prior to and after this treatment. Apoptosis was scored on haematoxylin/eosin‐stained tissue sections, and cell proliferation was assessed by the proliferation marker Ki‐67.

Results

: Ten out of 14 patients completed the study. The apoptotic score increased significantly in the tumour samples (pre‐treatment 14.6 ± 1.3 vs. post‐treatment 19.4 ± 0.8; P < 0.03). The apoptotic index in the normal mucosa was unchanged (pre‐treatment 3.1 ± 0.4 vs. post‐treatment 2.9 ± 0.3; N.S.). The cell proliferation in malignant tissue, according to the Ki‐67 score, was hardly affected by mesalazine (pre‐treatment 522 ± 38 vs. post‐treatment 493 ± 39; N.S.). There was no effect on the Ki‐67 index of normal mucosa (pre‐treatment 24.2 ± 2.0 vs. post‐treatment 28.3 ± 2.0; N.S.).

Conclusions

: This pilot study conducted in patients with colorectal cancer clearly shows that mesalazine selectively induces apoptosis of tumour cells. On the basis of these findings, which need to be confirmed in larger studies, it may be speculated that 5‐ASA could be useful in the chemoprevention of colorectal cancer.
A randomized dose–response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn’s disease and ulcerative colitis
Authors: Egan  , Sandborn  , Tremaine  , Leighton  , Mays  , Pike  , Zinsmeister  , Lipsky
Published: March 2003

Background and aims:

The optimum initial dose of methotrexate for steroid‐requiring inflammatory bowel disease is not known.

Aim:

To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome.

Methods:

A 16‐week randomized single‐blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid‐requiring Crohn’s disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels.

Results:

After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S.). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity.

Conclusions:

For induction of remission in steroid‐requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.
Complete resolution of heartburn symptoms and health‐related quality of life in patients with gastro‐oesophageal reflux disease
Authors: Revicki  , Crawley  , Zodet  , Levine  , Joelsson
Published: March 2003

Background:

Medical treatments for gastro‐oesophageal reflux disease (GERD) vary in their ability to completely resolve heartburn and other symptoms. Although GERD reduces health‐related quality of life (HRQL) little is known about the relationship between resolution of heartburn symptoms with medical therapy and HRQL. We evaluated the association between complete resolution of heartburn symptoms and functioning and well‐being in three samples of patients with GERD.

Methods:

We analysed baseline and follow‐up assessments of heartburn symptoms and HRQL scores from three clinical trials (total n=1351) comparing omeprazole and ranitidine for acute symptomatic treatment of GERD. Heartburn symptoms were measured using patient diaries and/or patient self‐report. HRQL was assessed using the Psychological General Well‐Being Index (PGWB) in all three clinical trials and the SF‐36 Health Survey in two clinical trials. Resolution of heartburn symptoms was defined as no heartburn reported during the assessment period.

Results:

We observed statistically significant differences favouring patients with no heartburn symptoms on the PGWB total score (P=0.018 to P < 0.0001) and anxiety (P=0.002 to P < 0.0001), general health (P=0.05 to P < 0.0001), positive well‐being (P=0.028 to P < 0.0001) and vitality (P=0.05 to P < 0.0001) sub‐scale scores at 4–14 weeks. Patients with no heartburn reported better SF‐36 pain (P=0.005 to P < 0.0001) and general health perceptions (P=0.032 to P < 0.0001) compared with patients still experiencing heartburn symptoms at 4–24 weeks. SF‐36 physical component summary scores were significantly better in patients with no heartburn symptoms compared with patients with heartburn symptoms at 4–24 weeks (P=0.013 to P=0.009), while mental component summary scores were only significantly different at 24 weeks (P=0.0005) in one of the two studies where the SF‐36 was utilized.

Conclusions:

Complete resolution of heartburn symptoms was consistently associated with improvement in HRQL; the greatest impact was observed on measures of psychological well‐being and physical functioning and well‐being. Effective treatment of GERD that completely resolves heartburn results in clinically significant improvement in patient HRQL.
Have we found the source of Helicobacter pylori?
Authors: Mégraud F. , Broutet N.
Published: March 2003

Besides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal–oral, oral–oral or gastro–oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.
Helicobacter pylori and gastric cancer − the clinicians' point of view
Authors: Huang J‐Q. , Hunt R. H.
Published: March 2003

Although the incidence of gastric cancer has declined dramatically in Western countries, the most recent data from the International Agency for Research on Cancer show that it remains the second most common cancer worldwide and caused 628 000 deaths in 1990. The incidence and prevalence of gastric cancer are projected to increase over the next few decades in less developed countries as a result of the increased longevity of H. pylori‐infected populations and improved therapies. Gastric carcinogenesis is a multistep and multifactorial process beginning with H. pylori‐associated gastritis in most cases. H. pylori infection, together with other environmental factors and individual susceptibility, determine the final risk for the development of gastric cancer. The magnitude of H. pylori infection as a risk factor for gastric cancer in the published H. pylori and gastric cancer epidemiology studies may have been underestimated due to the inclusion of improperly selected controls. Eradication of the infection has been shown to prevent the occurrence of metachronous gastric cancer following endoscopic resection of early gastric cancer in a Japanese study. However, the generalization of this study to other populations is difficult because of the vast differences in the definition of gastric atrophy and early gastric cancer between Japanese and Western pathologists. Until an international consensus on the pathological diagnosis of gastric atrophy and early gastric cancer is reached, interpretation of studies performed in different countries remains difficult. Clinicians rely on the correct pathological diagnosis to guide the management of H. pylori infection‐associated gastrointestinal diseases.
Does eradication of Helicobacter pylori alone heal duodenal ulcers?
Authors: Ge  , Zhang  , Xiao  , Chen  , Hu
Published: March 2003

Bakcground:

Eradication of Helicobacter pylori infection prevents duodenal ulcer (DU) relapse, but it remains uncertain whether eradication of H. pylori alone heals duodenal ulceration.

Aim:

To test the hypothesis that eradication of H. pylori infection is accompanied by healing of duodenal ulcer.

Methods:

A total of 115 consecutive patients with endoscopically confirmed H. pylori‐infected duodenal ulcer were randomly assigned to one of two groups. Group BTC patients received a 1‐week course of colloidal bismuth subcitrate 220 mg b.d., tinidazole 500 mg b.d., clarithromycin 250 mg b.d. Group OBTC patients received omeprazole 20 mg daily for 4 weeks with the BTC regimen during the first week. Endoscopy with antral biopsies and 13C‐urea breath test (UBT) were performed before and 4 weeks after completion of the 7‐day triple or quadruple therapy.

Results:

Eight patients dropped out (four in BTC and four in OBTC). Duodenal ulcer healing rates on an intention‐to‐treat basis in BTC and OBTC were 86% (95% CI: 77–95%) and 90% (95% CI: 82–98%), respectively. The eradication rates of H. pylori on an intention‐to‐treat basis in BTC and OBTC were 88% (95% CI: 79–96%) and 91% (95% CI: 84–99%), respectively. There were no statistically significant differences in ulcer healing rates and eradication rates between these two groups (P > 0.05). Epigastric pain resolved more rapidly in patients assigned to OBTC compared with those assigned to BTC. Both of the two regimens were well tolerated with only minor side‐effects (3% of the 115 patients) and the compliance was good.

Conclusions:

BTC is a very effective H. pylori eradication regimen. Almost all duodenal ulcers heal spontaneously after cure of H. pylori infection using a 1‐week low‐dose bismuth‐based triple therapy. Treating duodenal ulcer with simultaneous administration of omeprazole achieves ulcer pain relief more rapidly.
Review article: nitroimidazole resistance in Helicobacter pylori
Authors: Van Der Wouden  , Thijs  , Van Zwet  , Kleibeuker
Published: March 2003

The efficacy of a nitroimidazole‐containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are meta‐ bolized by H. pylori by several nitro‐reductases of which an oxygen‐insensitive NADPH nitroreductase encoded by the rdxA gene is the most important. Null mutations in this gene are associated with resistance.

Susceptibility testing to nitroimidazoles may give variable results. This is not only related to the slow growth under specific conditions, but also to variability in the activity of the other nitroreductases and the ability to deactivate toxic metabolites of an NI and to repair DNA damage. Moreover, co‐infections with resistant and susceptible bacteria are frequently found. The presence of nitroimidazole resistance is related to the previous use of this drug. The prevalence of resistance is rising and nowadays 10–50% of the isolates are resistant.

Resistance reduces the efficacy of a treatment regimen to a variable degree. This is related to efficacy of the other components of the regimen and the treatment duration. Whether a nitroimidazole is still effective in resistant strains remains unresolved.

When nitroimidazole resistance is present, a nitro‐imidazole‐containing regimen should be avoided or a regimen with other highly effective components should be used.
Similarities between ileal Crohn’s disease and indomethacin experimental jejunal ulcers in the rat
Authors: Anthony  , Pounder  , Dhillon  , Wakefield  ,   THE INFLAMMATORY BOWEL DISEASE STUDY GROUP
Published: March 2003

Background

: Both Crohn’s disease ileal ulcers and indomethacin‐induced jejunal ulcers in the rat have a predilection for the mesenteric margin of the bowel wall. Unlike the anti‐mesenteric margin, the mesenteric margin is supplied by small end‐arteries that might render it more sensitive to ischaemic injury.

Aim

: To examine, in both situations, the histological relationship between the precise localization of small bowel ulcers and the mesenteric margin.

Methods

: Ileal Crohn’s disease ulcers identified in surgical resection specimens (n=5) and indomethacin‐induced lesions in the rat jejunum (n=6) were examined macroscopically and histologically.

Results

: In both the human ileum and the rat jejunum, ulcers occurred consistently along the mesenteric margin, with the most extensive mucosal injury occurring at two adjacent sites on either side of the midline of this margin. At these two sites, feeding arteries entered the muscularis propria.

Conclusions

: For anatomical reasons apparently related to the vasculature of the human and rodent small bowel, specific sites along the mesenteric margin are susceptible to Crohn’s disease ulceration and NSAID damage, respectively.
Helicobacter pylori infection is associated with milder gastro‐oesophageal reflux disease
Authors: Wu  , Sung  , Chan  , Ching  , Ng  , Go  , Wong  , Ng  , Chung
Published: March 2003

Background:

We have previously demonstrated a negative relationship between the prevalence of Helicobacter pylori and gastro‐oesophageal reflux disease (GERD).

Aim:

To study the effects of H. pylori infection on the severity of GERD.

Methods:

Ethnic Chinese patients with frequent heartburn and/or endoscopic oesophagitis were studied. Endoscopic examination was performed to assess the severity of oesophagitis (modified Savary–Miller grading) and the presence of hiatus hernia. Biopsies were taken for rapid urease testing and confirmation of Barrett’s oesophagus. Risk factors which may affect the severity of oesophagitis (age, sex, smoking, drinking, diabetes mellitus, hiatus hernia, H. pylori status and body mass index) were evaluated by a multiple regression model. The cagA status of H. pylori infected GERD and age‐and‐sex matched controls were determined by Western blot. Age‐and‐sex matched non‐reflux patients were recruited as controls for comparison.

Results:

Two hundred and twenty‐five patients with GERD were studied, of whom 77 (34%) were infected with H. pylori. Oesophagitis and Barrett’s oesophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe oesophagitis compared to the uninfected group (P=0.022). All patients with Barrett’s oesophagus were uninfected. Factors that predicted severe oesophagitis included age over 60 years (P < 0.001) and hiatus hernia (P < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe oesophagitis (P=0.011). The prevalence of the cagA positive strain in endoscopy‐negative GERD, erosive oesophagitis and control subjects was 70, 76 and 78%, respectively (P=0.75).

Conclusions:

H. pylori infection is associated with milder GERD.
Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers
Authors: Kees  , Holstege  , Ittner  , Zimmermann  , Lock  , Schölmerich  , Grobecker
Published: March 2003

Background:

Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated.

Aims:

To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady‐state conditions in volunteers.

Methods:

In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy.

Results:

The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0–5.0 μg/mL vs. 0.3–0.4 μg/mL) and gastric tissue (antrum: 3.8–4.0 vs. 2.8 μg/g, fundus: 5.9–7.4 vs. 4.2–4.4 μg/g).

Conclusions:

Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.
Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR
Authors: Tomassetti  , Migliori  , Corinaldesi  , Gullo
Published: March 2003

Background:

Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days.

Aim:

To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours.

Methods:

A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non‐functioning pancreatic tumours, two with Zollinger–Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6–15 months).

Results:

In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5‐hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger–Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side‐effects were observed.

Conclusions:

Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.
Review article: potential gastrointestinal effects of long‐term acid suppression with proton pump inhibitors
Authors: Laine  , Ahnen  , Mcclain  , Solcia  , Walsh
Published: March 2003

This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long‐term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins.

Prolonged proton pump inhibitor use may lead to enterochromaffin‐like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long‐term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long‐term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger–Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high‐dose proton pump inhibitors for many years.

Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow‐up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long‐term acid suppression.