bluuebunny/crossref_metadata_2025_split huggingface dataset:
Essential fatty acid supplementation in chronic hepatitis B
Authors: JENKINS A. P. , GREEN A. T. , THOMPSON R. P. H. 
Published: October 2003

Background: Dietary supplementation with essential fatty acids and polyunsaturated lecithin may improve biochemical and histological parameters in liver disease. Methods: Ten patients with serological and histological evidence of chronic hepatitis B received capsules of the polyunsaturated fatty acid‐rich evening primrose oil in a dose of 4 g daily for 12 months, while a matched group received liquid paraffin capsules as a placebo. Results: Compared to the placebo group, the patients receiving evening primrose oil showed no improvement in either biochemical or histological indices of liver damage, or in the rate of loss of circulating e antigen. Conclusions: Dietary supplementation with this dose of essential fatty acids is unlikely to be of benefit in chronic hepatitis B.
Influence of loperamide on lactose handling and oral–caecal transit time
Authors: SZILAGYI A. , SALOMON R. , SEIDMAN E. 
Published: October 2003

Background: The influence of pharmacologically prolonged oral caecal transit time on lactose handling is examined in the wake of finding improved lactose handling during naturally occurring prolonged oral– caecal transit time. Methods: Sixteen normal male volunteers with lactose maldigestion were pretreated with 8 and 12 mg loperamide on different days and lactose handling was compared by measuring areas under the curve during lactose breath H2 testing (3 h). The oral–caecal transit time was similarly measured using lactulose and exhaled breath H2. Symptom scores were recorded and, in three subjects, blood sugar was simultaneously measured. Results: The mean±S.E.M. baseline oral–caecal transit time was 56.9±5.9 min. Loperamide significantly prolonged oral–caecal transit time (90.3±11.1 and 82.1±13.9 min for 12 and 8 mg loperamide, respectively; P<0.05). The lactose breath H2 area under the curve with 12 mg loperamide was significantly less than at baseline (7685±985.6 vs. 10243.1±1607, respectively; P<0.05). Significantly fewer symptoms were recorded with both doses of loperamide during the 3 h test but with 12 mg loperamide only on follow‐up. There was no significant rise in blood sugar at any time in the three subjects studied. Conclusions: Loperamide‐induced graded prolongation of oral–caecal transit time is associated with significantly improved lactose handling as measured by a reduction of the area under the curve. Symptoms of lactose intolerance may also be improved with loperamide. Prolongation of oral–caecal transit time with loperamide may be useful as adjunctive or primary therapy of carbohydrate intolerance in patients with rapid transit.
In vitro dissolution profiles of enteric‐coated microsphere/microtablet pancreatin preparations at different pH values
Authors: GAN K.‐H. , GEUS W. P. , BAKKER W. , LAMERS C. B. H. W. , HEIJERMAN H. G. M. 
Published: October 2003

Objectives: Enteric‐coated microsphere/microtablet pancreatin should stay intact in the stomach and dissolve promptly on entering the duodenum. Post‐prandial intraluminal pH in the distal duodenum is 5.75 and is lower in exocrine pancreatic insufficiency. The aim of the study was to measure in vitro dissolution times in buffer solutions with pH 4.0–6.0 for five currently available enteric‐coated microsphere/microtablet pancreatin preparations. Methods: The following preparations were tested: Creon, Creon Forte, Pancrease, Pancrease HL and Panzytrat. Two capsules were placed in the buffer solution at 37 °C in a USP dissolution testing apparatus. Buffer solutions with pH between 4.0 and 6.0 were used. Solutions were stirred at 125 r.p.m. and the rate of dissolution was monitored by taking 2‐mL samples at regular intervals and measuring extinction at 280 nm. Measurements were repeated six times. Results: All preparations failed to dissolve at pH 4.0. At pH 5.0 Pancrease HL showed 43% dissolution within 30 min, all other preparations 15% or less. Panzytrat and Pancrease HL showed more than 50% dissolution within 30 min at pH 5.2. Panzytrat, Pancrease HL and Creon Forte had more than 90% dissolution within 30 min at pH 5.6, and all preparations more than 90% dissolution within 30 min at pH 5.8 and higher. Conclusions: For the treatment of exocrine panceatic insufficiency conventional strength enteric‐coated microsphere/microtablet pancreatin preparations do not have an optimal dissolution profile. The newer, high lipase preparations such as Pancrease HL perform better, although still not optimally, at pH 5.4 and lower.
Rapid symptom relief in reflux oesophagitis: a comparison of lansoprazole and omeprazole
Authors: MEE A. S. , ROWLEY J. L. ,   THE LANSOPRAZOLE CLINICAL RESEARCH GROUP
Published: October 2003

Background: Lansoprazole, a substituted benzimidazole, is a proton pump inhibitor which is highly effective in the control of 24‐h intragastric acidity. The aim of this multicentre, randomized, double‐blind study was to compare lansoprazole 30 mg once daily and omeprazole 20 mg once daily in the symptom relief and healing of patients with reflux oesophagitis. Methods: Six hundred and four patients with endoscopically proven oesophagitis and a recent history of heartburn were randomly assigned to receive lansoprazole 30 mg or omeprazole 20 mg daily for 4–8 weeks. Daily assessment of symptoms was made by the patient using a 100‐mm Visual Analogue Scale. Clinical symptoms were evaluated at weeks 0, 1, 4 and 8. Endoscopic assessment of healing, defined by normalization of the oesophageal mucosal appearance, was made at weeks 4 and 8. Results: Two hundred and eighty‐two patients in the lansoprazole group and 283 patients in the omeprazole group were eligible for inclusion in the per protocol analysis. At 3 days, there was a significant improvement in daytime symptoms of heartburn for patients in the lansoprazole group compared with the omeprazole group (P=0.05). A similar but non‐significant trend was seen at 7 days (P=0.18). Clinical assessment at 7 days demonstrated significant improvement in daytime epigastric pain in the lansoprazole group compared with the omeprazole group (P=0.03), with a similar but non‐significant trend in night‐time epigastric pain (P=0.07). Healing rates of oesophagitis at 4 and 8 weeks were 70 and 87%, respectively, with lansoprazole, and 63 and 82%, respectively, with omeprazole. Logistic regression analysis of the cumulative healing rates, which included baseline factors affecting outcome, resulted in an odds ratio of 1.46 (95% CI=0.87–2.45), suggesting a higher chance of being healed with lansoprazole treatment compared with omeprazole treatment. A total of 615 adverse events were reported by 308 (51%) patients during the study period. The majority of events were mild in nature and the incidence was similar in both treatment groups. The most frequently reported events were headache, diarrhoea and nausea. Conclusion: Lansoprazole provides greater symptom relief compared with omeprazole during the first week of treatment. Both treatments were effective in healing oesophagitis.
A prospective follow‐up study of 5669 users of lansoprazole in daily practice
Authors: LEUFKENS H. , CLAESSENS A. , HEERDINK E. , VAN EIJK J. , LAMERS C. B. H. W. 
Published: October 2003

Background:Immediately after the introduction of the proton pump inhibitor lansoprazole, a 2‐year follow‐up study was started to evaluate patterns of use, safety and effectiveness of this drug in naturally occurring groups of patients in the Netherlands. Medical data were recorded by participating physicians while medication listings were provided by pharmacists.Methods:The study was designed according to the Safety Assessment of Marketed Medicines guidelines. The only inclusion criterion was the use of lansoprazole prior to entry into the study.Results:A total of 5669 lansoprazole users was included by 374 general practitioners and 117 specialists. Lansoprazole was mostly prescribed in patients with reflux oesophagitis (55.1%), `gastritis' (26.8%) and duodenal ulcers (11.4%), sometimes as part of a Helicobacter pylori eradication therapy (8.5%). For their complaints most patients (91.1%) had previously used acid‐related drugs. Improvement or disappearance of complaints was achieved in 88.9% and 90.5% of patients after 4 and 8 weeks of treatment, respectively. Diarrhoea (4.1%), headache (2.9%) and nausea (2.6%) were the most frequently reported adverse events.Conclusion:The patterns of use of lansoprazole in daily practice deviated from the recommendations in the information leaflet. Nevertheless, lansoprazole was found to be safe in this naturally occurring group of users. Effectiveness appeared to be comparable to results found in clinical trials of the registered indications for lansoprazole.
Twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) for treatment of Helicobacter pylori infection
Authors: GRAHAM D. Y. , HOFFMAN J. , EL‐ZIMAITY H. M. T. , GRAHAM D. P. , OSATO M. 
Published: October 2003

Background:Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being >95% effective, regardless of metronidazole resistance. We tested a 10‐day b.d. quadruple therapy for treatment of H. pylori infection.Methods:Anti‐H. pylori therapy consisted of lansoprazole 15 mg b.d. plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto‐Bismol caplets (2 b.d.) for 10 days. H. pylori status was evaluated by culture and histology before and 4 or more weeks after therapy.Results:The cure rate for intention‐to‐treat was 70%. Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns. The cure rate among the metronidazole‐sensitive isolates was 89.7% (26 of 29) vs. 41.2% (7 of 17) of the metronidazole‐resistant isolates (P < 0.005). Moderate (n = 1) or severe (n = 3) side‐effects were experienced in four patients with only one withdrawing because of side‐effects.Conclusion:Twice a day quadruple therapy is effective for metronidazole‐sensitive strains but its usefulness is markedly reduced by the presence of pre‐treatment metronidazole resistance. Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon. Possibly, 14‐day therapy or a higher dosage of metronidazole provide better results with metronidazole‐resistant H. pylori.
Lack of dose–response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults
Authors: OPEKUN Jr A. R. , SUTTON Jr F. M. , GRAHAM D. Y. 
Published: October 2003

BackgroundChoosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose–response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective.MethodsIn a randomized, single‐blind, cross‐over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20 000 units lipase), Pancrease MT16 (32 000 units lipase) or placebo. A 72‐h quantitative faecal collection was carried out for the last 3 days of the 6‐day period.ResultsThere was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P>0.05) but was significant (P=0.02) with the 20 000 units lipase and the 32 000 units lipase preparations (faecal fat excretion: placebo=42.1±29 g, lipase 8000 =22.1 ± 7.3 g, lipase 20 000 =10.2±4.5 g and lipase 32 000 = 15.8±12.5 g, P < for 20 000 units and 32 000 units lipase compared to placebo).ConclusionA dose–response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.
Prognostic factors for relapse of reflux oesophagitis and symptoms during 12 months of therapy with lansoprazole
Authors: HATLEBAKK J. G. , BERSTAD A. 
Published: October 2003

Background:Symptom relief and endoscopic healing are both important treatment goals in patients with reflux oesophagitis. Knowledge of predictive factors for treatment success could facilitate choice of treatment in individual patients.Aim:To assess the value of clinical data and data from baseline ancillary investigations in predicting the outcome of maintenance therapy with a proton pump inhibitor.Methods:After healing and symptom relief had been obtained on open therapy with lansoprazole 30 mg daily, 103 patients with reflux oesophagitis grade 1 or 2 were randomized to maintenance therapy with lansoprazole 15 or 30 mg daily, and time until recurrence of symptoms and/or endoscopic changes was recorded. The predictive value of the following variables was assessed by Cox regression analysis: dose of lansoprazole, symptom severity, grade of reflux oesophagitis, Helicobacter pylori infection status, lower oesophageal sphincter resting tone, percentage of 24 h with an oesophageal pH of <4.0, and median 24 h intragastric pH before start of treatment.Results:Dose of lansoprazole (P = 0.01) and symptom severity (P < 0.05) both significantly predicted time to relapse. Grade of reflux oesophagitis had only a borderline predictive value (P = 0.09), while H. pylori infection status and data from manometry and intraoesophageal 24‐hour pH‐metry did not predict relapse.Conclusions:Symptom severity before starting therapy is a significant predictive factor for treatment success during potent antisecretory therapy with lansoprazole, more so than endoscopic grade of reflux oesophagitis. In a group of patients with uncomplicated reflux oesophagitis being considered for maintenance therapy with lansoprazole, ancillary investigations with endoscopy, manometry and 24‐hour pH‐metry gave very limited prognostic information. H. pylori infected patients relapsed as early as patients who were not infected.
YF476 is a new potent and selective gastrin/cholecystokinin‐B receptor antagonist in vitro and in vivo
Authors: TAKINAMI Y. , YUKI H. , NISHIDA A. , AKUZAWA S. , UCHIDA A. , TAKEMOTO Y. , OHTA M. , SATOH M. , SEMPLE G. , MIYATA K. 
Published: October 2003

Background: We newly synthesized YF476 ((R)‐1‐[2,3‐dihydro‐2‐oxo‐1‐pivaloylmethyl‐5‐(2′‐pyridyl)‐1H‐1,4‐benzodiazepin‐3‐yl]‐3‐(3‐methylamino‐phenyl)urea) as a gastrin/cholecystokinin‐B (CCK‐B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo. Methods: We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK‐B receptors, and the effect of YF476 on secretagogue‐induced gastric acid secretion in rats and Heidenhain pouch dogs. Results: YF476 replaced the specific binding of [125I]CCK‐8 to the rat brain, cloned canine and cloned human gastrin/CCK‐B receptors, with Ki values of 0.068, 0.62 and 0.19 nM, respectively. The affinity of YF476 for rat brain gastrin/CCK‐B receptor was 4100‐fold higher than that for rat pancreatic CCK‐A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin‐induced acid secretion with an ED50 value of 0.0086 μmol/kg, but did not affect histamine‐ and bethanechol‐induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin‐stimulated gastric acid secretion in a dose‐dependent manner with ED50 values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine‐induced acid secretion. Conclusion: These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK‐B receptor antagonist, and that the gastrin/CCK‐B receptor is not involved in histamine‐ or bethanechol‐induced gastric acid secretion in dogs or rats.
Suppression of intestinal mucosal natural killer cells by corticosteroids
Authors: VAN IERSSEL A. J. H. M. , MIEREMET‐OOMS M. A. C. , VAN DER ZON J. M. , VAN HOGEZAND R. A. , GRIFFIOEN G. , LAMERS C. B. H. W. , VERSPAGET H. W. 
Published: October 2003

Background: Corticosteroid therapy of patients with inflammatory bowel disease can give rise to systemic side‐effects. Budesonide is a topically acting corticosteroid with low systemic bioavailability and is efficacious in the treatment of inflammatory bowel disease. Natural killer cells were previously found to be altered, both systemically and locally, in patients with inflammatory bowel disease. Modulatory effects of budesonide, prednisolone, dexamethasone, and cortisol on peripheral blood NK cells have already been described, but have never been assessed on mucosal NK cells from the intestine.Methods: The effect of the synthetic corticosteroids prednisolone and budesonide, the endogenous corticosteroid cortisol, and adrenocorticotropic hormone was analysed on NK cells isolated from the lamina propria of human intestinal resection specimens.Results: The three corticosteroids suppressed intestinal NK cell activity, not only during the cytotoxicity assay, but also after pre‐incubation of the lamina propria mononuclear cells. ACTH, however, did not affect the activity of intestinal NK cells. We previously showed that corticosteroid‐suppressed peripheral blood NK cell activity could be restored in vivo, but not in vitro, by the administration of ACTH. In the present study, the in vitro incubation of budesonide‐ or prednisolone‐suppressed mucosal NK cells with cortisol, alone or combined with ACTH, did not revert the suppressed NK cell activity. These findings are similar to our previous observations with peripheral blood NK cells.Conclusions: Intestinal mucosal NK cells can be suppressed by systemically as well as locally acting corticosteroids. This suppression in NK cell activity is not reversed by incubation with cortisol and/or ACTH.
FUSIDIC ACID INDUCED ACUTE IMMUNOLOGIC THROMBOCYTOPENIA
Authors: EL‐Kassar Nahed , Kalfon Pierre , Fromont Patricia , Vezinet Corinne , Godeau Bertrand , Duedari Najib , Bierling Philippe 
Published: October 2003

Fusidic acid is used in hospitals as second‐line therapy for multidrug‐resistant staphylococcal infections. We report the first fully documented case of fusidic acid induced thrombocytopenia, in a 48‐year‐old patient. The thrombocytopenia was abrupt and severe but resolved spontaneously 7 d after drug withdrawal. The thrombocytopenia transiently relapsed 6 d later, when fusidic acid was reintroduced. Haemorrhagic signs were observed, but no severe bleeding occurred. Platelet transfusions failed to increase the platelet count. We detected an IgG platelet antibody in the patient’s serum, that specifically recognized platelet glycoprotein IIb/IIIa only in the presence of fusidic acid.Fusidic acid induced thrombocytopenia should be considered as a possible cause for the thrombocytopenia frequently seen in the intensive care setting.
Nuclear translocation of protein kinase C‐α and ‐ζ isoforms in HL‐60 cells induced to differentiate along the granulocytic lineage by all‐trans retinoic acid
Authors: Zauli Giorgio , Visani Giuseppe , Bassini Alessandra , Caramelli Elisabetta , Ottaviani Emanuela , Bertolaso Lucia , Bertagnolo Valeria , Borgatti Paola , Capitani Silvano 
Published: October 2003

We investigated whether members of the protein kinase C (PKC) family of enzymes were involved in the nuclear events underlying granulocytic differentiation induced by 10−6 M all‐trans retinoic acid (ATRA) in HL‐60 cells. PKC activity was analysed by using a serine substituted specific peptide which enabled the evaluation of the whole catalytic activity of both Ca++‐dependent and Ca++‐independent PKC isoforms. In parallel, the subcellular distribution of various PKC isoforms was evaluated by Western blot, immunoprecipitation and in situ immunocytochemistry analyses.The level of PKC catalytic activity in the nuclei of HL‐60 cells significantly (P<0.01) and progressively increased from 1 h of ATRA treatment onwards. Consistently, PKC‐α and ‐ζ showed a striking and selective accumulation inside the nucleus upon treatment with ATRA. On the other hand, PKC‐βI and ‐βII, the only two other isoforms present at nuclear level, did not show any significant modification upon ATRA treatment. The remaining PKC isoforms were not detectable inside the nucleus and showed only modest and non‐significant variations, also in whole cell homogenates, upon ATRA treatment, except PKC‐δ which showed a progressive down‐regulation. Our data suggest that a selective nuclear translocation of PKC‐α and ‐ζ might be involved in the process of granulocytic differentiation induced by ATRA in HL‐60 cells.
Are macroinvertebrates in high altitude streams affected by oxygen deficiency?
Authors: Jacobsen Dean , Rostgaard Stig , Vásconez Juan José 
Published: October 2003

Summary1. The solubility of oxygen in water increases with decreasing temperature. This has led to a general perception of cold, high mountain streams as more oxygen rich than warmer lowland streams, and that macroinvertebrates inhabiting high altitude streams have had no need to adapt to critical oxygen conditions. However, this fails to take into account that oxygen solubility declines with decreasing atmospheric pressure, which may be of importance at high altitudes.2. Based on samples of macroinvertebrate benthos and in situ measurements of respiratory oxygen demand of macroinvertebrates in small streams from sea level to 4000 m a.s.l. in Ecuador, we determined predicted oxygen availability, oxygen demand and macroinvertebrate assemblage structure along this wide altitudinal gradient.3. We show that the predicted oxygen availability at 4000 m a.s.l. is only one fifth of that at sea level, whereas the mean weight‐specific respiratory rate of macroinvertebrates declined by only 50%, from 400 to 3800 m. We suggest that this disproportionately large gap between availability and demand of oxygen at high altitudes may imply a potential oxygen deficiency for the fauna, and we discuss how oxygen deficiency can be expected to affect macroinvertebrates in high altitude streams.4. Finally, we present preliminary data on the predicted response to oxygen deficiency of macroinvertebrate assemblages in high altitude streams. Compared with lowland streams, assemblages in natural high altitude streams include relatively few groups normally regarded as oxygen‐sensitive. Nevertheless, high altitude assemblages react more strongly to lowering of oxygen saturation, and are thus more sensitive to organic pollution.5. Oxygen deficiency has been overlooked completely in studies of the altitudinal distribution of species and aquatic communities. We argue that oxygen deficiency may be a potentially important factor, and that more focus on this topic is likely to produce significant new insights in aquatic community ecology.