bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Marginal Housing for People with a Mental Illness Living in Rural and Regional Areas
Authors: Grigg Margaret , Judd Fiona , Ryan Lisa , Komiti Angela
Published: December 2004

Objective: Homelessness among people with a mental illness is a serious issue. The purpose of the present study was to identify the types of housing available for people with a mental illness in the region, to develop an audit tool to assess the housing of patients of the mental health service, and to pilot this audit tool.

Methods: Key informants were interviewed to obtain information about the type of housing options available in the Loddon Campaspe Southern Mallee Region, Victoria, Australia. This information was used to develop a survey to audit the housing status of existing patients of the area mental health service. A pilot study using the survey was completed by case managers for 81 patients who were being case managed by the area mental health service

Results: There was a wide variety of housing options in the region but housing availability was not evenly distributed. Although most patients lived in owned or rented accommodation, a substantial proportion of patients had difficulties with accessing the required services, the affordability of their housing, uncertainty of tenure or were at risk of violence within their housing.

Conclusions: A substantial proportion of patients treated by a rural area mental health service had lived in impoverished housing.
Rural Integrated Primary Care Psychiatry Programme: a Systems Approach to Education, Training and Service Integration
Authors: Judd Fiona , Davis Julian , Hodgins Gene , Scopelliti Joe , Agin Biliana , Hulbert Carol
Published: December 2004

Objective: To describe the development of a rural primary care psychiatry programme, within a stepped collaborative care model.

Conclusion: Development of a system-wide approach to the provision of mental health services offers the opportunity to increase the proportion of people with mental health problems who receive effective treatment. In addition, it enables allocation of resources and matching of interventions to patient preference and clinical need. This is particularly important in rural areas where there is a shortage of specialist mental health services and practitioners.
O Anna: Being Bertha Pappenheim — Historiography and Biography
Authors: Kaplan Robert
Published: December 2004

Objective: To review the famous case of Anna O. (the index case of psychoanalysis) as seen by each generation, in the light of current knowledge and thinking.

Conclusions: The case was neither a catharsis nor a cure as described. Historical research has revealed a significantly different outcome, shedding new light on the motives of the chief protagonists, Breuer and Freud. No less interesting but greatly neglected is the life of Bertha Pappenheim, the real identity of Anna O.
Combined use of Amisulpride and Clozapine for Patients with Treatment-Resistant Schizophrenia
Authors: Cook Brian , Hoogenboom Gerry
Published: December 2004

Objective: To report on a trial of adding amisulpride to clozapine.

Methods: Description of six cases.

Results: Six patients who had been on clozapine were commenced on ami-sulpride. All patients had had unwanted effects with clozapine, particularly sedation, hypersalivation, or weight gain. Five patients reported a high level of satisfaction with the regimen, having a reduction in the level of sedation and improvement in levels of motivation and energy, without recurrence of positive symptoms.

Conclusion: The combined use of amisulpride and clozapine would appear to be an appropriate and beneficial treatment.
Drug driving among injecting drug users in Sydney, Australia: prevalence, risk factors and risk perceptions
Authors: Darke Shane , Kelly Erin , Ross Joanne
Published: December 2004

Aims  To examine the prevalence of drug driving, the prevalence of drug‐related motor vehicle accidents, risk perceptions of drug driving and factors associated with drug driving among injecting drug users (IDU).

Design  Cross‐sectional survey.

Setting  Sydney, Australia.

Participants  Three hundred current IDU.

Findings  Ninety‐five per cent had driven a vehicle, 74% in the previous 12 months (‘current drivers’). Eighty‐seven per cent of life‐time drivers reported having drug driven, and 88% of current drivers had drug driven in the previous 12 months. There were no significant sex differences in life‐time or recent drug driving. The most common drugs used before driving in the preceding year were: cannabis, heroin, amphetamines and cocaine. A third of life‐time drivers reported having had a drug driving accident, with males more likely to have done so, and 9% of current drivers reported a drug driving accident in the previous year. The most common drugs that had been used before the most recent drug driving accident were heroin, cannabis and alcohol. Alcohol was perceived to be the most dangerous substance for driving performance and cannabis the least dangerous. Recent drug drivers perceived drug driving to be less dangerous than non‐drug drivers. Recent drug drivers had driven more frequently over the preceding 12 months, had significantly higher levels of dependence, higher frequency of drug use, more extensive polydrug use and were more likely to have used and/or injected a drug in a car in the previous 12 months.

Conclusions  Drug driving and drug‐related accidents are large‐scale public health problems among IDU. These behaviours pose serious risks to IDU themselves and to the broader community.
Increased contribution of α1‐ vs. β‐adrenoceptor‐mediated inotropic response in rats with congestive heart failure
Authors: Sjaastad I. , Schiander I. , Sjetnan A. , Qvigstad E. , Bøkenes J. , Sandnes D. , Osnes J.‐B. , Sejersted O. M. , Skomedal T.
Published: December 2004

Aim:  In failing myocardium the mechanical response to β‐adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the β‐adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to α1‐ and β‐adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non‐failing and failing rat hearts were compared.

Methods:  Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non‐failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The α1‐adrenoceptor‐mediated inotropic response was not changed while the β‐adrenoceptor‐mediated response was substantially reduced in failing compared with non‐failing myocardium.

Results:  No change in potency for the agonists was observed at the α1‐adrenoceptors, while an increased potency for the agonists at the β‐adrenoceptors was found during heart failure. The lusitropic response to β‐adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The α1‐adrenoceptor‐mediated inotropic response became dominating compared with the β‐adrenoceptor‐mediated one in failing rat myocardium in contrast to the dominating role of the latter in non‐failing myocardium. The attenuation of the β‐adrenoceptor‐mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors.

Conclusion:  Increasing contractility through stimulation of α1‐adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during β‐adrenoceptor blockade.
Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research
Authors: Gehl J.
Published: December 2004

Electroporation designates the use of short high‐voltage pulses to overcome the barrier of the cell membrane. By applying an external electric field, which just surpasses the capacitance of the cell membrane, transient and reversible breakdown of the membrane can be induced. This transient, permeabilized state can be used to load cells with a variety of different molecules, either through simple diffusion in the case of small molecules, or through electrophoretically driven processes allowing passage through the destabilized membrane – as is the case for DNA transfer. Initially developed for gene transfer, electroporation is now in use for delivery of a large variety of molecules: From ions to drugs, dyes, tracers, antibodies, and oligonucleotides to RNA and DNA. Electroporation has proven useful both in vitro, in vivo
and in patients, where drug delivery to malignant tumours has been performed. Whereas initial electroporation procedures caused considerable cell damage, developments over the past decades have led to sophistication of equipment and optimization of protocols. The electroporation procedures used in many laboratories could be optimized with limited effort. This review (i) outlines the theory of electroporation, (ii) discusses factors of importance for optimization of electroporation protocols for mammalian cells, (iii) addresses particular concerns when using electroporation
in vivo,
e.g. effects on blood flow and considerations regarding choice of electrodes, (iv) describes DNA electrotransfer with emphasis on use in the
in vivo setting, and (v) sums up data on safety and efficacy of electroporation used to enhance delivery of chemotherapy to tumours in cancer patients.
Role of cyclooxygenase‐2 in the control of renal haemodynamics and excretory function
Authors: López R. , Roig F. , Llinás M. T. , Salazar F. J.
Published: December 2004

Aim:  The available evidence supporting the importance of cyclooxygenase‐2 (COX‐2) in the regulation of renal haemodynamics and excretory function is summarized. Cyclooxygenase‐2‐derived metabolites play a very important role in regulating renal haemodynamics when sodium intake is low whereas it plays a minor role in the control of cortical blood flow when sodium intake is normal or elevated. The importance of COX‐2 in the regulation of renal haemodynamics seems to be dependent on the endogenous production of other vasoactive products such as nitric oxide (NO) or noradrenaline. The activation of COX‐2 in response to a decrease in NO may represent a mechanism aimed at defending the renal vasculature in the face of a decrease in NO levels.

Conclusion:  Contrary to the important role of COX‐2 in the long‐term regulation of renal haemodynamics, the metabolites derived from COX‐2 seem to be only involved in the acute regulation of renal excretory function.
Twenty‐four‐hour intragastric acidity following early evening or bedtime administration of roxatidine in duodenal ulcer patients
Authors: LAZZARONI M. , SANGALETTI O. , BARGIGGIA S. , BENSI G. , CANALI A. , BIANCHI PORRO G.
Published: December 2004

Aim: To assess the usefulness of early evening administration of roxatidine 150 mg as an alternative to the traditional bedtime regimen.

Methods: Twenty‐four patients with healed duodenal ulcer were dosed according to a balanced incomplete‐block design, with two of the following regimens: placebo, roxatidine 150 mg at 07.30 h (early evening) or roxatidine 150 mg at 22.00 h (bedtime). Twenty‐four‐hour intragastric pH‐metry was started at 18.00 h on the first day of dosing. Median pH was determined for the 24‐h period, and for the following time intervals: 20.00–00.00 h, 00.00–08.00 h and 08.00–18.00 h. Percentage time in the 24‐h period with pH greater than 4.0 was also calculated.

Results: The two roxatidine regimens proved significantly superior to the placebo, decreasing 24‐h acidity for all the time intervals, except the 20.00–00.00 h period, when mean intragastric pH with the early evening regimen (4.5±1.1) proved significantly higher than after placebo (2.2±1.0) or when roxatidine was taken at bedtime (2.4±1.1).

Conclusion: Early evening administration of roxatidine may afford satisfactory control of 24‐h acidity, offering a useful alternative to conventional bedtime administration.
Repeat prescribing of ulcer healing drugs in general practice—prevalence and underlying diagnosis
Authors: GOUDIE B. M. , McKENZIE P. E. , CIPRIANO J. , GRIFFIN E. M. , MURRAY F. E.
Published: December 2004

Background: The long‐term use of ulcer healing drugs in the management of dyspepsia is controversial. We have investigated repeat prescribing of these drugs in a general practice population.

Aims: To identify the number of patients authorized to receive repeat prescriptions for ulcer healing drugs, and to review the investigation status and diagnosis in these patients.

Subjects: A total of 15495 patients registered with eight general practitioners in seven general practices in Dundee, UK.

Methods: Case ascertainment by review of practice repeat prescribing registers. Data regarding investigation and diagnosis obtained by retrospective review of general practice case records.

Results: Six hundred and seventy‐nine (4.4% of the total population) were authorized to receive repeat prescriptions for ulcer healing drugs. Six hundred and fifty‐one (4.2%) were authorized to receive repeat prescriptions for H2‐antagonists. Ranitidine was prescribed in 583 (86% of patients receiving ulcer healing drugs). Endoscopy had been performed in 426 (63%) and barium meal alone in 113 (17%); 140 (21%) had not been investigated. A diagnosis of peptic ulcer disease or oesophagitis was established in 382 (56%). However, 157 investigated patients (23% of all patients on ulcer healing drugs) did not have a peptic diagnosis.

Conclusions: The prevalence of repeat prescribing of ulcer healing drugs in the general practice population studied was 4.4%, but 44% of these patients did not have a confirmed diagnosis of acid peptic disease.
Gastrointestinal tolerability of lornoxicam compared to that of naproxen in healthy male volunteers
Authors: AABAKKEN L. , OSNES M. , FRENZEL W.
Published: December 2004

Background and Aim: Gastrointestinal effects are common adverse effects associated with nonsteroidal anti‐inflammatory drugs (NSAIDs). Lornoxicam is a new nonsteroidal anti‐inflammatory drug and its gastroduodenal tolerability was compared to that of naproxen in a randomized, double‐blind, crossover study.

Methods: Eighteen healthy male volunteers received lornoxicam 8 mg b.d. or naproxen 500 mg b.d. administered orally over two 7‐day dosing periods. Upper endoscopy was performed by two independent investigators at the beginning and end of each dosing regimen.

Results: Lornoxicam 8 mg b.d. caused significantly less mucosal injury than naproxen 500 mg b.d. in the stomach/duodenal bulb, as well as in the mid/distal duodenum.

Conclusion: These findings may have favourable implications for lornoxicam in the clinical setting, if this dose provides optimal control of arthritic pain.
Sulphasalazine treatment and the colorectal mucosa‐associated flora in ulcerative colitis
Authors: HARTLEY M. G. , HUDSON M. J. , SWARBRICK E. T. , GRACE R. H. , GENT A. E. , HELLIER M. D.
Published: December 2004

Aim: To study the influence of sulphasalazine treatment on the mucosa‐associated bacterial flora of rectal biopsy tissue specimens in patients with ulcerative colitis.

Patients: Twenty‐four patients had newly diagnosed active ulcerative colitis; 20 patients had acute relapse of ulcerative colitis (10 not taking maintenance sulphasalazine); (40 patients had quiescent ulcerative colitis; 21 not taking maintenance sulphasalazine). The influence of 3 weeks of sulphasalazine treatment on the mucosa‐associated flora was studied in the patients presenting with active disease.

Results: Comparison of patients according to sulphasalazine usage revealed few differences in the mucosal flora. In patients with quiescent ulcerative colitis, Escherichia coli was found at lower counts in patients taking maintenance sulphasalazine; however, this effect was not evident in patients with active disease. Inconsistent changes in other facultatives were seen between the two active disease groups, particularly for a miscellaneous group of unidentified Gram‐positive rods. Three patients, all receiving sulphasalazine, were colonized with Clostridium difficile, but this did not appear to influence their disease.

Conclusion: Sulphasalazine treatment in ulcerative colitis causes only minor disturbance to the populations of bacteria colonizing the colorectal mucosa.
Visceral hypersensitivity
Authors: Mertz H.
Published: December 2004

Visceral hypersensitivity is highly prevalent in all functional bowel disorders. Most also demonstrate wider patterns of somatic referral of intestinal pain or discomfort. This hypersensitivity may explain the symptoms as the sensitive gut can be more easily provoked by normal or abnormal motor events in the gut. Visceral hypersensitivity may increase during psychosocial stress and during periods of symptom exacerbation, although this requires confirmation. Pharmacological therapy to reduce visceral hypersensitivity is now possible using antagonists to neurotransmitters, opening up an exciting new era for the treatment of functional gastrointestinal disorders.
Rabeprazole‐based therapies in Helicobacter pylori eradication
Authors: Gisbert J. P. , Khorrami S. , Calvet X. , Pajares J. M.
Published: December 2004

Aim : To perform a systematic review of the efficacy of rabeprazole‐based therapies in Helicobacter pylori eradication, and to conduct a meta‐analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co‐prescribed with antibiotics.

Methods : Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta‐analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta‐analysis was performed by combining the odds ratios (OR) of the individual studies.

Results : The eradication rates were as follows: 14‐day rabeprazole–amoxicillin, 73%; rabeprazole–amoxicillin–clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low‐dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high‐dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7‐day rabeprazole–clarithromycin–nitroimidazole, 85%. Twelve comparative studies were included in the meta‐analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93–1.42). Sub‐analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences.

Conclusions : Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co‐prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.
Indicators and predictors of response to anti‐viral therapy in chronic hepatitis C
Authors: Lee S. S.
Published: December 2004

The complications of chronic hepatitis C, including cirrhosis and hepatocellular carcinoma, are expected to increase dramatically world‐wide over the next 10–20 years. Immunomodulatory/anti‐viral therapy, employing interferon alfa both alone and in combination with ribavirin, affords the only effective treatment for hepatitis C. Accurate early prediction of response to interferon therapy may decrease or eliminate unnecessary or ineffective treatment, permit greater flexibility in tailoring therapy on an individual basis, and enhance the cost‐effectiveness of treatment.

Liver biopsy provides valuable information about the baseline severity and subsequent progression of hepatitis C. Severe fibrosis or cirrhosis on the pre‐treatment liver biopsy is associated with decreased response rates. The measurement of viral RNA levels and genotyping may be used to optimize individual patient treatment. Genotype non‐1 and a low viral load are the most significant pre‐treatment indicators of sustained virological response.

The most reliable predictor of a poor virological response is continued seropositivity for viral RNA during therapy. Therefore, a decision to stop or continue treatment can be based on a positive viral RNA test at 12 weeks for interferon‐naive patients receiving interferon or pegylated interferon therapy.
Discrepancies between population‐based data and adverse reaction reports in assessing drugs as causes of acute pancreatitis
Authors: Lancashire R. J. , Cheng K. , Langman M. J. S.
Published: December 2004

Background : Many drugs are believed, clinically, to cause acute pancreatitis. We used information held on the UK General Practitioner Research Database to compare risks for drugs for which reports of pancreatitis were common or uncommon.

Methods : Drug prescriptions were examined in 3673 patients with acute pancreatitis and in matched controls. Odds ratios were calculated for recent (1–90 days before the episode), past (91–360 days before the episode) or continuing (prescription in both periods) use.

Results : Odds ratios were markedly increased for recent antisecretory use in non‐ulcer patients only [all H2‐antagonists, 12.4 (9.5–16.4); all proton pump antagonists, 9.3 (6.6–13.0)], with smaller increases for past [3.1 (2.5–3.7) and 3.5 (2.6–4.6), respectively] and continuing [2.6 (2.2–3.1) and 3.7 (2.9–4.7), respectively] use in patients without ulcer. Recent users of mesalazine showed a markedly increased risk [9.0 (1.8–44.6)], with smaller increases in past and continuing users [4.5 (1.3–16.0) and 2.5 (1.2–5.0), respectively]. Odds ratios for other drugs, suspect or not, were modestly increased, irrespective of whether the use was recent, past or continuing. The presence of gall‐stones was not associated with a modified risk.

Conclusions : Mesalazine, azathioprine and antisecretory drugs in non‐ulcer subjects may increase the risk of pancreatitis, but warnings of drug‐induced pancreatitis are generally not accompanied by increased population risks.
Gut‐focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome
Authors: Lea R. , Houghton L. A. , Calvert E. L. , Larder S. , Gonsalkorale W. M. , Whelan V. , Randles J. , Cooper P. , Cruickshanks P. , Miller V. , Whorwell P. J.
Published: December 2004

Background : We have previously shown that hypnotherapy alters rectal sensitivity in some patients with irritable bowel syndrome. However, this previous study used incremental volume distension of a latex balloon, which might be susceptible to subject response bias and might compromise the assessment of compliance. In addition, the study group was symptomatically rather than physiologically defined.

Aim : To assess the effect of hypnotherapy on rectal sensitivity in hypersensitive, hyposensitive and normally sensitive irritable bowel syndrome patients using a distension technique (barostat) that addresses these technical issues.

Methods : Twenty‐three irritable bowel syndrome (Rome I) patients (aged 24–72 years) were assessed before and after 12 weeks of hypnotherapy in terms of rectal sensitivity, symptomatology, anxiety and depression. Normal values for sensitivity were established in 17 healthy volunteers (aged 20–55 years).

Results : Compared with controls, 10 patients were hypersensitive, seven hyposensitive and six normally sensitive before treatment. Following hypnotherapy, the mean pain sensory threshold increased in the hypersensitive group (P = 0.04) and decreased in the hyposensitive group, although the latter failed to reach statistical significance (P = 0.19). Normal sensory perception was unchanged. Sensory improvement in the hypersensitive patients tended to correlate with a reduction in abdominal pain (r = 0.714, P = 0.07).

Conclusion : Hypnotherapy improves abnormal sensory perception in irritable bowel syndrome, leaving normal sensation unchanged.
Quality of life in Chinese patients with inflammatory bowel disease: validation of the Chinese translation of the Inflammatory Bowel Disease Questionnaire
Authors: Leong R. W. L. , Lee Y. T. , Ching J. Y. L. , Sung J. J. Y.
Published: December 2004

Background : Health‐related quality of life is an important outcome measure in inflammatory bowel disease. The Inflammatory Bowel Disease Questionnaire is a quality of life questionnaire that has not been validated previously in Chinese patients with inflammatory bowel disease.

Aim : To develop and validate a Chinese translation of the Inflammatory Bowel Disease Questionnaire, specifically determining its construct validity, discriminant ability, reliability and sensitivity to change.

Methods : We developed a Chinese version of the Inflammatory Bowel Disease Questionnaire. Chinese patients with Crohn's disease and ulcerative colitis completed the Chinese Inflammatory Bowel Disease Questionnaire and visual analogue scales measuring systemic, social, bowel and emotional well‐being. Patients also completed a validated Chinese SF‐36 generic quality of life questionnaire, the Crohn's disease activity index or the clinical activity index for ulcerative colitis.

Results : One hundred and thirty‐five patients (59 with Crohn's disease and 76 with ulcerative colitis) were enrolled, 99 of whom also completed the Chinese Inflammatory Bowel Disease Questionnaire for a second time. The Chinese Inflammatory Bowel Disease Questionnaire correlated well with the SF‐36 for all four domains (Spearman: r = 0.55–0.80), the Crohn's disease activity index (r = −0.62–0.72) and the clinical activity index for ulcerative colitis (r = −0.44–0.68), as well as with the visual analogue scales. The Chinese Inflammatory Bowel Disease Questionnaire accurately distinguished between active and inactive disease. Test–re‐test reliability showed excellent intra‐class correlation (0.76–0.92; all P < 0.001). The Chinese Inflammatory Bowel Disease Questionnaire was also sensitive to changes in disease activity (P < 0.05).

Conclusion : The Chinese Inflammatory Bowel Disease Questionnaire is a valid and reliable test that correlates well with the patients' subjective well‐being and clinical disease activity.
Meal‐stimulated gastric acid secretion and integrated gastric acidity in gastro‐oesophageal reflux disease
Authors: Gardner J. D. , Sloan S. , Miner P. B. , Robinson M.
Published: December 2004

Background : No current methods exist to determine meal‐stimulated gastric acid secretion in humans under conditions that approximate those of daily living with the ingestion of breakfast, lunch and dinner.

Methods : Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro‐oesophageal reflux disease. Meal‐stimulated gastric acid secretion was calculated from the buffer capacity of the meals determined in vitro and from the time required for the gastric pH to decrease to pH 2 in vivo following ingestion of the meal.

Results : There was a significant correlation between gastric secretion with each meal and the corresponding post‐prandial integrated gastric acidity. There was also a significant correlation between meal‐stimulated gastric secretion and integrated gastric acidity from 09.00 to 22.00 h in both subjects with gastro‐oesophageal reflux disease and controls. In subjects with gastro‐oesophageal reflux disease, gastric secretion and integrated gastric acidity from 09.00 to 22.00 h were significantly higher than those in controls. There was a significant correlation between oesophageal acidity and integrated gastric acidity from 09.00 to 22.00 h in subjects with gastro‐oesophageal reflux disease.

Conclusions : As post‐prandial gastric acidity is increased in subjects with gastro‐oesophageal reflux disease, it seems likely that increased gastric acidity is an important aetiological factor in this disease.
Azathioprine, mercaptopurine and birth outcome: a population‐based cohort study
Authors: Nørgård B. , Pedersen L. , Fonager K. , Rasmussen S.N. , Sørensen H. T.
Published: December 2004

Background : Data on the safety of azathioprine and mercaptopurine during pregnancy are very sparse.

Aim : To examine the risk of adverse birth outcomes in women who took up prescriptions for azathioprine or mercaptopurine during pregnancy.

Methods : This is a Danish cohort study based on data from a population‐based prescription registry, the Danish Birth Registry and the Hospital Discharge Registry. To examine the risk of congenital malformations, we included nine pregnancies exposed 30 days before conception or during the first trimester. To examine perinatal mortality, pre‐term birth and low birth weight, we included 10 pregnancies exposed during the entire pregnancy. Eleven different exposed women were included in the study. Outcomes were compared with those of 19 418 pregnancies in which no drugs were prescribed to the mothers.

Results : Fifty‐five per cent of the exposed women had inflammatory bowel disease and 45% other diseases. Adjusted odds ratios for congenital malformations, perinatal mortality, pre‐term birth and low birth weight were 6.7 (95% confidence interval, 1.4–32.4), 20.0 (2.5–161.4), 6.6 (1.7–25.9) and 3.8 (0.4–33.3), respectively.

Conclusions : Our results suggest that there is an increased risk of congenital malformations, perinatal mortality and pre‐term birth in children born to women treated with azathioprine or mercaptopurine during pregnancy. More data are needed to determine whether the associations are causal or occur through confounding.
A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea‐predominant irritable bowel syndrome
Authors: Kim H. J. , Camilleri M. , Mckinzie S. , Lempke M. B. , Burton D. D. , Thomforde G. M. , Zinsmeister A. R.
Published: December 2004

Aim : To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea.

Methods : Twenty‐five patients with diarrhoea‐predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2‐week run‐in period. Pre‐ and post‐treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10‐week study, which was powered to detect a 50% change in the primary colonic transit end‐point.

Results : There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre‐ or post‐therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 [mean post‐ minus pre‐treatment score, − 13.7; 95% confidence interval (CI), − 2.5 to − 24.9], but not with placebo (P = 0.54) (mean post‐ minus pre‐treatment score, − 1.7; 95% CI, 7.1 to − 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well.

Conclusion : VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea‐predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.
Development and validation of the Diabetes Bowel Symptom Questionnaire
Authors: Quan C. , Talley N. J. , Cross S. , Jones M. , Hammer J. , Giles N. , Horowitz M.
Published: December 2004

Background : Although gastrointestinal symptoms occur frequently, there is no validated measure of gastrointestinal symptoms in patients with diabetes mellitus.

Aim : To develop the Diabetes Bowel Symptom Questionnaire.

Methods : A questionnaire derived from previously validated symptom measures was compiled to assess all relevant gastrointestinal and diabetes items. Face and content validity were ascertained by expert review. One hundred and sixty‐eight patients with diabetes mellitus completed the instrument, and reliability was evaluated by a test–re‐test procedure 1 week later. Concurrent validity was evaluated by an independent physician interview (n = 33). Measures of glycaemic control (glycated haemoglobin and plasma glucose) were compared with self‐reported glycaemic control on a five‐point Likert scale in diabetic out‐patients (n = 166).

Results : The questionnaire had adequate face and content validity. There was good to excellent test–re‐test reliability for the gastrointestinal and diabetes items (median kappa: 0.63 and 0.79, respectively); concurrent validity was good to excellent (median kappa: 0.47 and 0.65, respectively), except for the items assessing the severity of gastrointestinal symptoms. Both glycated haemoglobin (P < 0.0001) and plasma glucose (P = 0.005) correlated significantly with self‐reported glycaemic control.

Conclusion : The Diabetes Bowel Symptom Questionnaire appears to be a useful measure of gastrointestinal symptoms and glycaemic control in diabetes mellitus, and should have applicability in epidemiological and clinical studies.
Combined scintigraphic and pharmacokinetic investigation of enteric‐coated mesalazine micropellets in healthy subjects
Authors: Wilding I. R. , Behrens C. , Tardif S. J. , Wray H. , Bias P. , Albrecht W.
Published: December 2004

Background : There is a growing clinical trend to increase the daily dose of mesalazine, which leads to significant compliance issues associated with multiple dosings of current preparations.

Aim : To examine the gastrointestinal performance and systemic exposure of a 1.5 g sachet (micropellets) mesalazine formulation, compared with three enteric‐coated tablets (500 mg each, Claversal).

Methods : A randomized, two‐way, cross‐over pharmacoscintigraphic (scintigraphy plus pharmacokinetics) study and a two‐way, cross‐over, pharmacokinetic‐only study were performed in 24 healthy volunteers (12 subjects per investigation).

Results : The relative bioavailability of mesalazine was 92% comparing micropellets with Claversal tablets, and the cumulative urine excretion was c. 26% for both preparations, suggesting comparable systemic exposure for the two types of preparation. In the majority of subjects, drug release from the micropellet formulation occurred predominantly in the terminal ileum and ascending colon. The Claversal tablets disintegrated in comparable intestinal sites, albeit at slightly later time points than the micropellets, principally due to slower gastric emptying for the single‐unit formulation.

Conclusion : The 1.5 g micropellet formulation offers comparable delivery properties to the marketed tablets, but with greater convenience of dosing.
Esomeprazole‐based one‐week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance
Authors: Miehlke S. , Schneider‐Brachert W. , Bästlein E. , Ebert S. , Kirsch C. , Haferland C. , Buchner M. , Neumeyer M. , Vieth M. , Stolte M. , Lehn N. , Bayerdörffer E.
Published: December 2004

Aim : This study aimed to investigate the effectiveness of a one‐week triple therapy with esomeprazole, clarithromycin and metronidazole for eradication of Helicobacter pylori infection in the absence of antimicrobial resistance.

Methods : Patients testing positive for H. pylori susceptible to metronidazole and clarithromycin (E‐test) were randomized to receive a one‐week regimen with either esomeprazole 2 × 20 mg or omeprazole 2 × 20 mg in combination with clarithromycin 2 × 250 mg and metronidazole 2 × 400 mg. Follow‐up endoscopy with histology and culture and/or rapid urease test was performed 4–8 weeks after the end of treatment.

Results : Eighty patients were randomized. Helicobacter pylori infection was cured in 38/39 patients of the esomeprazole group and 31/33 patients of the omeprazole group (per protocol 97.4% (95% confidence interval [CI], 86.2–99.9), 93.7% (95% CI, 79.2–99.2), P = 0.59); intention‐to‐treat 90.4% (95% CI: 77.4–97.3), 81.6% (95% CI: 65.7–92.3), respectively. No major side effects occurred. Minor side effects occurred in eight (20%) and six (23%) patients during esomeprazole and omeprazole therapy, respectively. Post‐treatment susceptibility testing revealed resistance to both metronidazole and clarithromycin in two of the three patients who failed.

Conclusion : We conclude that esomeprazole, clarithromycin and metronidazole as one‐week triple therapy is effective for eradication of H. pylori in the absence of antimicrobial resistance.
Meta‐analysis: interferon for the treatment of chronic hepatitis C in dialysis patients
Authors: Fabrizi F. , Dulai G. , Dixit V. , Bunnapradist S. , Martin P.
Published: December 2004

Background : The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.

Methods and aims : We evaluated the efficacy and safety of initial interferon monotherapy in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop‐out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses.

Results : We have identified 14 clinical trials (269 unique patients); two were controlled studies. The mean overall estimate for sustained virological response (SVR) and drop‐out rate was 37%[95% confidence interval (CI) 28–48] and 17% (95% CI 10–28), respectively. The most frequent side‐effects requiring interruption of treatment were flu‐like symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6% (95% CI 20.9–48). In the sub‐group of clinical trials (n = 5) with standard interferon administration (3 million units [MUI] thrice weekly, subcutaneous route, 24‐week treatment), the overall mean estimate of SVR was 39% (95% CI 25–56). The studies were heterogeneous with regard to SVR and drop‐out rate.

Conclusions : Tolerance to initial interferon monotherapy was lower in dialysis than nonuremic patients with chronic hepatitis C. However, more than one‐third of haemodialysis patients with chronic hepatitis C have been successfully treated with interferon. Longer duration of interferon monotherapy does not appear to have a beneficial effect on the response rate. Further studies are warranted to define the optimal anti‐viral regimen for chronic hepatitis C in dialysis population.
Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2‐receptor antagonist
Authors: Shimatani T. , Inoue M. , Kuroiwa T. , Horikawa Y. , Mieno H. , Nakamura M.
Published: December 2004

Background: Omeprazole 10 mg is used as maintenance therapy for gastro‐oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression.

Aim: To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes.

Methods: Eighteen healthy subjects withoutHelicobacter pyloriparticipated. After a 7‐day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2‐receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h.

Results: With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH > 4 holding time ratios between poor metabolizers (PMs,n = 6) and the others [homozygous extensive metabolizers (homo‐EMs,n = 6) and heterozygous extensive metabolizers (hetero‐EMs,n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg ≈ lafutidine 20 mg > omeprazole 10 mg in homo‐EMs, omeprazole 20 mg > omeprazole 10 mg ≈ lafutidine 20 mg in hetero‐EMs, and omeprazole 20 mg ≈ omeprazole 10 mg > lafutidine 20 mg in PMs.

Conclusions: Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.
Low‐dose furazolidone in triple and quadruple regimens for Helicobacter pylori eradication
Authors: Fakheri H. , Merat S. , Hosseini V. , Malekzadeh R.
Published: December 2004

Background : Furazolidone‐based regimens for the eradication of Helicobacter pylori are low cost and effective. Unfortunately, the usual dose of furazolidone is not tolerable in many patients. Lower doses of furazolidone are expected to cause fewer adverse effects.

Aim : To investigate the efficacy of low‐dose furazolidone in the eradication of H. pylori.

Methods : One hundred and fifty patients with duodenal ulcer and H. pylori infection were randomly assigned to one of three treatment groups: omeprazole 20 mg b.d., amoxicillin 1000 mg b.d. and furazolidone 100 mg b.d. for 14 days (OAF); omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 100 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF1); or omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 200 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF2).

Results : Of the 150 patients, 145 completed treatment. The intention‐to‐treat and per protocol eradication rates were 54% (27/50), 72% (36/50) and 92% (46/50) for the OAF, OABF1 and OABF2 groups, respectively. The OAF and OABF1 groups showed significantly lower eradication rates than the OABF2 group (P < 0.001 and P < 0.01, respectively).

Conclusions : Triple and quadruple furazolidone‐based H. pylori eradication regimens do not yield acceptable success rates when a low dose of furazolidone (100 mg b.d.) is used.
Needling revision of failed filtering blebs after trabeculectomy: a retrospective study
Authors: Fagerli Marit , Løfors Kjell T. , Elsås Tor
Published: December 2004

Purpose:  To determine the efficacy and safety of needling revision of failed filtering blebs.

Methods:  We reviewed retrospectively 26 eyes that had undergone needling revision for a failed trabeculectomy. The needling revisions were performed either with adjunctive use of Mitomycin C, 5‐Fluorouracil or without antimetabolites. The procedure was usually performed as a clinic procedure, using a 27‐gauge needle.

Results:  The mean follow‐up time was 14.5 ± 11.3 months (range 6.0–48.0 months). Intraocular pressure (IOP) decreased from 28.8 ± 6.8 mmHg (range 19.0–40.0 mmHg) to 15.3 ± 5.2 mmHg (range 7.0–35.0 mmHg). Twelve eyes (46.2%) achieved success, defined as IOP ≤ 18 mmHg without medication; 11 eyes (42.3%) achieved qualified success, defined as IOP ≤ 18 mmHg with antiglaucomatous medication, and three of 26 eyes (11.5%) were classified as failures. The success rate after the initial needling was 64% at 6 months and the same after 1 year and 2 years. The success rate after one or more needlings was 96% at 6 months and 77% at 1 year and 2 years. Complications developed in six of the 26 eyes (23.1%). These involved transient corneal epithelial defects in three eyes (11.5%), temporary conjunctival wound leak in two eyes (7.7%), and development of bullous keratopathy in one high risk eye (3.8%).

Conclusion:  Our results are comparable to the results of other studies. Needling revision appears to be a useful tool in the management of glaucoma.
Intravitreal triamcinolone acetonide for the treatment of chronic pseudophakic cystoid macular oedema
Authors: Karacorlu Murat , Ozdemir Hakan , Karacorlu Serra
Published: December 2004

Purpose:  To evaluate the effect of intravitreal triamcinolone acetonide for chronic pseudophakic cystoid macular oedema (CME) resistant to medical treatment.

Methods:  Six eyes of six patients with chronic pseudophakic CME, aged 58–74 years (average 66 years), made up the study population. All eyes had persistent CME despite having received medical treatment for at least 3 months. Intravitreal injection of 4 mg (0.1 ml) triamcinolone acetonide was offered to treat macular oedema. The visual and anatomic responses were observed as well as potential complications related to the injection procedure and corticosteroid medication.

Results:  The follow‐up period was between 6 and 10 months (mean 8.5 months). Baseline central macular thickness averaged 504 µm. At 1 month, a reduction in the mean central macular thickness of 52% from 504 µm to 264 µm was obtained. At 3 and 6 months, the mean central macular thicknesses were 240 µm and 232 µm, respectively. Five of the six eyes maintained a visual gain of 15 or more letters from baseline at 6 months. During follow‐up no patient had intraocular pressure (IOP) exceeding 21 mmHg. No injection‐related complications were encountered.

Conclusions:  Intravitreal triamcinolone acetonide is a promising therapeutic method for chronic pseudophakic CME resistant to medical treatment. Further study with a longer follow‐up period and larger series is warranted to assess the treatment's longterm efficacy and safety and the need for retreatment.
Age‐related Change of Somatostatin‐immunoreactive Neurones in the Main Olfactory Bulb of the Rat
Authors: Hwang I. K. , Lee J. C. , Park S.‐K. , An S.‐J. , Lee H. Y. , Lee Y.‐B. , Sohn H.‐S. , Lee I. S. , Kang T.‐C. , Won M. H.
Published: December 2004

Somatostatin is found in the olfactory system, including the main olfactory bulb (MOB), and is thought to be one of the neuroactive substances for olfaction. However, somatostatin immunoreactivity in the olfactory system has not been determined during ageing. Hence, we examined the age‐related changes of somatostatin‐immunoreactive (IR) neurones in the rat MOB over a period of 2 years, at the following various ageing stages: post‐natal month 1 (PM 1), PM 3, PM 6, PM 12 and PM 24. In PM 1 group, a few somatostatin‐IR neurones were detected in the granule cell layer (GCL), and had slender or oval somata and short processes. At PM 3, somatostatin‐IR neurones were observed in the glomerular, external plexiform and GCL. The size of somatostatin‐IR somata was larger than that at PM 1. In PM 6 group, the number and size of somatostatin‐IR neurones increased, and their processes became longer while running in various directions. At PM 12, somatostatin‐IR neurones increased in number, and their processes became markedly longer than those at PM 6. At this stage, somatostatin‐IR neurones had multipolar somata, and were the largest in size. In PM 24 group, somatostatin‐IR neurones were most numerous. However, the processes of somatostatin‐IR neurones were shorter than those at PM 12. This study suggests that the increased number of somatostatin‐IR neurones in the MOB of aged rats may play a role to compensate for any decrease of olfactory function.
‘Victoria on the Move’: Mental Health Services in a Decade of Transition 1992-2002
Authors: Meadows Graham , Singh Bruce
Published: December 2004

Objective: Australia adopted a national mental health strategy in the early 1990s and each State has had to go through its own implementation process in the intervening years. The present paper describes the process of reform in services in Victoria, and ventures explanations as to why the process may have been more comprehensive and successful than in other States.

Conclusions: Victoria adopted a Statewide ‘framework’, defining structural elements of area-based services, with rational resource distribution. A transitional process involving a population health approach and relatively rigid implementation of a tightly specified service framework, within a political environment that favoured strong health services management, was successful in achieving desired structural reforms in this State. This was undoubtedly at the cost of promoting a model of public mental health service delivery that is generally rationed so as to accept only a restricted range of types of referral. New initiatives from the current State government are explicitly targeted to correcting this situation.