bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of detecting insulin‐like growth factor binding protein‐1 in cervicovaginal secretions: comparison with nitrazine test and amniotic fluid volume assessment
Authors: Erdemoglu Evrim , Mungan Tamer
Published: December 2004

Objectives.  The diagnosis of premature rupture of membranes (PROM) is sometimes challenging, and common diagnostic tests are of limited value in the diagnosis. We aimed to study the accuracy of detecting insulin‐like growth factor binding protein‐1 (IGFBP‐1) in vaginal fluid by a rapid dipstick method in comparison with the nitrazine test and amniotic fluid index (AFI) and we studied the predictivity of these methods on the latency of pregnancy in patients with suspected PROM.

Material and method.  One hundred and fifty‐one patients (36 definite PROM, 35 no PROM and 80 suspected PROM) at 20–42 weeks' gestation were included in the study. Patients with preterm labor and PROM, patients at <20 gestational weeks, and those with multiple pregnancies were excluded. IGFBP‐1 in the cervicovaginal fluid was measured by a rapid dipstick method (PROM test). AFI was measured by the four‐quadrant method and an AFI of <80 mm was considered as oligohydroamnios.

Results.  The sensitivity, specificity and accuracy of the nitrazine test, the PROM test and AFI were 97, 16 and 56%, 97, 97 and 97% and 94, 91 and 92%, respectively. The nitrazine test results were affected by vaginal discharge but the PROM test results were not affected. Only a positive PROM test was associated with delivery within 7 days [odds ratio (OR) 12; 95% confidence interval (CI) 4.2–35, p < 0.001].

Conclusion.  The dipstick method of detecting IGFBP‐1 in the vaginal fluid is a rapid, reliable and noninvasive method. The PROM test is the most accurate diagnostic test and predictor of latency in patients with suspected PROM.
Double‐blind study to evaluate efficacy and safety of meloxicam 7.5 mg and 15 mg versus mefenamic acid 1500 mg in the treatment of primary dysmenorrhea
Authors: De Mello Nilson Roberto , Baracat Edmund Chada , Tomaz Geraldez , Bedone Aloísio José , Camargos Aroldo , Barbosa Ione Cristina , De Souza Rosival Nassar , Rumi Demetrio Ortega , Martinez Alcala Felix Octavio , Velasco Jorge Antonio Aldrete , Cortes Roberto Jose Risco
Published: December 2004

Objective.  Assessment of efficacy and safety of meloxicam 7.5 mg and 15 mg once a day (o.a.d.) compared with mefenamic acid 500 mg three times a day (t.i.d.), over a treatment period of 3–5 days, during three menstrual cycles, for primary dysmenorrhea.

Study design.  Multicenter, multinational, double‐blind, double‐dummy, three parallel groups, randomized trial, phase IIb, 337 patients. Treatment group comparisons of continuous variables were carried out using the Kruskal–Wallis test and Wilcoxon signed rank tests. Efficacy was analyzed using Fisher and χ2‐tests.

Results.  Meloxicam 7.5 mg and 15 mg showed a similar profile in pain reduction and dysmenorrhea symptoms when compared with mefenamic acid. Thirty‐five subjects presented with gastrointestinal (GI) adverse events (AEs). Two‐thirds of those 35 subjects were in the mefenamic acid group. There were no differences between the safety profiles of the two meloxicam dosages. Laboratory abnormalities did not differ in incidence among the treatment groups.

Conclusion.  Both of the daily doses of meloxicam tested were comparable to 500 mg mefenamic acid t.i.d. in relieving dysmenorrhea symptoms, and meloxicam seems to have a better gastrointestinal tolerability profile.
The effect of physical activity on endothelial function in man
Authors: Moyna N. M. , Thompson P. D.
Published: December 2004

Endothelial dysfunction occurs early in the atherosclerosis in response to elevated atherosclerotic risk factors, and endothelial dysfunction itself may exacerbate the atherosclerotic process. Treatments that reduce atherosclerotic risk factors also generally improve endothelial function. The present review seeks to summarize the effect of exercise training on endothelial function in human subjects. Cross‐sectional studies comparing healthy physically active and inactive subjects as well as longitudinal exercise training studies of healthy individuals show little effect of exercise training on endothelial function. In contrast, both cross‐section and longitudinal studies document improved endothelial function with exercise training in subjects with abnormal baseline endothelial function, including the elderly and patients with heart failure or coronary artery disease. Improvements in endothelial function with physical activity may explain some of the benefits of exercise in subjects with, or at risk for, vascular disease.
Effects of N‐nitro l‐arginine methyl ester (l‐NAME), a potent nitric oxide synthase inhibitor, on visual evoked potentials of rats exposed to different experimental stress models
Authors: Yargiçoǧlu P. , Yaraş N. , Aǧar A. , Gümüşlü S. , Abidin İ. , Bilmen S.
Published: December 2004

Aim:  The aim of our study was to investigate the effects of the nitric oxide synthase inhibitor, N‐nitro l‐arginine methyl ester (l‐NAME, 10 mg kg−1 day−1 i.p.), on visual evoked potentials (VEPs) and lipid peroxidation expected to occur during chronic stress (15 days).

Methods:  Eight experimental groups, each consisting of 10 rats, were formed: control group (C), the group injected with l‐NAME (L), groups exposed to cold stress (CS), immobilization stress (IS), and both cold and immobilization stress (CIS), groups exposed to stress and injected with l‐NAME (CSL, ISL, CISL).

Results:  l‐NAME decreased brain and retina nitrite levels in all experimental groups compared with their corresponding control groups. l‐NAME decreased glutathione peroxidase (GSH‐Px) activity in the brain and retina in the L group, but increased it in the CSL and CISL groups compared with the C group. Lipid peroxidation was increased in the brain and retina tissues of all stress groups with respect to the C group. l‐NAME markedly increased brain thiobarbituric acid reactive substances (TBARS) levels in the L group, while significantly decreasing brain and retina TBARS levels in all stress groups in comparison with their respective control groups.

l‐NAME caused a significant delay in all components of VEPs in the L group compared with the C group. However, l‐NAME significantly decreased latencies of P1, N1, P2 and P3 components in the CSL group and all components in the ISL and CISL groups with respect to their corresponding control groups.

Conclusion:  This study clearly indicated that lipid peroxidation may be one possible factor affecting VEP components.
Psychiatric comorbidity in first episode psychosis: the Early Psychosis Intervention Program (EPIP) experience
Authors: Sim K. , Swapna V. , Mythily S. , Mahendran R. , Kua E. H. , McGorry P. , Chong S. A.
Published: December 2004

Objective:To determine the prevalence rates of psychiatric comorbidity in a hospitalized Asian patient group with first episode psychosis and examine its clinical correlates.

Method:Seventy‐nine consecutively admitted patients with first episode psychosis were assessed using the Structured Clinical Interview for DSM‐IV‐axis I disorders (patient edition), Positive and Negative Symptom Scale (PANSS), Scale to assess Unawareness of Mental Disorders (SUMD) and Global Assessment of Functioning (GAF) scales.

Results:Psychiatric comorbidity was present in 36.7% (n = 29) of the patients. Patients with psychiatric comorbidity were younger (P < 0.05), had an earlier onset of illness (P < 0.05) and better insight on social consequences and flat affect items (P < 0.05) on the SUMD. No significant differences were found between the two groups with and without psychiatric comorbidity in gender, ethnicity, marital status, length of education, employment status, living arrangements, duration of hospitalization and untreated psychosis as well as total PANSS and GAF scores.

Conclusion:Psychiatric comorbidity is common thus calling for a greater awareness in clinicians of these conditions, which are often under‐recognized, under‐diagnosed and untreated.
Amphetamine‐like stimulant cessation in an abusing patient treated with bupropion
Authors: Tardieu S. , Poirier Y. , Micallef J. , Blin O.
Published: December 2004

Objective: Bupropion sustained release is considered to be a weak inhibitor of dopamine and serotonin reuptake.

Method: We report the case of an amphetamine‐abusing patient who self‐administered bupropion.

Results: Since 30 years, a 52‐year‐old women used amphetamine derivates. She explained her need for amphetamine use in order to perform daily activities. Recently, she decided to experiment with bupropion. She abruptly stopped taking clobenzorex and simultaneously started taking bupropion (150 mg/day). The seventh day she reported a concomitant intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she described experiencing an euthymic state without any compulsion to take amphetamine drugs and was able to perform daily activities. After stopping it, no symptoms of withdrawal were reported by the patient.

Conclusion: This observation supports an another report suggesting that bupropion may be of help in weaning from amphetamine users and should be confirmed by clinical trials.
The political pivot of geography
Authors: KEARNS GERRY
Published: December 2004

The paper examines the geographical work of Peter Kropotkin and Halford Mackinder, making clear the political choices behind their very different geographical imaginations. Both writers responded directly to Keltie's report on geographical education and the paper uses these manifestoes as the starting point for an analysis of their relations to geographical thought and geographical institutions.
Revisiting the ‘pivot’: the influence of Halford Mackinder on analysis of Uzbekistan's international relations
Authors: MEGORAN NICK
Published: December 2004

Since the end of the Soviet Union, many foreign policy intellectuals have peculiarly identified the Republic of Uzbekistan as the locus of Mackinder's 1904‘pivot’ designation. A century on from his original ‘Geographical pivot of history’ lecture, this paper examines the work of a Russian, an Uzbek, and an American who use Mackinder to understand contemporary Uzbekistani geopolitical orientations, in particular with reference to the USA. Drawing on critical work on the history of geopolitics, it highlights that whilst these texts claim objectivity, they betray political and subjective foreign policy choices. It suggests that whilst the revival of interest in Mackinder testifies to the continued attraction of his ideas, this has, with rare exceptions, been based upon a superficial reading of both his work and the body of secondary literature, and that this raises both disciplinary and ethical concerns.
Beyond the ‘Outer Crescent’: the Mackinder century in New Zealand geopolitics
Authors: MAYELL PETER
Published: December 2004

This paper proposes that, although Mackinder never mentions New Zealand in his influential 1904 paper and despite the absence of a formal Kiwi geopolitical tradition, ‘The geographical pivot of history’ provides a useful framework with which to approach New Zealand geopolitics. The argument uses two Mackinderian ideas to suggest three phases in New Zealand's security relationships during the Mackinder century. First, New Zealand's commitment to Mackinder's ‘pivot area’ notion of ‘imperial defence’ and ‘collective security’ characterized its dependent security phase. Between 1973 and 1990/91 there was a transitional security phase towards Mackinder's second ‘global interconnectedness’ idea. Third, this shift led to a current interdependent security phase which is characterized by the recognition that New Zealand's security relationships, despite its geographic isolation, are mutually dependent on political, economic, and military events around the world. The impact of 11 September 2001 and the consequent ‘war on terror’ are also considered. The paper concludes by suggesting that New Zealand's post‐conflict reconstruction efforts in Afghanistan and Iraq point to the continuing relevance of Mackinder's ‘The geographical pivot of history’ to New Zealand geopolitics.
Going around in circles — circuitous medical management plans
Authors: Sonnenberg A.
Published: December 2004

Physicians occasionally embark on a work‐up that, after a lengthy path, leads them to a clinical situation similar to that from which they started their original pursuit. This article aims to describe the characteristics of circular medical management and means for its avoidance. The underlying medical problem often presents itself initially as a bewildering array of consecutive outcomes similar to a complex decision tree. On closer inspection, however, few of the outcomes are associated with a high probability, and only one path stands out as the most likely one to take. This path usually ends in such options as expectant management, supportive measures or doing nothing, which are already available at the onset of work‐up. If medical management is drawn out and takes a long time to complete, sight of its circular nature is easily lost. If many different specialists care for a patient, little appreciation for circular paths occurs. A prospective outline of the management plan and the elimination of paths with low a priori probability can help to prevent unnecessary medical interventions. The physician may then come to realize that standing still and waiting become as effective and less costly than a lengthy circular work‐up.
Harm minimization in school drug education: final results of the School Health and Alcohol Harm Reduction Project (SHAHRP)
Authors: McBride Nyanda , Farringdon Fiona , Midford Richard , Meuleners Lynn , Phillips Mike
Published: December 2004

Aims  The School Health and Alcohol Harm Reduction Project (SHAHRP study) aimed to reduce alcohol‐related harm in secondary school students.

Design  The study used a quasi‐experimental research design in which randomly selected and allocated intervention and comparison groups were assessed at eight, 20 and 32 months after baseline.

Setting  Metropolitan, government secondary schools in Perth, Western Australia.

Participants  The sample involved over 2300 students. The retention rate was 75.9% over 32 months.

Intervention  The evidence‐based intervention, a curriculum programme with an explicit harm minimization goal, was conducted in two phases over a 2‐year period.

Measures  Knowledge, attitude, total alcohol consumption, risky consumption, context of use, harm associated with own use and harm associated with other people's use of alcohol.

Findings  There were significant knowledge, attitude and behavioural effects early in the study, some of which were maintained for the duration of the study. The intervention group had significantly greater knowledge during the programme phases, and significantly safer alcohol‐related attitudes to final follow‐up, but both scores were converging by 32 months. Intervention students were significantly more likely to be non‐drinkers or supervised drinkers than were comparison students. During the first and second programme phases, intervention students consumed 31.4% and 31.7% less alcohol. Differences were converging 17 months after programme delivery. Intervention students were 25.7%, 33.8% and 4.2% less likely to drink to risky levels from first follow‐up onwards. The intervention reduced the harm that young people reported associated with their own use of alcohol, with intervention students experiencing 32.7%, 16.7% and 22.9% less harm from first follow‐up onwards. There was no impact on the harm that students reported from other people's use of alcohol.

Conclusions  The results of this study support the use of harm reduction goals and classroom approaches in school drug education.
How can we increase the involvement of primary health care in the treatment of tobacco dependence? A meta‐analysis
Authors: Anderson Peter , Jané‐Llopis Eva
Published: December 2004

Aims A systematic review of studies testing the effectiveness of educational and practice base strategies to increase the involvement of primary health‐care practitioners in the treatment of tobacco dependence.

Data sources MEDLINE, EMBASE, CINAHL and the Cochrane Library (1966–2001). Selection criteria included studies that used randomized or controlled clinical designs, controlled before and after trials and interrupted time‐series designs and that presented objective and interpretable measures of practitioners’ behaviour and biochemically verified patient quit rates.

Review methods A meta‐analysis, using a random effects model, of 24 programmes identified in 19 trials. Effect sizes were adjusted by inverse variance weights to control for studies’ sample sizes.

Findings Analyses to explain the heterogeneity of effect sizes found that interventions were equally effective in changing practitioners’ screening and advice‐giving rates and their patients’ quit rates. Absolute increases for the intervention above the comparison groups were 15% (95% CI = 7–22) for screening rates, 13% (95% CI = 9–18) for advice‐giving rates and 4.7% (95% CI = 2.5–6.9) for biochemically verified patient quit rates. Practitioners in training programmes were effective in changing their patients’ quit rates but not their own screening rates; educational interventions were more effective than practice‐based interventions. For established practitioners, programmes were effective in changing their screening and advice‐giving rates, but not their patients’ quit rates; a combination of practice‐based and educational interventions were more effective.

Conclusions Primary health‐care practitioners can be engaged in the treatment of tobacco dependence to increase equally their screening and advice‐giving rates and their patients’ quit rates with outcomes of considerable public health and clinical significance. The provision of educational interventions for practitioners in training in combination with systematic outreach practice‐based support for established practitioners is likely to be an effective strategy to increase smoking quit rates throughout primary health care.
Inflammatory bowel disease and hospital treatment in Italy: the RING multi‐centre study
Authors: Soncini M. , Triossi O. , Leo P. , Magni G. ,   (ON BEHALF OF THE RING STUDY GROUP)
Published: December 2004

Aim : To explore the management of chronic inflammatory bowel disease, specifically Crohn's disease and ulcerative colitis, in Italian gastroenterology units.

Methods : The RING (Ricerca Informatizzata in Gastroenterologia) project is an observational study collecting hospital discharge forms from 56 centres. Factors associated with the length of hospital stay were studied using multivariate logistic regression.

Results : In 24 months starting from August 2000, out of 29 376 hospital discharge forms, 2131 (7.3%) were collected for inflammatory bowel disease (1163 for Crohn's disease and 968 for ulcerative colitis). The Crohn's disease and ulcerative colitis groups were compared according to demographic characteristics, diagnoses, procedures and hospital stay. In Crohn's disease, computed tomography/magnetic resonance imaging, x‐rays/barium enema, number of procedures and number of diagnoses were significantly associated with a hospital stay longer than 10 days. In ulcerative colitis, this association was found for parenteral nutrition, malnutrition, computed tomography/magnetic resonance imaging and number of procedures.

Conclusions : Crohn's disease was confirmed as a disabling disorder requiring more frequent hospital treatment than ulcerative colitis. For the latter, parenteral nutrition and malnutrition were related to a longer hospital stay. The number of procedures, especially abdominal computed tomography/magnetic resonance imaging, was a major item for both pathologies.
Successful oesophageal pH monitoring with a catheter‐free system
Authors: Ward E. M. , Devault K. R. , Bouras E. P. , Stark M. E. , Wolfsen H. C. , Davis D. M. , Nedrow S. I. , Achem S. R.
Published: December 2004

Background : Traditional catheter‐based oesophageal pH testing is limited by patient discomfort and the tendency for patients to alter their diet and activities during the study. A catheter‐free pH monitoring system (Bravo) designed to avoid these problems has recently become available, but the advantages and limitations of this device have not been fully explored.

Aim : To report our initial experience with this new technology.

Methods : The records of consecutive patients undergoing Bravo pH monitoring were reviewed. The squamo‐columnar junction was localized endoscopically and the pH capsule was placed 6 cm above this junction. All patients were re‐endoscoped immediately following placement to document mucosal attachment. Patients were monitored for 24–48 h and then returned the radiotelemetry recording device. Data were subsequently downloaded to a personal computer.

Results : Sixty studies were performed over an 11‐month period. In seven of the 60 (12%), the probe did not attach properly, but in six of these a replacement probe was prepared and deployed without difficulty. In one case, the probe could not be attached after two attempts and the procedure was abandoned. During one procedure, the probe was attached to the mucosa at a point 9 cm from the squamo‐columnar junction, but a positive test result was obtained. In two cases, the data were not initially retrievable from the recorder, but in one case the manufacturer was able to retrieve the data overnight. Finally, two patients were away from the data recorder for extended periods, resulting in a loss of data, in two cases, but there was sufficient information for interpretation in both studies. Therefore, adequate diagnostic data were obtained in 58 of the 60 (97%) studies.

Conclusions : Catheter‐free pH testing is a major advance in patient convenience and comfort. The technical difficulties associated with this new technology are minimal and appear to be no more frequent than those seen with catheter‐based systems.
Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease
Authors: Louis E. , El Ghoul Z. , Vermeire S. , Dall'Ozzo S. , Rutgeerts P. , Paintaud G. , Belaiche J. , De Vos M. , Van Gossum A. , Colombel J. ‐F. , Watier H.
Published: December 2004

Aim : To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcγRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody‐dependent cell‐mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non‐Hodgkin's lymphomas) and response to infliximab in Crohn's disease.

Methods : FCGR3A‐158 polymorphism was determined using an allele‐specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C‐reactive protein levels) were assessed in 200 and 145 patients, respectively.

Results : There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C‐reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27–1.61). In the sub‐group of patients with elevated C‐reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003).

Conclusion : Crohn's disease patients with FCGR3A‐158 V/V genotype have a better biological and, possibly, clinical response to infliximab.
Increased circulating and intrahepatic T‐cell‐specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapy
Authors: Apolinario A. , Diago M. , Lo Iacono O. , Lorente R. , Pérez C. , Majano P. L. , Clemente G. , García‐Monzón C.
Published: December 2004

Aims : To determine the serum and intrahepatic levels of T‐helper‐1‐associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus‐related chronic liver disease and type of therapeutic response.

Methods : Serum chemokine levels were determined by enzyme‐linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry.

Results : Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non‐responders. Increased serum interferon‐γ‐inducible protein‐10 levels at baseline in genotype 1‐infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non‐response (P = 0.01). In patients with genotype 1, basal serum interferon‐γ‐inducible protein‐10 levels greater than 299 pg/mL identified 80% of non‐responders and lower than 299 pg/mL identified 63% of responders.

Conclusions : Circulating and intrahepatic T‐helper‐1‐associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon‐γ‐inducible protein‐10 levels in genotype 1‐infected patients are associated with virological non‐response to peginterferon plus ribavirin combination therapy.
Helicobacter pylori eradication decreases blood neutrophil and monocyte counts
Authors: Kondo Y. , Joh T. , Sasaki M. , Oshima T. , Itoh K. , Tanida S. , Kataoka H. , Ohara H. , Nomura T. , Itoh M.
Published: December 2004

Background : The effect of Helicobacter pylori infection on systemic disorders is not well understood.

Aim : The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori.

Methods : A total of 164 H. pylori‐positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed.

Results : In the eradicated group (n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non‐eradicated group (n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group.

Conclusions : These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes.
Heme oxygenase‐1: a new therapeutic target for inflammatory bowel disease
Authors: Naito Y. , Takagi T. , Yoshikawa T.
Published: December 2004

Heme oxygenase (HO) is the rate‐limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). Three mammalian HO isozymes have been identified, one of which, HO‐1, is a stress‐responsive protein induced by various oxidative agents. HO‐2 and HO‐3 genes are constitutively expressed. Recent studies demonstrate that the expression of HO‐1 in response to different inflammatory mediators may contribute to the resolution of inflammation and have protective effects in several organs against oxidative injury. Although the mechanism underlying the anti‐inflammatory actions of HO‐1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the intestinal tract, HO‐1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO‐1 expression plays a critical protective role in intestinal damage models induced by trinitrobenzene sulphonic acid or dextran sulphate sodium, indicating that activation of HO‐1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the intestinal tract. These in vitro and in vivo data suggest that HO‐1 may be a novel therapeutic target in patients with inflammatory bowel disease.
The aetiopathogenesis of inflammatory bowel disease — immunology and repair mechanisms
Authors: Dignass A. U. , Baumgart D. C. , Sturm A.
Published: December 2004

Although the aetiopathogenesis of Crohn's disease and ulcerative colitis, remains unsolved, current evidence indicates that defective T‐cell apoptosis and impairment of intestinal epithelial barrier function play important roles in the pathogenesis of both conditions. Without appropriate control of T‐cell proliferation and death during an immune response, an inappropriate accumulation of T cells and subsequent intestinal inflammation may occur. Differences in T‐cell responses between Crohn's disease and ulcerative colitis have been identified, with mucosal T‐cell apoptosis being defective in Crohn's disease, but not in ulcerative colitis. Furthermore, cell cycling is considerably faster, with a vigorous clonal expansion, in Crohn's disease, whereas, in ulcerative colitis, T cells cycle normally, but have a remarkably reduced capacity to divide and expand. The elimination of excessive T cells therefore seems to be a reasonable approach to restore the gut to a physiological state or, at least, a controlled state of inflammation. The tumour necrosis factor‐α blocker, infliximab, exerts its beneficial effects, at least in part, by the induction of apoptosis in lamina propria T cells and monocytes. In addition, repeated damage and injury of the intestinal surface is a hallmark of inflammatory bowel disease and may facilitate the entry of luminal antigens into the mammalian organism and the initiation and perpetuation of both nonspecific and specific immune responses. A better understanding of and enhancement of intestinal repair mechanisms may thus provide future approaches for the treatment of inflammatory bowel disease.
Problematic proctitis and distal colitis
Authors: Gionchetti P. , Rizzello F. , Morselli C. , Campieri M.
Published: December 2004

About two‐thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure, and therefore may be effectively treated with topical treatment, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side‐effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short‐chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy.
Anti‐tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation
Authors: Yoshimizu N. , Otani Y. , Saikawa Y. , Kubota T. , Yoshida M. , Furukawa T. , Kumai K. , Kameyama K. , Fujii M. , Yano M. , Sato T. , Ito A. , Kitajima M.
Published: December 2004

Aim:  To demonstrate the antitumour effects of nobiletin (5,6,7,8,3′,4′‐hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK‐1, MKN‐45, MKN‐74 and KATO‐III.

Materials and methods:  3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, the TdT‐mediated dUTP biotin nick‐end labelling (TUNEL) method and cell‐cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control.

Conclusions:  Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.
Effect of cyclo‐oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin
Authors: Gu Q. , Xia H. H.‐X. , Wang W. H. , Wang J. D. , Wong W. M. , Chan A. O. O. , Yuen M. F. , Lam S. K. , Cheung H. K.‐L. , Liu X. G. , Wong B. C.‐Y.
Published: December 2004

Background : We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole.

Aim : To determine the effects of a cyclo‐oxygenase (COX)‐2‐specific inhibitor, SC‐236, and a non‐selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori.

Methods : Three H. pylori reference strains, and 18 clinical isolates were treated with SC‐236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E‐test respectively.

Results : SC‐236 and indometacin inhibited H. pylori growth in a dose‐dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC‐236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC‐236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC‐236 or 0.1 mm indometacin (all P < 0.001).

Conclusion : Both SC‐236 and indometacin suppressed the growth and urease activity of H. pylori in a dose‐dependent manner, and increased its susceptibility to the antibiotics.
Effects of effervescent ranitidine on gastric pH: comparison with almagate and placebo in fasting and postprandial conditions
Authors: Rey E. , Poves‐Francés C. , Sánchez G. , Fueyo A. , Badiola C. , Díaz‐Rubio M.
Published: December 2004

Aim : To compare the effect of effervescent ranitidine, almagate (magnesium carbonate‐aluminium hydroxide) and placebo on gastric pH, in fasting and postprandial conditions.

Methods : Twelve healthy volunteers underwent a gastro‐oesophageal pH monitoring on three different occasions after the administration of each of the following randomly allocated treatments: almagate, effervescent ranitidine and placebo. Treatment effects were assessed in fasting and postprandial conditions. Onset and duration of alkalinization, percentage of time with pH >4 and median gastric pH after treatments were calculated in both periods.

Results : Onset of action of effervescent ranitidine was similar to almagate in fasting [median 1.2 min (IQR: 0.6–12.7) vs. 2.9 min (0.4–227.6)] and postprandial conditions [1.4 min (0.5–4.9) vs. 4.1 min (1.3–63.8)] and both were significantly faster than placebo [fasting 211.1 min (2.7–240); postprandial 240 min (175.6–240)]. The duration of action of effervescent ranitidine was statistically significant longer than almagate in fasting [235 min (105.2–239.4) vs. 19.4 min (6.7–38.8)] and postprandial conditions [171.8 min (133.2–239.5) vs. 61.3 min (44.7–91.9)]. Effervescent ranitidine was more effective than almagate in increasing the percentage of time with a pH >4 both in fasting (73.9% vs. 7.3%) and postprandial (59.1% vs. 21.3%).

Conclusions : Effervescent ranitidine shows an effect on gastric pH as fast as almagate but provides a duration of alkalinization longer than almagate, in both fasting and postprandial conditions.
Review article: tegaserod for chronic constipation
Authors: Johanson J. F.
Published: December 2004

Constipation is one of the most common gastrointestinal conditions with limited effective treatment options. Tegaserod, a 5‐HT4 receptor agonist has demonstrated efficacy in relieving constipation‐related symptoms in patients suffering from irritable bowel syndrome with constipation. This paper reviews two recent reports that have evaluated the efficacy and safety of tegaserod in pateints with chronic constipation. Two double‐blind, randomized, placebo‐controlled trials have been reported; one in Europe and Asia (E2301) the other in North and South America (E2302). After a 2‐week baseline period, patients were randomized to treatment with tegaserod 2 mg b.d., tegaserod 6 mg b.d. or placebo for 12 weeks. Two thousand, six hundred and twelve patients were randomized, the majority were white females. In both studies, responder rates during weeks 1–4 were significantly greater in the tegaserod groups compared with placebo. A similar trend was seen over weeks 1–12. Statistically significant improvements over placebo were seen across the majority of secondary efficacy variables. Tegaserod was safe with no consistent differences in the frequency of adverse events among the various groups. In conclusion, treatment of chronic constipation with tegaserod was associated with significant improvement in bowel frequency as well as other constipation symptoms. Tegaserod was also well tolerated in this patient population.
Spatial heterogeneity of ecosystem carbon fluxes in a broadleaved forest in Northern Germany
Authors: Kutsch Werner L. , Liu Chunjiang , Hörmann Georg , Herbst Mathias
Published: December 2004

Carbon fluxes were investigated in a mature deciduous forest, located in Northern Germany (53°47′N–10°36′E), by means of eddy‐covariance technique, stand survey and models. This forest has been managed following a concept of nature‐oriented forestry since the 1980s. One of the goals of the study was to test whether changed management led to increased carbon sequestration. The forest contains several broadleaved tree species. Depending on wind direction, the fetch‐area of the eddy‐covariance data was dominated by different tree species. Three subplots dominated by Oak, Beech or Alder/Ash could be distinguished from the tower data. In each of these subplots, 30 × 30 m2 areas were defined to analyse leaf area index, litterfall and the increase of the wood biomass.

Eddy‐covariance analysis showed that the gross primary productivity (GPP′) was higher in the Oak subplot (−1794 g C m−2 yr−1) in comparison with the Beech plot and the Alder/Ash plot (−1470 and −1595 g C m−2 yr−1, respectively). The total ecosystem respiration (TER) was the highest in the Alder/Ash‐dominated subplot (1401 g  C m−2 yr−1) followed by the Oak plot and the Beech plot (1235 and 1174 g C m−2 yr−1, respectively). The resulting net ecosystem productivity (NEP) was −559 g C m−2 yr−1 for the Oak‐dominated subplot, −295 g C m−2 yr−1 for the Beech plot and −193 g C m−2 yr−1 for the Alder/Ash plot.

From Stand survey and modelling, the net primary productivity was estimated as 1103, 702 and 671 g C m−2 yr−1 in the Oak, Beech and Alder/Ash plot, respectively. Also carbon flux with litterfall was the highest in the Oak plot 343 g C m−2 yr−1 and lowest in Alder/Ash plot (197 g m−2 yr−1) with the Beech plot in between (228 g m−2 yr−1). The observations indicate an increase of the proportion of litterfall with increasing GPP′ and a different ability of carbon sequestration of the three stands in medium temporary scale. Only in the Oak stand that comprised the oldest trees and the most structured canopy the carbon sequestration was increased compared with conventionally managed forests.
The effects of chronic smoking on the ocular surface and tear characteristics: a clinical, histological and biochemical study
Authors: Satici Ahmet , Bitiren Muharrem , Ozardali Ilyas , Vural Huseyin , Kilic Adil , Guzey Mustafa
Published: December 2004

Purpose:  To investigate the effects of chronic smoking on the ocular surface and tear characteristics.

Methods:  The Schirmer I‐test, tear film break‐up time, rose Bengal staining scores, impression cytology, tear lysozyme concentration, eye irritation symptoms, and eye irritation indices were determined for 44 eyes in 44 healthy, chronic smokers who had smoked six or more cigarettes per day for the previous year. Thirty‐seven eyes in 37 healthy, non‐smokers were assessed in the same masked manner for comparison. Cytological specimens were obtained from the temporal interpalpebral bulbar conjunctiva by ‘impression’ technique. Goblet cells were counted in the specimens obtained and squamous metaplasia was graded following epithelial cell morphology assessment.

Results:  In chronic smokers, we found decreased tear film break‐up time (p = 0.022) and tear lysozyme concentration (p = 0.013), and increased Schirmer I‐test values (p = 0.047), squamous metaplasia scores (p = 0.016), eye irritation scores (p < 0.001) and eye irritation indices (p = 0.013), as compared with the control group. There were no statistically significant differences in goblet cell counts (p = 0.710) or rose Bengal staining scores (p = 0.827).

Conclusion:  These findings suggest that chronic smoking has a negative effect on the ocular surface and affects some tear characteristics. The chronic ocular irritative effects of cigarette smoking may lead to defects in ocular surface defence.
The influence of sex hormones on ocular blood flow in women
Authors: Toker Ebru , Yenice Özlem , Akpinar Ihsan , Aribal Erkin , Kazokoglu Haluk
Published: December 2004

Purpose:  To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre‐ and postmenopausal women.

Methods:  Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end‐diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle‐stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed.

Results:  After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p = 0.02) and a significantly higher RI (p = 0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r = 0.58, p = 0.04) and EDV (r = 0.73, p = 0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r = − 0.40, p = 0.04; postmenopausal r = − 0.32, p = 0.05). Peak systolic velocity in the central retinal artery correlated negatively (r = − 0.49, p = 0.04), whereas the RI correlated positively (r = 0.53, p = 0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r = − 0.53, p = 0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r = 0.48, p = 0.01; central retinal artery r = 0.61, p = 0.002).

Conclusion:  Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.
Regulation mechanisms of retinal pigment epithelial cell migration by the TGF‐β superfamily
Authors: Mitsuhiro Marcia Regina Kimie Higashi , Eguchi Shuichiro , Yamashita Hidetoshi
Published: December 2004

Purpose:  To investigate the expression of specific receptors, signal transducers and the effect of transforming growth factor‐β(TGF‐β) on retinal pigment epithelium (RPE) migration and proliferation.

Methods:  Human RPE cell line D407 was used in all experiments. The effect of TGF‐β on migration and proliferation were studied using a wound healing model and [3H]‐thymidine incorporation, respectively. The expression of RNA related to the TGF‐β superfamily receptors and SMAD1−4 were assayed by reverse transcriptase‐polymerase chain reaction (RT‐CPR). The effects of TGF‐β on the intracellular position of SMAD were studied by immunoperoxidase and immunofluorescence.

Results:  Transforming growth factor‐β 4 nm and activin A 0.36 nm stimulated RPE migration. There was no effect on proliferation. RNA for TGF‐β receptors types 1 and 2, and SMAD1−4 were detected in RPE culture. Transforming growth factor‐β signal transducer SMAD2 but not SMAD1 moved from the cytoplasm to the nucleus after TGF‐β stimulation.

Conclusion:  Transforming growth factor‐β can regulate RPE cell migration through specific signal transduction pathways.