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Objectives Synthesis of melatonin follows a circadian cycle, with high melatonin levels during the night and low levels during the day. Light exposure at night has been hypothesised as one of potential mechanisms of breast carcinogenesis in the night shift workers through inhibition of melatonin synthesis. The aim of the study was to examine a number of determinants for night shift work in relation to 6-sulfatoxymelatonin (MT6s), primary melatonin metabolite. Methods The cross-sectional study included 354 nurses and midwives (aged 40–60 years) currently working on rotating night shifts and 370 working days only. Data from questionnaires and 1-week diaries were used to characterise current job and total occupational history. Associations between rotating night shift work characteristics and MT6s (creatinine adjusted) in spot morning urine were tested in multiple linear regression models. Results No significant differences were found for MT6s concentrations between women currently working on rotating night shifts and those working only day shifts (means 47.2 vs 45.7 ng/mg Cr, respectively). The adjusted means among rotating night shift nurses and midwives varied depending on the department of employment, from 35.1 ng/mg Cr in neonatology to 68.2 ng/mg Cr in the orthopaedics department. Women working eight or more night shifts per month had significantly lower MT6s levels than those having fewer night shifts per month (37.9 vs 47.4 ng/mg Cr, respectively). Total night shift work history was not associated with MT6s. Conclusions The results of this study indicate that working eight or more night shifts per month may disrupt the synthesis of melatonin.

Background/aims To evaluate depression, coping with disease and stress, and the subjective impression of distress and/or life events as triggers for recurrences in HLA-B27-associated anterior uveitis (B27-AU), with attention to gender-specific characteristics. Methods 171 patients with a history of B27-AU responded to a postal survey performed between January 2006 and April 2008 using standardised psychological questionnaires: Beck Depression Inventory, Freiburg Questionnaire on Coping with Illness, and Stress Coping Inventory. Results Patients with B27-AU differed from healthy controls showing more depressive symptoms (Beck Depression Inventory, 31.6%), applying characteristic disease coping as well as negative stress coping strategies. Female B27-AU patients tended to react with depression and male patients to use negative stress coping strategies. 57.9% of patients believed that psychological distress was a trigger for relapses, and 34.5% stated specific life events. Together, this group of patients achieved higher depression scores and used more negative disease and stress coping styles than patients without perception of distress. Conclusion Patients with B27-AU patients exhibited significant psychopathology concerning depression and disease coping. Distress and life events were subjectively suspected to be a trigger. By imparting knowledge to the patients on probable development of depressive moods and the role of stress/life events as trigger for relapses, as well as offering behaviour therapy to optimise coping, may help patients to cope better with B27-AU.

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.

Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer and is secreted by the normal stomach. Secretion is impaired in Helicobacter pylori (H pylori) associated chronic gastritis. This study examined if eradication of H pylori improves gastric juice ascorbate values. Fasting gastric juice and plasma samples were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication. Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography. In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment. Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations, even though these did not change with treatment. By contrast, in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment. It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice. It is speculated that this increases protection against gastric cancer.

The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.

Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes.

Gastric biopsy specimens from patients who have undergone gastric surgery frequently exhibit foveolar hyperplasia, oedema, vasodilatation and congestion, and a paucity of inflammatory cells as consequences of entero-gastric reflux. Similar, albeit generally milder, changes were found in 47 of 316 (15%) non-surgical patients undergoing endoscopy for dyspeptic symptoms. To relate these changes to bile reflux or other potential gastric irritants the total bile acid concentration was measured in samples of fasting gastric juice, and the use of a symptom questionnaire ascertained the patients' cigarette consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and alcohol intake. When patients with reflux gastritis were compared with normal controls (n = 91), significant increases in associated peptic ulceration and NSAID use were found in the group with reflux, but no increases in bile acid concentrations. Indeed, only one patient had evidence of duodenogastric reflux. It is concluded that most cases of "reflux gastritis" in the intact stomach are not due to reflux of bile. Our findings indicate an important pathogenic role for long term NSAID use, in what might be usefully termed type C or "chemical" gastritis.

Ultrastructural examination of biopsies showing Helicobacter pylori associated chronic gastritis reveals close attachment between gastric surface epithelial cells and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response of intestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with H pylori positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune response--namely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors.

article i nfo Background: Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. Aim:The objectiveof thisstudywastoevaluate the impactofpreandearlypostnatal phthalate exposureon child psychomotor development based on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). Studydesign,subjectsandoutcomemeasures:Phthalate exposurewasdeterminedbymeasuring11phthalate me- tabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, OH-MiNP, oxo-MiNP, and MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at the 24th month of age (postnatal exposure). The analysis was performed by the HPLC- MS/MS method. Psychomotor development was assessed in children at the age of 2 years by the Bayley Scales of Infant and Toddler Development. Results: Child motor development was inversely associated with natural log concentrations (μg/g creatinine) of 3OH-MnBP (β = −2.3; 95% CI −4.0 to −0.6), 5OH-MEHP (β = −1.2; 95% CI −2.2 to −0.3), 5oxo-MEHP (β = −1.8; 95% CI −3.3 to −0.2) and sum of DEHP metabolites (β = −2.2; 95% CI −3.6 to −0.8), DnBP metabolites (β = −1.9; 95% CI −3.4 to −0.4), and high molecular weight phthalates (β = −2.5; 95% CI −4.1 to −0.9) in the urine collected from mothers during pregnancy after adjustment for a variety of potential confounders. Addi- tional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. Conclusions: The study findings add further support to the possibility that prenatal phthalate exposure may be det- rimental to child neurodevelopment and underscore the importance of policies and public health interventions aiming at reduction of such exposure.

Objectives To investigate the association between rotating night shift work and selected modifiable lifestyle factors among nurses and midwives. Method The cross-sectional study included 725 nurses and midwives aged 40–60 (354 rotating night shift and 371 daytime workers). Occupational history and data about potential confounders were collected through in-person interview. Weight and height were measured and BMI was calculated. Associations between night shift work characteristics such as current rotating night shift work, frequency of night duties, total duration of rotating night shift work and lifestyle factors, i.e. a) smoking cigarettes, b) alcohol consumption, c) physical activity and d) BMI were examined with logistic regression and linear regression analyses adjusted for age. Results Smoking cigarettes was associated significantly with current rotating night shift work (OR=1.4), frequency of night shifts (OR= 1.5 and OR=1.7 among women with 5–7 and ≥8 night duties/month, respectively) and longer duration of the night shift work (OR=2.1 for duration >25 yrs). The total physical activity was higher among rotating night shift nurses (242 vs. 203 MET*h/week), but OR of recreational inactivity was significantly increased among rotating night shift workers (OR=1.6). Mean BMI was significantly higher among postmenopausal women working night shifts when compared to day workers (BMI= 28.9 vs. 27.6 kg/m2), with increased OR of obesity (OR=2.8). No significant associations were observed between night shift work and alcohol consumption. Conclusions The results of our study indicate that rotating night shift work may be associated with poorer lifestyle, which may contribute to chronic diseases.

Objectives Night shift work and exposure to light at night suppress synthesis of melatonin and disrupt circadian rhythm. The pattern of secretion of many hormones, including prolactin, is dependent on circadian rhythm and prolactin has been found to play a role in breast cancer aetiology. So far, the data on the link between night shift work and prolactin are sparse. The aim of our study was to evaluate the association between rotating night shift work and prolactin concentration in nurses and midwives. Methods The cross-sectional study included 347 nurses and midwives currently working on rotating night shifts and 359 nurses and midwives working during the day. The prolactin concentration was measured in the morning blood samples using the ECLIA method. The associations were estimated by multiple linear regression models adjusted for: age, number of full-term births, current oral contraceptives use and time of blood collection. A potential modification by the menopausal status was analysed. Results No difference in the prolactin concentration was found between the women currently working on night shifts and the day nurses (geometric means (GM): 195.3 µU/ml vs. 194.7 µU/ml; p = 0.948). In women with 2 or more consecutive night shifts within one week before the blood collection, we observed a statistically significant increase of the prolactin concentration compared to the women who had only one night shift throughout that week (250.2 µU/ml vs. 216.9 µU/ml; p = 0.033). None of the examined associations were modified by the menopausal status. Conclusions The preliminary results of our study suggest that night shift work might modify prolactin secretion.

Objectives It has been hypothesised that night shift work might increase oxidative stress. To date, the data on oxidative stress biomarkers in night shift workers are sparse. The aim of our study was to evaluate the association between night shift work and important antioxidant enzymes activity: superoxide dismutase 1 (SOD1), cellular glutathione peroxidase 1 (GPx1) and extracellular glutathione peroxidase 3 (GPx3). Methods The cross-sectional study included 355 nurses and midwives currently working on rotating night-shifts and 370 nurses and midwives working during the day. Enzyme activities were measured in the morning blood samples using kinetics methods. Associations between current employment and SOD1, GPx1, and GPx3 were estimated by multiple linear regression models. Potential modification by menopausal status was analysed. Results No differences in SOD1 activity were found between women working on night shift and day nurses. Activity of GPx1 was significantly higher in the group of night shift nurses than day nurses (geometric means(GM): 21.8 u/g Hb vs 20.7 u/g Hb; p=0.001). Menopausal status modified the association between night shift work and GPx3, with lower GPx3 activity in postmenopausal night shift nurses when compared to day nurses (0.188 u/ml vs 0.196 u/ml; p=0.021), and opposite association seen in premenopausal women (0.196 u/ml vs 0.188 u/ml; p=0.006). Significant relationship between night shifts frequency GPx3 and GPx1 was found. Conclusions Preliminary results of our study suggests that night shift work might modify antioxidant enzymes activity.

Objectives Exposure to light at night might decrease secretion of melatonin in night shift workers. Experimental studies in animals have shown that melatonin might increase antioxidant enzymes activity, although, these observations has not been examined in humans yet. The aim of our study was to evaluate the association between concentration of melatonin metabolite (MT6s) and antioxidant enzymes activity: superoxide dismutase 1 (SOD1), cellular glutathione peroxidase 1 (GPx1) and extracellular glutathione peroxidase 3 (GPx3). Methods The cross-sectional study included 725 nurses and midwives. Enzymes activities were measured in the morning blood samples using kinetics methods. Melatonin metabolite (6-sulfatoxymelatonin) concentration in the morning urine samples was evaluated with ELISA assay method and adjusted for creatinine. Associations between MT6s concentration and SOD1, GPx1, and GPx3 activity were estimated by multiple linear regression models. Potential modification of the associations by current night shift work status was examined. Results No significant associations between MT6s concentration, GPx1, GPx3 and SOD1 activity were found (coef=-0.07, p=0.76; coef=0.0009, p=0.55; coef=-0.027, p=0.72 respectively), both in the total population as well as in the categories of day nurses and women working on night shifts. Conclusions Preliminary results of our study do not support previous findings in the experimental studies on association between melatonin and antioxidant enzymes activity.

Objectives 6-sulfatoxymelatonin (MT6s) in the morning urine is a valid biomarker of melatonin synthesis at night. Controlled experimental studies have shown decrease in melatonin synthesis after light exposure at night, however, only few epidemiological studies examined morning MT6s in nurses working rotating night shifts. The aim of our study was to investigate which characteristics of rotating night shift work influence melatonin synthesis. Methods The cross-sectional study included 355 nurses and midwives (aged 40–60) currently working on rotating night shifts. Data on the current job (hospital department, frequency of night shifts, activities, napping) and potential confounders were collected through a personal interview. MT6s concentrations were determined in the morning urine samples after night shift (ELISA assay, adjusted for creatinine). Associations between rotating night shift work characteristics and MT6s were tested in multiple linear regression models. Results The adjusted geometric means (GM) in the rotating night shift nurses and midwives varied depending on the department of employment from GM=32 ng/mg Cr at the neonatology department to GM=72 ng/mg Cr) at the orthopaedics department. Women working 8 or more night shifts per month had significantly lower MT6s than those having on average less night shifts per month (35 ng/mg Cr vs 43 ng/mg Cr respectively). MT6s concentrations were significantly lower in women working for more than 10 h when compared to those working fewer hours (p=0.025). Conclusions Preliminary results of our study indicate that the frequency of night shifts and number of working hours may influence MT6s levels.