Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease

BACKGROUND: Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. AIM: To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. METHODS: The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.     

Nocturia and obesity: a population-based study in Finland

The authors' aim in this study was to analyze the association of nocturia with overweight and obesity. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on nocturia was collected through questionnaires using the Danish Prostatic Symptom Score and the American Urological Association Symptom Index. Self-reported body weight and height were used to calculate body mass index (BMI; weight (kg)/height (m)2). Subjects were classified on the basis of BMI as nonoverweight (BMI<25), overweight (BMI 25-29.9 kgm2), or obese (BMI>or=30). Of the 6,000 subjects, 62.4% participated. Among men, the age-standardized prevalence of nocturia, defined as at least one void per night, was 33.4% (95% confidence interval (CI): 28.5, 38.3) in the nonoverweight, 35.8% (95% CI: 31.4, 40.1) in the overweight, and 48.2% (95% CI: 38.8, 57.6) in the obese. Among women, the corresponding figures were 37.2% (95% CI: 33.0, 41.5) in the nonoverweight, 48.3% (95% CI: 42.5, 54.2) in the overweight, and 53.6% (95% CI: 43.9, 63.2) in the obese. The associations remained similar when nocturia was defined as two or more voids per night. The age-standardized attributable fraction (population) of increased BMI for nocturia was 17.7% for men and 18.5% for women, corresponding to an 8.5% increase in the crude prevalence of nocturia in men and a 13.9% increase in women. The authors conclude that obesity is associated with increased nocturia, more strongly among women than among men.     

Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine

The antidepressant fluoxetine is administered as racemic mixture of two enantiomers (S- and R-fluoxetine). While S- and R-fluoxetine are equipotent in blocking serotonin reuptake, the enantiomers of the demethylated metabolite, norfluoxetine, show marked differences in pharmacological activity, S-norfluoxetine being about 20 times as potent as R- norfluoxetine as a serotonin reuptake inhibitor. In vitro and in vivo data suggest that the metabolism of fluoxetine to norfluoxetine is stereoselective and mediated, at least in part, by the polymorphic cytochrome P450 (CYP) isoenzymes CYP2D6, CYP2C9 and CYP2C19. In the present study, the influence of CYP2D6, CYP2C9 and CYP2C19 polymorphisms on the steady-state plasma concentrations of fluoxetine and norfluoxetine enantiomers was evaluated in 78 patients receiving chronic fluoxetine treatment (10-60 mg/day). The plasma concentrations of fluoxetine and norfluoxetine enantiomers were measured and CYP2D6, CYP2C9 and CYP2C19 genotypes were analyzed. No statistically significant relationship was identified between CYP2D6 or CYP2C19 genotypes and the dose normalised plasma concentrations of any of the enantiomers or the active moiety (i.e. the sum of S-fluoxetine, R-fluoxetine and S-norfluoxetine). However, the plasma concentration of S-norfluoxetine was very low in the only CYP2D6 poor metaboliser. Furthermore, the median S-norfluoxetine/S-fluoxetine ratios were higher in homozygous than in heterozygous extensive metabolisers (P<0.05). Among homozygous extensive metabolizers for CYP2D6, patients homozygous for CYP2C9*1 had lower dose-normalized R-fluoxetine concentrations and lower active moiety levels compared with those carrying detrimental CYP2C9 alleles (P<0.05). These results suggest that CYP2D6 and CYP2C9 polymorphisms contribute to the interindividual variability in fluoxetine pharmacokinetics at steady-state.     

Is coeliac disease screening in risk groups justified? A fourteen‐year follow‐up with special focus on compliance and quality of life

BACKGROUND: The benefits of serologic screening for coeliac disease in asymptomatic individuals are debatable. AIM: To investigate dietary compliance, quality of life and bone mineral density after long-term treatment in coeliac disease patients found by screening in risk groups. METHODS: The study comprised 53 consecutive screen-detected coeliac patients diagnosed 14 years (median) ago. Dietary compliance was assessed by interview, 4-day food record and serology. Quality of life was evaluated by the Psychological General Well-Being and SF-36 questionnaires, gastrointestinal symptoms by the Gastrointestinal Symptom Rating Scale and bone mineral density by dual-energy x-ray absorptiometry. Comparisons were made to 44 symptom-detected-treated coeliac patients, 110 non-coeliac subjects and the general population. RESULTS: A total of 96% of screen-detected and 93% of symptom-detected coeliac patients adhered to a strict or fairly strict gluten-free diet. In screen-detected patients, quality of life and gastrointestinal symptoms were similar to those in symptom-detected patients or non-coeliac controls and bone mineral density was similar to that in the general population. CONCLUSIONS: Long-term dietary compliance in screen-detected patients was good. Quality of life and bone mineral density were comparable with those in non-coeliac subjects and the general population. Active screening in coeliac disease risk groups seems to be reasonable rather than harmful.     

Effects of exercise intensity and duration on nocturnal heart rate variability and sleep quality

Acute physical exercise may affect cardiac autonomic modulation hours or even days during the recovery phase. Although sleep is an essential recovery period, the information on nocturnal autonomic modulation indicated by heart rate variability (HRV) after different exercises is mostly lacking. Therefore, this study investigated the effects of exercise intensity and duration on nocturnal HR, HRV, HR, and HRV-based relaxation, as well as on actigraphic and subjective sleep quality. Fourteen healthy male subjects (age 36 ± 4 years, maximal oxygen uptake 49 ± 4 ml/kg/min) performed five different running exercises on separate occasions starting at 6 p.m. with HR guidance at home. The effect of intensity was studied with 30 min of exercises at intensities corresponding to HR level at 45% (easy), 60% (moderate) and 75% (vigorous) of their maximal oxygen uptake. The effect of duration was studied with 30, 60, and 90 min of moderate exercises. Increased exercise intensity elevated nocturnal HR compared to control day (p < 0.001), but it did not affect nocturnal HRV. Nocturnal HR was greater after the day with 90- than 30- or 60-min exercises (p < 0.01) or control day (p < 0.001). Nocturnal HRV was lower after the 90-min exercise day compared to control day (p < 0.01). Neither exercise intensity nor duration had any impact on actigraphic or subjective sleep quality. The results suggest that increased exercise intensity and/or duration cause delayed recovery of nocturnal cardiac autonomic modulation, although long exercise duration was needed to induce changes in nocturnal HRV. Increased exercise intensity or duration does not seem to disrupt sleep quality.     

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Robotic-assisted laparoscopy is a feasible method for resection of deep infiltrating endometriosis,especially in the rectosigmoid area

ObjectiveThis study aimed to compare outcomes of mini-invasive surgical treatment of endometriosis, especially conventional laparoscopy with robotic-assisted laparoscopy, and to evaluate the quality of life.MethodsOne hundred three consecutive patients with endometriosis who had surgery from 2014 to 2017 owing to an indication of pain were enrolled in this retrospective study. The majority (n = 77, 75%) of patients underwent conventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. The quality of life was postoperatively assessed with a questionnaire.ResultsThe rates of parametrectomy (76% vs. 45%,) and rectovaginal resection (28% vs. 4%) were significantly higher in robotic-assisted laparoscopy than in laparoscopy. Additionally, the rate of bowel operations (50% vs. 17%), especially the shaving technique, was higher in robotic-assisted laparoscopy surgery than in laparoscopy (39% vs. 8%). There was no difference in the rate of postoperative complications between laparoscopy and robotic-assisted laparoscopy. Most (91%) of the patients who answered the questionnaire felt that surgical treatment had relieved their pain. In the laparoscopic and robotic-assisted groups, 88% of respondents felt that their quality of life had improved after surgery.ConclusionsThis study suggests that robotic-assisted laparoscopy is a feasible method to resect deep infiltrating endometriosis, especially in the rectosigmoid area.     

Liquid chromatography/tandem mass spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum and cerebrospinal fluid

A validated, accurate and sensitive LC–MS/MS method for determination of olanzapine and its metabolite N-desmethylolanzapine has been developed. The analytes were quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. Olanzapine and desmethylolanzapine were extracted from serum or cerebral spinal fluid samples, 200 μl, with tert-butyl methyl ether using olanzapine-D3 as internal standard. Calibrations for olanzapine and desmethylolanzapine were linear within the selected range of 0.2–30 ng/ml (6–96 nM) in cerebral spinal fluid and for olanzapine in plasma, in the range of 5–100 ng/ml (16–320 nM). The method was successfully used for the analysis of samples from patients treated with olanzapine in the dose range of 2.5–25 mg/day.