The association of sleep with inflammatory bowel disease in children and adolescents

Aim

To systematically review literature investigating sleep quality in children and adolescents with inflammatory bowel disease (IBD).

Methods

Electronic databases were searched (BASE, Cochrane Database of Systematic Reviews, DIMDI, PsychArticles, PsychInfo, Psychjournals, Psychline, PSYNDEX, Pubmed, Science Direct, Web of Science, Wiley Online Library) by two researchers. Eligible studies were all that studied sleep disorders in the context of IBD in children and adolescents (6–17 years of age).

Results

Out of 40 references identified, five studies (all cross-sectional, three of them controlled) were eligible and included in this study. The publications showed that children and adolescents with IBD have significant sleep problems, adding to their impaired quality of life.

Conclusion

The published data provide evidence suggesting an impact of IBD and its severity on sleep in children and adolescents. However, with regard to the low methodological quality, the incongruity of the studies concerning outcome measure, and their focus of exploration, further studies are warranted to highlight the interrelationship.

     

The effect of orally and vaginally administered misoprostol on inflammatory mediators and cervical ripening during early pregnancy

OBJECTIVES: The objective of the present study was to investigate the effect of vaginally and orally administered misoprostol on the local cervical inflammatory response. METHODS: Healthy women with a normal intrauterine pregnancy between 8 and 12 weeks of gestation presenting for an elective termination of pregnancy by vacuum aspiration were recruited into a cohort study with a control and a treatment group. In the treatment group, the women were randomized to misoprostol, 400 mug, given either orally or vaginally 3 h before surgery. Immunohistochemistry staining of CD45, CD68, MMP 8, MMP 9, TIMP 1 and TIMP 2 were assessed in cervical biopsies obtained directly prior to mechanical cervical dilatation and vacuum aspiration. RESULTS: In the treatment group, there was a greater amount of CD45-positive cells in the subepithelium region of the cervix compared to the control group. The staining of CD68 was similar in both groups. The immunostaining of MMP 8 and MMP 9 was greater in the treatment group, while the expression of TIMP 1 and TIMP 2 did not differ between control and treatment groups. CONCLUSIONS: Compared to untreated controls, treatment with misoprostol was associated with a greater expression of inflammatory cells. It could be hypothesized that administration of misoprostol mimics the cervical ripening at term pregnancy by a possible influx and activation of inflammatory cells, which increases MMP 8 and MMP 9 and thereby leads to the degradation of collagen and cervical softening.     

Microdialysis in postoperative monitoring of microvascular free flaps: Experiences with a decision algorithm

BackgroundReconstruction with free flaps has become a usual practice in maxillofacial surgery. Clinical monitoring is still the standard approach for postoperative follow-up, but can be difficult or impossible with intraorally situated or buried flaps. Microdialysis is a sampling technique that offers the possibility to monitor the metabolism of flaps continuously. It is a reliable method for early diagnosis of ischemia.Materials and methods48 microvascular free flaps applied following oral cancer resection were monitored with a microdialysis (MD) catheter, placed in the flap. Glucose, lactate, and lactate/pyruvate ratio were monitored using a bedside analyser for 5 days. 48 free flaps served as controls and were assessed (refill, flap temperature, and color) by clinical monitoring (CM).Results12 flaps monitored by MD showed abnormal metabolism and underwent revision. Eight flaps were saved and four were lost within the first 5 days postoperatively. In addition, two flaps were lost at days 15 and 30 postoperatively, without previous complications. Four flaps assessed by CM developed complications, underwent revision, and were saved. In addition, five flaps were lost between the 8th and 23rd days postoperatively, without revision, due to missing previous clinical signs.ConclusionPostoperative monitoring of free flaps using a microdialysis decision algorithm allows early diagnosis of anastomotic complications. It is a clinically feasible and sensitive monitoring method for microvascular flaps, allowing surgical revision to be undertaken before clinical alteration takes place.     

Effects of herbal medicinal products and food supplements on induction of CYP1A2, CYP3A4 and MDR1 in the human colon carcinoma cell line LS180

A selection of popular herbal medicinal products and food supplements were analysed for their potential to modulate the expression of the cytochrome P450 enzymes CYP1A2 and CYP3A4 and the transporter protein MDR1. A total of 31 products were analysed. Nine of the products have been approved by the Medical Products Agency (MPA) in Sweden and are marketed as herbal medicinal products. Twenty-two of the products have not been assessed by the MPA and are marketed as food supplements. LS180 cells were exposed to extracts from the different herbal products and real-time quantitative polymerase chain reaction, RT-QPCR, was subsequently used to analyse the relative mRNA levels of CYP1A2, CYP3A4 or MDR1 in treated and non-treated cells. Our results show that 17 of 31 products tested induced a two-fold expression or more for at least one of the genes analysed. Four products, of which a ginger-supplement was the most potent, induced all three genes.     

Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells)

We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers.     

Microscopic measurement of inflammation in synovial tissue: inter-observer agreement for manual quantitative, semiquantitative and computerised digital image analysis

Objectives

To evaluate inter‐observer agreement for microscopic measurement of inflammation in synovial tissue using manual quantitative, semiquantitative and computerised digital image analysis.

Methods

Paired serial sections of synovial tissue, obtained at arthroscopic biopsy of the knee from patients with rheumatoid arthritis (RA), were stained immunohistochemically for T lymphocyte (CD3) and macrophage (CD68) markers. Manual quantitative and semiquantitative scores for sub‐lining layer CD3+ and CD68+ cell infiltration were independently derived in 6 international centres. Three centres derived scores using computerised digital image analysis. Inter‐observer agreement was evaluated using Spearman''s Rho and intraclass correlation coefficients (ICCs).

Results

Paired tissue sections from 12 patients were selected for evaluation. Satisfactory inter‐observer agreement was demonstrated for all 3 methods of analysis. Using manual methods, ICCs for measurement of CD3+ and CD68+ cell infiltration were 0.73 and 0.73 for quantitative analysis and 0.83 and 0.78 for semiquantitative analysis, respectively. Corresponding ICCs of 0.79 and 0.58 were observed for the use of digital image analysis. All ICCs were significant at levels of p<0.0001. At each participating centre, use of computerised image analysis produced results that correlated strongly and significantly with those obtained using manual measurement.

Conclusion

Strong inter‐observer agreement was demonstrated for microscopic measurement of synovial inflammation in RA using manual quantitative, semiquantitative and computerised digital methods of analysis. This further supports the development of these methods as outcome measures in RA.Microscopic measurement of inflammation in synovial tissue is employed globally by centres working in the field of arthritis research.¹ Adequate and comparable synovial tissue can be safely obtained using blind‐needle biopsy or rheumatological arthroscopy.^2,3,4 In the acquired samples, various parameters may be examined, including cell populations, vascularity, cytokines and adhesion molecules. In rheumatoid arthritis (RA), many of these have been found to relate to disease activity, severity, outcome, and to exhibit a change after treatment with corticosteroids, disease‐modifying antirheumatic drugs (DMARDs) and biological therapy.^{5,6,7,8,9,10,11,12,13,14,15}Several analysis techniques have been employed to measure these parameters. Semiquantitative analysis is a relatively quick method and therefore may facilitate examining large quantities of tissue.⁷ Quantitative analysis is time‐consuming but more sensitive than semiquantitative scoring to change in individual patients.¹⁶ It has been shown in previous studies that these methods can reflect overall joint inflammation when applied to relatively limited amounts of synovial tissue, even though inflammation may differ widely between individual sites in a single joint.^17,18,19 Computerised digital image analysis has been applied more recently in this area and has been shown to correlate well with conventional methods of measurement.^20,21,22This multi‐centre study was undertaken to standardise and validate the methods mentioned previously by evaluating inter‐observer agreement between multiple examiners in the measurement of selected parameters of inflammation in RA synovial tissue by manual quantitative, semiquantitative and computerised image analysis.     

No Increase of Plasma Malondialdehyde after Primary Coronary Angioplasty for Acute Myocardial Infarction

Objective : Free radicals formed after coronary artery occlusion and reperfusion are assumed to produce myocardial stunning and possibly other forms of reperfusion injury as well. Malondialdehyde (MDA) is an end product in the lipid peroxidation chain reaction and is frequently used as a marker for free oxygen radical production. Increased levels of plasma MDA have been found following successful thrombolytic therapy. The aim of this study was to investigate whether plasma MDA levels also increase after successful primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). Design : In 23 patients with AMI, treated with primary PTCA, plasma MDA was analysed using a high-performance liquid chromatography method (HPLC). The results obtained with this method were compared with those obtained with a fluorimetric assay of thiobarbituric acid reactive substances (TBARS). This assay measures MDA but with a lower specificity. Results : We found a significant decrease of plasma MDA from baseline 0.99 to 0.87 µmol/l at 30 min and to 0.90 µmol/l at 90 min following the primary PTCA ( p = 0.048 and 0.014, respectively). No significant changes in TBARS method levels were observed. Conclusion : Instead of the expected increase in MDA following reperfusion we found a significant decrease. The results from measurements of MDA and TBARS were significantly incompatible. The results raise serious doubts as to the usefulness of increased plasma levels of MDA as a marker of oxidative stress caused by coronary reperfusion in patients treated with angioplasty.