Postoperative analgesia in children day surgery circumcision: Comparison of three methods

Objective: To compare three methods of postoperative analgesia in children who underwent day surgery circumcision. Methods: One hundred and eighty‐five boys who were admitted for day surgery circumcision were randomly allocated to one of three groups. Group 1 received caudal block, group 2 received dorsal penile nerve block and group 3 received a combination of rectal diclofenac and intravenous fentanyl (RD/IVFENT). Oral paracetamol was given to relieve postoperative pain; its requirement and postoperative complications were recorded. Results: There were no significant differences found among the three groups regarding post‐circumcision paracetamol requirements in the first 2 h and day of operation, and duration of analgesia. There was no increased wound bleeding and vomiting seen for group 3. Conclusion: RD/IVFENT is a useful alternative to caudal block and dorsal penile nerve block for providing post‐circumcision pain relief. Also, it is easier to administer and appears safe.     

Increased inducible nitric oxide synthase in lung carcinoma of smokers

BACKGROUND: Cigarette smoking is well known to play an important role in the development of lung cancer. Inducible nitric oxide synthase (iNOS) can either promote or inhibit cell proliferation and growth, which makes its role in the development of malignant tumors controversial. The relation between cigarette smoking and iNOS in human lung cancer is unknown. METHODS: The study examined the levels of iNOS/NO in nonsmall-cell lung cancer (NSCLC) tissues of smokers and nonsmokers and in NSCLC cells (NCI-H23) treated by 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen. RESULTS: The level of iNOS/NO was significantly higher in lung cancer tissues of smokers than that of nonsmokers. Unlike iNOS/NO, the activity of caspase-3 was reduced in the former compared with the latter. The expression of the cleaved caspase-3 was deceased in NCI-H23 cells treated with S-Nitroso-N-acetylpenicillamine (SNAP), an NO donor, whereas treatment with NG-methyl-L-arginine (NMA), an NO inhibitor, caused an increase in cleaved caspase-3. Consistent with the change in caspase-3, SNAP treatment inhibited cell death induced by UCN01, a potent cell death-inducer. NMA treatment greatly enhanced the sensitivity of the cells to UCN01. Further, the cells treated by NNK showed an increase in iNOS protein, accompanied by an elevation of cell proliferation. CONCLUSIONS: The study demonstrates that cigarette smoking promotes the level of iNOS/NO but suppresses the activity of caspase-3, which may lead to the proliferation and growth of lung cancer cells.     

Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: Identification of the interleukin‐7 signaling pathway in tissues with lymphoid neogenesis

Objective

In ∼25% of synovial tissues from rheumatoid arthritis (RA) patients, infiltrates of T cells, B cells, and follicular dendritic cells (FDCs) are spatially organized into structures resembling lymph nodes with germinal centers. The remainder of the tissues lack FDCs and show either a diffuse or an aggregated T cell and B cell infiltrate. To gain more insight into this specific disease process, we sought to identify the genes expressed in RA tissues with ectopic lymphoid structures.

Methods

Gene expression profiling of RA synovial tissues was determined by complementary DNA microarray analysis and quantitative real‐time polymerase chain reaction. The presence of lymphoid follicles and localization of interleukin‐7 (IL‐7) in synovial tissue sections was determined by immunofluorescence staining using specific antibodies.

Results

Findings of gene expression analysis confirmed previous reports that tissues with lymphoid structures showed elevated expression of CXCL13, CCL21, CCR7, and lymphotoxin α and β messenger RNA. In addition, the tissues also showed enhanced expression of the chemokines CXCL12 and CCL19 and the associated receptors CXCR4 and CXCR5, which are important for the attraction of T cells, B cells, and dendritic cells. Pathway analysis revealed increased expression of genes involved in JAK/STAT signaling, T cell– and B cell–specific pathways, Fcε receptor type I signaling in mast cells, and IL‐7 signal transduction in the tissues with ectopic lymphoid follicles, accompanied by increased expression of IL‐7 receptor α (IL‐7Rα)/IL‐2Rγ chains and IL‐7. Protein expression of IL‐7 in RA tissues was localized within fibroblast‐like synoviocytes, macrophages, and blood vessels and was colocalized with extracellular matrix structures around the B cell follicles.

Conclusion

Activation of the IL‐7 pathway may play an important role in lymphoid neogenesis, analogous to its role in the development of normal lymphoid tissue.

     

Fibroblast‐like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: Evidence of a link between an increased myofibroblast‐like phenotype and high‐inflammation synovitis

Objective

Given the heterogeneity of gene expression patterns and cellular distribution between rheumatoid arthritis (RA) synovial tissues, we sought to determine whether this variability was also reflected at the level of the fibroblast‐like synoviocyte (FLS) cultured from RA synovial tissues.

Methods

Gene expression profiles in FLS cultured from synovial tissues obtained from 19 RA patients were analyzed using complementary DNA microarrays and hierarchical cluster analysis. To validate the subclassification, we performed prediction analysis and principal components analysis. Genes that differed significantly in their expression between FLS cultures were selected using Statistical Analysis of Microarrays software. Real‐time quantitative polymerase chain reaction was performed to validate the microarray data. Immunocytochemistry was applied to study the expression of the genes of interest in FLS and synovial tissues.

Results

Hierarchical clustering identified 2 main groups of FLS characterized by distinctive gene expression profiles. FLS from high‐inflammation synovial tissues revealed increased expression of a transforming growth factor β/activin A–inducible gene profile that is characteristic of myofibroblasts, a cell type considered to be involved in wound healing, whereas increased production of growth factor (insulin‐like growth factor 2/insulin‐like growth factor binding protein 5) appeared to constitute a characteristic feature of FLS derived from low‐inflammation synovial tissues. The molecular feature that defines the myofibroblast‐like phenotype was reflected as an increased proportion of myofibroblast‐like cells in the heterogeneous FLS population. Myofibroblast‐like cells were also found upon immunohistochemical analysis of synovial tissue.

Conclusion

Our findings support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence of a possible link between the behavior of FLS and the inflammation status of RA synovium.

     

A randomized controlled trial with an anti‐CCL2 (anti–monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis

Objective

Chemokines such as CCL2/monocyte chemotactic protein 1 (MCP‐1) play a key role in leukocyte migration and are potential targets in the treatment of chronic inflammatory disorders. The objective of this study was to evaluate the effects of human anti–CCL2/MCP‐1 monoclonal antibody (ABN912) treatment in patients with rheumatoid arthritis (RA).

Methods

Patients with active RA were enrolled in a randomized, placebo‐controlled, dose‐escalation study of ABN912. Infusions were administered on day 1 and day 15. In the dose‐escalation phase, 4 cohorts of 8 patients each underwent serial arthroscopic biopsy of synovial tissue. Immunohistochemistry and digital image analysis were used to characterize biomarkers in synovial tissue. Laboratory evaluation included pharmacokinetic analysis and immunotypic studies of peripheral blood mononuclear cells. To assess the clinical effects of treatment with ABN912, an additional 21 patients were treated with the highest dose tolerated.

Results

The total study population comprised 45 patients: 33 patients received ABN912, and 12 patients received placebo. ABN912 treatment was well tolerated. Unexpectedly, there was a dose‐related increase in ABN912‐complexed total CCL2/MCP‐1 levels in peripheral blood, up to 2,000‐fold. There was no detectable clinical benefit of ABN912 compared with placebo, nor did treatment with the study drug result in a significant change in the levels of biomarkers in synovial tissue and peripheral blood.

Conclusion

ABN912 treatment did not result in clinical or immunohistologic improvement and may have been associated with worsening of RA in patients treated with the highest dose. The results might be related to the greatly increased level of total CCL2/MCP‐1 in serum that was observed following treatment with ABN912. This observation may be relevant for a variety of antibody‐based therapies.

     

Stimulated gastrointestinal hormone release and gallbladder contraction during continuous jejunal feeding in patients with pancreatic pseudocyst is inhibited by octreotide.

BACKGROUND: Continuous enteral feeding, the old-new therapeutic modality in the treatment of patients with acute pancreatitis and those with complications is considered to bypass the cephalic, the gastric, and (at least in part) the intestinal phase of pancreatic secretion. The aim of this study was to test the GI hormonal changes and gallbladder motility during CJF in patients with pancreatic pseudocysts following acute pancreatitis, with or without octreotide pretreatment. PATIENTS AND METHODS: In 15 patients with pancreatic pseudocysts, an 8-French (8F) nasojejunal catheter was positioned into the jejunum distal to the ligament of Treitz during duodenoscopy. On test d 1, blood samples were taken for CCK, gastrin, insulin-like immunoreactivity (IRI), glucagon, and glucose measurements prior to and at 20, 40, 60, and 120 min following jejunal saline infusion at a rate of 2 mL/min. The gallbladder volumes were determined simultaneously by ultrasonography. On test d 2, CJF (175 kcal/h) was started by the same route and at the same infusion rate. Analogous measurements were performed as indicated above. On test d 3, 100 microg of octreotide was administered subcutaneously and the previous procedure was repeated. The plasma level of CCK and glucagon and the serum levels of IRI and gastrin were determined by bioassay and radioimmunoassay (RIA), respectively. RESULTS: Significant changes in hormone levels were not observed during jejunal saline perfusion. However, the levels of CCK (5.7+/-0.9 pmol), gastrin (10.6+/-1.3 pmol/L), IRI (27.2+/-5.8 microIU/mL), glucagon (322.8+/-32.4 pg/mL), and glucose (5.8+/-1.0 mmol/L) were significantly increased at 20 min during CJF vs the saline controls (2.0+/-0.3 pmol, 6.8+/-1.1 pmol/L, 7.8+/-0.4 microIU/mL, 172.8+/-33.4 pg/mL, and 4.5+/-0.5 mmol/L, respectively) and remained elevated at 40, 60, and 120 min. Octreotide pretreatment eliminated the increases in CCK, gastrin, IRI, and glucagon levels observed during CJF alone. The significant decrease in gallbladder volume during CJF was also prevented by octreotide pretreatment. CONCLUSION: Continuous jejunal feeding (CJF) elicited significant increases in gastrointestinal (GI) regulatory hormone (cholecystokinin [CCK], gastrin, IRI, and glucagon) levels and evoked a consecutive gallbladder contraction. These biological responses are eliminated by octreotide pretreatment. Further clinical studies are needed to assess the eventual therapeutic effect of octreotide during CJF in patients with pancreatic pseudocyst.     

Dentists’ attitude to provision of care for people with learning disabilities in Udaipur,India

Scand J Caring Sci; 2013; 27; 57–62 Dentists’ attitude to provision of care for people with learning disabilities in Udaipur, India This study determines and compares the attitudes of dentists to the provision of care for people with learning disabilities according to gender, qualification, previous experience of treating patients with learning disabilities and work experience of dentists. A cross‐sectional study was conducted among 247 dentists (166 men and 81 women) using a pretested structured questionnaire. This questionnaire assessed the respondent’s attitude towards learning‐disabled patients in five categories: beliefs about treating them, their capabilities, discrimination against these patients, their social behaviour and quality of care to be received by these patients. The information on dentist’s gender, qualification, work experience and previous experience of treating patients with learning disabilities was also collected through questionnaire. The Student’s t‐test and anova test were used for statistical analysis. The mean attitude score was found to be 71.13 ± 8.97. A statistically significant difference was found in the mean attitude scores of dentists with work experience (p = 0.000). Study subjects with postgraduate qualification and previous experience of treating patients with learning disabilities had significantly greater mean attitude score than their counterparts (p = 0.000). The overall attitude of dentists towards provision of care for people with learning disabilities was favourable, which increased with higher qualification and past experience.