Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.

AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) < 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission were at the time of this study, 8.1 years ± 2.6 years post-discontinuation of infliximab, P < 0.001. The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment duration of 12 mo (range 3.6 mo-32 mo) (P = 0.45 relative to those who lost remission). CONCLUSION: There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.

The effect of spinal manipulative therapy on spinal range of motion: a systematic literature review.

BACKGROUND: Spinal manipulative therapy (SMT) has been shown to have an effect on spine-related pain, both clinically and in experimentally induced pain. However, it is unclear if it has an immediate noticeable biomechanical effect on spinal motion that can be measured in terms of an increased range of motion (ROM). OBJECTIVE: To assess the quality of the literature and to determine whether or not SMT is associated with an immediate increase in ROM. DESIGN: A systematic critical literature review. METHOD: Systematic searches were performed in Pubmed, the Cochrane Library and EMBASE using terms relating to manipulation, movement and the spine. Selection of articles was made according to specific criteria by two independent reviewers. Two checklists were created based on the needs of the present review. Articles were independently reviewed by two reviewers. Articles were given quality scores and the data synthesized for each region treated in the literature. Findings were summarized in tables and reported in a narrative fashion. RESULTS: Fifteen articles were retained reporting on experiments on the neck, lumbar spine, hip and jaw. The mean quality score was 71/100 (ranges 33/100 - 92/100). A positive effect of SMT was reported in both studies where mouth opening was assessed after cervical manipulation. In five of the nine studies on cervical ROM a positive effect was reported, whereas the remaining four studies did not show improvement. None of the three studies of the lumbar spine showed an effect of SMT on lumbar ROMs and one study of sacroiliac manipulation reported no effect on the ROM of the hip joint.In relation to the quality score, the seven highest ranked studies, showed significant positive effects of SMT on ROM. Continuing down the list, the other studies reported no significant differences in the outcomes between groups. CONCLUSION: SMT seems sometimes to have a small effect on ROM, at least in the cervical spine. Further research should concentrate on areas of the spine that have the potential of actually improving to such a degree that a change can be easily uncovered.

The effect of spinal manipulative therapy on experimentally induced pain: a systematic literature review.

BACKGROUND: Although there is evidence that spinal manipulative therapy (SMT) can reduce pain, the mechanisms involved are not well established. There is a need to review the scientific literature to establish the evidence-base for the reduction of pain following SMT. OBJECTIVES: To determine if SMT can reduce experimentally induced pain, and if so, if the effect is i) only at the level of the treated spinal segment, ii) broader but in the same general region as SMT is performed, or iii) systemic. DESIGN: A systematic critical literature review. METHODS: A systematic search was performed for experimental studies on healthy volunteers and people without chronic syndromes, in which the immediate effect of SMT was tested. Articles selected were reviewed blindly by two authors. A summary quality score was calculated to indicate level of manuscript quality. Outcome was considered positive if the pain-reducing effect was statistically significant. Separate evidence tables were constructed with information relevant to each research question. Results were interpreted taking into account their manuscript quality. RESULTS: Twenty-two articles were included, describing 43 experiments, primarily on pain produced by pressure (n = 27) or temperature (n = 9). Their quality was generally moderate. A hypoalgesic effect was shown in 19/27 experiments on pressure pain, produced by pressure in 3/9 on pain produced by temperature and in 6/7 tests on pain induced by other measures. Second pain provoked by temperature seems to respond to SMT but not first pain. Most studies revealed a local or regional hypoalgesic effect whereas a systematic effect was unclear. Manipulation of a "restricted motion segment" ("manipulable lesion") seemed not to be essential to analgesia. In relation to outcome, there was no discernible difference between studies with higher vs. lower quality scores. CONCLUSIONS: These results indicate that SMT has a direct local/regional hypoalgesic effect on experimental pain for some types of stimuli. Further research is needed to determine i) if there is also a systemic effect, ii) the exact mechanisms by which SMT attenuates pain, and iii) whether this response is clinically significant.

A randomized trial of topical anesthesia comparing lidocaine versus lidocaine plus xylometazoline for unsedated transnasal upper gastrointestinal endoscopy.

BACKGROUND: The optimal topical anesthesia regimen for unsedated transnasal endoscopy is unknown. The addition of a nasal decongestant, such as xylometazoline (X), to a topical anesthestic may improve patient comfort. OBJECTIVE: To determine the effectiveness of lidocaine (L) versus L plus X (LX) for anesthesia in unsedated transnasal endoscopy. METHODS: Consecutive participants of the Aklavik Helicobacter pylori project were prospectively randomly assigned to receive LX or L for unsedated transnasal 4.9 mm ultrathin endoscopy. The primary outcome was overall procedure discomfort on a validated 10-point visual analogue scale (1 = no discomfort, 10 = severe discomfort). Secondary outcomes included pain, endoscope insertion difficulty, gagging, adverse events and encounter times. Results were presented as mean +/- SD, difference in mean, 95% CI. RESULTS: A total of 181 patients were randomly assigned to receive LX (n=94) and L (n=87). Baseline characteristics between the two groups were similar (mean age 40 years, 59% women). Overall, patient procedural discomfort with LX and L were 4.2+/-2.4 versus 3.9+/-2.1, respectively (0.29; 95% CI -0.39 to 0.96). Transnasal insertion difficulty was significantly lower with LX than with L (2.4+/-2.1 versus 3.2+/-2.8, respectively [-0.80; 95% CI -1.54 to -0.06]). Compared with L, the use of LX was associated with significantly less time needed to apply anesthesia (2.4+/-1.8 min versus 3.5+/-2.2 min, respectively [-1.10; 95% CI -1.71 min to -0.50 min]) and less time for insertion (3.2+/-1.8 min versus 3.9+/-2.2 min, respectively [-0.70 min; 95% CI -1.30 min to -0.10 min]). Epistaxis was rare but occurred less frequently with LX (1.1%) than with L (4.6%) (P=0.19). CONCLUSIONS: LX did not improve patient comfort for transnasal endoscopy compared with L alone. However, LX was associated with less difficulty with endoscope transnasal insertion and reduced insertion time. Further studies on the optimal regimen and dosing of anesthesia are required.

Early experience with unsedated ultrathin 4.9 mm transnasal gastroscopy: a pilot study.

BACKGROUND: Unsedated transnasal gastroscopy is a technique with unverified clinical advantages. OBJECTIVE: To evaluate the efficacy and procedure times with transnasal gastroscopy by physicians with no previous experience in transnasal endoscopy. METHODS: Unsedated transnasal gastroscopy using 4.9 mm ultrathin transnasal gastroscopes with randomization to two different biopsy forceps was prospectively evaluated during a single day in January 2008. The outcomes included patient tolerance (scale: 1, no discomfort; 10, severe discomfort), physician technical assessment (1, excellent; 10, very poor), gastric biopsy quality, adverse events and procedure times. RESULTS: Twenty patients underwent transnasal gastroscopy. Nineteen patients (95%) successfully completed transnasal gastroscopy. The patient-reported mean (+/- SD) overall discomfort level during the procedure was 4.0+/-1.9 compared with a physician-estimated level of 3.2+/-1.7 (P=0.04). Only 10% (n=2) reported they would have preferred sedated over unsedated gastroscopy. Mean total encounter time from anesthesia to discharge was 33.5+/-9.3 min. The time from anesthesia to insertion was 7.0+/-5.3 min and from room exit to discharge 6.2+/-2.9 min. No patients who had gastric biopsies taken (zero of 14) had any of unacceptable quality. The only adverse event was distressing sensations (dyspnea, dizziness) in one patient that started during pre-endoscopy anesthetic application, persisting postendoscopy, but without any abnormalities in vital signs. CONCLUSION: Assuming the adverse event was a rare reaction, early experience with unsedated ultrathin transnasal gastroscopy was an efficient, effective and well-tolerated procedure for evaluation of the upper gastrointestinal tract.

sociedad opresora. La transicion del positivismo al materialismo historico

Contiene: La sociedad atrasada - Corrientes sociologicas de transicion - Corrientes historicas, antropologicas y etnograficas - Doctrinas sociologicas factograficas - La direccion irracionalista. El Spenglerismo - Teoria anarquista de la sociedad - Aproximacion al materialismo historico.