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- Electroacupuncture regulates apoptosis/proliferation of intramuscular interstitial cells of cajal and restores colonic motility in diabetic constipation rats. [Journal Article]
- Evid Based Complement Alternat Med 2013.:584179.
Injury of interstitial cells of Cajal (ICC) is associated with gut dysmotility in diabetic rats. We have shown an acceleration of the colonic contractility by electroacupuncture stimulation (EAS). However, little is known about potential roles of EAS on colonic transit and ICC. In this study, we evaluate the effect of EAS on colonic transit and investigate whether apoptosis/proliferation of ICC was involved in regulative effect of EAS on colonic transit. Rats were randomly assigned to normal, diabetic, diabetic-plus-sham stimulation, diabetic-plus-low-frequency stimulation, and diabetic-plus-high-frequency stimulation groups. Bead expulsion test was used for measuring the distal colonic transit. The Kit (ICC marker) was detected by western blot. Apoptotic ICC was detected by terminal dUTP nucleotide end labeling. Proliferating ICC was identified by Kit/Ki67 double immunofluorescent staining on whole mount preparations. Ultrastructure changes of ICC were studied using electron microscopy. Results showed that high-frequency stimulation significantly promoted colonic transit. Low- and high-frequency stimulation markedly rescued intramuscular ICC from apoptosis. Abundant proliferating intramuscular ICC was found in low- and high-frequency stimulation groups. Our results indicate that high-frequency EAS has stimulatory effect on the distal colonic transit, which may be mediated by downregulation of the apoptosis and upregulation of the proliferation of intramuscular ICC.
- Management of faecal incontinence and constipation in adults with central neurological diseases. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2013 Dec 18.:CD002115.
People with central neurological disease or injury have a much higher risk of both faecal incontinence and constipation than the general population. There is often a fine line between the two symptoms, with any management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. This is an update of a Cochrane review first published in 2001 and subsequently updated in 2003 and 2006. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease.To determine the effects of management strategies for faecal incontinence and constipation in people with a neurological disease or injury affecting the central nervous system.We searched the Cochrane Incontinence Group Trials Register (searched 8 June 2012), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE In-Process as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles.Randomised and quasi-randomised trials evaluating any type of conservative or surgical intervention for the management of faecal incontinence and constipation in people with central neurological disease or injury were selected. Specific therapies for the treatment of neurological diseases that indirectly affect bowel dysfunction were also considered.Two review authors independently assessed the risk of bias of eligible trials and independently extracted data from the included trials using a range of pre-specified outcome measures.Twenty trials involving 902 people were included.Oral medicationsThere was evidence from individual small trials that people with Parkinson's disease had a statistically significant improvement in the number of bowel motions or successful bowel care routines per week when fibre (psyllium) (mean difference (MD) -2.2 bowel motions, 95% confidence interval (CI) -3.3 to -1.4) or oral laxative (isosmotic macrogol electrolyte solution) (MD 2.9 bowel motions per week, 95% CI 1.48 to 4.32) are used compared with placebo. One trial in people with spinal cord injury showed statistically significant improvement in total bowel care time comparing intramuscular neostigmine-glycopyrrolate (anticholinesterase plus an anticholinergic drug) with placebo (MD 23.3 minutes, 95% CI 4.68 to 41.92).Five studies reported the use of cisapride and tegaserod in people with spinal cord injuries or Parkinson's disease. These drugs have since been withdrawn from the market due to adverse effects; as they are no longer available they have been removed from this review.Rectal stimulantsOne small trial in people with spinal cord injuries compared two bisacodyl suppositories, one polyethylene glycol-based (PGB) and one hydrogenated vegetable oil-based (HVB). The trial found that the PGB bisacodyl suppository significantly reduced the mean defaecation period (PGB 20 minutes versus HVB 36 minutes, P < 0.03) and mean total time for bowel care (PGB 43 minutes versus HVB 74.5 minutes, P < 0.01) compared with the HVB bisacodyl suppository.Physical interventionsThere was evidence from one small trial with 31 participants that abdominal massage statistically improved the number of bowel motions in people who had a stroke compared with no massage (MD 1.7 bowel motions per week, 95% CI 2.22 to 1.18). A small feasibility trial including 30 individuals with multiple sclerosis also found evidence to support the use of abdominal massage. Constipation scores were statistically better with the abdominal massage during treatment although this was not supported by a change in outcome measures (for example the neurogenic bowel dysfunction score).One small trial in people with spinal cord injury showed statistically significant improvement in total bowel care time using electrical stimulation of abdominal muscles compared with no electrical stimulation (MD 29.3 minutes, 95% CI 7.35 to 51.25).There was evidence from one trial with a low risk of bias that for people with spinal cord injury transanal irrigation, compared against conservative bowel care, statistically improved constipation scores, neurogenic bowel dysfunction score, faecal incontinence score and total time for bowel care (MD 27.4 minutes, 95% CI 7.96 to 46.84). Patients were also more satisfied with this method.Other interventionsIn one trial in stroke patients, there appeared to be a short term benefit (less than six months) to patients in terms of the number of bowel motions per week with a one-off educational intervention from nurses (a structured nurse assessment leading to targeted education versus routine care), but this did not persist at 12 months. A trial in individuals with spinal cord injury found that a stepwise protocol did not reduce the need for oral laxatives and manual evacuation of stool.Finally, one further trial reported in abstract form showed that oral carbonated water (rather than tap water) improved constipation scores in people who had had a stroke.There is still remarkably little research on this common and, to patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other.There was very limited evidence from individual trials in favour of a bulk-forming laxative (psyllium), an isosmotic macrogol laxative, abdominal massage, electrical stimulation and an anticholinesterase-anticholinergic drug combination (neostigmine-glycopyrrolate) compared to no treatment or controls. There was also evidence in favour of transanal irrigation (compared to conservative management), oral carbonated (rather than tap) water and abdominal massage with lifestyle advice (compared to lifestyle advice alone). However, these findings need to be confirmed by larger well-designed controlled trials which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.
- Aripiprazole alone or in combination for acute mania. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2013 Dec 17.:CD005000.
Bipolar disorder is a mental disorder characterised by episodes of elevated or irritable mood (manic or hypomanic episodes) and episodes of low mood and loss of energy (depressive episodes). Drug treatment is the first-line treatment for acute mania with the initial aim of rapid control of agitation, aggression and dangerous behaviour. Aripiprazole, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines. The British Association of Psychopharmacology guidelines report that, in monotherapy placebo-controlled trials, the atypical antipsychotics, including aripiprazole, have been shown to be effective for acute manic or mixed episodes.To assess the efficacy and tolerability of aripiprazole alone or in combination with other antimanic drug treatments, compared with placebo and other drug treatments, in alleviating acute symptoms of manic or mixed episodes. Other objectives include reviewing the acceptability of treatment with aripiprazole, investigating the adverse effects of aripiprazole treatment, and determining overall mortality rates among those receiving aripiprazole treatment.The Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) was searched, all years to 31st July 2013. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We also searched Bristol-Myers Squibb clinical trials register, the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov (to August 2013).Randomised trials comparing aripiprazole versus placebo or other drugs in the treatment of acute manic or mixed episodes.Two review authors independently extracted data, including adverse effect data, from trial reports and assessed bias. The drug manufacturer or the trial authors were contacted for missing data.Ten studies (3340 participants) were included in the review. Seven studies compared aripiprazole monotherapy versus placebo (2239 participants); two of these included a third comparison arm-one study used lithium (485 participants) and the other used haloperidol (480 participants). Two studies compared aripiprazole as an adjunctive treatment to valproate or lithium versus placebo as an adjunctive treatment (754 participants), and one study compared aripiprazole versus haloperidol (347 participants). The overall risk of bias was unclear. A high dropout rate from most trials (> 20% for each intervention in eight of the trials) may have affected the estimates of relative efficacy. Evidence shows that aripiprazole was more effective than placebo in reducing manic symptoms in adults and children/adolescents at three and four weeks but not at six weeks (Young Mania Rating Scale (YMRS); mean difference (MD) at three weeks (random effects) -3.66, 95% confidence interval (CI) -5.82 to -2.05; six studies; N = 1819, moderate quality evidence) - a modest difference. Aripiprazole was compared with other drug treatments in three studies in adults-lithium was used in one study and haloperidol in two studies. No statistically significant differences between aripiprazole and other drug treatments in reducing manic symptoms were noted at three weeks (YMRS MD at three weeks (random effects) 0.07, 95% CI -1.24 to 1.37; three studies; N = 972, moderate quality evidence) or at any other time point up to and including 12 weeks. Compared with placebo, aripiprazole caused more movement disorders, as measured on the Simpson Angus Scale (SAS), on the Barnes Akathisia Scale (BAS) and by participant-reported akathisia (high quality evidence), with more people requiring treatment with anticholinergic medication (risk ratios (random effects) 3.28, 95% CI 1.82 to 5.91; two studies; N = 730, high quality evidence). Aripiprazole also led to more gastrointestinal disturbances (nausea (high quality evidence), and constipation) and caused more children/adolescents to have a prolactin level that fell below the lower limit of normal. Significant heterogeneity was present in the meta-analysis of movement disorders associated with aripiprazole and other treatments and was most likely due to the different side effect profiles of lithium and haloperidol. At the three-week time point, meta-analysis was not possible because of lack of data; however, at 12 weeks, haloperidol resulted in significantly more movement disorders than aripiprazole, as measured on the SAS, the BAS and the Abnormal Involuntary Movement Scale (AIMS) and by participant-reported akathisia. By 12 weeks, investigators reported no difference between aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant-reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; N = 313).Aripiprazole is an effective treatment for mania in a population that includes adults, children and adolescents, although its use leads to gastrointestinal disturbances and movement disorders. Comparative trials with medicines other than haloperidol and lithium are few, so the precise place of aripiprazole in therapy remains unclear.
- Activation of TREK-1 by morphine results in analgesia without adverse side effects. [Journal Article]
- Nat Commun 2013 Dec 17.:2941.
Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K(+) channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence-three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.
- Chronic Functional Constipation in Children: Adherence and Factors Associated to Drug Treatment. [JOURNAL ARTICLE]
- J Pediatr Gastroenterol Nutr 2013 Dec 16.
To evaluate the treatment adherence of children with chronic functional constipation.This is a prospective and longitudinal study realized at a pediatric gastroenterology clinic of a Brazilian University Hospital, between August 2009 and October 2011. Roma III criteria and Bristol Scale were used to define constipation and to characterize feces, respectively. Drug treatment was prescribed for patients according to the protocols previously standardized in the clinic. Specific questionnaires, containing questions related to one dependent variable and independent variables were completed in the first and sixth month of the treatment. Independent variables related to the patients, their caregivers, the disease itself and the therapeutic plan were analyzed and compared with the dependent variable (adherence to the treatment). Adherence was considered when the patient returned with more than 75% of the prescribed medicine containers empty.Fifty children participated in both the first and sixth months of treatment. The mean age of the sample was of 77.6 ± 43.8 months and the mean age of the symptoms onset was of 18.8 ± 27.9 months. The adherence rate was 38% in the first month and 30% in the sixth month. Patients who were treated with polyethylene glycol had greater adherence than patients who were prescribed other laxatives, with statistical significance in the second moment of the study (p = 0.19 and p = 0.04, respectively).The study showed low adherence rates to drug treatment of constipation in children. It is necessary to seek new strategies to increase treatment adherence, while avoiding complications and reducing costs.
- Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations from ESPGHAN and NASPGHAN. [JOURNAL ARTICLE]
- J Pediatr Gastroenterol Nutr 2013 Dec 16.
Constipation is a pediatric problem commonly encountered by many healthcare workers in primary, secondary and tertiary care. To assist medical care providers in the evaluation and management of children with functional constipation, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) were charged with the task of developing a uniform document of evidence-based guidelines.Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to October 2011 using Embase, Medline, The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials and PsychInfo databases. The approach of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the GRADE system. Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence-Based Medicine. During three consensus meetings all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no Randomized Controlled Trials (RCTs) were available to support the recommendation.This evidence-based guideline provides recommendations for evaluation and treatment of children with functional constipation in order to standardize and improve their quality of care. In addition, two algorithms were developed, one for infants less than six months of age and a second for older infants and children.This document is intended to be used in daily practice and as a basis for further clinical research. Large well-designed clinical trials are necessary with regards to diagnostic evaluation and treatment.
- Lubiprostone In Pediatric Functional Constipation. [JOURNAL ARTICLE]
- J Pediatr Gastroenterol Nutr 2013 Dec 16.
- Predictors of early postoperative pain after stapled haemorrhoidopexy. [JOURNAL ARTICLE]
- Colorectal Dis 2013 Dec 18.
Moderate to severe pain after stapled haemorrhoidopexy (SH) is not uncommon. This study was designed to identify the predictors of postoperative pain after SH in a single centre.Seventy-six patients with Grade II to IV haemorrhoids who underwent SH were selected from a prospectively compiled database. Preoperative data, including patient characteristics, manometry results, and surgical data, were documented. Pain was evaluated during the first 24h after the operation. Its intensity was classified into three grades according to the visual analogue scale (VAS) score: mild (VAS≤3), moderate (VAS>3 to <5) and severe (VAS≥5). Analgesics were not routinely given but were administrated if the patient had moderate or severe pain. Both univariate and multivariate analyses were used to determine the predictors of postoperative pain.Moderate and severe pain was noted in 43 (58.9%) patients. No patient was readmitted due to persistent anal pain during the one month following discharge. Postoperative pain was significantly associated with gender (p=0.017), age (p=0.014), first initial sensory volume (p=0.023) and constipation (p=0.005) in univariate analysis. Multivariate analysis identified male gender as an independent predictor of postoperative moderate to severe pain (p =0.037; OR=3.1; 95%CI, 1.07-9.09). The initial sensory volume and preoperative coexisting constipation were negative predictors of postoperative moderate to severe pain after SH (p=0.037; OR=0.320; 95% CI, 0.110-0.934 and p=0.036; OR=0.255; 95% CI, 0.071-0.913; respectively).Male gender and the initial sensory volume are predictors of postoperative pain after SH. Anal manometry is recommended before the SH procedure. An active analgesia protocol should be considered for male patients with a low initial sensory volume after SH. This article is protected by copyright. All rights reserved.
- Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome. [JOURNAL ARTICLE]
- Scand J Gastroenterol 2013 Dec 18.
Abstract Objective. Enteropathy is a very common feature in patients with primary immunodeficiencies. In patients with Del22 gastrointestinal (GI) alterations, including feeding disorders and congenital abnormalities have been often reported, mostly in the first year of life. Material and methods. Aim of this monocentric study is to better define the GI involvement in a cohort of 26 patients affected with Del22 syndrome. Anamnestic information was retrospectively collected for each patient. Weight and height parameters at the time of the screening were recorded. Plasma levels of hemoglobin, iron, ferritin, albumin, total protein, calcium, phosphorus, transaminase levels, antigliadin (AGA) IgA and IgG, and antitissue transglutaminase (anti-TGase) titers were measured. Results. A GI involvement was identified in the 58% of patients. The prominent problems were abdominal pain, vomiting, gastroesophageal reflux and chronic constipation. Weight deficiency, short stature and failure to thrive were reported in 54, 42, and 30% of the patients, respectively. The evidence of sideropenic anemia, in keeping with hypoproteinemia, impaired acid steatocrit or cellobiose/mannitol test suggested an abnormal intestinal permeability. In this cohort, a high prevalence of AGA IgA and IgG positivity was observed. Celiac disease (CD) was suspected in three patients, and in one of them confirmed by histology. In this patient, a long-lasting gluten-free diet failed to restore the intestinal architecture. Conclusions. In conclusion, GI involvement is a very common feature in Del22 patients. A better characterization of GI involvement would be very useful to improve the management of these patients.
- An international survey of practice patterns and difficulties in cancer pain management in Southeastern Europe: A Turkish & Balkan Oncology Group common initiative. [Journal Article]
- J BUON 2013 Oct-Dec; 18(4):1082-7.