Fatigue in irritable bowel syndrome: characterization and putative role of leptin

OBJECTIVES: Fatigue has received little attention in the irritable bowel syndrome. Emerging evidence exists that leptin may be involved in the pathogenesis of fatigue in several conditions. We aimed to evaluate the occurrence of fatigue and its characteristics in irritable bowel syndrome and to analyze the relationship between fatigue and leptin. METHODS: We enrolled 51 consecutive irritable bowel syndrome patients and 22 healthy controls without fatigue. None of them were depressed. The Fatigue Impact Scale was used to evaluate fatigue. RESULTS: In all, 62.7% of irritable bowel syndrome patients verbally expressed fatigue and rated more than 4 on the visual analog scale. The total score of fatigue was significantly higher in irritable bowel syndrome than in controls. In irritable bowel syndrome patients, but not in controls, a significant association was found between the total score of fatigue and leptin and this association was more pronounced in 32 irritable bowel syndrome patients who verbally expressed fatigue (r=0.60; P=0.0003). In irritable bowel syndrome, leptin correlated with fatigue independently from age, sex, fat mass and body mass index. CONCLUSIONS: Our study shows that fatigue occurs in 62.7% of irritable bowel syndrome patients when systematically asked for. Fatigue influences all three domains of the Fatigue Impact Scale in irritable bowel syndrome, the most being the physical and the psychosocial domains. Fatigue is associated with circulating leptin levels independently from age, sex, fat mass and body mass index in irritable bowel syndrome. The metabolic sequence involved in the occurrence of fatigue remains to be determined.     

Gemcitabine combined with oxaliplatin is safe and effective in patients with previously untreated advanced pancreatic adenocarcinoma

AIM: The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1% with a 12.5% complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. CONCLUSION: These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patients with locally-advanced disease.     

Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver

Cold ischemia-warm reperfusion (CI-WR) injury of the liver is characterized by marked alterations of sinusoidal endothelial cells (SECs), whereas hepatocytes appear to be relatively unscathed. However, the time course and mechanism of cell death remain controversial: early versus late phenomenon, necrosis versus apoptosis? We describe the occurrence and nature of cell death after different periods of CI with University of Wisconsin (UW) solution and after different periods of WR in the isolated perfused rat liver model. After 24- and 42-hour CI (viable and nonviable livers, respectively), similar patterns of liver cell death were seen: SEC necrosis appeared early after WR (10 minutes) and remained stable for up to 120 minutes. After 30 minutes of WR, apoptosis increased progressively with WR length. Based on morphological criteria, apoptotic cells were mainly hepatocytes within liver plates or extruded in the sinusoidal lumen. In addition, only after 42-hour CI were large clusters of necrotic hepatocytes found in areas of congested sinusoids. In these same livers, the hepatic microcirculation, evaluated by means of the multiple-indicator dilution technique, revealed extracellular matrix disappearance with no-flow areas. In conclusion, different time courses and mechanisms of cell death occur in rat livers after CI-WR, with early SEC necrosis followed by delayed hepatocyte apoptosis. These processes do not appear to be of major importance in the mechanism of graft failure because they are similar under both nonlethal and lethal conditions; this is not the case for the loss of the extracellular matrix found only under lethal conditions and associated with hepatocyte necrosis.     

In vivo thorax 3D modelling from costovertebral joint complex kinematics

Background

The costovertebral joint complex is mechanically involved in both respiratory function and thoracic spine stability. The thorax has been studied for a long time to understand its involvement in the physiological mechanism leading to specific gas exchange. Few studies have focused on costovertebral joint complex kinematics, and most of them focused on experimental in vitro analysis related to loading tests or global thorax and/or lung volume change analysis. There is however a clinical need for new methods allowing to process in vivo clinical data. This paper presents results from in vivo analysis of the costovertebral joint complex kinematics from clinically-available retrospective data.

Methods

In this study, in vivo spiral computed tomography imaging data were obtained from 8 asymptomatic subjects at three different lung volumes (from total lung capacity to functional residual capacity) calibrated using a classical spirometer. Fusion methods including 3D modelling and kinematic analysis were used to provide 3D costovertebral joint complex visualization for the true ribs (i.e., first seven pairs of ribs).

Findings

The 3D models of the first seven pairs of costovertebral joint complexes were obtained. A continuous kinematics simulation was interpolated from the three discrete computerized tomography positions. Helical axis representation was also achieved.

Interpretation

Preliminary results show that the method leads to meaningful and relevant results for clinical and pedagogical applications. Research in progress compares data from a sample of healthy volunteers with data collected from patients with cystic fibrosis to obtain new insights about the costovertebral joint complex range of motion and helical axis assessment in different pathological conditions.     

Investigational drugs for treating agitation in persons with dementia

Introduction: Agitation is common and distressing in persons with dementia, but safe, effective treatments remain elusive. In this review, the authors describe investigational compounds in ongoing or recently completed clinical trials for this indication and provide an opinion on how they may meet current therapeutic needs.

Areas covered: Phase II and phase III clinical trials for agitation in persons with dementia were searched in US and EU clinical trial registries and in the medical literature for the period January 2013-February 2016

Expert opinion: The authors searches identified 24 recent clinical trials investigating new treatments for agitation in persons with dementia. Candidate drugs in phase III development included the antipsychotic brexpiprazole, the antidepressant citalopram, the novel compound AVP-786 (deuterated-dextromethorphan/quinidine combination) and the cannabinoid nabilone. Of the compounds in phase II clinical trials, ELND005 (scyllo-inositol) is intended to progress into phase III development, based on evidence from a subgroup analysis and biomarker data. After many years without an FDA/EMA (Food and Drug Administration/European Medicines Agency) approved medication to treat agitation in persons with dementia, we may see the arrival of the first approved drug in the near future.     

A weight-bearing, water-based exercise program for osteopenic women: Its impact on bone, functional fitness, and well-being

Objective: To evaluate the effects of a weight-bearing, waterbased, exercise program designed for women with low bone mass.Design: A test-retest cross-sectional, prospective study.Setting: Community-dwelling women from a Canadian city.Participants: Seventy-seven postmenopausal women, 50 to 70 years of age, with spinal or femoral bone density below the fracture threshold.Intervention: Subjects exercised in a pool with waist-high water for 60 minutes, 3 days a week, over a 12-month period. Forty minutes of each session were devoted to successive jumps and muscular exercises designed to promote bone accretion, strength, and endurance.Main Outcome Measures: Spinal and femoral bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, functional fitness (flexibility, coordination, agility, strength/endurance, and cardiorespiratory endurance) assessed with the American Alliance for Health, Physical Education, Recreation and Dance battery, and psychological states evaluated with Dupuy's General Well-Being Schedule.Results: Spinal BMD decreased significantly (p < .001), whereas there was no change in femoral neck BMD (p = .90). Four of the parameters chosen to assess functional fitness, namely, flexibility, agility, strength/endurance, and cardiorespiratory endurance, were affected positively by the exercise program (all p values <.001). Psychological well-being also improved significantly after participation in the exercise program (p < .001).Conclusion: The intervention was successful in improving the functional fitness and psychological well-being of the participants, despite a lack of effect on the skeletal system. Future studies are needed to identify water exercises that are safe yet exert enough stress on the bones to initiate a bone response.     

Comparative study of oral conditions in schoolchildren of Strasbourg, France, 1974–85

A representative sample of 1650 children randomly selected in the 6-15-yr-old schoolchild population of Strasbourg was examined by well-calibrated examiners. The prevalence of caries was determined with the DMFT, DMFS and dft indices using bitewing radiographs. Plaque, calculus and gingival indices were also determined. The results obtained were compared with the initial study of 1974 performed in Strasbourg using the same epidemiologic methods. Whereas no important variations were observed in caries prevalence of primary teeth, a significant reduction of caries activity was observed in DMFT and DMFS indices in all age groups. There was a reduction of these two indices of respectively 32% and 33% in the 12-yr-old children. The reduction was the most significant on approximal surface lesions. A statistically significant decrease of the calculus and gingival indices was also observed between 1974 and 1984. A less significant decrease was observed for the plaque index.     

Discussion of prevalence and management of discomfort when swallowing pills: orodispersible tablets expand treatment options in patients with depression

Many patients experience discomfort when trying to swallow tablets and capsules, but this issue is rarely discussed between patients and physicians. Discomfort when swallowing pills is common and arises due to the morphology of the oropharynx and esophagus, which are not well suited to swallowing rigid objects of small volume. Compliance with medication is poor in patients with chronic diseases such as depression. An inability or unwillingness to swallow medication can further reduce acceptance of and compliance with medication, which has an impact on effectiveness. Recognition that patient acceptance of prescribed medication is an important component of compliance has led to the development of pill-swallowing training programs and alternative formulations. Orodispersible tablets do not need to be taken with water and can be packaged discreetly in single doses. Orodispersible tablets have been shown to be effective in a number of therapy areas including depression.     

Adherence to guidelines by French psychiatrists in their real world of clinical practice

The treatment modalities of bipolar disorder and adherence to international guidelines recommendations in France were investigated. We conducted an observational survey among 210 French psychiatrists concerning their prescribing practice in bipolar disorder, and whether they use guidelines or not. Simple mania is mainly treated with valproate, whereas second-generation antipsychotics are preferred for delusional mania. Lithium is mostly used as second-line treatment by "young psychiatrists." Personal experience appears in the foreground (41% of psychiatrists) in the choice of therapy. Young psychiatrists refer more to guidelines (32% of responders) as compared with other psychiatrists. The main reason for the lack of use of guidelines is because they refer mostly to an Anglo-Saxon medical practice, which is considered different from the French practice. Guidelines for treatment of bipolar disorder are not frequently used. French psychiatrists' age and practice type are the most important variables correlated to the level of use of guidelines.