Effect of food intake on commonly used pulsed Doppler and tissue Doppler measurements

Objective: This study evaluates the effect of food intake on commonly used pulsed Doppler and tissue Doppler measurements. Methods: Twenty‐three healthy subjects aged 25.6 ± 4.5 years were investigated. A wide selection of pulsed Doppler and tissue Doppler variables were measured before a standardized meal as well as and 30 and 110 minutes afterwards. Results: The following variables increased significantly (P < 0.05) 30 minutes after food intake: left ventricular stroke volume, left ventricular cardiac output, left ventricular outflow velocity–time integral, peak of early diastolic (E) and late diastolic (A) mitral flow velocities, pulmonary vein peak velocities in systole (S) and in diastole (D), S/D, pulsed tissue Doppler peak systolic velocities, and late diastolic velocities. Deceleration time of E‐wave decreased significantly (P < 0.05). The change in measured variables between fasting and 30 minutes after the food intake ranged from 7% to 28%. There were no significant (P > 0.05) changes in E/A, early diastolic tissue Doppler velocities (e’), and E/e’. Most, but not all variables returned to baseline values 110 minutes after food intake. Conclusions: This study shows that food intake affects several echocardiographic variables used to routinely assess diastolic function and hemodynamics. Further studies are warranted in older healthy subjects and in patients with various cardiac diseases to determine whether the findings are reproducible in such populations. (Echocardiography 2011;28:843‐847)     

Bone disease from monoclonal gammopathy of undetermined significance to multiple myeloma: pathogenesis, interventions, and future opportunities

Manifestations of bone disease-osteopenia, osteolytic lesions, and fractures-are the hallmark of multiple myeloma (MM) and occur clinically in the vast majority of patients. These abnormalities can have devastating clinical effects by increasing both the morbidity and mortality of patients. Bone disease is usually found when patients are diagnosed with active MM; however, recent data suggest that it is present in early myelomagenesis, including patients with myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS). The primary mechanisms of abnormal bone remodeling are increased osteoclastic activity, which occurs in close proximity to active myeloma cells, and decreased activity of the surrounding osteoblasts. Better understanding of the pathogenesis of bone disease in MM will allow us to enhance our current therapeutic options in the treatment of bone disease. In patients with active MM and at least one lytic lesion, intravenous bisphosphonates have been shown to decrease skeletal-related events and pain, improve performance status, and maintain quality of life. Emerging evidence suggests that intervention at earlier stages of disease may prevent skeletal-related events at time of progression, but there is no evidence that bisphosphonates in this setting change the natural history of the disease.     

Hypercoagulability in multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance

Patients with multiple myeloma are at an increased risk of venous thromboembolism (VTE), especially when treated with the immunomodulatory drugs, thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy. Several studies have shown that patients with multiple myeloma precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) also have a higher risk of thrombosis compared to the general population. The underlying mechanisms for the hypercoagulable state are not completely understood. In this review, we discuss risk factors for thrombosis in multiple myeloma, as well as prophylactic strategies, the evidence for thrombosis among patients with MGUS, and proposed mechanisms for the hypercoagulability.     

European Palliative Care Research Collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review

According to a Cochrane review on opioid switching, sound evidence on the practice of substituting one strong opioid with another to improve pain control and reduce adverse effects was lacking in 2004. A systematic search strategy was developed to include studies after 2004, with adult cancer patients switching between strong opioids and reporting estimates of effect on pain and adverse effects. The search retrieved 288 publications (71 duplicates); 187 abstracts and 19 full papers were excluded. Eleven papers met the inclusion criteria; none were randomized controlled trials/meta-analyses. Studies comprised 280 patients (group size 10-32). A variety of opioids and switching strategies were studied. Pain intensity was significantly reduced in the majority of studies. Serious adverse effects were improved. Due to serious design limitations, the level of evidence was low (D). Randomized trials, with standardization of cohort classification, use of outcomes and analysis are warranted to establish the practice of opioid switching.     

A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: results from two randomized, parallel-group, placebo-controlled trials

BACKGROUND. Non-steroidal anti-inflammatory drugs are associated with poor upper gastrointestinal (UGI) tolerability and increased ulcer risk, but patient adherence to gastroprotective co-therapy is frequently inadequate. A fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg was evaluated: efficacy is reported by Hochberg et al. (Curr Med Res Opin 2011;27:1243-53); tolerability findings are reported here. PATIENTS AND METHODS. In two 12-week double-blind, placebo-controlled, multicenter, phase III studies (PN400-307 and PN400-309), patients aged ≥ 50 years with symptomatic knee osteoarthritis randomly (2:2:1) received naproxen/esomeprazole magnesium BID, celecoxib 200 mg QD, or placebo. Tolerability end-points included: modified Severity of Dyspepsia Assessment (mSODA); heartburn severity; and UGI adverse events (AEs). RESULTS. Overall, 619 (PN400-307) and 615 (PN400-309) patients were randomized; mSODA scores improved (baseline to week 12) in each group, with no significant treatment differences between naproxen/esomeprazole magnesium and celecoxib (95% CIs: PN400-307: -0.4, 1.9; PN400-309: -1.8, 0.6). Naproxen/esomeprazole magnesium-treated patients reported significantly more heartburn-free days versus celecoxib (95% CIs: PN400-307: 2.1, 12.7; PN400-309: 2.5, 13.4). UGI AE incidence (PN400-307: 17.3%; PN400-309: 20.3%) was similar between treatment groups. UGI AEs resulted in few discontinuations (< 4%, either study). CONCLUSIONS. Naproxen/esomeprazole magnesium has comparable UGI tolerability to celecoxib in patients with osteoarthritis.     

Characteristics of recurrent musculoskeletal pain in children with cerebral palsy aged 8 to 18 years

Aim The aim of this study was to explore the prevalence, predictors, severity, and impact of recurrent musculoskeletal pain in children and adolescents with cerebral palsy (CP). Method One hundred and fifty‐three participants (81 males, 72 females) aged 8 to 18 years were assessed by clinical examination, interview, and questionnaires. CP type distribution was 38% unilateral spastic, 55% bilateral spastic, 6% dyskinetic, and 1% ataxic. Gross Motor Function Classification System (GMFCS) levels were as follows: level I, 54; level II, 56; level III, 20; level IV, 8; and level V, 15. Sixty‐four children and 89 parents recorded pain on the Child Health Questionnaire, 56 children and 85 parents indicated impact of pain on 0 to 10 numeric rating scales, and 72 children indicated pain intensity on the Faces Pain Scale‐Revised. Results Ninety‐five (62%) children across all GMFCS levels experienced recurrent musculoskeletal pain. Age above 14 years was the only significant predictor (OR 2.90, 95% CI 1.22–7.80, p=0.02, adjusted for sex, CP type, gross motor function and mother’s education). Children reported recurrent musculoskeletal pain to be moderate. Parents reported pain to be more severe and with higher impact on sleep than their children did. Children and parents reported similar impact of pain on general activity and walking. Interpretation Recurrent musculoskeletal pain is the dominating pain problem in children and adolescents with CP. Monitoring of musculoskeletal pain should be part of the medical follow‐up across the whole range of motor impairment.     

Noggin and Wnt3a enable BMP4-dependent differentiation of telencephalic stem cells into GluR-agonist responsive neurons

Early telencephalic development is dependent on the spatially and temporally coordinated regulation by essential signaling factors. For example, members of the Bone Morphogenetic Protein (BMP) family, such as BMP4, are crucial for proper development of dorsal telencephalic structures. Stimulation of multipotent telencephalic neural stem cells (NSCs) with BMP4 induces differentiation primarily into astrocytic and mesenchymal cells. However, BMP4-mediated mesenchymal differentiation is inhibited at certain culture conditions of NSCs, corresponding to in vivo developmental contexts. These inhibitory mechanisms are not fully understood and the terminal fate of non-astrocytic BMP4 treated NSCs under these conditions is unclear. Here we show that secreted factors inhibited BMP4-mediated mesenchymal differentiation of telencephalic NSCs. BMP4 mediated a dramatic and direct up-regulation of endogenous noggin levels, that in turn exerted a concentration-dependent inhibition of BMP4-mediated mesenchymal differentiation of NSCs. Instead, BMP4 exposure of NSCs induced neuronal differentiation in mesenchyme-preventing conditions, whereas treatment with recombinant noggin alone did not. Wnt signaling is known to be essential for the development of neurons derived from the dorsal telencephalon, and co-stimulation of NSCs with BMP4+Wnt3a resulted in a synergistic effect yielding significantly increased number of mature neurons compared to stimulation with each factor alone. Thus whereas only a subset of BMP4-induced neurons derived from telencephalic NSCs, responded to glutamate receptor (GluR) agonists, over 80% of BMP4+Wnt3a-induced neurons responded appropriately to GluR-agonists. Our results increase the understanding of the role for BMP4 in differentiation of telencephalic multipotent progenitors, and reveal novel implications for noggin and Wnt3a in these events.