Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans. METHODS: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints. RESULTS: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice. CONCLUSIONS: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.     

Physiotherapists in private practice in France

In France, most of the physiotherapists providing ambulatory care are in private practice: they are paid on a fee-for-service basis by the patients who are reimbursed by the Sickness Insurance Fund. A survey on a sample of 2000 (out of 40,000) private practitioners was undertaken in early 2004. As concerns their workload, only 4% think that it is "not sufficient" whereas 66% estimate it "certainly sufficient". Such a feature is noteworthy, as private practitioners are most often fearful of lack of work. In the coming years, one physiotherapist out of 10 envisages to increase his workload, whereas 27% are in favour of a reduction. Furthermore, the survey shows that more than one third of private physiotherapists plan to offer to patients services which are not listed in the contractual agreement document signed by their profession and the Sickness Insurance Fund. The trend is most noticeable among the young practitioners. As the feeling of medical doctors shortage is currently widespread in France, the public debates are focused on the issue of task delegation. After the survey, 54% private physiotherapists are in favour of task delegation, 24% have an opposite opinion and 22% do not express a clear-cut position. However, an in-depth analysis of the written answers to the question shows that a large majority do not accept to replace medical doctors for performing the tasks which are of a subordinate level, are not significant or are time-consuming (e.g. filling out the administrative forms). The question of vocabulary is fundamental in the matter. Moreover, a process of task delegation implies that certain tasks carried out by an overburdened profession are transferred to an other profession less heavily surcharged. Is it the case of French private physiotherapists whose two thirds declare that "their workload is certainly sufficient"?     

Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.     

Radiofrequency Ablation for Supraventricular Tachycardia in Children ≤15 kg Is Safe and Effective

Risks associated with radiofrequency ablation (RFA) have been reported to be increased in children ≤15 kg. We sought to compare the safety and efficacy of RFA in children <15 kg with those between 15.1 and 20 kg. Clinical, electrophysiologic, and RFA data for all patients ≤20 kg who underwent RFA for supraventricular tachycardia between January 1994 and January 2003 were reviewed. Patients were divided into those ≤15 kg (group 1, n = 25) and those between 15.1 and 20 kg (group 2, n = 44). The two groups differed significantly in age and weight by design (group 1: mean weight, 11.9 ± 3.0 kg; age, 2.8 ± 1.9 years; group 2: weight, 18.0 ± 1.5 kg; age, 5.1 ± 1.1 years). There were no significant differences in other baseline characteristics except for incidence of structural heart disease (28% group 1 vs 7% group 2, p < 0.01). No significant differences in mechanism of tachycardia, arrhythmia cycle length, number of total and brief RFA applications, total RFA time, average and maximum RFA temperatures, total procedure duration, short-term success rate (96% group 1 vs 86% group 2, p = 0.17), long-term success rate (91% group 1 vs 89% group 2, p = 0.76), or major complications (8.0% group 1 vs 2.3% group 2, p = 0.39) were found. There were no procedure-related deaths in either group. These data suggest that, in two large volume electrophysiology centers, the procedural risks and outcomes of RFA are similar between patients weighing less than 15 kg and those between 15.1 and 20 kg.     

Efficacy of contrast medium use for neuroimaging at 3.0 T: utility of IR-FSE compared to other T1-weighted pulse sequences

As inversion-recovery (IR) technique improves T1 contrast at high field strength, signal enhancement by T1-shortening contrast media may be affected. To clarify the different enhancement properties at 3.0 T, the authors compared T1-weighted sequences. Twelve contrast-enhancing lesions were investigated by spin-echo (SE), inversion recovery fast spin-echo (IR-FSE), two-dimensional gradient-echo (2D GE), and magnetization-prepared three-dimensional gradient-echo (3D GE) sequences and evaluated by comparing signal-intensity enhancements within the lesions. In addition, signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were measured. On average, signal enhancement of the lesions amounted to 60% for SE, 57% for IR-FSE, 32% for 2D GE, and 35% for 3D GE images. CNR of gray matter versus white matter was significantly higher for IR SE and GE imaging than for genuine SE and 2D GE acquisitions (Wilcoxon test), while 2D GE imaging alone had an excellent SNR. As IR-FSE images provide an excellent CNR for gray and white matter in the brain and contrast enhancement performs almost similarly well compared with SE imaging, this technique appears to be well suited for T1-weighted neuroimaging without and with contrast enhancement at 3.0 T. However, the inherent blurring of the IR-FSE can lead to poor performance for very small lesions.     

Risk of ventricular proarrhythmia with selective opening of the myocardial sarcolemmal versus mitochondrial ATP-gated potassium channel

Myocardial ATP-gated potassium channels (K-ATPs) are critical in the intracellular signaling cascade resulting in ischemic preconditioning (IP). Mitochondrial K-ATP channels seem to be responsible for IP, whereas the functions of K-ATP channels in the sarcolemmal membrane are less well understood. The proarrhythmic potential of specific versus nonspecific opening of K-ATP channels has not been investigated. In this study, Langendorff-perfused rabbit hearts were exposed to either pinacidil (1.25 microM), a nonselective K-ATP channel agonist, or selective mitochondrial or sarcolemmal K-ATP channel agonists or antagonists. The hearts were then subjected to 12 min of hypoxic perfusion and 40 min of reoxygenation. Hearts were monitored for the induction of ventricular fibrillation (VF). No heart subjected to hypoxia-reoxygenation without drug treatment developed VF (0 of 5). Pinacidil pretreatment induced VF (12 of 14; p = 0.004 versus control). Pinacidil's effect was blocked by HMR-1098 (1-[5-[2-(5-chloro-o-anisamide)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea) (1 microM), a selective sarcolemmal K-ATP channel antagonist (1 of 7; p = 0.007 versus pinacidil; N.S. versus control). Hearts pretreated with 5-hydroxydecanoate (5-HD) (100 microM), a putatively selective mitochondrial K-ATP channel blocker developed VF in one of eight trials (N.S. versus control). 5-HD did not alter the effects of pinacidil (6 of 8; p < 0.05 versus control; N.S. versus pinacidil alone). Selective mitochondrial K-ATP channel activation with [(3R)-trans-4-((4-chlorophenyl)-N-(1H-imidazol-2-ylmethyl)dimethyl-2H-1-benzopyran-6-carbonitril monohydrochloride] (BMS-191095) (6 microM) resulted in zero of five hearts developing VF (N.S. versus control). Our data suggest that selective opening of the sarcolemmal K-ATP channel during hypoxia-reoxygenation induced VF, whereas opening of the mitochondrial channel was not associated with VF. The findings suggest that caution should be exercised when developing compounds aimed at inducing IP, and nonspecific opening of the K-ATP channel should be avoided.     

Increased responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in newborns with atopic disposition

In previous studies, atopic patients showed attenuated cortisol responses to psychosocial stress which is suggestive of a hyporeactive hypothalamus-pituitary-adrenal (HPA) axis in this patient group. Regarding the anti-inflammatory role of glucocorticoids, reduced responsiveness of the HPA axis under stress may be one potential explanation of stress-induced exacerbation of atopic symptoms. The present study evaluated whether hyporeactivity of the HPA axis is a feature related to the disposition of atopy rather than a consequence of an ongoing chronic allergic inflammatory process. Newborns with an atopic disposition (parental atopy; n=31) and without atopic disposition (no parental atopy; n=20) were recruited. To further assess atopic disposition, total IgE levels were determined in the cord blood of the neonates. Three days after birth, a blood sample was obtained by a heel prick which is part of a standard pediatric examination. Blood sampling by heel prick is well known to be a significant stressor resulting in activation of the HPA axis in newborns. Analysis of salivary cortisol indicated a significant increase of cortisol levels in the newborns after the stressor with a trend towards an elevated cortisol response in babies with a family history of atopy or with elevated levels of cord IgE (> or = 0.5 kU/l). Neonates with a positive parental atopic heritage and elevated cord IgE were found to show significantly elevated cortisol responses to the heel prick stress when compared to newborns without a parental atopic history and normal cord IgE values. Moreover, cord IgE levels were significantly correlated with basal cortisol levels and the cortisol response to the stressor. These findings suggest that atopic disposition in neonates is associated with altered responsiveness of the HPA axis to stress which may increase the vulnerability to develop manifestation of atopy in later life.     

Helicobacter pylori eradication is beneficial in the treatment of functional dyspepsia

AIM: To assess whether the eradication of Helicobacter pylori leads to long-term relief of symptoms in functional dyspepsia. METHODS: Eight hundred patients with functional dyspepsia were randomized to receive double-blind treatment with twice-daily 30 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L30AC), twice-daily 15 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L15AC), or once-daily 15 mg lansoprazole for 14 days (LP). Dyspepsia and reflux symptoms were monitored for 12 months. RESULTS: In intention-to-treat analysis, the non-ulcer dyspepsia sum score showed a statistically significant benefit in terms of symptom relief in the L30AC group (P = 0.0068) compared with the LP group, but there was no significant difference between the L15AC and LP groups (P = 0.2). When all patients in the two eradication therapy arms were considered together, successful eradication had a significant benefit with regard to the complete absence of symptoms (P < 0.04). H. pylori eradication did not lead to an increase in reflux symptoms. CONCLUSION: This study suggests that H. pylori infection causes dyspeptic symptoms in a subset of patients with functional dyspepsia, and that these patients may obtain long-term symptomatic benefit following H. pylori eradication.     

Thoracic aortic stent graft: comparison of contrast-enhanced MR angiography and CT angiography in the follow-up: initial results

The objective of this study was to compare contrast-enhanced magnetic resonance angiography (CE MRA) and multislice computed tomographic angiography (MS CTA) in the follow-up of thoracic stent-graft placement. The CE MRA and MS CTA were performed following nitinol stent-graft treatment due to thoracic aneurysm (n=4), intramural bleeding (n=2) and type-B aortic dissection (n=5). Corresponding evaluation of arterial-phase imaging characteristics focused on the stent-graft morphology and leakage assessment. Stent-graft and aneurysm extensions were comparable between both techniques. Complete exclusion (aneurysm, n=4; dissection, n=2) was assessed with high confidence with CE MRA and MS CTA. Incomplete exclusion (intramural bleeding, n=2; dissection, n=3) was assigned to lower confidence scores on CE MRA compared with MS CTA. On CE MRA the stent-graft lumen demonstrated an inhomogeneous signal, the stent struts could not be assessed. The CE MRA can be used as alternative non-invasive imaging for follow-up of nitinol stent grafts. Arterial-phase leak assessment can be less evident in CE MRA compared with MS CTA studies; therefore, the use of late-phase imaging seems to be necessary. The diagnostic gap of stent-graft fracture evaluation using MRA may be filled with plain radiographs.