Long Term Effect

Introduction: While there is an increasing demand for minimally invasive operative techniques in Ear, Nose and Throat surgery, these operations are difficult to learn for junior doctors and demanding to supervise for experienced surgeons. The motivation for this study was to overcome ...

Most of the previous studies dealing with the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the synthesis of inflammatory mediators involved in joint damage have been done in cells culturedin vitro or in blood cells from patients treated for short periods of time. In this work we have evaluated the long-term effect of aceclofenac, a new NSAID, and diclofenac on the production of a series of inflammatory mediators by blood cells from 30 patients with severe knee osteoarthritis. Both aceclofenac and diclofenac significantly inhibited prostaglandin E2 (PGE2) synthesis by blood mononuclear and polymorphonuclear cells after 180 days of treatment. However, no clear effect was noted on leukotriene B4 (LTB4) and platelet activating factor (PAF) production. The generation of O 2− by polymorphonuclear cells, stimulated with FMLP, was decreased after 15 days of treatment with both drugs, but reached normal values after 180 days. Interleukin-1β (IL-1β) production decreased significantly at 180 days with both drugs in the group of high producer patients. In a few (n=3) patients with high basal mononuclear cell tumor necrosis factor α (TNFα) production, this also decreased on treatment for 180 days with the NSAIDs. In the remaining low TNFα-producing patients, TNFα production tended to increase. Interleukin-6 (IL-6) synthesis was not affected by aceclofenac while it was diminished by diclofenac. The decrease in IL-6 in all treated patients was significantly correlated with a worsening of the clinical condition. On the whole, these data could afford a pathogenetic basic for the long-term employment of these drugs in patients with inflammatory conditions.

To present a critical review and meta-analysis of studies evaluating the long-term effects of pulmonary rehabilitation in patients with asthma and chronic obstructive pulmonary disease (COPD). A database of articles published over the last 45 years, compiled by using medical subject heading key words pulmonary, obstructive, rehabilitation, and exercise. Articles not written in English, Dutch, or German and abstracts were excluded. Selected studies (1) evaluated the effects of pulmonary rehabilitation, (2) included patients with asthma or COPD older than 18 years, (3) evaluated outcome measures of exercise capacity or health related quality of life (HRQL), and (4) included a control condition lacking exercise training. Independent extraction by two reviewers. For each outcome, summary effects were computed by pooling standardized mean differences as well as raw mean differences. Significant improvements were found for all outcomes (p < .001). Sensitivity analyses for methodological quality of the selected studies did not change summary effect sizes. Effect sizes were significantly heterogeneous for the outcome endurance time (p < .0001). Pooling raw mean differences revealed overall effects in 6-minute walking distance (49+/-26 m) and all 4 dimensions of the chronic respiratory questionnaire (range, 0.5+/-0.3 to 0.8+/-0.3 points), indicating substantial improvements in these outcomes. Significant summary effect sizes were found up to 9 months after finishing rehabilitation for maximal exercise capacity (p < .003) and 6-minute walking distance (p < .005). Patients with asthma and COPD benefit from pulmonary rehabilitation.

AMP-activated protein kinase (AMPK) activation increases fatty acid oxidation in skeletal muscle by decreasing malonyl CoA concentrations. However, this may not explain the long-term effects of AMPK activation. Here we show that AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) increases mRNA expression of PPARalpha target genes and PGC-1 in cultured muscle cells and mouse skeletal muscle, and that inhibition of PPARalpha and PGC-1 by siRNAs prevents AICAR-stimulated increase in fatty acid oxidation. These data suggest that a novel transcriptional regulatory mechanism involving PPARalpha and PGC-1 exists that is responsible for long-term stimulation of fatty acid oxidation in skeletal muscle by AICAR.

The authors put forward a sales response model to explain the differences in immediate and dynamic effects of promotional prices and regular prices on sales. The model consists of a vector autoregression rewritten in error-correction format which allows to disentangle the immediate effects from the dynamic effects. In a second level of the model, the immediate price elasticities, the cumulative