Systematic reviews and meta-analyses on treatment of asthma: critical evaluation

ObjectiveTo evaluate the clinical, methodological, and reporting aspects of systematic reviews and meta-analyses on the treatment of asthma and to compare those published by the Cochrane Collaboration with those published in paper based journals.DesignAnalysis of studies identified from Medline, CINAHL, HealthSTAR, EMBASE, Cochrane Library, personal collections, and reference lists.StudiesArticles describing a systematic review or a meta-analysis of the treatment of asthma that were published as a full report, in any language or format, in a peer reviewed journal or the Cochrane Library.Results50 systematic reviews and meta-analyses were included. More than half were published in the past two years. Twelve reviews were published in the Cochrane Library and 38 were published in 22 peer reviewed journals. Forced expiratory volume in one second was the most frequently used outcome, but few reviews evaluated the effect of treatment on costs or patient preferences. Forty reviews were judged to have serious or extensive flaws. All six reviews associated with industry were in this group. Seven of the 10 most rigorous reviews were published in the Cochrane Library.ConclusionsMost reviews published in peer reviewed journals or funded by industry have serious methodological flaws that limit their value to guide decisions. Cochrane reviews are more rigorous and better reported than those published in peer reviewed journals.     

Inhibition of the synthesis of glycosphingolipid by a ceramide analogue (PPMP) in the gastrulation of Bufo arenarum

In the present study the role of glycosphingolipids (GSL) in amphibian development was investigated. We analysed the de novo synthesis of neutral GSL and gangliosides through the initial stages of Bufo arenarum embryo development and their participation during gastrulation using 1-phenyl-2-palmitoyl-3-morpholino-1-propanol (PPMP), a potent inhibitor of glucosylceramide synthase. Ganglioside synthesis began at the blastula stage and reached a maximum during gastrulation (stages 10-12) while neutral GSL synthesis showed a slight gradual increase, the former being quantitatively more significant than the latter. Ganglioside synthesis was reduced by 90% while neutral GSL synthesis was inhibited by 65% when embryos at blastula stage were cultured for 24 h in 20 microM PPMP. The depletion of GSL from amphibian embryos induced an abnormal gastrulation in a dose-dependent manner. We found that PPMP had a pronounced effect on development since no embryos exhibited normal gastrulation; their developmental rate either slowed down or, more often, became totally arrested. Morphological analysis of arrested embryos revealed inhibition of the gastrulation morphogenetic movements. Analysis of mesodermal cell morphology in those embryos showed a severe decrease in the number and complexity of cellular extensions such as filopodia and lamellipodia. Mesodermal cells isolated from PPMP-treated embryos had very low adhesion percentages. Our results suggest that glycosphingolipids participate in Bufo arenarum gastrulation, probably through their involvement in cell adhesion events.     

Synthesis of glycosyl(thio)ureido sugars via carbodiimides and their conformational behaviour in water

The preparation of sugar ureas and thioureas by nucleophilic addition of water or hydrogen sulfide, respectively, to sugar-derived carbodiimides has been examined. Acetic acid efficiently catalysed the formation of ureas, whereas silica gel was found to be a more convenient catalyst in the case of the thioxo analogues. The procedures have been exploited in the development of an amine- and isocyanate-free synthesis of urea- and thiourea-tethered pseudooligosaccharides via the corresponding glycosylcarbodiimido sugars. The fully unprotected compounds adopted, preferentially, the (Z,Z) configuration at the pseudoamide bonds in water solution.     

The Ideal Therapy Must Be Def ined in Each Geographical Area: Experience with a Quadruple Therapy in Spain

Background. Multiple therapeutic combinations have been tested to determine the optimal regimen(s) for Helicobacter pylori eradication, leading to very different results depending on the geographical area. Our goal was to evaluate the efficacy of a "quadruple" therapy with omeprazole, tetracycline, bismuth and metronidazole in our area.
Materials and Methods. We investigate 106 consecutive patients with active peptic ulcer disease (duodenal, gastric or both) and Helicobacter pylori infection. One-week therapy with omeprazole 20 mg b.i.d., tetracycline hydrochloride 500 mg q.i.d., colloidal bismuth subcitrate 120 mg q.i.d., and metronidazole 250 mg t.i.d was prescribed. Between the days 30 and 40 after treatment ended follow-up endoscopy was performed. Eradication was defined as both negative urease test and histology. Between days 90 and 360 a ¹³C urea breath test was performed in 100 patients.
Results. Of the 106 patients in the study, 91 had duodenal ulcer, 12 had gastric ulcer, and 3 had both. Side effects were observed in 25% of the cases. Eradication was achieved in 87.7% (93/106; CI 79.9–93.3). Healing was obtained in 95.2% (100/105; CI 89.2–98.4); 97.8% (CI 92.4–99.7) in those eradicated and 75% (CI 42.8–94.5) in non-eradicated ( p < .01).
Conclusions. Quadruple therapy with omeprazole, tetracycline, bismuth subcitrate and metronidazole achieves healing rates up to 95–100%. The 87.7% eradication rate obtained suggests that the regimen we used is a reasonable therapeutic alternative in our area.     

The significance of fire intensity in creating local patchiness in the Chilean matorral

The hypothesis that high and low intensity human-made fires can produce ecologically different effects in the Chilean matorral is examined. We compared the abundance of naturally established seedlings under shrubs burned by low and high intensity fires on five north and five south facing slopes. On south facing slopes, we found 54 shrubs burned by low intensity fires and only 4 shrubs burned by high intensity fires. In contrast, north facing slopes had approximately the same number of shrubs burned by low and high fire intensity fires (24 versus 19, respectively). We only found seedlings under shrubs burned by low intensity fires and most of them were of Muehlenbeckia hastulata and Trevoa trinervis. Also viable seeds were only found under shrubs burned by low intensity fires. Results indicate that fire intensity can be an important factor determining species distribution patterns in the matorral.