Accidentally embedded foreign bodies in the extremities

Objectives: To assess the problem of injuries to the limbs from accidentally embedded foreign bodies

Elucidation of the Mechanism by Which Catecholamine Stress Hormones Liberate Iron from the Innate Immune Defense Proteins Transferrin and Lactoferrin ▿

The ability of catecholamine stress hormones and inotropes to stimulate the growth of infectious bacteria is now well established. A major element of the growth induction process has been shown to involve the catecholamines binding to the high-affinity ferric-iron-binding proteins transferrin (Tf) and lactoferrin, which then enables bacterial acquisition of normally inaccessible sequestered host iron. The nature of the mechanism(s) by which the stress hormones perturb iron binding of these key innate immune defense proteins has not been fully elucidated. The present study employed electron paramagnetic resonance spectroscopy and chemical iron-binding analyses to demonstrate that catecholamine stress hormones form direct complexes with the ferric iron within transferrin and lactoferrin. Moreover, these complexes were shown to result in the reduction of Fe(III) to Fe(II) and the loss of protein-complexed iron. The use of bacterial ferric iron uptake mutants further showed that both the Fe(II) and Fe(III) released from the Tf could be directly used as bacterial nutrient sources. We also analyzed the transferrin-catecholamine interactions in human serum and found that therapeutically relevant concentrations of stress hormones and inotropes could directly affect the iron binding of serum-transferrin so that the normally highly bacteriostatic tissue fluid became significantly more supportive of the growth of bacteria. The relevance of these catecholamine-transferrin/lactoferrin interactions to the infectious disease process is considered

Comparative Clinical Effectiveness of Management Strategies for Sciatica: Systematic Review and Network Meta-Analyses

Background There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. Purpose To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. Study design Systematic review and network meta-analysis. Methods: We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews, for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research (NIHR) HTA programme; there are no potential conflict of interests. Results Of 122 relevant studies, 90 were randomised controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, non-opioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy and exercise therapy were significantly inferior to epidural injections or surgery. For pain reduction as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, non-opioids, and opioids, or radiofrequency treatment. Opioids, education/advice alone, bed rest, and percutaneous discectomy and radiofrequency treatment were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. Conclusions For the first time many different treatment strategies for sciatica have been compared in the same systematic review and meta-analysis. This approach has provided new data to assist shared decision-making. The findings support the effectiveness of non-opioid medication, epidural injections and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments such as anti-inflammatory biological agents, may be considered. The findings do not support the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy or traction. The issue of how best to estimate the effectiveness of treatment approaches according to their order within a sequential treatment pathway remains an important challenge