Radiology of wrist and hand injuries in athletes

Traumatic injuries are a major cause of hand and wrist pain in athletes. Wrist injuries include fractures, dislocations, and instability patterns. Hand injuries include tendon injuries, ligamentous injuries, and fractures. In this article we have presented the radiographic appearance of the more common of these injuries.     

Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism

We investigated whether prostaglandin ethanolamides (prostamides) E(2), F(2alpha), and D(2) exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D(2), E(2), and F(2alpha) exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP(1-4), FP, IP, and TP prostanoid receptors. Prostamide F(2alpha) was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.     

Pharmacological characterization of a novel antiglaucoma agent,Bimatoprost (AGN 192024)

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.     

Criteria for choosing clinically effective glaucoma treatment: A discussion panel consensus

Abstract

Background:

In the clinical management of patients at risk for or diagnosed with primary open-angle glaucoma (POAG), the aim of medical treatment is to reduce intraocular pressure (IOP) and then maintain it over time at a level that preserves both the structure and function of the optic nerve.

Objective:

The objective of this report was to establish a consensus on the criteria that should be used to determine the characteristics of IOP-lowering medication.

Methods:

Discussion was held among a panel of 12 physicians considered to be experts in glaucoma to develop a consensus on the criteria used by them to determine the characteristics of the IOP-lowering medication chosen for initial monotherapy and adjunctive treatment of ocular hypertension (OHT) or POAG. Consensus development combined available evidence and the impressions of these physicians regarding the clinical effectiveness of IOP-lowering medication for OHT and POAG. Once the panel identified the criteria, the order of priority and the relative importance of these criteria were then established in the setting of 3 risk categories (low, medium, and high) for a patient to experience significant visual disability from glaucoma over their expected life span.

Results:

The panel identified 5 criteria to determine the characteristics of IOP-lowering medication for OHT and POAG: IOP-lowering effect, systemic adverse events (AEs), ocular tolerability, compliance/administration, and cost of treatment. IOP-lowering effect was consistently ranked as the highest priority and cost as the lowest. The priority of compliance/administration did not vary by clinical situation. Systemic AEs and ocular tolerability were ranked as higher priorities in initial monotherapy than in adjunctive treatment and ranked lower as the risk for visual disability increased. The priority given to the criteria used to determine clinical effectiveness varied both with the risk for functional vision loss from glaucoma and whether initial monotherapy or adjunctive treatment was being considered.

Conclusion:

Glaucoma treatment should be assessed with regard to the need not only to lower IOP but also to minimize systemic and ocular AEs, promote patient compliance, and minimize cost. The order of priority and relative importance given to these treatment criteria will vary as part of individualizing patient care.Key Words: consensus, criteria, intraocular pressure, glaucoma     

Penetrating Missile Injuries During the Iraqi Insurgency

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.     

Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.