Musculoskeletal injuries in terrorist attacks--a comparison between the injuries sustained and those related to motor vehicle accidents, based on a national registry database

Terror-related injuries are becoming more prevalent. The predominant mechanism of damage is related to blast effects. These include penetrating injury due to material in the explosives and blunt trauma due to objects falling after detonation. However, the more commonly encountered severe trauma in civilian centres is related to motor vehicle accidents. A comparison between the two, although problematic, might enhance the knowledge of orthopaedic traumatologists dealing with these injuries. Thus 1072 in-patients, treated in levels I and II centres in Israel for orthopaedic injuries due to terrorist attack from November 2000 to December 2003, were compared with 9714 similar in-patients injured in motor vehicle accidents (controls). Analysis included age, gender, severity of injuries, diagnoses, lengths of intensive care unit and hospital stay, operations and mortality. The victims of terrorist attack included significantly more young adults, males, severe associated injuries and operations, and increased lengths of stay and mortality. Prompt recognition and awareness of the unique character of terror-related injuries is required.     

Herniation of Part of the Breast Through a Congenital Defect of the Superficial Fascia of the Anterior Thoracic Wall

This report describes the management of a 28-year-old female patient who had herniation of part of her left breast through a defect in the superficial fascia of the anterior thoracic wall. Closure of the defect was associated with correction of the deformity. To the best of our knowledge, this is the first report describing such a lesion.     

Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats

Antagonists of the vanilloid receptor TRPV1 (transient receptor potential vanilloid type 1) have been reported to produce antihyperalgesic effects in animal models of pain. These antagonists, however, also caused concomitant hyperthermia in rodents, dogs, monkeys, and humans. Antagonist-induced hyperthermia was not observed in TRPV1 knockout mice, suggesting that the hyperthermic effect is exclusively mediated through TRPV1. Since antagonist-induced hyperthermia is considered a hurdle for developing TRPV1 antagonists as therapeutics, we investigated the possibility of eliminating hyperthermia while maintaining antihyperalgesia. Here, we report four potent and selective TRPV1 modulators with unique in vitro pharmacology profiles (profiles A through D) and their respective effects on body temperature. We found that profile C modulator, (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)acrylamide (AMG8562), blocks capsaicin activation of TRPV1, does not affect heat activation of TRPV1, potentiates pH 5 activation of TRPV1 in vitro, and does not cause hyperthermia in vivo in rats. We further profiled AMG8562 in an on-target (agonist) challenge model, rodent pain models, and tested for its side effects. We show that AMG8562 significantly blocks capsaicin-induced flinching behavior, produces statistically significant efficacy in complete Freund's adjuvant- and skin incision-induced thermal hyperalgesia, and acetic acid-induced writhing models, with no profound effects on locomotor activity. Based on the data shown here, we conclude that it is feasible to modulate TRPV1 in a manner that does not cause hyperthermia while maintaining efficacy in rodent pain models.     

Transforming growth factor-beta gene expression studies in nasal mucosal biopsies in naturally occurring allergic rhinitis

Introduction

Evidence has been provided of enhanced epithelial transforming growth factor-beta (TGF-β) immunoreactivity in allergic rhinitis, including correlation with intra-epithelial mast cell numbers, and the co-localisation of TGF-β receptors to mast cells, suggesting that the epithelial expression of TGF-β may represent an important biological process involved in either the recruitment or retention of mast cells within the epithelium in naturally occurring allergic rhinitis.

Patients and Methods

In order to extend the above findings, evaluation was undertaken in whole nasal biopsies from subjects with naturally occurring allergic rhinitis, of levels of TGF-β isotypes and receptors gene expression using real-time quantitative polymerase chain reaction (TaqMan RT-PCR), and the results compared to those for tumour necrosis factor-alpha (TNF-α), as a positive control. The study was also extended to evaluate gene expression for connective tissue growth factor (CTGF) and Smad proteins, as downstream markers of TGF-β bioactivity, in the same populations.

Results

There were no significant differences between the rhinitic and non-rhinitic groups in the expression of TGF-β isoforms or Smad-3, Smad-6 and Smad-7 proteins; however, there was increased gene expression for TGF-βRI and TGF-βRII along with CTGF in seasonal allergic rhinitis. TNF-α gene expression was also increased in seasonal allergic rhinitis, consistent with a more acute inflammatory response in this form of rhinitis.

Conclusions

This study advances our understanding of the role of TGF-β in the pathogenesis of the inflammatory response in allergic rhinitis.     

Efficacy of increasing the therapeutic index of irinotecan, plasma and tissue selenium concentrations is methylselenocysteine dose dependent

This study was designed to understand the basis for the efficacy of methylselenocysteine (MSC) in increasing the therapeutic index of irinotecan against human tumor xenografts. Nude mice bearing human head and neck squamous cells carcinoma xenografts (FaDu and A253) were treated orally with different doses of MSC and irinotecan. Plasma, tumor and normal tissue samples were collected at different times after MSC treatments and were analyzed for selenium (Se) concentration using electrothermal atomic absorption spectrophotometry. MSC is highly effective in modulating the therapeutic index of irinotecan. Enhanced irinotecan efficacy was greater in FaDu tumors (100% CR) than in A253 tumors (60% CR), and depended on MSC dose with a minimum effective dose of 0.01 mg/dx28. The highest plasma Se concentration was achieved 1h after a single dose and 28 d after daily treatments of MSC. The ability of FaDu tumors to retain Se was significantly better than A253 tumors, and the highest Se concentration in normal tissue was achieved in the liver. Peak plasma and tissue Se concentrations were functions of the dose and duration of MSC treatment. The MSC-dependent increase in Se level in normal tissues may contribute to the protective effect against irinotecan toxicity observed in those tissues. Intratumoral total Se concentration was not found to be predictive of the combination therapy response rates. There is a critical need to develop a method to measure the active metabolite of MSC, rather than total Se.     

Underreduced supracondylar fracture of the humerus in children: clinical significance at skeletal maturity

BACKGROUND: Although supracondylar fractures of the humerus in children are common, the literature is sparse regarding acceptable limits of reduction of these fractures in the sagittal plane. METHODS: We retrospectively reviewed 223 pediatric cases of supracondylar fractures of the elbow treated in our hospital between the years 1996 and 2000. RESULTS: In 30 patients, we found some degree of underreduction of the extension component of the fracture. Twenty-two of them were followed and evaluated at or close to skeletal maturity. The mean age at the time of fracture was 5.4 years, the mean follow-up was 8.2 years. Radiographic remodeling, range of elbow motion, and awareness of the patients to the functional limitation were evaluated. At final follow-up, 17 (77%) of the patients had radiographic abnormality of the humerocondylar angle (a difference of 5 degrees or more compared with the uninjured side). Eleven patients (50%) had limited elbow flexion, and 7 (31%) were aware of this deficit. Most of the underreductions occurred when reduction was attempted in the emergency department, when the angulation was not appreciated, and when the cast was applied without any reduction attempt. Patients who were left to heal with some degree of extension developed limited end-elbow flexion and were aware of it. Although only 3 patients felt minor subjective functional disability at the last follow-up, 10 patients had unsatisfactory results according to Flynn criteria for motion restriction. CONCLUSIONS: The treating surgeon must be aware of this possible outcome and be more demanding in the reduction of the extension component of the fracture. Otherwise, clinically significant limitation in elbow flexion may occur. Although the reduction of moderately displaced fractures may seem simple, it should be performed under general anesthesia and with radiographic control of reduction and pin placement.     

Brief Report: Judging Pain Intensity in Children with Autism Undergoing Venepuncture: The Influence of Facial Activity

The biasing effect of pain sensitivity information and the impact of facial activity on observers' judgements of pain intensity of children with autism were examined. Observers received information that pain experience in children with autism is either the same as, more intense than, or less intense than children without autism. After viewing six video clips of children with autism undergoing venepuncture, observers estimated pain intensity using a visual analogue scale. Facial activity as coded by Chambers et al. (Child Facial Action Coding System Revised Manual, 1996) had a significant impact on observers' estimates of pain intensity; pain sensitivity information did not. These results have important implications for the assessment and management of pain in children with autism.