Staging canine patients with appendicular osteosarcoma utilizing fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography compared to whole body computed tomography.

Few studies have investigated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) for staging veterinary patients with appendicular osteosarcoma. The purpose of this study was to evaluate the efficacy of 18 F-FDG-PET/CT compared to whole-body CT (WBCT) for staging canine patients with appendicular osteosarcoma. The 18 F-FDG-PET/CT imaging studies of 66 dogs with appendicular osteosarcoma were anonymized and separated into two detached studies (one with whole body pre- and post-contrast CT images and the other with the whole body pre- and post-contrast CT images with the associated 18 F-FDG-PET overlay). Image assessment was performed retrospectively by five board-certified veterinary radiologists. The radiologists were instructed to assign a predefined categorical score (1-4) to each pre-designated anatomic region based on a devised lesional scoring system. A score of 1 was normal, 2 abnormal but not neoplastic, 3 abnormal and concerning for neoplasia, and 4 abnormal, most likely neoplastic. Overall, the likelihood of detection of '3 or 4' was found to be significantly higher with 18 F-FDG PET/CT when compared to WBCT after adjusting for the effect of evaluator and the subject. Most significantly, 13 osseous lesions concerning for metastasis (scored 3-4) were identified in 10/66 dogs by at least one reviewer on 18 F-FDG PET/CT, which were not identified by any reviewer on WBCT. Additionally, four comorbid neoplastic lesions were identified with 18 F-FDG PET/CT and not with WBCT. The results of this study suggest that 18 F-FDG PET/CT is more efficacious in detecting metastatic and comorbid neoplastic lesions compared to WBCT in dogs with appendicular osteosarcoma.

Associations Between Dust Storms and Intensive Care Unit Admissions in the United States, 2000-2015.

Anthropogenic climate change is influencing the incidence of dust storms and associated human exposure to coarse particulate matter (PM2.5-10) in the United States. Studies have found adverse health consequences related to dust exposure. These consequences include respiratory disease exacerbations and premature mortality, resulting in increased health care utilization. However, the impact of dust storms on critical care demand has not been studied in the United States. We seek to quantify the relationship between dust storms and surges in critical care demand by investigating the association between dust storms and intensive care unit (ICU) admissions at nearby hospitals from 2000 to 2015. ICU data were acquired from Premier, Inc. and encompass 15-20% of all ICU admissions in the United States. Dust storm, meteorology, and air pollutant data were downloaded from the U.S. National Weather Service, the U.S. National Climatic Data Center, and the U.S. Environmental Protection Agency websites, respectively. Associations between ICU admission and dust storms, controlling for temperature, dew point temperature, ambient PM2.5 and ozone, as well as seasonally varying confounders, were estimated using a distributed lag conditional Poisson model with overdispersion. We found a 4.8% (95% CI: 0.4, 9.4; p = 0.033) increase in total ICU admissions on the day of the dust storm (Lag 0) and a 9.2% (95% CI: 1.8, 17.0; p = 0.013) and 7.5% (95% CI: 0.3, 15.2; p = 0.040) increase in respiratory admissions at Lags 0 and 5. North American dust storms are associated with increases in same day and lagged demand for critical care services at nearby hospitals.

The application of the fast, multi-hit, pixel imaging mass spectrometry sensor to spatial imaging mass spectrometry.

Imaging mass spectrometry is a powerful technique that allows chemical information to be correlated to a spatial coordinate on a sample. By using stigmatic ion microscopy, in conjunction with fast cameras, multiple ion masses can be imaged within a single experimental cycle. This means that fewer laser shots and acquisition cycles are required to obtain a full data set, and samples suffer less degradation as overall collection time is reduced. We present the first spatial imaging mass spectrometry results obtained with a new time-stamping detector, named the pixel imaging mass spectrometry (PImMS) sensor. The sensor is capable of storing multiple time stamps in each pixel for each time-of-flight cycle, which gives it multi-mass imaging capabilities within each pixel. A standard velocity-map ion imaging apparatus was modified to allow for microscope mode spatial imaging of a large sample area (approximately 5 × 5 mm(2)). A variety of samples were imaged using PImMS and a conventional camera to determine the specifications and possible applications of the spectrometer and the PImMS camera.

Comparison of total, complexed and free prostate-specific antigens and their ratios in the detection of prostate cancer in a non-screened population.

BACKGROUND: The role of prostate-specific antigen (PSA) isoforms in the detection of prostate cancer in a non-screened population in the UK remains to be determined. METHODS: Consecutive patients undergoing diagnostic transrectal ultrasound-guided biopsy of the prostate were studied. Prior to biopsy, a blood sample was obtained and total, complexed and free PSA concentrations measured. RESULTS: Of the 171 patients included in the study, 103 were found to have prostate cancer. There were significant differences in total and complexed PSA concentrations and in the ratio of free-to-total PSA (all P <0.001) between patients with prostate cancer and those with benign disease. Receiver operating characteristics (ROC) curve analysis showed that the corresponding areas under the curves were similar. Restricting the analysis to the 77 patients who had total PSA concentrations between 2 and 10 micro g/L, ROC curve analysis showed that total and complexed PSA concentrations failed to discriminate between benign and malignant disease. In contrast, the areas under the ROC curve were greater for the free-to-total ratio (P = 0.033). CONCLUSION: These results show that in patients with total PSA concentrations between 2 and 10 micro g/L, the free-to-total PSA ratio was superior to total PSA concentration in discriminating between patients with benign and malignant disease.

Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus).

Native and recombinant human bone morphogenetic/osteogenic proteins (BMPs/ OPs) singly initiate bone induction in vivo. The finding of synchronous but spatially different BMPs/OPs expression during periodontal tissue morphogenesis suggests novel therapeutic approaches using morphogen combinations based on recapitulation of embryonic development. Twelve furcation defects prepared in the first and second mandibular molars of three adult baboons (Papio ursinus) were used to assess whether qualitative histological aspects of periodontal tissue regeneration could be enhanced and tissue morphogenesis modified by combined or single applications of recombinant hOP-1 and hBMP-2. Doses of BMPs/OPs were 100 microg of each protein per 1 g of insoluble collagenous bone matrix as carrier. Approximately 200 mg of carrier matrix was used per furcation defect. Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications. Combined applications of hOP-1 and hBMP-2 did not enhance alveolar bone regeneration or new attachment formation over and above the single applications of the morphogens. The results of this study, which is the first to attempt to address the structure-activity relationship amongst BMP/OP family members, indicate that tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, with hOP-1 inducing substantial cementogenesis. hBMP-2 treated defects, on the other hand, showed limited cementum formation but a temporal enhancement of alveolar bone regeneration and remodelling. The demonstration of therapeutic mosaicism in periodontal regeneration will require extensive testing of ratios and doses of recombinant morphogen combinations for optimal tissue engineering in clinical contexts.

Efficacy of prehospital critical care teams for severe blunt head injury in the Australian setting.

OBJECTIVE: To determine whether prehospital critical care teams (CCT) would result in improved functional outcomes for road trauma related severe head injury in the Australian setting, when compared with standard advanced life support measures provided by paramedics. METHODS: Retrospective review of 250 patients treated by paramedics and 46 patients treated by CCT transported directly from the accident scene, with a prehospital Glasgow coma scale (GCS)< or =8. RESULTS: CCT-treated patients had longer median prehospital times (113 versus 45 min, P<0.001), and a higher prehospital intubation rate (100% versus 36%, P<0.001) than paramedic-treated patients. On multivariate analysis, revised trauma score > or =4.45 (odds ratio [OR] 2.31, 95% CI: 1.15-4.65), lower injury severity score (OR 1.04, 95% CI: 1.02-1.06), age< or =25 years (OR 1.76, 95% CI: 1.13-2.75), absence of an acute subdural haematoma (OR 3.36, 95% CI: 1.89-5.95) and prehospital treatment by a CCT (OR 2.70, 95% CI: 1.48-4.95) independently predicted better outcome. CONCLUSION: The range of advanced interventions provided by the CCT were associated with improved functional outcome. Further studies are required to determine the individual factors responsible.

Bone induction by BMPs/OPs and related family members in primates.

BACKGROUND: In a series of studies in the primate Papio ursinus, we have examined the capacity of bone morphogenetic proteins (BMPs/OPs) delivered in a variety of biomaterial carrier systems to elicit bone formation in heterotopic and orthotopic sites. In this review, we compare the osteoinductive effects of different biomaterial delivery systems that have or have not been pretreated with BMPs/OPs. In particular, we focus on the geometric induction of bone formation by sintered porous hydroxyapatite (SPHA) discs with concavities on their planar surfaces, which elicit bone formation without exogenously applied BMPs/OPs. METHODS: Heterotopic bone formation was examined by bilaterally implanting 100-mg pellets of a collagenous carrier containing BMPs/OPs in the rectus abdominis muscle of the adult baboon. Orthotopic bone formation was examined by implanting 1 g of a collagenous carrier containing BMPs/OPs into two full-thickness critical-sized 25-mm-diameter defects on each side of the calvaria of adult baboons. The BMPs/OPs whose effects were examined included recombinant human osteogenic protein-1 (rhOP-1), recombinant human transforming growth factor-beta1 (rhTGF-beta1), rhTGF-beta2, and porcine platelet derived transforming growth factor-beta1 (pTGF-beta1). Tissue from the rectus abdominis muscle was harvested 30 or 90 days after implantation. Tissue from the orthotopic calvarial model was examined at 1, 3, 6, 9, and 12 months after implantation. To demonstrate the effect of surface geometry on bone induction, hydroxyapatite powders were sintered to form solid discs with a series of concavities on the planar surfaces of the SPHA discs. The discs were either pretreated with exogenous rhOP-1 or not treated with exogenous OP-1. They were then implanted heterotopically or orthotopically into calvarial defects. Bone formation was evaluated histologically in undecalcified sections stained with Goldner's trichrome stain or 0.1% toluidine blue. RESULTS: Naturally derived BMPs/OPs or rhOP-1 in a collagenous carrier elicit heterotopic bone formation and the complete healing of 25-mm-diameter critical-sized defects by day 90 following implantation. Binary applications of TGF-beta1 together with rhOP-1 in the collagen carrier induced massive endochondral ossicles in heterotopic sites and bone formation in calvarial defects. pTGF-beta1, rhTGF-beta1, and rhTGF-beta2 are powerful inducers of heterotopic endochondral bone formation but elicit limited bone formation in calvarial defects. SPHA discs pretreated with rhOP-1 elicited extensive bone formation in both heterotopic and orthotopic sites. However, SPHA without rhOP-1 also elicited bone formation in heterotopic and orthotopic sites and complete healing of the calvarial defects. CONCLUSION: We have prepared SPHA discs with concavities on their planar surfaces that induce bone formation in heterotopic or orthotopic critical-sized calvarial defects without exogenously applied BMPs/OPs. This biomaterial induces bone formation by intrinsic osteoinductivity regulated by the geometry of the substratum. The incorporation of specific biological activities into biomaterials by manipulating the geometry of the substratum, defined as geometric induction of bone formation, may make it possible to engineer morphogenetic responses for therapeutic osteogenesis in clinical contexts. CLINICAL RELEVANCE: We have implemented a clinical trial using naturally derived BMPs/OPs extracted and purified from bovine bone matrices and implanted in craniofacial defects in humans. In addition, the discovery that specific geometric and surface characteristics of sintered hydroxyapatites can induce intrinsic osteoinductivity in primates paves the way for formulation and therapeutic application of porous substrata designed to obtain predictable intrinsic osteoinductivity in clinical contexts.

A comparison of acute and postdischarge predictors of employment 2 years after traumatic brain injury.

OBJECTIVE: To examine whether adding postdischarge psychosocial predictors to premorbid and injury-related variables improved the capacity to predict employment 2 years after rehabilitation for traumatic brain injury (TBI). DESIGN: Data were collected prospectively at 6 and 24 months after discharge from rehabilitation. Logistic regression analyses examined predictors of employment status. SETTING: Inpatient and community TBI rehabilitation service attached to a major Australian teaching hospital. PARTICIPANTS: Fifty-five patients with TBI, aged 16 or older, who were consecutively admitted to a brain injury unit with complete longitudinal data and who agreed to participate in the study. INTERVENTION: Measured injury severity (Glasgow Coma Scale scores, posttraumatic amnesia); functional independence (Functional Assessment Measure cognitive subscale) at admission and discharge from rehabilitation; self-report of employment (premorbid, postdischarge); postdischarge psychosocial status at 6 months and 2 years (Community Integration Questionnaire, General Health Questionnaire, Trauma Complaints List, Overt Aggression Scale, Alcohol Use Disorders Inventory Test, Satisfaction with Life Scale). MAIN OUTCOME MEASURES: Employment status (employed, unemployed) was used to reflect vocational outcome. Predictor variables comprised premorbid work status, injury-related variables (age, injury severity), and postdischarge variables (employment, community integration, psychologic, cognitive status). RESULTS: Adding postdischarge predictors to premorbid and acute variables significantly improved the ability to predict work status 2 years after rehabilitation. Age at the time of injury, premorbid employment status, work status, and psychologic distress 6 months postdischarge were significant predictors of employment. CONCLUSIONS: It is important to consider postdischarge psychologic well-being, in conjunction with premorbid and acute factors, in vocational interventions after TBI.

Induction of bone formation by recombinant human osteogenic protein-1 and sintered porous hydroxyapatite in adult primates.

A critical issue in tissue engineering and morphogenesis of bone is the development of novel biomimetic biomaterials that are capable of optimizing the biological activity of recombinant human bone morphogenetic and osteogenic proteins, which are molecules that initiate bone formation in vivo. From a therapeutic perspective, a carrier matrix is required for the local delivery of these proteins to evoke a desired osteogenic effect. In view of the affinity of these proteins for hydroxyapatite, which may reflect the in vivo supramolecular assembly of bone proteins bound to both the extracellular matrix and the mineral component of bone, we investigated the efficacy of single applications of different doses of human osteogenic protein-1 (hOP-1) adsorbed onto sintered porous hydroxyapatites for bone induction in orthotopic calvarial defects in 12 adult male baboons (Papio ursinus) and heterotopically in the rectus abdominis of four additional baboons. In orthotopic specimens, pretreatment of sintered porous hydroxyapatites with 100 microgram of hOP-1 in 500 microliter of 5 mM hydrochloric acid resulted in rapid and diffuse osteoinduction restricted within the porous spaces of the hydroxyapatite, as evaluated by histology and histomorphometry on day 30. Hydroxyapatites treated with 500 microgram of hOP-1 showed a different pattern of bone formation and distribution on day 30 as compared with the lower dose of the recombinant morphogen. Although bone formation was extensive with the higher dose, it was found on the endocranial and pericranial aspects of the specimens, enveloping the implanted hydroxyapatite carrier, and the internal porous spaces were occupied by a rich vascular network without any bone formation. By 90 and 365 days after the implantation of both doses of hOP-1, however, there was remodelling and complete penetration of the newly induced bone within the available porous spaces. The combination of hOP-1 and hydroxyapatite also showed extensive bone formation in heterotopic specimens harvested from the rectus abdominis muscle of the baboon using doses of 5, 25, and 45 microgram of hOP-1 per implant. These findings in the adult primate demonstrate extensive bone formation by hOP-1 adsorbed onto sintered porous hydroxyapatites and suggest that predictable osteogenesis in clinical contexts for treatment of craniofacial bone defects may be engineered using inorganic, nonimmunogenic, and carvable delivery systems that initiate osteogenesis with relatively low doses of recombinant osteogenic proteins, thus mimicking the macrostructure and microstructure of living bone.

Posttraumatic stress disorder and psychosocial functioning after severe traumatic brain injury.

The aim of this study was to investigate the influence of posttraumatic stress disorder (PTSD) on rehabilitation after severe traumatic brain injury (TBI). Ninety-six patients with severe TBI patients were assessed 6 months after hospital discharge with the Posttraumatic Stress Disorder Interview, the Functional Assessment Measure (FAM), the Community Integration Questionnaire (CIQ), the Overt Aggression Scale (OAS), the General Health Questionnaire (GHQ), the Beck Depression Inventory (BDI), and the Satisfaction with Life Scale (SWL). PTSD was diagnosed in 27% of patients. Patients with PTSD reported higher scores on the GHQ and BDI, and lower scores on the FAM, CIQ, OAS, and SWLS than those without PTSD. Effective rehabilitation after severe TBI may be enhanced by management of PTSD.

Transforming growth factor-beta1 supports the rapid morphogenesis of heterotopic endochondral bone initiated by human osteogenic protein-1 via the synergistic upregulation of molecular markers.

Members of the transforming growth factor-beta (TGF-beta) superfamily of proteins, the bone morphogenetic proteins (BMPs) and the TGF-beta isoforms, are involved in the coordination of cartilage and bone differentiation both in embryonic development and in postnatal life. Both osteogenic protein-1 (OP-1) and TGF-beta1 have been shown to be potent regulators and inducers of heterotopic endochondral bone induction in non-human primates. In marked contrast, TGF-beta1 does not induce heterotopic endochondral bone in rodents. In the primate, the osteogenic properties of OP-1 are synergistically enhanced by the combined administration of TGF-beta1. The binary application of OP-1 (0.1, 0.3, 1.0 and 3.0 microg) and TGF-beta1 (0.01, 0.03 and 0.1 microg) to 25 mg of guanidinium-inactivated insoluble collagenous bone matrix as carrier in the rodent heterotopic bioassay for 7, 12 and 21 days resulted in a classical synergistic, dose-dependent and temporal up-regulation of OP-1-induced endochondral bone formation. There were significant increases in alkaline phosphatase activity (day 12) and calcium content (days 12 and 21). mRNA expression of OP-1, TGF-beta1, BMP-3 and collagens type II and IV, markers of bone formation, showed an up-regulation of the genes (days 12 and 21) by the binary applications of the morphogens. Histologically, single applications of OP-1 elicited a dose dependent induction of endochondral bone formation while the binary applications resulted in a temporal acceleration of the morphogenetic cascade. The optimal ratio of OP-1/TGF-beta1 was 30:1 by weight for endochondral bone formation and expression of molecular markers. The present data provides insights to the mechanisms of synergistic molecular therapeutics for endochondral bone formation in clinical contexts.

Long-term evaluation of bone formation by osteogenic protein 1 in the baboon and relative efficacy of bone-derived bone morphogenetic proteins delivered by irradiated xenogeneic collagenous matrices.

To investigate the long-term efficacy of irradiated recombinant human osteogenic protein 1 (hOP-1) in bone regeneration and morphogenesis, hOP-1 was combined with a bovine collagenous matrix carrier (0, 0.1, 0.5, and 2.5 mg hOP-1/g of matrix), sterilized with 2.5 Mrads of y-irradiation, and implanted in 80 calvarial defects in 20 adult baboons (Papio ursinus). The relative efficacy of partially purified bone-derived baboon bone morphogenetic proteins (BMPs), known to contain several osteogenic proteins, was compared with the recombinant hOP-1 device in an additional four baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 90 and day 365 showed that gamma-irradiated hOP-1 devices induced regeneration of the calvarial defects by day 90, although with reduced bone area compared with a previous published series of calvarial defects treated with nonirradiated hOP-1 devices. One year after application of the irradiated hOP-1 devices, bone and osteoid volumes and generated bone tissue areas were comparable with nonirradiated hOP-1 specimens. Moreover, 365 days after healing regenerates induced by 0.5 mg and 2.5 mg of irradiated hOP-1 devices showed greater amounts of bone and osteoid volumes when compared with those induced by nonirradiated hOP-1 devices. On day 90, defects treated with 0.1 mg and 0.5 mg of bone-derived baboon BMPs, combined with irradiated matrix, showed significantly less bone compared with defects receiving irradiated devices containing 0.1 mg and 0.5 mg hOP-1; 2.5 mg of partially purified BMPs induced bone and osteoid volumes comparable with the 0.1-mg and 0.5-mg hOP-1 devices. Control specimens of y-irradiated collagenous matrix without hOP-1 displayed a nearly 2-fold reduction in osteoconductive bone repair when compared with nonirradiated controls. These findings suggest that the reduction in bone volume and bone tissue area on day 90 may be caused by a reduced performance of the irradiated collagenous matrix substratum rather than to a reduction in the biological activity of the irradiated recombinant osteogenic protein. This is supported by the results of in vitro and in vivo studies performed to determine the structural integrity of the recovered gamma-irradiated hOP-1 before application in the baboon. Recoveries by high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate/ polyacrylamide gel electrophoresis (SDS/PAGE)/immunoblot analyses indicated that doses of 2.5-3 Mrads of gamma-irradiation did not significantly affect the structural integrity of the recovered hOP-1. Biological activity of the recovered hOP-1 was confirmed in vitro by showing induction of alkaline phosphatase activity in rat osteosarcoma cells (ROS) and in vivo by de novo endochondral bone formation in the subcutaneous space of the rat. These findings in the adult primate indicate that a single application of gamma-irradiated hOP-1 combined with the irradiated xenogeneic bovine collagenous matrix carrier is effective in regenerating and maintaining the architecture of the induced bone at doses of 0.5 mg/g and 2.5 mg/g of carrier matrix.

Are dedicated bladder films necessary as part of intravenous urography for haematuria?

OBJECTIVE: To determine the use and assess the value of full-bladder films during intravenous urography (IVU) which, despite the widespread availability of flexible cystoscopy, remain part of IVU in many radiology departments. Materials and methods A telephone survey of all Scottish radiology departments where IVU is regularly used showed that half routinely included a full-bladder film in the series. The reports of all IVU over 2 years in the authors' department were analysed retrospectively. The index urogram of all patients with bladder tumours confirmed during this period was reviewed independently by three observers, and together with the initial radiological reports was correlated with the cystoscopic and histological findings. RESULTS: From 2625 patients, 139 (5.2%) IVU reports commented on the bladder; 1423 patients presented with no haematuria. None of the patients without haematuria, where a comment was made about the bladder, had pathological evidence of a tumour. Overall 121 of 464 (26%) new bladder tumours were diagnosed on IVU before cystoscopy. Multiple tumours were always undetected and large tumours were often overlooked. CONCLUSIONS: Despite its continuing popularity, IVU is a poor means of identifying bladder tumours and routine views of the full bladder should be abandoned.

Induction of endochondral bone formation by recombinant human transforming growth factor-beta2 in the baboon (Papio ursinus).

Members of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic and osteogenic proteins (BMPs/OPs) but not the TGF-beta proteins themselves, induce endochondral bone formation in vivo, when implanted in extraskeletal heterotopic sites of rodents. Here we show that recombinant human TGF-beta2 (hTGF-beta2) induces endochondral bone formation 30 days after implantation in heterotopic intramuscular sites of the baboon (Papio ursinus) at doses of 1, 5 and 25 microg per 100 mg of guanidinium-inactivated collagenous bone matrix as carrier. On day 90 there was generation of large radiopaque and corticalized intramuscular ossicles. Five and 25 microg hTGF-beta2 induced large ossicles in the rectus abdominis of the primate as evaluated by key parameters of bone formation, including generated tissue area, mineralized bone and osteoid volumes, and tissue alkaline phosphatase activity. On day 30 and 90 after healing, hTGF-beta2 also induced bone formation when implanted in the rectus abdominis in conjunction with a sintered porous hydroxyapatite as carrier. mRNA expression in tissues from heterotopic specimens showed OP-1 (BMP-7) and BMP-3 transcripts in low abundance and with a linear dose-dependent increase both in collagenous matrix and hydroxyapatite samples. Type IV collagen mRNA expression, a marker of angiogenesis, was stronger in collagenous than hydroxyapatite samples. Growth and differentiation factor-10 (GDF-10) mRNA transcripts were expressed in ossicles with a distinctly chondrogenic phase, but its expression was greater in ossicles generated in porous hydroxyapatites, in which bone formation is not via a chondrogenic phase, but is rather intramembranous, without expression of type II collagen mRNA. In the same animals, however, 10 and 100 microg of the recombinant morphogen delivered by identical carriers (collagenous matrix and sintered hydroxyapatite) failed to heal calvarial defects. Thus in the primate, TGF-betas themselves are inducers of endochondral bone formation, although the present data strongly indicate that the bone inductive activity of hTGF-beta2 is site and tissue specific, since a single application of hTGF-beta2, or hTGF-beta1 in previously published experiments, did not induce bone in calvarial defects, but did induce endochondral bone differentiation in heterotopic sites.

Coping style and post-traumatic stress disorder following severe traumatic brain injury.

There is increasing evidence that a proportion of severe traumatically brain injured (TBI) patients do suffer post-traumatic stress disorder (PTSD). The aim of this study was to investigate the predictors of PTSD following severe TBI in a sample of 96 patients who sustained a severe TBI, of whom 27% satisfied diagnostic criteria for PTSD. The Post-traumatic Stress Disorder Interview, the Coping Style Questionnaire, and the Functional Assessment Measure was administered to these patients 6 months after hospital discharge. Avoidant coping style, behavioural coping style, and a history of prior unemployment were the significant predictors of PTSD severity. These findings indicate that reduction of PTSD and management of severe TBI may be facilitated by teaching patients more adaptive coping strategies.

Posttraumatic stress disorder after severe traumatic brain injury.

OBJECTIVE: This study indexed the profile of posttraumatic stress disorder (PTSD) after severe traumatic injury to the brain. METHOD: Patients who sustained a severe traumatic brain injury (N=96) were assessed for PTSD 6 months after the injury with the PTSD Interview, a structured clinical interview based on DSM-III-R criteria. RESULTS: PTSD was diagnosed in 26 (27.1%) of the patients. While only 19.2% (N=5) of the patients with PTSD reported intrusive memories of the trauma, 96.2% (N=25) reported emotional reactivity. Intrusive memories, nightmares, and emotional reactivity had very strong positive predictive values for the presence of PTSD. CONCLUSIONS: These findings indicate that PTSD can develop after severe traumatic brain injury. The predominance of emotional reactivity and the relative absence of traumatic memories in patients with PTSD who suffered impaired consciousness during trauma suggest that traumatic experiences can mediate PTSD at an implicit level.

Immunolocalization of Bone Morphogenetic Protein-2 and -3 and Osteogenic Protein-1 during murine tooth root morphogenesis and in other craniofacial structures.

The distribution of Bone Morphogenetic Protein-2, and -3 (BMP-2 and BMP-3) and Osteogenic Protein-1 (OP-1, also known as BMP-7) during root morphogenesis and in other craniofacial structures was examined in sections of 12- to 18-d-old mouse heads using polyclonal and monoclonal antibodies. BMP-3 and OP-1 were localized in alveolar bone, cementum, and periodontal ligament, whereas BMP-2 was only localized in the alveolar bone of periodontium. All three BMPs were localized in predentine, dentine, odontoblasts, osteoblasts, osteocytes, osteoid, cartilage, chondrocytes and spiral limbus. BMP-2 and OP-1 were also localized in spiral ligament and interdentate cells of the cochlea, whilst BMP-3 was restricted to the spiral ganglion. BMP-3 was also localized in ducts of submandibular and sublingual salivary glands, acini of the lacrimal gland, Purkinje cells in the cerebellum, nerve fibres of the cerebellum and brain, afferent cells of the dorsal root ganglia, inferior alveolar nerve, and peripheral processes of the vestibulocochlear nerve. OP-1 was also localized in hair and whisker follicles, sclera of the eye and in ameloblasts. The demonstration of BMP-3 in the nervous system suggests that this protein may be neurotrophic during development and maintenance of the nervous system. The composite expression of BMPs/OPs during periodontal tissue morphogenesis suggests that optimal therapeutic regeneration may entail the combined use of different BMPs/OPs.

Dysautonomia after traumatic brain injury: a forgotten syndrome?

OBJECTIVES: To better establish the clinical features, natural history, clinical management, and rehabilitation implications of dysautonomia after traumatic brain injury, and to highlight difficulties with previous nomenclature. METHODS: Retrospective file review on 35 patients with dysautonomia and 35 sex and Glasgow coma scale score matched controls. Groups were compared on injury details, CT findings, physiological indices, and evidence of infections over the first 28 days after injury, clinical progress, and rehabilitation outcome. RESULTS: the dysautonomia group were significantly worse than the control group on all variables studied except duration of stay in intensive care, the rate of clinically significant infections found, and changes in functional independence measure (FIM) scores. CONCLUSIONS: Dysautonomia is a distinct clinical syndrome, associated with severe diffuse axonal injury and preadmission hypoxia. It is associated with a poorer functional outcome; however, both the controls and patients with dysautonomia show a similar magnitude of improvement as measured by changes in FIM scores. It is argued that delayed recognition and treatment of dysautonomia results in a preventable increase in morbidity.

Utility of the functional assessment measure after discharge from inpatient rehabilitation.

OBJECTIVE: To assess the relationship between the Functional Independence Measure (FIM) and the Functional Assessment Measure (FAM), and community integration and return to work in patients with severe traumatic brain injuries (TBI). DESIGN: A cross-sectional, prospective design was used to collect data at 6 and 24 months postdischarge. The Return to Work Scale (RTW) and Community Integration Questionnaire (CIQ) were selected to assess return to work and community functioning. Predictor variables included the motor and cognitive subscales of the FIM and the FAM. SETTING: Follow-up database of an inpatient and community TBI Rehabilitation Unit. PARTICIPANTS: All consenting patients with TBI admitted to the unit, aged 16 or above. There were 88 patients at 6 and 79 patients at 24 month follow-up. RESULTS: At 6 months follow-up, the FAM and the FIM were roughly equivalent in their ability to predict RTW and CIQ scores. At 24 months, FAM motor was the only significant predictor of CIQ, and FAM cognitive scores displayed an advantage over the FIM in predicting employment status. CONCLUSIONS: The FAM subscales produced only modest gains in prediction of employment status and community integration at 24 months postdischarge. This may reflect ceiling effects on the functional measures, a limited range on the RTW measure, poor ecologic validity of functional disability measures in assessing handicap, or a combination of these factors.

Interaction of posttraumatic stress disorder and chronic pain following traumatic brain injury.

OBJECTIVE: To investigate the association between posttraumatic stress disorder (PTSD) and chronic pain in patients who had sustained a severe traumatic brain injury (TBI). DESIGN: Correlational relationships between pain variables and PTSD measures were examined in a cohort study. SETTING: An adult tertiary care center brain injury clinic. PATIENTS: Ninety-six persons with severe TBI. OUTCOME MEASURES: The Posttraumatic Stress Disorder Interview (PTSD-I), a modified McGill Pain Questionnaire, the Beck Depression Inventory (BDI), the General Health Questionnaire (GHQ), the Community Integration Questionnaire (CIQ), the Satisfaction with Life Scale (SWL), and the Coping Style Questionnaire (CSQ). RESULTS: More persons with chronic pain reported PTSD than did those without pain. The relationship between pain severity and depression, functional adjustment, and satisfaction with life was mediated by severity of PTSD. Pain severity was significantly associated with an avoidant coping style. CONCLUSIONS: Effective rehabilitation of persons with chronic pain following severe TBI should recognize the role of posttraumatic stress in the maintenance of dysfunctional reactions. Specific interventions that address adaptive coping mechanisms to reduce PTSD may enhance rehabilitation for persons with TBI who suffer chronic pain.