Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone.

AIM: The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. METHODS: In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin. RESULTS: Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (-0.89%, -1.03% and -0.26%; p < 0.001); reductions with canagliflozin 100 and 300 mg were maintained at week 52 (-0.92% and -1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (-2.5 and -3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin. CONCLUSION: Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks.

Faunal record identifies Bering isthmus conditions as constraint to end-Pleistocene migration to the New World.

Human colonization of the New World is generally believed to have entailed migrations from Siberia across the Bering isthmus. However, the limited archaeological record of these migrations means that details of the timing, cause and rate remain cryptic. Here, we have used a combination of ancient DNA, 14C dating, hydrogen and oxygen isotopes, and collagen sequencing to explore the colonization history of one of the few other large mammals to have successfully migrated into the Americas at this time: the North American elk (Cervus elaphus canadensis), also known as wapiti. We identify a long-term occupation of northeast Siberia, far beyond the species's current Old World distribution. Migration into North America occurred at the end of the last glaciation, while the northeast Siberian source population became extinct only within the last 500 years. This finding is congruent with a similar proposed delay in human colonization, inferred from modern human mitochondrial DNA, and suggestions that the Bering isthmus was not traversable during parts of the Late Pleistocene. Our data imply a fundamental constraint in crossing Beringia, placing limits on the age and mode of human settlement in the Americas, and further establish the utility of ancient DNA in palaeontological investigations of species histories.

Development of flax/carbon fibre hybrid composites for enhanced properties.

Uni-directional (UD) and cross-ply (CP) cellulosic flax fibre epoxy composites were produced by hybridising UD carbon fibre prepreg onto flax system. A compression moulding technique was used to produce both flax and carbon/flax hybridised laminates. The effect of carbon fibre hybridisation on the water absorption behaviour, thermal and mechanical properties of both UD and CP flax specimens were investigated by means of water absorption, tensile, thermogravemetric analysis and flexural testing. The results showed that water absorption behaviour of hybrid samples are markedly improved compared to those without hybridisation. Similarly, the thermal stability, tensile and flexural properties of the hybrid composites are significantly improved in comparison with UD and CP flax composites without hybridisation. The experimental results suggest that cellulosic flax fibre reinforcement contributed to improve the toughness properties by promoting crack propagation whereas the carbon fibre contributed in improving thermal stability, water absorption behaviour and the overall strength and the stiffness of the hybrid composites.

Proteins secreted by embryonic stem cells activate cardiomyocytes through ligand binding pathways.

Human embryonic stem cells (hESC) underlie embryogenesis but paracrine signals associated with the process are unknown. This study was designed to 1) profile native proteins secreted by undifferentiated hESC and 2) determine their biological effects on primary neonatal cardiomyocytes. We utilized multi-analyte, immunochemical assays to characterize media conditioned by undifferentiated hESC versus unconditioned media. Expression profiling was performed on cardiomyocytes subjected to these different media conditions and altered transcripts were mapped to critical pathways. Thirty-two of 109 proteins were significantly elevated in conditioned media ranging in concentration from thrombospondin (57.2+/-5.0 ng/ml) to nerve growth factor (7.4+/-1.2pg/ml) and comprising chemokines, cytokines, growth factors, and proteins involved in cell adhesion and extracellular matrix remodeling. Conditioned media induced karyokinesis, cytokinesis and proliferation in mono- and binucleate cardiomyocytes. Pathway analysis revealed comprehensive activation of the ROCK 1 and 2 G-protein coupled receptor (GPCR) pathway associated with cytokinesis, and the RAS/RAF/MEK/ERK receptor tyrosine kinase (RTK) and JAK/STAT-cytokine pathway involved in cell cycle progression. These results provide a partial database of proteins secreted by pluripotent hESC that potentiate cell division in cardiomyocytes via a paracrine mechanism suggesting a potential role for these stem cell factors in cardiogenesis and cardiac repair.

Cardiac fibroblasts influence cardiomyocyte phenotype in vitro.

Cardiac fibroblasts impact myocardial development and remodeling through intercellular contact with cardiomyocytes, but less is known about noncontact, profibrotic signals whereby fibroblasts alter cardiomyocyte behavior. Fibroblasts and cardiomyocytes were harvested from newborn rat ventricles and separated by serial digestion and gradient centrifugation. Cardiomyocytes were cultured in 1) standard medium, 2) standard medium diluted 1:1 with PBS, or 3) standard medium diluted 1:1 with medium conditioned > or =72 h by cardiac fibroblasts. Serum concentrations were held constant under all media conditions, and complete medium exchanges were performed daily. Cardiomyocytes began contracting within 24 h at clonal or mass densities with <5% of cells expressing vimentin. Immunocytochemical analysis revealed progressive expression of alpha-smooth muscle actin in cardiomyocytes after 24 h in all conditions. Only cardiomyocytes in fibroblast-conditioned medium stopped contracting by 72 h. There was a significant, sustained increase in vimentin expression specific to these cultures (means +/- SD: conditioned 46.3 +/- 6.0 vs. control 5.3 +/- 2.9%, P < 0.00025) typically with cardiac myosin heavy chain coexpression. Proteomics assays revealed 10 cytokines (VEGF, GRO/KC, monocyte chemoattractant protein-1, leptin, macrophage inflammatory protein-1alpha, IL-6, IL-10, IL-12p70, IL-17, and tumor necrosis factor-alpha) at or below detection levels in unconditioned medium that were significantly elevated in fibroblast-conditioned medium. Latent transforming growth factor-beta and RANTES were present in unconditioned medium but rose to higher levels in conditioned medium. Only granulocyte-macrophage colony-stimulating factor was present above threshold levels in standard medium but decreased with fibroblast conditioning. These data indicated that under the influence of fibroblast-conditioned medium, cardiomyocytes exhibited marked hypertrophy, diminished contractile capacity, and phenotype plasticity distinct from the dedifferentiation program present under standard culture conditions.

New carbon dates link climatic change with human colonization and Pleistocene extinctions.

Drastic ecological restructuring, species redistribution and extinctions mark the Pleistocene-Holocene transition, but an insufficiency of numbers of well-dated large mammal fossils from this transition have impeded progress in understanding the various causative links. Here I add many new radiocarbon dates to those already published on late Pleistocene fossils from Alaska and the Yukon Territory (AK-YT) and show previously unrecognized patterns. Species that survived the Pleistocene, for example, bison (Bison priscus, which evolved into Bison bison), wapiti (Cervus canadensis) and, to a smaller degree, moose (Alces alces), began to increase in numbers and continued to do so before and during human colonization and before the regional extinction of horse (Equus ferus) and mammoth (Mammuthus primigenius). These patterns allow us to reject, at least in AK-YT, some hypotheses of late Pleistocene extinction: 'Blitzkrieg' version of simultaneous human overkill, 'keystone' removal, and 'palaeo-disease'. Hypotheses of a subtler human impact and/or ecological replacement or displacement are more consistent with the data. The new patterns of dates indicate a radical ecological sorting during a uniquely forage-rich transitional period, affecting all large mammals, including humans.

Long-term analysis of a full-scale activated sludge wastewater treatment system exhibiting seasonal biological foaming.

The seasonal accumulation of biological foam on the activated sludge system of the Urbana-Champaign Sanitary District Northeast (UCSD-NE) wastewater treatment plant was investigated over an 8-year period by statistical analyses including path analysis, multivariate regression, and principal component analysis. Results of these analyses suggested that variation in the activated sludge reactor temperature and the use of a stream bypassing the primary clarifier were the two main factors determining the observed temporal foam profile. Characterization of the primary clarifier influent and effluent suggested the involvement of high lipid loading rates from the bypass stream in foam accumulation. In light of these results, it is hypothesized that increasing temperatures and lipid loading rates are responsible for foam formation through the same mechanism: the foam-forming microbial population is specialized in consuming lipids, substrates classified as slowly degradable. When the temperature increases, the rate of lipid hydrolysis becomes sufficiently high for this population to become abundant, accumulate on the surfaces of the aeration basins, and cause biological foaming.

Molecular dynamics of the compensatory response to myocardial infarct.

Myocardial infarct via occlusion of the left anterior descending coronary in rats caused overriding depression in transcription, signal transduction, inflammation and extracellular matrix pathways in the infarct zone within 24 h. In contrast, remote zone gene expression was reciprocally activated during the immediate post-infarct period. Infarct zone signal transduction occurred primarily through TGFbeta1 induction while the remote zone exhibited elevated WNT, NOTCH, GPCR and transmembrane signaling. A minimal day 1 acute phase, inflammatory response was detected in the infarct zone while interleukins (IL1alpha, IL1beta, IL6, IL12alpha, IL18) and the TNFalpha superfamily were activated in the remote zone. Different cytochrome subsets were activated in each left ventricular region on day 1 while anti-oxidant genes were elevated only in the remote zone. The infarct zone exhibited mixed early transcription factor activation across all binding domains with a balance favoring constitutive gene activation and differentiation pathways as opposed to cell proliferation. In contrast, the remote zone exhibited activation of extensive developmental transcription factors involved in specification of cell phenotype, tissue-specific interactions and position-specific cell proliferation on day 1. The day 28 infarct zone response mirrored the day 1 remote zone response including activation of genes associated with matrix remodeling (metallothionein and metalloproteinase 9, 12, 23), as well as genes associated with cell proliferation and phenotype specification (MYC, EGR2, ATF3, HOXA1) recapitulating developmental histogenesis programs.

Radiocarbon evidence of mid-Holocene mammoths stranded on an Alaskan Bering Sea island.

Island colonization and subsequent dwarfing of Pleistocene proboscideans is one of the more dramatic evolutionary and ecological occurrences, especially in situations where island populations survived end-Pleistocene extinctions whereas those on the nearby mainland did not. For example, Holocene mammoths have been dated from Wrangel Island in northern Russia. In most of these cases, few details are available about the dynamics of how island colonization and extinction occurred. As part of a large radiocarbon dating project of Alaskan mammoth fossils, I addressed this question by including mammoth specimens from Bering Sea islands known to have formed during the end-Pleistocene sea transgression. One date of 7,908 +/- 100 yr bp (radiocarbon years before present) established the presence of Holocene mammoths on St Paul Island, a first Holocene island record for the Americas. Four lines of evidence--265 accelerator mass spectrometer (AMS) radiocarbon dates from Alaskan mainland mammoths, 13 new dates from Alaskan island mammoths, recent reconstructions of bathymetric plots and sea transgression rates from the Bering Sea--made it possible to reconstruct how mammoths became stranded in the Pribilofs and why this apparently did not happen on other Alaskan Bering Sea islands.

Rapid body size decline in Alaskan Pleistocene horses before extinction.

About 70% of North American large mammal species were lost at the end of the Pleistocene epoch. The causes of this extinction--the role of humans versus that of climate--have been the focus of much controversy. Horses have figured centrally in that debate, because equid species dominated North American late Pleistocene faunas in terms of abundance, geographical distribution, and species variety, yet none survived into the Holocene epoch. The timing of these equid regional extinctions and accompanying evolutionary changes are poorly known. In an attempt to document better the decline and demise of two Alaskan Pleistocene equids, I selected a large number of fossils from the latest Pleistocene for radiocarbon dating. Here I show that horses underwent a rapid decline in body size before extinction, and I propose that the size decline and subsequent regional extinction at 12,500 radiocarbon years before present are best attributed to a coincident climatic/vegetational shift. The present data do not support human overkill and several other proposed extinction causes, and also show that large mammal species responded somewhat individualistically to climate changes at the end of the Pleistocene.

Effect of muscle origin and phenotype on satellite cell muscle-specific gene expression.

Satellite cells from adult mouse tongue, diaphragm, vastus lateralis, rectus femoris, tibialis anterior, soleus, and extensor digitorum longus muscles were isolated, expanded, and differentiated under identical culture conditions. Proliferating myoblasts and differentiated myofiber cultures were analyzed via SDS-PAGE, immunochemical, and PCR methods for expression of myosin heavy chains (MyHC) and muscle creatine kinase (MCK) as indices of muscle fiber type. Contralateral muscles were harvested for simultaneous, parallel analysis utilizing these assays. The MyHC profile of differentiated primary satellite cells was equivalent across all cultures with MyHC(2A) and MyHC(1/slow) co-expressed in all myotube and myofiber structures. Trace amounts of MyHC(2B) and MyHC(neo) were detected in a few myofibers. MCK was expressed at a uniform, similar level among these cultures. In contrast, contralateral muscles expressed each muscle-specific indicator at levels correlated with the fiber-type distribution within each muscle. MM14 and C2C12 cells, mouse satellite cell lines, were expanded and compared to primary cell cultures. MM14 cells had a high differentiation index (>95%) and co-expressed MyHC(2A) and MyHC(1/slow) along with trace amounts of MyHC(neo) throughout myotube cultures. Myofibers obtained from C2C12 cells exhibited less differentiation (~75%) with MyHC(2A) as the dominant isoform. These data indicate that primary satellite cells from adult muscle form a uniform differentiated cell type regardless of the fiber-type, anatomic location, and embryonic origin of the donor muscles. MM14 cells expressed an adult MyHC isoform profile similar to primary satellite cells. The results suggest that satellite cells provide a uniform cell source for use in autologous transplantation studies and do not acquire a heritable fiber-type-specific phenotype from their host muscle.

Omapatrilat provides long-term control of hypertension: a randomized trial of treatment withdrawal.

Omapatrilat simultaneously inhibits neutral endopeptidase and angiotensin-converting enzyme, increasing levels of vasodilatory peptides while decreasing production of angiotensin II. This study evaluated the clinical effects of withdrawal of omapatrilat after a patient's hypertension had been controlled (seated diastolic blood pressure <90 mm Hg) on omapatrilat for at least 6 months, with or without adjunctive antihypertensive medications. This double-blind study randomized 83 patients to receive either their established omapatrilat dose or placebo for 8 weeks; any concomitant antihypertensive medications were kept constant. Patients continuing on omapatrilat had no change in blood pressure. Patients whose chronic omapatrilat treatment was replaced by placebo had clinically important increases in both systolic (+16.5 mm Hg) and diastolic ((+9.6 mm Hg) blood pressures (both p<0.001). An increase in blood pressure was also seen in patients who were taking adjunctive antihypertensive medications prior to withdrawal of omapatrilat. This study demonstrates that when compared to withdrawal placebo, omapatrilat maintains clinically and statistically significant blood pressure reductions.

Community-acquired lower respiratory tract infections: etiology and treatment.

The current therapy for community-acquired lower respiratory tract infections is often empiric, usually involving administration of a beta-lactam or macrolide. However, the increasing prevalence of antibiotic resistance in frequently isolated respiratory tract pathogens has complicated the antimicrobial selection process. This review will discuss the incidence of various respiratory pathogens, as well as update the clinician on the various antimicrobial alternatives available, with particular emphasis on the role of the newer fluoroquinolones in the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia.

The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program.

BACKGROUND: Noncompliance with cardiovascular therapy and prevention initiatives is well documented. OBJECTIVES: The purpose of the First Myocardial Infarction (MI) Risk Reduction Program, an open-label drug registry involving mainly primary-care patients at increased risk of a first MI, was to examine the effects of postal and telephone reminders, as well as demographic and other baseline characteristics, on patient self-reported compliance with pravastatin treatment. A second objective was to determine whether regimen adherence was associated with the adoption of other lifestyle modifications recommended to decrease the risk of coronary artery disease. METHODS: Patients with risk scores of > or = 4 on a scale of -1 to +16 for men and -1 to +17 for women on the First Heart Attack Risk Test were considered to be at increased risk of a first MI and eligible for enrollment in the registry program. An elevated total cholesterol level despite dietary interventions was an additional inclusion criterion. Patients were prospectively randomized (4:1) to either an intervention involving postal and telephone reminders (about coronary risk reduction and medication compliance), which were sent during the first 2 months of pravastatin treatment, or usual care. Both groups received reminder postcards at 4 and 5 months, in addition to counseling by physicians about coronary risk reduction. At 3 and 6 months (or study discontinuation), patients completed and mailed to the program-coordinating center questionnaires concerning compliance with care, including current use of prescribed pravastatin, as well as self-reported adoption of other lifestyle modifications, such as changing eating habits, losing weight, increasing physical activity, and/or quitting smoking. Compliance with pravastatin therapy and with these coronary risk-reducing behaviors was also assessed by physicians at the 3-month follow-up visit. RESULTS: A total of 10,335 patients were in the intervention group, and 2765 received usual care. The 2 groups were well balanced at baseline with respect to age, race, and total cholesterol values. Neither early reminders nor baseline patient characteristics were significantly associated with reported pravastatin compliance rates, which were approximately 79% overall. However, according to self-reports at 6 months, regimen compliance was associated with the adoption of other coronary risk-reducing behaviors. CONCLUSIONS: The results of this study suggest that early telephone and postal reminders do not improve compliance with drug treatment or with recommended coronary risk-reducing behaviors.

Urinary leukotriene E(4) excretion during the first month of life and subsequent bronchopulmonary dysplasia in premature infants.

BACKGROUND: Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. OBJECTIVES: To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD. DESIGN: Prospective, blinded, controlled study. SETTING: Neonatal ICUs of a tertiary-care university hospital. METHODS: Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups. RESULTS: Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD. CONCLUSION: Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.

Hypnotizability in acute stress disorder.

OBJECTIVE: This study investigated the relationship between acute dissociative reactions to trauma and hypnotizability. METHOD: Acutely traumatized patients (N=61) with acute stress disorder, subclinical acute stress disorder (no dissociative symptoms), and no acute stress disorder were administered the Stanford Hypnotic Clinical Scale within 4 weeks of their trauma. RESULTS: Although patients with acute stress disorder and patients with subclinical acute stress disorder displayed comparable levels of nondissociative psychopathology, acute stress disorder patients had higher levels of hypnotizability and were more likely to display reversible posthypnotic amnesia than both patients with subclinical acute stress disorder and patients with no acute stress disorder. CONCLUSIONS: The findings may be interpreted in light of a diathesis-stress process mediating trauma-related dissociation. People who develop acute stress disorder in response to traumatic experience may have a stronger ability to experience dissociative phenomena than people who develop subclinical acute stress disorder or no acute stress disorder.

Compensation: problems with the concept of disability and the use of American Medical Association Guides.

The Western Australia Liberal Government made radical changes to the Workers Compensation and Rehabilitation Act 1981 (WA) in 1993. One of the significant changes was the greater application of the American Medical Association Guides to the assessment of permanent injury. In 1999 further amendments to the same legislation required the application of the Guides to workers who wished to proceed with common law claims for negligence against their employers. Recent cases have shown the difficult in reconciling the language of the law with commonly used medical terms. This article surveys the use of the American Medical Association Guides in compensation legislation in Australia with some specific comments on the Western Australian system. It makes some suggestions for reform of the Western Australian system.

Cotinine levels in Southeast Asian smokers.

Understanding the contribution of race to factors associated with cigarette smoking and nicotine metabolism is essential for the characterization of patterns of tobacco use, nicotine dependence and incidence of tobacco-related diseases. This paper reports an investigation of cotinine levels among Southeast Asian smokers in two separate studies. Study 1 included 327 male and female smokers who participated in community-based interviews where smoking history information was obtained and a saliva continine sample was collected. Results indicated that subjects smoked an average of 11.2 cigarettes/day, with men reporting significantly higher consumption rates as compared to women (p < 0.0001). Subjects' mean cotinine level was 65 ng/ml with an average cotinine/cigarette ratio of 8.2. In Study 2, plasma and saliva cotinine in six Southeast Asian adult smokers were measured during 2 days of smoking followed by 6 days of abstinence. On day 1, mean plasma and saliva continine levels were 268 and 235 ng/ml, respectively. After 6 days of abstinence, mean levels had dropped to 12 ng/ml for plasma and 8 ng/ml in saliva. On average, it required at least 4.7 days for saliva continine levels to reach < 14 ng/ml. Mean cotinine concentrations during smoking differed in these two separate studies. Implications of these findings are discussed and future research recommendations are presented.

Attempting suppression of traumatic memories over extended periods in acute stress disorder.

This study investigated the influence of attempted suppression and thought control strategies on traumatic memories. Survivors of civilian trauma with acute stress disorder (ASD; n = 20) and without ASD (n = 20) monitored their trauma-related thoughts for three 24-h periods. In period 1, participants were instructed to think about anything. In period 2, participants were administered suppression or nonsuppression instructions relating to thoughts of the trauma. In period 3, participants were again instructed to think about anything. The results revealed no evidence for an increase in trauma-related thoughts following suppression instructions. Punishment and worry thought control strategies correlated significantly with both anxiety and suppression ratings. Frequency of intrusions was associated with a distraction cognitive strategy. These findings point to the importance of traumatised individuals' cognitive strategies in mediating the management and occurrence of posttraumatic intrusions.

A prospective study of psychophysiological arousal, acute stress disorder, and posttraumatic stress disorder.

This study investigated the role of acute arousal in the development of posttraumatic stress disorder (PTSD). Hospitalized motor-vehicle-accident survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month of the trauma and were reassessed (n = 113) for PTSD 6 months posttrauma. Heart rate (HR) and blood pressure (BP) were assessed on the day of hospital discharge. Participants with subclinical ASD had higher HR than those with ASD and no ASD. Participants who developed PTSD had higher HR in the acute posttrauma phase than those without PTSD. Diagnosis of ASD and resting HR accounted for 36% of the variance of the number of PTSD symptoms. A formula composed of a diagnosis of ASD or a resting HR of > 90 beats per minute possessed strong sensitivity (88%) and specificity (85%) in predicting PTSD. These findings are discussed in terms of acute arousal and longer term adaptation to trauma.