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Background Knee pain associated with osteoarthritis is a significant contributor to decreased physical function. Recent evidence supports the inter-individual heterogeneity associated with knee pain presentation, but whether there is similar heterogeneity in physical performance among these individuals has not been previously examined. The aim of the present study was to characterize the variability in physical performance profiles and the pain evoked by their performance (i.e., movement-evoked pain). Methods In a secondary analysis of the community-based study Understanding Pain and Limitations in Osteoarthritic Disease (UPLOAD), individuals (n = 270) completed functional, pain, psychological, and somatosensory assessments. Hierarchical cluster analysis was used to derive physical function profiles that were subsequently compared across several clinical, psychological and experimental pain measures. Results Our results support the hypothesis that among persons with knee OA pain, three different physical performance profiles exist with varying degrees of movement-evoked pain. Even as all three groups experienced moderate to severe levels of spontaneous knee pain, those individuals with the most severe movement-evoked pain and lowest physical functional performance also had the least favorable psychological characteristics along with increased mechanical pain sensitivity and temporal summation. Conclusions Our findings support the need for the assessment and consideration of movement-evoked pain during physical performance tasks as these have the potential to increase the value of functional and pain assessments clinically. The identification of the mechanisms driving pain burden within homogeneous groups of individuals will ultimately allow for targeted implementation of treatments consistent with a biopsychosocial model of pain.

Summary: Accurate repair of DNA double-strand breaks (DSBs) in developing germ cells is critical to promote proper chromosome segregation and to maintain genome integrity. To directly detect homolog-independent (intersister/intrachromatid) meiotic DSB repair, we exploited the genetics and germline physiology of C. elegans to (1) induce a single DSB in nuclei across discrete stages of meiotic prophase I; (2) detect repair of that DSB as a homolog-independent crossover or noncrossover; and (3) sequence the resultant product to assess mechanisms of recombination.For complete details on the use and execution of this protocol, please refer to Toraason et al. (2021).

During meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes.1 In meiotic prophase I, double-strand DNA breaks (DSBs) are induced and a subset of these DSBs are repaired as interhomolog crossovers to ensure proper chromosome segregation. DSBs not resolved as crossovers with the homolog must be repaired by other pathways to ensure genome integrity.2 To determine if alternative repair templates can be engaged for meiotic DSB repair during oogenesis, we developed an assay to detect sister and/or intra-chromatid repair events at a defined DSB site during Caenorhabditis elegans meiosis. Using this assay, we directly demonstrate that the sister chromatid or the same DNA molecule can be engaged as a meiotic repair template for both crossover and noncrossover recombination, with noncrossover events being the predominant recombination outcome. We additionally find that the sister or intra-chromatid substrate is available as a recombination partner for DSBs induced throughout meiotic prophase I, including late prophase when the homolog is unavailable. Analysis of noncrossover conversion tract sequences reveals that DSBs are processed similarly throughout prophase I. We further present data indicating that the XPF-1 nuclease functions in late prophase to promote sister or intra-chromatid repair at steps of recombination following joint molecule processing. Despite its function in sister or intra-chromatid repair, we find that xpf-1 mutants do not exhibit severe defects in progeny viability following exposure to ionizing radiation. Overall, we propose that C. elegans XPF-1 may assist as an intersister or intrachromatid resolvase only in late prophase I.

Drained peatlands are major sources of CO2 to the atmosphere, yet the effects of land management and hydrological extremes have been little-studied at spatial scales relevant to agricultural enterprises. We measured fluxes of CO2 using the eddy covariance (EC) technique at two adjacent dairy farms on a drained peatland in Aotearoa New Zealand with remaining peat depths 5.5–8 m. One site (SD) had shallow surface drains and mean water table depth (WTD) −657 mm, while the other site (BD) had deep field border drains and mean WTD −838 mm. Net ecosystem CO2 production (NEP) was similar at the two sites when the soils were moist but diverged during late-summer drying, with site BD having 4.56 t C ha−1 greater CO2 emission than site SD over the four-month dry period. Soil drying reduced gross primary production (GPP) at both sites, while ecosystem respiration (ER) was reduced at site SD but not at site BD. The low dry season respiration rates at site SD contributed to near-zero annual NEP, while higher respiration rates at site BD led to annual CO2 loss of −4.95 ± 0.59 t C ha−1 yr−1. Accounting for other imports and exports of carbon, annual net ecosystem carbon balances were −2.23 and −8.47 t C ha−1 yr−1 at sites SD and BD, respectively. It is likely that the contrasting dry season respiration rates resulted from differences in soil physical properties affecting soil moisture vertical redistribution and availability to plants and microbes rather than from the relatively small differences in WTD. These differences could be caused by soil physical disturbances during pasture renewal or paddock recontouring, or time since initial drainage. Therefore, improved soil management might provide practical mitigation against excessive CO2 emissions during dry conditions, including droughts.

Cellular translation surveillance rescues ribosomes that stall on problematic mRNAs. During translation surveillance, endonucleolytic cleavage of the problematic mRNA is a critical step in rescuing stalled ribosomes. Here we identify NONU-1 as a factor required for translation surveillance pathways including no-go and nonstop mRNA decay. We show that (1) NONU-1 reduces nonstop and no-go mRNA levels; (2) NONU-1 contains an Smr RNase domain required for mRNA decay; (3) the domain architecture and catalytic residues of NONU-1 are conserved throughout metazoans and eukaryotes, respectively; and (4) NONU-1 is required for the formation of mRNA cleavage fragments in the vicinity of stalled ribosomes. We extend our results in C.elegans to homologous factors in S.cerevisiae, showing the evolutionarily conserved function of NONU-1. Our work establishes the identity of a factor critical to translation surveillance and will inform mechanistic studies at the intersection of translation and mRNA decay.

Telomere length, a measure of cellular aging, is negatively associated with chronic pain severity and serves as an indicator of overall system functioning. While psychological resilience factors such as optimism, acceptance, positive affect and active coping have been associated with lower levels of clinical pain and greater physical functioning, it is unknown whether resilience may buffer against telomere shortening in individuals with chronic pain. Additionally, a broader conceptualization of resilience that includes biobehavioral and social factors may improve our understanding of the relationship between resilience, chronic pain, and health outcomes. We hypothesized that: 1) psychological resilience factors would be associated with longer telomere length, and 2) a combined biobehavioral/psychosocial composite would strengthen the association. A total of 79 individuals (34% Male, 66% Female) with/without knee pain completed psychological/psychosocial resilience (optimism, affect, active coping, perceived stress and social support) and biobehavioral measures (smoking status, and waist/hip ratio). Clinical cut points for each measure were established based on previously published normative data or means where applicable and used to create summative psychological (optimism, affect, coping, perceived stress) and biobehavioral/psychosocial (psychological resilience + social support, smoking, waist/hip ratio), resilience composites. Blood samples were collected and telomere length determined. Regression analyses were completed with sex, race, age, and GCPS characteristic pain intensity as additional predictors. A positive relationship emerged such that greater psychological resilience and biobehavioral/psychosocial resilience were associated with longer telomeres (p = .0295 and p = .0116, respectively). When compared with psychological resilience alone, the biobehavioral/psychosocial composite was significantly more predictive of telomere length than the psychological resilience composite (p

Studies indicate that improving sleep decreases reported pain in patients with knee osteoarthritis, but it is unclear if this association extends to experimentally induced pain responses. A community-based sample of 88 African American and 52 non-Hispanic white adults (45–76 years) with knee osteoarthritis completed the Insomnia Severity Index and the arousal subscale of the Sleep Hygiene and Practices Scale. Participants underwent quantitative sensory testing, including measures of pain sensitivity and facilitation at the knee, and pain inhibition. Outcomes were analyzed with multiple Tobit hierarchical regression models, with adjustment for relevant covariates. Ethnicity and sex by sleep interactions were also entered into the models. After covariate adjustment, main associations were not observed. However, sex interacted with insomnia severity to predict greater temporal summation of heat and punctate pressure pain among women and lower heat temporal summation among men. Men and women who engaged in frequent arousal-associated sleep behaviors demonstrated higher and lower heat temporal summation, respectively. Non-Hispanic whites with greater insomnia severity displayed lower pressure pain thresholds and pain inhibition. Our findings are the first to demonstrate that disrupted sleep is associated with altered pain processing differentially by sex and ethnicity/race among people with knee osteoarthritis. Perspective This article presents the association between insomnia severity, maladaptive sleep behaviors, and experimentally induced pain responses among people with knee osteoarthritis. Disrupted sleep was associated with altered pain processing by sex and ethnicity/race. Offering sleep interventions may help ameliorate pain, but treatment may need to be tailored by sex and ethnicity/race.

The purpose of this study was to summarize sport concussion incidence data, identify sports that present higher injury frequency, reveal the degree of risk in some lesser-known sports, and outline specific details within the sports literature that raise additional concerns, such as helmet-to-helmet contact and player positions that experience frequent impact.A systematic literature review of Pub Med using keyword search on injury, concussion, and sports was performed through May 2012. Abstracts were identified, selections were made based upon inclusion criteria, and full-length articles were obtained. Additional articles were considered following review of reference sections. Articles were reviewed and tabulated according to sport.Two hundred eighty-nine articles were screened, and 62 articles were reviewed. The overall incidence of concussion in sport ranged from 0.1 to 21.5 per 1000 athletic exposures. The lowest incidence was reported in swimming and diving. Concussion incidence was highest in Canadian junior ice hockey, but elevated incidence in American football remains a concern because of the large number of participants.The literature reviewed included incidence of concussion on the field of play under real-world conditions and influenced by the current culture of sport. The studies examined in this article show that there is risk of concussion in nearly every sport. Some sports have higher concussion frequency than others, which may depend upon the forces and roles of the positions played in these sports. Younger athletes have a higher incidence of concussion, and female incidence is greater than male in many comparable sports. Headgear may reduce concussion in some sports but may also give athletes a false sense of protection.

Summary Objective Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. Design In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. Results Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. Conclusions These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.

Recent years have seen a dramatic expansion in the application of radiation and isotopes to security screening. This has been driven primarily by increased incidents involving improvised explosive devices as well as their ease of assembly and leveraged disruption of transportation and commerce. With global expenditures for security-screening systems in the hundreds of billions of dollars, there is a pressing need to develop, apply, and harmonize standards for x-ray and gamma-ray screening systems used to detect explosives and other contraband. The National Institute of Standards and Technology has been facilitating the development of standard measurement tools that can be used to gauge the technical performance (imaging quality) and radiation safety of systems used to screen luggage, persons, vehicles, cargo, and left-behind objects. After a review of this new suite of national standard test methods, test objects, and radiation-measurement protocols, we highlight some of the technical trends that are enhancing the revision of baseline standards. Finally we advocate a more intentional use of technical-performance standards by security stakeholders and outline the advantages this would accrue.

Introduction Cancer associated thrombosis is a well-recognized phenomenon that results in considerable patient morbidity and mortality. Malignancy conveys an increased risk for thrombosis and chemotherapy further elevates this risk. The pathophysiological mechanisms underlying this process remain poorly defined. Materials and Methods A human acute monocytic leukemia cell line (THP-1) was treated with commonly used anthracycline chemotherapeutics at concentrations similar to those found in the plasma of cancer patients. Cells were analyzed for tissue factor (TF) mRNA, protein, and activity. Microparticle (MP) TF activity was also measured. Phosphatidylserine (PS) exposure on cells and MPs was analyzed by flow cytometry. PS levels on MPs was also evaluated in an annexin V capture assay. Results Anthracycline treatment of THP-1 cells resulted in a concentration-dependent increase in cellular TF activity without a change in TF protein, which was associated with increased PS exposure on the cell surface and apoptosis. The increase in TF activity was abolished by annexin V or lactadherin indicating that PS exposure was required. Anthracycline treatment of THP-1 cells also increased the number of TF-positive MPs. Conclusion Treatment of THP-1 cells with anthracyclines induces apoptosis and increases cellular TF activity. The increased activity required an increase in exposure of PS. Additionally, anthracyclines increase the release of TF-positive MPs from THP-1 cells. We propose that the increase in cellular TF activity in circulating leukemic cells, combined with increased numbers of TF-positive MPs, may contribute to thrombosis in cancer patients receiving chemotherapy.

Given our limited ability to predict analgesic efficacy, further research is needed to understand factors influencing analgesic response patterns. The aim of this study was to better understand the relationship between morphine and butorphanol analgesic efficacy tested against multiple pain modalities within the same individuals. Participants included healthy men (n = 72) and women (n = 67) who underwent thermal, pressure, and ischemic experimental pain testing before and after the double-blind administration of morphine and butorphanol during separate testing sessions. Factor analysis revealed 6 factors with analgesic effects grouped primarily by pain modality and specific to either morphine or butorphanol. Hierarchical cluster analysis of individual factor scores led to 4 distinct drug response profiles. Three groups displayed exceptional analgesic efficacy produced by 1 type of opioid on 1 pain stimulus modality, whereas the fourth drug response profile was characterized by average analgesic efficacy across all pain modalities for both opioids. These findings suggest that opioids with varying efficacy at the μ and κ receptors produce independent effects on unique pain mechanisms and that individual responsiveness for some is dependent on pain mechanism and opioid type, although a subset of the population is moderately responsive to opioids regardless of efficacy of receptor binding or predominant pain mechanism being activated. Perspective This investigation provides a foundation for understanding patterns of opioid efficacy in varying types of pain. Our findings suggest that opioid response patterns are more complex than originally thought with about half of individuals exhibiting opioid and pain modality specific analgesic response profiles.

Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 microM against the enzyme.

We compare ab initio broad spectrum calculations of the K-edge X-ray absorption spectra of copper and molybdenum against accurate experimental measurements and tabulated standards on an absolute scale. Comparisons are also presented for the fine structure in the spectra.

The limiting uncertainty in recent high accuracy measurements of the mass attenuation coefficient is the measurement of the integrated column density. An improvement in the design of the absorption foil holder is described which reduces the integrated column density uncertainty. The new design allows the edges of the foil to be more accurately mapped by the X-ray beam by reducing the largest source of uncertainty in the foil mapping: the uncertainty in the points along the foil edge. The method is shown to reduce the uncertainty in measurements of the mass attenuation coefficient of zinc foils. The reduced uncertainty in the full-foil mapping will allow the X-ray Extended Range Technique (XERT) to be applied to small non-metallic absorption foils more accurately.

Introduction During surgery on the thoracic and lumbar spine, SEPs to lower limb (LL) stimulation are used to monitor the dorsal column somatosensory pathways from the legs. SEPs to upper limb (UL) stimulation are often also recorded, to monitor for brachial plexus or peripheral nerve dysfunction related to the positioning of the patient’s arms and to serve as a ”control” for the effects of anesthesia on the LL SEPs. The latter use presumes that cortical SEPs to UL and LL stimulation are affected equally by anesthesia. We examined this assumption by measuring amplitude changes in UL and LL SEPs associated with the transition from TIVA (total intravenous anesthesia) with propofol and a narcotic to a halogenated inhalational anesthetic (HIA) during closing in a neurologically normal patient population. Methods We retrospectively identified surgeries for idiopathic scoliosis in adolescents without neuromuscular disease during which there were no adverse SEP or MEP changes and at least 2 runs of both UL and LL SEPs were recorded after the transition to inhalational anesthesia. The average SEP amplitudes were calculated for those runs and for several SEP waveforms immediately preceding the anesthetic change. Percentage amplitude changes were calculated for SEPs for each limb, the results for the left and right sides were averaged together, and the amplitude ratios (amplitudes under HIA divided by amplitudes under TIVA) for UL SEPs were compared to those for LL SEPs. In all cases, the SEPs were elicited by ulnar nerve and posterior tibial nerve stimulation. Results We identified 17 surgeries meeting inclusion criteria; desflurane was used in 9 and sevoflurane in 8. The patients included 12 girls and 5 boys ages 12–17 years. In one patient the UL SEPs were larger after the anesthetic change (amplitude ratio = 118%); in the other patients the amplitude ratio for UL SEPs ranged from 29% to 91%. Overall, the mean amplitude ratio for UL SEPs was 76%. For LL SEPs, the amplitude ratios ranged from 50% to 97% with a mean of 74%. In 10 patients the relative difference between the amplitude ratios for UL SEPs and LL SEPs was ⩽ 15% and in 6 patients it was between 16% and 40%. In the patient with the largest relative difference, the amplitude ratio was 29% for UL SEPs and 55% for LL SEPs. Conclusion Cortical SEPs were almost always smaller under HIA than under TIVA. On average, the anesthetic effects in the UL SEPs were very similar to those in the LL SEPs (mean amplitude ratio 76% vs. 74%). The effects on UL SEPs versus LL SEPs were also similar in most individual patients, but there were some patients in whom the quantitative effects on UL SEPs and LL SEPs differed by more than 15%. In conclusion, in this patient population UL SEPs provide a good anesthetic control for LL SEPs overall, but it should not be assumed that they can accurately predict quantitative amplitude changes in LL SEPs in individual patients.

We present a new method for investigating roughness for surface structure and internal inhomogeneity down to the nano-scale for thin, nano-structured and opaque materials. The method uses careful measurements of the X-ray mass-attenuation coefficient and is applied to measure the magnitude of the roughness of gold foils. The technique is unique, providing insight into both surface and internal roughness. We show that moments of the distribution function of surface and internal structure can be investigated using this method, and discuss observable signatures. The approach is non-destructive and very sensitive as a local in situ measurement and as a diagnostic for accurate characterisation.

Responses to painful stimuli are characterized by tremendous interindividual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism of the mu-opioid receptor gene ( OPRM1 ) was associated with responses to three different experimental pain modalities in a sample of 167 healthy volunteers (96 female, 71 male). Responses to thermal, mechanical, and ischemic pain were assessed in all subjects, and genotyping of OPRM1 was performed, which revealed that the rare A118G allele occurred in 24 females (25%) and 12 males (17%). Statistical analyses indicated that subjects with a rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. Also, a sex by genotype interaction emerged for heat pain ratings at 49 degrees C, such that the rare allele was associated with lower pain ratings among men but higher pain ratings among women. These data indicate an association of a common single nucleotide polymorphism of OPRM1 with mechanical pain responses and that this genotype may be associated with heat pain perception in a sex-dependent manner. This study examines the association of the A118G SNP of OPRM1 to experimental pain sensitivity. The results indicate that the rare allele is associated with higher pressure pain thresholds. These results support previous contentions that OPRM1 may be a pain-relevant gene; however, replication of these findings is needed.

Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.

To evaluate the dosing and safety of intravenous magnesium sulfate administered via continuous infusion for refractory wheezing.All patients admitted to the pediatric intensive care unit (PICU) between January 1998 and March 2001 who were prescribed magnesium sulfate via continuous infusion were identified via retrospective chart review. The patient's medical history, demographic data, vital signs, magnesium dosing history, and concurrent medications were recorded.Forty PICU patients represent our study population. The mean age was 82.6 +/- 64.6 mo; 18 patients were boys.The mean magnesium loading dose (mg/kg) was 29.6 +/- 13.2 with a mean infusion dose (mg/kg/h) of 18.4 +/- 6.5 with a significant difference in dosing noted between patients weighing less than 30 kg and those with a higher weight. The mean magnesium loading dose (mg/kg) in the less than 30 kg group was 35.3 +/- 12.7 compared with 21.9 +/- 9.9 in the higher weight group (P.05). Mean infusion doses (mg/kg/h) were 21.6 +/- 6 and 14.6 +/- 4.2, respectively (P.05). There was no significant difference between the mean concentrations (mg/dL) reported between the 2 groups (less than 30 kg group = 3.9 +/- 0.6; higher weight group = 3.6 +/- 0.5). All patients received nebulized albuterol, ipratropium, and intravenous methylprednisolone before magnesium therapy. Aminophylline and ketamine were prescribed to 28 and 4 patients, respectively. No cardiovascular adverse effects were noted during magnesium therapy.For the treatment of refractory wheezing, intravenous magnesium sulfate administered via continuous infusion represents a safe mode of drug delivery.

Background: Sedatives are frequently used to facilitate mechanical ventilation of critically ill pediatric patients. Many of these drugs are used in children before appropriate clinical pharmacology and efficacy/safety trials are performed in the targeted pediatric population. Objective: This study assesses the prescribing patterns and clinical utility of propofol as a sedative before anticipated extubation in mechanically ventilated pediatric patients in the absence of pediatric dosing guidelines. Methods: We conducted a retrospective chart review of patients admitted to the Pediatric Intensive Care Unit at Rainbow Babies and Children's Hospital between January 1993 and July 1994 who received propofol as a sedative to facilitate extubation. Results: Forty-eight patients received propofol as a sedative to facilitate extubation. All patients were immediately sedated after the first propofol loading dose. In their attempts to optimize sedation, clinicians made numerous propofol dose adjustments and administered repeat loading doses. Forty-one of these patients were successfully extubated; deterioration in clinical status unrelated to propofol infusion prevented extubation in the remaining 7 patients. Adverse effects possibly associated with propofol administration included hypotension (24 patients), transient decrease in heart rate (1), hypercholesterolemia (4), hypertriglyceridemia (5), abnormal base excess (3), and neurologic events (3). Propofol was discontinued in only 1 hypotensive patient because of perceived drug-induced adverse effects. Five hypotensive patients were managed with fluid therapy, and all laboratory abnormalities resolved either during propofol infusion or after discontinuation. Most patients with elevated blood lipids had received concurrent intravenous lipid therapy. Conclusions: These data suggest that without effective age-appropriate dose recommendations for new drugs with definite pediatric applications, clinicians must depend on bedside clinical observations and pharmacologic data derived from adult patients to determine drug dosing. This lack of pediatric pharmacologic data delays optimal therapy, leading to unnecessary clinical interventions that affect patient care, patient safety, and cost. Despite these limitations, the results of this study suggest that propofol appears to be well tolerated when used to facilitate extubation in mechanically ventilated pediatric patients.

Absolute values of the column densities [ ρ t ] c of four gold foils were measured using micrometry combined with the 2D X-ray attenuation profile. The absolute calibration of [ ρ t ] c was made with a reference foil and the [ ρ t ] c of other foils were determined following the thickness transfer method. By this method, we obtain absolute calibration to 0.1% or better which was not possible using only the X-ray map of a single foil over its central region.

Purpose: We have developed techniques to isolate endothelial cell (EC) progenitors from human peripheral and umbilical cord blood. Methods: Human adult peripheral and umbilical cord blood monocytes were isolated by centrifugation, and progenitor cells were separated with the use of magnetic polystyrene beads that were coated with a monoclonal antibody specific for the CD34 cell–membrane antigen. Cells were propagated in selective media, and developing cultures were immunostained for CD31, CD34, factor VIII, and vascular endothelial growth factor cell receptors. ECs that developed were transfected with a gene for prourokinase and used to line ePTFE grafts, which were evaluated in vitro in a pulsatile flow system. Results: Umbilical cord monocyte cultures demonstrated colonies that resembled ECs at approximately 2 weeks, with growth being best supported by EC growth media plus 20% calf serum with iron. Immunostaining of colonies was positive for CD31 and factor VIII. After 18 days in culture, CD34 + cells from adult peripheral blood were noted, which had the typical cobblestone appearance of ECs and immunostained positively for CD31 and factor VIII–related antigens. Cultures of umbilical cord–derived cells and adult peripheral blood–derived cells developed complex line formations within 1 week in culture that stained positively for vascular endothelial growth factor receptor-2. Urokinase-transfected ECs were shown to overexpress urokinase. Prosthetic grafts lined with transfected cells showed 87.33% ± 4.97% cell adherence after 2 hours in a pulsatile flow system at clinically relevant shear stress. Conclusion: We conclude that endothelial progenitor cells can be isolated from human adult peripheral and umbilical cord blood and developed into EC cultures as a source of cells for vascular graft seeding and gene therapy. (J Vasc Surg 2000;31:181-9.)

To indicate a prohibited activity, pictorials are frequently overlaid with a red circle and 45° left-to-right slash. Previous research suggests that the combination of the slash and symbol may affect the overall identifiability of the warning. The purpose of the present research was to determine whether people's judgments of four types of the circle-slash (a slash over the symbol, a slash under the symbol, a partial slash, and a translucent slash) would differ in perceived effectiveness. Sixteen pictorials with semantically different message content (e.g., NO TRUCKS, DO NOT CLIMB TOWER), in both left-facing and right-facing orientations were viewed by 60 participants. The results revealed that the over and under slashes were preferred to the translucent or partial slashes. Both orientation and slash type influenced preference for a subset of nonsymmetrical symbols. Some of the pictorials with the over slash were given lower evaluations when critical features were concealed. The general preference for the over and under slashes may be due to familiarity and its concordance with Gestalt principles of good figures. Implications for the development of prohibitive pictorials are discussed. Relevance to industry Pictorials are increasingly being used to communicate safety information in cases where the target audience may use different languages. The present research examines different versions of the circle-slash negation symbol for the purpose of determining when critical pictorial elements may be obscured. Implications for pictorial recognition are discussed.

Background: We have evaluated the efficacy of using three-dimensional reconstruction of amplitude Doppler imaging data to quantitatively assess carotid artery bifurcation stenoses. Methods: Sixty-four consecutive frames of amplitude (power) Doppler images are stored to be reassembled into a three-dimensional image representing the patent lumen. These images can then be rotated by any angle necessary to clearly view the vascular anatomy and to make quantitative ultrasound caliper measurements of the stenotic lumen and normal vessel caliber. Results: Three-dimensional Doppler images accurately classified 53 of 61 vessels (87%) into categories of stenosis compared with angiography. All stenoses with >60% diameter reduction were detected and classified as such, for a sensitivity of 100%. Conclusions: Three-dimensional vascular imaging based on amplitude (power) Doppler data provides an accurate noninvasive technique for quantitative diagnosis of carotid bifurcation atherosclerotic disease, with selectable viewing projections that eliminate vessel overlap and other artifacts, and complements the hemodynamic data already available with two-dimensional duplex ultrasound.183

Purpose: We have evaluated the progression of isolated superficial venous thrombosis to deep vein thrombosis in patients with no initial deep venous involvement. Methods: Patients with thrombosis isolated to the superficial veins with no evidence of deep venous involvement by duplex ultrasound examination were evaluated by follow-up duplex ultrasonography to determine the incidence of disease progression into the deep veins of the lower extremities. Initial and follow-up duplex scans evaluated the femoropopliteal and deep calf veins in their entirety; follow-up studies were done at an average of 6.3 days, ranging from 2 to 10 days. Results: From January 1992 to January 1996, 263 patients were identified with isolated superficial venous thrombosis. Thirty (11%) patients had documented progression to deep venous involvement. The most common site of deep vein involvement was progression of disease from the greater saphenous vein in the thigh into the common femoral vein (21 patients, 70%), with 18 of these extensions noted to be nonocclusive and 12 having a free-floating component. Three patients had extended above-knee saphenous vein thrombi through thigh perforators to occlude the femoral vein in the thigh, three patients had extended below-knee saphenous disease into the popliteal vein, and three patients had extended below-knee thrombi into the tibioperoneal veins with calf perforators. At the time of the follow-up examination all 30 patients were being treated without anticoagulation. Conclusions: Proximal saphenous vein thrombosis should be treated with anticoagulation or at least followed by serial duplex ultrasound evaluation so that definitive therapy may be initiated, if progression is noted. More distal superficial venous thrombosis should be carefully followed clinically and repeat duplex ultrasound scans performed, if progression is noted or patient symptoms worsen. (J Vasc Surg 1996;24:745-9.)

Purpose: We have prospectively evaluated the need for serial venous duplex ultrasound examinations in an inpatient population with an initially normal study result. Methods: Patients were selected for study on the basis of clinical suspicion of pulmonary embolism and possible lower extremity deep vein thrombosis, a comorbid condition contributing to a nondiagnostic ventilation/perfusion lung scan, and an initially normal bilateral venous duplex ultrasound examination that included complete evaluation of the femoropopliteal system and the deep calf veins. Repeat duplex examinations were done during the same hospital admission between 5 and 14 days after the initial study. Results: Ninety-four patients with an initially normal duplex ultrasound examination result had repeat studies done at an average of 7.9 ± 2.6 days. Ninety-two examination results remained normal bilaterally. Two patients had isolated intramuscular calf vein deep vein thrombosis: one in the gastrocnemius system of both calves with associated calf tenderness at 11-day follow-up and one in a mid-calf soleal vein without associated symptoms at 10 days. No patients had any evidence of deep vein thrombosis in the femoropopliteal or tibioperoneal venous systems. Conclusions: Serial follow-up duplex ultrasound evaluation is unnecessary after an initially complete, normal study in patients with symptoms who have suspected pulmonary embolism and nondiagnostic ventilation-perfusion lung scans. (J Vasc Surg 1996;24:732-7.)

This study investigated the contribution of unstable self-esteem as a predictor of cardiovascular reactivity (CVR) during a challenging and ego-threatening task. A sample of male and female adults monitored self-esteem perceptions multiple times daily to provide self-esteem stability scores. Participants also engaged in a competitive task that involved the rapid mental calculation of complex addition/ subtraction problems. The task was made more stressful through a manipulation in which participants were made aware that their performance was being monitored and evaluated. Self-esteem stability scores and cynicism scores were used as predictors of systolic and diastolic blood pressure increases and heart rate increases. Results obtained through multiple regression analyses revealed that for men, but not for women, self-esteem instability, relative to cynicism, was a better predictor of increases in systolic blood pressure and heart rate. Neither of these predictors accounted for reactivity in our sample of women, despite the fact that women displayed near equivalent levels of reactivity and equivalent degrees of self-esteem instability. Results suggest that, for men, self-esteem instability may play an important role in the prediction of cardiovascular reactivity to threat that is more dramatic than the contribution of cynicism. Results are also discussed relative to the observed gender differences.

Background. Because of the rapid growth in requests for lower extremity venous duplex ultrasonographic examinations, we have evaluated test results to determine the appropriate indications for testing and whether there is overuse of this technique. Methods. We reviewed the records of all patients who had duplex ultrasonogram during an 18-month period to rule out deep vein thrombosis (DVT). Test outcome was evaluated with data on the age, gender, outpatient or inpatient status, duration of symptoms, physical findings, and risk factors of the patients. Results. We reviewed 3474 examinations; 1265 outpatients and 1231 inpatients were evaluated to rule out DVT, and 978 patients were evaluated to rule out a source of pulmonary embolism. More outpatients were female, and they tended to be younger; outpatients also had more acute femoropopliteal DVT. The presence of sudden onset of unilateral swelling was a strong predictor of acute DVT in all three groups: 52% of such patients were found to have DVT. Mild unilateral symptoms with a coexistent risk factor was associated with a 10% to 20% prevalence of acute DVT. Chronic unilateral swelling was associated with acute DVT only with a coexistent risk factor and only in 1% of such patients. Bilateral swelling was only associated with acute DVT in the inpatient population, with 17% of studies having positive results. If calf tenderness was the only symptom with no associated risk factors, seven (1.6%) of 415 patients had acute DVT and six of these were tibioperoneal. No patients with cellulitis or isolated joint pain had acute DVT. With clinically suspected pulmonary embolism in patients without associated symptoms or risk factors, 7 (1.5%) of 447 studies showed tibioperoneal disease with no acute femoropopliteal disease. Conclusions. The physical examination and clinical history of the patient remain important indicators of the presence (or absence) of lower extremity DVT and can guide the appropriate use of duplex ultrasonography for the diagnosis.

Individuals with anterior cruciate ligament (ACL) injury use greater extensor torques at the hip and ankle and lower extensor torques and joint power at the knee during gait compared to healthy subjects. These adaptations may be mediated by (1) altered neuromuscular strategies due to the injury, (2) training effects produced by rehabilitation protocols, and (3) training effects due to the functional knee brace (FKB) used during rehabilitation. The purpose of the study was to test the hypothesis that a FKB can cause individuals to walk and run with the torque and power patterns observed in rehabilitated ACL-injured individuals. Ten healthy subjects were tested walking and running with and without a FKB. Kinematic and ground reaction data were collected and combined with inverse dynamics to estimate the joint torques and powers. Data were analyzed with a two-way repeated measures ANOVA (gait vs knee condition). In walking, the hip and ankle extensor torques were 14.3% (p < 0.038) and 5.1% (p < 0.003) greater with FKB. In running, the hip extensor torque was 17.0% greater with FKB (p < 0.023). Knee torque was not different between conditions. In walking, the work performed at the hip and knee were 11.6% greater (p < 0.013) and 17.7% lower with FKB (p < 0.025), respectively. Results supported the hypothesis and it was concluded that a FKB may be one causative factor in the development of the unique joint torque and power patterns seen in ACL-injured gait.

Significant hematologic changes are known to occur following intraoperative autotransfusion of shed blood, but the clinical importance of cell washing prior to reinfusion has not been substantiated. To evaluate these changes and their relationship to the use of blood bank products and postoperative morbidity, 26 patients undergoing elective abdominal aortic aneurysm repair were prospectively randomized to reinfusion with washed shed blood or to the use of a collection system in which filtered, but unwashed, whole blood was reinfused intraoperatively. Each patient was evaluated with respect to standard metabolic and hematologic laboratory parameters preoperatively, immediately postoperatively, and 12 to 18 hours postoperatively. Patient demographic data were similar for both groups. Perioperative survival was 100% for both groups. Total blood loss and blood volume autotransfused were significantly greater in the unwashed cell group compared with the washed cell group (p = 0.00014 and p = 0.00011, respectively). Hemoglobin, fibrinogen, prothrombin time, and partial thromboplastin time levels were not significantly different between the two groups at any time perioperatively; fibrin split product and d-dimer levels were significantly higher in the unwashed cell group postoperatively (p = 0.016 and p0.001, respectively). Serum free hemoglobin levels were significantly higher in the immediate postoperative period in the unwashed cell group compared with the washed cell group (p = 0.0013); by 12 to 18 hours postoperatively, this difference was not significant. Haptoglobin levels were significantly lower in the unwashed cell group at both postoperative times (123 +/- 86 mg/dL versus 41 +/- 50 mg/dL, p = 0.0086; 102 +/- 66 mg/dL versus 24 +/- 36 mg/dL, p = 0.0001); however, there was no perioperative renal failure in either group. Furthermore, homologous blood product use was not significantly different between the two groups, with an average of 1.5 +/- 2.5 units of packed red blood cells given to patients in the unwashed cell group versus 0.8 +/- 1.7 units in the washed cell group (p = 0.419). Overall complications were higher and critical care and total hospital stays were longer in the unwashed cell group but did not result from autotransfusion of unwashed blood. We conclude that the intraoperative reinfusion of unwashed shed blood is safe and effective, causing transient hematologic abnormalities that normalize in the early postoperative period, and is not associated with increased mortality, or hematologic, cardiopulmonary, or renal complications.

Prolonged intraoperative renal ischemia requires modalities to reduce the incidence of acute tubular necrosis, but there exists no definitive prophylactic regimen. We studied the effects of enalaprilat, an angiotensin-converting enzyme inhibitor, in an attempt to identify such a protective drug. Thirty-four mongrel dogs underwent 90 min of bilateral renal pedicle clamping. Group I was a control of 6 animals. Group II comprised 10 animals who received 12.5 g iv mannitol 15 min prior to clamping and 1 mg/kg iv furosemide immediately after clamp removal. Group III also comprised 10 animals who received enalaprilat 1 mg/kg iv enalaprilat each 15 min prior to clamp placement. Group IV consisted of 8 dogs, each of which received 12.5 g mannitol and 1 mg/kg iv enalaprilat 15 min prior to clamping and 1 mg/kg iv furosemide immediately upon removal of the clamps. Serum blood urea nitrogen (BUN) and creatinine levels were drawn preoperatively and at 12, 24, 48, and 72 hr postoperatively in each animal. The serum BUN levels in group III were significantly lower than those in group I at all times postoperatively (P < 0.05) and were not significantly different from those of group II at any time postoperatively. Similarly, the serum creatinine levels in group III were significantly lower than those of group I (P < 0.05) and were not significantly different from those in group II at any time postoperatively. Neither the serum BUN nor the serum creatinine levels in group IV were different from those of group I at any time postoperatively. We conclude that intravenous enalaprilat offers significant protection against postischemic renal failure and is as effective as a regimen of mannitol and furosemide. However, the combination of all three offers no protection whatsoever relative to controls.

This study is the first to compare chronic healing characteristics of immediately seeded grafts with those of grafts lined by autogenous venous endothelial cells in tissue culture prior to implantation. Ten mongrel dogs had a segment of external jugular vein excised for enzymatic harvest of endothelial cells. After approximately 21 days growth in tissue culture, 4 × 10 6 cells/ml were inoculated into a 6-cm length of 4 mm i.d. ePTFE for formation of a confluent lining in culture media. The remaining external jugular vein had its endothelial cells enzymatically harvested for immediate seeding of an identical length of preclotted ePTFE. Both grafts were implanted end-to-end in the carotid position and excised after 30 days. In 6 of the 10 dogs, grafts were patent bilaterally; all others were occluded. Planimetric measurements on patent grafts with immediate seeding showed a thrombus-free surface area of 56 ± 39% compared to 86 ± 15% for culture-lined grafts ( P = 0.046). Endothelial coverage was 70 ± 24% for immediately seeded grafts and 29 ± 21% for culture-lined grafts ( P = 0.016). We conclude that immediate seeding and culture lining of autogenous endothelial cells in small diameter ePTFE grafts produce equivalent short-term patency. While culture-lined grafts have an initially less thrombogenic luminal surface, subsequent development of a confluent endothelial lining is slower than that with an immediate seeding preparation, and thus would appear to offer no significant clinical benefit, especially in light of the complexity culture lining adds to the procedure.

In summary, vertebral artery hemodynamics can be readily evaluated both qualitatively and quantitatively. Duplex ultrasonography provides a very reliable noninvasive technique for this assessment. Flow in the vertebral artery system can be noninvasively quantified in greater than 95 per cent of all patients examined using this technique, and such measurements help identify subgroups of patients whose symptoms may be related to posterior circulation ischemia. Further evaluation of the spectral flow patterns is often helpful in diagnosing the cause of these ischemic symptoms. Unfortunately, quantitative flows are rarely obtained during routine carotid ultrasound studies. Such data, however, may provide an objective basis for the following kinds of surgical decisions: 1. Recommendations for carotid surgery in patients with high-grade carotid stenosis but nonlocalizing symptoms. 2. Recommendations for no surgery in patients who have vertebrobasilar symptoms but diminished flow characteristic of poor cardiac output. 3. Recommendations for surgery to augment vertebral artery flow in patients who have vertebrobasilar symptoms, decreased vertebral flow on the basis of proximal stenosis, and normal carotid artery flow. Obviously, there is a need to confirm these hypotheses by studying patients thoroughly before and after surgery. Other investigators must begin gathering data on vertebral artery flow to determine its impact and utility in making surgical decisions.

Corrigendum to “Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis” [Osteoarthritis and Cartilage 2013;21:1243e1252] C.D. King y *, K.T. Sibille y, B.R. Goodin z, Y. Cruz-Almeida y, T.L. Glover y x, E. Bartley y, J.L. Riley y, M.S. Herbert k, A. Sotolongo k, J. Schmidt k, B.J. Fessler k, D.T. Redden {, R. Staud #, L.A. Bradley k, R.B. Fillingim y