Integration and Implementation of Patient-Reported Outcomes: A Prospective, Observational Clinical Quality Improvement Study.

BACKGROUND: Implementation of patient-reported outcomes (PROs) represents a critical barrier to their widespread use and poses challenges to workflow and patient satisfaction. The authors sought to implement PRO surveys into surgical practice and identify principles for successful and broader implementation. METHODS: Outpatient surgical encounters from 2016 through 2019 related to hernia, breast surgery, or postbariatric body contouring were assessed with the Abdominal Hernia-Q, BREAST-Q, or BODY-Q surveys, respectively. Outcomes were implementation rates per quarter and time to optimal implementation (≥80%). Successful implementation principles were identified during the first implemented PRO instrument and applied to subsequent ones. Logistic regression models were used to estimate increase in rate of implementation per quarter by instrument controlling for clinic volume. Risk-adjusted generalized linear models determined predicted mean differences in total clinic time and patient satisfaction. RESULTS: A total of 1206 encounters were identified. The overall survey implementation rate increased from 15% in the first quarter to 90% in the last quarter ( P < 0.01). Abdominal Hernia-Q optimal implementation was reached by 15 months. Principles for successful implementation of PROs were workflow optimization, appropriate patient selection, staff engagement, and electronic survey integration. Consistent application of these principles optimized time to optimal implementation for BREAST-Q [9 months; 18.1% increase in implementation per quarter (95% CI, 1.5 to 37.5); P < 0.01] and BODY-Q [3 months; 56.3% increase in implementation per quarter (95% CI, 26.8 to 92.6); P = 0.03]. Neither patient clinic time ( P = 0.16) nor patient satisfaction differed during the implementation of PROs process ( P = 0.98). CONCLUSIONS: Prospective implementation of PROs can be achieved in surgical practice without an adverse effect on patient satisfaction or workflow. The proposed principles of implementation may be used to optimize efficiency for implementation of PROs.

Prospective Assessment of the Abdominal Hernia-Q (AHQ)-Patient Burden, Reliability, and Longitudinal Assessment of Quality of Life in Hernia Repair.

OBJECTIVE: This study assesses the user burden, reliability, and longitudinal validity of the AHQ, a novel VH patient-reported outcomes measure (PROM). BACKGROUND: We developed and psychometrically validated the AHQ as the first VH-specific, stakeholder-informed PROM. Yet, there remains a need to assess the AHQ's clinical applicability and further validate its psychometric properties. METHODS: To assess patient burden, pre- and postoperative patients were timed while completing the corresponding AHQ form. To measure test-retest reliability, a subset of patients completed the AHQ within a week of initial completion, and consecutive responses were correlated. Lastly, patients undergoing VH repair were prospectively administered the pre- and postoperative AHQ forms, the Hernia-Related Quality of Life Survey and the Short Form-12 both preoperatively and at postoperative intervals, up to over a year after surgery. Quality-of-Life scores were correlated from the 3 PROMs and effect sizes were compared using analysis of normal variance. RESULTS: Median response times for the pre- and postoperative AHQ were 1.1 and 2.7 minutes, respectively. The AHQ demonstrates high test-retest reliability coefficients for pre- and postoperative instruments ( r = 0.91, 0.89). The AHQ appropriately and proportionally measures expected changes following surgery and significantly correlates with all times points of theHernia-Related Quality of Life Survey and Short Form-12 MS and 4/5 (80%) SF12-PS. CONCLUSION: The AHQ is a patient-informed, psychometrically-validated, clinical instrument for measuring, quantifying, and tracking PROMs in VH patients. The AHQ exhibits low response burden, excellent reliability, and effectively measures hernia-specific changes in quality-of-Life following ventral hernia repair.

Comparing para-rowing set-ups on an ergometer using kinematic movement patterns of able-bodied rowers.

While numerous studies have investigated the biomechanics of able-bodied rowing, few studies have been completed with para-rowing set-ups. The purpose of this research was to provide benchmark data for handle kinetics and joint kinematics for able-bodied athletes rowing in para- rowing set-ups on an indoor ergometer. Able-bodied varsity rowers performed maximal trials in three para-rowing set-ups; Legs, Trunk and Arms (LTA), Trunk and Arms (TA) and Arms and Shoulders (AS) rowing. The handle force kinetics of the LTA stroke were comparable to the values for able-bodied literature. Lumbar flexion at the catch, extension at the finish and total range of motion were, however, greater than values in the literature for able-bodied athletes in the LTA set-up. Additionally, rowers in TA and AS set-ups utilised more extreme ranges of motion for lumbar flexion, elbow flexion and shoulder abduction than the LTA set-up. This study provides the first biomechanical values of the para-rowing strokes for researchers, coaches and athletes to use while promoting the safest training programmes possible for para-rowing.

Randomized clinical trial of tranexamic acid-free fibrin sealant during vascular surgical procedures.

BACKGROUND: This study evaluated the safety and haemostatic effectiveness of a fibrin sealant (EVICEL(™) Fibrin Sealant (Human)) during vascular surgery. METHODS: This prospective randomized controlled trial compared the haemostatic effectiveness of fibrin sealant (75 patients) or manual compression (72) in polytetrafluoroethylene (PTFE) arterial anastomoses. The primary endpoint was the absence of bleeding at the anastomosis at 4 min after randomization. Secondary endpoints included haemostasis at 7 and 10 min, treatment failures and the incidence of complications potentially related to bleeding. Adverse events were recorded. RESULTS: A higher percentage of patients who received fibrin sealant versus manual compression achieved haemostasis at 4 min (85 versus 39 per cent respectively; odds ratio 11·34, 95 per cent confidence interval 4·67 to 27·52; P < 0·001). Similarly, a higher percentage of patients who received fibrin sealant achieved haemostasis at 7 and 10 min (both P < 0·001). The incidence of treatment failure was lower in the fibrin sealant group (P < 0·001). The rate of complications potentially related to bleeding was similar (P = 0·426). Some 64 per cent of patients who received fibrin sealant experienced at least one adverse event, compared with 71 per cent who received manual compression. CONCLUSION: This fibrin sealant was safe, and significantly shortened the time to haemostasis in vascular procedures using PTFE. REGISTRATION NUMBER: NCT00154141 (http://www.clinicaltrials.gov).

Long-term follow-up of Greenfield inferior vena cava filter placement in children.

OBJECTIVE: The long-term results of Greenfield inferior vena cava (IVC) filter placement have been well documented in adults; however, similar data do not exist for pediatric patients. The potential for growth and the increased life expectancy in younger patients may contribute to a difference in the natural history of filters placed in children. The objective of this study was to evaluate the long-term outcome of pediatric patients with IVC filters. METHODS: At the University of Massachusetts Memorial Medical Center, medical records and radiographs of patients 18 years old or younger at the time of IVC filter placement were reviewed. Follow-up data were obtained by interview, physical examination, and venous duplex ultrasound scanning. RESULTS: A total of 15 IVC filters were placed in children 18 years old or younger between 1983 and 1999. In 10 patients the indications for IVC filter placement were lower-extremity deep venous thrombosis (DVT) and/or pulmonary embolism. In five patients, prophylactic filters were placed in the absence of DVT because of a high risk for the development of pulmonary embolism. Surgical exposure of the right internal jugular vein was used to place the first eight filters. The remainder were inserted percutaneously through the right internal jugular vein or the right common femoral vein. There were no complications or mortality related to filter insertion. Follow-up of the surviving 14 patients ranged from 19 months to 16 years. During long-term follow-up, no patient had a pulmonary embolus. Of the nine patients who had lower-extremity DVT, three developed mild common femoral venous reflux documented by duplex scan. Of the five patients who had prophylactic filters, four had no symptoms or duplex evidence of reflux. The other patient, who was paraplegic, had bilateral leg edema but no venous varicosities and no reflux on duplex scan 11 years after filter placement. No patient in either group had chronic venous obstruction. CONCLUSION: In long-term follow-up there were no instances of pulmonary embolism, IVC thrombosis, significant postphlebitic symptoms, or significant filter migration among 14 pediatric patients with Greenfield IVC filters. This suggests a safety profile and efficacy similar to that seen in adults.

Stratification of flare intensity identifies placebo responders in a treatment efficacy trial of patients with osteoarthritis.

OBJECTIVE: Studies evaluating osteoarthritis treatment often use increased arthritis activity ("flare") as a selection criterion, although no standardized assessments are available to quantify flare intensity and little is known about how this criterion affects treatment comparisons. This study evaluated the reliability of a flare assessment and how pretreatment flare intensity impacts conclusions on treatment efficacy. METHODS: Using data from a double-blind, randomized, controlled trial (n = 182), we compared 3 osteoarthritis treatments with placebo in patients who met 3 of 4 flare criteria. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to document levels of pain, stiffness, and physical functioning at baseline and at the final visit. Following factor analytic evaluation, the flare items were standardized and summed to create a flare intensity index, which was used to identify patient subgroups. Analysis of covariance was applied to compare change in WOMAC scale scores from baseline to final visit for assessment of treatment differences among the flare intensity subgroups. RESULTS: The flare indicators appeared unidimensional. Analyses were stratified by tertiles of flare intensity. Mean WOMAC scores improved in the patients receiving active treatment who were categorized into the 2 lowest flare intensity subgroups, but mean WOMAC scores improved in patients in all 4 treatment groups (active and placebo) in the most intense flare subgroup. CONCLUSION: Patients with higher intensity flares may be more likely to report substantial improvement in functional status regardless of treatment. Failure to account for flare intensity in analyses of data from pain trials with flare-based designs may inflate the risk of Type I and Type II errors in the interpretation of study results.

Judging jury service: results of the North Carolina administrative office of the courts juror survey.

This study examined venirepersons' and jurors' levels of satisfaction with jury service. Surveys were distributed to all persons who reported for state court jury service during two one-week periods in each North Carolina county. Questions concerned satisfaction with various aspects of jury service, the effects of service, hardships experienced, details of and reactions to cases heard, and basic demographic information. Responses were obtained from 82 of the 100 counties and 4,654 venirepersons (of whom 1,478 served as jurors). Consistent with prior research on juror experiences, results generally revealed high levels of satisfaction and positive opinions about various aspects of jury service. Service did not influence opinions about the courts for most respondents, and those whose opinions changed tended to become more positive about jury service. Suggestions for future research emphasize giving higher priority to publishing unpublished research on jury experience, explaining the high satisfaction levels observed in samples of jurors, and examining the impact of trial reform on juror satisfaction levels.

A comparison of cilostazol and pentoxifylline for treating intermittent claudication.

PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks. RESULTS: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups. CONCLUSION: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.

Recombinant thrombomodulin inhibits arterial smooth muscle cell proliferation induced by thrombin.

PURPOSE: Restenosis after angioplasty or bypass grafting to restore circulation to ischemic organs is still an unsolved problem. Thrombin generated in high concentrations at the sites of vascular injury plays a central role in thrombosis and hemostasis. alpha-Thrombin has also been implicated as a mitogen for smooth muscle cell (SMC) proliferation that contributes to arterial restenosis. Thrombomodulin has a high affinity of binding with thrombin and converts thrombin from a procoagulant to an anticoagulant. This study was designed to examine whether thrombomodulin could also moderate the thrombin-mediated SMC proliferative response. METHODS: Porcine carotid artery SMCs (passages 4-7) were plated onto 96-well plates and incubated for 3 days. After growth arrest in a defined serum-free medium for 2 to 3 days, SMCs were subjected to the reagents as follows: (1) human alpha-thrombin, (2) recombinant human soluble thrombomodulin containing a chondroitin sulfate moiety, (3) thrombin receptor agonist peptide (SFLLRNPNDKYEPF), and (4) alpha-thrombin or thrombin receptor agonist peptide combined with recombinant thrombomodulin (rTM). The viability and proliferation status of SMCs were quantified with MTT (thiazolyl blue) mitochondrial function and bromodeoxyuridine (BrdU)-DNA incorporation assays. RESULTS: Human alpha-thrombin increased SMC proliferation in a dose dependent manner by more than 25% and 30% with thrombin 1 U/mL to 3 U/mL compared with control groups on day 7 (P <.006). rTM concentrations from 0.5 microg/mL to 3 microg/mL have no significant effect on SMC growth. The stimulation of SMC proliferation induced by alpha-thrombin at 0.5 U/mL, 1 U/mL, and 2 U/mL was significantly inhibited with rTM at 2 microg/mL and 3 microg/mL on days 3, 7, and 10 as evaluated with MTT assay (P <.01 to <.05) and BrdU-DNA incorporation assay on day 3 (P <.008). Thrombin receptor agonist peptide increased SMC BrdU-DNA incorporation at 48 hours (P <.007), and its effect was not altered by rTM. CONCLUSION: rTM containing all of the extracellular domains of thrombomodulin inhibits the effect of thrombin on SMC proliferation in vitro. Because thrombin is a mitogenic mediator of SMC in vascular injury, inhibition of its function in vivo could help to prevent SMC hyperplasia. The success of further studies in vivo may lead to use of rTM for decreasing or preventing arterial restenosis.

Real-time imaging of the dynamics of secretory granules in growth cones.

Secretory granules containing a hybrid protein consisting of the regulated secretory protein tissue plasminogen activator and an enhanced form of green fluorescent protein were tracked at high spatial resolution in growth cones of differentiated PC12 cells. Tracking shows that granules, unlike synaptic vesicles, generally are mobile in growth cones. Quantitative analysis of trajectories generated by granules revealed two dominant modes of motion: diffusive and directed. Diffusive motion was observed primarily in central and peripheral parts of growth cones, where most granules diffused two to four orders of magnitude more slowly than comparably sized spheres in dilute solution. Directed motion was observed primarily in proximal parts of growth cones, where a subset of granules underwent rapid, directed motion at average speeds comparable to those observed for granules in neurites. This high-resolution view of the dynamics of secretory granules in growth cones provides insight into granule organization and release at nerve terminals. In particular, the mobility of granules suggests that granules, unlike synaptic vesicles, are not tethered stably to cytoskeletal structures in nerve terminals. Moreover, the slow diffusive nature of this mobility suggests that secretory responses involving centrally distributed granules in growth cones will occur slowly, on a time scale of minutes or longer.

A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial.

BACKGROUND: Effective medication is limited for the relief of intermittent claudication, a common manifestation of arterial occlusive disease. Cilostazol is a potent inhibitor of platelet aggregation with vasodilation effects. OBJECTIVE: To evaluate the safety and efficacy of cilostazol for the treatment of intermittent claudication. METHODS: Thirty-seven outpatient vascular medicine clinics at regional tertiary and university hospitals in the United States participated in this multicenter, randomized, double-blind, placebo-controlled, parallel trial. Of the 663 screened volunteer patients with leg discomfort, a total of 516 men and women 40 years or older with a diagnosis of moderately severe chronic, stable, symptomatic intermittent claudication were randomized to receive cilostazol, 100 mg, cilostazol, 50 mg, or placebo twice a day orally for 24 weeks. Outcome measures included pain-free and maximal walking distances via treadmill testing, patient-based quality-of-life measures, global assessments by patient and physician, and cardiovascular morbidity and all-cause mortality survival analysis. RESULTS: The clinical and statistical superiority of active treatment over placebo was evident as early as week 4, with continued improvement at all subsequent time points. After 24 weeks, patients who received cilostazol, 100 mg, twice a day had a 51% geometric mean improvement in maximal walking distance (P<.001 vs placebo); those who received cilostazol, 50 mg, twice a day had a 38% geometric mean improvement in maximal walking distance (P<.001 vs placebo). These percentages translate into an arithmetic mean increase in distance walked, from 129.7 m at baseline to 258.8 m at week 24 for the cilostazol, 100 mg, group, and from 131.5 to 198.8 m for the cilostazol, 50 mg, group. Geometric mean change for pain-free walking distance increased by 59% (P<.001) and 48% (P<.001), respectively, in the cilostazol, 100 mg, and cilostazol, 50 mg, groups. These results were corroborated by the results of subjective quality-of-life assessments, functional status, and global evaluations. Headache, abnormal stool samples or diarrhea, dizziness, and palpitations were the most commonly reported potentially drug-related adverse events and were self-limited. A total of 75 patients (14.5%) withdrew because of any adverse event, which was equally distributed between all 3 treatment groups. Similarly, there were no differences between groups in the incidence of combined cardiovascular morbidity or all-cause mortality. CONCLUSION: Compared with placebo, long-term use of cilostazol, 100 mg or 50 mg, twice a day significantly improves walking distances in patients with intermittent claudication.

Real-time imaging of the axonal transport of granules containing a tissue plasminogen activator/green fluorescent protein hybrid.

A hybrid protein, tPA/GFP, consisting of rat tissue plasminogen activator (tPA) and green fluorescent protein (GFP) was expressed in PC12 cells and used to study the distribution, secretory behavior, and dynamics of secretory granules containing tPA in living cells with a neuronal phenotype. High-resolution images demonstrate that tPA/GFP has a growth cone-biased distribution in differentiated cells and that tPA/GFP is transported in granules of the regulated secretory pathway that colocalize with granules containing secretogranin II. Time-lapse images of secretion reveal that secretagogues induce substantial loss of cellular tPA/GFP fluorescence, most importantly from growth cones. Time-lapse images of the axonal transport of granules containing tPA/GFP reveal a surprising complexity to granule dynamics. Some granules undergo canonical fast axonal transport; others move somewhat more slowly, especially in highly fluorescent neurites. Most strikingly, granules traffic bidirectionally along neurites to an extent that depends on granule accumulation, and individual granules can reverse their direction of motion. The retrograde component of this bidirectional transport may help to maintain cellular homeostasis by transporting excess tPA/GFP back toward the cell body. The results presented here provide a novel view of the axonal transport of secretory granules. In addition, the results suggest that tPA is targeted for regulated secretion from growth cones of differentiated cells, strategically positioning tPA to degrade extracellular barriers or to activate other barrier-degrading proteases during axonal elongation.

Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial.

BACKGROUND: Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication. METHODS AND RESULTS: Study inclusion criteria included age > or =40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Treatment and control groups were similar with respect to age, severity of symptoms, ankle pressures, and smoking status. Statistical analyses used intention-to-treat analyses for each of 77 subjects who had > or =1 treadmill test after initiation of therapy. Comparisons between groups were based on logarithms of ratios of ICD and ACD changes from baseline using ANOVA test at last treatment visit. The estimated treatment effect showed a 35% increase in ICD (P<0.01) and a 41% increase in ACD (P<0.01). There was no significant change in resting or postexercise ankle/brachial indexes. Patients' and physicians' subjective assessments corroborated the measured improvements in walking performance observed in the cilostazol-treated group. CONCLUSIONS: Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.

Spontaneous tibial artery thrombosis associated with varicella pneumonia and free protein S deficiency.

Pneumonia is the most common serious complication of varicella infection in adults. A variety of thrombotic complications including purpura fulminans and disseminated intravascular coagulation have been reported in children with varicella but not in adults. Two men with varicella pneumonia who had profound lower extremity ischemia caused by thrombosis of the profunda femoris and tibial arteries are reported. Both patients had free protein S deficiency and vascular thrombosis in association with varicella pneumonia without overt evidence of disseminated intravascular coagulation or purpura fulminans. Antiphospholipid immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the other had evidence of the lupus anticoagulant. The proposed pathogenesis and management options including intraarterial thrombolytic therapy with urokinase and the need for long-term anticoagulation are discussed.

Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.

PURPOSE: This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease. METHODS: The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing. RESULTS: Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness. CONCLUSIONS: Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.

Adenosine A2a receptors increase arterial endothelial cell nitric oxide.

BACKGROUND: Adenosine is a potent vasodilator of vascular smooth muscle. Endothelium-derived nitric oxide (NO) elicits vasodilation. We have previously reported that adenosine stimulates the production of NO from porcine carotid arterial endothelial cells (PCAEC) via a receptor-mediated mechanism. This study was to determine whether adenosine also enhances NO production from human arterial endothelium and to define the involvement of adenosine A1 and A2 receptors. MATERIALS AND METHODS: Human iliac arterial endothelial cells (HIAEC) and PCAEC were harvested and cultured in dishes. NO production was evaluated with a NO electrode sensor which measured continuously real-time NO production. RESULTS: NO content of the medium bathing HIAEC and PCAEC was significantly increased with adenosine (100 micromol/L). Ethylcarboxamidoadenosine (NECA), a nonselective adenosine receptor agonist, and carboxyethyl-phenethylamino-ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A2a receptor agonist, increased NO production by HIAEC and PCAEC with respective EC50 values of 3.32 and 6.96 nmol/L for NECA and 30.97 and 29.47 nmol/L for CGS-21680. Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 micromol/L), an adenosine A1 and A2 receptor antagonist, and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385; 1 micromol/L), a selective adenosine A2a receptor antagonist, inhibited the effect of CGS-21680. Chlorocyclopentyl-adenosine (CCPA; 1 micromol/L), an adenosine A1 receptor agonist, significantly depressed NO production by both HIAEC and PCAEC: This effect was inhibited by cyclopentyl-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist. CONCLUSIONS: The results demonstrate that adenosine A2a receptors increase, and adenosine A1 receptors decrease, the production of NO by human and porcine arterial endothelial cells.

Chromatin dynamics in interphase nuclei and its implications for nuclear structure.

Translational dynamics of chromatin in interphase nuclei of living Swiss 3T3 and HeLa cells was studied using fluorescence microscopy and fluorescence recovery after photobleaching. Chromatin was fluorescently labeled using dihydroethidium, a membrane-permeant derivative of ethidium bromide. After labeling, a laser was used to bleach small (approximately 0.4 microm radius) spots in the heterochromatin and euchromatin of cells of both types. These spots were observed to persist for >1 h, implying that interphase chromatin is immobile over distance scales >/=0.4 microm. Over very short times (<1 s), a partial fluorescence recovery within the spots was observed. This partial recovery is attributed to independent dye motion, based on comparison with results obtained using ethidium homodimer-1, which binds essentially irreversibly to nucleic acids. The immobility observed here is consistent with chromosome confinement to domains in interphase nuclei. This immobility may reflect motion-impeding steric interactions that arise in the highly concentrated nuclear milieu or outright attachment of the chromatin to underlying nuclear substructures, such as nucleoli, the nuclear lamina, or the nuclear matrix.

Is coronary angiography necessary for vascular surgery patients who have positive results of dipyridamole thallium scans?

PURPOSE: Because dipyridamole thallium (DT) scanning is a useful predictor of perioperative cardiac events, a positive results of a DT scan is frequently the basis for performing more invasive cardiac evaluation and for consideration for performing coronary revascularization procedures before performing peripheral vascular surgery. The rationale for this approach has been that the treatment of anatomically significant coronary artery disease would lower the risk of performing a subsequent vascular operation. However, the benefit of performing aggressive diagnostic and therapeutic cardiac procedures in such patients remains unproved. To examine this issue, data from patients who underwent coronary angiography because of thallium redistribution were compared with data from matched control subjects who underwent peripheral vascular operations without further cardiac evaluation. METHODS: The medical records of 70 consecutive patients who underwent coronary angiography because of the presence of two or more segments of redistribution on DT scan were reviewed and compared with 70 other patients matched with respect to age, gender, peripheral vascular operation, and number of segments of redistribution on DT scan who did not undergo additional cardiac evaluation. RESULTS: DT scans were performed on 934 preoperative peripheral vascular surgery patients to help in the assessment of operative risk. Ischemic responses, defined as two or more segments of redistribution, were observed in 297. Of these, 70 underwent cardiac catheterization and 25 underwent coronary revascularization procedures. Adverse outcomes affected 46% of the coronary angiography group and 44% of the control group (p = NS). Patients who underwent coronary angiography and were considered for myocardial revascularization had fewer cardiac events with a subsequent vascular operation than did the control subjects. However, any possible benefit from invasive cardiac evaluation was offset by the three deaths and two myocardial infarctions (MIs) that complicated the cardiac evaluation. There was no significant difference between the angiography group and the matched control subjects with respect to perioperative nonfatal MI (13% vs 9%), fatal MI (4% vs 3%), late nonfatal MI (16% vs 19%), or late cardiac death (10% vs 13%). In long-term follow-up, MIs occurred later in patients who underwent coronary angiography than the control subjects (p = 0.049), but this difference was not associated with an improvement in the overall survival rate. CONCLUSIONS: The risks of extended cardiac evaluation and treatment did not produce any improvement in either the perioperative or the long-term survival rate. For most vascular surgery patients who have a positive result of a DT scan, coronary angiography does not provide any additional useful information.

How effective is the motion-to-suppress safeguard? Judges' perceptions of the suggestiveness and fairness of biased lineup procedures.

The motion-to-suppress safeguard is designed to prevent false eyewitness identifications from leading to wrongful convictions. This safeguard is effective only if judges are sensitive to factors that influence lineup suggestiveness. The present study assessed judge sensitivity to foil, instruction, and presentation biases. Judges (N = 99) read a description of a hypothetical crime, perpetrator, and identification procedure followed by a motion to suppress the identification. Judges completed a questionnaire in which they ruled on the motion and rated the lineup's suggestiveness and fairness. Foil bias and instruction bias influenced judges' rulings and lineup evaluations as predicted. Hypotheses concerning presentation bias were not supported. These results suggest that judges are somewhat sensitive to lineup suggestiveness but there is room for improvement.

Heparin and protamine stimulate the production of nitric oxide.

Heparin has been shown to decrease total vascular resistance while protamine stimulates endothelium-dependent vasodilation. This study was undertaken to determine whether heparin and/or protamine could enhance endothelium-derived relaxing factor (EDRF), as determined by nitric oxide (NO) production. Porcine carotid artery endothelial cells (PAECs) were seeded on multiwell plates, grown to confluence, and exposed to heparin (1-20 U/ml) or protamine (50-200 microg/ml) for 24 hours. With the addition of the NO synthase inhibitor, N(G)-monomethyl-L-arginine (NMMA), to heparin and/or protamine, the medium samples were collected in one hour. In a parallel clinical study, plasma samples were collected from patients undergoing cardiopulmonary bypass (CPB). The NO production was measured as reflected by the formation of nitrite (NO2-) and nitrate (NO3-), the stable end-metabolites of NO. NO production by PAECs was significantly increased by heparin > or = 5 U/ml or protamine > or = 50 microg/ml in a concentration-dependent manner. The increase of NO production was prevented by the addition of NMMA. In CPB patients, plasma NO2-/NO3- concentration was significantly increased after heparin administration compared to the preoperative value, at which time the mean plasma heparin level was 4.9+/-0.5 U/ml. Following slow protamine infusion, there was no significant difference in plasma NO2-/NO3- concentration compared to preoperative value. In conclusion NO production increases following exposure of PAECs to heparin and/or protamine. In patients, NO concentration significantly increased after heparin administration by IV bolus, but not with a slow infusion of protamine after CPB.