Improvements in Air Quality and Health Outcomes Among California Medicaid Enrollees Due to Goods Movement Actions.

INTRODUCTION: In 2006, the California Air Resources Board (CARB) and local air quality management districts implemented an Emission Reduction Plan for Ports and Goods Movement program (referred to hereinafter as GM policy actions) (CARB 2006). The GM policy actions comprise approximately 200 actions with an estimated investment value of $6 to $10 billion. These actions targeted the major sources and polluters related to goods movements, such as highways; ports and railyard trucks; ship fuel and shore power; cargo equipment; and locomotives. These actions aimed to reduce total statewide domestic GM emissions to 2001 levels or lower by the year 2010; to reduce the statewide diesel particulate matter (DPM) health risk from GM by 85% by the year 2020; and to reduce the nitrogen oxides (NOx) emissions from international GM in the South Coast Air Basin by 30% from projected 2015 levels and 50% from projected 2020 levels. The years 2006 and 2007 marked an important milestone in starting to regulate GM polluters and adopting stricter standards for traffic-related air pollution.This project aimed to examine the impact of the GM policy actions on reductions in ambient air pollution and subsequent improvements in health outcomes of Medi-Cal fee-for-service (FFS) beneficiaries with chronic conditions in 10 counties in California. Specifically, we examined whether the GM policy actions reduced air pollution near GMC corridors more than in control areas. We subsequently assessed whether there were greater decreases in emergency room (ER) visits and hospitalizations for enrollees with chronic conditions who lived in the GM corridors (GMCs) than for those who lived in other areas. METHODS: The study used a quasi-experimental design. We defined areas within 500 m of truck-permitted freeways and ports as GMCs. We further defined non-goods movement corridors (NGMCs) as locations within 500 m of truck-prohibited freeways or 300 m of a connecting roadway, and areas out of GMCs and NGMCs as controls (CTRLs). We defined years 2004-2007 as the pre-policy period and years 2008-2010 as the post-policy period. We developed linear mixed-effects land use regression models and created annual air pollution surfaces for nitrogen dioxide (NO2), fine particulate matter (PM2.5), and ozone (O3) across California for years 2004-2010 at a spatial resolution of 30 m, then assigned them to enrollees' home addresses.We used a retrospective cohort of 23,000 California Medicaid (Medi-Cal) FFS adult beneficiaries living in 10 California counties with six years of data (September 1, 2004, to August 31, 2010). Cohort beneficiaries had at least one of four chronic conditions, including asthma, chronic obstructive pulmonary disease (COPD), diabetes, and heart disease.We used a difference-in-differences (DiD) model to assess whether air pollutant concentration and health care utilization (ER visits and hospitalizations) for cohort beneficiaries declined more for those living in intervention corridors (GMCs, NGMCs) than those living in CTRLs. All the models controlled for age, sex, language spoken, race/ethnicity, number of comorbidities in baseline years, county, time-varying health indicator variables, and several neighborhood variables.To facilitate interpretation, we calculated the DiD estimates in each of the three years after the policy intervention. The DiD was used to assess the causal impact of regulatory policy on reductions of air pollution, as well as for the improvements in health outcomes.We explored whether improvements in health outcomes were due to the air pollution reduction by using a multi- level mediation model, in which the effect of GM actions on health outcomes was mediated through the effect of actual air pollution reductions in the post-policy years. We used the Generalized Structural Equation Models for the estimation and combined the effects of NO2 and PM2.5 in the model. To further verify the causal inferences of the GM actions on reductions of exposures and improvements in health outcomes, we performed sensitivity analyses with propensity score weighting. RESULTS: We observed statistically significant reductions in pollutant NO2 and PM2.5 concentrations for enrollees in all 10 counties. The enrollees in GMCs experienced greater reductions in NO2 and PM2.5 from the pre- to the post-policy periods than those in CTRLs. Greater reductions were also observed among beneficiaries living in NGMCs versus those in CTRLs, but those reductions were smaller than among beneficiaries living in GMCs. For O3 concentrations, an opposite trend was observed.Furthermore, we observed significantly greater reductions in ER visits for patients with asthma and COPD living in GMCs than those in CTRLS in the post-policy years. For example, we saw in the DiD modeling results there were 170 fewer ER visits for 1,000 beneficiaries with asthma per year in GMCs if the regionwide trend in the CTRL group was considered not related to the GM policy. Similarly, among the beneficiaries with COPD, there were 180 fewer ER visits per 1,000 patients estimated in the GMCs for the third year after the implementation of the policy.We also observed greater reductions in ER visits among those with asthma, when comparing NGMCs with CTRLs, but reductions were smaller than comparisons between GMCs and CTRLs. The ER visits for those with COPD, diabetes, and the total sample in NGMCs also had downward trends in the post-policy year in comparison with those in CTRLs but the differences were not statistically significant; similar phenomena were also observed for the ER visits among those with diabetes and heart diseases and in the total sample when GMCs versus CTRLs and GMCs versus NGMCs were compared. Although hospitalizations also decreased more in GMCs than in NGMCs and more in NGMCs than in CTRLs in the post-policy period, results were not statistically significant.Using the mediation models, we observed 0.129 more reductions in the expected number of ER visits among individuals with asthma for a composite reduction in one unit NO2 and one unit PM2.5 (DiD = -0.129, P < 0.05) from the pre-policy years to the post-policy years. The reductions in NO2 and PM2.5 due to policy change estimated by the mediation model are essentially the same as shown in the respective DiD models. Mediation analyses suggested that the effects of GM policy interventions on health improvements were largely due to exposure reductions. Finally, sensitivity analyses with propensity scores produced similar DiD results. CONCLUSIONS: This project has produced empirical evidence that air pollution control actions reduced pollution exposures among disadvantaged and susceptible populations. More importantly, our findings suggest that the reductions in air pollution led to health outcome improvements among low-income people with chronic conditions. Our investigation also contributed to scientific methods for assessing the health effects of long-term, large-scale, and complex regulatory actions with routinely collected pollutants and medical claims data. Therefore, the results strongly support both short-term and long-term efforts to improve air quality for all members of society and future studies on the impact of air pollution control policies.

Serum miR-17 levels in patients with hepatitis B virus induced liver fibrosis.

OBJECTIVE: To investigate the clinical significance of detecting serum level of miR-17 in patients with hepatitis B virus (HBV) induced liver fibrosis. PATIENTS AND METHODS: A total of 200 HBV patients undergoing liver biopsy in Henan Provincial People's Hospital from June 2016 to December 2018, and 200 healthy subjects during the same period were included. Serum miR-17 level was detected by qRT-PCR. Multivariate Logistic regression analysis was conducted to evaluate independent risk factors of liver fibrosis in HBV patients. Meanwhile, ROC curves were used to assess the value of miR-17 in determining liver fibrosis severity of HBV patients. RESULTS: 200 HBV patients were classified into 4 groups based on the severity of liver fibrosis, including 52 cases in S0-1, 47 cases in S2, 53 cases in S3, and 48 cases in S4. Serum level of miR-17 was lower in healthy subjects than that in HBV patients. In addition, the serum level of miR-17 was negatively correlated with liver fibrosis severity. The relative levels of aspartate aminotransferase (AST), HBV-DNA, albumin (ALB), platelets (PLT), aspartate aminotransferase-to-platelet ratio index (APRI) and miR-17 were the independent factors of advanced liver fibrosis in HBV patients. Serum level of miR-17 exerted a predictive potential in diagnosis of the severity of HBV-induced liver fibrosis. CONCLUSIONS: Serum miR-17 level is highly expressed in HBV patients, and negatively correlated with liver fibrosis severity, which could be utilized as a non-invasive hallmark assessing liver fibrosis severity in HBV patients.

PARP-1 Involvement in Autophagy and Their Roles in Apoptosis of Vascular Smooth Muscle Cells under Oxidative Stress.

Autophagy and poly(ADP-ribose) polymerase 1 (PARP-1) are activated and involved in a series of cell processes under oxidative stress, which is associated with pathogenesis of atherosclerosis. Research on their relationship under oxidative stress has been limited. In this study, we aimed to investigate the activation, relationship, and role of autophagy and PARP-1 in vascular smooth muscle cell (VSMC) death under oxidative stress. This study explored the signal molecule PARP-1 and autophagy in VSMCs using gene silencing and the hydrogen peroxide (H2O2)-stimulated oxidative stress model. We observed that H2O2 could induce autophagy in VSMCs, and the inhibition of autophagy could protect VSMCs against oxidative stress-mediated cell death. Meanwhile, PARP-1 could also be activated by H2O2. Additionally, we analysed the regulatory role of PARP-1 in oxidative stress-mediated autophagy and found that PARP-1 was a novel factor involved in the H2O2-induced autophagy via the AMPK-mTOR pathway. Finally, PARP-1 inhibition protected VSMCs against caspase-dependent apoptosis. These data suggested that PARP-1 played a critical role in H2O2-mediated autophagy and both of them were involved in apoptosis of VSMCs.

RESEARCH ARTICLE Molecular cloning and expression analysis of a matrix Gla protein gene in the spinyhead croaker, Collichthys lucidus.

The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics. The Gla domain and the invariant unit ErraEtCedyspC, which has been identified in all known vitamin K-dependent vertebrate proteins, were highly conserved in Cl-MGP, suggesting that it uses the same mechanism to function as the known proteins. An alignment analysis revealed that Cl-MGP had the highest identity with Larimichthys crocea (93%), which had lost five amino acid residues in the C-terminal. A quantitative real-time polymerase chain reaction revealed that Cl-MGP expression was highest in the gill, followed by the cholecyst and spleen, with almost no expression in the blood, muscle, or testes. The high Cl-MGP expression in the gill is similar to that observed in other fish species, but the relatively high expression found in the cholecyst and spleen is not seen in all species. Future studies should investigate the tissue distributions of both mRNA and proteins in different species, in order to understand the function and evolution of MGP in different species.

Optimization of selective breeding through analysis of morphological traits in Chinese sea bass (Lateolabrax maculatus).

Determining correlations between certain traits of economic importance constitutes an essential component of selective activities. In this study, our aim was to provide effective indicators for breeding programs of Lateolabrax maculatus, an important aquaculture species in China. We analyzed correlations between 20 morphometric traits and body weight, using correlation and path analyses. The results indicated that the correlations among all 21 traits were highly significant, with the highest correlation coefficient identified between total length and body weight. The path analysis indicated that total length (X1), body width (X5), distance from first dorsal fin origin to anal fin origin (X10), snout length (X16), eye diameter (X17), eye cross (X18), and slanting distance from snout tip to first dorsal fin origin (X19) significantly affected body weight (Y) directly. The following multiple-regression equation was obtained using stepwise multiple-regression analysis: Y = -472.108 + 1.065X1 + 7.728X5 + 1.973X10 - 7.024X16 - 4.400X17 - 3.338X18 + 2.138X19, with an adjusted multiple-correlation coefficient of 0.947. Body width had the largest determinant coefficient, as well as the highest positive direct correlation with body weight. At the same time, high indirect effects with six other morphometric traits on L. maculatus body weight, through body width, were identified. Hence, body width could be a key factor that efficiently indicates significant effects on body weight in L. maculatus.

Characterization and expression analysis of the prophenoloxidase activating factor from the mud crab Scylla paramamosain.

Prophenoloxidase activating factors (PPAFs) are a group of clip domain serine proteinases that can convert prophenoloxidase (pro-PO) to the active form of phenoloxidase (PO), causing melanization of pathogens. Here, two full-length PPAF cDNAs from Scylla paramamosain (SpPPAF1 and SpPPAF2) were cloned and characterized. The full-length SpPPAF1 cDNA was 1677 bp in length, including a 5'-untranslated region (UTR) of 52 bp, an open reading frame (ORF) of 1131 bp coding for a polypeptide of 376 amino acids, and a 3'-UTR of 494 bp. The full-length SpPPAF2 cDNA was 1808 bp in length, including a 5'-UTR of 88 bp, an ORF of 1125 bp coding for a polypeptide of 374 amino acids, and a 3'-UTR of 595 bp. The estimated molecular weight of SpPPAF1 and SpPPAF2 was 38.43 and 38.56 kDa with an isoelectric point of 7.54 and 7.14, respectively. Both SpPPAF1 and SpPPAF2 proteins consisted of a signal peptide, a characteristic structure of clip domain, and a carboxyl-terminal trypsin-like serine protease domain. Expression analysis by qRT-PCR showed that SpPPAF1 mRNA was mainly expressed in the gill, testis, and hemocytes, and SpPPAF2 mRNA was mainly expressed in hemocytes. In addition, SpPPAF1 and SpPPAF2 mRNA was expressed in a time-dependent manner after Vibrio parahaemolyticus challenge. The results showed that expression of both SpPPAF1 and SpPPAF2 was related to the bacterial challenge but the expression patterns differed. These findings suggest that SpPPAF is a serine proteinase and may be involved in the pro-PO activation pathway of the crab innate immune system.

Bedside clinical methods useful as screening test for aspiration in elderly patients with recent and previous strokes.

INTRODUCTION: This study was undertaken to ascertain the usefulness of clinical screening tools for dysphagia in a heterogeneous group of older stroke patients. The usefulness of bedside clinical assessment tools for detecting dysphagia on different consistencies of feeds was also studied. MATERIALS AND METHODS: Fifty patients referred to a speech therapist for the assessment of possible dysphagia were recruited. The clinical tools studied included the water swallow test, the oxygen desaturation test and the combination of both tests (termed "clinical aspiration test"). The outcomes of the clinical assessments were compared with a fibreoptic endoscopic examination of swallowing (FEES) conducted at the same sitting. Fifty patients underwent an examination of their ability to swallow 50 mL of water in 10-mL aliquots. They underwent a FEES with different food consistencies by a speech therapist and oxygen saturation with pulse oximetry was monitored during the procedure. Oxygen desaturation of more than 2% was considered to be clinically significant. RESULTS: The water swallow test had a sensitivity of 79.4% and specificity of 62.5% for the detection of aspiration, with a positive predictive value (PPV) of 81.8% and a negative predictive value (NPV) of 58.8%. The oxygen desaturation test had a sensitivity of 55.9% and a specificity of 100% with PPV of 100% and NPV of 51.6%. When both tests were combined, a sensitivity of 94.1% and a specificity of 62.5% was attained, with PPV of 84.2% and NPV of 83.3%. Using the clinical assessment test, we were able to pick up 3 aspirators who would otherwise have been missed if they were assessed with the water swallow test using thin fluids alone. CONCLUSION: Simple clinical assessment tools can be used to screen for dysphagia in a heterogeneous group of older patients with stroke disease, and clinical testing using feeds of different consistencies should be considered.

Cardiovascular disease risk stratification and comparison in a California population.

This study was designed to identify the need for primary prevention of cardiovascular disease in an HMO population and to develop appropriate interventions for individuals in different risk groups, based on risk stratification and comparison. The analysis is based on a cross-sectional survey of the HMO members of a large employer group. Respondents (n=17,878) were stratified based on the Framingham model; 34% of respondents without cardiovascular disease were classified as moderate to high attributable risk for the disease, and 66% were classified as low attributable risk. Results of logistic regression analyses suggest that, compared with respondents with pre-existing cardiovascular disease, moderate- to high-risk respondents are more likely to smoke, have unhealthy diets, and be overweight, hypertensive, and hypercholesterolemic. More low-risk respondents had unhealthy diets than did those with pre-existing cardiovascular disease. There were no differences between these groups for physical activity and stress. Respondents had fewer modifiable risk factors and healthier lifestyles than did those who were at risk. These findings suggest that primary prevention should be enhanced, especially among those with significantly increased risk for the disease. Moreover, the approaches of this project-population-based risk assessment, stratification, and comparison-were instrumental in identifying the target population and designing appropriate interventions. (c) 2001 by CHF, Inc.

Disenrollment from an HMO and its relationship with the characteristics of Medicare beneficiaries.

To examine the relationship between Medicare beneficiaries' characteristics and disenrollment, a longitudinal study was conducted in an HMO in California. Approximately 10 percent of the Medicare beneficiaries disenrolled within the first year of enrollment. There was no difference between those who continuously enrolled and those who disenrolled in terms of age, gender, mental and physical health status, previous utilization, and anticipated utilization in the coming year. However, people with limited social activities and people not living in a single-family house were more likely to disenroll. The authors also examined the disenrollment rates among physicians groups. The rates were significantly different.

Diabetes and disenrollment in a health maintenance organization setting: a 4-year longitudinal study with a matched cohort.

OBJECTIVE: The increasing enrollment of Medicare beneficiaries in health maintenance organizations (HMOs) in recent years has caused concern about whether HMOs and their providers have created an unfavorable environment for members who are chronically ill. This study was designed to examine whether there are any differences in disenrollment rates among enrollees with diabetes and enrollees without diabetes. RESEARCH DESIGN AND METHODS: This was a 4-year longitudinal follow-up study with a matched cohort. Medicare beneficiaries (aged > or =65 years) with diabetes identified through pharmacy records in 1994 were matched with a comparison group according to age, sex, comorbidities, and type of provider groups in an HMO in California. RESULTS: The overall distribution of the characteristics of members in the diabetic and matched nondiabetic group is almost identical. The matched-pair chi2 tests indicated that there were no statistical differences in disenrollment rates between diabetic and nondiabetic members during all three follow-up periods (P = 0.16-0.85). CONCLUSIONS: We found that the HMO members with diabetes did not disenroll from the HMO at a higher rate than those without diabetes. The findings should alleviate some of the concern that HMOs and their contracted providers have created an unattractive environment for members who have chronic diseases such as diabetes.

Compliance with US asthma management guidelines and specialty care: a regional variation or national concern?

The objective of this study was to examine the compliance with the National Asthma Education Program (NAEP) guidelines among asthmatic members of eight health plans (regions) in seven states, as well as the factors related to the compliance. Information was gathered by means of a cross-sectional survey in a managed care environment. The participants were 6703 respondents (ages 14-65) with moderate or severe asthma. The main outcome measures were compliance with the NAEP guidelines on the use of inhaled steroids, inhaled beta2-agonists, peak flow measurement, and allergy evaluations. Among the results of this survey we found that although these health plans are located from the West Coast to the East Coast and the socioeconomic status of their members varied greatly, compliance with the NAEP guidelines was low among asthmatic members across all geographical regions. The major areas of low compliance identified were inappropriate pharmacological therapy, lack of objective measurement of lung function through peak flow meter, and insufficient environmental trigger control. The regression analyses indicated that the effect of the health plan explained little of the variation in compliance across these regions (only 0.3% at maximum). Low compliance was associated with young age, smoking, moderate asthma, being asthmatic for a few years, currently working, and being treated by a generalist rather than a specialist. In conclusion, this study showed that the compliance with the national guidelines for asthma care was consistently low across different geographical regions in the nation. Improvement in care for asthmatics will require greater commitment and involvement by all stakeholders including physicians, patients, health plans, and employers. We suggest a need for a national strategy to disseminate clinical guidelines not only to the medical community but also to patients themselves.

Preventive pharmacologic therapy among asthmatics: five years after publication of guidelines.

BACKGROUND: Guidelines from the National Heart, Lung, and Blood Institute first published in 1991 have recommended anti-inflammatory (AI) agents as a first-line therapy and the bronchodilator as an acute reliever of symptoms. OBJECTIVE: To examine the current usage of anti-inflammatory steroids (inhaled corticosteroids, Cromolyn, systemic steroids) and bronchodilators and compare them with the national guidelines. The relationship between preventive AI usage and the characteristics of the asthma patients and their providers was also examined. METHODS: Cross-sectional survey data linked with 6-month pharmacy claims of asthmatic members at an HMO in California. RESULTS: AI usage increased with current severity (mild, 36.9%; moderate, 47.3%; and severe, 56.8%), though a large percentage are not receiving this emphasized treatment. Bronchodilators were used at a higher rate and 24% of asthmatics relied solely on bronchodilators. Use of bronchodilators without AI (BWAI) was present at all severity levels (mild, 19.5%; moderate, 24.6%; and severe, 24.7%). Advancing age, increasing severity, care by an asthma specialist, and not smoking increased the likelihood of using AIs. Increasing severity, longer duration of asthma, smoking, younger age group, care by a generalist, and no chronic bronchitis increased the likelihood of BWAI. CONCLUSIONS: These results suggest that there is a low level of AI usage despite emphasis in guidelines. Current asthma management in a community-based setting depicts a significant underutilization of long-term control agents and, conversely, an overutilization of symptom relief agents compared with guidelines published 5 years ago. Actively involving patients in the guideline dissemination process, rather than just the medical community, may increase preventive medication usage.

Validity of clinical information from a maternity survey.

This research was designed to validate data collected through a survey--an inexpensive way to provide information for quality measurement. The survey was sent to health maintenance organization (HMO) enrollees who had given birth(s) between October 1, 1994, and May 31, 1995. The responses were compared with the medical records. A sample of 407 women was randomly selected from the completed surveys. Medical records were reviewed for 89.9% (362/407) of the sample based on medical record availability. Over 98% of responses agreed with the medical record information regarding whether there were cesarean sections for previous deliveries (kappa = 1.0), cesarean section for recent delivery (kappa = 0.95), and vaginal birth after cesarean section (kappa = 0.96). Over 99% of the mothers agreed with the information regarding whether the newborn birth weight was under 2500 g (kappa = 0.91). The findings strongly support the validation of this instrument. Using this validated instrument enables health plans to cost-effectively obtain crucial information.

Satisfaction with access to and quality of health care among Medicare enrollees in a health maintenance organization.

This study was designed to determine the levels and predictors of Medicare enrollees' satisfaction with access to medical care and quality of health care in a health maintenance organization. Data collected by an instrument adapted from the Group Health Association of America's Consumer Satisfaction Survey were analyzed after being linked with administrative data. In general, Medicare enrollees reported high satisfaction with both access to and quality of health care. Most members (96%) rated skill, experience, and training of physicians and the friendliness and courtesy of the staff favorably. A lower percentage of members (77%) rated favorably the ability to contact a physician after hours. Levels of satisfaction were essentially not explained by patient characteristics such as age, sex, geographic region, medications, or utilization. Stepwise regression identified the ease of arranging appointments as the strongest predictor of satisfaction, with access to care and outcomes of medical care as the strongest predictor of overall satisfaction with quality of health care. These findings indicate that items that members rated least favorably, such as ability to contact a physician after hours, added little to the prediction of satisfaction with access to and quality of health care.

Inhibition of thrombin attenuates stenosis after arterial injury in minipigs.

OBJECTIVES: We sought to determine whether brief, profound inhibition of thrombin or prothrombin activation by factor Xa limits neointimal formation and stenosis after arterial injury. BACKGROUND: Thrombin has been implicated as a mediator of neointimal formation, but adjunctive administration of anticoagulant agents has not proven effective to decrease restenosis in patients undergoing coronary angioplasty. METHODS: We infused recombinant desulfatohirudin (r-hirudin, bolus of 2 mg/kg body weight followed by 2 mg/kg per h, n = 9), heparin (100 U/kg per h, n = 6) or recombinant tick anticoagulant peptide (rTAP, 1-mg/kg bolus followed by 3 mg/kg per h, n = 5), a specific inhibitor of factor Xa, intravenously, beginning 15 min before and for up to 3 h after repetitive balloon hyperinflations sufficient to disrupt the internal elastic lamina in a carotid artery of minipigs with hypercholesterolemia induced by feeding them an atherogenic diet. RESULTS: Partial thromboplastin time was increased six- to sevenfold over baseline levels at the end of the infusions of the anticoagulant agents. Lumen stenosis measured histologically 4 weeks after balloon-induced carotid injury was 29 +/- 16% (mean +/- SEM) in r-hirudin-treated, 52 +/- 19% in rTAP-treated and 76 +/- 18% in heparin-treated pigs (p < 0.02 for r-hirudin vs. heparin treatment). CONCLUSIONS: The marked reduction of stenosis in r-hirudin-treated animals indicates that thrombin plays a major role in neointimal formation after balloon-induced arterial injury. A relatively brief interval of profound, direct inhibition of thrombin may be particularly effective to attenuate restenosis after balloon angioplasty.

Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa.

BACKGROUND: Rethrombosis limits the efficacy of coronary thrombolysis and may result from surface-associated thrombin, de-novo prothrombin activation, or both. This study was designed to determine the relative roles of thrombin, factor Xa, and the complex of tissue factor and factor VIIa in the procoagulant activity on injured arteries with evolving thrombi. METHODS: Extensive vascular injury and platelet-rich thrombi were induced in the abdominal aorta of 25 anesthetized rabbits by applying anodal current through a transluminal electrode for 3 h. Injured vessel segments were excised and placed in a chamber permitting perfusion over the luminal surface and associated thrombus. RESULTS: Vessel segments perfused with recalcified, citrated human plasma induced marked increases in the concentration of fibrinopeptide A, a marker of thrombin-induced fibrin formation, in the effluent plasma after 10 min (4636 +/- 1894% of fibrinopeptide A in the nonperfused plasma, n = 5). Perfusion with plasma depleted of vitamin K-dependent coagulation factors prevented the increase in fibrinopeptide A (122 +/- 30%, n = 4), indicating the lack of preformed functional thrombin. Furthermore, appearance of fibrinopeptide A was attenuated by perfusion with plasma containing 0.1 mumol/l recombinant tick anticoagulant peptide, a specific inhibitor of factor Xa (594 +/- 320%, n = 3), and by preincubation of vessel segments with a monoclonal antibody to rabbit tissue factor (438 +/- 220%, n = 3). CONCLUSIONS: Procoagulant activity on injured vessels and associated thrombi is mediated by factor Xa, a product of the functional initiation of coagulation by factor VIIa associated with tissue factor. Accordingly, inhibition of tissue factor-mediated coagulation may be effective for attenuation of active thrombogenesis on injured vessels and during thrombolysis.

Maintenance of coronary patency after fibrinolysis with tissue factor pathway inhibitor.

BACKGROUND: Pharmacological coronary fibrinolysis induces procoagulant effects that contribute to delayed recanalization and early reocclusion. This study was designed to determine whether brief inhibition of activation of the coagulation cascade with tissue factor pathway inhibitor, a physiological inhibitor of activated factor X and its activation by the tissue factor/factor VII complex, would facilitate fibrinolysis, sustain patency of recanalized arteries, or both. METHODS AND RESULTS: Platelet-rich coronary thrombi were induced with anodal current that elicited intimal injury in 21 conscious dogs. Each was randomized to human recombinant tissue-type plasminogen activator (rTPA 1.0 mg/kg IV over 1 hour) with infusion of 50 micrograms.kg-1.min-1 of human recombinant tissue factor pathway inhibitor (rTFPI, n = 7), 100 micrograms.kg-1.min-1 of rTFPI (n = 8), or 300 mmol/L arginine phosphate buffer as a control (n = 6) concomitant with and for 1 hour after infusion of the plasminogen activator. Recanalization, verified with proximal Doppler flow probes, occurred in all but 1 dog given the high dose of rTFPI. It was not accelerated by conjunctive rTFPI. Reocclusion occurred within 90 minutes after infusion of rTPA in all 6 control dogs. However, reocclusion was delayed and patency was sustained for the entire 24-hour observation interval in 2 of 6 dogs (excluding 1 that did not survive) given the low dose and in 4 of 6 dogs (excluding 1 that did not receive the desired amount) given the high dose of rTFPI (P < .05 compared with controls). Cyclic flow variations indicative of platelet aggregation and disaggregation locally were virtually eliminated by rTFPI (3 +/- 4[SD]/h in dogs given the low dose and 2 +/- 2/h in those given the high dose of rTFPI compared with 13 +/- 12/h in controls, P < .05). In addition, rTFPI increased activated partial thromboplastin time and prothrombin time only at the high dose (1.4 +/- 0.3 and 2.1 +/- 0.9 times baseline) and had no effects on platelet aggregation assayed ex vivo and only minimal effects on bleeding time assayed in vivo. CONCLUSIONS: Brief inhibition of the coagulation system by administration of rTFPI sustains patency of arteries recanalized by pharmacological fibrinolysis without markedly perturbing hemostatic mechanisms.

Potentiation of endogenous nitric oxide with superoxide dismutase inhibits platelet-mediated thrombosis in injured and stenotic arteries.

OBJECTIVES: We tested the hypothesis that dismutation of superoxide anion increases endogenous levels of nitric oxide, resulting in inhibition of cyclic variations in blood flow in arteries that are injured and stenotic. BACKGROUND: Platelet adhesion and aggregation leading to cyclic flow variations might result, in part, from generation of superoxide anion that can deplete endogenously produced nitric oxide. METHODS: Spontaneous cyclic flow variations, monitored with a proximal Doppler probe, were induced in the carotid artery of anesthetized rabbits by clamping the vessel with forceps and placing a high grade stenosis at the site of injury. Bovine copper/zinc superoxide dismutase (12 mg/kg body weight, n = 5), a synthetic low molecular weight mimetic (12 mg/kg, n = 8) or buffer vehicle (n = 8) was administered intravenously as divided boluses over 45 min, and the frequency of cyclic flow variations was monitored for 4 h. RESULTS: Cyclic flow variations remained stable for 4 h in vehicle-treated animals (15 +/- 1 [mean +/- SEM]/30 min at baseline and 16 +/- 1/30 min after 4 h, n = 8) but exhibited a marked and persistent reduction in animals given copper/zinc superoxide dismutase (from 14 +/- 1/30 min at baseline to 4 +/- 1/30 min after 4 h) or the mimetic (from 15 +/- 1/30 min at baseline to 3 +/- 1/30 min after 4 h, p < 0.005). They were restored in three of four mimetic-treated animals during infusion of NG-monomethyl- L-arginine (100 mg/kg), an inhibitor of nitric oxide production. In addition, levels of cyclic guanosine 5'-monophosphate in platelets were elevated after administration of the mimetic (from 2.4 +/- 0.5 fmol/10(6) platelets at baseline to 4.9 +/- 0.6 fmol/10(6) platelets 45 min after the mimetic, p < 0.03, n = 6), whereas mean arterial blood pressure was decreased and flow velocity in the carotid artery was increased consistent with mediation of the effect on cyclic flow variations by increased endogenous nitric oxide. CONCLUSIONS: Dismutation of superoxide anion appears to attenuate platelet thrombus formation at a site of vessel injury by potentiation of endogenously produced nitric oxide. This approach may have utility to inhibit platelet-rich thrombosis in injured and stenotic arteries where production of superoxide anion is increased.

Medical technology transfer in major Chinese medical schools.

This paper examines how the decision-making process and its consequences affect medical technology transfer in major Chinese medical schools. Data are from a 1987 survey of 13 key medical universities, directly supervised by the Ministry of Public Health in the People's Republic of China. This paper limits itself to four types of laboratory equipment--electron microscopes, UV/VIS spectrophotometers, high-performance liquid chromatographs, and polygraphs. Decisions on the transfer of medical technology have been more decentralized in China since the economic reform in 1978. The major reason for schools to import these four types of equipment is their dissatisfaction with the quality of domestic products. Chinese medical schools depend heavily on the information provided at medical equipment exhibits and their neighboring schools. Their decisions to acquire the equipment are based more on the quality and service available than on the prices. Chinese medical schools face serious infrastructure problems in acquiring and maintaining these pieces of equipment. A number of suggestions are made for improving the efficiency of medical technology transfer in China.