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Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 19 recordsLinked to original sources

Ammonia and nitrous oxide emissions from two acidic soils of Nova Scotia fertilised with liquid hog manure mixed with or without dicyandiamide.

Gaseous nitrogen (N) loss from field-applied manure in the form of ammonia (NH(3)) and nitrous oxide (N(2)O) has negative agronomic, environmental and health implications. This study was undertaken to evaluate the combined effect of soil type and dicyandiamide (DCD) on NH(3) and N(2)O emissions following application of liquid hog manure. Soil samples (100g) were placed in 500 mL screw-top Mason-jars and de-ionised water was added to bring the soil samples to 50%, 70% and 90% water-filled pore space (WFPS). Slurry and slurry+DCD treatments were applied at a rate of 116000 l ha(-1). The jars were then sealed and incubated at 21 degrees C for 21 d. Ammonia volatilisation was quantified using boric acid traps while N(2)O gas concentrations were analysed using gas chromatography. Results showed that DCD had no effect (p>0.05) on either NH(3) or N(2)O emissions. However, soil type had a significant effect (p<0.05) on both gases. Overall, the Pugwash soil produced 3 and 2.5 times more NH(3) and N(2)O, respectively, than the Acadia soil. N(2)O emissions from both soils increased with an increase in %WFPS, indicating that during the spring and fall in Atlantic Canada, when soils are generally wet, a significant amount of N(2)O may be emitted from these soils. The relationship between cumulative N(2)O and %WFPS was best described by an exponential function R(2)=0.83 and p<0.05 (both soils). Therefore, soil type should be taken into consideration when formulating N(2)O emission factors. The addition of DCD together with slurry may not be a viable strategy to mitigate N(2)O emissions from acidic soils. To reduce emissions of both gases, livestock slurry should not be applied on wet soils.

Acids↗

Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study.

OBJECTIVES: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. METHODS: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases <3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. RESULTS: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. CONCLUSIONS: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.

Adult↗

Identification of ultrastructural changes in liver allografts of patients experiencing primary nonfunction.

BACKGROUND: Primary nonfunction (PNF) after liver transplantation is fatal without timely retransplantation. PNF has been associated with many risk factors, but the etiology remains unknown in most cases. Using electron microscopy, we examined the hepatic ultrastructure of donor allografts in patients experiencing PNF and compared the findings with a well-matched group of other donor allografts. MATERIALS AND METHODS: Archival paraffin-embedded pre- and post-reperfusion donor liver biopsies were examined by electron microscopy in 10 patients with PNF and in 10 controls, matched by donor age +/- 5 years, gender, cold ischemic time +/- 1 hour, and donor cause of death. Mitochondria, endoplasmic reticulum, sinusoidal endothelial cells, and the glycogen content of the cells were assessed. The donors' serum peak transaminases, bilirubin and sodium levels, as well as the recipient age and serum creatinine were compared. RESULTS: There were no significant differences in recipient age at the time of transplantation, peak recipient serum creatinine, donor peak serum transaminase, sodium or bilirubin levels. In all cases, the endoplasmic reticulum and sinusoidal endothelial cells were ultrastructurally normal. Hepatocytes had variable degrees of glycogen pooling. Hepatic steatosis and intramitochondrial inclusions cells were present in 5/10 PNF compared to 0/10 controls patients on preperfusion liver biopsy (P = .17). CONCLUSION: Liver allografts from patients suffering from PNF can have mitochondrial ultrastructural changes on preperfusion biopsies.

Adult↗

Basis and lattice polarization mechanisms for light transmission through nanohole arrays in a metal film.

The extraordinary light transmission through double-hole and elliptical nanohole arrays in a thin gold film is investigated for different orientations of the holes relative to the lattice. Even though these bases have similar symmetry characteristics, the polarization follows the orientation of the basis for the ellipse but remains fixed along a lattice vector for the double holes. Furthermore, the maximum transmitted intensity for linearly polarized light is constant for the ellipse, but decreases for the double holes as they are rotated away from being aligned with the lattice. Finite-difference time-domain simulations agree well with the experimental findings. These experiments show how the basis determines both the coupling into the surface plasmon waves and the evanescent transmission through the nanoholes. Both of these effects need to be considered when designing nanophotonic devices using the extraordinary transmission phenomenon.

Anisotropy↗

Harmonic oscillation in a spatially finite array waveguide.

A waveguide array is presented that behaves as an oscillator, showing periodic image reconstruction, focusing, and transverse wave-packet oscillation. The oscillator has a finite width, which removes the need for premature truncation. The array waveguide oscillator shows properties analogous to those of a pedagogically important one-dimensional quantum harmonic oscillator, which are fundamentally different from previously demonstrated oscillations in Wannier-Stark waveguide arrays. Calculations of the entire array waveguide oscillator are presented that quantify higher-order corrections to the coupled-mode approach. These results can be extended to waveguide oscillators in other systems, such as electrons in superlattices.

Journal Article↗

Strong polarization in the optical transmission through elliptical nanohole arrays.

Strong polarization dependence is observed in the optical transmission through nanohole arrays in metals. It is shown that the degree of polarization is determined by the ellipticity and orientation of the holes; the polarization axis lies perpendicular to the broad edge of the ellipse. Furthermore, the depolarization ratio shows a squared dependence on the aspect ratio of the holes, which is discussed in terms of coupling into and out of the surface plasmon modes. The observed results will be useful for tailoring the polarization behavior of metallic nanophotonic elements in many applications, including surface plasmon enhanced optical sensing and ultrafast optical switching.

Journal Article↗

Stereotactic co-registration of magnetic resonance imaging and histopathology in post-mortem multiple sclerosis brain.

A number of groups have examined the pathological substrate of signal changes on magnetic resonance imaging (MRI) in post-mortem (PM) brain of patients with multiple sclerosis (MS). Such studies will benefit from using a standardized method to reliably co-register regions of interest on MRI and tissue specimens. We investigated the usefulness of a stereotactic navigation system for this purpose. We also addressed the sensitivity of different standard MRI sequences with regard to lesion conspicuity in PM MS brain. Post-mortem brains of eight patients with MS were studied. Formalin-fixed coronal slices were placed in the head frame of a stereotactic system. Proton density-, T2-weighted and fast fluid-attenuated inversion recovery (FLAIR) scans were obtained and visually matched with scans that had been previously obtained on the same, but fresh, specimens. Guided by the stereotactic target points, the dissection of the fixed specimens was performed. After processing the blocks for embedding in paraffin, sections were stained with haematoxylin-eosin and Luxol fast blue. T2-weighted MRI of fixed brain revealed 24 areas suspected to be MS lesions, all of which were confirmed histologically. Three of these lesions were not visible on macroscopic inspection. There were 14 additional hyperintensities on T2-weighted or FLAIR MRI of the fresh specimens, five of which did not correlate to MS lesions histologically. Stereotactic navigation is a useful approach to co-register MRI and histopathology in PM brain of MS patients and may improve the precision of MRI-guided sampling of tissue specimens. Standard T2-weighted MRI appeared to be the single most useful approach for lesion detection in fresh and fixed specimens.

Brain↗

XAFS at the Pacific Northwest Consortium-Collaborative Access Team undulator beamline.

The Pacific Northwest Consortium-Collaborative Access Team (PNC-CAT) has begun operating an insertion device beamline at the Advanced Photon Source. The beamline has been extensively used for XAFS studies. This paper summarizes its capabilities, and our initial operational experience. The beamline is based on APS undulator A, and incorporates full undulator scanning. The monochromator is liquid nitrogen cooled and has both Si(111) and Si(311) crystals in a side-by-side configuration. Crystal changes only take a few minutes. The crystals cover the energy range from 3-50 keV with fluxes as high as 2x10(13) ph/sec. Microbeams can be produced using Kirkpatrick-Baez mirrors (spot size 1-3 microm) or tapered capillaries (sub-microm spots). When these optics are combined with a 13-element Ge detector, the beamline provides powerful microbeam imaging and spectroscopy capabilities. Experimental examples from the environmental field and in-situ UHV film growth will be discussed.

Journal Article↗

Inhibitors of trypsin-like serine proteases prevent DNA damage-induced neuronal death by acting upstream of the mitochondrial checkpoint and of p53 induction.

We have previously shown that the pharmacological agents 4-(2-aminoethyl)=benzenesulfonylfluoride hydrochloride (AEBSF) and Na-p-tosyl-L-lysine chloromethylketone (TLCK), inhibitors of trypsin-like serine proteases, prevent the death of trophic factor-deprived PC12 cells and sympathetic neurons. Both AEBSF and TLCK inhibit caspase activation in this model, but it is unclear whether they do so indirectly or through a direct effect at the level of the caspases. In the current study, we have used these agents in another model of neuronal death that is induced by DNA damage. We find that both agents delay the death of DNA-damaged PC12 cells, neonatal rat sympathetic neurons and embryonic rat cortical neurons. As in the trophic deprivation model, they act upstream of the caspases. In addition, they prevent mitochondrial alterations, such as cytochrome c release or loss of transmembrane potential. In contrast, the general caspase inhibitor bok-asp-fmk does not prevent cytochrome c release and has only a partial and transient effect on loss of transmembrane potential. Interestingly, both AEBSF and TLCK prevent the induction and nuclear accumulation of p53 that is induced by DNA damage in cortical neurons. Therefore, these serine protease inhibitors act at a point upstream in the apoptotic pathway, prior to p53 induction and the mitochondrial checkpoint, to delay neuronal death in this model, and do not act at the level of the caspases. We conclude that therapeutic strategies based on serine protease inhibition may be useful in preventing neuronal cell death.

Animals↗

Risk stratification and outcomes of transluminal endografting for abdominal aortic aneurysm: 7-year experience and long-term follow-up.

PURPOSE: To determine early and late outcomes of transluminal endografting (TE) in patients with abdominal aortic aneurysm (AAA), stratified by predicted risk of procedure-related mortality with conventional operation. MATERIALS AND METHODS: A retrospective study was conducted in consecutive risk-stratified AAA patients undergoing TE at a not-for-profit cardiovascular referral center from March 1994 through November 2000 with follow-up through February 2001. With use of conventional risk strata (0 = low, 1 = minimal, 2 = moderate, and 3 = high), predicted procedure-related mortalities were 0%-1% in stratum 0 (n = 40), 1%-3% in stratum 1 (n = 118), 3%-8% in stratum 2 (n = 116), and 8%-30% in stratum 3 (n = 31). Main outcome measures were: (i) TE procedural success, (ii) procedure-related mortality, (iii) major nonfatal complications, (iv) composite adverse outcome (ii + iii), (v) length of stay (LOS), (vi) freedom from AAA rupture, (vii) late survival, (viii) late complications, and (ix) endoleaks and their classification and management. RESULTS: Women were significantly less likely than men to qualify for and undergo endografting: 24 of 91 (26.4%) women underwent TE, compared to 281 of 684 (41.1%) men. Of 305 attempted TE procedures, 291 (95.4%) were successful, four (1.3%) were urgently converted to open repair, and 10 (3.3%) were aborted. Procedure-related mortalities occurred in eight cases (2.6%) overall and one of 40 (2.5%), one of 118 (0.8%), four of 116 (3.4%), and two of 31 (6.5%) cases for risk strata 0-3, respectively. Perioperative survivors were significantly younger than nonsurvivors (74.3 y +/- 9 vs 81.6 y +/- 5.1; P =.0087). Forty-six patients (15.1%) had major complications. Composite adverse outcome was worse for patients in stratum 3 than those in stratum 1 (P =.0296) and those in strata 0, 1, and 2 combined (P =.026). Procedure-related mortality declined with institutional experience, from 4% among the first 100 patients undergoing TE to 1% among the last 105. For strata 0-3, median LOS were 2, 3, 3, and 4 days, respectively. Seventy patients (22.9%) had 75 endoleaks, of which 30 necessitated additional procedures, 17 self-resolved, and 22 were untreated as of March 1, 2001. Five patients with endoleak died of unrelated causes. One late-onset type IA endoleak (26 mo) resulted in the only AAA rupture and death in the follow-up period among the 291 patients who underwent successful transluminal endograft implantation. Actuarial survival rates at 1 year after TE were 90.3% +/- 1.9% for the overall study group and 97.5% +/- 2.5%, 94% +/- 2.5%, 86.9% +/- 3.3%, and 81.3% +/- 7.7% for risk strata 0-3, respectively. At 5 years, overall actuarial survival was 69.6% +/- 6.1%. Thirty-eight late deaths were attributable to post-TE AAA rupture (n = 1), AAA rupture late after failed TE with no further treatment (n = 1), other cardiovascular disorders (n = 7), cancer (n = 15), other causes (n = 10), and unknown causes (n = 4). Late deaths occurred in risk strata 0-3 at the following rates: two of 40 (5%), 10 of 118 (8.5%), 16 of 116 (13.8%), and 10 of 31 (32.3%), respectively (stratum 0 vs stratum 3, P =.0017; stratum 1 vs stratum 3, P =.003). CONCLUSIONS: TE is safe and confers durable protection against AAA rupture in treated populations. Still, protection is not absolute in patients with endoleaks, because late AAA enlargement and even rupture can occur. Given current knowledge, technology, and practice, careful patient selection and close surveillance of patients after implantation of transluminal endografts is essential.

Age Distribution↗

Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is an important cause of renal artery stenosis, particularly in young females. Polymorphisms of the renin-angiotensin (RA) system have been implicated in the pathogenesis of hypertension and atherosclerotic vascular disease, and may play a role in the development of FMD. Examination of polymorphisms by PCR for angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT1R) A1166C and angiotensinogen (AGT) M235T and T174M was undertaken in 43 patients with typical multifocal renal arterial FMD (MF-FMD) and in 89 controls. The age of MF-FMD patients at the time of diagnosis of hypertension did not differ (38.6 + 11.1 years vs 35.5 +/- 10.3 years, P = 0.12) from controls and the proportion (95% vs 86%, P = 0.14) of females was similar. Allele frequencies did not differ significantly between groups, except that MF-FMD patients had a significantly higher frequency of the ACE I allele than control subjects (0.62 vs 0.47, P = 0.026). Since the ACE I allele is associated with lower circulating ACE levels and possibly lower tissue levels of angiotensin II (Ang II), and since Ang II modulates vascular smooth muscle cell growth and synthetic activity, the I allele might predispose to defective remodelling of the arterial media, and thus to the development of MF-FMD. This contrasts with atherosclerotic renal artery stenosis, coronary stent restenosis and carotid intimal thickening, which are diseases affecting the arterial intima, and which are associated with increased frequency of the D allele.

Adult↗

Lack of skin fibrosis in tight skin (TSK) mice with targeted mutation in the interleukin-4R alpha and transforming growth factor-beta genes.

Scleroderma is a disorder characterized by fibrosis of the skin and internal organs and autoimmunity. Whereas the cause is unknown, interleukin-4 and transforming growth factor-beta have been postulated to play a major part in the fibrosis. To investigate the part played by these cytokines, we prepared TSK/+ mice with a targeted mutation in the interleukin-4R alpha or transforming growth factor-beta genes. The breeding failed to produce TSK/+ transforming growth factor-beta -/- mice so analysis of the role of transforming growth factor-beta was limited to TSK/+ transforming growth factor-beta +/- mice. We observed that TSK/+ interleukin-4R alpha -/- did not develop dermal thickening, and deletion of one allele of the transforming growth factor-beta gene resulted in diminished dermal thickness compared with TSK/+ mice; however, the deletion of interleukin-4R alpha or transforming growth factor-beta had no effect on lung emphysema, which is another characteristic of TSK syndrome. Electron microscopic analysis of skin showed that the collagen fibrils in TSK/+ interleukin-4R alpha -/- mice exhibit normal periodicity but have a smaller diameter than the fibers found in C57BL/6 mice. Analysis of skin and serum samples showed that the deletion of interleukin-4R alpha or one allele of transforming growth factor-beta prevented the increase of skin thickness paralleled with a decrease in the dermal hydroxyproline content and development of autoantibodies associated with TSK syndrome. These results demonstrate the importance of interleukin-4 and transforming growth factor-beta for the development of cutaneous fibrosis in vivo and suggest an important part for these cytokines in wound healing and connective tissue maintenance in general.

Animals↗

Significance of the clinical course and early upper gastrointestinal studies in predicting complications associated with repair of esophageal atresia.

BACKGROUND/PURPOSE: In many centers, use of upper gastrointestinal (UGI) contrast studies in the early postoperative period after esophageal atresia (EA) repair is considered routine. Indications for this are many, including searching for existing problems and predicting future complications. However, most major complications, both early and late, usually are identified clinically before any radiologic studies. The purpose of this study was to investigate factors that may anticipate the development of postoperative complications after EA repair, looking particularly at the predictive value of routine early postoperative UGI studies. METHODS: A total of 111 consecutive cases of EA were identified retrospectively over a 10-year period from 2 major Canadian pediatric health centers. One hundred one were associated with a distal tracheoesophageal fistula (TEF), of which, 90 had repairs. Ninety-seven percent of these had a UGI study at a median of 9.1 postoperative days (range, 2 to 23) before consideration of oral feeding. Charts were reviewed looking at patient variables, surgical factors, early UGI findings, and postoperative courses. Complications that required intervention were noted, including anastomotic leaks, gastroesophageal reflux (GER), strictures, and recurrent and missed fistulae. All initial UGI studies were reexamined by 1 of 2 pediatric radiologists. Logistic regression was used to examine relationships between these clinical and radiologic variables and outcomes. RESULTS: Of the variables analyzed, univariate analysis showed clinically significant leaks to be associated with intraoperative factors (subjective degree of anastomotic tension, and the use of myotomies) and early postoperative clinical evidence suggesting a leak. In a multivariate model, all remained independently significant except for the use of myotomies. Later development of clinically significant GER also was associated with the degree of tension. It had no relationship, however, with findings of dysmotility, esophageal shortening, or reflux at the initial UGI study. Development of a stricture requiring dilatations or resection was associated with a history of clinically evident GER only; no relationships were seen with a history of an anastomotic leak or any other clinical, operative, or radiographic variables. Missed or recurrent fistulae were all suspected clinically before radiologic confirmation. CONCLUSIONS: Early and late complications after repair of EA can be identified and potentially anticipated based on clinical findings at the time of repair and during the postoperative period. The use of early "routine" UGI studies, with no suspicion of a problem, has little value in terms of predicting complications or future clinical course.

Analysis of Variance↗

BICAV: a block-iterative parallel algorithm for sparse systems with pixel-related weighting.

Component averaging (CAV) was recently introduced by Censor, Gordon, and Gordon as a new iterative parallel technique suitable for large and sparse unstructured systems of linear equations. Based on earlier work of Byrne and Censor, it uses diagonal weighting matrices, with pixel-related weights determined by the sparsity of the system matrix. CAV is inherently parallel (similar to the very slowly converging Cimmino method) but its practical convergence on problems of image reconstruction from projections is similar to that of the algebraic reconstruction technique (ART). Parallel techniques are becoming more important for practical image reconstruction since they are relevant not only for supercomputers but also for the increasingly prevalent multiprocessor workstations. This paper reports on experimental results with a block-iterative version of component averraging (BICAV). When BICAV is optimized for block size and relaxation parameters, its very first iterates are far superior to those of and more or less on a par with ART. Similar to CAV, BICAV is also inherently parallel. The fast convergence is demonstrated on problems of image reconstruction from projections, using the SNARK93 image reconstruction software package. Detailed plots of various measures of convergence, and reconstructed images are presented.

Algorithms↗

The effect of temperature on the fatty acids and isozymes of a psychrotrophic and two mesophilic species of Xenorhabdus, a bacterial symbiont of entomopathogenic nematodes.

In the first part of this study, generation times relative to temperature, together with cardinal and conceptual temperatures, were determined for four strains of Xenorhabdus bacteria that represented three geographically distinct species. The data showed that the NF strain of Xenorhabdus bovienii, like the Umeå strain of the same species, is psychrotrophic, while Xenorhabdus sp. TX strain resembles Xenorhabdus nematophila All strain in being mesophilic. In the second part, the capacity of these bacteria to adapt to changes in temperature, shown by changes in fatty acid composition, was investigated. As temperature declined, the proportions of the two major unsaturated fatty acids, palmitoleic (16:1omega7) acid and oleic (18:1omega9) acid, increased significantly in all of the strains. The proportion of the prevalent saturated fatty acid, which was palmitic acid (16:0), decreased. In the All, NF, and Umeå strains, myristic acid (14:0), margaric acid (17:0), cyclopropane (17:0c), and arachidic acid (20:0) decreased with decreasing temperature. In the third part of the study, the synthesis of isozymes in response to changing temperature was investigated. For the seven enzymes studied, the numbers for which isozyme synthesis was temperature related were as follows: five for Umeå, four for All, three for NF, and two for TX. Where the study dealt with fatty acid composition and isozyme synthesis, the results show a broad capacity for physiological temperature adaptation among strains of different climatic origin.

Animals↗

Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.

We report here the preclinical profile of etoricoxib (MK-0663) [5-chloro-2-(6-methylpyridin-3-yl)-3-(4-methylsulfonylphenyl) pyridine], a novel orally active agent that selectively inhibits cyclooxygenase-2 (COX-2), that has been developed for high selectivity in vitro using whole blood assays and sensitive COX-1 enzyme assays at low substrate concentration. Etoricoxib selectively inhibited COX-2 in human whole blood assays in vitro, with an IC(50) value of 1.1 +/- 0.1 microM for COX-2 (LPS-induced prostaglandin E2 synthesis), compared with an IC(50) value of 116 +/- 8 microM for COX-1 (serum thromboxane B2 generation after clotting of the blood). Using the ratio of IC(50) values (COX-1/COX-2), the selectivity ratio for the inhibition of COX-2 by etoricoxib in the human whole blood assay was 106, compared with values of 35, 30, 7.6, 7.3, 2.4, and 2.0 for rofecoxib, valdecoxib, celecoxib, nimesulide, etodolac, and meloxicam, respectively. Etoricoxib did not inhibit platelet or human recombinant COX-1 under most assay conditions (IC(50) > 100 microM). In a highly sensitive assay for COX-1 with U937 microsomes where the arachidonic acid concentration was lowered to 0.1 microM, IC(50) values of 12, 2, 0.25, and 0.05 microM were obtained for etoricoxib, rofecoxib, valdecoxib, and celecoxib, respectively. These differences in potency were in agreement with the dissociation constants (K(i)) for binding to COX-1 as estimated from an assay based on the ability of the compounds to delay the time-dependent inhibition by indomethacin. Etoricoxib was a potent inhibitor in models of carrageenan-induced paw edema (ID(50) = 0.64 mg/kg), carrageenan-induced paw hyperalgesia (ID(50) = 0.34 mg/kg), LPS-induced pyresis (ID(50) = 0.88 mg/kg), and adjuvant-induced arthritis (ID(50) = 0.6 mg/kg/day) in rats, without effects on gastrointestinal permeability up to a dose of 200 mg/kg/day for 10 days. In squirrel monkeys, etoricoxib reversed LPS-induced pyresis by 81% within 2 h of administration at a dose of 3 mg/kg and showed no effect in a fecal 51Cr excretion model of gastropathy at 100 mg/kg/day for 5 days, in contrast to lower doses of diclofenac or naproxen. In summary, etoricoxib represents a novel agent that selectively inhibits COX-2 with 106-fold selectivity in human whole blood assays in vitro and with the lowest potency of inhibition of COX-1 compared with other reported selective agents.

Algorithms↗