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D Cox

Publications and source records attributed to D Cox.

At least 19 recordsLinked to original sources
PubMed2005

Cyclooxygenase-1 haplotype modulates platelet response to aspirin.

BACKGROUND: Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A2. Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the concept of 'aspirin resistance.' AIMS: To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX-1 gene may affect aspirin response and thus contribute to aspirin resistance. PATIENTS AND METHODS: Aspirin response, determined by serum TXB2 levels and AA-induced platelet aggregation, was prospectively studied in patients (n = 144) with stable CAD taking aspirin (75-300 mg). Patients were genotyped for five single nucleotide polymorphisms in COX-1 [A-842G, C22T (R8W), G128A (Q41Q), C644A (G213G) and C714A (L237M)]. Haplotype frequencies and effect of haplotype on two platelet phenotypes were estimated by maximum likelihood. The four most common haplotypes were considered separately and less common haplotypes pooled. RESULTS: COX-1 haplotype was significantly associated with aspirin response determined by AA-induced platelet aggregation (P = 0.004; 4 d.f.). Serum TXB2 generation was also related to genotype (P = 0.02; 4 d.f.). CONCLUSION: Genetic variability in COX-1 appears to modulate both AA-induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX-1 genotype.

Adult↗
PubMed2005

The significance of mammotome core biopsy specimens without radiographically identifiable microcalcification and their influence on surgical management--a retrospective review with histological correlation.

The aim of this study is to assess core specimens which do not contain radiographically visible calcification at stereotactic vacuum assisted core biopsy (SVACB) of indeterminate microcalcification, to determine what influence they may have on the surgical management of patients with breast disease. Review was made of the core biopsy and surgical histology results of 104 SVACB biopsies of indeterminate microcalcification over a 26 month period. Cores were placed in separate pots; POT A for cores containing microcalcification and POT B for cores without radiographically visible microcalcification before being sent to histology. Of 104 biopsies, 25% contained B3-B5 pathology in POT B and at surgery this correlated with a higher grade of ductal carcinoma in situ (DCIS) and an increased likelihood of invasive disease. The presence of B3-B5 pathology in POT B itself however did not act as a strong indicator of radiological-histological size discrepancy in this study.

Adult↗
PubMed2005

Chronic intermittent asphyxia increases platelet reactivity in rats.

Sleep-disordered breathing is associated with chronic intermittent asphyxia and with a variety of cardiovascular abnormalities. Cardiovascular morbidity and mortality are linked to altered platelet function, and platelet function is affected in sleep-disordered breathing. As there is evidence that chronic continuous hypoxia may alter platelet number and function, the aim of the present study was to test the hypothesis that chronic intermittent asphyxia affects platelet count, activation and aggregation. Rats were treated with a hypercapnic hypoxic gas mixture (minimum of 6-8% O2, maximum of 10-14% CO2) for 15 s, twice per minute for 8 h per day for 3 weeks. Blood was analysed for platelet count, platelet activation (CD62p expression using flow cytometry), response to low dose ADP, haematocrit, red cell count and haemoglobin concentration. A platelet function analyser measured the closure time of an aperture, dependent on platelet aggregation. Compared to controls (n = 16), chronic intermittent asphyxia (n = 13) reduced body weight and increased right ventricular weight but had no significant effect on platelet count (control, 880.4 +/- 20.1; treated: 914.1 +/- 35.2 x 10(3) microl(-1); mean +/- S.E.M.), on the reduction in platelet count in response to ADP (control, reduced to 206.7 +/- 49.0; treated, reduced to 193.8 +/- 35.9 x 10(3) microl(-1)), or on the percentage of platelets positive for CD62p (control, 5.2 +/- 0.7; treated, 6.0 +/- 0.8%). Chronic intermittent asphyxia significantly (P = 0.037) reduced the closure time (control, 90.9 +/- 7.7; treated, 77.7 +/- 3.8 s), indicating greater adhesion and aggregation. There was no significant difference in haematocrit, red cell count and haemoglobin concentration. In conclusion, chronic intermittent asphyxia has no effect on platelet count but does increase platelet aggegation in rats. These data support the idea that chronic intermittent asphyxia alters platelet function in sleep-disordered breathing.

Animals↗
PubMed2005

Organizing and delivering training for acute mental health services: a discussion paper.

Recent policy statements that address the quality of care provided by acute mental health services have highlighted an urgent need for specialist nurse education and training. However, examples of how to design and implement such training initiatives are sparse. Drawing on recent experience of developing an innovative training programme for acute psychiatric settings, this paper seeks to examine some of the key issues associated with current training provision for acute inpatient mental health workers. The methodological and practical concerns surrounding this type of initiative are discussed with the main aspects of programme content, service user participation, team training and organizational challenges being explored. Resulting from this work, several recommendations regarding the content, organization and delivery of future training initiatives are made.

Acute Disease↗
PubMed2004

Young male smokers have altered platelets and endothelium that precedes atherosclerosis.

BACKGROUND: Cigarette smoking results in abnormalities of platelets and endothelium with platelet dysfunction implicated in vascular complications. Healthy endothelium plays a pivotal role in regulating hemostasis via the inhibition of platelet activation and aggregation. Thus, we examined if platelet dysfunction correlated with serum vWF levels-a circulating marker of endothelial dysfunction. MATERIALS AND METHODS: We tested this hypothesis in young male smokers. The parameters of platelet function tested included: CD62/CD63; Glycoprotein (GP) IIb/IIIa; Platelet function analzyer (PFA) studies, platelet aggregometry, flow assessment of platelet microparticles, platelet-leukocyte interactions and receptor numbers. Endothelial dysfunction was assessed with serum von Willebrand Factor (vWF). RESULTS: There was a significant increase in platelet CD62 receptor expression and aggregation with an associated delay in time to aggregation using PFA. Endothelial dysfunction was represented by higher serum levels of von Willebrand Factor. All other platelet parameters tested were within the standardized reference range. CONCLUSIONS: These initial data suggests that anti-platelet therapy may have a role in reduction of platelet activation and aggregation in young smokers and possibly alter vascular endothelial abnormalities.

Adenosine Diphosphate↗
PubMed2003

Clinical and electrophysiological differences between patients with arrhythmogenic right ventricular dysplasia and right ventricular outflow tract tachycardia.

AIMS: Radiofrequency catheter ablation is considered first line treatment for symptomatic patients with right ventricular outflow tract tachycardia (RVOT). The role of ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more limited. As such, differentiating between the two conditions is essential. METHODS AND RESULTS: This study compared non-invasive findings, magnetic resonance images (MRI), invasive electrophysiological characteristics, results of ablation and long-term outcome in 50 consecutive patients with RVOT (33) or ARVD (17). Structural abnormalities were uniform in the ARVD group; in addition 18 (54%) of the RVOT tachycardia group had MRI abnormalities. At electrophysiological study the tachycardia in the ARVD group displayed features of re-entry in over 80%, but behaved with a triggered automatic basis in 97% with RVOT. Ablation was complete or partial success in 12 (71%) patients with ARVD and ventricular tachycardia (VT) recurred in eight (48%). In the RVOT patients, ablation was a complete success in 97% with recurrent VT in 6%. Long-term success in the RVOT patients was 95% in both patients with and without MRI abnormalities. CONCLUSIONS: Electrophysiological characterization can differentiate ARVD from RVOT. The finding of abnormalities on MRI does not have any bearing on arrhythmia mechanism, acute or long-term success of RFA.

Adolescent↗
PubMed2003

Helicobacter pylori induces cyclooxygenase-1 and cyclooxygenase-2 expression in vascular endothelial cells.

BACKGROUND: Helicobacter pylori induces cyclooxygenase activity in the stomach, although the COX isoform and cellular source are unclear. A potential source is the vascular endothelial cell, which plays a role in regulating mucosal blood flow and inflammatory cell infiltration. METHODS: We examined the effect of four strains (toxigenic and non-toxigenic) of H. pylori on COX isoform expression in vascular endothelial cells. Prostaglandin synthesis was measured by enzyme immunoassay and COX isozyme expression determined by Western blot and RT-PCR. Gene induction was examined using 5' deletion constructs of the COX-1 and COX-2 promoters coupled with luciferase. RESULTS: All H. pylori strains induced prostaglandin generation and expression of both COX-1 and COX-2 in HUVEC, although this was most pronounced with the highly toxigenic strain H. pylori 60190. Treatment of the cells with selective COX inhibitors demonstrated that COX-1 was predominantly responsible for the enhanced generation of prostacyclin induced by H. pylori 60190. Similar results were seen with H. pylori broth culture filtrates, suggesting that a secreted product was responsible. Induction of COX-2 reflected both enhanced gene expression and stabilization of the mRNA. CONCLUSIONS: H. pylori increased both COX-1 and COX-2 activity in vascular endothelial cells. This increased generation of endothelial cell prostacyclin may play a role in modulating mucosal blood flow, platelet function and inflammatory cell infiltration in response to H. pylori infection. The regulation of COX-1 at the transcriptional level by H. pylori described in this study is a novel finding and calls into question the traditional description of COX-1 as a purely constitutive, housekeeping gene.

Blotting, Western↗
PubMed2002

Genetic toxicity of a standardized mixture of citrus polymethoxylated flavones.

Flavonoids are a ubiquitous family of phytochemicals that display a variety of biological effects, both beneficial and adverse depending on the individual compound. Certain flavonoids are genotoxic while others inhibit the genotoxicity of other mutagens. In the present studies, the mutagenicity of a mixture of polymethoxylated flavones (PMFs) purified from citrus peel oil was evaluated. The mixture consisted of nobiletin (32.5%), 3,3',4',5,6,7,8-heptamethoxyflavone (25.0%), tangeretin (14.0%), trimethylscutellarein (9.1%), sinensetin (3.9%), 5-demethyl-nobiletin (2.8%), hexa-O-methylquercetagetin (3.3%), 5-demethyl-tetramethylscutellarein (0.7%), 5-hydroxy-3,3',4',6,7,8-hexamethoxyflavone (0.7%), and a small quantity of unidentified flavonoid compounds (3.9%). In vitro addition of the PMF mixture over a concentration range that spanned four log doses (0.0005-5.0 mg/plate) did not reveal any evidence of mutagenicity in five bacterial tester strains (Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537) either in the absence or presence of S9 activation. The PMF mixture exhibited a statistically significant increase in mutagenicity of L5178Y tk(+/-) mouse lymphoma cells at 0.05 (38.5 x 10(-6); P<0.05) and 0.1 mg/ml (61 x 10(-6); P<0.01) compared with vehicle-treated controls (mutation frequency=19.7 x 10(-6)). However, these responses were within historical values observed in negative control cultures and extremely small compared to the positive control (EMS 0.5 microl/ml; 1685.3 x 10(-6)). Furthermore, in the presence of S9 there was no indication of genetic toxicity in L5178Y tk(+/-) cells. These results demonstrate that the PMF mixture is not genotoxic in in vitro assay systems.

Animals↗
PubMed2001

Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials.

BACKGROUND: Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion. METHODS AND RESULTS: Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow. CONCLUSIONS: Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.

Aged↗
PubMed2001

Final results of a randomized trial comparing the MULTI-LINK stent with the Palmaz-Schatz stent for narrowings in native coronary arteries.

The MULTI-LINK (ML) stent is a novel second generation coronary stent. The ACS MultiLink Stent Clinical Equivalence in De Novo Lesions Trial (ASCENT) randomized 1,040 patients with single, de novo native vessel lesions to treatment with the ML stent or the benchmark Palmaz-Schatz (PS) stent, to demonstrate that the ML stent was not inferior to (i.e., equivalent or better than) the PS stent in terms of target vessel failure by 9 months. Successful stent delivery was achieved in 98.8% versus 96.9% of patients, with a slightly lower postprocedural diameter stenosis (8% vs 10%, p = 0.04), and no difference in 30-day major adverse cardiac events (5.0% vs 6.5%) for the ML stent versus the PS stent. The primary end point of target vessel failure at 9 months was seen in 15.1% of ML-treated patients versus 16.7% of PS-treated patients, with the ML proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). In a prespecified subset, angiographic restudy showed a nonsignificant trend for reduced ML restenosis (16.0% vs 22.1%). Thus, the ML stent showed excellent deliverability and acute results, with 9-month clinical and 6-month angiographic outcomes that were equivalent or better than the PS stent.

Aged↗
PubMed2001

A regulatory role for Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) in phagocytosis mediated by Fc gamma receptors and complement receptor 3 (alpha(M)beta(2); CD11b/CD18).

The Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) is recruited to immunoreceptor tyrosine-based inhibition motif (ITIM)-containing proteins, thereby suppressing phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathways. The role of SHIP in phagocytosis, a PI 3-kinase-dependent pathway, is unknown. Overexpression of SHIP in macrophages led to an inhibition of phagocytosis mediated by receptors for the Fc portion of IgG (Fc gamma Rs). In contrast, macrophages expressing catalytically inactive SHIP or lacking SHIP expression demonstrated enhanced phagocytosis. To determine whether SHIP regulates phagocytosis mediated by receptors that are not known to recruit ITIMs, we determined the effect of SHIP expression on complement receptor 3 (CR3; CD11b/CD18; alpha(M)beta(2))-dependent phagocytosis. Macrophages overexpressing SHIP demonstrated impaired CR3-mediated phagocytosis, whereas macrophages expressing catalytically inactive SHIP demonstrated enhanced phagocytosis. CR3-mediated phagocytosis in macrophages derived from SHIP(-/-) mice was up to 2.5 times as efficient as that observed in macrophages derived from littermate controls. SHIP was localized to Fc gamma R- and CR3-containing phagocytic cups and was recruited to the cytoskeleton upon clustering of CR3. In a transfected COS cell model of activation-independent CR3-mediated phagocytosis, catalytically active but not inactive SHIP also inhibited phagocytosis. We conclude that PI 3-kinase(s) and SHIP regulate multiple forms of phagocytosis and that endogenous SHIP plays a role in modulating beta(2) integrin outside-in signaling.

Animals↗
PubMed2001

Data mining: Efficiency of using sequence databases for polymorphism discovery.

An open question in research on Single Nucleotide Polymorphisms (SNPs) is, what is the percentage of true SNPs found by in silico pre-screening? To this end, we selected 13 genes, and determined the complete collection of "true" polymorphisms, or polymorphisms experimentally detected, existing in these genes in our laboratory using Denaturing High Performance Liquid Chromatography (DHPLC) and fluorescent sequencing, or in other laboratories using comparable methods. The genes studied by our group were PTGS2, IGFBP1, IGFBP3, and CYP19. GenBank sequence information was then aligned using two methods, and sequence differences termed "candidate" polymorphisms. We then compared the series of SNPs obtained experimentally and in silico and we have found that in silico methods are relatively specific (up to 55% of candidate SNPs found by SNPFinder have been discovered by experimental procedure) but have low sensitivity (not more than 27% of true SNPs are found by in silico methods).

Aromatase↗
PubMed2001

Multiple sclerosis: empirical literature for the clinical health psychologist.

This article reviews the empirical literature related to clinical health psychology in multiple sclerosis (MS). MS is a disease in which the immune system attacks the central nervous system. As such, the interactions between medical and psychological variables are complex, and potentially of considerable importance to patients. Common neuropsychological and psychological problems associated with MS and their etiologies are reviewed. The effects of stress and depression on MS exacerbation are discussed, including clinical, immune, endocrine, and neuroimaging findings. The types of coping common in MS and their effects on adjustment are discussed. The empirical literature on psychological and neuropsychological intervention is reviewed. The small literature on caregiving in MS is also summarized.

Adaptation, Psychological↗
PubMed2001

Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system.

Phagocytosis is a phylogenetically ancient process by which eukaryotic cells engulf insoluble substances whose size exceeds approximately 0.5 microm. The engulfment process requires the concerted action of several fundamental cellular pathways and is governed by multiple transmembrane signaling events. Here we focus on phagocytosis mediated by a well-studied class of phagocytic receptors that recognize the Fc portion of IgG (Fc(gamma)Rs ).

ADP-Ribosylation Factor 6↗
PubMed2001

Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our results suggest that within families siblings with the A variant in the PPARgamma2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations.

Adult↗
PubMed2001

Immunotoxicity of a standardized citrus polymethoxylated flavone extract.

Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity, the current studies were conducted to assess the potential for a standardized citrus PMF mixture to suppress humoral and innate immune functions. PMFs were isolated from orange peel oil using a procedure that obtained a consistent mixture of PMFs both in identity and proportion. The mixture consisted of nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%), trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl-nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl-tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8) were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On day 25, mice were sensitized to sRBC by tail vein injection and AFC response determined 4 days later. Humoral immunity was insensitive to suppression following exposure to all concentrations of the PMF mixture. Suppression of NK cell activity was observed only following 500 mg/kg/day for 28 days. Body weights were not affected by exposure to any concentration of the PMF mixture in sRBC immunized or non-immunized mice. However, in sRBC-immunized mice, higher concentrations of PMF were associated with a statistically insignificant increase in spleen weight (P>0.05). No change in spleen weight was observed in non-immunized mice. As anticipated, based on previously published in vitro observations, long-term, high-dose exposure to a standardized mixture of citrus PMFs caused a mild suppression of NK cell activity; however, humoral immunity was not sensitive to suppression at the same exposure levels.

Animals↗
PubMed2001

A psychophysiological marker of attention deficit/hyperactivity disorder (ADHD)--defining the EEG consistency index.

This study continues our research to further validate the idea that ADHD (Attention Deficit/Hyperactivity Disorder) interferes with transition from one task to another and this interference can be quantified by a Consistency Index (CI) derived from a specific mathematical representation of EEG data. We reanalyze 32 previously reported data sets present new data for 35 boys and girls, ages 7-12, ADHD or control. Each data set contains EEG, recorded and digitized while participants perform consecutive 10-min tasks: video, reading, and math. For boys, the CI in ADHD was four times lower than in controls, p < .005, for girls this difference was two times, p < .05. ADHD/control classification based on the CI coincided with the DSM-IV criteria for 88% of the boys and for 67% of the girls. Post hoc analysis indicated that the classification utility of the CI diminished with age. A CI below 40% could be a discriminating, reliable, and reproducible marker of ADHD in young boys.

Attention Deficit Disorder with Hyperactivity↗