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PubMed1999

Bcl-2 expression correlates with apoptosis induction but not tumor growth delay in transplantable murine lymphomas treated with different chemotherapy drugs.

PURPOSE: Previously, we have reported that the bcl-2-expressing murine lymphoma cell line LY-ar is resistant to chemotherapy-induced apoptosis when compared to the non-bcl-2-expressing LY-as cell line. The intent of the present study was to determine whether this relationship extends to lymphomas produced from these cell lines in syngeneic mice, after treatment with the same chemotherapy agents. METHODS: LY-ar and LY-as tumors were grown in the hind legs of syngeneic mice. They were subsequently exposed to graded doses of cisplatin (CP), etoposide (VP-16), Adriamycin (ADR), cytarabine (ara-C), cyclophosphamide (CY), or camptothecin (CAM). Apoptotic bodies were scored in histological sections of tumors that had been stained with hematoxylin and eosin. Tumor growth delay was determined on tumors that were treated when they were 8 mm in diameter. Thereafter, tumor diameter was measured daily with a vernier caliper until they had grown to a maximum of 16 mm in diameter. RESULTS: When transplanted into host animals, tumors derived from these two cell lines and treated in vivo with CP, VP-16, ADR, ara-C, CY, and CAM displayed apoptotic propensities similar to those seen in the same cell lines when treated in vitro. Generally, for all the drugs tested, apoptotic indices in LY-as tumors were significantly higher than in LY-ar tumors. However, tumor growth delay measurements could not be predicted with any accuracy from the apoptotic indices. For some drugs LY-ar tumors were more sensitive than LY-as tumors (CP, Vp-16, ADR, ara-C), yet LY-ar tumors were more resistant to CY. CONCLUSIONS: Despite considerable interest in using apoptotic indices as predictors of treatment outcome, the data presented here suggest that these relationships are very complex. This may be especially true for chemotherapy agents for which effects in vivo are complicated by pharmacokinetics, host effects, and tumor cell heterogeneity.

Animals↗

PubMed1983

Risk-taking and drug-use behaviour: an examination.

The purpose of the present study was to investigate the relationship between several forms of drug-use behaviour and risk-taking propensity. Jackson's (1976) risk-taking measure was employed among a sample of high school students (N = 634) selected from a province-wide probability survey on student drug use. The authors predicted that risk-taking would be associated with: (i) the dependence potential of a given drug; (ii) level of drug use; (iii) polydrug use. No conclusive evidence was found confirming the first two hypotheses; however, the data clearly demonstrated that level of polydrug use was significantly related to risk scores. The authors suggest that risk-taking as a general personality trait may more readily distinguish non-users from users of various drugs than discriminate among degrees of use in the latter.

Adolescent↗

PubMed2006

Relationship between stress and relapse in multiple sclerosis: Part I. Important features.

OBJECTIVE: The aim of this two-year prospective study was to examine the relationship between multiple aspects of life-event stress and relapse in multiple sclerosis (MS) patients. BACKGROUND: Few studies have defined the critical features of this life-event stress; for example, stressor duration, frequency, severity, disease-dependency, valency, or stressor constructs, such as the propensity to cause emotional distress/threat or the frustration of life goals. METHODS: 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life events were assessed at study-entry and at three-monthly intervals for two years. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: Acute events, but not chronic difficulties (CDs), predicted relapse occurrence: acute stressor frequency counts predicted greater relapse risk, along with low disability score (EDSS) and being male. We also confirmed the bi-directional stress-illness hypothesis: stressors predicted relapse, and relapse separately predicted stressors. CONCLUSIONS: Life-event stress impacts to a small degree on MS relapse. The number and not the severity of acute stressors are most important; chronic stressors do not predict later relapse. Males and those with early stage disease are also at greater risk of relapse. MS patients should be encouraged to reduce acute stressors during times of high stress, and feel reassured that disease-related chronic stressors do not increase their relapse risk.

Acute Disease↗

PubMed1978

The noninvasive diagnosis of thrombophlebitis in the lower extremities: clinical value of plethysmography combined with augmentation methods and a new scoring system.

Venous impedance plethysmography and respiratory-compression Doppler augmentation responses have proved to be diagnostically valuable in suspected thrombophlebitis of the lower extremities. These noninvasive methods can provide quantitative and reproducible data on the basis of which the presence of increased deep venous resistance can be confirmed, suspected, or doubted. A new scoring system for the composite evaluation of data from 100 consecutive patients with possible thrombophlebitis, pulmonary embolism, or both, is presented. These procedures assume added importance in view of the diagnostic limitations, and even potential hazards, of other methods. These methods indluce lung scanning, radioactive fibrinogen scanning, venography, and pulmonary angiography. Serial studies can be performed with impunity for following highrisk patients and evaluating various therapeutic or prophylactic measures. The importance of monitoring the femoral-popliteal segment is emphasized, because of the greater propensity for massive pulmonary thromboembolism from thrombi in these veins than in the calf vessels. Clinical observations coupled with these studies underscore the fallacy of several widely-held diagnostic biases pertaining to deep venous thrombosis and pulmonary thromboembolism. The long-term followup of 12 patients in whom inferior vena cava unbrellas has been inserted for life-threatening pulmonary embolism is presented. The possible propensity to deep vein thrombosis from vitamin E therapy is raised.

Adult↗

PubMed1996

Radiation-induced apoptosis in normal and pre-neoplastic mammary glands in vivo: significance of gland differentiation and p53 status.

The tumor suppressor gene p53 maintains the integrity of the genome by stimulating apoptosis in cells that have sustained DNA damage. The p53 gene is frequently altered in human cancers, including breast cancer, and such alterations are thought to result in genomic instability and aneuploidy, 2 hallmarks of anaplastic cells. We used radiation as a DNA-damaging agent to test the role of p53 in controlling apoptosis propensity in pre-neoplastic mammary lesions in mice. Four different pre-neoplastic mammary outgrowth lines, D1, TM2H, TM4 and TM12, were maintained by serial transplantation in the cleared mammary fat pads of syngeneic BALB/c mice. These lines have known alterations in p53 expression: TM12 has normal expression, D1 over-produces wild-type protein, TM2H contains a deletion resulting in a null phenotype and TM4 produces a mutant protein. Mice bearing the various outgrowths were irradiated with 5 Gy, and apoptosis was scored by examination of histological sections prepared from the outgrowths 6 hr after irradiation. The TM12 outgrowths, but not the TM2H outgrowths, exhibited radiation-induced apoptosis. The D1 and TM4 lines expressed radiation-induced apoptosis while the fat pads were being repopulated; however, the induced apoptosis declined to low levels as the mice aged. These results are consistent with the hypothesis that normal p53 function is important if mammary cells with DNA damage are to be deleted by apoptosis.

Animals↗

PubMed1990

New narcissism scales for the California Psychological Inventory and MMPI.

New Narcissism scales for the California Psychological Inventory (CPI) and the Minnesota Multiphasic Personality Inventory (MMPI) were developed on the basis of DSM-III criteria and the writings of Akhtar and Thomson (1982), Kernberg (1975) and Kohut (1971, 1977). Self-report protocols from 152 adults and 198 college students were utilized. Rationally selected preliminary items were retained or discarded according to their alignment with the total score on these items. The resulting 49-item CPI and 39-item MMPI scales correlated .81 with each other, and significantly so at p less than .01 with ratings of narcissism, the Raskin-Hall Narcissistic Personality Inventory (NPI) and the MMPI Narcissism scale of Morey, Waugh, and Blashfield. Personological implications of the two new scales were examined in relation to other measures and to observers' adjectival and Q-sort descriptions. Intrascale factor analyses identified five common themes: Cathexis of Power, Risk-Seeking Propensity, Need for Attention, Disesteem for Others, and Impatient Willfulness.

Adult↗

PubMedDate not supplied

Rotator cuff repair in patients with type I diabetes mellitus.

Insulin-dependent diabetes mellitus is associated with shoulder stiffness and a propensity toward postoperative wound complications and infection. We compared our results of open repair of full-thickness rotator cuff tears in 30 diabetic patients with those of a matched, nondiabetic population. No differences were observed in preoperative range of motion, although at a mean of 34 months, significant differences in shoulder active range of motion and passive range of motion were found postoperatively at 6 weeks, 6 months, and final follow-up (P <.05). On the basis of American Shoulder and Elbow Surgeons shoulder scoring, there were 27 (90%) and 28 (93%) good or excellent results in the diabetic and comparison groups, respectively. Complications occurred in 5 diabetic patients (17%), with 2 failures (7%) and 3 infections (10%), as compared with 1 failure (3%) and no infections in the comparison group. Repair of the diabetic rotator cuff may be performed with the expectation of improved motion and function, although less than nondiabetic counterparts. The surgeon should remain cognizant that a higher rate of complications, infection in particular, may occur after rotator cuff repair in the diabetic population.

Adult↗

PubMed2003

Mining a tandem mass spectrometry database to determine the trends and global factors influencing peptide fragmentation.

A database of 5500 unique peptide tandem mass spectra acquired in an ion trap mass spectrometer was assembled for peptides derived from proteins digested with trypsin. Peptides were identified initially from their tandem mass spectra by the SEQUEST algorithm and subsequently validated manually. Two different statistical methods were used to identify sequence-dependent fragmentation patterns that could be used to improve fragmentation models incorporated into current peptide sequencing and database search algorithms. The currently accepted "mobile proton" model was expanded to derive a new classification scheme for peptide mass spectra, the "relative proton mobility" scale, which considers peptide ion charge state and amino acid composition to categorize peptide mass spectra into peptide ions containing "nonmobile", "partially mobile", or "mobile" protons. Quantitation of amide bond fragmentation, both N- and C-terminal to any given amino acid, as well as the positional effect of an amino acid in a peptide and peptide length on such fragmentation, has been determined. Peptide bond cleavage propensities, both positive (i.e., enhanced) and negative (i.e., suppressed), were determined and ranked in order of their cleavage preferences as primary, secondary, or tertiary cleavage effects. For example, primary positive cleavage effects were observed for Xaa-Pro and Asp-Xaa bond cleavage for mobile and nonmobile peptide ion categories, respectively. We also report specific pairwise interactions (e.g., Asn-Gly) that result in enhanced amide bond cleavages analogous to those observed in solution-phase chemistry. Peptides classified as nonmobile gave low or insignificant scores, below reported MS/MS score thresholds (cutoff filters), indicating that incorporation of the relative proton mobility scale classification would lead to improvements in current MS/MS scoring functions.

Algorithms↗

PubMed1986

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.

Adenocarcinoma↗

PubMed1990

On the use of DNA fingerprints for linkage studies in cattle.

To find a marker for the bovine "muscular hypertrophy" gene and for the "roan" locus, we have typed six cattle pedigrees totaling 540 animals for nine blood group systems, for 12 biochemical markers, for RFLPs at four loci, and with five probes revealing multilocus DNA fingerprints. Segregation analysis of the fingerprint bands showed that, in cattle, a fingerprint probe will reveal a mean of 7.6 clearly resolvable bands, behaving as simple, highly informative Mendelian entities characterized by a mean mutation rate of +/- 1/4500 gametes. For one of the bands, we observed a "mutation burst" generating germline mosaicism. Because some of the fingerprint bands were allelic or corresponded to clustered minisatellites, a mean of only 5.7 independent loci is explored per probe. Fingerprint bands revealed by different probes also show a clear propensity for close linkage, pointing toward nonrandom distribution of minisatellite sequences or the existence of minisatellite clusters. Although this reduces the power of fingerprints for linkage analysis substantially, we were able to demonstrate genetic linkage between fingerprint bands and at least three of the classical markers, to exclude the roan locus from 4.5 Morgans of the bovine genome with the DNA fingerprints and for an additional 2.5 Morgans with the classical markers, and to identify a solid candidate marker for the bovine muscular hypertrophy gene, yielding a lod score greater than or equal to 2.84 without any obliged recombinant.

Animals↗

PubMed2004

A Bayesian connectivity-based approach to constructing probabilistic gene regulatory networks.

MOTIVATION: We have hypothesized that the construction of transcriptional regulatory networks using a method that optimizes connectivity would lead to regulation consistent with biological expectations. A key expectation is that the hypothetical networks should produce a few, very strong attractors, highly similar to the original observations, mimicking biological state stability and determinism. Another central expectation is that, since it is expected that the biological control is distributed and mutually reinforcing, interpretation of the observations should lead to a very small number of connection schemes. RESULTS: We propose a fully Bayesian approach to constructing probabilistic gene regulatory networks (PGRNs) that emphasizes network topology. The method computes the possible parent sets of each gene, the corresponding predictors and the associated probabilities based on a nonlinear perceptron model, using a reversible jump Markov chain Monte Carlo (MCMC) technique, and an MCMC method is employed to search the network configurations to find those with the highest Bayesian scores to construct the PGRN. The Bayesian method has been used to construct a PGRN based on the observed behavior of a set of genes whose expression patterns vary across a set of melanoma samples exhibiting two very different phenotypes with respect to cell motility and invasiveness. Key biological features have been faithfully reflected in the model. Its steady-state distribution contains attractors that are either identical or very similar to the states observed in the data, and many of the attractors are singletons, which mimics the biological propensity to stably occupy a given state. Most interestingly, the connectivity rules for the most optimal generated networks constituting the PGRN are remarkably similar, as would be expected for a network operating on a distributed basis, with strong interactions between the components.

Algorithms↗

PubMed1999

Dimensional approach to delusions: comparison across types and diagnoses.

OBJECTIVE: A dimensional approach to the characterization of delusions was used to examine the use of non-content-related descriptors of delusions in revealing differences across diagnostic categories and delusion types. METHOD: Interviews with 1,136 acutely hospitalized psychiatric patients identified subjects as definitely or possibly delusional on the basis of screening questions derived from the Diagnostic Interview Schedule. Subjects with delusions were given the MacArthur-Maudsley Delusions Assessment Schedule, which generates scores on six dimensions of delusions. Delusions were classified by type, and diagnoses were assigned by using the DSM-III-R checklist. RESULTS: A total of 328 subjects (29%) were rated as definitely or possibly delusional. Their ratings on dimensions of the MacArthur-Maudsley Delusions Assessment Schedule were significantly but modestly intercorrelated. Subjects with schizophrenia generally had more intense delusions than those in other diagnostic categories. Grandiose and religious delusions were held with the greatest conviction, whereas persecutory delusions were marked by strong negative affect and a propensity to act. Factor analysis of the dimensions revealed a consistent two factor solution-"intensity and scope" and "affect and action"-regardless of the diagnosis or delusion type. CONCLUSIONS: The stability of the dimensional structure of delusions across diagnoses and delusion types suggests that even seemingly diverse delusions are more like than unlike each other; this is consistent with common etiologic mechanisms. The utility of a dimensional approach is indicated, in addition, by the ability to characterize delusions of different types and diagnoses so as to highlight therapeutic and other implications.

Acute Disease↗

PubMed2005

Participatory decision making, asthma action plans, and use of asthma medication: a population survey.

Use of controller asthma medication and possession of asthma action plans remains suboptimal. Our aim was to investigate the association of the propensity of physicians to involve patients in their care (participatory decision-making style) and their asthma management in a representative population sample of 3015 adults. Current doctor-diagnosed asthma was reported by 393 (13.0%). People who rated their doctors as more participatory were significantly more likely to report more regular use of controller medications and possession of a written asthma action plan, but not less asthma morbidity. Possession of a written action plan was associated with more participatory interactions (OR 2.3; 95% CI 1.1-4.7, for upper tertile scores compared to lowest tertile); more severe symptoms (OR 4.8; 95% CI 1.7-13.0), being female (OR 2.2; 95% CI 1.2-4.3), those with higher education, and residence outside the metropolitan area (OR 2.1; 95% CI 1.1-4.0). Increasing patient participation in their own care is associated with better asthma management, independent of asthma symptoms. Longitudinal studies are needed to examine if increasing participation in decisions can also improve asthma outcomes.

Adolescent↗

PubMed2001

Studies on the effect of polyvinyl pyrrolidone on the activity of chlorhexidine mouthrinses: plaque and stain.

BACKGROUND, AIMS: Polyvinyl pyrrolidone (PVP) was shown in vitro to reduce chlorhexidine induced, dietary staining without affecting the uptake of the antiseptic to the test substrate. The aim of these studies in vivo was to determine whether PVP affected plaque and dietary staining by a low concentration chlorhexidine rinse. METHODS: The plaque and stain studies used a double blind, randomised 6, treatment crossover design involving healthy subjects with a high standard of oral hygiene and gingival health. The rinse formulations under test were: (A) aqueous alcohol (placebo control), (B) 0.03% chlorhexidine, (C) 0.06% chlorhexidine, (D) 0.06% chlorhexidine+1.2% PVP, (E) 0.06% chlorhexidine+5% PVP, (F) 0.06% chlorhexidine+10% PVP. In the plaque study, on day 1 of each period, subjects were rendered plaque free and then rinsed with 15 ml of the test rinse for 60 s. No further tooth cleaning was performed and subjects returned 24 h later for plaque scoring by area. In the stain study, on day 1 of each period, the tongue and teeth of each subject were rendered stain free. Subjects then rinsed under supervision for 60 s with 15 ml of the allocated rinse 8 x a day between 09:00 h and 17:00 h for 3 days. Immediately after each rinse with the test formulation, subjects rinsed for 120 s with 15 ml of warm black tea. Subjects were requested to also drink at least 5 cups of tea or coffee per day. On day 4, stain was scored by area and intensity from designated teeth and dorsum of the tongue. Washout periods were at least 7 days in both studies. RESULTS: Plaque areas were greatest with placebo and least with 0.06% chlorhexidine. Plaque scores increased with increasing concentrations of PVP in the 0.06% chlorhexidine rinse and were significantly higher than 0.06% chlorhexidine without PVP rinse. Tooth stain areas were comparable for placebo, 0.03% and 0.06% chlorhexidine rinses, but significantly reduced with the PVP/chlorhexidine rinses compared to the 0.06% chlorhexidine rinse. Tooth stain intensity was significantly increased with 0.06% chlorhexidine rinses compared to placebo and chlorhexidine/PVP rinses. Tongue stain area and intensity were significantly reduced with 5% and 10% PVP/chlorhexidine rinses compared to 0.06% chlorhexidine rinse. CONCLUSION: PVP, at the concentrations tested, reduced the stain propensity of a 0.06% chlorhexidine rinse but at the expense of some loss of plaque inhibition.

Adolescent↗

PubMed2003

Add-on fluvoxamine improves primary negative symptoms: evidence for specificity from response analysis of individual symptoms.

Establishing that treatment for negative symptoms improves primary features of schizophrenia rather than similar symptoms of other etiology is an important clinical issue. Primary negative symptoms may also differ among themselves in the propensity to respond to a given treatment. In this study, we examined the response of negative symptoms to add-on fluvoxamine by analyzing discrete symptoms independently and controlling for potential confounding variables. Data from two published controlled studies comparing fluvoxamine to placebo were pooled for the analysis. Eleven of sixteen Scale for the Assessment of Negative Symptoms items tested, including key negative symptoms such as affective flattening and alogia, improved. The improvement was not related to baseline levels of depressive, extrapyramidal, and positive symptoms or to changes in the symptom scores during the study. The findings support the view that fluvoxamine augmentation can improve primary negative symptoms in chronic schizophrenia patients.

Affect↗

PubMed2002

The association between psychological factors and oro-facial pain: a community-based study.

OBJECTIVE: To examine the hypothesis that psychological factors of psychological distress, maladaptive response to illness and perception of happiness in childhood, are associated with self-reported oro-facial pain (OFP). METHOD: A cross-sectional population-based study was conducted in South-East Cheshire, UK. The adjusted participation rate was 74%, and 2504 adults aged 18-65 years participated in the study. RESULTS: A report of not having had a happy childhood was associated with risk of 1.6 (95% CI 1.4-2.0) of reporting OFP. An increased propensity to report symptoms associated with OFP was seen for those individuals with higher levels of psychological distress measured using the general health questionnaire (GHQ) with the risk of 2.7 (95% CI 2.3-3.2) in the highest category. All components of the illness behaviour questionnaire (IBQ) were associated with presence of OFP. There was a linear increase in risk (test for trend, P<0.01) associated with the report of OFP for general hypochondriasis, disease conviction, affective inhibition, affective disturbance, and irritability. However there was a significant decrease in risk with a high score for perception of illness (0.6; 95% CI 0.6-0.7) and denial (0.6; 95% CI 0.5-0.7). None of the factors showed significant change in estimates when adjusted for age and gender. CONCLUSIONS: This large cross-sectional community-based study showed significant association for all of the factors considered. The obtained data raise interesting questions of cause and effect for which further, longitudinal studies are required to establish temporal relationship between these factors and the onset, cause, and treatment of OFP.

Adolescent↗

PubMed2006

Bullying in Turkish white-collar workers.

OBJECTIVES: To determine the prevalence of reported workplace bullying among a group of white-collar workers, to evaluate the association between reported bullying and its effect on health and to assess the effects of support at work for bullied workers. METHODS: A cross-sectional questionnaire survey among full-time government employees in the health, education and security sectors. Bullying was assessed using a 20-item inventory. The potential effects of reported bullying were assessed using the Job Induced Stress Scale, the Hospital Anxiety and Depression Scale, Job Satisfaction Scale and the Propensity to Leave Scale. RESULTS: The response rate was 79% (944/1,200) and 877 questionnaires were analysed after exclusion of non-complete data. Of respondents, 55% (483) reported experiencing one or more types of bullying in the previous year and 47% (416) had witnessed the bullying of others. The bully was most likely to be a superior. Sixty per cent of victims had tried to take action against bullying, but most were dissatisfied with the outcome. There were significant differences in anxiety, depression, job-induced stress and support at work scores between those reporting bullying and those not reporting bullying at work. Those who reported bullying with low support at work had the poorest scores on the mental health scales. CONCLUSIONS: Bullying is a serious problem in this group of workers and may lead to health consequences. Feeling that the work environment is supportive appears to have a protective effect in terms of the health outcomes.

Adult↗

PubMed2001

Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence.

In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel showed a statistically significant superiority over aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients with symptomatic atherosclerosis. More recently, post-hoc analysis of the data also showed that repeat hospitalization for ischaemic or bleeding events was decreased with clopidogrel compared with aspirin. Complementary analyses show that the benefit of clopidogrel over aspirin is amplified in a large population at very high risk of further atherothrombotic events (diabetics, patients with high cholesterol, and patients with previous manifestations of atherothrombosis). A potential clinically useful advantage of clopidogrel is its low propensity for adverse interaction with angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial - a randomized comparison of warfarin, clopidogrel and aspirin in patients with chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further demonstrated in a study in healthy volunteers where there was a markedly lower gastroduodenal erosion score after 8 days' administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) trial, other studies of clopidogrel plus aspirin have been initiated or are planned. These include Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients with recent stroke or transient ischaemic attack.

Arteriosclerosis↗