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Biomedical subjects

P Blin

Publications and source records attributed to P Blin.

At least 19 recordsLinked to original sources
PubMed2007

The CADEUS study: methods and logistics.

PURPOSE: At the request of the French Health authorities, a study called CADEUS (COX-2 inhibitors and NSAIDs: description of users) aimed to describe the users of cyclo-oxygenase (COX)-2 inhibitors and traditional non-selective non-steroidal anti-inflammatory drugs (tNSAIDs). We report here the methodology, logistics and study design performances. METHODS: CADEUS is a cohort study designed to include 40,000 patients randomly sampled monthly in the French National Healthcare Insurance database, who received at least one dispensation of celecoxib, rofecoxib or tNSAIDs (1:1:2), from September 2003 to August 2004. Patients and prescribers were asked to fill a questionnaire on indication, medical history, risk factors and hospitalizations since drug acquisition. There was no reminder. For each respondent, healthcare resources used for the 6 months before and after inclusion were extracted from the database. Response rate, response delay, responders and non-responders characteristics were assessed. RESULTS: Of the 222,879 patients and their prescribers contacted, 20.8% patients and 32.6% prescribers responded. Median response delay was 16 days for patients and 17 days for physicians. Factors associated with patient response were age, cohort, type of prescriber and period of inclusion. CONCLUSION: This is the first study of this design in France, combining data from a claims database and direct patient and prescriber questionnaires.

Adult↗
PubMed2006

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine.

Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a 2-year period. We evaluated 283 lamivudine-naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load, at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period.

Adolescent↗
PubMed2005

[Neuroleptic drug utilization among schizophrenic outpatients].

BACKGROUND: Our objective was to describe and compare neuroleptic drug utilization patterns among French schizophrenic outpatients in public and private care settings. METHODS: A cross sectional survey was carried out by a random sample of 61 public and 112 private psychiatrists who registered for one month all schizophrenic adult outpatients treated with a neuroleptic drug. Among registered patients, each psychiatrist was to include a maximum of 18 patients (public setting) or 9 patients (private setting). Statistical analysis was weighted to take into account for psychiatrist activity level, assessed by patient registration. RESULTS: Psychiatrists included 934 patients in the public care setting and 927 patients in the private care setting. Patients were (mean+/-sd) 40.1+/-12.1 years old, 60.9% men. The patients' social and clinical characteristics were less favorable in the public setting than in the private setting: no professional activity (78.9% vs 65.1%), living in institution (7.2% vs 3.7%), under legal protection (35.1% vs 14.5%), drug abuse (9.6% vs 5.6%). An atypical neuroleptic was prescribed for 63.0% of patients and a classic neuroleptic for 49.7%, an association of neuroleptics for 22.0%. In both settings, the most prescribed neuroleptics were olanzapine (28.0%) and risperidone (18.6%) with a higher mean daily dosage in the public care setting. At least one neuroleptic treatment change (drug and/or dosage) occurred during the previous year for 44.9% and 39.2% patients, in public and private settings, respectively. In both settings, reasons for changes were mainly lack of efficacy (55.1%) and side effects (49.8%). CONCLUSION: Public and private care populations were different but not as much as expected. In both settings, atypical neuroleptics were the predominant drugs used in the treatment of schizophrenia outpatients. The high frequency of drug change for lack of efficacy or side effects demonstrates the difficulties with the use of the present neuroleptic armamentarium.

Adolescent↗
PubMed2004

Assessment of migraine severity using the MIGSEV scale: relationship to migraine features and quality of life.

We have recently developed an instrument to describe and categorize severity of migraine attacks from patient self-report, the MIGSEV questionnaire. We have now performed a large prospective survey using this tool to evaluate migraine severity in 2979 patients consulting for headache in France, included by 1164 general practitioners, 174 neurologists and 82 gynaecologists. The objective of the study was to determine the prevalence of severity grades in a large population who consults for migraine, to test the concordance between severity calculated from physician-derived and patient-derived data, and to test the relevance of the concept of severity as applied to diagnosis, other measures of the burden of migraine, and to health-related quality of life. Severe attacks were reported in around one-fifth of the sample. Physician- and patient-derived data provided concordant estimates of severity in 71% of cases, the discordant cases representing principally an underestimate by the physician of headache severity. Migraine severity was associated with frequent, long-lasting and treatment-resistant attacks, and with poor quality of life. The MIGSEV questionnaire is proposed as a simple measure of severity for the diagnosis and management of migraineurs, suitable for use both by physicians and patients.

Adolescent↗
PubMed2003

[Infections by Candida sp. in intensive care. Survey of French practices].

OBJECTIVE: The isolation of Candida sp in nosocomial infections is on the increase and over the past 10 years many guidelines for "good" practices and recommendations have been published on the modalities for the management of systemic candidiasis. The aim of this paper was to assess the habits in the intensive care units in this domain in France. METHOD: A transversal survey on the habits was conducted from March to May 2001, using a questionnaire mailed to 200 intensive care units. RESULTS: One hundred eighty questionnaires (surgical reanimation: 12%, medical: 18%, medico-surgical: 70%) out of 200 (92.5%) were returned. The indirect diagnostic examinations: serology, search for antigenemia and PCR (Polymerase Chain Reaction) were never used in 21, 35 and 65% of cases. The systematic search for colonisation (a mean of 4 areas sampled) was conducted in all the patients by 19% of the investigators, in some patients by 53%, and never by 28%. An antifungal treatment was prescribed: in the presence of a positive haemoculture alone, once out of twice if the sample had been taken from a central catheter and in 2 cases out of 3 when the sample was peripheral. It was prescribed 6 times out of 10 after isolation of Candida sp following surgery or on needle aspiration of an intra-abdominal abscess, varyingly in the case of cadiduria, isolation of a Candida sp in a broncho-pulmonary sample or in abdominal draining and positive culture of a catheter, depending on the intensity of the colonisation, the severity of the clinical picture and the presence of factors of risk for Candida infection. It is still prescribed empirically depending on the same elements and the absence of explanation for worsening. When faced with candidemia in a non-neutropenic patient, a central catheter is not changed in 18% of cases. Depending on the microbiology, fluconazole is prescribed in: the identification of yeast without further precision (78% of cases), Candida sp without further precision (86% of cases), Candida non albicans without further precision (57% of cases), C. albicans (93% of cases), Candida non albicans other than C. krusei and C. glabrata (62% of cases), C. glabrata (36% of cases) with an increase in dose in 1 out of 2 cases. In the presence of C. glabrata or C. krusei, amphotericin B is the choice in respectively 51 and 75% of cases. To adapt the treatment.

Adult↗
PubMed2003

[Compliance with hormone replacement therapy in menopausal women: results of a two-year prospective French study comparing transdermal treatment with fixed oral combination therapy].

OBJECTIVES: To evaluate rates of continuation with hormone replacement therapy (HRT) at 2 years in 2 cohorts of female patients, one of which was treated with a set combination of oral oestradiol valerate and medroxyprogesterone acetate and the other with percutaneous 17 beta-oestradiol gel combined with an oral progestogen selected by the prescribing doctor. PATIENTS AND METHODS: A prospective, randomised, open study, including 885 patients followed for 2 years whose 477 were in the oral HRT cohort and 408 were in the dermal cohort. Randomisation was done by group with prescription of the selected HRT for the cohort. The 2 treatment groups were compared using chi(2) tests and Fisher's exact test for qualitative variables, Student's t test or Wilcoxon's test for qualitative variables and Kaplan-Meier survival curves for continuation of HRT, with comparisons using the log-rank test. The prognostic value of baseline parameters on subsequent continuation of HRT was studied using the Cox model (Wald test, odds ratio). RESULTS; Among the 885 treated patients, 711 received the HRT assigned to their cohort (382 in the oral HRT cohort, 329 in the dermal HRT cohort). After 2 years, 77.9% of the patients in the oral HRT cohort and 73.4% of the patients in the dermal HRT cohort were continuing to take their prescribed HRT (P = 0. 076): 37.9% of patients in the oral HRT cohort and 20.2% of patients in the dermal HRT cohort (P < 0.001) continued taking their treatment without any modification. CONCLUSION: Although there was no significant difference in the level of compliance in the 2 groups, it is nonetheless worth noting that the HRT compliance with a sequential fixed estroprogestogen combination was, in this trial, at least equal to that with the free combination of a transdermal estrogen and a progestogen whose nature, dosage and sequence duration are selected by the prescriber. On the other hand, treatment modifications occurred more frequently in the cutaneous HRT group, which is logical as free combination affords to adapt the treatment to each patient.

Administration, Cutaneous↗
PubMed2001

Conventional antihypertensive drug therapy does not prevent the increase of pulse pressure with age.

Increased pulse pressure (PP), an independent predictor of cardiovascular risk, may be quantified on the basis of the prevalence of isolated systolic hypertension (ISH) in the population at large. The purpose of this study was to estimate the prevalence of ISH and its relation to age and drug therapy in a large group of outpatient hypertensive subjects in France. Between March and December 1999, 2975 French general practitioners included 17 716 consecutive patients with uncontrolled hypertension (systolic blood pressure [SBP] >140 mm Hg and/or diastolic blood pressure [DBP] >90 mm Hg), either treated or not treated. They were asked to complete a questionnaire concerning associated cardiovascular risk factors and ongoing antihypertensive therapy. Subjects were classified according to 5 age ranges (from 18 to 103 years). In each age range, SBP, DBP, mean blood pressure, and PP were significantly lower (P<0.001) in treated subjects than in untreated subjects, with the exception of PP in subjects >75 years. The latter finding resulted from a significant increase of SBP and PP with age, together with a significant lowering of DBP with age, irrespective of drug treatment. Subsequently, the prevalence of ISH increased with age from 20.4% to 35.2% in men and women. In any given age range, drug therapy for hypertension is associated with marginally lower values of PP. In the studied populations, the increase of PP with age is independent of gender and of the presence of antihypertensive drug treatment, leading to an increased prevalence of ISH and a subsequent increase of cardiovascular risk with age.

Adult↗
PubMed2000

[Two years follow-up of a heroin users cohort treated with high dosage buprenorphine. Results of the SPESUB study (pharmacoepidemiologic follow-up of general practice Subutex)].

BACKGROUND: Since February 1996, French GPs are allowed to prescribe high dosage buprenorphine for maintenance treatment of major opioid drug addiction. A prospective cohort of major opioid addicts was initiated in order to assess patient outcomes: follow-up, retention rate in treatment, drug use, intravenous injection and social situation evolution. METHODS: Each GP, known to be involved in drug user management, had to include the first 10 opioid drug addict patients to whom he prescribed high dosage buprenorphine, with a maximum inclusion period of 3 months. Patients were followed up for two years and a regular standardized information was collected (usual data on drug users and prescription modalities). RESULTS: Between May and July 1996, 919 patients (664 men and 255 women, mean age: 30 years) were included by 101 GPs. They had a long and serious history of drug addiction, important parallel consumption of cocaine, codeine and other illicit drugs and psychiatric problems (28% of definite problems and 45% of probable) and frequent hepatic conditions (hepatitis B: 23%, hepatitis C: 21%). Two years later, 55% of patients were still followed-up by the same GP and an additional 12% were followed by another GP or in a health care service (hospitalized or receiving methadone in a specialized centre). 13% were not followed, but GPs were able to describe their situation. 8% had been included by GPs who had dropped the study. Finally, 12% of patients were lost to follow-up. Among the 508 patients still followed-up by the same GP after 2 years, the substitution treatment rate was 84%. The dosage bracket had widened (inclusion: mean dosage=7.8 mg +/-4.5, minimum=0.8, maximum=28, median=8; after 2 years: mean=7.6 mg +/-5.4, minimum=0.4, maximum=28, median=8) and the duration of the prescription and dispensing had increased. Declaration of heroin intake in the previous month had fell from 40% to 11% and declaration of drug intake from 53% to 20%. Social situation had improved on average (housing conditions and work). There were 12 seroconversions for hepatitis B, 21 for hepatitis C and 4 for HIV. 14% of patients had declared intravenous injection of high dosage buprenorphine in the previous month. CONCLUSION: After two years of follow-up, 55% of patients were still followed-up by the same GP and an additional 12% was followed by another GP or in a health care service. Among patients still followed up by the same GP, a reduction of drug related harm (seroconversions for hepatitis B, hepatitis C and HIV) was observed.

Adult↗
PubMed1999

[Impact of an information campaign on cardiovascular risk factors. 5-year results at the study town Epernon].

OBJECTIVES: Information campaigns are implemented to improve knowledge of cardiovascular disease and risk factors. The impact of these programs must be evaluated to determine whether they truly contribute to modifying risk factors in the population. METHODS: A 5-year information campaign on cardiovascular disease and risk factors was conducted in Epernon, France. The main objectives of the campaign focused on stopping smoking, regular physical exercise and balanced nutrition. Data were collected from a representative sample of the female and male population aged 20 to 65 years selected from the study town Epernon (500 subjects), and in control towns, Magny-en-Vexin and Moret-sur-Loing (200 subjects). The study town and control towns were comparable for population, demographic characteristics and geographic localization (distance from Paris). The subjects were invited to respond to a questionnaire on demographic data, attitudes toward health, risk factors and diet and underwent a clinical examination with blood tests. RESULTS: The initial sample included 961 subjects and 68.5% participated in the final survey. We were unable to evidence any significant difference in risk factors or the 10-year risk score calculated from the Framingham equation adapted to France. The information campaign was well accepted, the population not expression a feeling of lassitude. The campaign had a minimal effect on the way individuals relate to health. There was a fall in mean energy intake, mainly fat calories, which was similar in all three towns. CONCLUSION: No major modification in cardiovascular risk factors was observed in this low-risk population, suggesting that future information campaigns should be aimed at targeted populations with a higher risk profile using simple and selected messages.

Adult↗
PubMed1999

[Use of a structured diagnostic interview to identify depressive episodes in an epidemiologic study: a posteriori internal validation].

BACKGROUND: During these last years, many structured and standardized diagnostic interviews have been developed in order to identify psychiatric disorders in a standardized way. These tools enable a systematic investigation of these disorders according to international classifications. Their main drawback is to be long. To assess the care of depression, we used a shorter and more simple tool: the Mini International Neuropsychiatric Interview (MINI) to identify depressive subjects. METHOD: The study was conducted in the Gazel cohort from the French National Electricity and Gas Company. A stratified sample of 2394 civil servants selected in order to over-represent depressive subjects was asked to answer to the MINI interview through a phone interview. An epidemiological and statistical analysis was performed to test the MINI internal validity: prevalence of depressive disorders using different threshold of diagnosis (number of symptoms required to identify someone as depressive), frequency of different symptoms, variability between investigators and potential biases. RESULTS: Respondents to the phone interview (1108 civil servants) had more often presented depression markers for the last 5 years. Prevalence of depressive episodes changed little when we varied the threshold of diagnosis and did not stress any threshold problem. The variability between investigators was important, but the estimation of prevalence remained stable when we excluded extreme rates of prevalence. The choice of a classification system affected the prevalence estimation. Using the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) from the American Psychiatric Association, the prevalence of depressive episodes was lower and closer to the estimations shown in the literature than using the International Classification of Disease (ICD 10). Moreover, the stratification assigned very unbalanced weights to the stratification strata. By excluding depressive episodes observed in the stratum "control" (no depression "marker" from 1989 to 1994 in the database), the prevalence was very lower, whatever the classification was. Finally, factors which appeared linked to care of depression with the ICD definition remained the same when the DSM diagnosis definition was used, and relative risks were quite similar. CONCLUSION: The MINI appears to be a short and simple tool, suited to the epidemiological studies. This analysis does not highlight any failure in the internal consistency of the MINI. The remaining question is what the MINI really measures, particularly comparing to a psychiatrist's diagnosis.

Cross-Sectional Studies↗
PubMed1998

Alcohol or drug use and compliance with safer sex guidelines for STD/HIV infection. Results from the French National Survey on Sexual Behavior (ACSF) among heterosexuals. Analyse des Comportements Sexuels en France.

BACKGROUND: Available literature shows that association of alcohol and/or drug use with unsafe sexual practices is not established, in contradistinction to the well-established association between such substance use and the sexual milieu itself. GOAL: To analyze these two kinds of associations in a population-based sample of heterosexuals in France. STUDY DESIGN: Cross-sectional telephone survey of the French adult heterosexual population in the early 1990s (n = 4213). RESULTS: Subjects at risk were more likely than those not at risk to have consumed alcohol before sex; this was not the case for drug use. However, at-risk subjects who engaged in unsafe practice(s) were not more likely to have consumed alcohol or drugs. CONCLUSION: Alcohol consumption appears to be a marker for being in an at-risk situation in France and may be used as such by public health providers. In contrast, the association between alcohol/drug use and unsafe sexual practices is not supported by our study and thus conflicts with prevention strategies to increase compliance with safer sex through alcohol/drug abstinence.

Adolescent↗
PubMed1998

Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps.

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

Adult↗
PubMed1998

[Sports activities and declared health status].

A cross-section study on sports and health was carried out among 8666 subjects from 15 to 49 years old, for a large range of practices. The analysis compared three groups, 2048 non-athletics, 5381 "moderately" athletic, and 1237 "highly" athletic. Compared to non-athletics, the "moderately" athletic group has a higher opinion of their state of health, with a similar frequency of declared health problems (hospitalisations, absences from work, traumatisms). The intensive practices are accompanied by an opinion of health status similar to the moderately athletic group, with a larger frequency of declared health problems. These results suggest a poor control of sports risks among those who practice the most.

Absenteeism↗
PubMed1997

Controlled efficacy study of fluoxetine in dysthymia.

BACKGROUND: There have been very few controlled studies of antidepressants in dysthymia, particularly in samples diagnosed reliably and with an adequate length of follow-up. In this investigation, we measured the long-term outcome in a large group of patients meeting DSM-III-R criteria for dysthymia. This study was designed to investigate whether fluoxetine is effective in the treatment of dysthymia. METHOD: This randomised study including 140 patients, compared fluoxetine (91 patients) and placebo (49 patients) on a double-blind basis in two distinct phases: a short-term end-point (3 months with 20 mg/day fluoxetine) and a medium-term end-point (6 months) where the initial responders continued double-blind treatment unchanged and non-responders received an additional treatment of 20 mg/day fluoxetine. RESULTS: After three months of treatment, response was seen more frequently in the fluoxetine group (42/72) than in the placebo group (14/39, P < 0.0001). Improved patients at 3 months were still improved at 6 months. Furthermore, 50% of the nonresponders at 3 months improved and rated as responders at 6 months, after fluoxetine was increased to 40 mg daily. CONCLUSIONS: This study showed the significant and persistent action of fluoxetine on dysthymia. The finding that 50% of the non-responders at 3 months were improved at 6 months, after fluoxetine dosage was increased to 40 mg daily, argues in favour of treating dysthymic patients for at least 6 months, and with a higher dosage if the initial doses are ineffective.

Adult↗
PubMed1997

[4-month follow-up of 198 heroin addicts by general practitioners].

This study aimed to describe the short term follow-up of a cohort of 198 i.v. heroin users by 44 highly motivated General Practitioners (GPs). The study showed that for these GPs, the work-load linked with the care of these patients was heavy. Nearly half of them saw at least one drug-addict every day. These GPs work within a network and stated they benefit from a regular training on drug addiction topics. The profile of i.v. heroin users, followed by these GPs, is different from the ones usually described in other health care structures (higher percentage of women and better social insertion). The two main motives to consult a GP are the demand of drugs concerning their addiction and medical concern (due to infectious diseases especially). The answer of GPs, concerning the demand of drugs, divide physicians into two groups: those who never prescribe morphine like drugs as substitution and those who do so. In addition, both of them often prescribe psychotropic drugs to some of their patients. Nevertheless, these prescriptions are just one of the elements of a follow-up contract between a GP and his patients. Morphine like prescription is more frequently described among long term drug-addicts already well-known by GPs. This selection prohibits a straight comparison of the results of two groups of patients (with and without morphine like substitution). But the main fact is that patients under morphine like substitution are followed better (in terms of continuity) after 4 months of observation.

Adult↗
PubMed1996

The effect of fluoxetine on anxiety and depression symptoms in cancer patients.

Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients. A double-blind placebo-controlled study was therefore designed to assess the effectiveness of 20 mg fluoxetine. Of 115 cancer patients who fulfilled entry criteria for levels of distress, 45 patients were randomized to a fluoxetine treatment group (FA) and 46 patients to a placebo group (PA) after a 1-week placebo period designed to exclude placebo responders. The Montgomery and Asberg Depression Scale (MADRS), the Hamilton Anxiety Scale (HAS), the Hospital Anxiety and Depression Scale (HADS), the Revised Symptom Checklist (SCL90-R) and the Spitzer Quality of Life Index (SQOLI) were used to assess the efficacy of fluoxetine. The response rate, defined by a HADS score lower than 8 after 5 weeks of treatment, was not significantly higher in the FA group (11%) compared to the PA group (7%). Compared to the PA group, patients in the FA group showed a significantly greater decrease in SCL90-R mean total score after 5 weeks, but not a greater decrease in HADS mean score. No difference between the two groups was found in observer-reported assessments (MADRS, HAS and SQOLI). Significantly more drop-outs were observed in the FA group (n = 15) than in the PA group (n = 7), although the frequencies of side-effects were not significantly different.

Adult↗
PubMed1995

15-Lipoxygenase expression in smooth muscle cells from atherosclerotic rabbit aortas.

To determine the extent and origin of the stimulation of 15-lipoxygenase activity in atherosclerotic aortas, formation of hydroxy-derivatives from arachidonic acid was measured by HPLC-analysis and 15-lipoxygenase mRNA expression was investigated by RNA blot and in situ hybridization in atherosclerotic and normal rabbit aortic tissues. The synthesis of hydroxy-eicosatetraenoic acids (HETE) from exogenously added [14C]arachidonic acid was unchanged in atherosclerotic aortas in comparison with healthy aortas, but pretreatment with indomethacin demonstrated that 15-HETE production resulted essentially (75%) from cyclooxygenase activity in healthy aorta and from lipoxygenase activity in atherosclerotic aorta. The RNA blot and in situ hybridization with radiolabelled oligonucleotide probe demonstrated that 15-lipoxygenase mRNA was strictly localized in intimal thickening of atherosclerotic aortas. The immunostaining using anti-alpha smooth muscle actin, revealed that smooth muscle cell rich areas of the intimal thickening expressed 15-lipoxygenase mRNA. In addition, RNA blot hybridization indicated that cultured smooth muscle cells from atherosclerotic aortas expressed strongly 15-lipoxygenase mRNA. These results demonstrate that augmentation of 15-lipoxygenase activity in atherosclerotic aortas is correlated with 15-lipoxygenase mRNA expression in atherosclerotic plaque, and that intimal smooth muscle cells were involved, in addition to macrophages, in the expression of 15-lipoxygenase.

Animals↗