Hazardous drinking is associated with hypnotic consumption in medical students in the BOURBON nationwide study: psychological factors explored.

France has been identified with one of the highest rates of hazardous drinking and hypnotic consumption in Western countries. Medical students have been identified at risk for hazardous drinking yet we lacked of national data on their hypnotic consumption and associated factors to guide public health policies. To determine the prevalence of hazardous drinking and dependence among French medical students and their association with psychotropic drug consumption and psychosocial factors. Medical students were recruited from 35 French universities of medicine through administration mailing lists and social networks, between December 13, 2016 and May 15, 2017. Hazardous drinking was defined by an Alcohol Use Disorder Identification Test (AUDIT) score ≥ 7 for men and ≥ 6 for women. 10,985 medical students with a mean aged of 21.8 years (± 3.3) were included, 32% of which were male. Overall, 3713 (34%) students reported hazardous drinking (41% for men vs. 31% for women) and 820 participants (8%) reported alcohol dependence (12% for men vs. 6% for women). In multivariate analyses, hazardous drinking was independently associated with age, male gender, hypnotic consumption, psychiatric follow-up, mourning, parents divorce, exposure to sexual and physical assault. Alcohol dependence was associated with male gender, tobacco and cannabis consumption, and sexual and physical assault. Second year was reported as the year at higher risk for increased alcohol consumption vs. decreased risk in first and fourth year. Hazardous drinking identified in one third of medical students is associated with hypnotic consumption and some psychological factors suggesting self-medication behavior that could be targeted by psychological interventions.

Prevalence and associated factors of cannabis consumption in medical students: the BOURBON nationwide study.

France has been identified with one of the highest rates of cannabis consumption of Western European countries. Yet we lack data in medical students who are at risk of addictive behavior. The objective of the study is to determine the prevalence of cannabis consumption and cannabis use disorder (CUD) among French medical students and their association with psychotropic drug consumption and psychosocial factors. Medical students were recruited from 35 French universities of medicine through administration mailing lists and social networks, between December 2016 and May 2017. Cannabis consumption was self-declared by anonymous questionnaire and CUD was defined by a Cannabis Abuse Screening Test (CAST) score ≥ 3. 10,985 medical students with a mean age of 21.8 years (± 3.3) were included, 32% of which were men. Overall, 1642 [14.9 (14.3; 15.6)%] reported cannabis consumption and 622 [5.7 (5.2; 6.1)%] students were identified with CUD at screening. Men were at two-time higher risk of cannabis consumption and three-time higher risk of CUD (22.4% and 10.6% for men vs. 11.5% and 3.4%, respectively, for women). In multivariate analyses, men sex, alcohol use disorder, tobacco smoking, parents' divorce, and history of physical assault and lower rates of lower rates of ≥ 40 weekly worked hours were identified as common associated factors for cannabis consumption and CUD. Hypnotic consumption, psychiatric follow-up, and history of sexual assault were identified as factors associated specifically with CUD, suggesting that these factors were associated with more severe cannabis consumption. Only 17% of students identified with CUD reported a psychiatric follow-up. Altogether, these results suggest that health policies should target cannabis consumption in medical students that is frequent, especially in men, with low rates of psychiatric follow-up. We have identified psychological factors and increased hypnotic drug consumption in CUD participants suggesting that psychiatric follow-up should be systematically proposed to this group.

Repeated bullying at the workplace in medical students and young doctors: the MESSIAEN national study.

Despite clues indicating high Bullying at the Work Place (BWP) rates in French hospitals, there has been no quantitative study so far. To determine the prevalence of repeated BWP in a national sample of French young physicians; its risk factors, and the mental health consequences of BWP. The study is a cross-sectional observational epidemiological national study addressed to young physicians. The online internet anonymous questionnaire was elaborated according to previous studies exploring BWP. In addition, we explored the quality of initial training. BWP was defined according to the French legal definition. Mental health was assessed by Hamilton Anxiety and Depression scale, psychotropic drug consumption and psychotherapy follow-up. A Structured Equation Modeling (SEM) was carried out to confirm our theoretical model. 2003 participants of the 37 French medical faculties were included. At least one history of BWP was identified in 41.7% of the participants. The SEM model showed good fit (RMSEA = 0.025, CFI = 0.93, TLI = 0.92, WRMR = 1.285). In the SEM model, BWP was associated with age and number of monthly night shifts and weekly worked hours. Obstetric gynecology, psychiatry, surgery, and medical specialties and low-quality initial training were associated with higher risk of BWP. BWP was associated with increased anxiety and depressive symptoms, daily antidepressant and anxiolytic consumption, and psychotherapy follow-up. Decreasing worked hours and night shifts and improving the quality of the initial training may help preventing BWP among medical students and young physicians. Obstetric gynecology, surgical and medical specialties, and psychiatry should be targeted with a focus on developing prevention programs.

[Exposure to professional violence by young physicians in the hospital: MESSIAEN national study]. / Exposition aux violences professionnelles à l'hôpital chez les jeunes médecins : l'étude nationale MESSIAEN.

BACKGROUND: Hospital professional violence is defined as hostile and aggressive behavior exerted by health professionals on other health professionals. No quantitative study has been carried out to date on French hospital professional violence among young physicians, while recent qualitative studies have suggested a potential high frequency. The main objective was to determine the prevalence of exposure of young doctors to hospital violence. The secondary objective was to determine their characteristics and consequences as well as to determine if students and young physicians (resident and young MD) differed. METHODS: The study was a national cross-sectional observational epidemiological study that included 4th-year medical students and young physicians (MD for less than 2 years). Thirty-seven French faculties of medicine were contacted for email recruitment of participants. Social networks were used to increase the visibility of the study. The questionnaire was developed after exhaustive review of the international literature dealing with professional violence in hospitals, its characteristics and its consequences in terms of mental health, addiction, personal and professional life. The report of these events was also explored. RESULTS: In total, 2003 participants have been included. More than nine out of ten participants were exposed to hospital violence at least once and nearly 42% to moral harassment as defined by the French law. This violence does not differ between the students and the residents/young MDs, suggesting that working time in the hospital does not seem to affect this risk. Nearly 80 % of interns and young MDs reported working more than the legal time. The perpetrators of violence include in almost all cases at least one man, often a senior doctor, but students reported the presence of at least one woman among the perpetrators in ¾ of cases. The victims are as often men as women. Compared to the undergraduate medical students, residents and young MDs more frequently reported poor outcomes on their mental health, addictive behavior, personal and professional lives. The majority of victims reported the event to a peer but fewer than 10% to the head of the department, a professor or an instance that could have acted. In almost all cases, participants reported the continuation of abusive behavior after the event. In total, 42% of students think that this is simple part of medical studies that they must endure. CONCLUSION: These results suggest the need to develop specific information and prevention programs for professional hospital violence in France.

Hyaluronic acid-amphotericin B nanocomplexes: a promising anti-leishmanial drug delivery system.

The development of an effective amphotericin B (AmB) formulation to replace actual treatments available for leishmaniasis, which present serious drawbacks, is a challenge. Here we report the development of hyaluronic acid-amphotericin B self-assembled nanocomplexes (HA-AmB), processed by freeze-drying (FD) or nano spray-drying (SD), using a simple process that favors the non-covalent drug-polysaccharide association in an amorphous state. These water-soluble formulations, which presented a nanometric size (300-600 nm), high colloidal stability (zeta potential around -39 mV) and an AmB loading (15-18%) in aggregated and super aggregated states, demonstrated less in vitro cytotoxic and hemolytic effects compared to the free-drug. A significant decrease in the number of intramacrophagic L. infantum amastigotes upon treatment (IC50 of 0.026 and 0.030 µM for HA-AmB FD and HA-AmB SD, respectively) was also observed, and the best selectivity index (SI) was observed for the HA-AmB SD nanocomplex (SI of 651). Intravenous administration of the HA-AmB SD nanocomplex for 3 alternate days showed an effective parasite reduction in the spleen and liver of C57BL/6 mice without signs of toxicity commonly observed upon free-AmB treatment. Although lower than that achieved with AmBisome® in the liver, the observed parasite reduction for the nanocomplex was of a similar order of magnitude. The efficacy, stability, safety and low cost of the HA-AmB SD nanocomplex highlight its potential as an alternative treatment for leishmaniasis.

Sexual-orientation based discrimination is associated with anxiety and depression in young physicians. A national study.

INTRODUCTION: The professional risk factors for depression and anxiety are underexplored in young physicians. While there has been increasing research on the mental health and well-being of lesbian, gay and bisexual patients, few studies have examined the mental health and well-being of lesbian, gay and bisexual young physicians. OBJECTIVE: The objective of the present study was to determine the prevalence of Sexual Orientation-Based Discrimination (SOBD) in French young physicians and if SOBD was associated with increased anxiety and depression in this population. METHOD: This national study is a cross-sectional observational epidemiological national study. The participants were recruited between April 1st 2019 and June 31st 2019. One question with binary answer was asked on SOBD. Mental health was assessed by Hamilton Anxiety & Depression scales. RESULTS: On the 2003 participants, 148 (7%) reported SOBD exposure, 647 (32%) current anxiety disorders and 174 (9%) a current major depressive disorder according to their HAD score. SOBD was almost twice more frequently reported in participants with anxiety disorder and major depression (respectively 10%,vs 6% and 12% vs. 7%, p<0.05). In the first model of multivariate analyses, current anxiety disorder was significantly associated with being woman (adjusted odds ratio aOR=1.688, 95%CI 1.350-2.110, p<0.001) and SOBD (aOR=1.729, 95%CI 1.226-2.440, p=0.002). In the second model of multivariate analyses, current major depression was significantly associated with only SOBD (aOR=1.748, 95%CI 1.057-2.888, p=0.029). CONCLUSION: SOBD has been associated with increased rates of anxiety disorder and major depression in young physicians and should be targeted in mental health prevention programs.

Sexual harassment exposure and impaired mental health in medical students. The MESSIAEN national study.

BACKGROUND: A previous national study has suggested that around 20% of French working women reported sexual harassment (SH) at work but we lack of data in medical students of French hospitals to guide prevention programs. OBJECTIVES: To determine SH prevalence in a national sample of French medical students and to validate a theoretical model explaining SH causes and its impact of mental health. METHODS: The study is a cross-sectional observational epidemiological national study. SH was defined according to the French legal definition. We further explored other discriminations and their potential association with impaired mental health in medical students. Mental health was assessed by Hamilton Anxiety & Depression scale, psychotropic drug consumption and psychotherapy follow-up. A Structured Equation Modeling was carried out to confirm our theoretical model. RESULTS: 2003 participants were recruited. SH was reported by 15.7% of the participants (19.8% of women and 5.2% of men). The SEM model showed good fit (RMSEA=0.024, CFI=0.90, TLI=0.87, WRMR=1.165). SH was associated with risk factors such as feminine gender and surgical and anesthesiology specialties. SH was also associated with exposure to discriminations based on the specialty choice and sexual orientation. SH was associated with impaired mental health. CONCLUSION: French medical student women reported similar rates of SH than other working women, suggesting that SH prevention programs are needed in French hospitals. Surgery and anesthesiology should be targeted in priority. The prevention programs should also target other discriminations and should be evaluated in terms of potential mental health improvement.

First-year French medical students consume antidepressants and anxiolytics while second-years consume non-medical drugs.

BACKGROUND: First year exams are a major source of stress amongst first-year medical students. OBJECTIVE: To explore antidepressant and anxiolytic consumption and addictive behavior of medical students before and after exams. METHODS: Medical students of the 35 French medical schools were recruited through mailing lists and social networks between December 2016 and May 2017 and completed online Internet anonymized questionnaires. RESULTS: Overall, 4345 medical students were included (3051 first year vs. 1294 second year). In multivariate analyses, compared to those in the first year of medicine, second year students were found to have lower anxiolytic (adjusted odd ratio (aOR)=0.56, p = 0.01) and antidepressant consumption (aOR=0.21, p<0.0001) but higher psychiatric follow-up (aOR=1.95, p<0.0001) after adjustment for age, gender and relationship status. Whilst second year students reported slightly higher quality of life (especially for mental health), they also reported more daily tobacco smoking (aOR=1.78, p<0.0001), more cannabis use disorders (aOR=2.37, p<0.0001), hazardous drinking (aOR=3.61, p<0.0001), and alcohol dependence (aOR=3.66, p<0.0001). Second year medical students reported fewer difficulties relating to studying in comparison to first year students (aOR=0.60, p<0.0001) yet they reported a higher rate of recreational drugs use with a variety of reasons including self-treatment of anxiety; disinhibition and to copy their peers (all p<0.05). LIMITS: These results should be confirmed by longitudinal studies. CONCLUSION: First year medical students who are faced with challenges relating to studying consume more antidepressants and anxiolytics, whilst second year students have a higher consumption of recreational drugs for a range of reasons. This suggests that the first two years at medical school are an important contributor to adverse mental health and therefore present a window of opportunity for preventative intervention.

Anxiolytic consumption is associated with tobacco smoking and severe nicotine dependence. Results from the national French medical students (BOURBON) study.

Tobacco smoking remains common among medical students, something which may impact on their abililty to promote smoking cessation during their future careers. OBJECTIVES: To determine the prevalence of smoking and consumption among French medical students and explore the link between both the presence of psychosocial factors and consumption of psychotropic medication and the severity of nicotine dependence and daily smoking behavior. METHODS: Medical students were recruited from 35 French universities of medicine through administration mailing lists and social networks, between December 13, 2016 and May 15, 2017. Data was collected via anonymized Internet questionnaire which included questions regarding current daily tobacco smoking behaviors. Severe nicotine dependence was defined by a short Fagerström test equal or >4. RESULTS: 10,985 medical students with a mean aged of 21.8 years (+/-3.3) were included, 31.6% of which were male. 2078 (18.9%) were identified as current daily tobacco smokers and 59 (2.8%) were classed as having severe nicotine dependence. In multivariate analyses, tobacco smoking was independently associated with anxiolytic consumption, alcohol use disorder, cannabis use disorder, financial difficulties, and history of sexual and physical assault. Severe nicotine dependence was independently associated with anxiolytic consumption, cannabis use disorder, domestic violence, physical assault and financial difficulties. CONCLUSION: Tobacco smoking has been found in almost one on 5 medical students and is associated with anxiolytic consumption as well as professional and personal factors.

Psychiatric and psychological follow-up of undergraduate and postgraduate medical students: Prevalence and associated factors. Results from the national BOURBON study.

BACKGROUND: Physicians are at risk of burnout, anxiety and depression. Prevention is needed from the beginning of the medical studies to detect early poor mental health outcomes. OBJECTIVE: To determine the prevalence and associated of psychiatric or psychological follow-up in a national sample of undergraduate and postgraduate medical students (UPMS). METHODS: UPMS of the 35 French Medicine faculties were recruited through mailing lists and social networks between December 2016 and May 2017 and fulfilled Internet anonymised questionnaires. RESULTS: Overall, 10,985 UPMS were included in the present study (2165 (19.7%) postgraduate, 31.6% males, mean aged 21.8 years). Overall, 1345 (12.2%) were followed-up by a psychiatrist and/or a psychologist, 20.5% of them were regular anxiolytic consumers and 17.2% of them were regular antidepressant consumers. In multivariate analyses, being followed-up by a psychiatrist and/or psychologist was associated with older age (aOR = 1.2[1.2-1.2], p < 0.0001), female gender (aOR = 0.5[0.5-0.7], p < 0.0001), current alcohol use disorder (aOR = 1.3[1.3-1.5], p < 0.0001), higher anxiolytic (aOR = 3.1[2.5-3.7],p < 0.0001) and antidepressant (aOR = 11.7[7.6-18.0],p < 0.0001) consumption, and with lower self-reported general health, social functioning and mental health quality of life (all aORs = 0.9, all p < 0.05). The UPMS followed-up by psychiatrist and/or psychologist reported to have been more frequently exposed to sexual assault (5.1% vs. 0.9%, aOR = 2.5[1.3-4.7], p < 0.0001), domestic violence (3.3% vs. 0.8% aOR = 2.1[1.2-4.0], p = 0.01) and parents divorce (11% vs. 6.4%, aOR = 1.5[1.2-1.9], p = 0.001). Students followed-up by a psychiatrist and/or psychologist reported more frequently to seek alleviating anxiety (aOR 1.9[1.6-2.3], p < 0.0001), depression (aOR 1.7[1.3-2.1],p < 0.0001), coping with studies difficulties (aOR 1.5[1.2-1.8],p < 0.0001), experiencing more stress at hospital (aOR = 2.3[1.6-3.5],p < 0.001) and more burnout syndrome (aOR = 1.4[1.1-1.8], p = 0.03). CONCLUSIONS: Around 12% of UPMS are followed-up by a psychiatrist and/or a psychologist. These students reported higher antidepressant and anxiolytic consumption, psychic suffering and altered quality of life, associated with professional pressure and personal issues. Public health programs should be developed to help these students through their studies to prevent later mental /addictive issues and professional suffering. Improving UPMS mental health may also improve the later quality of care of their patients and global stress at hospital.

Venus and Mars on the benches of the faculty: Influence of gender on mental health and behavior of medical students. Results from the BOURBON national study.

Medical student wellness has emerged as an important issue in medical education. OBJECTIVE: To evaluate the gender influence on psychiatric and/or psychological follow-up, psychotropic and illicit drug consumption, addictive behaviors, quality of life and motives for consumption in a large multicentric national sample of medical students. METHODS: Medical students of the 35 French Medicine faculties were recruited through mailing lists and social networks between December 2016 and May 2017 and fulfilled Internet anonymized questionnaires. RESULTS: Overall, 10,985 medical students were included in the present study (mean age 21.8 years, 9640 (87.8%) women). Compared to men, women were found to smoke tobacco and cannabis less frequently (aOR = 0.8 [0.7-0.9], p < 0.0001 and aOR = 0.3 [0.3-0.4], p < 0.0001 respectively), to have lower rate of alcohol use disorders (aOR = 0.7 [0.6-0.7], p < 0.0001). Men were also found to consume more frequently ecstasy, cocaine, mushrooms, amphetamine, LSD, codeine and ketamine (all p < 0.0001) for pleasure and novelty seeking, group effect, but also alleviating anxiety, sedative and stimulant effect and stress before exam (all p < 0.001) while women were more frequently followed-up by a psychiatrist and/or a psychologist (aOR = 2.0 [1.7-2.3],p < 0.0001), consumed more frequently anxiolytics (aOR = 1.6[1.3-1.9], p < 0.0001) and antidepressants (aOR = 1.4[1.1-1.9], p = 0.01), reported lower rates of physical and mental quality of life in all subscores (all p < 0.0001). They were more frequently exposed to sexual assault (aOR = 4.1 [2.5-6.9], p < 0.0001) and domestic violence (aOR = 1.6[1.1-2.5], p = 0.02) while men were more frequently exposed to physical assault (aOR = 0.4[0.4-0.5], p < 0.0001) during their medical studies. CONCLUSIONS: Medical students are mostly women. While men and women are both exposed to professional and personal stress with differences, men are more frequently involved in addictive behavior and psychoactive substance consumption while women are mostly followed-up by psychiatrist and/or psychologist and psychotropic drug consumers, with more impaired self-reported mental and physical quality of life scores. These results should orientate future health strategies for the prevention of later mental illness onset and stress at work in hospital.

Psychiatry: A discipline at specific risk of mental health issues and addictive behavior? Results from the national BOURBON study.

BACKGROUND: Physicians are at risk for burnout, anxiety and depression. OBJECTIVE: To explore the self-reported mental health status, substance use behavior and motives of a national sample of interns in psychiatry compared to other specialties. METHODS: Interns of the 35 French Medicine faculties were recruited through mailing lists and social networks between December 2016 and May 2018 and fulfilled internet anonymized questionnaires. RESULTS: Overall, 2165 interns (302 interns in psychiatry and 1863 in other specialties) mean aged 25.9 years (±2.8), 35% males were included in the present study. In multivariate analyses, interns in psychiatry were found to have higher rates of current tobacco smoking (aOR = 1.9 [1.4-2.5], p < 0.001), alcohol use disorder (aOR = 1.5 [1.2-2.0], p = 0.001), cannabis use disorder (aOR = 2.7 [1.8-4.2], p < 0.001)). They were more frequently followed by a psychiatrist and/ or a psychologist (aOR = 2.5 1.9-3.3], p < 0.001), they consumed more often antidepressants (aOR = 3.8 [2.2-6.6], p < 0.001) and anxiolytic (aOR = 1.8[1.2-2.8]; p = 0.006). They reported to have been more frequently exposed to sexual assault (aOR = 2.2 [1.1-4.8], p = 0.04) and physical assault (aOR = 1.9[1.3-2.9], p = 0.002), and to have lower vitality (ß = 3.5 [0.6-6.4], p = 0.02). Interns in psychiatry reported to have more often experienced ecstasy (aOR = 1.6 [1.2-2.3], p = 0.004), mushrooms (aOR = 1.5 [1.1-2.2], p = 0.04), amphetamines (aOR = 1.9 [1.2-3.1], p = 0.009) and LSD (aOR = 1.8 [1.1-3.1], p = 0.04). Beyond classical motives for this consumption (party, group effect), interns in psychiatry reported to seek more frequently disinhibition (aOR = 1.7 [1.3-2.2], p < 0.001), dealing with anxiety (aOR = 1.7 [1.3-2.3], p = 0.001), and to seek both stimulant (aOR = 1.4 [1.1-1.9], p = 0.04) and sedative effects (aOR = 1.9[1.3-2.7], p = 0.001). CONCLUSIONS: Interns in psychiatry are more exposed to violence during medical studies, they report lower vitality and increased substance use behavior. Their motives for consumption suggest mental health problems associated with increased engagement in psychotherapy and self-medication of antidepressant/anxiolytic. This population should be targeted as a specific vulnerable population among interns in medicine to prevent ulterior bad health outcomes.

The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. METHODS: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. RESULTS: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg). CONCLUSIONS: The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp.

Morphometric and metabolic profile of the distal segment of the internal mammary artery: caution on its use for coronary anastomoses.

OBJECTIVE: Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibility to develop intimal changes were undertaken in order to evaluate the reliability of its use as an anastomotic site for bypass grafting. METHODS: Twenty distal segments of IMA were harvested from patients who had undergone myocardial revascularization. Histologic, enzyme-histochemical and morphometric studies were undertaken on these arterial segments. RESULTS: Histologic examinations indicated an elastomuscular structure in 13 patients, a muscular structure in 6 and an elastic structure in 1. Of the 20 IMAs, none was found to have intimal thickening of greater than 25% of the diameter of the lumen. The enzyme-histochemical profile of the proliferating cells found in the intimal thickening differed from normal contractile smooth muscle medial cells in the loss of myosin and mitochondrial ATPase, plasma membrane 5' nucleotidase, moderately decreased aerobic dehydrogenase and increased lactate dehydrogenase activity and ribonucleoprotein-linked pyroninophilia. Lysosomal beta-glucuronidase and sulfatase were strongly active. This enzyme behavior is unfavorable to contractile function and favorable to cell proliferation and lipid accumulation, two events strongly involved in the atherogenic process. CONCLUSION: Intimal proliferative changes were observed in the distal segment of the IMA. Although there was no histologic evidence of atherosclerotic plaque, the enzyme-histochemical profile of this intimal thickening was favorable to cell proliferation and lipid accumulation. These findings suggest that it may be beneficial to avoid coronary anastomoses with the distal end of the IMA and to use a more proximal/elastic segment.