Differentially expressed genes associated with tryptophan-dependent pigment synthesis in Malassezia furfur--a comparison with the recently published genome of Malassezia globosa.

Malassezia (M.) furfur, a commensal organism found on the human skin, produces a wide range of pigments and fluorochromes when cultured with tryptophan as a sole nitrogen source. Some compounds of this pigment metabolism may provide an explanation for clinical characteristics of pityriasis versicolor (PV), a frequent skin disease in humans characterised by long-lasting pigmentary changes. Malassezia globosa is currently regarded as the causative agent of PV, but tryptophan-dependent pigment production has not yet been demonstrated in this species. In a previous study, we identified M. furfur genes that were differentially expressed 3 and 5 h, respectively, after induction of tryptophan-dependent pigment production. The recent publication of the genome of M. globosa prompted us to check the M. furfur sequences for homologues in M. globosa. The 3-h pool contained 79 sequences and the 5-h pool contained 91 sequences. A translated vs. translated BLAST search resulted in 62 sequences (78%) of the 3-h pool and 61 sequences (67%) of the 5-h pool showing similarity to a sequence from M. globosa. It appears that M. globosa possesses homologues to most of the genes that are differentially expressed during pigment production in M. furfur.

Analysis of differentially expressed genes associated with tryptophan-dependent pigment synthesis in M. furfur by cDNA subtraction technology.

Malassezia species are associated with pityriasis versicolor (PV) and its depigmented variant pityriasis versicolor alba (PVa), widespread fungal skin infections in humans. The pathogenesis of PV and PVa remains unclear, including their clinical and histological symptoms such as hyper- and depigmentation, reduced responsiveness to ultraviolet radiation and lack of inflammatory reaction despite high fungal load. Pigments produced by M. furfur are possibly involved in the pathogenesis of PV. In vitro, M. furfur produces a wide range of pigments and fluorochromes when cultured with tryptophan as the sole nitrogen source. We have begun to analyse the molecular basis of pigment production by searching for genes associated with tryptophan-based pigment production. A suppression subtractive hybridization (SSH) protocol was used to identify genes expressed in M. furfur cells producing pigments, but not in non-induced cells. SSH was performed 3 and 5 h after onset of pigment induction. Up-regulation of genes in the pigment-producing cells was confirmed by reverse northern analysis. More than 1,500 cDNA sequences of both the indicated time points were analysed. We identified a wide variety of genes associated with metabolism and several genes with unknown function are specifically expressed during pigment production. Furthermore, a fraction of genes possibly involved in different steps of the newly discovered indolic pathway of M. furfur were expressed in pigment producing cells. These data provide the first molecular insight into pigment production of M. furfur.

[Malassezia yeasts and their significance in dermatology]. / Malassezia-Hefen und ihre Bedeutung in der Dermatologie.

Yeasts of the genus Malassezia belong to the normal microflora of the human skin. In addition they are known to cause a variety of skin diseases; the most frequent of which is pityriasis versicolor. Malassezia yeasts are also thought to be associated with seborrheic dermatitis, dandruff and Malassezia folliculitis. Recently the significance of Malassezia yeasts as a trigger factor for atopic dermatitis of the head and neck region has been pointed out. The role of the Malassezia yeasts in these different diseases has been controversial in the past and remains an issue because of difficulties in isolation, culture and differentiation of the organism. Thanks to molecular techniques, 10 species can actually be differentiated. The article presents the different Malassezia-associated diseases, their clinical picture, diagnosis and appropriate therapy. In addition the speciation of Malassezia is reviewed.

[Mycotic infections of the anogenital region]. / Anogenitale Pilzerkrankungen.

Mycotic infections of the anogenital region are very common in dermatological practice. While dermatophyte infections are more frequent in men, genital candidosis is a more striking problem in women. The increasing prevalence of non-albicans species (esp. C. glabrata, C. krusei, C. guilliermondii) with their resistance against azole derivatives may be responsible for therapeutic failures and a relapsing course in some instances. Most superficial infections of the anogenital area respond satisfactorily to topical antifungal treatment, especially if provocative factors and the possibility of sexual transmission are considered. Systemic treatment is recommended in cases of widespread dermatophyte infections, candidosis or systemic mycosis.

["The fungal jungle". Medical mycology on the Internet]. / "The fungal jungle". Medizinische Mykologie im Internet.

The World Wide Web offers an enormous variety of information about medical mycology. To go through the "fungal jungle" and find the website containing the information that is needed requires a great deal of effort and a lot of time. This article provides help in finding information about medical mycology and describes the contents of preselected websites in German and English. These pages address physicians, scientists, and students interested in dermato-mycology. Most of the pages also contain information about mycoses relevant to other medical specialties.

Fabry disease in patients with hypertrophic cardiomyopathy (HCM).

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.

History of cardiovascular pathology.

This brief paper is chiefly based on main lectures about a few principal topics presented during the past 75 years at the congresses of the German Society for Circulation Research and its successor, the German Cardiac Society. Rudolf Virchow is often considered as an advocate of an inflammatory theory of atherosclerosis. But his conception of inflammation differed widely from our contemporary definition. Weigert (1880) realized the causal significance of coronary occlusion in the pathogenesis of myocardial infarction. This coronarogenic theory was supported by the very close correspondence between poststenotic supplying areas and the localization and extent of myocardial infarctions (Hort 1979). Sinapius (1965) was one four pathologists who independently recognized that almost all fatal coronary thromboses are due to ruptures of fibrous caps. Aschoff (1934) contributed brilliant papers on the pathogenesis of thromboses. Büchner (1934) observed small foci of necroses in the internal layers of left ventricular wall after attacks of angina pectoris. W. Schaper and his group (1979) gained many new insights into the development of collaterals. Linzbach (1950) established milestones in the quantitative microscopic morphology of the heart describing the myocardial cell-constancy, the critical heart weight and structural dilatation.

Gene expression profiles in the acutely dissected human aorta.

OBJECTIVES: heritable connective tissue abnormalities and arterial hypertension may predispose to aortic dissection. This study evaluates gene expression profiles in the acutely dissected human aorta. DESIGN, MATERIALS AND METHODS: Atlas Human Broad Arrays I, II, and III (Clontech) were used to compare gene expression in acutely dissected (6 patients) and normal ascending aortas (6 multiorgan donors). The tissues were also compared macroscopically. RESULTS: of 3537 genes analysed, 1250 (35%) were expressed in aortic tissue. For statistical analysis we focused on 627 genes, which had an intensity>0.95 of the mean patients or controls. Dissected and adjacent macroscopically intact aorta displayed similar gene expression patterns. On the contrary, 66 genes were expressed significantly different in dissected aorta, compared with undiseased control aorta of multiorgan donors. Genes, predominantly upregulated in dissection, are involved in inflammation, in extracellular matrix proteolysis, in proliferation, translation and transcription. Predominantly downregulated genes code for extracellular matrix proteins, adhesion proteins and cytoskeleton proteins. CONCLUSION: our results demonstrate for the first time the complexity of the dissecting process on a molecular level. The ultimate dissection seems to be the dramatic endpoint of a long-lasting process of degradation and insufficient remodelling of the aortic wall. Altered patterns of gene expression suggest a pre-existing structural failure of the aortic wall, resulting in dissection.

[Circular hemorrhagic subendocardial necrosis after heart arrest and resuscitation]. / Zirkuläre hämorrhagische Innenschichtnekrose nach Herzstillstand und Reanimation.

A 19 year old boy, previously healthy suffered a cardiac arrest by getting up. Ten minutes afterwards the general practitioner commenced cardiopulmonary resuscitation, 15 minutes later ventricular fibrillation developed and the emergency physician carried out intubation and repeated defibrillation. During the next few hours a stabilization of the circulatory system was achieved. Five days after the cardiac arrest brain death occurred. The postmortem findings on the heart (only a heart section was performed) showed extensive circular hemorrhagic subendocardial necrosis with initial organization of the left ventricular wall and the septum with a well-preserved subendocardial area. In the right ventricular wall only a few small areas of organization were observed. All lesions were consistent with the cardiac arrest suffered 5 days previously. The morphological changes differ from those of a usual hemorrhagic infarction and of the sequences of a cardiopulmonary resuscitation. The circular subendocardial necroses occur after a cardiac arrest which exceeds the resuscitation time of the heart. They do not respect the area of coronary distribution and their hemorrhagic component develops after successful reanimation within the necrotic myocardium.

[The site and extent of arteriosclerosis. Comparative planimetric studies of the left descending coronary artery, internal carotid artery, superficial femoral artery and abdominal aorta in 104 cadavers]. / Lokalisation und Ausdehnung der Arteriosklerose. Vergleichende planimetrische Untersuchungen an der linken absteigenden Kranzarterie, den Aa. carotides internae, den Aa. femorales superficiales und der Bauchaorta von 102 Verstorbenen.

BACKGROUND: Arteriosclerosis is generally considered to be a generalized disease, involving different vascular regions to approximately the same extent. PATIENTS AND METHODS: In order to assess the extent of ateriosclerosis quantitatively, all arteriosclerotic lesions and additionally the complicated (calcified, ulcerated, thrombosed) arteriosclerotic lesions of the abdominal aorta, the superficial femoral arteries, the left descending coronary artery and the internal carotid arteries were measured by planimetry in 102 autopsies (64 male, 38 female; mean age: 62 +/- 16 years). RESULTS: Arteriosclerosis increased with age. The overall extent of arteriosclerotic lesions of each artery was classified to one of the following 4 degrees of intimal involvement (0-25, 26-50, 51-75%, 76-100%). When comparing the 4 different vascular regions of each patient we found maximal deviations by 1 degree in 34%, by 2 degrees in 41% and by 3 degrees in 20%. In only 5% of the patients studied were all arteriosclerotic lesions of the same degree. In order to analyze the complicated plaques 7 degrees were used (intimal involvement: 0, 1-10, 11-20, 21-30, 31-40, 41-50% and > 50%). In 14 patients we found no complicated plaques. The remaining 88 showed complicated lesions in at least 1 vascular region. Deviations by 1 degree were found in 22%, by 2 degrees in 32%, and by 3 or more degrees in 46%. In the paired arteries (carotid, femoral) there were no significant differences comparing the mean values of the extent of arteriosclerotic lesions on the right and left side. In many cases, however, remarkable intraindividual differences occurred. Patients with main risk factors usually had more pronounced arteriosclerotic lesions than those without. In patients who died from coronary artery disease the extent of arteriosclerotic lesions was also usually larger in the other vascular regions as compared to those patients who died from other reasons. Comparing postmortem and intravital extent of arteriosclerotic lesions some peculiarities of postmortem specimens should be considered. CONCLUSIONS: A uniform involvement of all vascular regions by arteriosclerosis occurs only rarely. Considerable intraindividual differences are the rule and a severe, generalized uniform affection is an exception. This, however, does not exclude in patients with severe arteriosclerosis of one region that a larger involvement of other vascular regions may also occur, as this was found for patients with severe arteriosclerosis in coronary arteries. Regarding the extent of arteriosclerosis there are artery- and additional localization-specific features.

[Congenital tubular supravalvular aortic stenosis with massive coronary artery dilatation in a 35-year-old man]. / Kongenitale, tubuläre supravalvuläre Aortenstenose mit massiver Koronararteriendilatation bei einem 35-jährigen Mann.

Supravalvular aortic stenosis is a rare cause of left ventricular outflow obstruction in adults. It occurs as an isolated defect sporadically or on a hereditary basis with an autosomal dominant trait without further phenotypical anomalies, or as part of the Williams syndrome with mental retardation and multiple other anomalies. This lesion was proved to result from a defect of the elastin coding gene. Supravalvular aortic stenosis is frequently associated with cardiovascular defects, particularly of the peripheral pulmonary arteries, thoracic aorta, carotid, subclavian, and coronary arteries and the aortic valve. The coronary arteries are subject to an increased perfusion pressure leading to dilatation, tortuosity and accelerated arteriosclerosis. We give details of a 35-year-old patient in whom a previously asymptomatic supravalvular aortic stenosis is associated with an excessive dilatation of the right coronary artery and the left anterior descending coronary artery as well as an ostium stenosis of the left common carotid artery. The patient did not present any phenotypical anomalies of the Williams syndrome.

Surgical treatment of 50 carotid dissections: indications and results.

PURPOSE: This article analyzes the course of 48 patients with 49 chronic carotid dissections (who were treated surgically at our institution after a median anticoagulation period of 9 months because of a persistent high-grade stenosis or an aneurysm) and the course of one additional patient with acute carotid dissection (who underwent early operative reconstruction 12 hours after onset because of fluctuating neurologic symptoms). METHODS: All medical and surgical records and imaging studies were reviewed retrospectively. All histologic specimens were reevaluated by a single pathologist to assess the cause of dissection. Follow-up of 41 patients (85%) after 70 months (range, 1-190 months) consisted of an examination of the extracranial vessels in the neck by Doppler ultrasound scanning and a questionnaire about the patients' medical history and their personal appraisals of cranial nerve function. RESULTS: Seventy percent of the dissections had developed spontaneously; 18% were caused by trauma; 12% of all patients (22% of the women) had a fibromuscular dysplasia. Indication for surgery was a high-grade persisting stenosis and a persisting or newly developed aneurysm. Flow restoration was achieved by resection and vein graft replacement in 40 cases (80%) and thromboendarterectomy and patch angioplasty in three cases (6%). Gradual dilatation was performed and effective in two cases (4%). Five internal carotid arteries (10%) had to be clipped because dissection extended into the skull base. One patient died of intracranial bleeding. Five patients (10%) experienced the development of a recurrent minor stroke (ipsilateral, 4 patients; contralateral, 1 patient). Cranial nerve damage could not be avoided in 29 cases (58%) but were transient in most of the cases. During follow-up, one patient died of unrelated reasons, and only one patient had experienced the development of a neurologic event of unknown cause. CONCLUSION: Chronic carotid dissection can be effectively treated by surgical reconstruction to prevent further ischemic or thromboembolic complications, if medical treatment for 6 months with anticoagulation failed or if carotid aneurysms and/or high-grade carotid stenosis persisted or have newly developed.

Impact of school and vocational education on smoking behaviour: results from a large-scale study on adolescents and young adults in Germany.

While level of school education has been related to prevalence of cigarette smoking in a number of studies, less information is available on the role of vocational education and related occupational contexts. This study analyses the relative contribution of different types of educational experience to explaining prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees in Germany. A standardized questionnaire on smoking behaviour and educational performance was applied in 27 educational centers across the country, covering a total of 20,527 respondents (77.3% of the original sample; women: 59.5%, men: 40.5%). Bivariate analysis revealed a high prevalence of current smokers among vocational trainees, both men (51.2%) and women (49.4%). Men were more likely to be heavy smokers, especially with increasing age. In both sexes, prevalence of smoking was particularly high in the following occupational groups: hairdressers, butchers, painters, service personnel (hotels, restaurants), shop assistants/sellers and cooks. Multivariate analysis taking educational level, type of vocational training (occupation), age, sex and urban-rural background into account revealed the highest prevalence odds ratios (POR) of smoking in subjects with the lowest educational level (POR = 5.19 for men and 4.56 for women). Even stronger effects were observed with smoking intensity (> or = 20 cigarettes/day): in men with the lowest educational level the risk of being a heavy smoker was 8.92, and in women 13.54 compared to subjects with a high-school leaving qualification. Poor school education must be considered the relatively strongest predictor of prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees. Preventive efforts should be directed at specific target groups such as those identified by this study.

[Transmyocardial laser revascularization--morphologic, pathophysiologic and historical principles of indirect revascularization of the heart muscle]. / Transmyokardiale Laserrevaskularisation--morphologische, pathophysiologische und historische Grundlagen der indirekten Revaskularisation des Herzmuskels.

Under normal conditions the coronary system of the human heart is not hermetically isolated from the surrounding structures nor the ventricles, but is in various ways connected to the adjacent arteries and the cardiac chambers. These natural connections have been models for most surgical efforts to revascularize the myocardium. Numerous anastomoses between the aorta and the coronary branches functionally resemble aorto-coronary bypass grafts. Coronaro-ventricular anastomoses do also exist in the myocardium and therefore transmyocardial laser revascularization should allow blood to penetrate from the ventricle into the myocardium. This process should not be called "reptilization" of the human heart, as in large reptilian hearts the nutrition of an extensive amount of myocardium only by diffusion is highly unlikely. Transmyocardial laser revascularization results in a relevant reduction of clinical symptoms and an increase of exercise capacity in approximately two thirds of the patients treated. Objective data of enhanced myocardial perfusion as assessed by positron emission tomography and stress echocardiography has up to now only been presented by smaller studies. Open laser channels are rarely visualized by conventional ventriculography for the limited resolution of the technique. Possibly contrast-echocardiography may offer a more appropriate option to proof the systolic filling of the laser channels, as recently reported in patients. This would allow a correlation between clinically successful revascularization and functioning channels in contrast to an early or late failure due to the closure of the channels. As to the current opinion, transmyocardial laser revascularization is no alternative to established medical, interventional or surgical therapies but may in conjunction with bypass surgery or as a sole procedure offer a new option for those patients, who were recently considered to be refractory to conventional treatment. Experimental studies in particular should contribute to the understanding of therapeutic mechanisms and lead to standardized indications in the surgical treatment of end-stage coronary heart disease. Even though in transmyocardial laser revascularization the perioperative risk depends mainly on the degree of cardiac disease and the overall state of the patient, and impaired left ventricular function is per se no exclusion criterium, if viable myocardium is detectable. Many questions concerning indications, long-term prognosis and pathophysiological mechanisms are still open to discussion and have to be answered in order to find standardized applications for treatment of end-stage coronary artery disease.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): response to methotrexate and mercaptopurine.

We report a 3-year-old girl presenting with bilateral cervical lymph node enlargement persisting for > 3 months. Leukocytosis, elevated erythrocyte sedimentation rate, a marked hypergammaglobulinemia, and a moderate hepatosplenomegaly were also found. The diagnosis of sinushistiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, was established histologically by the demonstration of characteristic sinushistiocytosis with lymphocytophagocytosis. Treatment was started with high dose steroids, and a decline of lymph node size and a normalization of laboratory parameters occurred. However, when steroids were tapered, lymph node size rapidly reincreased. Chemotherapeutic treatment was started using etoposide, which was completely ineffective. Therefore, treatment was changed to a combinatory low dose methotrexate therapy and 6-mercaptopurine for 4 months. Whereas a prompt and complete remission was reached, single 6-mercaptopurine therapy was maintained and treatment has been discontinued after a total of 2 years. The child has remained healthy for 7 years. This case would recommend the use of methotrexate and 6-mercaptopurine for treatment of complicated SHML.

Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake, free adenosine and oxidative/glycolytic enzyme activity.

The spatial heterogeneity of myocardial perfusion and metabolism was studied in 11 anaesthetized dogs under resting conditions. In each heart local myocardial blood flow was assessed using the tracer microsphere technique in 256 samples (mean mass: 83.1 mg) taken from the left anterior ventricular wall. In the same samples, the following biochemical parameters were determined: accumulation of [3H]-deoxyglucose (a measure of glucose uptake), free cytosolic adenosine (S-adenosylhomocysteine accumulation technique, a measure of tissue oxygenation and a possible mediator of blood flow regulation), and the specific activities of oxidative (citrate synthase, cytochrome-c-oxidase) and glycolytic (hexokinase, phosphoglycerate kinase) enzymes. Capillary density and mitochondrial and myofibril volume densities were determined by morphometry. Myocardial perfusion in each sample (average 0.77 ml min-1 g-1) varied between 0.1 and 2.5 times the mean (coefficient of variation 0.30+/-0.02). [3H]-deoxyglucose was deposited locally in proportion to perfusion. Samples showing low flow (<0.2 ml min-1 g-1) did not exhibit increased levels of cytosolic adenosine. The specific activities of the oxidative and glycolytic enzymes, however, were uniformly distributed between low and high flow areas. Furthermore, capillary density and mitochondrial and myofibril densities were similar in high and low flow regions. The results show firstly that local glucose metabolism in the heart occurs in proportion to local blood flow, suggesting that high flow regions have a higher than average metabolic rate. Secondly, regions of low flow are not compromized by critical oxygenation and most likely have a lower than average oxygen demand and finally, the homogeneous distribution of oxidative and glycolytic enzymes, as well as the homogeneous myocardial ultrastructure, suggest that areas with high and low blood flow under resting conditions may increase their metabolic rate to similar levels when required.

Color-flow Doppler-assisted duplex imaging fails to detect ulceration in high-grade internal carotid artery stenosis.

PURPOSE: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. METHODS: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (> or = 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. RESULTS: Interobserver reliabilities for detecting carotid plaque ulceration were kappa= 0.57 for ultrasonography and kappa = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomically defined ulceration (chi square = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). CONCLUSIONS: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions.

[An interventional study against cigarette smoking among Dusseldorf high school students 1992-94]. / Interventionsstudie gegen das Zigarettenrauchen von Düsseldorfer Hauptschülern 1992-94.

Between 1992 and 1994, an interventional program was held in the secondary schools ("Hauptschulen") in Düsseldorf contra cigarette smoking. The program was conducted in the following way. Half of the schools (intervention schools) were involved in this program which consisted of 15 sessions. The other schools served as control groups. During the first year of this program school-teachers and a physician taught students about the function and the abilities of the healthy heart and lung. The students developed adversions to smoking. In addition, the students learned by role-plays how to say no to a cigarette without embarrassment. These role-plays were videotaped. During the second year of this program the role-plays were repeated and teaching about the heart and the lungs was augmented. Also, every student got the opportunity to meet and talk with a famous athlete. Furthermore, smoking-cessation programs were hold in four intervention schools. The program started in the sixth grade with a questionnaire administered to 878 schoolchildren. During this time the average age of the children was 13 years. Because of a large fluctuation, the questioning could be repeated with only 630 of these children (71.8%) after 2 years. At the end of the study the number of smokers had increased two times greater in the control schools than in the intervention schools (boys: 20.5% points vs 9.4% points; girls: 44.3% points vs 21.0% points). Obviously, the continuation of the program during the second year was important in making the program successful. Among the participants of the intervention program there was a trend to stop smoking. But the program was not able to prevent non-smokers from starting the habit. On the other hand, of the children who started smoking during the program, more girls in the intervention schools quit smoking than in the control schools. At the end of the program more girls than boys (mean age 15 years) smoked. Almost one-fourth of the boys, and from the control schools one-third of the girls were already daily smokers. The smokers obtained cigarettes from kiosks, from friends, vending machines, vendors or shops, but seldom from their homes.

Plaque ulceration and lumen thrombus are the main sources of cerebral microemboli in high-grade internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Previous work has shown that rates of cerebral microemboli downstream of high-grade internal carotid artery stenosis are higher in recently symptomatic compared with asymptomatic patients. In addition, microembolic rates decline after carotid endarterectomy. We conducted a prospective investigation of 40 consecutive asymptomatic or recently symptomatic patients undergoing carotid endarterectomy for 70% to 95% internal carotid artery stenosis to determine the relationship between microembolic rate and pathoanatomic features of the carotid plaque. METHODS: Transcranial Doppler monitoring including automated emboli detection was performed preoperatively to assess the rate of cerebral microemboli of the ipsilateral middle cerebral artery. The corresponding endarterectomy specimens were evaluated histologically with respect to the occurrence of plaque fissuring, intraplaque hemorrhage, plaque ulceration, or intraluminal thrombosis. RESULTS: There were strong associations between plaque ulceration, intraluminal thrombosis, and downstream cerebral microemboli (P < or = .005, respectively). There were no correlations of microembolism with plaque fissuring or intraplaque hemorrhage (P = .82 and P = .28, respectively). CONCLUSIONS: We conclude that ulceration and luminal thrombosis of the atheromatous plaque are the main sources of downstream cerebral microemboli in patients with high-grade internal carotid artery stenosis. Our data support the view that these pathoanatomic features may also play a key role in symptom development.