Mental health training for secondary school teachers in Haiti: a mixed methods, prospective, formative research study of feasibility, acceptability, and effectiveness in knowledge acquisition.

BACKGROUND: Engagement and training of educators in student mental health holds promise for promoting access to care as a task sharing strategy but has not been well-studied in low-income regions. METHODS: We used a prospective and convergent mixed methods design to evaluate a customized school mental health 2½ day training for teachers in rural Haiti (n = 22) as the initial component of formative research developing a school-based intervention to promote student mental health. Training prepared teachers to respond to student mental health needs by providing psychoeducational and practical support to facilitate access to care. We examined level of participation and evaluated feasibility, acceptability, and perceived effectiveness by calculating mean scores on self-report Likert-style items eliciting participant experience. We examined effectiveness of the training on improving mental health knowledge and attitudes by comparing mean scores on an assessment administered pre- and post-training. Finally, we examined self-report written open-ended responses and focus group discussion (FGD) interview data bearing on perceived feasibility, acceptability, and effectiveness to contextualize participant ratings of training and to identify recommendations for enhancing the utility of mental health training locally for educators. RESULTS: Mean scores of knowledge and attitudes significantly improved between the pre-test and post-tests; e.g., knowledge improved from 58% correct at baseline to 68% correct on the second post-test (p = 0.039). Mean ratings of the training were favorable across all categories and FGD data demonstrated widespread participant endorsement of training acceptability and effectiveness; participants recommended extending the duration and number of training sessions. CONCLUSIONS: Findings support feasibility, acceptability, and a limited scope of effectiveness of brief mental health training for secondary school teachers in Haiti. Further development of approaches to engage teachers in promoting school mental health through training is warranted.

The association between sports participation and athletic identity with eating pathology among college-aged males and females.

The current study examined associations among sports participation (SP), athletic identity (AI), weight status, and eating pathology, and whether these relations differed by gender. Data come from male and female first-year college students who participated in the Tufts Longitudinal Health Study (TLHS) between 1999-2007 (N=712). Relations among SP, AI, actual and perceived weight statuses, Eating Disorders Inventory (EDI) subscale scores, and indices of body shape concern and restrictive eating were examined with hierarchical ordinary least squares (OLS) regression. Associations between SP and eating pathology among females were moderated by perceived weight status. By contrast, relations between males' EDI subscales scores and SP were moderated by ethnicity, as well as by actual weight status. Our findings support that sports participation alone neither promotes nor protects against eating pathology among males and females.

A latent profile analysis of the typology of bulimic symptoms in an indigenous Pacific population: evidence of cross-cultural variation in phenomenology.

BACKGROUND: Previous efforts to derive empirically based eating disorder (ED) typologies through latent structure modeling have been limited by the ethnic and cultural homogeneity of their study populations and their reliance on DSM-IV ED signs and symptoms as indicator variables. METHOD: Ethnic Fijian schoolgirls (n=523) responded to a self-report battery assessing ED symptoms, herbal purgative use, co-morbid psychopathology, clinical impairment, cultural orientation, and peer influences. Participants who endorsed self-induced vomiting or herbal purgative use in the past 28 days (n=222) were included in a latent profile analysis (LPA) to identify unique subgroups of bulimic symptomatology. RESULTS: LPA identified a bulimia nervosa (BN)-like class (n=86) characterized by high rates of binge eating and self-induced vomiting, and a herbal purgative class (n=136) characterized primarily by the use of indigenous Fijian herbal purgatives. Both ED classes endorsed greater eating pathology and general psychopathology than non-purging participants, and the herbal purgative class endorsed greater clinical impairment than either the BN-like or non-purging participants. Cultural orientation did not differ between the two ED classes. CONCLUSIONS: Including study populations typically under-represented in mental health research and broadening the scope of relevant signs and symptoms in latent structure models may increase the generalizability of ED nosological schemes to encompass greater cultural diversity.

Naturalistic study of course, effectiveness, and predictors of outcome among female adolescents in residential treatment for eating disorders.

Few empirical data address naturalistic outcomes of residential eating disorder (ED) treatment. Study aims were to evaluate course, effectiveness, and predictors of outcome in a residential treatment program. We evaluated 80 consecutively admitted female adolescents with the SCID-IV. Primary outcomes were treatment completion, subsequent readmission, clinical global impressions, and changes in body weight. Mean length of stay was 51 days, and 80% of patients were discharged according to treatment plans. Mean expected body weight (EBW) for AN patients increased from 80% to 91%. Patients reported significant improvements in ED symptoms, depression, and quality of life. Low admission %EBW and previous psychiatric hospitalizations were associated with premature termination. Overall, findings support that residential treatment is largely acceptable to patients, and that residential care may provide an opportunity for substantive therapeutic gains.

Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Breast and cervical cancer screening for women with mental illness: patient and provider perspectives on improving linkages between primary care and mental health.

OBJECTIVE: Previous research suggests that women with mental illness may be at increased risk for breast and cervical cancer. This qualitative study of patients and primary care and mental health providers explored challenges to accessing and providing breast and cervical cancer screening for women with mental illness. METHOD: Key informant patient and provider participants were recruited from a community health setting and teaching hospital. Narrative data from 1) interviews with women in a community primary care setting (n = 16); 2) telephone interviews with women with mental illness (n = 16); and 3) focus groups with primary care providers (n = 9) and mental health providers (n = 26) were collected. RESULTS: Patient, provider, and system factors that may contribute to suboptimal cancer screening among women with mental illness were identified. Communication between primary care and mental health providers was noted as a key area for intervention to enhance screening. Barriers to and possibilities for a more proactive role for mental health providers were also considered. CONCLUSIONS: Both patient and provider study participants emphasized the need to address communication gaps between primary care and mental health providers and to promote the active collaboration of mental health providers in preventive cancer screening for women with mental illness.

Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction.

BACKGROUND: C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques. AIMS: To investigate the simultaneous presence of macrophages, CRP, membrane attack complex C5b-9 (MAC), and oxidised low density lipoprotein (oxLDL) in atherectomy specimens from patients with different coronary syndromes. METHODS: In total, 54 patients with stable angina (SA; n = 21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18) underwent directional coronary atherectomy for coronary lesions. Cryostat sections of atherosclerotic plaques were immunohistochemically stained with monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and 12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and neointima tissues, atheroma, and media. Quantitative analysis was performed using image cytometry with systematic random sampling (percentage immunopositive/total tissue area). RESULTS: Macrophages, CRP, MAC, and oxLDL were simultaneously present in a higher proportion of fibrous tissue and atheroma of atherectomy specimens from patients with UA and MI compared with SA (p<0.05). Quantitative analysis showed significantly higher mean percentages of macrophages in plaques from patients with MI (44%) than UA (30%; p<0.01) and SA (20%; p<0.001). Significantly higher mean percentages of CRP were also seen in MI (25%) and UA (25%) compared with SA (12%; p<0.05). CONCLUSIONS: The presence of CRP, complement, and oxLDL in a high proportion of plaque tissue from patients with unstable coronary artery disease implies that these surrogate markers have important proinflammatory effects inside atherosclerotic plaques. This may increase vulnerability to plaque rupture and thrombosis, with subsequent clinical sequelae.

Role of plaque inflammation in acute and recurrent coronary syndromes.

Inflammation plays an important role in the initiation, development, progression and complications of atherosclerotic vascular disease. Our present knowledge of the elementary role of inflammation for the onset of plaque rupture in atherosclerotic coronary lesions primarily stems from autopsy studies. However, the introduction of directional coronary atherectomy catheters has provided a unique opportunity to directly investigate the role of inflammation in coronary syndromes. In this report we describe the role of coronary plaque inflammation, as determined by immunohistochemistry, on the presentation of coronary syndromes and on the clinical outcome following percutaneous interventions.

Sudden unexpected death in young adults. Discrepancies between initiation of acute plaque complications and the onset of acute coronary death.

AIMS: To study the time relationship between the onset of coronary thrombosis and sudden unexpected cardiac death in young adults. METHODS AND RESULTS: Hearts of 11 young adults (< or = 35 years), who had died within 1h after onset of symptoms and presented with a coronary thrombotic occlusion were studied retrospectively for the type of underlying plaque complication and the time of onset of thrombus formation. In all cases tissue blocks were taken from the occluded artery and sectioned for microscopic evaluation. Of 11 culprit lesions 10 were mainly fibrocellular; only one was lipid-rich. Inflammatory cells were found in all plaques, albeit in highly variable amounts. Plaque erosion had occurred in nine; deep ruptures in two. Analysis of the plaque-related occluding thrombus revealed fresh thrombosis in three (both ruptured plaques and one erosion); the other eight, however, showed occlusion with different histological stages of organization of thrombus. CONCLUSIONS: Despite strict inclusion criteria for sudden death in these young adults, the majority must have had plaque instability for some time, since thrombus formation had occurred at least days to weeks prior to the acute event.

Expression of a hepatocyte growth-factor activator protein in turkey (Meleagris gallopavo) deferent duct epithelial cells.

In previous research, we discovered that turkey deferent duct epithelial cells express a serine protease. Our experimental objective was to identify the gene that encodes this protein. A lambda phage cDNA library from duct cell mRNA was constructed. The library was screened using monoclonal antibodies previously produced against the turkey deferent-duct serine protease. Phage containing the protease cDNA was excised and re-circularized into plasmids. E. coli were transformed with plasmids containing protease cDNA, which was then isolated for sequencing. NCBI BLAST searches within the GenBank database returned 63.5 and 61.7% identity with murine and human hepatocyte growth-factor activator (HGFA) precursor, respectively. The turkey protease cDNA was then cloned into the pQE-32 expression vector and transformed into M15 cells for HIS-tagged expression of the recombinant protein, which was then purified using nickel-chelated Sepharose spin columns. Afterwards, Western blot analysis of the purified recombinant turkey protein revealed recognition by a monoclonal antibody specific to the proteolytic subunit of the turkey deferent duct protease. Therefore, these findings indicate that the recombinant HGFA precursor isolated from the deferent duct is the turkey seminal plasma protease that is secreted from the deferent duct. HGFA, a member of the Kringle-serine proteinase superfamily, can initiate diverse mitogenic, morphogenic and motogenic effects through its substrate hepatocyte growth factor. Although the presence of hepatocyte growth factor and its c-MET receptor have been reported in male mammalian reproductive tracts, our novel findings on the secretion of HGFA precursor from turkeys may help to elucidate the regulation of activated hepatocyte growth factor.

Cardiac pathology in neuronal ceroid lipofuscinoses--a clinicopathologic correlation in three patients.

We report the clinical details and the pathology of the heart at autopsy of three neuronal ceroid lipofuscinosis (NCL) patients. Two patients were diagnosed as classical juvenile NCL and one as a variant juvenile NCL (JNCL) with granular osmiophilic deposits (GRODs). Cardiac findings during life were retrospectively evaluated and included left ventricular hypertrophy with repolarization disturbances (ECG findings) in two patients with classical JNCL and severe bradycardia with periods of sinus arrest in one of them, severe supraventricular tachycardias during anaesthesia in the variant JNCL-patient. At autopsy myocardial and valvular storage of lipopigments, diagnostic for NCL, was observed histologically and confirmed ultrastructurally in all three cases. In two patients with JNCL the storage was associated with hypertrophy and dilation of both ventricles, degenerative myocardial changes, interstitial fibrosis and fatty replacement. Abundant accumulation and degeneration were seen in all components of the conduction system in three patients, which outreached at several places by far the storage of the adjacent myocardium. Our observations indicate a prominent involvement of the heart in NCL, with preference of storage for the conduction system of the heart.

Pregnancy complications and neonatal outcomes in women with eating disorders.

OBJECTIVE: This study reported pregnancy complications and neonatal outcomes for 49 live births in a group of women with eating disorders who were prospectively followed. METHOD: Subjects were recruited from 246 women participating in a longitudinal study of anorexia nervosa and bulimia nervosa, now in its 12th year. Subjects were interviewed by trained assistants and completed a brief self-report instrument that assessed both birth statistics and birth-related complications. Medical records and/or self-report data describing the neonates' birth status were obtained. RESULTS: The majority of the women with eating disorders had normal pregnancies, resulting in healthy babies. Across the group, the mean length of pregnancy was 38.7 weeks, the mean birth weight was 7.6 lb, and mean Apgar scores at 1 and 5 minutes after birth were 8.2 and 9.0, respectively. Most outcomes were positive; however, three babies (6.1%) had birth defects, and 17 (34.7%) of the women experienced postpartum depression. The mean number of obstetric complications in the group was 1.3, and 13 (26.5%) of the women delivered by cesarean section. Women who showed symptoms of either anorexia nervosa or bulimia nervosa during pregnancy had a higher frequency of birth by cesarean section and postpartum depression than did nonsymptomatic women. CONCLUSIONS: Pregnant women with active eating disorders appear to be at greater risk for delivery by cesarean section and for postpartum depression. Pregnant women with past or current eating disorders should be viewed as being at high risk and monitored closely both during and after pregnancy to optimize maternal and fetal outcomes.

Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation.

BACKGROUND: The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively. METHODS AND RESULTS: One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by >/=15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2+/-8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by >/=15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9+/-8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential). CONCLUSIONS: Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.

Interleukin-15 expression in atherosclerotic plaques: an alternative pathway for T-cell activation in atherosclerosis?

T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of T-cell activation independent of antigen stimulation, mediated by the cytokine interleukin (IL)-15, was recently described. We investigated IL-15 expression in atherosclerotic plaques in relation to plaque morphology, inflammatory cells, T-cell activation, and oxidation-specific epitopes by use of immunohistochemistry. In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied the proliferative response of plaque-derived T-cell lines to IL-15 in vitro using [(3)H]thymidine incorporation. Fresh-frozen specimens were classified as fibrous (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4) served as reference. Expression of IL-15 mRNA and protein was found almost solely in fibrolipid and lipid-rich plaques, associated with oxLDL-positive macrophages. Sequential immunostains revealed colocalization between IL-15- and CD40L-positive T cells. Moreover, plaque-derived T-cell lines were highly responsive to IL-15. Hence, IL-15 could provide a pathway for antigen-independent T-cell activation.

Immunohistochemical detection of interferon-gamma: fake or fact?

Immunohistochemistry is a widely accepted tool to investigate the presence and immunolocalization of cytokines in tissue sections at the protein level. We have tested the specificity and reproducibility of IFNgamma immunohistochemistry on tissue sections with a large panel of anti-IFNgamma antibodies. Thirteen different commercially available anti-IFNgamma antibodies, including seven advertised and/or regularly applied for immunohistochemistry/-cytochemistry, were tested using a three-step streptavidin-biotin-peroxidase technique and a two-step immunofluorescence (FACS) analysis. Immunoenzyme double staining was used to identify the IFNgamma-positive cells. Serial cryostat sections were used of human reactive hyperplastic tonsils, rheumatoid synovium, and inflammatory abdominal aortic aneurysms, known to possess a prominent Th1-type immune response. In vitro phorbol myristate acetate/ionomycin-stimulated T-cells served as positive control; unstimulated cells served as negative control. Cultured T-cells were used adhered to glass slides (immunocytochemistry), in suspension (FACS), or snap-frozen and sectioned (immunohistochemistry). Immunocytochemistry and FACS analysis on stimulated cultured T-cells showed positive staining results with 12 of 13 anti-IFNgamma antibodies. However, immunohistochemistry of sectioned stimulated T-cells was negative with all. Unstimulated cells were consistently negative. IFNgamma immunohistochemical single- and double staining analysis of the tissue sections showed huge variations in staining patterns, including positivity for smooth muscle cells (n = 8), endothelial cells (n = 4), extracellular matrix (n = 4), and CD138+ plasma cells (n = 12). Specific staining of T-cells, as the sole positive staining, was not achieved with any of the 13 antibodies. IFNgamma-immunohistochemistry appears unreliable because of lack of specificity to stain T-cells in situ. In fact, depending on the type of anti-IFNgamma antibody used, a variety of different cell constituents were nonspecifically stained. Consequently, data based on IFNgamma-immunohistochemistry must be interpreted with great caution.

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.

Recurrent unstable angina after directional coronary atherectomy is related to the extent of initial coronary plaque inflammation.

OBJECTIVES: This study was performed to evaluate the relationship between plaque inflammation of the initial culprit lesion and the incidence of recurrent angina for one year after directional coronary atherectomy (DCA). BACKGROUND: A positive correlation between coronary plaque inflammation and angiographic restenosis has been reported. METHODS: A total of 110 patients underwent DCA. Cryostat sections were immunohistochemically stained with monoclonal antibodies CD68 (macrophages), CD-3 (T lymphocytes) and alpha-actin (smooth muscle cells [SMCs]). The SMC and macrophage contents were planimetrically quantified as a percentage of the total tissue area. T lymphocytes were counted as the number of cells/mm2. The patients were followed for one year to document recurrent unstable angina pectoris (UAP) or stable angina pectoris (SAP). RESULTS: Recurrent UAP developed in 16 patients, whereas recurrent SAP developed in 17 patients. The percent macrophage areas were larger in patients with recurrent UAP (27 +/- 12%) than in patients with recurrent SAP (8 +/- 4%; p = 0.0001) and those without recurrent angina (18 +/- 14%; p = 0.03). The number of T lymphocytes was also greater in patients with recurrent UAP (25 +/- 14 cells/mm2) than in patients with recurrent SAP (14 +/- 8 cells/mm2; p = 0.02) and those without recurrent angina (14 +/- 12 cells/mm2; p = 0.002). Multiple stepwise logistic regression analysis identified macrophage areas and T lymphocytes as independent predictors for recurrent UAP. CONCLUSIONS: There is a positive association between the extent of initial coronary plaque inflammation and the recurrence of unstable angina during long-term follow-up after DCA. These results underline the role of ongoing smoldering plaque inflammation in the recurrence of unstable angina after coronary interventions.

Suicide in contemporary China: a review of China's distinctive suicide demographics in their sociocultural context.

Suicide is a complex phenomenon--arguably a social and a moral deed--occurring within associated psychological, biological, and cultural contexts. We present data on suicide rates in China for 1988, 1990, and 1992 and provide an analysis of their social context. These figures, from the Chinese Public Health Annuals, have never before been publicly reported. These and other recent data indicate that suicide rates in China, although reportedly low in the past, are by global standards alarmingly high among certain demographic groups. They also reveal distinctive epidemiological patterns of suicide in China that contrast with the patterns characteristic of Western societies-for example, higher rates in rural than in urban areas and, among some demographic groups, higher among women than among men. As in the West, however, suicide among the elderly is a major problem in China. The sociocultural context of these data is examined as a means toward understanding their distinctive patterning.

The role of inflammation and infection in coronary artery disease.

New insights into atherosclerosis, the most common disease affecting coronary arteries, may change therapeutic strategies from largely symptomatic to causal. Atherosclerotic plaques contain a lipid-related, immune-mediated inflammation, with release of secretory products capable of changing plaque morphology. Plaques prone to complications contain large numbers of inflammatory cells; stable plaques contain little inflammation. Similarly, atherectomy specimens from patients with coronary syndromes revealed more inflammatory cells in unstable than in stable patients. These observations, and the fact that acute coronary syndromes are associated with increased blood levels of inflammatory markers, have renewed interest in the possible relationship between infection and atherogenesis. Of all potential candidate antigens, Chlamydia pneumoniae presently is considered the most likely because a substantial number of patients with unstable syndromes contain C. pneumoniae-reactive T cells, both in blood and within the atherosclerotic plaque, suggesting enhancement of intraplaque inflammation.

Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses.

Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally contain nodular aggregates resembling lymphoid follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated lymphoid tissue (MALT). This concept was evaluated by studying the micro-anatomy and cellular composition of adventitial infiltrates associated with advanced atherosclerosis of the aorta. Sections of 22 atherosclerotic aortas were stained immunohistochemically for cellular markers characteristic for lymphoid follicles, such as HECA-452-positive endothelial cells, CD20-positive B cells, CD21-positive follicular dendritic cells, and CD68-positive macrophages. Ki-67 was used as a proliferation marker. The TUNEL technique was used to study the presence of apoptotic cells. Specimens containing MALT served as comparison and positive controls. Seven of the 22 atherosclerotic aortas contained adventitial infiltrates resembling lymphoid follicles. The organized nodular centres were composed of CD45RA+ B cells, follicular dendritic cells (CD21+), a few T lymphocytes (CD3+) and 'tingible body' macrophages (CD68+). A large number of cells were Ki-67-positive; apoptotic bodies were numerous and phagocytosed by macrophages. The parafollicular area contained CD45RO-positive T cells and HECA-452-positive vessels. Vessels elsewhere were always HECA-452-negative. Specimens with MALT showed similar features. This study reveals a close resemblance between adventitial lymphoid infiltrates in advanced atherosclerotic aortic disease and MALT, suggesting local generation of a humoral immune response, likely to be initiated by antigens released during a process of long-standing tissue injury and inflammation as part of advanced atherosclerosis.