Outcomes of Investigating T Wave Inversion With Echocardiography in an Unselected Young Male Preparticipation Cohort.

BACKGROUND Electrocardiography (ECG) may be performed as part of preparticipation sports screening. Recommendations on screening of athletes to identify individuals with previously unrecognized cardiac disease are robust; however, data guiding the preparticipation screening of unselected populations are scarce. T wave inversion (TWI) on ECG may suggest an undiagnosed cardiomyopathy. This study aims to describe the prevalence of abnormal TWI in an unselected young male cohort and the outcomes of an echocardiography-guided approach to investigating these individuals for structural heart diseases, focusing on the yield for cardiomyopathies. METHODS AND RESULTS Consecutive young male individuals undergoing a national preparticipation cardiac screening program for 39 months were studied. All underwent resting supine 12-lead ECG. Those manifesting abnormal TWI, defined as negatively deflected T waves of at least 0.1 mV amplitude in any 2 contiguous leads, underwent echocardiography. A total of 69 714 male individuals with a mean age of 17.9±1.1 years were studied. Of the individuals, 562 (0.8%) displayed abnormal TWI. This was most frequently observed in the anterior territory and least so in the lateral territory. A total of 12 individuals (2.1%) were diagnosed with a cardiomyopathy. Cardiomyopathy diagnoses were significantly associated with deeper maximum TWI depth and the presence of abnormal TWI in the lateral territory, but not with abnormal TWI in the anterior and inferior territories. No individual presenting with TWI restricted to solely leads V1 to V2, 2 inferior leads or both was diagnosed with a cardiomyopathy. CONCLUSIONS Cardiomyopathy diagnoses were more strongly associated with certain patterns of abnormal TWI. Our findings may support decisions to prioritize echocardiography in these individuals.

Flavonoids from fruit and vegetables: a focus on cardiovascular risk factors.

Epidemiological studies suggest that high intakes of dietary flavonoids are associated with decreased cardiovascular disease mortality and risk factors. Less is known about the cardioprotective effects of flavonoids from fruit and vegetables. This review summarizes data from studies which examine the effects of commonly consumed fruit and vegetables on cardiovascular disease risk biomarkers in healthy volunteers or at-risk individuals. Although flavonoids from apples, berries, and onions appear to impact positively on blood pressure, vascular function, and serum lipid levels, further research is required to find out the optimal quantity and food matrix for conferring substantial clinical benefit. The benefits from citrus flavonoids are still inconclusive. Further robust, longer-term dietary intervention studies, with the inclusion of placebo or control arms, are required to improve the credibility of the findings and confirm current observations. An improved understanding of the impact of flavonoids from fruit and vegetables can help one make discerning food choices for optimal cardiovascular health.

Use of double pigtail stent in hypospadias surgery.

OBJECTIVE: Various types and materials of stents have been used for urinary diversion in hypospadias surgery. We evaluated whether double pigtail stents are superior to straight silicone stents. METHODS: We conducted a retrospective chart review of all patients who underwent hypospadias surgery with straight silicone or double pigtail stents between November 1997 and October 2005. Comparisons were made between the two groups specifically with regard to the complication rates. RESULTS: A total of 86 patients were included. The complication rates in patients who received double pigtail stents were significantly reduced as compared with those who received straight silicon stents. There was less wound disruption associated with early stent dislodgement in the double pigtail group compared with the straight silicone group (3.2%vs. 17.4%, p< 0.05). The rate of urethrocutaneous fistula was also lower in the double pigtail stent group (12.7%vs. 30.4%). Subjectively, there was also improved patient comfort and parent anxiety in the double pigtail stent group. CONCLUSION: Double pigtail stent is a suitable material for urinary diversion in hypospadias surgery. It not only reduces patient discomfort, but also decreases complication rates in hypospadias surgery.

CXCR3-dependent accumulation and activation of perivascular macrophages is necessary for homeostatic arterial remodeling to hemodynamic stresses.

Sustained changes in blood flow modulate the size of conduit arteries through structural alterations of the vessel wall that are dependent on the transient accumulation and activation of perivascular macrophages. The leukocytic infiltrate appears to be confined to the adventitia, is responsible for medial remodeling, and resolves once hemodynamic stresses have normalized without obvious intimal changes. We report that inward remodeling of the mouse common carotid artery after ligation of the ipsilateral external carotid artery is dependent on the chemokine receptor CXCR3. Wild-type myeloid cells restored flow-mediated vascular remodeling in CXCR3-deficient recipients, adventitia-infiltrating macrophages of Gr1(low) resident phenotype expressed CXCR3, the perivascular accumulation of macrophages was dependent on CXCR3 signaling, and the CXCR3 ligand IP-10 was sufficient to recruit monocytes to the adventitia. CXCR3 also contributed to selective features of macrophage activation required for extracellular matrix turnover, such as production of the transglutaminase factor XIII A subunit. Human adventitial macrophages displaying a CD14(+)/CD16(+) resident phenotype, but not circulating monocytes, expressed CXCR3, and such cells were more frequent at sites of disturbed flow. Our observations reveal a CXCR3-dependent accumulation and activation of perivascular macrophages as a necessary step in homeostatic arterial remodeling triggered by hemodynamic stress in mice and possibly in humans as well.

MyD88-dependent, superoxide-initiated inflammation is necessary for flow-mediated inward remodeling of conduit arteries.

Vascular remodeling normalizes abnormal hemodynamic stresses through structural changes affecting vessel size and wall thickness. We investigated the role of inflammation in flow-mediated vascular remodeling using a murine model of partial outflow reduction without flow cessation or neointima formation. Common carotid arteries decreased in size after ipsilateral external carotid artery ligation in wild-type mice, but not in myeloid differentiation protein-88 (MyD88)-deficient mice. Inward remodeling was associated with MyD88-dependent and superoxide-initiated cytokine and chemokine production, as well as transient adventitial macrophage accumulation and activation. Macrophage depletion prevented flow-mediated inward vascular remodeling. Expression of MyD88 by intrinsic vascular cells was necessary for cytokine and chemokine production and changes in vessel size, whereas MyD88 expression by bone marrow-derived cells was obligatory for changes in vessel size. We conclude that there are at least two distinct roles for MyD88 in flow-mediated inward remodeling of conduit arteries. Our findings suggest that inflammation is necessary for vascular adaptation to changes in hemodynamic forces.

Amelioration of human allograft arterial injury by atorvastatin or simvastatin correlates with reduction of interferon-gamma production by infiltrating T cells.

BACKGROUND: Graft arteriosclerosis (GA) is an important factor limiting long-term outcomes after organ transplantation. We have used a chimeric humanized mouse system to model this arteriopathy in human vessels, and found that the morphologic and functional changes of experimental GA are interferon (IFN)-gamma dependent. This study evaluated whether 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, described as inhibitors of IFN-gamma production, affect GA in our model. METHODS: C.B.-17 severe combined immunodeficiency-beige mice were transplanted with human artery segments as aortic interposition grafts and inoculated with allogeneic human peripheral blood mononuclear cells (PBMCs) or replication-deficient adenovirus encoding human IFN-gamma. Transplant arteries were analyzed from recipients treated with vehicle vs. atorvastatin or simvastatin at different doses. The effects of statins on T-cell alloresponses to vascular endothelial cells were also investigated in vitro. RESULTS: Graft arteriosclerosis-like arteriopathy induced by PBMCs was reduced by atorvastatin at 30 mg/kg/day or simvastatin at 100 mg/kg/day that correlated with decreased graft-infiltrating CD3+ T cells. Circulating IFN-gamma was also reduced, as were graft IFN-gamma and IFN-gamma-inducible chemokine transcripts and graft human leukocyte antigen-DR expression. Graft arteriosclerosis directly induced by human IFN-gamma in the absence of human PBMCs was also reduced by atorvastatin, but only at the highest dose of 100 mg/kg/day. Finally, atorvastatin decreased the clonal expansion and production of interleukin-2, but not IFN-gamma, by human CD4+ T cells in response to allogeneic endothelial cells in coculture. CONCLUSIONS: Our results suggest that a benefit of statin administration in transplantation may include amelioration of GA primarily by inhibiting alloreactive T-cell accumulation and consequent IFN-gamma production and secondarily through suppression of the arterial response to IFN-gamma.

Evaluation of small intestinal submucosa as scaffolds for intestinal tissue engineering.

BACKGROUND: Biodegradable scaffolds have been used for regenerating the small intestine. The aim of this study was to evaluate the feasibility of small intestinal submucosa (SIS) as scaffolds for intestinal regeneration in a rat model. MATERIALS AND METHODS: A tubular one-ply or four-ply SIS was interposed between isolated jejunal segments in rats. The scaffolds were harvested at 2, 4, and 8 weeks after implantation, and the specimens were examined grossly and histologically. RESULTS: Significant contractions were observed in SIS scaffolds after implantation. The one-ply SIS contracted to 44% of its initial length at 2 weeks and continued to contract to 6% of its initial length at 8 weeks. The contraction of four-ply SIS scaffolds was less than that of the one-ply SIS, reaching 29% of its initial length at 8 weeks. Minimal epithelial and smooth muscular regeneration was observed in the SIS scaffolds after implantation. CONCLUSIONS: A significant shrinkage was observed in the SIS scaffolds after implantation. Although the four-ply SIS contracted less than the one-ply SIS, neither scaffold supported significant amount of intestinal regeneration.

Endothelial nitric oxide synthase stimulates aneurysm growth in aged mice.

BACKGROUND/AIMS: Age-associated changes in endothelial nitric oxide synthase (eNOS) expression have not been definitively linked to the pathophysiology of aortic aneurysms. We examined the role of eNOS in human patients and an age-appropriate mouse model. METHODS: eNOS transcripts and immunodetectable protein were assessed by quantitative PCR and immunohistochemistry in human ascending thoracic aneurysms (n = 29) and referent aortae (n = 31). Carotid aneurysms were induced with CaCl2 in young adult (3 months) and aged (18 months) C57BL/6 and eNOS-knockout (eNOS-KO) mice. RESULTS: eNOS transcripts and protein were reduced in human aneurysms compared with controls, although aortic eNOS expression also decreased with patient age. Aged wild-type mice had significantly larger aneurysm diameter than young adult mice. Aged wild-type mice had reduced eNOS transcripts and protein compared with young adult mice. Aged eNOS-KO mice had smaller aneurysms compared with aged wild-type mice but similar size aneurysms compared with young eNOS-KO and young wild-type mice. CONCLUSION: eNOS expression is reduced in both aged human and aged mouse endothelium and eNOS expression is linked to aneurysm expansion in aged but not young adult mice. These findings support the relevance of age-associated changes in eNOS expression in clinical aneurysmal disease.

Violence-related behaviours among Malaysian adolescents: a cross sectional survey among secondary school students in Negeri Sembilan.

INTRODUCTION: The aim of this study was to determine the prevalence of violence-related behaviours among adolescents and the factors associated with it. MATERIAL AND METHODS: This was a cross-sectional school survey conducted on 4500 adolescent students, using a structured questionnaire. Data were collected using the supervised self-administered questionnaire [a modified version of the Youth Risk Behavior Surveillance in the Malaysian National Language (Bahasa Malaysia)]. RESULTS: Our study showed that 27.9% of students had been involved in a physical fight, 6.6% had been injured in a fight, 5.9% had carried a weapon, 7.2% had felt unsafe, 18.5% had had their money stolen and 55.0% had had their property stolen. Adolescents who carried weapons to school, smoked, used drugs, felt sad or hopeless and played truant were more likely to be involved in physical fights after adjusting for age, sex, and ethnicity. CONCLUSION: Violence-related behaviours among adolescents, especially involvement in physical fights, are common and are positively associated with certain factors such as smoking, taking drugs, playing truant, feeling sad or hopeless. Interventions designed at targeting adolescent violence should also address these factors and target the high-risk groups. There may be a need to identify and provide services for adolescents who exhibit these factors.

Violence-related behaviours among Malaysian adolescents: a cross sectional survey among secondary school students in Negeri Sembilan

<p><b>INTRODUCTION</b>The aim of this study was to determine the prevalence of violence-related behaviours among adolescents and the factors associated with it.</p><p><b>MATERIAL AND METHODS</b>This was a cross-sectional school survey conducted on 4500 adolescent students, using a structured questionnaire. Data were collected using the supervised self-administered questionnaire [a modified version of the Youth Risk Behavior Surveillance in the Malaysian National Language (Bahasa Malaysia)].</p><p><b>RESULTS</b>Our study showed that 27.9% of students had been involved in a physical fight, 6.6% had been injured in a fight, 5.9% had carried a weapon, 7.2% had felt unsafe, 18.5% had had their money stolen and 55.0% had had their property stolen. Adolescents who carried weapons to school, smoked, used drugs, felt sad or hopeless and played truant were more likely to be involved in physical fights after adjusting for age, sex, and ethnicity.</p><p><b>CONCLUSION</b>Violence-related behaviours among adolescents, especially involvement in physical fights, are common and are positively associated with certain factors such as smoking, taking drugs, playing truant, feeling sad or hopeless. Interventions designed at targeting adolescent violence should also address these factors and target the high-risk groups. There may be a need to identify and provide services for adolescents who exhibit these factors.</p>

Sustainability of mechanically lengthened bowel in rats.

INTRODUCTION: It has been shown that the length of an intestinal segment may be doubled by applying gradual mechanical stretching. This study evaluated whether the lengthened intestinal segment retained the structure and function after the stretching device was removed. METHODS: A 1.5-cm jejunal segment was separated from intestinal continuity in 20 rats. After advancing a screw into the isolated jejunal segment by 5 mm 3 times a week until it was stretched by 3 cm, the screw was removed. Three weeks later, the jejunal segments were retrieved for analyses. Comparisons were made between the lengthened jejunal segments. RESULTS: The jejunal segment doubled its length after gradual stretching and retained this length 3 weeks after the screw removal (3.1 +/- 0.8 vs 3.2 +/- 0.4 cm, P > .05). The villous height, the muscular thickness, and the total alkaline phosphatase and lactase activities of the stretched jejunal segments were also unchanged 3 weeks after the screw removal. CONCLUSIONS: Mechanical force induced the sustained lengthening of isolated jejunal segments in rats. The histologic and enzymatic alterations also persisted 3 weeks after the mechanical force was removed. This phenomenon may provide a novel method for the treatment of short bowel syndrome.

Factors relating to adolescent suicidal behavior: a cross-sectional Malaysian school survey.

PURPOSE: This study was undertaken to examine factors relating to adolescent suicide behavior. METHOD: This was a cross-sectional school survey of 4,500 adolescent students based on a structured questionnaire. Data were collected using the supervised self-administered questionnaire (modified version of the Youth Risk Behavior Surveillance in the Malaysian National Language, Bahasa Malaysia). RESULTS: Seven percent (312 of 4,454) of the adolescent students had seriously considered attempting suicide. Among the adolescents, 4.6% had attempted suicide at least once during the 12 months preceding the survey. Female adolescents were more likely to put their suicidal thoughts into suicidal action than were male adolescents. Malay and Indian people are more likely than the Chinese to respond, "Felt sad and hopeless." However, Malay adolescents had the lowest rate of attempted suicide. Based on multiple logistic regression, factors significantly related to urban adolescents' suicide behavior are "Felt sad or hopeless," "Number of days felt unsafe to go to school," "Riding with a driver who had been drinking alcohol," "Physical fight," and "Number of days absent from school." In comparison, factors relating to rural adolescents' suicide behavior are "Felt sad or hopeless," "Physical fight," "Physical fight resulting in injury," and "Drive a vehicle after drinking alcohol." CONCLUSION: Adolescent suicide behavior should be viewed as a serious problem. Measures can be taken to prevent suicide by looking at the factors significantly linked to suicidal behavior among adolescents. Steps can then be taken to identify adolescents who have serious suicidal ideation so that intervention can be taken to reduce the suicidal rate.

Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms.

BACKGROUND: Progressive medial degeneration and atrophy is thought to be a cause of ascending thoracic aortic aneurysms in the elderly. Extensive apoptosis of vascular smooth muscle cells (VSMCs) has been demonstrated in the media of abdominal aortic aneurysms. We investigated whether medial atrophy from loss of VSMCs occurs in primary ascending thoracic aortic aneurysms. METHODS AND RESULTS: Morphometric analysis of 28 nonaneurysmal ascending thoracic aortas and 29 ascending thoracic aortic aneurysms was performed by directly measuring the thickness of their vascular layers and by indirectly calculating the area of their vascular compartments. The cellular and matrix composition of the media was assessed at the structural, protein, and transcript levels. Despite thinning of the media secondary to vascular dilatation, there was an overall increase in the medial area of aneurysms. VSMC density was preserved, implying cellular hyperplasia as a result of the increased medial mass. There was decreased expression of matrix proteins, despite sustained synthesis of these molecules, which was associated with evidence of increased matrix degradation. The remodeling and expansion of the media was most evident in comparisons between nonaneurysmal aortas versus smaller aneurysms and did not evolve further in larger aneurysms. CONCLUSIONS: The mechanisms for luminal enlargement in thoracic and abdominal aortic aneurysms differ significantly with regard to the survival of VSMCs and atrophy of the media but share common pathophysiology involving degeneration of the matrix. Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms may be an initial adaptive response to minimize increased wall stress resulting from vascular dilatation.

Transmural inflammation by interferon-gamma-producing T cells correlates with outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Arterial pathology manifests as aneurysmal or obstructive disease depending on changes in lumen size due to vascular remodeling (change in vessel external diameter) and/or intimal expansion. Recent clinical and experimental observations in abdominal aortic aneurysms have led to the emerging dogma that Th2-dominant immune responses result in expansive vascular remodeling and luminal ectasia, whereas Th1 immune responses cause intimal hyperplasia and luminal stenosis. We tested this hypothesis by descriptive analyses of 31 non-aneurysmal and 29 aneurysmal ascending thoracic aortic specimens. Approximately half the aneurysms were distinguished by transmural inflammation. The remaining aneurysms and all the non-aneurysmal aortas had a similar leukocytic infiltrate that spared the inner media. Aneurysm tissue had increased expression of the prototypical Th1 cytokine, interferon (IFN)-gamma, and undetectable Th2 cytokines. Specimens with inner media infiltration displayed robust production of IFN-gamma, induction of the IFN-gamma-inducible chemokines IP-10 and Mig, and recruitment of lymphocytes bearing their cognate receptor CXCR3. Transmural inflammation and IFN-gamma production were associated with increased aortic external diameter, intimal thickening, preserved vascular smooth muscle cell density, and decreased matrix proteins. Th1, but not Th2, immune responses have a positive correlation with both outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Recruitment of CXCR3+ and CCR5+ T cells and production of interferon-gamma-inducible chemokines in rejecting human arteries.

Chemokine receptors preferentially expressed by Th1 cells and their IFN-gamma-inducible ligands predominate in experimental and clinical allograft rejection. Previous chemokine-related transplantation studies have focused on parenchymal and microvascular inflammation which are of importance in acute rejection, but are not necessarily relevant in immune-mediated injury of conduit arteries. We have recently described a model of progressive human T cell-mediated infiltration and injury of allogeneic coronary artery segments using immunodeficient mouse hosts. In the present study, we investigated if recruitment of allogeneic T cells to different vascular compartments correlated with the expression of chemokines and their receptors. Transcripts were quantified by laser capture microdissection/real-time RT-PCR and their distribution was correlated to the corresponding protein expression detected by immunohistochemistry. Infiltrating T cells, confined to the adventitia and intima, expressed CXCR3 and CCR5, but were not recruited into the media despite production by vascular smooth muscle cells of IP-10, Mig, I-TAC, RANTES and MIP-1beta. Chemokine mRNA was detected primarily in vascular cells, although chemokine protein largely localized to infiltrating leukocytes which uniquely expressed their cognate receptors. These data explain the recruitment of IFN-gamma-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege.

Smoking among secondary school students in Negeri Sembilan, Malaysia.

This study was done to determine the prevalence of smoking and factors influencing cigarette smoking among secondary school students in Negeri Sembilan, Malaysia. This is a cross-sectional school survey conducted on 4500 adolescent students based on a structured questionnaire. Data was collected using the supervised self-administered questionnaire the Youth Risk Behaviour Surveillance in the Malaysian National Language Bahasa Malaysia. The prevalence of smoking among the students was 14.0%. About a third of the students (37.8%) started smoking at 13 to 14 years of age. The prevalence of smoking among the male students was higher (26.6%) compared to the female students (3.1%). Adolescent smoking was associated with (1) sociodemographic factors (age, ethnicity, rural/urban status); (2) environmental factors (parental smoking, staying with parents); (3) behavioural factors (playing truant and risk-taking behaviours such as physical fighting, drug use, alcohol use, sexual activity, lack of seatbelt use, riding with a drunk driver); (4) lifestyle behaviours (being on diet and lack of exercise); (5) personal factors (feeling sad and suicidal behaviours). In conclusion, smoking is a major problem among Malaysian adolescents. Certain groups of adolescents tend to be at higher risk of smoking. This problem should be curbed early by targeting these groups of high risk adolescents.

Interferon-gamma plays a nonredundant role in mediating T cell-dependent outward vascular remodeling of allogeneic human coronary arteries.

Vascular remodeling (change in vessel diameter) rather than intimal hyperplasia is the most important predictor of luminal loss in immune-mediated arterial injury, yet little is known about its mechanisms. Here, we show that outward vascular remodeling and intimal thickening, two manifestations of arteriosclerosis with opposing effects on luminal size, result from immune effector mechanisms that are T-cell dependent and interferon (IFN)-gamma mediated. In our in vivo model of human coronary artery injury by allogeneic peripheral blood mononuclear cells, both processes occur concurrently and are characterized by T-cell infiltrates with a predominantly IFN-gamma-producing cytokine profile. Neutralization of IFN-gamma inhibits the arterial and intimal expansion, whereas administration of IFN-gamma enhances these effects. The nonredundant role of IFN-gamma in T-cell-dependent remodeling of human coronary arteries demonstrated here presents a new therapeutic target for preservation of vessel lumen in arteriosclerosis.