Tissue diffusion and retention of metalloproteinases in ascending aortic aneurysms and dissections

Histopathological alterations in human aneurysms and dissections of the thoracic ascending aorta include areas of mucoid degeneration within the medial layer, colocalized with areas of cell disappearance and disruption of extracellular matrix elastic and collagen fibers. We studied the presence of matrix metalloproteinases in relation to their capacity to diffuse through the tissue or to be retained in areas of mucoid degeneration in aneurysms and dissections of the ascending aorta. Ascending aortas from 9 controls, 33 patients with aneurysms, and 14 with acute dissections, all collected at surgery, were analyzed. The morphological aspect was similar whatever the etiology or phenotypic expression of the pathological aortas, involving areas of extracellular matrix breakdown and cell rarefaction associated with mucoid degeneration. Release of proMMP-2, constitutively expressed by smooth muscle cells, was not different between controls and aneurysmal aortas, whereas the aneurysmal aortas released more of the active form. Release of pro and active MMP-9 was also similar between controls and aneurysmal aortas. Immunohistochemical staining of MMP-2 and MMP-9 was weak in both control and pathological aortas. In contrast, released MMP-7 (matrilysin) and MMP-3 (stromelysin-1) could not be detected in conditioned media but were present in tissue extracts with no detectable quantitative difference between controls and pathological aortas. Immunohistochemical staining of MMP-7 and MMP-3 revealed their retention in areas of mucoid degeneration, and semiquantitative evaluation of immunostaining showed more MMP-7 in pathological aortas than in controls. In conclusion, areas of mucoid degeneration, the hallmark of aneurysms, and dissections of thoracic ascending aortas, whatever their etiology, are not inert and can retain specific proteases.     

Epstein-Barr Virus-Related Diarrhea or Exacerbation of Inflammatory Bowel Disease: Diagnostic Dilemma

While the presence of Epstein-Barr virus (EBV) in colonic specimens from patients with inflammatory bowel disease (IBD) has been documented, diarrhea secondary to gastrointestinal involvement by EBV in the context of primary EBV infection in patients with IBD has not been reported. We describe a patient with IBD who presented with diarrhea and primary EBV infection and propose a role for colonic involvement by EBV in the pathogenesis of his symptoms.     

Reducing Psychosocial and Behavioral Pregnancy Risk Factors: Results of a Randomized Clinical Trial Among High-Risk Pregnant African American Women

Objectives. We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes (cigarette smoking, secondhand smoke exposure, depression, and intimate partner violence).Methods. Pregnant African American women (N = 1044) were randomized to an intervention or usual care group. Clinic-based, individually tailored counseling sessions were adapted from evidence-based interventions. Follow-up data were obtained for 850 women. Multiple imputation methodology was used to estimate missing data. Outcome measures were number of risks at baseline, first follow-up, and second follow-up and within-person changes in risk from baseline to the second follow-up.Results. Number of risks did not differ between the intervention and usual care groups at baseline, the second trimester, or the third trimester. Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group (odds ratio = 1.61; 95% confidence interval = 1.08, 2.39; P = .021).Conclusions. In comparison with usual care, a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care.Adverse pregnancy outcomes are particularly common among women who are members of racial/ethnic minority groups.^1–4 African American infants are 3.4 times more likely than are White infants to die in the neonatal period, a disadvantage that persists even when mothers have appropriately early and equal access to prenatal care.⁵ In Washington, DC, death rates among non-Hispanic African American infants remain unacceptably high (17.0 per 1000 live births in 2005) despite an overall decline in infant mortality from 18.6 per 1000 live births in 1992 to 14.0 per 1000 births in 2005.⁶ Psychosocial and behavioral risks are recognized as potential contributors to poor reproductive outcomes.^7–9 Poverty,¹⁰ limited social support,¹¹ smoking,¹² illicit drug use,¹³ depression,¹⁴ anxiety,^14,15 and intimate partner violence (IPV)^16,17 are all associated to varying degrees with pregnancy complications, premature and low-birthweight deliveries, stillbirths, and infant mortality.There is increasing recognition of the role of primary care in screening, diagnosis, and treatment of behavioral, mental health, and psychosocial concerns,^18–27 because of the significant association between medical morbidity and behavioral and mental health problems.²⁸ Although interventions involving primary care providers may have limited success, they can be cost-effective.^18,24 Because access to and use of behavioral and mental health care remain problematic, especially among members of underserved minority groups,^29–32 making such care available through primary care services may avert missed opportunities.Prenatal care may be a venue to address behavioral and mental health issues that can potentially affect the health of pregnant women and their unborn children.³³ The guidelines of the American College of Obstetrics and Gynecology and the American Academy of Pediatrics^34,35 suggest ways primary care providers can screen for behavioral and psychosocial risk factors. Despite these guidelines, many providers still fail to screen pregnant women,^35–38 with screening rates varying according to type of provider,^36,39 risk factors,³⁶ population group,⁴⁰ and provider risk perceptions.⁴¹ Furthermore, when implemented, psychosocial and behavioral interventions have been only moderately successful.^42,43Such inconsistent results may arise from multiple factors, including differences in study design, participant engagement, and intervention content or implementation, including approaches that address only 1 of multiple, co-occurring psychosocial or behavioral risk factors. Behavioral and psychosocial factors associated with poor pregnancy outcomes are related to and serve as risk factors for one another⁴⁴; therefore, an alternative approach would be to provide an intervention simultaneously addressing multiple psychosocial and behavioral risk factors among pregnant women, as has been done in relation to other health risks.^45–47A recent study focusing on 3569 Medicaid-eligible pregnant women examined the effects of the Prenatal Plus Program in Colorado with respect to smoking, inadequate prenatal weight gain, and “psychosocial problems” (defined as “significant or severe stress as a result of personal or family safety needs, lack of support systems, or an inability to meet basic needs”).^48(p1955) Women who had at least 10 Prenatal Plus visits were more likely than were women who did not to reduce these risks; in addition, only 7.0% of women who resolved all of their risks delivered low-birthweight infants, whereas 13.2% of those who resolved none of their risks did so. In spite of these promising results, the nonexperimental nature of the Colorado study may have created unquantifiable biases favoring the intervention.Moreover, only 4% of all births in Colorado, and 7% of Prenatal Plus deliveries, occurred among African American women, the group at greatest risk of adverse pregnancy outcomes. Thus, further experimental investigations in which rigorous randomized trial designs are used to assess vulnerable African American women are needed to better appreciate the potential merits of an integrated intervention focusing on psychosocial and behavioral risk factors during pregnancy.We conducted a randomized clinical trial testing the efficacy of an integrated intervention targeting multiple behavioral and psychosocial risk factors among pregnant African American women in the District of Columbia. The risk factors we chose to address were cigarette smoking, secondhand smoke exposure, depression, and IPV.     

Extraction of a large self-amputated colonic lipoma: A case report

Despite being the most common benign tumor of nonepithelial origin in the colon, colonic lipomas are nonetheless considered a rare occurrence. The minority of patients presenting with symptomatic colonic lipoma are generally treated with resection. We report a case of a symptomatic patient who, on presentation, was found to have a partially obstructing, self-amputated colonic mass on colonoscopy, requiring endoscopic fragmentation to extrude what was later histologically diagnosed to be a lipoma.     

The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy

Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance of AC elevation, stable clones of DU145 cells with AC overexpression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa.     

Severity of erectile dysfunction could predict left ventricular diastolic dysfunction in patients without overt cardiac complaint

IntroductionIt has been repeatedly demonstrated that presence of erectile dysfunction (ED) may predate the occurrence of overt event of coronary artery disease. However, the association between severity of ED and left ventricular diastolic dysfunction (LVDD) was rarely reported.AimThe aim of this study was to assess the association between severity of ED and LVDD in patients without overt cardiac complaint.Main Outcome MeasuresThe International Index of Erectile Function (IIEF) was used to assess erectile function. Diastolic Doppler parameters measurements and tissue Doppler imaging were used to assess left ventricular diastolic function.MethodsA total of 230 male ED patients without overt cardiac complaint were enrolled in this study. Erectile function was assessed using the IIEF. Patients were also screened for socio demographic data and medical comorbidities that included age, smoking, diabetes, hypertension, and dyslipidemia. All patients were referred to cardiologist for cardiac assessment. Left ventricular diastolic function that included diastolic Doppler parameters measurements and tissue Doppler imaging were also assessed.ResultsMean age ± standard deviation was 57.5 ± 5.6 (range of 42–81). There were significant associations between the following risk factors: age, obesity, smoking, hypertension, dyslipidemia, and increased severity of ED (P < 0.05 for each). Of the patients, 77.4%, 74.8%, 80%, and 66.1% had abnormal transmitral E/A (E/A) ratio, deceleration time (DT), isovolumic relaxation time (IVRT), mitral E velocity/tissue Doppler imaging E velocity (E/Em) ratio, respectively. Only the means of IVRT and (E/Em) ratio had significant associations with increased severity of ED (P < 0.001 for each). There were significant associations between increased severity of ED and the following categorical echo parameters: grades 1 and 2 of E/A ratio, DT, IVRT, and grades 1, 2, and 3 of (E/Em) ratio (P < 0.05 for each).Conclusions. The current study clearly demonstrated that LVDD is prevalent among patients with ED‐associated medical comorbidities without overt cardiac complaint. There were significant associations between increased severity of ED and presence of LVDD in those patients. El‐Sakka AI, Morsy AM, and Fagih BI. Severity of erectile dysfunction could predict left ventricular diastolic dysfunction in patients without overt cardiac complaint. J Sex Med 2011;8:2590–2597.     

Hepatic granuloma: decreasing trend in a high‐incidence area

Background: Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology. Methods: A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty‐six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed. Results: Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018). Conclusion: The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.