High Shear Stress at the Surface of Enhancing Plaque in the Systolic Phase is Related to the Symptom Presentation of Severe M1 Stenosis

The computational fluid dynamics methods for the limited flow rate and the small dimensions of an intracranial artery stenosis may help demonstrate the stroke mechanism in intracranial atherosclerosis. We have modeled the high wall shear stress (WSS) in a severe M1 stenosis. The high WSS in the systolic phase of the cardiac cycle was well-correlated with a thick fibrous cap atheroma with enhancement, as was determined using high-resolution plaque imaging techniques in a severe stenosis of the middle cerebral artery.     

Nardostachys jatamansi extract protects against cytokine-induced β-cell damage and streptozotocin-induced diabetes

AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was conf irmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were c...     

Adoptive Transfer of Human Papillomavirus E7-specific CTL Enhances Tumor Chemoresponse Through the Perforin/Granzyme-mediated Pathway

Adoptive cytotoxic T lymphocyte (CTL) therapy has an important implication in treating cancer patients. Here, we investigate whether adoptive transfer of human papillomavirus (HPV) E7-specific CTL can enhance tumor chemoresponse using an established cervical cancer animal model. Cisplatin-based chemotherapy plus CTL therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. Cisplatin treatment dose-dependently increased the expression of Fas, intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC) class I antigens (Ags) on tumor cells in vitro. However, CTL-expressing FasL failed to improve antitumor activity in vitro and in animals, resulting from nonfunctional Fas expressed on tumor cells. In contrast, ethylene glycol tetraacetic acid (EGTA) treatment blocked increased sensitivity of cisplatin-treated tumor cells to CTL-mediated killing in vitro, suggesting an important role of the perforin/granzyme-mediated pathway for improved therapeutic effectiveness. This notion was further confirmed by perforin knockout animal studies. Thus, this study shows that (i) modulation of Ag (Fas, ICAM-1) expression by tumor cells has little effect on their increased sensitivity to CTL-mediated killing, (ii) improved therapeutic effectiveness is mediated mainly through the perforin/granzyme-mediated tumor killing pathway, and (iii) a combination of chemotherapy and adoptive E7-specific CTL transfer augments antitumor therapeutic activity in vivo. This finding may have important implications for treating HPV-associated cervical cancer.     

Accumulation of coronary artery disease risk factors over three years: data from an international inception cohort

OBJECTIVE: To examine the accumulation of risk factors over 3 years in a multicenter, international inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: The Systemic Lupus International Collaborating Clinics registry for atherosclerosis comprises 27 centers from 11 countries. An inception cohort of 935 patients with SLE was assembled, according to a standardized protocol, from 2000 to 2006 to study risk factors for atherosclerosis. Both classic and other coronary artery disease (CAD) risk factors were collected at entry and through 3 years of followup. Therapy was documented over the 3 years. The Framingham 10-year risk factor profile was calculated for each patient at year 1 and year 3. RESULTS: A total of 278 patients from the inception cohort were followed for 3 years and constituted the population for this study. At enrollment a substantial number of patients already demonstrated several risk factors for CAD, both classic and other. All risk factors increased from enrollment over the 3 years of followup. Treatment of hypertension and hypercholesterolemia also increased over 3 years, but less so for hypercholesterolemia. The Framingham 10-year CAD risk profile was higher in men than in women both at entry and at 3 years, and remained unchanged over the 3 years. Corticosteroid use increased only slightly over 3 years, but use of antimalarials and immunosuppressive agents increased to a greater extent. CONCLUSION: Patients with SLE should be monitored for CAD risk factors from the time of diagnosis and appropriate treatment should be instituted early.     

Males seropositive for hepatitis B surface antigen are at risk of lower bone mineral density: the 2008–2010 Korea National Health and Nutrition Examination Surveys

Background

Hepatic osteodystrophy has been reported in patients with various chronic liver diseases, including liver cirrhosis. However, it has not been well investigated in patients with hepatitis B virus infection. The aim of this study was to investigate the association between hepatitis B surface antigen (HBsAg) seropositivity and bone mineral density (BMD) in a population representative of normal Koreans.

Methods

Subjects with both HBsAg and BMD levels examined during the 2008–2010 Korea National Health and Nutrition Examination Surveys were included. HBsAg-seropositive (+) subjects were compared with those who were HBsAg-seronegative (?). BMD was measured at the lumbar spine and femur by dual-energy X-ray absorptiometry. Multivariable logistic regression was performed for BMD.

Results

In total, 11,306 participants were included in this study, among which 423 (3.7 %) were HBsAg(+): 153 premenopausal female (3.4 %), 83 postmenopausal female (3.5 %), and 187 male (4.2 %). Multivariable logistic regression analysis adjusted for age and body mass index showed that HBsAg(+) male had significantly lower BMD of the femoral neck than HBsAg(?) male (0.810 ± 0.009 vs. 0.827 ± 0.002 g/cm², p = 0.035). Further adjustment for waist circumference, smoking, drinking, exercise, income, occupation, and vitamin D levels showed that HBsAg(+) male had significantly lower BMD of the femur neck (0.810 ± 0.010 vs. 0.831 ± 0.002 g/cm², p = 0.032) and lumbar spine (0.953 ± 0.011 vs. 0.974 ± 0.003 g/cm², p = 0.049) than HBsAg(?) male.

Conclusions

HBsAg seropositivity was significantly associated with lower BMD in male. Future long-term prospective studies investigating bone turnover markers and hormones are needed to better understand the pathophysiology and clinical significance of chronic hepatitis B virus-related hepatic osteodystrophy.

     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

Objective

To investigate the proxy‐reported health‐related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).

Methods

In this multinational, multicenter, cross‐sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.

Results

A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean ± SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 ± 10.6 versus 54.6 ± 4.0, P < 0.0001; psychosocial: 47.6 ± 8.7 versus 51.9 ± 7.5, P < 0.0001), with the physical well‐being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10‐cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.

Conclusion

We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well‐being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.     

Intracranial hemorrhage after carotid angioplasty: a pooled analysis.

PURPOSE: To use a pooled analysis of the literature to find the incidence of and characteristics common to intracranial hemorrhage (ICH) associated with carotid artery stenting (CAS). METHODS: A search of the English-language literature (1996-2005) was performed in PubMed to find cases of CAS-associated ICH. Information was derived from the identified case studies in 5 categories and 19 aspects: (1) incidence of CAS-associated ICH; (2) demographic data (sex, age, symptom presentation, and presence of preexisting hypertension); (3) imaging data (side of lesion, degree of maximal stenosis, lesion location, status of the contralateral carotid artery, collateral circulation, and preprocedural imaging features); 4) procedure-related characteristics (antithrombotic medication, use of cerebral protection devices, residual stenosis, symptoms, interval from the procedure to ICH, type of ICH, and blood pressure changes); and (5) clinical outcome. RESULTS: Fifty-four cases of CAS-associated ICH were reviewed: 51 cases from 36 published articles and our own 3 cases. The incidence of CAS-associated ICH was 0.63% (95% CI 0.38% to 0.97%) in studies consisting of >100 cases, which was significantly lower (p<0.0001) than that of case series consisting of <100 cases (2.69%, 95% CI 1.75% to 3.94%). Distinctive features included symptomatic lesions, severe stenosis (> or =90%), maximal stenosis in the internal carotid artery (ICA) distal to the bifurcation, and preexisting cerebral infarction. CONCLUSION: The incidence of CAS-associated ICH was significantly lower in series consisting of >100 cases. More caution should be directed toward patients with symptomatic lesions, severe stenosis, maximal ICA stenosis distal to the carotid bifurcation, and preexisting cerebral infarction.