Aortic Complications of Giant Cell Arteritis: A Diagnostic and Management Dilemma

Abstract We describe three giant cell aortitis patients who were operatively managed at our institution over the last seven years and review the recent relevant literature to highlight the specific features of the disease and the salient points of management in relation to the cardiac surgeon. (J Card Surg 2010;25:572‐581)     

In Vitro inhibitory potential of decursin and decursinol angelate on the catalytic activity of cytochrome P-450 1A1/2, 2D15, and 3A12 isoforms in canine hepatic microsomes

Danggui is one of the most popular herbal medicines consumed by patients in different clinical settings in Asian countries. In this study, the two major pyranocoumarin compounds extracted from the Korean Angelica gigas root decursin (DC) and decursinol angelate (DA) were examined in vitro with regard to their abilities to inhibit hepatic CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities in canine liver microsomes. The two components were capable of inhibiting CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities, but the potencies varied. DC and DA selectively and noncompetitively inhibited CYP1A1/2 activity, with K _i values of 90.176 and 67.560 μM, respectively. On the other hand, they exhibited slight inhibitory effects on CYP2D15 and CYP3A12 with K _i values of 666.180 and 872.502 μM, 990.500 and 909.120 μM (1’hydroxymidazolam, MDZ1’H), and 802.800 and 853.920 μM (4-hydroxymidazolam, MDZ4H), respectively. Additionally, they showed increased inhibition after preincubation, which suggests the involvement of a mechanism-based inhibition. In sum, this in vitro data should be heeded as a signal of possible in vivo interactions. The use of human liver preparations would considerably strengthen the practical impact of the data generated from this study. The two authors contributed equally to this paper.     

Addressing the workforce crisis: the professional aspirations of pharmacy students in Ghana

Objective A lack of skilled health professionals, and net migration from developing to more developed countries, are widely recognised as barriers to the delivery of effective health care. However, few studies have investigated this issue from the perspective of pharmacists, although they are increasingly viewed as a potentially valuable and underexploited health care resource. The objectives of this study were to examine the professional aspirations and perceived opportunities of final year pharmacy students in a developing country; and consider what developments may encourage them to remain in, and contribute to, health care in their home country. Method Final year pharmacy students from the Faculty of Pharmacy, KNUST, Kumasi, Ghana, were randomly selected and invited to participate in in-depth interviews. These were audio-recorded (with permission of respondents) and transcribed verbatim to enable a qualitative analysis. Main outcome measure: professional aspirations, and perceived opportunities and barriers to their achievement in Ghana and abroad. Results Participants viewed themselves, and wished to be viewed by others, as health professionals. They described a commitment to applying their clinical knowledge and to education beyond their first degree. However, they identified significant barriers to the achievement of professional aspirations in Ghana, which would diminish their opportunities to contribute to health care. Whilst most students expressed the expectation or desire to travel at some point, usually early, in their career, they all demonstrated a commitment to their country and stated a wish to return. Conclusion Overall the study highlighted prospective pharmacists in Ghana as ambitious, committed potential health professionals. The study indicates that a lack of attention by policy makers and professional bodies to ways of exploiting the contribution of pharmacists to public health, may represent a lost potential human resource for health in developing countries.     

Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications

PURPOSE: More than 1,300,000 prostate needle biopsies are done annually in the United States with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer on subsequent needle biopsies in prostate-specific antigen-screened populations. In contemporary series, prostate cancer is detected in approximately 20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histologic subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in prostate cancer has also been shown to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion prostate cancer is associated with a more aggressive clinical course. EXPERIMENTAL DESIGN: In this study, we assessed a series of HGPIN lesions and paired prostate cancer for the presence of TMPRSS2-ERG gene fusion. RESULTS: Fusion-positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances, the matching cancer shared the same fusion pattern. Sixty percent of TMPRSS2-ERG fusion prostate cancer had fusion-negative HGPIN. CONCLUSIONS: Given the more aggressive nature of TMPRSS2-ERG prostate cancer, the findings of this study raise the possibility that gene fusion-positive HGPIN lesions are harbingers of more aggressive disease. To date, pathologic, molecular, and clinical variables do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding TMPRSS2-ERG fusion prostate cancer in subsequent biopsies.     

Evaluation of a human papillomavirus assay in cervical screening in Zimbabwe

Objective To determine the utility of an assay for high risk genital human papillomavirus (HPV) in cervical screening in Zimbabwe, Africa.
Design Cross-sectional study.
Setting Harare, Zimbabwe.
Population Zimbabwe women (   n = 2140  ), 25 to 55 years old, recruited in clinics in Chitungwiza and Greater Harare.
Methods Genital specimens were assessed for HPV, using the HPV DNA test Hybrid Capture II (probe B). Further assessment of the women was conducted using colposcopy and biopsy as indicated. High grade squamous intraepithelial lesions were diagnosed in 215 women. Colposcopy and/or biopsy showed low grade lesions in 346 women.
Results The overall prevalences were: 42.7% for HPV, 10% for high grade squamous intraepithelial lesions and 16% for low grade lesions. Prevalence for HPV decreased significantly with increase in age (   P for trend < 0.0001  ) and increased significantly with increasing disease severity, from 35% in normal women, to 53% in women with low grade lesions and 81% in women with high grade lesions (   P for trend < 0.001  ). In specimens positive for HPV, the amount was 14-fold higher in women with high grade lesions compared with normal women. In screening for high grade lesions the assay for HPV had a sensitivity of 81% (CI 75%–86%); sensitivity for low grade lesions was 64% (CI 60%–68%). Specificity was 62% (CI 59%–64%) for high grade lesions and 65% (CI 62%–67%) for low grade lesions. The positive predictive value was 19% (CI 17%–22%) for high grade lesions and 39% (CI 36%–42%) for low grade lesions.
Conclusion For high grade squamous intraepithelial lesions the sensitivity of the Hybrid Capture II HPV DNA test was high, but the specificity was relatively low. The test may therefore be most useful in conjunction with other screening tests.