Cervical cancer prevention and treatment research in Africa: a systematic review from a public health perspective.

BACKGROUND: Women living in Africa experience the highest burden of cervical cancer. Research and investment to improve vaccination, screening, and treatment efforts are critically needed. We systematically reviewed and characterized recent research within a broader public health framework to organize and assess the range of cervical cancer research in Africa. METHODS: We searched online databases and the Internet for published articles and cervical cancer reports in African countries. Inclusion criteria included publication between 2004 and 2014, cervical cancer-related content pertinent to one of the four public health categories (primary, secondary, tertiary prevention or quality of life), and conducted in or specifically relevant to countries or regions within the African continent. The study design, geographic region/country, focus of research, and key findings were documented for each eligible article and summarized to illustrate the weight and research coverage in each area. Publications with more than one focus (e.g. secondary and tertiary prevention) were categorized by the primary emphasis of the paper. Research specific to HIV-infected women or focused on feasibility issues was delineated within each of the four public health categories. RESULTS: A total of 380 research articles/reports were included. The majority (54.6 %) of cervical cancer research in Africa focused on secondary prevention (i.e., screening). The number of publication focusing on primary prevention (23.4 %), particularly HPV vaccination, increased significantly in the past decade. Research regarding the treatment of precancerous lesions and invasive cervical cancer is emerging (17.6 %), but infrastructure and feasibility challenges in many countries have impeded efforts to provide and evaluate treatment. Studies assessing aspects of quality of life among women living with cervical cancer are severely limited (4.1 %). Across all categories, 11.3 % of publications focused on cervical cancer among HIV-infected women, while 17.1 % focused on aspects of feasibility for cervical cancer control efforts. CONCLUSIONS: Cervical cancer research in African countries has increased steadily over the past decade, but more is needed. Tertiary prevention (i.e. treatment of disease with effective medicine) and quality of life of cervical cancer survivors are two severely under-researched areas. Similarly, there are several countries in Africa with little to no research ever conducted on cervical cancer.

Health status among black African-born women in Kansas City: a preliminary assessment.

BACKGROUND: Health information and statistics for Black foreign-born women in the United States are under-reported or not available. Black foreign-born women typically are classified under the general category of African American, ignoring the heterogeneity that exists in the United States Black population. It is important to identify health issues and behaviors of African-born women to effectively address health disparities. METHODS: Black African-born women (N = 29), 20 years or older completed a survey about general and women's health, health history, acculturation, lifestyle, social and health challenges, beliefs about breast cancer. Data were analyzed using SPSS 14.0 software. Categorical variables were summarized with frequencies and percentages and continuous variables were summarized with means and standard variation. A Likert scale (strongly agree, agree, disagree, and strongly disagree) was used to assess beliefs about breast cancer. RESULTS: Most (71.4%) participants had a high school education or more, 70% were employed, and 50% had health insurance. Two-thirds received health care from primary care doctors, 20.7% from health departments, and 39.3% got annual checkups. Lack of jobs, healthcare cost, language barrier, discrimination, and child care were the top social issues faced by participants. High blood pressure, obesity, oral health, HIV/AIDS, and diabetes were indicated as the most common health problems. The percent of participants (60%) that had not had a mammogram within the previous 2 years was more than the state average (24%) for women 40 years and older reported by the Kansas Department of Health and Environment. The percent of participants (40%) that had a mammogram within the previous 2 years was lower than the national average (73.2%) for African American women. CONCLUSIONS: Study provides a snapshot of social concerns and health issues in an African population residing in Midwestern United States. Understanding the socio-cultural characteristics of this population is necessary to address health disparities.

A pilot study of health priorities of Somalis living in Kansas City: laying the groundwork for CBPR.

African immigrant and refugee communities remain medically underserved in the United States. Formative efforts are being directed to address the local needs of communities by researchers, community agencies, and local populations. However, there is a paucity of data and sparse documentation regarding these efforts. The objectives for this pilot study were to identify the health priorities of the Kansas City Somali community and to establish a working relationship between an academic medical university and the local Somali community. Our team used community-based participatory research principles and interviewed Somali community members (n = 11). Participants stated that chronic and mental health conditions were of primary concern. Medical system navigation and literacy struggles were identified as barriers. Participants offered possible solutions to some health issues, e.g., using community health workers and Qur'anic readers. Preliminary findings will help guide future research and inform strategies to improve the health and well-being of this community.

American Indian Men's Perceptions of Breast Cancer Screening for American Indian Women.

Screening, especially screening mammography, is vital for decreasing breast cancer incidence and mortality. Screening rates in American Indian women are low compared to other racial/ethnic groups. In addition, American Indian women are diagnosed at more advanced stages and have lower 5-year survival rate than others. To better address the screening rates of American Indian women, focus groups (N=8) were conducted with American Indian men (N=42) to explore their perceptions of breast cancer screening for American Indian women. Our intent was to understand men's support level toward screening. Using a community-based participatory approach, focus groups were audio-taped, transcribed verbatim, and analyzed using a text analysis approach developed by our team. Topics discussed included breast cancer and screening knowledge, barriers to screening, and suggestions to improve screening rates. These findings can guide strategies to improve knowledge and awareness, communication among families and health care providers, and screening rates in American Indian communities.

Assessment of mammography experiences and satisfaction among American Indian/Alaska Native women.

BACKGROUND: American Indian/Alaska Native (AI/AN) women have lower breast cancer (BCA) screening and 5-year survival rates than non-Hispanic Whites. Understanding reasons for low screening rates is important to combatting later stage diagnoses. The purpose of this study was to assess mammography experiences and satisfaction among AI/AN women. METHODS: Nine focus groups were held with rural (N = 15) and urban (N = 38) AI/AN women 40 years and older in Kansas and Kansas City, Missouri, living both near and far from Indian Health Service (IHS) and tribal facilities, to examine experiences and satisfaction with mammography. Transcripts were coded and themes identified using a community-based participatory research approach. FINDINGS: Themes were classified under knowledge, communication, and awareness of BCA; barriers to mammography; mammogram facility size; impressions of mammogram technologist; motivations for getting a mammogram; and how to improve the mammogram experience. Participants had knowledge of prevention, but described cultural reasons for not discussing it and described better experiences in smaller facilities. Participants indicated having a mammogram technologist who was friendly, knowledgeable, respectful, competent, and explained the test was a determining factor in satisfaction. Other factors included family history, physician recommendation, and financial incentives. Barriers included transportation, cost, perceptions of prejudice, and time constraints. Participants on reservations or near IHS facilities preferred IHS over mainstream providers. Suggestions for improvement included caring technologists, better machines with less discomfort, and education. CONCLUSIONS: Interventions to enhance the professionalism, empathy, and cultural awareness of mammogram technologists; reduce barriers; and provide positive expectations and incentives could improve satisfaction and compliance with screening mammography.

Breast cancer screening perceptions among American Indian women under age 40.

Breast cancer mortality rates are the second leading cause of cancer death in American Indian (AI) women. AI breast cancer screening rates have been decreasing, and AI women have some of the lowest screening rates compared to other racial/ethnic groups. Our research team investigated breast cancer and breast cancer screening education prior to recommended age for screening. It is imperative to examine the perspectives of young AI women toward breast cancer screening to better understand screening perceptions among AI women. Following a community-based participatory research approach, we conducted five focus groups and four interviews with AI women aged 25-39 (N = 48) in Kansas and Missouri. Nine themes emerged from the focus groups and relate to topics such as the following: knowledge of breast cancer and breast cancer screening, barriers to screening and treatment, suggestions to improve access, and perceptions and use of health-care systems. Specifically, we found that AI women lacked knowledge of details about screenings and their risks for getting breast cancer, cost was cited as a primary barrier to screening, additional education was needed (particularly materials that were AI focused), breast health was generally not discussed with others, and more instruction was requested for techniques used to identify bodily changes or abnormalities. Understanding attitudes of AI women not of recommended screening age may provide an insight into low screening rates among AI women. Furthermore, the results may inform outreach strategies to improve current and future screening rates.

An assessment of American Indian women's mammography experiences.

BACKGROUND: Mortality from breast cancer has increased among American Indian/Alaskan Native (AI/AN) women. Despite this alarming reality, AI/AN women have some of the lowest breast cancer screening rates. Only 37% of eligible AI/AN women report a mammogram within the last year and 52% report a mammogram within the last two years compared to 57% and 72% for White women. The experiences and satisfaction surrounding mammography for AI/AN women likely are different from that of women of other racial/ethnic groups, due to cultural differences and limited access to Indian Health Service sponsored mammography units. The overall goals of this study are to identify and understand the mammography experiences and experiential elements that relate to satisfaction or dissatisfaction with mammography services in an AI/AN population and to develop a culturally-tailored AI/AN mammography satisfaction survey. METHODS AND DESIGN: The three project aims that will be used to guide this work are: 1) To compare the mammography experiences and satisfaction with mammography services of Native American/Alaska Native women with that of Non-Hispanic White, Hispanic, and Black women, 2) To develop and validate the psychometric properties of an American Indian Mammography Survey, and 3) To assess variation among AI/AN women's assessments of their mammography experiences and mammography service satisfaction. Evaluations of racial/ethnic differences in mammography patient satisfaction have received little study, particularly among AI/AN women. As such, qualitative study is uniquely suited for an initial examination of their experiences because it will allow for a rich and in-depth identification and exploration of satisfaction elements. DISCUSSION: This formative research is an essential step in the development of a validated and culturally tailored AI/AN mammography satisfaction assessment. Results from this project will provide a springboard from which a maximally effective breast cancer screening program to benefit AI/AN population will be developed and tested in an effort to alter the current breast cancer-related morbidity and mortality trajectory among AI/AN women.

In vitro inhibition and induction of human liver cytochrome p450 enzymes by milnacipran.

Milnacipran (Savella) inhibits both norepinephrine and serotonin reuptake and is distinguished by a nearly 3-fold greater potency in inhibiting norepinephrine reuptake in vitro compared with serotonin. We evaluated the ability of milnacipran to inhibit and induce human cytochrome P450 enzymes in vitro. In human liver microsomes, milnacipran did not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6 (IC(50) >or= 100 microM); whereas, a comparator with dual reuptake properties [duloxetine (Cymbalta)] inhibited CYP2D6 (IC(50) = 7 microM) and CYP2B6 (IC(50) = 15 microM) with a relatively high potency. Milnacipran inhibited CYP3A4/5 in a substrate-dependent manner (i.e., midazolam 1'-hydroxylation IC(50) approximately 30 microM; testosterone 6beta-hydroxylation IC(50) approximately 100 microM); whereas, duloxetine inhibited both CYP3A4/5 activities with equal potency (IC(50) = 37 and 38 microM, respectively). Milnacipran produced no time-dependent inhibition (<10%) of P450 activity, whereas duloxetine produced time-dependent inhibition of CYP1A2, 2B6, 2C19, and 3A4/5. To evaluate P450 induction, freshly isolated human hepatocytes (n = 3) were cultured and treated once daily for 3 days with milnacipran (3, 10, and 30 microM), after which microsomal P450 activities were measured. Whereas positive controls (omeprazole, phenobarbital, and rifampin) caused anticipated P450 induction, milnacipran had minimal effect on CYP1A2, 2C8, 2C9, or 2C19 activity. The highest concentration of milnacipran (30 microM; >10 times plasma C(max)) produced 2.6- and 2.2-fold increases in CYP2B6 and CYP3A4/5 activity (making it 26 and 34% as effective as phenobarbital and rifampin, respectively). Given these results, milnacipran is not expected to cause clinically significant P450 inhibition or induction.

An in vitro evaluation of the victim and perpetrator potential of the anticancer agent laromustine (VNP40101M), based on reaction phenotyping and inhibition and induction of cytochrome P450 enzymes.

Laromustine (VNP40101M, also known as Cloretazine) is a novel sulfonylhydrazine alkylating (anticancer) agent. Laromustine generates two types of reactive intermediates: 90CE and methylisocyanate. When incubated with rat, dog, monkey, and human liver microsomes, [(14)C]laromustine was converted to 90CE (C-8) and seven other radioactive components (C-1-C-7). There was little difference in the metabolite profile among the species examined, in part because the formation of most components (C-1-C-6 and 90CE) did not require NADPH but involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Laromustine caused direct inhibition of CYP2B6 and CYP3A4/5 (the two enzymes involved in C-7 formation) as well as of CYP2C19. K(i) values were 125 microM for CYP2B6, 297 muM for CYP3A4/5, and 349 microM for CYP2C19 and were greater than the average clinical plasma C(max) of laromustine (25 microM). There was evidence of time-dependent inhibition of CYP1A2, CYP2B6, and CYP3A4/5. Treatment of primary cultures of human hepatocytes with up to 100 microM laromustine did not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4/5, but the highest concentration of laromustine decreased the activity and levels of immunoreactive CYP3A4. The results of this study suggest the laromustine has 1) negligible victim potential with respect to metabolism by cytochrome P450 enzymes, 2) negligible enzyme-inducing potential, and 3) the potential in some cases to cause inhibition of CYP2B6, CYP3A4, and possibly CYP2C19 during and shortly after the duration of intravenous administration of this anticancer drug, but the clinical effects of such interactions are likely to be insignificant.

Cocaine-protein targets in mouse liver.

Cocaine has been shown to be hepatotoxic in mice, rats and humans. N-Oxidative metabolism of cocaine is required for this effect, and it has been proposed that binding of cocaine reactive metabolites formed via this pathway might be responsible for cytotoxicity. To explore this hypothesis, cocaine-protein adducts in liver following cocaine treatment in naive ICR mice were examined by Western blot analysis and compared with those formed in mice pretreated with phenobarbital or beta-naphthoflavone. Phenobarbital and beta-naphthoflavone pretreatments have been shown previously to shift the hepatic necrosis in ICR mice from the midzonal region to periportal and perivenular regions, respectively. Similar patterns of cocaine-protein adduction were detected in naive, phenobarbital-pretreated and beta-naphthoflavone-pretreated mice, however, suggesting a consistent set of target proteins regardless where within the lobule toxicity occurs. To confirm that Western blot analysis using anti-cocaine antibody was capable of detecting all of the major cocaine-protein adducts, a separate experiment was conducted in which mice were treated with 14C-labeled cocaine and cocaine-protein adducts were detected fluorographically. This technique detected essentially the same protein adducts as the Western blots. Two of the protein adducts were isolated, subjected to N-terminal sequence analysis, and found to have homology with hsp 60 and transferrin. Western blot analysis using anti-hsp 60 and anti-transferrin antibodies following two-dimension PAGE separation was used to confirm the identity of these protein targets. Impairment of function of either protein could plausibly contribute to cocaine hepatotoxicity, although this remains to be demonstrated.