Factors associated with anaemia among women of reproductive age in Ethiopia: Multilevel ordinal logistic regression analysis

Anaemia has prevailed as a mild to severe public health problem in Ethiopian women of reproductive age. Many studies carried out on anaemia have been limited to subnational assessments and subgroups of women. The effects of potential factors thought to affect anaemia and severity levels of anaemia have not been well considered. Therefore, this study identifies individual, household and community level factors associated with anaemia among women of reproductive age in Ethiopia applying multilevel ordinal logistic regression models. Proportional odds assumption was tested by likelihood ratio test. About 35.6% of the variation on anaemia was due to between household and community level differences. Pregnancy (adjusted odds ratio [AOR] = 2.30, 95% confidence interval [CI]: 1.82, 2.91), HIV (AOR = 2.40, 95% CI: 1.76, 3.25), giving birth once (AOR = 1.2, 95% CI: 1.05, 1.40), giving birth more than once (AOR = 1.4, 95% CI: 1.19, 1.71), living with five or more family members (AOR = 1.24, 95% CI: 1.05, 1.47), living in poorest households (AOR = 1.34, 95% CI: 1.2, 1.61) and rural area (AOR = 1.57, 95% CI: 1.28, 1.92) were associated with greater odds of more severe anaemia compared with their respective counter parts. Secondary and above education (AOR = 0.83, 95% CI: 0.70, 0.97) and use of pills, implants or injectable (AOR = 0.67, 95% CI: 0.59, 0.77) were associated with lower odds of more severe anaemia. Anaemia prevention and control programmes need to be strengthened for women living with HIV/AIDS and during pregnancy. Household poverty reduction and social protection services need to be strengthened and integrated in anaemia prevention and management activities in women.     

Risk factors for anemia among pregnant women attending antenatal clinic at Jimma University Hospital, southwest Ethiopia

OBJECTIVE: to determine anemia and its risk factors among pregnant women METHODS: A cross-sectional analytic study was carried out among pregnant women who came for antenatal care follow up for the first time to Jimma University hospital, Jimma town, southwestern Ethiopia from May-June 2005. RESULTS: A total of 168 pregnant women who came for their first antenatal care visit to Jimma University hospital were enrolled in the study. A structured and interviewer administered questionnaire was used to collect data on the socio-demographic variables, dietary habit and other gynecologic and obstetric history. Dietary data were collected using food frequency questionnaire prepared for assessing nutritional factors for anemia. Sahli hemoglobinometer and a microscope were used for assessing hemoglobin level and stool for hookworm infection, respectively. Data were cleaned, edited and entered in to a computer and analyzed using SPSS for windows, version 11.0. Statistical tests were performed at the level of significance of 5%. The prevalence of anemia was 64/168 (38.2%) and the mean hemoglobin level was 11.3 mg/dl. Anemic cases were 4 times likely to have history of excess menstrual bleeding prior to the index pregnancy 2 times likely to have hook worm infection and 3 times likely not to have shoe wearing habit, 3 times likely to have birth intervals less than 24 moths between the previous pregnancy and index pregnancy (p < 0.05). CONCLUSION: This finding suggests the need for strengthening of interventions related to child spacing and raising awareness about family planning methods. All ANC attendants should be screened for anemia and hookworm infection at first visit and those anemic mothers and infected with hookworm should be treated appropriately. Health education should be given to pregnant mothers on family planning, and the need to gynecologic evaluation before pregnancy and the importance of wearing shoes to decrease hook worm infection and subsequent anemia.     

Kinetics of sedimentation rate, viral load and TNF-alpha in relation to HIV co-infection in tuberculosis

The kinetics of potential surrogate markers in HIV-positive (HIV+) and HIV-negative (HIV-), smear-positive tuberculosis (Tb+) patients in Gondar, Ethiopia (n = 60) was investigated. Clinical symptoms, sputum conversion, sedimentation rate (SR), HIV viral load and serum levels of TNF-alpha were determined before and 8 weeks after treatment initiation. The co-infection rate of HIV was 45%. There were significantly higher initial levels of SR and TNF-alpha in HIV+/Tb+ patients (79 +/- 29 mm/h and 13.5 +/- 7.6 pg/ml), than in HIV-/Tb+ patients (60 +/- 23 mm/h and 6.8 +/- 5.9 pg/ml, P<0.001). In HIV-/Tb+ patients, there was a marked decrease in SR compared with co-infected patients (46% [33 +/- 24 mm/h at week 8] vs. 24% [61 +/- 27 mm/h at week 8]). The HIV viral load (4.99 [range 3.70-5.92] to 4.90 [range 3.96-5.78] log10 copies/ml from week 0 to 8) and TNF-alpha (13.5 +/- 7.6 to 12.0 +/- 6.0 pg/ml) remained high in HIV+/Tb+ patients. In Tb patients, SR was significantly increased in HIV+ compared with HIV- patients. Additionally, TNF-alpha and HIV viral load remained elevated in HIV+/Tb+ patients following treatment despite clinical improvement comparable to HIV-/Tb+ patients.     

Thyroid neoplasms in Tikur Anbessa Hospital, Addis Ababa: a retrospective review with emphasis on cancer

Reportedly, thyroid cancer is a rare disease in most parts of the world. In Ethiopia, the prevalence of the disease is not known. This study aims to present the experience on thyroid cancer of a main central referral hospital. During the period 1993-02, 137 cases of thyroid neoplasms were operated on in Tikur Anbessa Teaching Hospital, Addis Ababa. Of these, 114 of 130 patients whose records were retrieved were retrospectively reviewed Neoplastic disease of the thyroid was found to be more common in younger age groups (mean age, 37 years) and in females (F: M ratio, 1.7: 1.0). Features of advanced malignant disease were not rare (21 cases). Of the 75 thyroid cancers, papillary carcinoma was the most common histologic type (72%). The extent of surgical treatment included partial, subtotal, near total and total thyroidectomy. In 15 cases, the lesions were found to be unresectable. The long-term outcome of treatment was difficult to evaluate, as the follow-up time was short. We believe that this paper will give base-line information on the frequency of thyroid cancer (7.5%) for a more comprehensive study in the future.     

Vesicular trafficking of tyrosine kinase receptors and associated proteins in the regulation of signaling and vascular function

Receptor tyrosine kinases (RTKs) play a pivotal role in the development and function of the cardiovascular system. Ligand-activated RTKs promote numerous downstream signal transduction pathways that lead to vascular permeability, as well as proliferation, migration, and differentiation of vascular endothelia and smooth muscle cells. Ligand binding also promotes internalization of the activated receptors either to downregulate the signaling via degradation of the ligand/receptor complex or to signal from endosomes. However, the outcomes of receptor internalization via clathrin-dependent or caveolar pathways and trafficking mechanisms are incompletely clarified in vascular systems. Activity modulation through endocytosis and vesicular trafficking significantly impacts downstream targets of RTKs such as endothelial nitric oxide synthase (eNOS) and VE-cadherin. RTKs and their associated targets are also transported to the nucleus, where they may directly impact nuclear signaling. Although the nuclear transport pathways are just beginning to be unraveled, it appears that endocytosis and vesicular trafficking are involved. In this review, we discuss the mechanisms by which activated RTKs and the downstream targets eNOS and VE-cadherin may be internalized and transported to various intracellular compartments. How localization and interacting proteins impact protein function and influence signaling is an important theme, as is the potential for modulating signaling through therapeutic targeting of activated receptors and components of the endocytic machinery.     

Binding and activation of human and mouse complement by Cryptosporidium parvum (Apicomplexa) and susceptibility of C1q- and MBL-deficient mice to infection

Cryptosporidium parvum is a protozoan parasite (Apicomplexa) that causes gastrointestinal disease in animals and humans. Whereas immunocompetent hosts can limit the infection within 1 or 2 weeks, immunocompromised individuals develop a chronic, life-threatening disease. The importance of the adaptive cellular immune response, with CD4+ T-lymphocytes being the major players, has been clearly demonstrated. Several non-adaptive immune mechanisms have been suggested to contribute to the host defence, such as interferon-gamma (IFN-gamma) from NK cells, certain chemokines, beta-defensins and pro-inflammatory cytokines, but the influence of the complement systems has been less well studied. We analysed the in vitro binding and activation of the human and mouse complement systems and tested the susceptibility to infection in complement-deficient mouse strains. We found that C. parvum can activate both the classical and lectin pathways, leading to the deposition of C3b on the parasite. Using real-time PCR, parasite development could be demonstrated in adult mice lacking mannan-binding lectin (MBL-A/C-/-) but not in mice lacking complement factor C1q (C1qA-/-) or in wild type C57BL/6 mice. The contribution of the complement system and the lectin pathway in particular to the host defence against cryptosporidiosis may become apparent in situations of immunodeficiency such as HIV infections or in early childhood.     

Gene expression studies demonstrate that the K-ras/Erk MAP kinase signal transduction pathway and other novel pathways contribute to the pathogenesis of cumene-induced lung tumors

National Toxicology Program (NTP) inhalation studies demonstrated that cumene significantly increased the incidence of alveolar/bronchiolar adenomas and carcinomas in B6C3F1 mice. Cumene or isopropylbenzene is a component of crude oil used primarily in the production of phenol and acetone. The authors performed global gene expression analysis to distinguish patterns of gene regulation between cumene-induced tumors and normal lung tissue and to look for patterns based on the presence or absence of K-ras and p53 mutations in the tumors. Principal component analysis segregated the carcinomas into groups with and without K-ras mutations, but failed to separate the tumors based on p53 mutation status. Expression of genes associated with the Erk MAP kinase signaling pathway was significantly altered in carcinomas with K-ras mutations compared to tumors without K-ras mutations or normal lung. Gene expression analysis also suggested that cumene-induced carcinomas with K-ras mutations have greater malignant potential than those without mutations. In addition, significance analysis of function and expression (SAFE) demonstrated expression changes of genes regulated by histone modification in carcinomas with K-ras mutations. The gene expression analysis suggested the formation of alveolar/bronchiolar carcinomas in cumene-exposed mice typically involves mutation of K-ras, which results in increased Erk MAP kinase signaling and modification of histones.     

Inhalation delivery dramatically improves the efficacy of topotecan for the treatment of local and distant lung cancer

Topotecan is potent anti-cancer drug approved for various malignancies but hematopoietic toxicities undermine its wider application and use of its most effective dose. This study aims to improve these limitations through inhalation-delivery. The pharmacokinetics, efficacy, and toxicity of 2–5 times lower inhalation doses of topotecan dry-powder were compared with the standard intravenous (IV) delivery once/twice-a-week. Human-derived EGFR-mutant (H1975), KRAS-mutant (A549), and EGFR/KRAS wild-type (H358) orthotopic and distant lung tumors were evaluated in murine models. Inhalation of 1 mg/kg topotecan significantly improved the half-life and drug exposure (area under the curve, AUC) compared to 5 mg/kg via IV-delivery. AUCs (h*ng/mL) for inhaled/IV topotecan in plasma, lung, liver, and brain were, 831/888, 60,000/1080, 8380/4000, and 297/15, respectively; while the half-life was also greatly increased in these tissues. The average lung tumor burden of H358-derived tumors was reduced from 15.0 g to 8.4 g (44%) in rats treated once-a-week with 2 mg/kg IV and 1.8 g (88%) with 1 mg/kg inhaled topotecan, corroborating previous findings using A549- and H1975-derived orthotopic lung tumors. Importantly, inhaled topotecan showed superior efficacy in suppressing lung tumors at distant sites. The growth of H1975- and H358-derived subcutaneous xenografts were completely arrested and A549-derived tumors were significantly reduced in mice treated twice-a-week with 1 mg/kg inhaled topotecan compared to a minor (H1975 and H358) or no reduction (A549) with twice-a-week 5 mg/kg IV topotecan.