BioMed Central - Latest Articles

In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures

Wenbi Xiong — 2009-07-11T00:00:00Z

Background Shikonin derivatives have cytotoxic and antitumor effects. This study aims to investigate the antitumor effects of acetylshikonin isolated from a Chinese medicinal herb Arnebia euchroma (Royle) Johnst. Methods The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of acetylshikonin on human lung adenocarcinoma cell line A549, human hepatocellular carcinoma cell line Bel-7402, human breast adenocarcinoma cell line MCF-7 and mouse Lewis lung carcinoma (LLC) cell line. C57BL/6 mice with LLC model were used to study the in vivo antitumor effects of acetylshikonin. The expression of bax, bcl-2 and caspase-3 proteins in LLC tissue was determined with immunohistochemical staining. Results In A549, Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. IC50 (means +/- SD) were 5.6+/-0.86ug/ml, 6.82+/-1.5ug/ml, 3.04+/-0.44ug/ml and 2.72+/-0.38ug/ml respectively. Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition rate of acetylshikonin (2mg/kg) was 42.85%. Immunohistochemical staining revealed that in the acetylshikonin groups the expression of bax and caspase-3 increased, whereas the expression of bcl-2 decreased, suggesting that acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3. Conclusion Acetylshikonin isolated from Arnebia euchroma (Royle) Johnst cell suspension cultures exhibits specific in vivo and in vitro antitumor effects.

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

Alberto Alvarado-Miranda — 2009-07-11T00:00:00Z

Background: Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. Methods: One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2 (FAC), or doxorubicin 50mg/m2 and cyclophosphamide 500mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60Gy breast irradiation and weekly mitomycin 5mg/m2, 5-fluorouracil 500mg/m2, and dexamethasone 16mg, or cisplatin 30mg/m2, gemcitabine 100mg/m2 and dexamethasone 16mg), and 6-8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results: Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR=3.8; 95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity profile was acceptable. Conclusions: This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

Evaluation of a Portable Hemoglobin Photometer in Pregnant Women in a High Altitude Area: a pilot study

Xiaoyan Zhou — 2009-07-11T00:00:00Z

Background: Anemia is a widespread public health problem associated with an increased risk of morbidity and mortality, especially in pregnant women. This study examined the agreement between a portable hemoglobin photometer and a laboratory analyzer in determining hemoglobin level in pregnant women. Methods: This study recruited 69 pregnant women in Tibet, China. Capillary blood samples were taken to measure hemoglobin concentration using the hemoglobin photometer and the laboratory analyzer. Limit of agreement, concordance and intraclass correlation coefficient were used to evaluate the agreement. Laboratory measurement was considered as the standard reference method. Sensitivity and specificity were calculated to assess the error in screening for anemia. Results: Mean difference between the two methods was -2.1 g/l. wide 95% limits of agreement were found (-22.6 g/l to 18.4 g/l). The intraclass correlation coefficient was 0.795, and concordance correlation coefficient was 0.793. Sensitivity and specificity were 94.9% and 76.7% respectively. Positive predictive value was 84.1%, and negative predictive value was 92.0%. Conclusions: This hemoglobin photometer is not recommended for determining hemoglobin concentration in pregnancy in a high altitude area.

Incidence and predictors of onboard injuries among Sri Lankan flight attendants

Suneth Agampodi — 2009-07-11T00:00:00Z

Background: Occupational injuries among flight attendants have not been given appropriate attention in Sri Lanka. The purpose of this study was to estimate the incidence of onboard injury among Sri Lankan flight attendants and to describe the determinants of onboard injury. Methods: A descriptive cross-sectional study was carried out among Sri Lankan flight attendants. All flight attendants undergoing their annual health and first aid training were invited to participate. Flight attendants who flew continuously for a six-month period prior to data collection were included in the study sample. Recall history of injuries for a period of six months was recorded. Results: The study sample consisted of 98 (30.4%) male and 224 (69.6%) female flight attendants. The mean age of the study sample was 31 years (SD=8) and the average duration of service was 10 years (SD=7). A total of 100 onboard falls, slips or trips in the previous six months were reported by 52 (16.1%) respondents. Of the total sample, 128 (39.8%) cabin crew members reported an injury in the six months preceding the study. This represents a total injury incidence of 795 per 1000 person years. The leading causes of injury was pulling, pushing or lifting (60.2%). The commonest type of injuries were strains and sprains (52.3%). Turbulence related injuries were reported by 38 (29.7%) flight attendants. The upper limbs (44.5%) and the back (32%) were the commonest sites affected. After controlling for other factors, female flight attendants had 2.9 times higher risk (95% CI 1.2-7.2) of sustaining and injury than males. Irrespective of sex, body weight less than 56 kilograms (OR 2.9, 95% CI 1.4-5.8) and less than seven years of on board experience (OR 10.5, 95% CI 3.6-31.0) were associated with higher risk of injury. Conclusions: Work related injury is a major occupational hazard to flight attendants. Appropriate preventive strategies are required to minimize them.

The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens

Linbo Wang — 2009-07-11T00:00:00Z

Background: Preoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR) of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods: 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide), VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide) and EFC (epirubicin+5-fluorouracil+cyclophosphamide) were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results: There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p<0.05). HER2 expression is significantly associated with increased PR in DEC regimen (p<0.05), but not predictive for PR in EFC and VFC groups. No significant correlation was found between biomarkers PgR, Topo-II, P-gp, MRP or GST-pi and PR to any tested PCT regimen. After adjusted by a stratification variable of ER or HER2, DEC regimen was more effective in inducing PR in comparison with VFC and EFC regimens. Conclusions: ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

Patent arterial duct

Jonathan Forsey — 2009-07-10T00:00:00Z

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation secondary to a left-to-right shunt must be excluded. Coronary, systemic and pulmonary arteriovenous fistula, peripheral pulmonary stenosis and ventricular septal defect with aortic regurgitation and collateral vessels must be differentiated from PAD on echocardiogram. In preterm infants with symptomatic heart failure secondary to PAD, treatment may be achieved by surgical ligation or with medical therapy blocking prostaglandin synthesis (indomethacin or ibuprofen). Transcatheter closure of the duct is usually indicated in older children. PAD in preterm and low birth weight infants is associated with significant co-morbidity and mortality due to haemodynamic instability. Asymptomatic patients with a small duct have a normal vital prognosis but have a lifetime risk of endocarditis. Patients with moderate-to-large ducts with significant haemodynamic alterations may develop irreversible changes to pulmonary vascularity and pulmonary hypertension.

A review of injury epidemiology in the UK and Europe: some methodological considerations in constructing rates

Roxana Alexandrescu — 2009-07-10T00:00:00Z

Background: Serious injuries have been stated as a public health priority in the UK. However, there appears to be a lack of information on population-based rates of serious injury (as defined by a recognised taxonomy of injury severity) at national level from either official statistics or research papers. We aim to address this through a search and review of literature primarily focused within the UK and Europe. Methods: The review summarizes research papers on the subject of population based injury epidemiology published from 1970 to 2008. We examined critically methodological approaches in measuring injury incident rates including data sources, description of the injury pyramid, matching numerator and denominator populations as well as the relationship between injury and socioeconomic status. Results: National representative rates come from research papers using official statistics sources, often focusing on mortality data alone. Few studies present data from the perspective of an injury pyramid or using a standardized measure of injury severity, i.e. Injury Severity Score (ISS). The population movement that may result in a possible numerator - denominator mismatch has been acknowledged in five research studies and in official statistics. The epidemiological profile shows over the past decades in UK and Europe a decrease in injury death rates. No major trauma population based rates are available within well defined populations across UK over recent time periods. Both fatal and non-fatal injury rates occurred more frequently in males than females with higher rates in males up to 65 years, then in females over 65 years. Road traffic collisions and falls are predominant injury mechanisms. Whereas a straightforward inverse association between injury death rates and socio-economic status has been observed, the evidence of socioeconomic inequalities in non-fatal injuries rates has not been wholly consistent. Conclusions: New methodological approaches should be developed to deal with the study design inconsistencies and the knowledge gaps identified across this review. Trauma registries contain injury data from hospitals within larger regions and code injury by Abbreviated Injury Scale enabling information on severity; these may be reliable data sources to improve understanding of injury epidemiology.

Complexity, cofactors, and the failure of AIDS policy in Africa

Eileen Stillwaggon — 2009-07-10T00:00:00Z

Global AIDS policy still treats HIV as an exceptional case, abstracting from the context in which infection occurs. Policy is based on a simplistic theory of HIV causation, and evaluated using outdated tools of health economics. Recent calls for a health systems strategy - preventing and treating HIV within a programme of comprehensive health care - have not yet influenced the silo approach of AIDS policy.Evidence continues to accumulate, showing that multiple factors, such as malnutrition, malaria and helminthes, increase the risk of sexual and vertical transmission of HIV. Moreover, complementary interventions that reduce viral load, improve immune response, and interrupt pathways of transmission could increase the effectiveness of antiretroviral drugs and other tools of AIDS policy.In health economics, the omission of estimates of increasing returns generated by disease or treatment synergies biases cost-effectiveness analysis against multiple, yet inexpensive, interventions. Current tools of cost-effectiveness analysis only identify local maxima in a complex landscape, and can play, at best, a marginal role in the epidemic, especially where it is already generalized.Cost-effectiveness analyses for HIV that are based on the wrong epidemiological model can generate Type III errors: we get precise answers to the wrong questions about how to intervene. To control the epidemic, AIDS policy needs to utilize an epidemiological model that reflects the interactions of biological as well as behavioural variables that determine the course of HIV epidemics around the world. Cost-effectiveness analysis can benefit from using economic concepts of externalities and increasing returns to incorporate disease interaction and beneficial treatment spillovers for coinfections in HIV-prevention policy.

Ethics of conducting research in conflict settings

Nathan Ford — 2009-07-10T00:00:00Z

Humanitarian agencies are increasingly engaged in research in conflict and post-conflict settings. This is justified by the need to improve the quality of assistance provided in these settings and to collect evidence of the highest standard to inform advocacy and policy change. The instability of conflict-affected areas, and the heightened vulnerability of populations caught in conflict, calls for careful consideration of the research methods employed, the levels of evidence sought, and ethical requirements. Special attention needs to be placed on the feasibility and necessity of doing research in conflict-settings, and the harm-benefit ratio for potential research participants.

Systematic review of economic evaluations of human cell-derived wound care products for the treatment of venous leg and diabetic foot ulcers

Astrid Langer — 2009-07-10T00:00:00Z

Background: Tissue engineering is an emerging field. Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of diabetic foot and venous leg ulcers for both patients and health care systems. However, they frequently are very costly. Based on a systematic review of the literature, this study assesses the cost-effectiveness of these growth factors and tissue-engineered artificial skin for treating chronic wounds. Methods: On the basis of an extensive explorative search, an appropriate algorithm for a systematic database search was developed. The following databases were searched: BIOSIS Previews, CRD databases, Cochrane Library, EconLit, Embase, Medline, and Web of Science. Only completed and published trial- or model-based studies which contained a full economic evaluation of growth factors and bioengineered skin substitutes for the treatment of chronic wounds were included. Two reviewers independently undertook the assessment of study quality. The relevant studies were assessed by a modified version of the Consensus on Health Economic Criteria (CHEC) list and a published checklist for evaluating model-based economic evaluations. Results: Eleven health economic evaluations were included. Three biotechnology products were identified for which topical growth factors or bioengineered skin substitutes for the treatment of chronic leg ulceration were economically assessed: (1) Apligraf(R), a bilayered living human skin equivalent indicated for the treatment of diabetic foot and venous leg ulcers (five studies); (2) Dermagraft(R), a human fibroblast-derived dermal substitute, which is indicated only for use in the treatment of full-thickness diabetic foot ulcers (one study); (3) REGRANEX(R) Gel, a human platelet-derived growth factor for the treatment of deep neuropathic diabetic foot ulcers (five studies). The studies considered in this review were of varying and partly low methodological quality. They calculated that due to shorter treatment periods, fewer complications and fewer inpatient episodes the initial cost of the novel biotechnology products may be offset, making the treatment cost-effective or even cost-saving. The results of most studies were sensitive to initial costs of the products and the evidence of effectiveness. Conclusions: The study results suggest that some growth factors and tissue-engineered artificial skin products feature favourable cost-effectiveness ratios in selected patient groups with chronic wounds. Despite the limitations of the studies considered, it is evident that health care providers and coverage decision makers should take not only the high cost of the biotechnology product but the total cost of care into account when deciding about the appropriate allocation of their financial resources. However, not only the cost-effectiveness but first of all the effectiveness of these novel biotechnology products deserve further research.