MDR1 gene expression and drug resistance of AML cells

We investigated the cellular drug resistance to aclarubicin (Acla), cytosine arabinoside (Ara-C), daunorubicin (Dau), doxorubicin (Dox), etoposide (Etop) and mitoxantrone (Mitox) using the MTT assay at time of disease presentation in 93 cases of acute myeloid leukaemia (AML). In 31 cases we concomitantly investigated MDR1 (multiple drug resistance 1 gene) expression (semi-quantitative competitive RT-PCR) of the leukaemic cells. Drug resistance towards Dau, Dox and Etop was correlated to the MDR1 expression of the AML cells ( P  < 0.05) with high MDR1 expression being associated with high drug resistance towards these drugs. Although the data did not allow firm conclusions to be drawn on the correlation between MDR1 expression and drug resistance towards Ara-C and Mitox, the drug resistance towards Acla clearly was not correlated to, or dependent on, the MDR1 expression level of the AML blast cells. In addition, when examining the cross-activities among the six drugs distinct patterns emerged. Thus, high to very high degrees of cross-activity were found to exist between Dau, Dox, Etop and Mitox, whereas Ara-C had moderate cross-activity with the other drugs except Acla, which showed absent to moderate cross-activity with the other drugs. We conclude that MDR1 gene expression is of significance for cellular drug resistance towards specific (MDR1-related) drugs in AML, whereas it is not of significance regarding drug resistance towards other drugs, which is the case with the anthracycline Acla. We suggest that in the place of other more or less complicated ways to circumvent MDR1-mediated drug resistance, Acla may be used to replace Dau, Dox and other MDR1-related drugs if proven as potent as the drug it is to substitute.     

International Aid and Natural Disasters: A Pre- and Post-Earthquake Longitudinal Study of the Healthcare Infrastructure in Leogane,Haiti

The reconstruction of healthcare systems in developing countries after natural disasters is poorly understood. Using data collected before and after the 2010 Haiti earthquake, we detail the response of aid agencies and their interaction with local healthcare providers in Leogane, the city closest to the epicenter. We find that the period after the earthquake was associated with an increase in the total number of healthcare facilities, inpatient beds, and surgical facilities and that international aid has been a driving force behind this recovery. Aid has funded 12 of 13 new healthcare facilities that have opened since the earthquake as well as the reconstruction of 7 of 8 healthcare facilities that have been rebuilt. Despite increases in free, aid-financed healthcare, private Haitian healthcare facilities have remained at a constant number. The planned phase-out of several aid-financed facilities, however, will leave Leogane with fewer inpatient beds and healthcare services compared with the pre-earthquake period.     

Short uncemented stems allow greater femoral flexibility and may reduce peri-prosthetic fracture risk: a dry bone and cadaveric study

BackgroundShort femoral stems for uncemented total hip arthroplasty have been introduced as a safe alternative to traditional longer stem designs. However, there has been little biomechanical examination of the effects of stem length on complications of surgery. This study aims to examine the effect of femoral stem length on torsional resistance to peri-prosthetic fracture.ResultsSynthetic femora implanted with short stems fractured at a significantly higher torque (27.1 vs. 24.2 Nm, p = 0.03) and angle (30.3° vs. 22.3°, p = 0.002) than those implanted with long stems. Fracture patterns of the two groups were different, but showed remarkable consistency within each group. These characteristic fracture patterns were closely replicated in the pair of cadaveric femora.ConclusionsThis new short-stemmed press-fit femoral component allows more femoral flexibility and confers a higher resistance to peri-prosthetic fracture from torsional forces than long stems.     

Correlates of HIV Testing Refusal Among Emergency Department Patients in the Opt-Out Testing Era

Opt-out HIV screening is recommended by the CDC for patients in all healthcare settings. We examined correlates of HIV testing refusal among urban emergency department (ED) patients. Confidential free HIV screening was offered to 32,633 ED patients in an urban tertiary care facility in Washington, DC, during May 2007–December 2011. Demographic differences in testing refusals were examined using χ² tests and generalized linear models. HIV testing refusal rates were 47.7 % 95 % CI (46.7–48.7), 11.7 % (11.0–12.4), 10.7 % (10.0–11.4), 16.9 % (15.9–17.9) and 26.9 % (25.6–28.2) in 2007, 2008, 2009, 2010 and 2011 respectively. Persons 33–54 years of age [adjusted prevalence ratio (APR) 1.42, (1.36–1.48)] and those ≥55 years [APR 1.39 (1.31–1.47)], versus 33–54 years; and females versus males [APR 1.07 (1.02–1.11)] were more likely to refuse testing. Opt-out HIV testing is feasible and sustainable in urban ED settings. Efforts are needed to encourage testing among older patients and women.