Pharmacokinetics of amodiaquine and desethylamodiaquine in pregnant and postpartum women with Plasmodium vivax malaria

In order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and with Plasmodium vivax malaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n = 24) and postpartum (n = 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment of P. vivax infections during pregnancy.     

Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria

Dihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days. Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma dihydroartemisinin and piperaquine concentrations were analyzed by liquid chromatography-mass spectrometry. Piperaquine and dihydroartemisinin pharmacokinetics were well described. There were no significant differences in total piperaquine exposure (P = 0.80) or drug exposure during the terminal elimination phase (72 h to infinity) (P = 0.64) between the two groups. The apparent volume of distribution of piperaquine was significantly smaller (602 liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women (P = 0.0057), and the terminal elimination half-life was significantly shorter (17.8 days versus 25.6 days; P = 0.0023). Dihydroartemisinin exposure after the first dose was significantly lower (844 h × ng/ml versus 1,220 h × ng/ml, P = 0.0021) in pregnant women, but there were no significant differences in total dihydroartemisinin exposure or maximum concentrations between the two groups. There were no significant differences in any pharmacokinetic parameters between the second and third trimester. These results obtained through noncompartmental analysis suggest that in the treatment of falciparum malaria, there are no clinically important differences in the pharmacokinetics of dihydroartemisinin or piperaquine between pregnant and nonpregnant women. However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life.     

The effect of hyperbaric oxygen on apoptosis and proliferation in severe acute pancreatitis

Objectives:

This paper investigates the significance of apoptosis in severe acute pancreatitis (SAP) and the possible modulating effects of hyperbaric oxygen (HBO).

Methods:

Wistar rats (250–350 g) were induced with SAP by biliopancreatic infusion of 4% sodium taurocholate. Rats were randomized for HBO treatment. Pancreatic tissue was stained for apoptosis with immunohistochemistry (anti-CASPASE-3 antibody and TUNEL), and histopathology haematoxylin and eosin (H&E). Acini were stained for proliferation with an anti-KI67 antibody. ImageProPlus was used to quantify apoptosis and proliferation in acinar cells. Statistical analysis was performed with two-independent-sample t-test or non-parametric Mann–Whitney test.

Results:

In normal acini there is a low rate of apoptosis (0.165 ± 0.157%, 0.181 ± 0.168%, 0.130 ± 0.298% in CASPASE-3, H&E and TUNEL, respectively) and proliferation (0.951 ± 0.926%) (mean ± standard deviation [SD]). When compared with normal, apoptosis (CASPASE-3: 1.28 ± 1.12%, P= 0.008; 2.40 ± 3.04%, P= 0.101; 1.23 ± 0.87%, P= 0.091; H&E: 0.47 ± 0.36%, P= 0.051; 0.69 ± 0.63%, P= 0.001; 0.68 ± 0.28%, P= 0; TUNEL: 1.08 ± 1.42%, P= 0; 1.96 ± 1.87%, P= 0; 2.36 ± 2.26%, P= 0) and proliferation (1.96 ± 1.89%, P= 0.187; 1.73 ± 1.76%, P= 0.165; 1.36 ± 1.40%, P= 0.571) were increased on days 1, 2 and 3 post-induction, respectively. In comparison with the untreated controls, HBO increased apoptosis on day 1 (CASPASE-3: 3.11 ± 1.97%, P= 0.04; H&E: 0.97 ± 0.76%, P= 0.005) and day 2 (TUNEL: 3.61 ± 3.05%, P= 0.034). Treatment with HBO increased proliferation (3.04 ± 3.14%, P= 0.519; 7.33 ± 7.55%, P= 0.153) on days 2 and 3, respectively, compared with the untreated controls.

Conclusions:

During SAP, acini apoptosis and proliferation were increased. Hyperbaric oxygen therapy may improve the condition of SAP by promoting apoptosis and proliferation.     

Better reproductive healthcare for women with disabilities: a role for nursing leadership

This paper examines the reproductive healthcare experiences of women with disabilities in the light of commonly accepted principles of biomedical ethics. Recommendations are made for nursing to assume a leadership role in reducing gender and disability inequity in health care.     

Medical physics aspects of cancer care in the Asia Pacific region: 2011 survey results

Background:

Medical physicists are essential members of the radiation oncology team. Given the increasing complexity of radiotherapy delivery, it is important to ensure adequate training and staffing. The aim of the present study was to update a similar survey from 2008 and assess the situation of medical physicists in the large and diverse Asia Pacific region.

Methods:

Between March and July 2011, a survey on profession and practice of radiation oncology medical physicists (ROMPs) in the Asia Pacific region was performed. The survey was sent to senior physicists in 22 countries. Replies were received from countries that collectively represent more than half of the world’s population. The survey questions explored five areas: education, staffing, work patterns including research and teaching, resources available, and job satisfaction.

Results and discussion:

Compared to a data from a similar survey conducted three years ago, the number of medical physicists in participating countries increased by 29% on average. This increase is similar to the increase in the number of linear accelerators, showing that previously identified staff shortages have yet to be substantially addressed. This is also highlighted by the fact that most ROMPs are expected to work overtime often and without adequate compensation. While job satisfaction has stayed similar compared to the previous survey, expectations for education and training have increased somewhat. This is in line with a trend towards certification of ROMPs.

Conclusion:

As organisations such as the International Labour Organization (ILO) start to recognise medical physics as a profession, it is evident that despite some encouraging signs there is still a lot of work required towards establishing an adequately trained and resourced medical physics workforce in the Asia Pacific region.     

Tuberculosis among foreign-born persons, Singapore, 2000-2009

We determined the proportion of foreign-born persons with tuberculosis (TB) in Singapore. This proportion increased from 25.5% in 2004 to 37.6% in 2009. Unskilled workers from countries with high incidences of TB accounted for the highest number of and greatest increase in foreign-born TB case-patients.