Pharmacokinetics of doxorubicin in pregnant women

Purpose

Our objective was to evaluate the pharmacokinetics (PK) of doxorubicin during pregnancy compared to previously published data from non-pregnant subjects.

Methods

During mid- to late-pregnancy, serial blood and urine samples were collected over 72 h from seven women treated with doxorubicin for malignancies. PK parameters were estimated using non-compartmental techniques. Pregnancy parameters were compared to those previously reported non-pregnant subjects.

Results

During pregnancy, mean (±SD) doxorubicin PK parameters utilizing 72 h sampling were: clearance (CL), 412 ± 80 mL/min/m²; steady-state volume of distribution (Vss), 1,132 ± 476 L/m²; and terminal half-life (T_1/2), 40.3 ± 8.9 h. The BSA-adjusted CL was significantly decreased (p < 0.01) and T_1/2 was not different compared to non-pregnant women. Truncating our data to 48 h, PK parameters were: CL, 499 ± 116 ml/min/m²; Vss, 843 ± 391 L/m²; and T_1/2, 24.8 ± 5.9 h. The BSA-adjusted CL in pregnancy compared to non-pregnant data was significantly decreased in 2 of 3 non-pregnant studies (p < 0.05, < 0.05, NS). Vss and T_1/2 were not significantly different.

Conclusions

In pregnant subjects, we observed significantly lower doxorubicin CL in our 72 h and most of our 48 h sampling comparisons with previously reported non-pregnant subjects. However, the parameters were within the range previously reported in smaller studies. At this time, we cannot recommend alternate dosage strategies for pregnant women. Further research is needed to understand the mechanism of doxorubicin pharmacokinetic changes during pregnancy and optimize care for pregnant women.     

Clinical investigation of the interface pressure in the trans-tibial socket with Dermo and Seal-In X5 liner during walking and their effect on patient satisfaction

BACKGROUND: The interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee's satisfaction and comfort. Liners provide a comfortable interface by adding a soft cushion between the residual limb and the socket. The Dermo and the Seal-In X5 liner are two new interface systems and, due to their relative infancy, very little are known about their effect on patient satisfaction. The aim of this study was to compare the interface pressure with these two liners and their effect on patient satisfaction. METHODS: Nine unilateral transtibial amputees participated in the study. Two prostheses were fabricated for each amputee, one with the Seal-In liner and one with the Dermo liner. Interface pressure was measured at the anterior, posterior, medial and lateral regions during walking on the level ground. Each subject filled in a Prosthetic Evaluation Questionnaire (PEQ) regarding the satisfaction with the two liners. Findings The mean peak pressures with the Seal-In liner was 34.0% higher at the anterior, 24.0% higher at the posterior and 7.0% higher at the medial regions of the socket (P=0.008, P=0.046, P=0.025) than it was with the Dermo Liner. There were no significant differences in the mean peak pressures between the two liners at the lateral regions. In addition, significant difference was found between the two liners both for satisfaction and problems (P<0.05). Interpretation There was less interface pressure between the socket and the residual limb with the Dermo liner. The results indicated that the Dermo liner provides more comfort in the socket than the Seal-In liner.     

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study

Background

Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC).

Methods

Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs).

Results

Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24–22.15)], preeclampsia [aOR:7.78 (1.62–37.47)], APH [aOR:3.46 (1.28–9.33)], emergency CS [aOR:2.64 (1.43–4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51–10.10)], LBW [aOR:3.11 (1.04–9.30)] and NICU admission [aOR:4.36 (1.82–10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50–16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31–12.89)], emergency CS [aOR: 2.01 (1.09–3.73] and LGA [aOR: 5.20 (1.07–25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02–11.68), preeclampsia 5.29 (1.03–27.09), and NICU admission [aOR: 2.53 (1.05–6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group.

Conclusion

The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

     

A comparison between size of the occluder device and two-dimensional transoesophageal echocardiographic sizing of the ostium secundum atrial septal defect

Objectives

Transcatheter closure of a secundum atrial septal defect (ASD II) has become an effective alternative for surgical treatment. In this study we evaluated the correlation between the two-dimensional transoesophageal echocardiographic (2D TEE) sizing of ASDs and the actual diameter of occluders in patients undergoing device closure.

Methods

The records of 54 patients who underwent transcatheter ASD closure were reviewed. ASD characteristics and maximum defect diameter were evaluated using preprocedure 2D TEE images. Appropriate device size was determined by the balloon sizing method, which measures the balloon occlusive diameter (BOD) via TEE and fluoroscopy. ASD closure was performed under continuous TEE monitoring using the Amplatzer occluder in all patients.

Results

The mean of the TEE-derived maximum defect diameter was significantly lower than the mean of the BOD (17.8 ± 4.5 vs 22.1 ± 5.1 mm; p < 0.001) and the mean size of the implanted occluder device (17.8 ± 4.5 vs 23.3 ± 5.1 mm; p < 0.001). However, a good correlation was found between the TEE-derived defect size and the BOD (BOD = 0.898 × TEE defect size + 6.212, R = 0.824; p < 0.001) and between the TEE measurement and the final size of the implanted Amplatzer (device size = 0.928 × TEE defect size + 6.853, R = 0.822; p < 0.001).

Conclusions

2D TEE may provide a good equation to predict the BOD or the size of the occluder device; however, further studies are needed to investigate whether it is feasible to perform transcatheter ASD occlusion without balloon sizing.     

Identification of Toxoplasma gondii protein fractions induce immune response against melanoma in mice

Dendritic cells (DCs) play a crucial role in the initiation of adaptive immune responses against tumor cells. We recently found that protein components of Toxoplasma gondii (T. gondii) could mature DCs efficiently. Therefore, in this study, we aimed to find the most effective protein components of T. gondii which are able to mature DCs and consequently instruct immune responses in tumor‐bearing mice. Soluble tachyzoite antigens (STAgs) were fractionated by ammonium sulfate precipitation and subsequently by anion‐exchange HPLC. Immature DCs (iDCs) were treated by these protein fractions and were monitored for IL‐12p70 and IL‐10 production. Moreover, the capacity of mature DCs (mDCs) to induce lymphocyte proliferation was investigated. Ultimately, we analyzed the ability of mDCs in instructing immune responses in tumor‐bearing mice. We found that ammonium sulfate fraction one (A1) matured‐DCs produced higher IL‐12 level and IL‐12/IL‐10 ratio; therefore, this fraction was selected for further fractionation by anion‐exchange HPLC. The results showed that anion‐exchange HPLC fraction 14 (C14) matured‐DCs secrete higher levels of IL‐12p70 and IL‐12p70/IL‐10 ratio. Survival of the mice matured by A1 fraction increased significantly compared to other groups. Moreover, SDS‐PAGE electrophoresis showed that different obtained fractions have distinct proteins based on their size. These results demonstrate that two protein fractions of T. gondii are able to mature DCs more efficient.