Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.     

Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis

OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.     

Serious toxicity associated with continuous nevirapine-based HAART in pregnancy

Objective  This study was designed to determine the safety of nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in a cohort of HIV-positive pregnant women.
Design  This was a prospective cohort study of HIV-positive pregnant women.
Population and setting  All HIV-positive women treated with HAART during pregnancy from January 1997 to February 2004 at the British Columbia (BC) Women's Hospital in Vancouver, BC, Canada.
Methods  Demographic and clinical data were collected to compare antiretroviral drug toxicities in women treated antenatally with NVP-based or non-NVP-based HAART. Multivariate analyses were then used to investigate determinants of toxicity.
Results  From 1997 to 2004, 103 HIV-positive pregnant women received HAART. Equivalent numbers of women were initially treated with NVP-based (54%) and non-NVP-based (46%) HAART. The groups did not differ by clinical or demographic parameters and duration of HAART exposure was similar between groups. Toxicities necessitating treatment discontinuation were observed in 6 of 56 NVP-exposed women (2 cases each of grade 2, 3, and 4 toxicity) compared with 1 of 47 in the non-NVP-exposed women. First time use of NVP approached significance as a predictor for toxicity, with a toxicity rate of 12.5% (6/48) observed among those taking NVP for the first time (adjusted OR 2.68, 95% CI 0.49–14.6).
Conclusion  Continuous NVP use in pregnancy resulted in a relatively higher rate of toxicity, and all cases of NVP toxicity occurred in women exposed to NVP for the first time during pregnancy.     

Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM technology.

OBJECTIVE: To compare MaM technology with current methods of assessing blood pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended that the average of repeated measures is used to confirm hypertension in pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM" mode using the average of at least 3 BP readings 15 seconds apart. This allows rapid assessment of BP. The difference between each measurement is calculated and influences the percentage contribution to the final average reading. We compared MaM with readings taken in a conventional manner. METHODS: Blood pressure was measured in 30 hypertensive pregnant patients recruited from the obstetric day unit of a large teaching hospital. Single BP measurements were taken at 0, 15, 30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with the first single reading, but diastolic BP did not (p = 0.54). The difference between the first MaM and the first single reading was significantly different for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p = 0.39). The mean of all single readings and the first MaM reading were similar for both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p = 0.87). Conclusions: White-coat hypertension exists for systolic BP in the obstetric day unit. The MaM technology allows rapid and accurate characterization of blood pressure equivalent to repeated measures over 90 minutes.     

Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilization. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after 12 and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys.