The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomized breast cancer chemoprevention trial.

BACKGROUND: We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomized breast cancer prevention trial (Decensi A et al (2002) Circulation106 10 1224-8). Here, we investigate the changes in lipids and clotting profile in patients of the same trial. METHODS AND RESULTS: Recent post-menopausal women were randomised to either oral CEE 0.625 mg/day and placebo (n = 55), CEE and fenretinide 200 mg/day (n = 56), transdermal E2 50 mg/day and placebo (n = 59) or E2 and fenretinide 200 mg/day (n = 56). Sequential medroxyprogesterone acetate 10 mg/day was given in each group. After 12 months, there was a statistically significant effect of the route of administration of hormone replacement therapy (HRT) on fibrinogen levels; the median percentage change being -5.7% with CEE and -1.1% with E2 (p = 0.012). Total cholesterol decreased in all arms (p < 0.0001). HDL-C decreased significantly with transdermal E2 (p = 0.006) compared to oral CEE and with fenretinide relative to placebo (p<0.001). Triglycerides exhibited an opposite modulation in the HRT route, with a 21.4% median increase with oral CEE and an 8.6% reduction with transdermal E2 (p < 0.0001). Antithrombin-III showed a 4% borderline significant reduction in the fenretinide arm relative to placebo, irrespective of the HRT administration route (p = 0.055). CONCLUSIONS: Our data indicate that transdermal E2 may be preferable to oral CEE based on its safer cardiovascular risk profile. Fenretinide modified some cardiovascular risk biomarkers and confirmed a safer profile compared to other retinoids.

Labor course and delivery in epidural analgesia: a case-control study.

BACKGROUND: We aimed to establish if epidural analgesia is associated with a higher incidence of operative vaginal delivery, longer duration of labor and more frequent use of oxytocin than labor without analgesia. METHODS: We analyzed a cohort of 207 women with no risk factors who delivered with epidural analgesia in the labor unit of Spedali Civili, Brescia, Italy, during 2001. Length of the first and second stage of labor, mode of delivery, neonatal cord blood pH, neonatal Apgar score and neonatal outcomes were evaluated. RESULTS: Epidural analgesia was performed on request in 6%: in this group (group A) there were 141 (68%) nulliparae and 66 (32%) pluriparae; mean ( +/- standard deviation) gestational age at delivery was 39.4 +/- 1.3 weeks (range: 34.1-41.5 weeks). In this group, 184 (89%) had vaginal delivery and 23 (11%) delivered by Cesarean section. Among controls (group B), 368 (89%) had a vaginal delivery and 46 (11%) delivered by Cesarean section; vacuum extraction was used in 18 deliveries (9%) in group A and in 13 deliveries (3%) in group B. The duration of the second stage of spontaneous labor in the nulliparae of group A was significantly longer than in group B. No statistically significant differences were found between mean umbilical artery pH values of groups A and B. CONCLUSION: Our results confirm that epidural analgesia does not affect the rate of Cesarean delivery, while increasing the use of oxytocin augmentation, the duration of the second stage of labor and the rate of instrumental vaginal delivery.

[Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A comparison between two clinical protocols]. / Monitoraggio della gravidanza complicata da isoimmunizzazione materno-fetale. Due protocolli clinici a confronto.

AIM: Invasive techniques such as amniocentesis and cordocentesis are used for the diagnosis and treatment of fetus at risk for anemia due to maternal red-cell alloimmunization. The purpose of this study was to determine the value of non invasive measurements of the peak velocity middle cerebral artery in the fetus (PVMCA) for the diagnosis of fetal anemia. METHODS: From 1996 to September 2002, we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women (from 1996 to 1999) fetal anemia was detected by invasive techniques (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to 2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was significantly increased, cordocentesis was performed in order to rule out fetal anemia and to provide in utero transfusions. RESULTS: In the 1(st) period we performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11 women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we performed only 2 cordocentesis in women in which PVMCA was increased; the blood sampling confirmed fetal anemia in both cases. CONCLUSION: PVMCA and fetal hematocrit are highly significantly correlated: high values of PVMCA are associated with fetal anemia. Doppler velocity of PVMCA is related to fetal anemia with positive predictive value 100% and negative predictive value 100%. The middle cerebral artery blood velocity is a non invasive technique for detecting anemia in pregnancies complicated by alloimmunization.

Penetration of pefloxacin into cerebrospinal fluid of patients with meningitis.

We evaluated the diffusion of pefloxacin into the cerebrospinal fluid (CSF) in 15 patients with bacterial meningitis or ventriculitis, 14 of whom were treated with other antibiotics. Three doses of pefloxacin were administered at 12-h intervals to 11 patients intravenously and to 4 patients orally. Individual doses were 7.5 mg/kg in seven patients and 15 mg/kg in eight patients. Plasma and CSF levels were determined by a high-performance liquid chromatographic assay. The concentrations of pefloxacin in CSF were measured 2 h after the third intravenous dose and 4 h after the third oral dose. In patients receiving 7.5 mg/kg, peak levels in plasma ranged from 6.8 to 16 micrograms/ml, and trough levels were from 2 to 7.5 micrograms/ml. Concentrations in CSF ranged from 2.4 to 9 micrograms/ml. In patients receiving 15 mg/kg, peak levels in plasma ranged from 14 to 18.6 micrograms/ml, and trough levels were from 4 to 13.2 micrograms/ml. Concentrations in CSF ranged from 6.5 to 13 micrograms/ml. These preliminary data indicate that pefloxacin diffuses well into the CSF of patients with inflamed meninges.

Pefloxacin in rabbits: protein binding, extravascular diffusion, urinary excretion and bactericidal effect in experimental endocarditis.

The serum protein binding, extravascular diffusion and urinary excretion of pefloxacin were studied in rabbits. The effect of furosemide on the urinary excretion of pefloxacin was investigated. In an experimental model of Escherichia coli endocarditis, diffusion into heart valves and infected vegetations and bactericidal effect of pefloxacin were also studied. We observed a serum protein binding of 25%. Extravascular concentrations found were within the range of the minimal inhibitory concentrations for most susceptible strains. Pefloxacin appeared to be reabsorbed by renal tubules (fractional excretion: 61 +/- 21%). Furosemide significantly increased the renal excretion of pefloxacin through a tubular process. We observed a good penetration of pefloxacin into normal heart valves and infected vegetations. Pefloxacin reduced the colony counts in infected vegetations after seven im injections of the drug (given as 15 mg/kg/12 h).