Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 μg/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 ± 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.     

Induction of Suicidal Erythrocyte Death by Cantharidin

The natural phosphoprotein phosphatase inhibitor cantharidin, primarily used for topical treatment of warts, has later been shown to trigger tumor cell apoptosis and is thus considered for the treatment of malignancy. Similar to apoptosis of tumor cells, erythrocytes may undergo eryptosis, a suicidal cell death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide, oxidative stress and dysregulation of several kinases. Phosphatidylserine abundance at the erythrocyte surface was quantified utilizing annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide from antibody binding, and reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. A 48 h treatment of human erythrocytes with cantharidin significantly increased the percentage of annexin-V-binding cells (≥10 μg/mL), significantly decreased forward scatter (≥25 μg/mL), significantly increased [Ca²⁺]_i (≥25 μg/mL), but did not significantly modify ceramide abundance or ROS. The up-regulation of annexin-V-binding following cantharidin treatment was not significantly blunted by removal of extracellular Ca²⁺ but was abolished by kinase inhibitor staurosporine (1 μM) and slightly decreased by p38 inhibitor skepinone (2 μM). Exposure of erythrocytes to cantharidin triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect sensitive to kinase inhibitors staurosporine and skepinone.     

3D Non-Fluoroscopic Cryoablation of Right-Sided Accessory Pathways in Children: Monocentric Study and Literature Review

Background: Cryoablation of accessory pathways (APs) is effective and very safe in children, as previously reported by our group. The aim of this retrospective study was to evaluate the current efficacy of 3D non-fluoroscopic cryoablation of right sided APs in children, comparing results obtained with the Ensite Velocity^TM and the more recent Ensite Precision^TM 3D mapping systems. Methods and Results: From January 2016 to December 2019, 102 pediatric patients [mean age 12.5 ± 2.8, 62 males (61% of total cohort)] with right APs underwent 3D non-fluoroscopic transcatheter cryoablation at our Institution. Fifteen (14.7%) patients had previously undergone catheter ablation. Acute procedural success rate was 95.1% (n = 97). No significant differences were detected in acute success rates achieved with Ensite Velocity^TM or Ensite PrecisionTM systems nor between manifest (94%) and concealed APs (100%). No permanent complications occurred. During follow-up (428 ± 286 days, median 396 days [interquartile range 179-713]), 19 patients (19.6%) had recurrences. Recurrences were more frequent for parahissian/anterior APs compared to midseptal/posterior and lateral APs (p = 0.043). Recurrences were not related to the Ensite system used. A redo ablation procedure was attempted in 13 cases, 11 cryoablation and 2 radiofrequency ablations: the former was successful in 10 cases out of 11 (90.9%). Conclusion: 3D cryoablation of right-sided APs is associated with a very high acute success rate with limited use of fluoroscopy, resulting in great benefit to the children. Recurrence rates are not high and patients can be retreated with cryo-energy with higher success rates.     

Incidence of Posterior Vessel Wall Puncture During Ultrasound‐guided Vessel Cannulation in a Simulated Model

Objectives: The incidence of posterior vessel wall puncture (PVWP) during central line placement with possible subsequent injury to structures lying behind the vein is unknown. At times the internal jugular vein lies immediately anterior to the carotid artery rather than lateral to it, leading to potential arterial puncture should the needle pass through the vein completely. The objective of this study is to evaluate the incidence of PVWP during simulated ultrasound (US)‐guided vessel cannulation. Methods: Enrolled subjects were emergency medicine resident and attending physicians. Subjects performed US‐guided venous access on simulated blood vessels within gelatin‐based US phantoms. While blinded to the purpose of the study, each subject performed successful cannulation of the vessel on separate phantoms, with wire placement confirmed by expert review of a follow‐up US. Each phantom was subsequently deconstructed to manually inspect for PVWP. Results: Thirty‐five subjects with a range of experience in the technique participated, each performing both transverse and long‐axis approaches for a total of 70 cannulations. The overall incidence of PVWP was 34% (95% confidence interval [CI] = 22.9% to 45.1%). Conclusions: This study found a high incidence of inadvertent PVWP during simulated US‐guided vessel cannulation in this model. ACADEMIC EMERGENCY MEDICINE 2010; 17:1138–1141 © 2010 by the Society for Academic Emergency Medicine     

Effect of center- versus patient-specific factors on variations in dialysis adequacy

Efforts to improve the delivery of hemodialysis have focused mostly on identifying patient-related factors that lead to inadequate dialysis. Less consideration has been given to the impact of the dialysis center on adequacy. This study evaluated whether the dialysis facility or individual-level factors were the primary influence on variations in dialysis adequacy. This was a retrospective analysis of 4971 hemodialysis patients in 189 centers with urea reduction ratio (URR) values obtained in the final quarter of 1997. The between-center variation and the within-center correlation in URR values were quantified to determine the contribution of a center effect on variations in adequacy; furthermore, the proportion of variance attributable to the centers' effect and individual-level dialysis covariates were compared. There was a wider between-center variation in mean URR values (SD, 4.8%) than expected if there were no center effect (SD, 2.5%). There was a strong within-center correlation in URR values, measured by the parameter rho, which was only minimally diminished after adjusting for individual-level covariates (adjusted rho, 0.14; P < 0.0001). The variation in URR attributable to the center effect, quantified by R(2), was greater than that related to individual-level dialysis factors (facility- and individual-level dialysis covariates R(2), 23.6 and 11.3%, respectively). Initiatives to improve the delivery of dialysis in patients with end-stage renal disease should be directed at facility policies governing dialysis care, along with patient-specific problems, because center effects have a major influence on dialysis adequacy.