Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot.

OBJECTIVE: Kaolin-based activated clotting time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combined with aprotinin during cardiopulmonary bypass (CPB). However, aprotinin is known to prolong not only celite-based but also kaolin-based activated clotting time. Overestimation of activated clotting times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel 'aprotinin-insensitive' activated clotting time test has been developed for the SONOCLOT analyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin. METHODS: Blood samples were taken from 44 elective cardiac surgery patients at the following measurement time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60 min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement time point, activated clotting time was assessed with HkACT and SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson's correlation, and ANOVA with post hoc Bonferroni-Dunn correction. RESULTS: Monitoring anticoagulation with SaiACT showed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean+/-SD) were 44+/-118 s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4-T6; 89+/-152 s, P=0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r2=0.473 and 0.487, respectively; P=0.794), but was lower for HkACT after aprotinin administration (r2=0.481 and 0.361, respectively; P=0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACT and HkACT. CONCLUSIONS: The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotinin.     

BLOOD MANAGEMENT: Large‐dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized,controlled trial

BACKGROUND: The objective was to evaluate efficacy and safety of rapid, large‐dose intravenous (IV) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding. STUDY DESIGN AND METHODS: In a randomized, controlled trial, 477 women with anemia, iron deficiency, and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose (≤1000 mg over 15 min, repeated weekly to achieve a total calculated replacement dose) or 325 mg of ferrous sulfate (65 mg elemental iron) prescribed orally thrice daily for 6 weeks. RESULTS: Compared to those assigned to ferrous sulfate, more patients assigned to ferric carboxymaltose responded with a hemoglobin (Hb) increase of 2.0 g/dL or more (82% vs. 62%, 95% confidence interval for treatment difference 12.2‐28.3, p < 0.001), more achieved a 3.0 g/dL or more increase (53% vs. 36%, p < 0.001), and more achieved correction (Hb ≥ 12 g/dL) of anemia (73% vs. 50%, p < 0.001). Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue (p < 0.05). There were no serious adverse drug events. CONCLUSIONS: In patients with iron deficiency anemia due to heavy uterine bleeding, rapid IV administration of large doses of a new iron agent, ferric carboxymaltose, is more effective than oral iron therapy in correcting anemia, replenishing iron stores, and improving quality of life.     

Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery

The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an "activated" phenotype, consisting of CD30, HLA-DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human recombinant cytokines in pharmacologic doses (2 granulocyte-macrophage colony stimulating factor, 1 inter-leukin-3). Three patients in this series also received human recombinant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human recombinant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.     

Effects of S20749, a Close Analogue of Sumatriptan,on Porcine Carotid Haemodynamics and Human Isolated Coronary Artery

Abstract: Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT_1D receptor agonists, have the ability to constrict porcine arteriovenous anastomoses. Sumatriptan also constricts the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of S20749 (1-[2-(dimethylamino)ethyl]-naphthalene-7-methylsulfonamide), a close analogue of sumatriptan. S20749 (30, 100 , 300 and 1000 μg · kg^?1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was moderately increased. These changes were statistically significant with the highest two doses. S20749 moderately constricted the human isolated coronary artery (pD₂: ≤4.5; E_max: >11% of the contraction to 100 mM K⁺). The above results suggest that S20749 should be able to abort migraine headaches in patients.     

Spread of acetylcholine sensitivity in the neocortex following lesion of the nucleus basalis

Neuronal responses to the iontophoretic application of acetylcholine, carbachol and nicotine were studied in rats, 2 or 3 weeks following bilateral lesions of the nucleus basalis region, and compared to those obtained in normal animals. The percentage of cortical neurons excited by acetylcholine and their individual sensitivity were higher in lesioned animals. Furthermore, the laminar distribution of the responses to acetylcholine and the proportion of responses to carbachol and nicotine were also modified.     

Endothelial expression of intercellular adhesion molecule (ICAM-1) is unaffected by marrow aplasia-inducing chemotherapy

Sequential skin biopsies were obtained from five patients receiving chemotherapy for acute myelocytic leukemia. The first specimen was taken on the fourth day of initial chemotherapy and subsequent specimens were obtained at weekly intervals thereafter, until discharge. In all cases, clinically normal skin was selected as the biopsy site. A panel of monoclonal antibodies was applied to frozen tissue sections, including anti-intercellular adhesion molecule-1 (ICAM-1), anti-lymphocyte function-associated antigen-1 (LFA-1), and anti-HLA-DR. Bound antibody was detected using the avidin-biotin complex method. Endothelial cell expression of ICAM-1 and lymphocyte expression of LFA-1 were unaffected over the course of the ensuing, profound marrow aplasia. This finding suggests that this mechanism of lymphocyte trafficking in the skin remains operational despite the administration of antileukemic agents.