Comparison of heparin administration using the Rapidpoint Coag and Hepcon HMS

A retrospective chart review was conducted of patients who underwent cardiopulmonary bypass (CPB) to compare the quantities of heparin administered, postoperative blood loss, and homologous blood products transfused during their procedure and subsequent stay in the intensive care unit. The primary purpose of this review was to determine if any difference in heparin administration resulted when two different devices were used for dosing and monitoring heparin. Postoperative blood loss and amount of blood products transfused were also quantified, as any differences would potentially be a result of a difference in administration of heparin. The first group (n = 341) underwent CPB using the Hepcon HMS, Medtronic Inc., Minneapolis, MN, for heparin dosing and monitoring. The Rapid Point Coag, Bayer Healthcare LLC, Tarrytown, NY was used for the second group (n = 345). The two populations were compared for similarity on: age, body surface area (BSA), CPB time (minutes), aortic-cross clamp time (minutes), baseline activated clotting time, and baseline hematocrit. No significant difference was found between the two groups. The second group, using the Rapidpoint Coag, received less heparin during CPB than the group using the Hepcon HMS. In addition, there were decreases in amounts of some blood products transfused as well as mediastinal drainage from the Hepcon HMS to the Rapidpoint Coag group. A summary of the findings can be found in Table 1. A secondary purpose of this study was to determine the influence of hemodilution on the Heparin Management Test (HMT). Citrated whole blood was diluted to varying degrees at various concentrations to determine whether hemodilution with crystalloid would alter the HMT measurements. At all heparin levels and degrees of dilution, the HMT remained stable, with coefficients of variation (CV) of less than 5% at all heparin levels even while incorporating excessive crystalloid dilution (up to 75%).     

Synthesis and anti-tubulin activity of a 3'-(4-azidophenyl)-3'-dephenylpaclitaxel photoaffinity probe

The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopure side chain precursor to 7-TES-baccatin III and subsequent silyl ether deprotection afforded 3'-(4-azidophenyl)-3'-dephenylpaclitaxel, which was shown to be as active as paclitaxel in tubulin assembly and cytotoxicity assays.     

Evidence for zolpidem-induced hyperphagia, but not anxiolysis, in a successive negative contrast paradigm

Zolpidem is an imidazopyridine which binds to certain benzodiazepine receptor types with varying degrees of affinity. The effect of zolpidem on successive negative contrast was investigated in three experiments. In each experiment, a contrast group was given brief access to 32% sucrose for 10 days, then shifted to 4% sucrose for 2 days; a procedure that elicits anxiety primarily on the second postshift day. One control group was given only 4% sucrose. Experiments 2 and 3 included a 2% sucrose group as an intake rate-dependent control. In Experiment 1, zolpidem (4.0 and 0.5 mg/kg) dose-dependently reduced contrast on the two postshift days. Contrast occurred during the first postshift consummatory burst. Zolpidem prolonged the first postshift burst equally in both shifted and unshifted groups, suggesting a general facilitation of intake masked by a ceiling effect in controls. In Experiment 2, zolpidem's (4.0 mg/kg) anti-contrast action was equivalent to its hyperphagic effect in the 2% control group. Zolpidem prolonged the first postshift burst equally in all three groups, again consistent with general intake facilitation. In Experiment 3, 8.0 mg/kg zolpidem produced an anti-contrast effect not present in 2% controls on both postshift days. This does not appear attributable to anxiolysis, however, as the effect was equivalent during stressful and non-stressful phases of the postshift period, and zolpidem extended the duration of the first postshift burst equally in all three sucrose groups. Thus, unlike benzodiazepines, zolpidem is not anxiolytic in this paradigm.     

Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies

Purpose To determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid tumors and to describe any preliminary antitumor activity associated with this regimen.Materials and methods Patients received combination therapy with ZD9331 as a 30-min infusion on days 1 and 8 of a 21-day cycle at doses of 100 or 130 mg/m², followed by cisplatin at 50 or 75 mg/m² as a 30- to 60-min infusion on day 1 only.Results A total of 16 patients received 59 cycles of ZD9331 and cisplatin. Patients were enrolled at three dose levels: ZD9331/cisplatin 100/50 (n=3), 130/50 (n=9), 130/75 (n=4). DLTs at 130/75 included thrombocytopenia, neutropenia, fatigue, nausea, vomiting and stomatitis. Among 15 evaluable patients, 2 showed a partial response (patients with mesothelioma and head and neck cancer) and 6 showed stable disease (for a median of 5.5 cycles).Conclusions ZD9331 in combination with cisplatin was well tolerated at a dose of 130/50 mg/m² after establishing the principal DLTs of neutropenia and thrombocytopenia. The combination shows evidence of antitumor activity in a pretreated population.This work was supported by a grant from AstraZeneca.     

Basal ganglia activity remains elevated after movement in focal hand dystonia

Although previous studies of focal hand dystonia have detected cortical sensorimotor abnormalities, little is known about the role of the basal ganglia in this disorder. We report here that when focal hand dystonic patients performed finger-tapping tasks, functional magnetic resonance imaging showed persisting elevations of basal ganglia activity after the tasks ended. We posit that inhibitory control of the basal ganglia may be faulty in focal hand dystonia, and that the increases we observe in "resting" activity may mask basal ganglia abnormalities in standard imaging contrast analyses.     

Depleted and natural uranium: chemistry and toxicological effects

Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium is comprised of three radioactive isotopes: (238)U, (235)U, and (234)U. This enrichment process reduces the radioactivity of DU to roughly 30% of that of natural uranium. Nonmilitary uses of DU include counterweights in airplanes, shields against radiation in medical radiotherapy units and transport of radioactive isotopes. DU has also been used during wartime in heavy tank armor, armor-piercing bullets, and missiles, due to its desirable chemical properties coupled with its decreased radioactivity. DU weapons are used unreservedly by the armed forces. Chemically and toxicologically, DU behaves similarly to natural uranium metal. Although the effects of DU on human health are not easily discerned, they may be produced by both its chemical and radiological properties. DU can be toxic to many bodily systems, as presented in this review. Most importantly, normal functioning of the kidney, brain, liver, and heart can be affected by DU exposure. Numerous other systems can also be affected by DU exposure, and these are also reviewed. Despite the prevalence of DU usage in many applications, limited data exist regarding the toxicological consequences on human health. This review focuses on the chemistry, pharmacokinetics, and toxicological effects of depleted and natural uranium on several systems in the mammalian body. A section on risk assessment concludes the review.     

New molecular targets in melanoma

Metastatic melanoma remains a disease with few therapeutic options and no regimen that prolongs survival. Peptide and whole-cell vaccines that use cell surface proteins unique to melanoma to engender a specific immune response have not been associated with significant antitumor activity in patients with unresectable metastatic disease. The commonly used chemotherapeutic agents have limited efficacy and do not capitalize on abnormalities that are unique to melanoma [1]. Therapies that target the molecular pathophysiology of metastatic melanoma provide hope that more effective treatments will soon be available.