Erythropoiesis: Short Report: Translation of Analysis Results between Serum Ferritin Assays, Ferritin RIA AmershamTM and Abbott AxSYMTM Ferritin

The serum ferritin assays, Ferritin RIA Amersham(TM) and Abbott AxSYM(TM) Ferritin were compared in order to translate values from one assay to the other. Serum ferritin was analysed with both assays in 102 samples. Logarithmic transformation of the results was performed in order to stabilize the variance. The relationship between the untransformed values was most exactly expressed by a proportionality: AxSYM Ferritin = 0.873 * RIA Ferritin. Due to this proportionality, the numerical difference between the assays increases with the ferritin concentration, although the percentage difference between the assays remains constant.     

A POSTOPERATIVE PROGNOSTIC NOMOGRAM FOR RENAL CELL CARCINOMA

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.     

Limited value of the urinary phenytoin metabolic ratio for the assessment of cytochrome P4502C9 activity in vivo

Relationships between the ratio of p -hydroxyphenytoin (p-HPPH), the major metabolite of phenytoin, to unchanged phenytoin excreted in urine (the urinary metabolic ratio or MR) were compared with a number of indices of the metabolic clearances of phenytoin and tolbutamide published previously for seventeen subjects separately administered these known cytochrome P4502C9 (CYP2C9) substrates. Significant correlations ( r _s=0.50–0.60, P <0.05) were observed between the phenytoin MR, derived from either 0–24 or 24–48  h urine collections, and inverse areas under the plasma unbound concentration-time curves (measured over various time intervals) of phenytoin and with plasma unbound tolbutamide clearance. Significant correlations ( r _s =0.59–0.74) were also observed between the phenytoin MRs and metabolic unbound clearances for p -hydroxyphenytoin formation. Despite the significant correlations, variability in tolbutamide and phenytoin metabolic clearance parameters tended to account for <50% of the variability in phenytoin MR. Correlations between the renal clearance of phenytoin and the phenytoin MRs suggest that variability in the renal clearance of unchanged drug limits the usefulness of the phenytoin MR for the investigation of factors influencing CYP2C9 activity in vivo .     

Structural Requirements for the Direct and Cytochrome P450-dependent Reaction of Cyclic α,β-Unsaturated Carbonyl Compounds with Glutathione: a Study with Coumarin and Related Compounds

Abstract— The interaction of glutathione (GSH) with coumarin, or one of a series of compounds related to coumarin, was assessed in the absence and presence of liver microsomes (direct reaction and indirect reaction, respectively) to determine the structural requirements for direct and mono-oxygenase-mediated reaction of cyclic α,β-unsaturated carbonyls with GSH. Acrolein was used as a positive control for the direct reaction, and produced complete or nearly complete depletion of GSH under all assay conditions. 5,6-Dihydro-2H-pyran-2-one and 2-cyclohexen-1-one also produced substantial depletion of GSH in the direct reaction, which was not increased by the addition of liver microsomes. Coumarin, 2H-pyran-2-one and precocene I (a substituted pyran lacking the 2-one structure) were not substrates for the direct reaction but did cause depletion of GSH when incubated in the presence of rat or human liver microsomes. These depletions were dependent on a functioning mono-oxygenase system as judged by the effects of omission of cofactors, addition of competitive or inactivating inhibitors of cytochrome P450, and induction. Dihydrocoumarin, ?-valerolactone, cyclohexanone and 4H-pyran-4-one were not substrates for either the direct or indirect reaction. These findings are rationalized on the basis of a direct nucleophilic attack of GSH on the α,β-centre of the α,β-unsaturated carbonyl compounds, which is hindered by benzenoid resonance in coumarin and 2H-pyran-2-one, for which enzyme-mediated reaction with GSH, probably via a 3,4-epoxide, is the favoured mechanism.     

Anesthesia for videoscopic left cardiac sympathetic denervation in children with congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia – a case series

Objective: To describe our experience in the anesthetic management of pediatric patients who have undergone left cardiac sympathetic denervation (LCSD) for congenital long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Background: Long QT syndrome and CPVT predispose patients to ventricular arrhythmias and sudden death. One treatment option for these patients is LCSD. When these patients present for LCSD or other surgical procedures, anesthetic management is challenging, as many medications may exacerbate QT prolongation. Methods: Retrospective review of the electronic medical records of 22 pediatric patients who underwent LCSD between November 2005 and December 2008. Results: Six patients (27%) received midazolam as a premedication. Eleven patients (50%) underwent inhalation induction with sevoflurane. Eighty‐six percentage received either sevoflurane or isoflurane for maintenance of anesthesia, while the remaining 14% received a propofol infusion. Nine patients (41%) received esmolol infusions intraoperatively, while one patient (4.5%) received a labetalol infusion. Three patients (14%) received lidocaine infusions. No significant cardiac or other events occurred in any of these patients in the perioperative period. Conclusions: Important anesthetic considerations in this population include avoidance of sympathetic stimulation, correction of any abnormal electrolytes, and the immediate availability of a defibrillator and magnesium sulfate to treat arrhythmias. Anxious patients may benefit from premedication to reduce sympathetic tone. We have safely used both volatile agents and propofol for induction and maintenance of anesthesia. In our experience, intraoperative infusions of β‐blockers and lidocaine seem to be helpful in reducing arrhythmogenic potential, especially in patients with profound QT prolongation.     

Turbulent Stresses Downstream of Porcine and Pericardial Aortic Valves Implanted in Pigs

Because late valve-related complications such as hemolysis and thromboembolic events are considered related to flow disturbances caused by the inserted valve, velocity fields downstream of aortic valve prostheses were studied in pigs. Acute hemodynamic evaluation of size 25-mm porcine and pericardial aortic valve prostheses 1 diameter downstream of the valve ring was performed using dynamic three-dimensional visualization of velocity profiles and spatial distribution of turbulence. Point blood velocity signals obtained with a 1-mm hot-film anemometer needle probe were used to compute Reynolds normal stresses (RNS) by calculation of the turbulent velocity energy of the axial velocity component in the systole. The porcine valves caused a skewed velocity and turbulence profile revealing mean spatial systolic RNS at 70 nm-2 +/- 35 nm-2 (+/- SD). The spatial maximum RNS was 275 +/- 139 nm-2. Corresponding values for the pericardial valves were 20 +/- 11 nm-2 and 72 +/- 46 nm-2. The pericardial valves revealed plug-shaped velocity profiles and turbulent profiles with slightly higher RNS values at the stent posts. From a hemodynamic point of view, these acute studies indicate superiority of the pericardial valves compared to the porcine valves. The turbulent stresses found in this study are of a magnitude that may cause blood corpuscular and endothelial damage.