Analysis of carboplatin dosing in patients with a glomerular filtration rate greater than 125 mL/min: To cap or not to cap? A retrospective analysis and review.

The use of the Calvert formula to calculate carboplatin doses allows clinicians to achieve the appropriate carboplatin area under the concentration (AUC) curve. Thrombocytopenia is the dose limiting toxicity of carboplatin and optimizing AUC minimizes the risk of thrombocytopenia. Carboplatin clearance directly correlates with glomerular filtration rate (GFR) and, therefore, an accurate estimation of the renal function is needed. The Calvert formula was designed using the GFR measured by 51Cr-EDTA; however, many clinicians substitute estimated creatinine clearance (CrCl) as calculated by the Cockcroft-Gault (C-G) equation. The potential for overestimating AUC occurs when clinicians substitute actual weight in obese patients or use a low serum creatinine when calculating C-G estimated CrCl. In 2010, the National Cancer Institute recommended the GFR value within the Calvert formula should not exceed 125 mL/min, thereby capping the carboplatin dose. However, there are studies demonstrating that certain patients' actual GFR values do exceed 125 mL/min. Therefore, capping the carboplatin dose in these patients may lead to underestimating the carboplatin AUC. A single-center, retrospective study was performed to evaluate the change in platelet count pre- and post-carboplatin exposure in patients with C-G estimated CrCl greater than 125 mL/min receiving capped versus uncapped carboplatin doses. A review of carboplatin dosing strategies is also presented. This study indicated there was a larger mean difference in pre- and post-platelet count in patients receiving uncapped carboplatin compared to patients receiving capped carboplatin with no differences in toxicities. Dose capping this patient population will likely lead to a lower AUC rather than the intended AUC target, which could ultimately lead to substandard outcomes.

Two-step laser mass spectrometry of asphaltenes.

Defined by their solubility in toluene and insolubility in n-heptane, asphaltenes are a highly aromatic, polydisperse mixture consisting of the heaviest and most polar fraction of crude oil. Although asphaltenes are critically important to the exploitation of conventional oil and are poised to rise in significance along with the exploitation of heavy oil, even as fundamental a quantity as their molecular weight distribution is unknown to within an order of magnitude. Laser desorption/ionization (LDI) mass spectra vary greatly with experimental parameters so are difficult to interpret: some groups favor high laser pulse energy measurements (yielding heavy molecular weights), arguing that high pulse energy is required to detect the heaviest components of this mixture; other groups favor low pulse energy measurements (yielding light molecular weights), arguing that low pulse energy is required to avoid aggregation in the plasma plume. Here we report asphaltene mass spectra recorded with two-step laser mass spectrometry (L2MS), in which desorption and ionization are decoupled and no plasma is produced. L2MS mass spectra of asphaltenes are insensitive to laser pulse energy and other parameters, demonstrating that the asphaltene molecular weight distribution can be measured without limitation from insufficient laser pulse energy or plasma-phase aggregation. These data resolve the controversy from LDI, showing that the asphaltene molecular weight distribution peaks near 600 Da and previous measurements reporting much heavier species suffered from aggregation effects.

Monitoring tylosin and sulfamethazine in a tile-drained agricultural watershed using polar organic chemical integrative sampler (POCIS).

This study evaluated the influence of temporal variation on the occurrence, fate, and transport of tylosin (TYL) and sulfamethazine (SMZ); antibiotics commonly used in swine production. Atrazine (ATZ) was used as a reference analyte to indicate the agricultural origin of the antibiotics. We also assessed the impact of season and hydrology on antibiotic concentrations. A reconnaissance study of the South Fork watershed of the Iowa River (SFIR), was conducted from 2013 to 2015. Tile drain effluent and surface water were monitored using polar organic integrative sampler (POCIS) technology. Approximately 169 animal feeding operations (AFOs) exist in SFIR, with 153 of them being swine facilities. All analytes were detected, and detection frequencies ranged from 69 to 100% showing the persistence in the watershed. Antibiotics were detected at a higher frequency using POCIS compared to grab samples. We observed statistically significant seasonal trends for SMZ and ATZ concentrations during growing and harvest seasons. Time weighted average (TWA) concentrations quantified from the POCIS were 1.87ngL-1 (SMZ), 0.30ngL-1 (TYL), and 754.2ngL-1 (ATZ) in the watershed. SMZ and TYL concentrations were lower than the minimum inhibitory concentrations (MIC) for E. coli. All analytes were detected in tile drain effluent, confirming tile drainage as a pathway for antibiotic transport. Our results identify the episodic occurrence of antibiotics, and highlights the importance identifying seasonal fate and occurrence of these analytes.

Brain tumors associated with psychogenic non-epileptic seizures: Case series.

OBJECTIVE: The association of psychogenic non-epileptic seizures (PNES) with primary or secondary brain tumors has not been well described in the literature. We aim to discuss their association, and their impact in brain tumor treatment. PATIENTS AND METHODS: We identified four patients retrospectively from our practice. The diagnosis of PNES was based on clinical suspicion and standard EEG, supplemented with video-EEG recording in 2 patients. RESULTS: The initial diagnosis of brain tumor was associated with a new onset seizure prior to diagnosis. The majority of the patients presented with ES followed by recurrent PNES during the course of their disease. Patients were treated with multiple anti-epileptic drugs, requiring frequent schedule adjustments. The preferred tumor treatment modality was chemotherapy, followed by surgical resection. The patients were offered psychological consultation achieving partial control of their events. These patients manifested recurrent disabling clinical events that required multiple medical consultations. None of these patients presented clinical evidence of tumor progression at the time of PNES presentation. CONCLUSION: A high index of suspicion and early psychological consultation referral will likely mitigate the quality of life impact of PNES in these patients.

Characterization of Helicobacter pylori gamma-glutamyltranspeptidase reveals the molecular basis for substrate specificity and a critical role for the tyrosine 433-containing loop in catalysis.

Helicobacter pylori gamma-glutamyltranspeptidase (HpGT) is a member of the N-terminal nucleophile hydrolase superfamily. It is translated as an inactive 60 kDa polypeptide precursor that undergoes intramolecular autocatalytic cleavage to generate a fully active heterodimer composed of a 40 kDa and a 20 kDa subunit. The resultant N-terminus, Thr 380, has been shown to be the catalytic nucleophile in both autoprocessing and enzymatic reactions. Once processed, HpGT catalyzes the hydrolysis of the gamma-glutamyl bond in glutathione and its conjugates. To facilitate the determination of physiologically relevant substrates for the enzyme, crystal structures of HpGT in complex with glutamate (1.6 A, Rfactor = 16.7%, Rfree = 19.0%) and an inactive HpGT mutant, T380A, in complex with S-(nitrobenzyl)glutathione (1.55 A, Rfactor = 18.7%, Rfree = 21.8%) have been determined. Residues that comprise the gamma-glutamyl binding site are primarily located in the 20 kDa subunit and make numerous hydrogen bonds with the alpha-amino and alpha-carboxylate groups of the substrate. In contrast, a single hydrogen bond occurs between the T380A mutant and the remainder of the ligand. Lack of specific coordination beyond the gamma-glutamyl moiety may account for the substrate binding permissiveness of the enzyme. Structural analysis was combined with site-directed mutagenesis of residues involved in maintaining the conformation of a loop region that covers the gamma-glutamyl binding site. Results provide evidence that access to this buried site may occur through conformational changes in the Tyr 433-containing loop, as disruption of the intricate hydrogen-bond network responsible for optimal placement of Tyr 433 significantly diminishes catalytic activity.

Synthesis, structure, and characterization of molybdenum(VI) imido complexes with N-salicylidene-2-aminophenol.

Diimido complexes of the type Mo(NAr)2Cl2(dme) (dme = 1,2-dimethoxyethane) react with N-salicylidene-2-aminophenol (sapH2) in methanol in the presence of 2 equiv of triethylamine to form complexes with the general formula Mo(NAr)(1,2-OC6H4NH)(sap). The structures of three of these compounds (NAr = 2,6-dimethylphenylimido (1), 2,4,6-trimethylphenylimido (2), 2-tert-butylphenylimido3) have been determined by X-ray crystallography. The coordination sphere around the Mo is a distorted octahedron. The oxygen from the 2-aminophenol is trans to the imido nitrogen, whereas the amido nitrogen and the tridentate sap occupy the four equatorial positions. The Mo-N-C imido linkages have angles of 167.5(2) degrees (1), 163.2(2) degrees (2), and 162.4(1) degrees (3). A precursor complex to the imido-amido complex, Mo(NAr)(sap)(OCH3)2 (4, NAr = 2,4,6-trimethylphenylimido), has been isolated and characterized. Compound 4 reacts with 2-aminophenol to form 2, with 2-aminothiophenol to form Mo(NAr)(1,2-SC6H4NH)(sap) (5), with catechol to form Mo(NAr)(1,2-OC6H4O)(sap) (6), with naphthalene-2,3-diol to form Mo(NAr)(naphthalene-2,3-diolate)(sap) (7), with 1,2-benzenedithiol to form Mo(NAr)(1,2-SC6H4S)(sap) (8), and with 1,2-phenylenediamine to form Mo(NAr)(1,2-HNC6H4NH)(sap) (9). The structures of compounds 5-9 have been determined by X-ray crystallography. With the exception of compound 8, the structures are similar to those of 1,2, and 3, with the bidentate ligand occupying one axial and one equatorial position. In 8, 1,2-benzendithiolate occupies two equatorial positions, and the nitrogen from sap is located trans to the imido nitrogen. All complexes were characterized by 1H NMR spectroscopy, cyclic voltammetry, and UV-vis spectroscopy. When a solution of 4 is exposed to moisture-containing air, MoO2(sap)(CH3OH) (10) is formed. The structure of 10 was also determined.