Novel high-performance liquid chromatographic assay using fluorescence detection for the quantitation of plasma gamma-methylene-10-deazaaminopterin and its major metabolite, 7-hydroxy-gamma-methylene-10-deazaaminopterin, in patients with solid cancers in a phase I trial

Gamma-methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-gamma-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 microM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase I trial.     

Recent developments in two-pack water-based epoxy coatings

In recent years new curing agent technology has been developed which allows water-based curing agents to be introduced into high performance coating, these are classified according to the type of epoxy resin used. Type I utilises low molecular weight, liquid epoxy resins and Type II pre-formed dispersions of higher molecular weight solid epoxy resins. The chemical composition of the binder of water-borne epoxy coatings plays a critical role in their performance properties, hence some of the structural properties of the amine hardeners will be reviewed. New curing agents will be discussed which demonstrate the versatility these products can offer to the coating formulator. Performance data of clear coats and anti-corrosive primers confirm the applicability of the new systems for the long term protection of steel and concrete surfaces.     

Case report of ruptured endometriotic cyst in pregnancy treated by laparoscopic ovarian cystectomy

Pregnancy is thought to have an ameliorating effect on endometriosis, inducing a state of quiescence. We report a case of ruptured endometriotic cyst in pregnancy successfully treated by laparoscopic ovarian cystectomy. Our patient subsequently progressed uneventfully to deliver a healthy baby girl at term. Laparoscopic ovarian cystectomy in pregnancy, even with ruptured cysts, appeared to be safe in trained hands with similar benefits of reduced post-operative morbidity.     

Impact of gender on coronary bypass operative mortality

I examine trends in single mothers' living arrangements using data from the 1970-1995 Current Population Surveys. I create a consistent trend by correcting a coding problem that stemmed from the misidentification of children living in multigenerational households before 1984. Revised estimates show that the number of single mothers in each of these years was undercounted by 200,000-300,000. All of these women were subfamily heads living with their parents, and the problem occurred disproportionately among teens and black women. The uncorrected trend falsely indicates a large increase in the share of single mothers living with their parents. In reality, there was little change in the percentage of single mothers living in this arrangement over the time period. However, the data indicate a large increase in the rate of cohabitation and a comparable decline in the rate of living independently among this population.     

Glutathione synthetase is dispensable for growth under both normal and oxidative stress conditions in the yeast Saccharomyces cerevisiae due to an accumulation of the dipeptide gamma-glutamylcysteine

Glutathione (GSH) synthetase (Gsh2) catalyzes the ATP-dependent synthesis of GSH from gamma-glutamylcysteine (gamma-Glu-Cys) and glycine. GSH2, encoding the Saccharomyces cerevisiae enzyme, was isolated and used to construct strains that either lack or overproduce Gsh2. The identity of GSH2 was confirmed by the following criteria: 1) the predicted Gsh2 protein shared 37-39% identity and 58-60% similarity with GSH synthetases from other eukaryotes, 2) increased gene dosage of GSH2 resulted in elevated Gsh2 enzyme activity, 3) a strain deleted for GSH2 was dependent on exogenous GSH for wild-type growth rates, and 4) the gsh2 mutant lacked GSH and accumulated the dipeptide gamma-Glu-Cys intermediate in GSH biosynthesis. Overexpression of GSH2 had no effect on cellular GSH levels, whereas overexpression of GSH1, encoding the enzyme for the first step in GSH biosynthesis, lead to an approximately twofold increase in GSH levels, consistent with Gsh1 catalyzing the rate-limiting step in GSH biosynthesis. In contrast to a strain deleted for GSH1, which lacks both GSH and gamma-Glu-Cys, the strain deleted for GSH2 was found to be unaffected in mitochondrial function as well as resistance to oxidative stress induced by hydrogen peroxide, tert-butyl hydroperoxide, and the superoxide anion. Furthermore, gamma-Glu-Cys was at least as good as GSH in protecting yeast cells against an oxidant challenge, providing the first evidence that gamma-Glu-Cys can act as an antioxidant and substitute for GSH in a eukaryotic cell. However, the dipeptide could not fully substitute for the essential function of GSH in the cell as shown by the poor growth of the gsh2 mutant on minimal medium. We suggest that this function may be the detoxification of harmful intermediates that are generated during normal cellular metabolism.     

Arrhythmia detection and response in a monitoring technician and pocket paging system

Technologically advanced telemetry systems have begun to produce alternatives to the need for continuous visual observation of the electrocardiogram (ECG). Few studies have been conducted to determine the efficacy of these systems in the clinical setting. The purpose of this study was to describe two different approaches to communication of arrhythmia events and corresponding nurse response. One approach, on a cardiac medical unit, utilized a monitoring technician to continuously observe ECGs at a central monitoring technician station (MTS) and notify the nurse of changes. The other approach, on a general medical unit, eliminated the use of the monitoring technician and utilized a pocket paging system (PPS). The PPS interfaced with the computerized arrhythmia detection system from the ECG monitor, which directly alerted the nurse to arrhythmia events. A quasi-experimental comparative post-test design was used. The sample consisted of 50 randomly selected, 2-hour observation periods on each unit during a 3-month period. Data collectors recorded the interaction of the monitoring technician with the arrhythmia detection system and the nurse on the MTS unit, or the nurse using the PPS. Results of this study revealed all arrhythmia events activated an alarm by the computerized arrhythmia detection system. Length of time to notify the nurse was within 0 to 1 minute for both systems. This study demonstrated that the PPS is a viable approach to arrhythmia detection and communication in the medical/cardiac patient population.