Close collaboration between local and specialist multidisciplinary teams allows 'fast-tracking' of patients with colorectal liver metastases.

Aim: The ongoing evolution of treatment strategies for colorectal liver metastases necessarily requires all patients to be reviewed at some point by the specialist hepatobiliary unit. This process can be streamlined through close collaboration with the local colorectal multidisciplinary team (MDT). The study was performed to see if a local colorectal MDT was able to make a correct decision regarding potential operability of liver metastases, by comparing its decision with that of two hepatobiliary surgeons in our referral centre.

Diagnostic transitions from childhood to adolescence to early adulthood.

Background: Quantifying diagnostic transitions across development is needed to estimate the long-term burden of mental illness. This study estimated patterns of diagnostic transitions from childhood to adolescence and from adolescence to early adulthood.

Methods: Patterns of diagnostic transitions were estimated using data from three prospective, longitudinal studies involving close to 20,000 observations of 3,722 participants followed across multiple developmental periods covering ages 9-30.

Synthesis through simulation: insights on the epidemiology of mood and anxiety disorders in Canada.

Objective: Prevalence estimates for mood and anxiety disorders in Canada are available, but various methodological approaches have produced inconsistent results. Simulation studies involve careful examination of available data by an expert modelling team working together with subject matter experts. Simulation can integrate datasets and literature-based estimates from various sources into a coherent mathematical representation of the underlying total population epidemiology.

Potential pediatric intensive care unit demand/capacity mismatch due to novel pH1N1 in Canada.

Objective: To investigate the possibility of pediatric intensive care unit shortfalls, using pandemic models for a range of attack rates and durations. The emergence of the swine origin pH1N1 virus has led to concerns about shortfalls in our ability to provide pediatric ventilation and critical care support.

Design: Modeling of pediatric intensive care demand based on pH1N1 predictions using simulation techniques.

Pharmacokinetic comparison of an oral diclofenac potassium liquid-filled soft gelatin capsule with a diclofenac potassium tablet.

Objective: To compare the pharmacokinetic profiles of diclofenac potassium liquid-filled soft gelatin capsules (DPSGC) using patented ProSorb dispersion technology with an immediate-release, diclofenac potassium 50-mg comparator tablet in two open-label, single-dose, randomized, crossover relative bioavailability studies in healthy volunteers.

Methods: In Study 1, volunteers (n = 21) received DPSGC 50 mg or a diclofenac potassium 50-mg comparator tablet in two inpatient study periods. In Study 2 (n = 54), volunteers received DPSGC 25 mg, DPSGC 50 mg, or a diclofenac potassium 50-mg comparator immediate-release tablet in three inpatient study periods.

Single-dose pharmacokinetic study of rapidly dispersing diclofenac potassium formulations in healthy volunteers.

Objective: The clinical utility of diclofenac potassium, a commonly prescribed analgesic that provides mild to moderate pain relief, may be hindered by its delayed, depressed, and/or inconsistent absorption characteristics. A diclofenac potassium formulation using proprietary dispersion technology (ProSorb) was developed to overcome these limitations. The authors evaluated and compared the pharmacokinetics (PK) of 2 investigational diclofenac potassium liquid filled soft gelatin capsule (DPSGC) preparations and one investigational diclofenac liquid formulation, each incorporating the proprietary dispersion technology, to establish bioequivalence and identify a formulation for further clinical study.

Potential intensive care unit ventilator demand/capacity mismatch due to novel swine-origin H1N1 in Canada.

Purpose: To investigate the ability of Canadian intensive care units (ICUs) and ventilators to handle widespread re-emergence of the swine-origin H1N1 virus in the context of an aggressive strategy of vaccination.

Method: Data collected during the first wave in Winnipeg, Manitoba, were applied to a variety of second wave pandemic models to determine potential ICU and ventilator demand.

Results: For attack rates greater than 20% to 25%, significant shortages in ventilators may be expected across Canada regardless of the duration of the pandemic if vaccination is not considered.

Determination of guaifenesin in human serum by capillary gas chromatography and electron capture detection.

A method for the quantitation of guaifenesin in human serum has been developed and validated. The procedure involves liquid-liquid extraction of the serum sample in the presence of mephenesin as an internal standard, followed by derivatization and analysis using capillary gas chromatography (GC) and electron capture detection (ECD). Different solvents were tested for extraction of guaifenesin from serum.

Fine structure of dark matter halos and its effect on terrestrial detection experiments.

Terrestrial dark matter detection experiments probe the velocity-space distribution of dark matter particles in the vicinity of the Earth. We present a novel method, to be used in conjunction with standard cosmological simulations of hierarchical clustering, that allows one to extract a truly local velocity-space distribution in exquisite detail. Preliminary results suggest a new picture for this distribution which is decidedly non-Maxwellian but instead is characterized by randomly positioned peaks in velocity space.

All-trans-retinoic acid modulation of drug-metabolizing enzyme activities: investigation with selective metabolic drug probes.

Purpose: All-trans-retinoic acid (ATRA) is a retinoid analogue that has been shown to be effective in acute promyelocytic leukemia. It is currently being investigated for efficacy in the treatment and prevention of various types of cancer. One of the factors limiting its use is the observed increase in ATRA clearance and elimination which occurs shortly after treatment is started, leading to reduced levels of drug in the body and loss of effectiveness.

A phase II trial of all-trans-retinoic acid in hormone-refractory prostate cancer: a clinical trial with detailed pharmacokinetic analysis.

Retinoids have been shown to have substantial anticancer activity in a number of preclinical and clinical situations. There are considerable epidemiologic, in vitro and in vivo data which indicate that retinoids may have a role in the prevention and therapy of human prostate cancer. Based on anecdotal evidence of response in one patient with hormone-refractory prostate cancer (HRPC), we conducted a phase II trial in HRPC during which we also examined changes in pharmacokinetics of all-trans-retinoic acid (ATRA) which occurred during therapy.

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma and urine by high-performance liquid chromatography.

A sensitive and reproducible method is described for the determination of the cytochrome P450 enzyme 2E1 substrate chlorzoxazone and its primary metabolite 6-hydroxychlorzoxazone in human plasma and urine. Plasma or diluted urine were acidified, incubated with beta-glucuronidase and then were extracted with diethyl ether. Separation of the analytes was achieved on a C18 column with UV detection set at 283 nm.

Pain perception and serum beta-endorphin in trauma patients.

Acute traumatic injury engenders the production of beta-endorphin (BE) and other endogenous opioids. Elevated BE concentration putatively correlates with pain perception in trauma patients. The authors examined traumatic injury severity, pain perception, and BE concentration in patients admitted to an urban trauma center.

FK 506 (Tacrolimus) metabolism by rat liver microsomes and its inhibition by other drugs.

The in vitro metabolism of FK 506 and its inhibition by other drugs was studied with hepatic microsomes from rats pre-treated with dexamethasone, a selective cytochrome P-450 IIIA inducer. Nonspecific inhibitors of cytochrome P-450, such as ketoconazole, itraconazole, fluconazole and SKF 525 A, and most of the cytochrome P-450 IIIA specific substrates used in this study significantly inhibited FK 506 metabolism. Although cyclosporine is a known substrate of cytochrome P-450 IIIA, it had no effect on FK 506 metabolism.

Modulation of [3H]flunitrazepam binding by natural and synthetic progestational agents.

Progesterone is metabolized by ring-A reduction with subsequent oxidoreduction to 3 alpha-hydroxy-5 alpha-dihydroprogesterone (3 alpha-OH-5 alpha-DHP), a naturally occurring metabolite that has been shown to enhance [3H]flunitrazepam ([3H]FNZ) binding. Medroxyprogesterone acetate (MPA), a commonly prescribed progestational agent, is a synthetic progesterone derivative that has a metabolic profile similar to that of progesterone. In this study, the effects of MPA and its ring-A reduced metabolites DHMPA and THMPA on [3H]FNZ binding were investigated.

Sensitive high-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma.

A rapid and sensitive high-performance liquid chromatographic assay was developed for the quantitation of chlorzoxazone and its major metabolite 6-hydroxychlorozoxazone in plasma. These compounds, as well as the internal standard 5-fluorobenzoxazolone, were extracted from plasma (0.5 ml) using C18 solid-phase extraction columns.

Metabolism of FK 506 in differentially induced rat liver microsomes.

The in vitro hepatic metabolism of FK 506 was studied in microsomes prepared from control rats as well as in microsomes prepared from rats treated with the selective cytochrome P-450 isozyme inducers 3-methylcholanthrene (IA), phenobarbital (IIB), and dexamethasone (IIIA). The metabolism of FK 506 was similar for control microsomes and for microsomes prepared from phenobarbital and 3-methylcholanthrene induced animals. The percentage of FK 506 metabolized by these tissue preparations ranged from 21.

Maternal side effects of prenatal dexamethasone therapy for fetal congenital adrenal hyperplasia.

Unlabelled: Prenatal treatment of virilizing congenital adrenal hyperplasia in female fetuses via maternal dexamethasone (Dex) therapy (1-1.5 mg/day) from first trimester to birth was associated with excessive weight gain (47-56 pounds at 35-37 weeks gestation), Cushingoid facial features, severe striae resulting in permanent scarring, and hyperglycemic response (8-11.7 nmol/L) to oral glucose administration in all our experience (three cases).

Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative.

1. The metabolism of zonisamide in vitro was characterized through aerobic and anaerobic incubations with rat liver subcellular fractions and cultured gastrointestinal microflora. 2.

Metabolism of the anticonvulsant agent zonisamide in the rat.

The metabolism of zonisamide [3-(sulfamoylmethyl)-1,2-benzisoxazole], a new anticonvulsant, has been studied. In rats dosed with [14C]zonisamide (100 mg/kg, ip) 86.5% of the radioactive dose was excreted in the urine over 72 hr.

The lack of effectiveness of (-)-epicatechin against alloxan induced diabetes in Wistar rats.

(-)-Epicatechin, a naturally occurring flavonoid, has been reported to protect pancreatic beta cells from alloxan-induced diabetes (1) and to stimulate beta cell regeneration when given after alloxan administration (2,3). However, in the present study, we have not been able to confirm these findings. Administration of (-)-epicatechin (100 mg/kg/day for 15 days) beginning three days after alloxan administration (140 mg/kg) had no significant effect on blood glucose levels when compared to alloxan control animals.