Evolutionary history of the enolase gene family.

The enzyme enolase [EC 4.2.1.

A new method for rapid measurement of lactate in fetal and neonatal blood.

A prospective trial to determine the accuracy and precision of the Boehringer Mannheim Accusport handheld lactate meter in measuring plasma lactate levels in umbilical cord blood and neonatal blood microsamples was performed in the labour ward and the neonatal intensive care unit of the NepeanHospital. Specimens were collected from the umbilical artery of 160 consecutive deliveries covering gestations from 26 to 42 weeks, and from 110 umbilical artery catheters covering a range of gestations from 26 to 41 weeks. Serum was also obtained from an exchange transfusion for coefficient of variation analysis.

Is Bergmann's Rule Valid for Mammals?

Bergmann's rule states that, within species of mammals, individuals tend to be larger in cooler environments. However, the validity of the rule has been debated. We examined the relationship between size and latitude as well as size and temperature within various species of mammals.

High-dose chemotherapy (CTM) for breast cancer.

We designed and implemented a new mitoxantrone-based high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninety-one breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60 mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM.

Music therapy in critical care: indications and guidelines for intervention.

Music therapy is an effective intervention for critically ill patients for such purposes as anxiety reduction and stress management. The therapy is readily accepted by patients and is an intervention patients thoroughly enjoy. The MAIT is one resource that nurses caring for critically ill patients can use to implement music therapy in clinical practice.

Developmental Instability as a Means of Assessing Stress in Plants: A Case Study Using Electromagnetic Fields and Soybeans.

Developmental instability is often assessed using deviations from perfect bilateral symmetry. Here, we review the literature describing previous studies, suggest mechanisms that may account for both the generation and disruption of bilateral symmetry, and examine the influence of electromagnetic fields on the asymmetry of soybean leaves. Leaves from plants under high-voltage power lines generating pulsed magnetic fields of <3 to >50 mG were more asymmetrical for two parameters (the terminal leaflet widths and lateral rachilla lengths) than leaves of plants even 50 or 100 m away from power lines.

Factors affecting the degradation rate of poly(lactide-co-glycolide) microspheres in vivo and in vitro.

The purpose of this work was to study the degradation of poly(lactide-co-glycolide) (PLG) microspheres in vivo and in vitro. Degradation rate constants were determined by measuring the polymer molecular weight as a function of time by gel-permeation chromatography. The effects of PLG chemistry and the effects of encapsulating the sparingly soluble salt zinc carbonate and the protein recombinant human growth hormone (rhGH) on the degradation rate were assessed.

Biocompatibility of poly (DL-lactide-co-glycolide) microspheres implanted into the brain.

The delivery of therapeutic molecules to the brain has been limited in part due to the presence of the blood-brain barrier. One potential solution is the implantation of biodegradable polymers with sustained release of drugs. Poly (DL-lactide-co-glycolide) (PLG) is a bioerodible polymer with a long and successful history of use as a suture material.

Adsorption of serum albumin to thin films of poly(lactide-co-glycolide).

Protein adsorption has been implicated in the variability of drug release from biodegradable microspheres. We used optical reflectometry to measure the extent and kinetics of bovine serum albumin (BSA) adsorption to smooth spin-cast films prepared from two poly(lactide-co-glycolide) (PLG) samples that have different end-groups, one being a hydrophilic carboxylic end group and the other a hydrophobic ester end group. One of us has previously shown that these end-groups influence microsphere degradation (Tracy et al.

Preclinical development and current status of the fluorinated 2-nitroimidazole hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR 4554, CRC 94/17): a non-invasive diagnostic probe for the measurement of tumor hypoxia by magnetic resonance spectroscopy and imaging, and by positron emission tomography.

Hypoxia occurs to a variable extent in a vast majority of rodent and human solid tumors. It results from an inadequate and disorganized tumor vasculature, and hence an impaired oxygen delivery. A probe for the non-invasive detection of tumor hypoxia could find important utility in the selection of patients for therapy with bioreductive agents, anti-angiogenic/anti-vascular therapies and hypoxia-targeted gene therapy.

1,2,4-Benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with antitumor activity.

Tirapazamine (1,2,4-benzotriazin-3-amine 1,4-dioxide, SR 4233, WIN 59075) is the lead compound representing this class of anticancer drugs. It is also the first compound to be introduced in the clinic as a pure bioreductive cytotoxic agent. Tirapazamine represents a completely novel approach to the treatment of solid tumors and has generated considerable interest, with research being carried out on all aspects of the its anticancer activity.

Development and scale-up of a microsphere protein delivery system.

This paper reviews the development path for the ProLease injectable microsphere delivery system for proteins using human growth hormone as an example. The process consists of four stages, the selection of a lead formulation for clinical testing, the preclinical evaluation of the lead formulation including toxicology and stability studies, the manufacture of phase I clinical supplies, and the scale-up for phase II and phase III clinical trials. The approaches used to overcome obstacles during each stage are summarized including ways of stabilizing the protein, obtaining desirable release kinetics, and manufacturing sterile batches for clinical testing.

The relationship between tumour oxygenation determined by oxygen electrode measurements and magnetic resonance spectroscopy of the fluorinated 2-nitroimidazole SR-4554.

The relationship between two methods of assessing tumour oxygenation in vivo, namely oxygen electrode measurement and magnetic resonance spectroscopy (MRS) of the fluorinated 2-nitroimidazole SR-4554, was investigated. Using three tumour models (two sites), no linear correlation was observed between 19F retention index and pO2 parameters (r < or = 0.3).

Bioreductive metabolism of the novel fluorinated 2-nitroimidazole hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitroimidazolyl) acetamide (SR-4554).

The aim of this work was to study the metabolic characteristics of the novel fluorinated 2-nitroimidazole hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitroimidazolyl) acetamide (SR-4554). HPLC and 19F NMR methods were employed to evaluate the rate of reductive metabolism of SR-4554 and the nature of the resulting metabolites, respectively. SR-4554 was enzymatically reduced by mouse liver microsomes (1.

Strength capability while kneeling.

Work sometimes has to be carried out kneeling, particularly where jobs are performed in confined spaces as is common for miners, aircraft baggage handlers and maintenance workers. In order to assess the risks in performing forceful tasks under such conditions, data is needed on strength capabilities of kneeling subjects. A study was undertaken to measure isometric strength in single-handed exertions for male subjects and to investigate the effects on this of task layout factors (direction of force exertion, reach distance, height of the workpiece and orientation relative to the subject's sagittal plane).

Force exertion in awkward working postures--strength capability while twisting or working overhead.

Isometric strength data have been collected for three of the awkward work situations often imposed by workplace constraints in industry, as found in jobs such as maintenance and repair. The effects of the task layout factors (location of the workpiece, reach distance and direction of force exertion) were investigated and the data has been tabulated to show the degree to which strength may be reduced in different situations. Strength measurements in the present study were found to be considerably higher than previous measurements, apparently due to differences in instructions on foot placement that were given to subjects, which indicates that even small constraints on posture within the workplace may have large effects on the ability to exert force.

Preclinical evaluation of the fluorinated 2-nitroimidazole N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554) as a probe for the measurement of tumor hypoxia.

A novel probe, N-(2-hydroxy-3,3,3,-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554), has been used to detect tumor hypoxia noninvasively by 19F magnetic resonance spectroscopy (19F MRS). The compound was designed to undergo a hypoxia-dependent, one-electron reduction to metabolites that are selectively retained in tumors and has attractive pharmacokinetic, toxicological, and detection sensitivity properties. As a prelude to clinical studies, we report here for the first time on the ability to detect a MR signal following SR-4554 administration in various transplantable tumors and describe validation studies, consisting of a correlation between signal retention and radiobiological hypoxic fraction, and the effects of modulating the degree of hypoxia by hydralazine and carbogen breathing.

A novel limb-support system to reduce postural load in theaters.

Theatre nurses regularly stress their body when they support patients' limbs for prepping. This makes nurses vulnerable to back or upper limb pain. The Victoria Infirmary in Glasgow and the West of Scotland Department of Clinical Physics and Bio-Engineering, have developed an electrically braked limb support system to take the weight from the nurse.

The one-electron reduction potential of 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine): a hypoxia-selective bioreductive drug.

The one-electron reduction potential of 3-amino-1,2,4-benzotriazine 1,4-dioxide, tirapazamine (SR 4233) in aqueous solution has been determined by pulse radiolysis. Reversible electron transfer was achieved between radiolytically-generated one-electron reduced radicals of tirapazamine (T), and quinones or benzyl viologen as redox standards. The reduction potential Em7(T/T-) was -0.

Chemical properties which control selectivity and efficacy of aromatic N-oxide bioreductive drugs.

Pulse radiolysis was used to generate radicals from one electron reduction of 1,2,4-benzotriazine-1,4-dioxides (derivatives of tirapazamine), and of imidazo [1,2-a]quinoxaline-4-oxides (analogues of RB90740), which have selective toxicity towards hypoxic cells. Radicals from the mono N-oxides (from the latter compounds) react with oxygen approximately 10-40 times faster than does the tirapazamine radical. Radicals from the tirapazamine analogues studied react with oxygen up to approximately 10 times slower than tirapazamine radicals.

Biodistribution of the nitroimidazole EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide) in mice bearing subcutaneous EMT6 tumors.

The characteristic reduction and binding of nitroimidazoles to cellular macromolecules in the absence of oxygen allows their use for detection and characterization of hypoxia. The biodistribution of a new nitroimidazole, EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide), in mice bearing EMT6 tumors is described. Detection methods based on radioactivity and monoclonal antibody techniques are compared for liver and tumor.