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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 19 recordsLinked to original sources
PubMed2005

Detection of sputtered metals with cavity ring-down spectroscopy.

We report on use of cavity ring-down spectroscopy (CRDS) as a means to detect and quantify ion sputtering of refractory metal species. CRDS measurements are made with a neodymium:YAG-pumped optical parametric oscillator laser system in the 375-400 nm region. CRDS sputtering measurements are presented for argon ions incident on iron, aluminum, molybdenum, and titanium. The measurements are based on absorption from fine-structure levels of the electronic ground-state multiplets. For each species, characteristic spectra are provided, the dependence of sputtered particle number density on the beam current is examined, measured densities are compared with a sputter model, and detection limits are determined. For iron, aluminum, and titanium we probe multiple fine-structure levels within the ground-state multiplet and obtain information on their relative populations.

Journal Article↗
PubMed2005

Assessment of anosognosia in persons with frontal lobe damage: clinical utility of the Mayo-Portland Adaptability Inventory (MPAI).

OBJECTIVES: To determine if the Mayo-Portland Adaptability Inventory (MPAI) demonstrates clinical utility in differentiating between persons with severe TBI and frontal lobe damage/anosognosia and persons with mild TBI and no frontal lobe damage. PARTICIPANTS: Forty-three persons with TBI and documented frontal lobe damage (mean age = 34; mean time since injury = 5.2 years) and 69 persons with mild TBI and no frontal lobe damage (mean age = 34.3; mean time since injury = 4.8 4.8 years). MEASURE: MPAI. RESULTS: Total inventory and select sub-category difference scores were significantly greater in the frontal lobe group than in the non-frontal lobe group. However, as expected, there was no significant difference between the two groups on the mobility sub-category difference scores. CONCLUSIONS: The MPAI appears to be potentially clinically useful in assessing for frontal lobe damage and associated anosognosia in patients with TBI.

Adult↗
PubMed2004

Comparison of separation efficiency of early phase active pharmaceutical intermediates by steady state recycle and batch chromatographic techniques.

Chromatographic resolution of enantiomers has become the accepted method for generation of active pharmaceutical intermediates (APIs) in early phase development. Continuous processes such as simulated moving bed (SMB) are recognized as alternative approaches for manufacturing of larger quantities of enantiomerically pure compounds. Steady state recycle (SSR) technology was initially described in 1998 [C.M. Grill, L. Miller, J. Chromatogr. A 827 (1998) 359] and has recently become a common technique in some laboratories. Batch chromatography, SSR, and SMB processes should be considered "phase appropriate" technologies. Phase appropriate technology refers to the scale of separation required in a step of the drug development process. SSR is phase appropriate technology for producing 100 g to several kilogram quantities of material. In this report, we will describe development and scale up of chiral separations utilizing the SSR technique for six different APIs utilizing several different chiral stationary phases and compare the efficiencies of both SSR and batch chromatographic techniques.

Chromatography, Liquid↗
PubMed2002

Development of emission factors for polycarbonate processing.

Emission factors for selected volatile organic compounds (VOCs) and particulate emissions were developed while processing eight commercial grades of polycarbonate (PC) and one grade of a PC/acrylonitrile-butadiene-styrene (ABS) blend. A small commercial-type extruder was used, and the extrusion temperature was held constant at 304 degrees C. An emission factor was calculated for each substance measured and is reported as pounds released to the atmosphere/million pounds of polymer resin processed [ppm (wt/wt)]. Scaled to production volumes, these emission factors can be used by processors to estimate emission quantities from similar PC processing operations.

Air Pollutants↗
PubMed2001

Isolation of the components of a complex mixture by means of column switching for their enhanced detection by mass spectrometry.

Mass spectral characterization of low-level impurities in drug substances and formulations may be challenging when using a validated HPLC method developed for optimal chromatographic performance. In many cases, either the mobile phase contains non-volatile additives that are deleterious to the operation of the mass spectrometer, or some of the related substances fail to ionize effectively under electrospray ionization or atmospheric pressure chemical ionization conditions. This paper describes a way to capture these low-level compounds from an analytical HPLC column using a small trapping column. Mixture components are retained on the trapping column by means of reducing the solvent strength of the eluent. Subsequent elution of trapped compounds using mobile phases more amenable to mass spectral analysis yields improved detection and characterization of low-level compounds of interest. Possible applications of peak trapping and elution include: (1) analysis of compounds separated using a mobile phase containing high concentrations of non-volatile additives, (2) analysis of organic acids separated using a low-pH mobile phase (containing trifluoroacetic acid), and (3) improving the detection limit of a low-level compound of interest through multiple collections. The peak trapping apparatus and optimization experiments are described.

Chromatography, High Pressure Liquid↗
PubMed2001

Automated molecular weight assignment of electrospray ionization mass spectra.

Process improvements in the synthesis of therapeutic agents and their intermediates are often facilitated by identification of reaction by-products. Analysis by liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization is a powerful approach for obtaining molecular weight information for these compounds. Such analyses are well suited for 'open-access' mass spectrometry using generic chromatographic conditions, provided spectral interpretation for unknown compounds is facile. We have developed a software application (MassAssign) that facilitates automated data processing and molecular weight assignment for chromatographic peaks detected by any standard ultraviolet-visible wavelength detector. The program assigns [M + H](+) ions (and thus molecular weight) in the mass spectra using predetermined criteria. This evaluation process differentiates [M + H](+) ions from other signals in a complex mass spectrum such as those resulting from chromatographic coelution or the presence of multiple species (i.e., fragment ions, singly charged ions, doubly charged ions, adduct ions, proton-bound dimers, etc.). Once the program has evaluated all ions in a mass spectrum that exceed a preset abundance threshold, MassAssign reports either a numeric value-indicating the chromatographic peak consists of a single component having the displayed molecular weight, 'MC'-indicating the peak consisted of multiple components, or 'ND'-that a molecular weight could not be determined unequivocally. The performance of the program was evaluated by comparing mass assignments made by MassAssign against manual interpretation for 55 samples analyzed by positive electrospray ionization using a generic HPLC method. Correct molecular weight assignments were obtained in 90% of the cases.

Algorithms↗
PubMed2001

Classification of oral cephalosporins. A matter for debate.

There are many cephalosporins available and various ways of classifying them for clinical use. Oral cephalosporins probably need a classification of their own. This informal discussion was prompted by the appearance of the recommendations of an expert committee of the Paul Ehrlich Gesellschaft. The views of several other commentators are included. There is considerable individual variation in preference for different styles of classification depending on what the classification is for.

Administration, Oral↗
PubMed2001

Antibiotic resistance in hospital pathogens--acquisition or spread?

Hospital resistant pathogens are a problem of hospital use allowing acquisition of multi-resistant strains. The use of antibiotics in the community and on the farm has little impact on hospital infection rates and prevalence of resistance in hospital bacteria. Once acquisition occurs the main problem is spread of clones to highly vulnerable patients. Attention to protective methods for such patients ought to be a priority in hospital infection control.

Animals↗
PubMed2001

Non-antimicrobial activities of macrolides.

While using macrolides for the treatment of infectious diseases, some non-microbiological effects have been observed. The stimulation of gastrointestinal motility, which is a common side-effect of macrolides, may be advantageous in patients with poor upper gut motility. Macrolides, as well as directly inhibiting bacterial growth, may exert immunomodulatory effects. Utilisation of these properties may be useful in the treatment of chronic inflammatory conditions, especially if bacterial infection is also implicated. Preliminary evidence also suggests that the currently available macrolide antibiotics possess antitumour activity. In the future, an increased understanding of the structure-activity relationships of macrolides may result in the development of new structurally related compounds that concentrate on these pharmacological properties in addition to, or instead of, antimicrobial activity.

Anti-Bacterial Agents↗
PubMed2001

Evaluation of the safety of macrolides.

The safety of all drugs is established by animal studies, administration to healthy volunteers and the observations during clinical studies to confirm efficacy. During these studies, patients are questioned about side-effects and extensive laboratory testing of blood and urine samples is performed. Despite these extensive studies, new problems may arise during post marketing surveillance which is designed to identify any rare side-effects. Today, all studies suggest that macrolides, and especially the more recently developed agents, are well tolerated. Some variations in tolerability may be due to the size of the macrocyclic ring and the presence of different esters. There are very few instances of irreversible organ damage.

Animals↗
PubMed2001

Mass spectral fragmentation reactions of a therapeutic 4-azasteroid and related compounds.

Mass spectra were acquired for a therapeutic 4-azasteroid (dutasteride), and some related compounds, using various ionization conditions (EI, CI, APCI and ESI) in both positive and negative ion modes. The ionization and fragmentation behavior of the compound dutasteride, its precursors and several analogs is reported. Positive atmospheric pressure chemical ionization (APCI+) and positive electrospray ionization (ESI+) produced distinctive collision-induced dissociation (CID) spectra for the respective [MH]+ ions of dutasteride. The spectral differences are attributed to ion populations having either different structures or different internal energy distributions (as a consequence of the method of ionization). Irrespective of their origin, the protonated molecules undergo interesting fragmentation reactions when collisionally activated. The identity of the major fragmentation products was confirmed by accurate mass measurement. The negative APCI mass spectrum of dutasteride displays extensive dehydrohalogenation, apparently due to the thermal component of the APCI process. Some of the resulting radical anions display remarkable stability toward collisional decomposition. Details of the fragmentation behavior for the negative ion species and their relationship to the positive ion results are discussed.

5-alpha Reductase Inhibitors↗
PubMed2001

Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

BACKGROUND: In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. METHODS: One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. RESULTS: In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. CONCLUSIONS: These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.

Adult↗
PubMed2001

Differentiation of hypnosis and relaxation by analysis of narrow band theta and alpha frequencies.

Narrow band theta and alpha activity were recorded over anterior and posterior sites before, during, and after hypnosis in high and low hypnotically susceptible subjects (N = 16). In theta, high susceptibles had greater activity posthypnosis, otherwise there were no group differences. These findings common to low and high susceptibles suggest that theta is an index of relaxation that continues after hypnosis in highs. In alpha in high susceptibles, posterior power increased from the prehypnosis to hypnosis conditions and decreased posthypnosis. Exactly the converse effects were seen in lows. Furthermore, highs had greater alpha power than lows during both prehypnosis and hypnosis conditions, demonstrating an association of alpha with hypnotic susceptibility. The results indicate that, whereas theta indexes relaxation, alpha indexes the hypnotic experience and susceptibility.

Adult↗