PubMed Health⌕ Search

Biomedical subjects

J Barr

Publications and source records attributed to J Barr.

At least 19 recordsLinked to original sources
PubMed2005

Low-temperature rotational relaxation of CO in self-collisions and in collisions with Ne and He.

The low-temperature rotational relaxation of CO in self-collisions and in collisions with the rare-gas atoms Ne and He has been investigated in supersonic expansions with a combination of resonance-enhanced multiphoton ionization (REMPI) spectroscopy and time-of-flight techniques. For the REMPI detection of CO, a novel 2 + 1' scheme has been employed through the A(1)Pi state of CO. From the measured data, average cross sections for rotational relaxation have been derived as a function of temperature in the range 5-100 K. For CO-Ne and CO-He, the relaxation cross sections grow, respectively, from values of approximately 20 and 7 A(2) at 100 K to values of approximately 65-70 and approximately 20 A(2) in the 5-20 K temperature range. The cross section for the relaxation of CO-CO grows from a value close to 40 A(2) at 100 K to a maximum of 60 A(2) at 20 K and then decreases again to 40 A(2) at 5 K. These results are qualitatively similar to those obtained previously with the same technique for N(2)-N(2), N(2)-Ne, and N(2)-He collisions, although in the low-temperature range (T < 20 K) the CO relaxation cross sections are significantly larger than those for N(2). Some discrepancies have been found between the present relaxation cross sections for CO-CO and CO-He and the values derived from electron-induced fluorescence experiments.

Journal Article↗
PubMed2005

Alginate microparticles prepared by spray-coagulation method: preparation, drug loading and release characterization.

A spray-coagulation method was developed for the preparation of large scale of porous alginate microparticles. The effect of three variables on porosity was evaluated: (1) alginate solution concentration (2) the concentration of CaCl2 in the coagulation medium and (3) the ratio of guluronic acid to manuronic acid of the alginate. Methylene blue (MB), a highly water-soluble compound and a practically water-insoluble compound, 4-phenylazoaniline (PAA) were used as the model drugs to study drug loading and release characteristics from alginate microparticles. The release of the model compounds from the microparticles was found to depend upon the release medium. Incomplete in vitro release of both model drugs in deionized (DI) water was observed. The release of MB in simulated gastrointestinal fluid (0.1N HCl) was fast and complete, while the release of PAA was slow in 0.1N HCl and fast in phosphate buffer solution (pH 6.8). Interactions between the model drugs and alginate microparticles were identified from scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) analysis. The results indicated that (1) porous alginate microparticles can be produced by the spray-coagulation method; (2) drugs can be loaded by the adsorption method; (3) and the obtained microparticles may be used for delaying the release of drugs of low water solubility in acidic conditions.

Adsorption↗
PubMed2004

Selenium supplementation for critically ill adults.

BACKGROUND: Selenium is a trace mineral essential to human health, which has an important role in the immune response, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. OBJECTIVES: This review assessed the effects of selenium supplementation including the selenium-containing compound, ebselen, on adults recovering from critical illness. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2003), MEDLINE, (1966 to July 2003), EMBASE (1980 to Week 30 2003),CAB NAR (1973 to March 2003), BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003), HEALTHSTAR (1975 to September 2002), Current Controlled Trials, and reference lists. We contacted investigators, and handsearched four journals. Date of the most recent search: December 2003. SELECTION CRITERIA: Randomized trials of selenium or ebselen supplementation by any route, in adults with critical illness (including burns, head injury, brain haemorrhage, cerebrovascular accident and surgery). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. We sought additional information as required from trialists. We also undertook pooling of data for outcomes and selected exploratory analyses were undertaken. MAIN RESULTS: Seven randomized trials involving813participants were included. The quality of trials, as reported, was poor, particularly for allocation concealment. The availability of outcome data was limited and trials involving selenium supplementation, were small. Thus the results must be interpreted with caution. Because of heterogeneity, results are presented for the random effects models. Four selenium trials showed no statistically significant difference in mortality (relative risk (RR) 0.52, 95% confidence interval (CI) 0.20 to 1.34). Three trials of ebselen also showed no statistically significant difference in mortality (RR 0.83, 95% CI 0.51 to 1.35). One trial of selenium found no statistically significant difference between groups for participants developing infection (RR 1.33, 95% CI 0.55 to 3.24). Three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis), which was not statistically significant (RR 0.60, 95% CI 0.36 to 1.02). No clear evidence emerged for the benefits of selenium or ebselen supplementation for the outcomes of days on a ventilator, length of intensive care unit stay, length of hospital stay or quality of life. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend supplementation of critically ill patients with selenium or ebselen. Trials are required which overcome the defects of the reviewed studies, particularly inadequate size and methodology. This review will be updated when four ongoing trials are completed.

Adult↗
PubMed2004

Photodissociation and multiphoton dissociative ionization processes in CH(3)S(2)CH(3) at 193 nm studied using velocity-map imaging.

Dissociation and ionization processes in dimethyl disulfide, CH(3)S(2)CH(3), induced by one- or two-photon absorption of 193 nm light, have been studied using velocity-map ion imaging. The analysis of the ion images of the CH(3)S(2) (+), CH(3)S(+), S(2) (+), and S(+) fragments has allowed the characterization of the scattering dynamics of some of the main photolysis and dissociative-ionization processes. In particular, the experiments corroborate the formation of electronically excited SCH(3)((2)A(1)) products in the 193 nm photodissociation of dimethyl disulfide seen in earlier studies, and show that laser ionization provides a very sensitive method for their detection. The data have also allowed determination of the recoil energy and angular distributions of the CH(3)S(2) (+) and CH(3)S(+) products of the two-photon dissociative-ionization of the CH(3)S(2)CH(3) molecule. The measured distributions for these products are consistent with the formation of a transient parent ion which dissociates after a substantial intramolecular rearrangement, possibly yielding the most stable isomeric forms of the fragments, namely CH(2)S(2)H(+) and CH(2)SH(+).

Journal Article↗
PubMed2003

High-performance liquid chromatography method to analyze free and total urinary pyridinoline and deoxypyridinoline.

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption measured in blood and urine and are used to investigate bone metabolism and manage bone diseases. Unfortunately, the currently observed interlaboratory variability caused by inconsistent assay calibration limits the optimal use of these markers. A high-performance liquid chromatography (HPLC)-based assay was developed using synthetic PYD and DPD as calibrators to analyze free and total PYD and DPD in urine. The spectroscopic characteristics of the synthetic calibrators were identical to those of calibrators isolated from bone. The mean intraassay variabilities of the HPLC method were 4.1 and 3.8%, respectively, for total DPD and PYD and 9.8 and 9.5%, respectively, for free DPD and PYD. The mean interassay variabilities were 9.1 and 8.2% for total DPD and PYD and 8.6 and 7.0% for free DPD and PYD, respectively. The mean recoveries were 98.1% for total DPD, 100.8% for total PYD, 98.6% for free DPD, and 94.9% for free PYD. The method exhibits a good correlation with a commercial immunoassay and with other HPLC assays currently used in hospital laboratories.

Amino Acids↗
PubMed2003

N-acetyl aspartate estimation: a potential method for determining neuronal loss in the transmissible spongiform encephalopathies.

Neurodegenerative pathology is typical of the transmissible spongiform encephalopathies (TSEs), and is thought to underlie clinical disease. Some morphometric studies have shown early focal neurone loss, but the full extent of TSE induced neuronal loss in the central nervous system is not known, and can only be accurately estimated using intensive morphometric techniques. We have used a murine scrapie model in which we determined the levels of N-acetyl aspartate (NAA), a putative neuronal marker, by both high-performance liquid chromatography and high resolution, proton magnetic resonance spectroscopy in samples taken sequentially from the hippocampus. This scrapie model develops severe neuronal loss in the hippocampus, and the NAA levels showed a significant positive correlation with our previous morphometric estimates of neurone number. NAA measurement may therefore provide a practical alternative to intensive morphometric techniques in the investigation of neurodegeneration in the TSEs.

Animals↗
PubMed2003

Use of block copolymers of poly(ortho esters) and poly (ethylene glycol) micellar carriers as potential tumour targeting systems.

Amphiphilic AB and ABA block copolymers have been prepared from poly (ortho esters) and poly (ethylene glycol). Such block copolymers readily form micellar dispersions in water, or buffers. The CMC is in the range of 3 x 10(-4)-5 x 10(-4) g/l which is a value low enough to assure retention of micelle integrity upon intravenous injection. The size, as determined by dynamic light scattering was in the 40-70 nm range. The micelles can be stored in lyophilized form for at lest 8 months and easily reconstituted to the original properties. The micelles are stable in PBS at pH 7.4 and 37 degrees C for 3 days and in a citrate buffer at pH 5.5 and 37 degrees C for 2 h. Stability in the presence of bovine serum albumin depends on the structure of the block copolymer and especially the length of the POE block.

Drug Carriers↗
PubMed2002

Development and applications of injectable poly(ortho esters) for pain control and periodontal treatment.

Poly(ortho esters) with a low glass transition temperature are semi-solid materials so that therapeutic agents can be incorporated at room temperature, without the use of solvents, by a simple mixing procedure. When molecular weights are limited to < 5 kDa, such materials are directly injectable using a needle size no larger than 22 gauge. Somewhat hydrophilic polymers can be produced by using the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane and triethylene glycol (TEG), while hydrophobic materials can be produced by using the diketene acetal and 1,10-decanediol. Molecular weight can be reproducibly controlled by using an excess of the diol, or by use of an alcohol that acts as a chain-stopper. Erosion rates can be controlled by varying the amount of latent acid incorporated into the polymer backbone. Toxicology studies using the TEG polymer have been completed and have shown that the polymer is non-toxic. Toxicology studies using the decanediol polymer are underway. Development studies using the TEG polymer aimed at providing a sustained delivery of an analgesic agent to control post-surgical pain are under development and human clinical trials using the decanediol polymer for the treatment of periodontitis are also underway.

Anesthetics, Local↗
PubMed2002

Randomised controlled trial of continuous positive airway pressure and standard oxygen therapy in acute pulmonary oedema; effects on plasma brain natriuretic peptide concentrations.

AIMS: The study aim was to compare the effects of continuous positive airway pressure (CPAP) on clinical outcomes and plasma neurohormonal concentrations in patients with acute pulmonary oedema. METHODS AND RESULTS: In addition to standard therapy, 58 consecutive patients were randomized to receive 60% inhaled oxygen with or without CPAP at 7.5 cmH(2)O pressure. Clinical variables, symptoms and oxygenation were monitored and plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) concentrations estimated at 0, 1, 6 and 24 h. CPAP was associated with less breathlessness at 1 h (P<0.001), no treatment failures and more rapid resolution in respiratory rate (P<0.001), heart rate (P<0.001) and acidosis (P<0.005). Length of hospital stay was similar but there was a trend for a reduction in overall hospital mortality in the CPAP group (0.10>P>0.05). Plasma BNP concentrations rose progressively (P<0.001) before falling below admission concentrations at 24 h. Plasma neurohumoral concentrations were unaffected by CPAP treatment but were elevated in patients who died or had acute myocardial infarction. CONCLUSION: CPAP produces a more rapid clinical and symptomatic improvement in patients with acute pulmonary oedema, particularly within the first hour. CPAP is a useful adjunctive treatment in the early management of acute heart failure.

Acute Disease↗
PubMed2002

Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: preliminary trial in humans.

The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37 degrees C, for up to 14 days. Total polymer degradation concomitant with drug release was obtained. Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis. In the first trial including 6 patients, single-rooted teeth and molar teeth with furcations were treated immediately after scaling and root planing. Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period. However, retention of the formulation was minimal in this first study. An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets. For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens.

Adult↗
PubMed2002

The relation between adrenal function and the severity of bronchial hyperresponsiveness in children as measured by the methacholine provocation test.

BACKGROUND: There is no satisfactory explanation why some individuals experience severe attacks of asthma, yet others, exposed to similar stimuli, have a milder form of the disease. OBJECTIVE: We tested the hypothesis that children with more severe disease may have relative adrenal insufficiency compared to the children with milder disease. PATIENTS AND METHODS: Sixteen children with chronic asthma aged 8-16 years old were studied. Adrenal function was evaluated by the 24-h excretion of urinary free cortisol (UFC) before and after ACTH stimulation, and by plasma cortisol levels before and 60 min after ACTH administration. The severity of bronchial hyperresponsiveness was evaluated by the methacholine provocation test. RESULTS: Nine children had 20% fall in forced expiratory volume in 1 sec (FEV1) after a provocative concentration (PC20FEV1) of methacholine > or =2.5 mg/ml and were considered as having mild-moderate bronchial hyperresponsiveness (Group A). Seven children had a PC20FEV1 of < or =1.25 mg/ml and were considered as having severe bronchial hyperresponsiveness (Group B). No significant difference was found between the peak plasma cortisol response to ACTH between the two groups (634+/-182 and 586+/-137 nmol/l, respectively). However, there was a significant statistical difference (p <0.01) in the 24-h UFC response to ACTH between the children from Group A (345+/-107 nmol/m2 ) and the children from Group B (161+/-125 nmol/m2). CONCLUSIONS: Based on the low levels of 24-h UFC secretion in severely asthmatic children in our study, we propose the encouragement of provision of a short course of inhaled steroids to be kept at home for the emergency therapy of those children identified as having high-risk asthma.

Adolescent↗
PubMed2001

Release of BSA from poly(ortho ester) extruded thin strands.

A solventless procedure was used where powdered polymer and micronized protein were intimately mixed and then extruded into 1 mm strands that were cut to the desired length. The polymers used were poly(ortho esters) specifically designed to allow extrusion in the neighborhood of 70 degrees C. At these temperatures many proteins maintain activity in the dry state. In vitro erosion and BSA release results indicate that after a fairly long lag-time, BSA release and polymer erosion occur concomitantly indicating an erosion-controlled process. The lag-time could be eliminated by the addition to the mixture prior to extrusion between 1 and 5 wt% poly(ethylene glycol) or its methoxy derivatives. The lag-time could also be eliminated by using an AB-block copolymer where A is poly(ortho ester) and B is poly(ethylene glycol).

Crystallization↗
PubMed2001

Optimization of a novel bioerodible device based on auto-catalyzed poly(ortho esters) for controlled delivery of tetracycline to periodontal pocket.

Local delivery of antimicrobial agents in inflamed periodontal pocket has been shown to be effective in reducing periodontopathic microorganisms. This research focuses on developing and characterizing bioerodible formulations based on auto-catalyzed poly(ortho esters) (POExLAy) for modulated release of tetracycline over 2 weeks. POExLAy are a new versatile family of POE-containing lactoyl lactyl dimers in the polymer backbone. By modifying the proportion of lactic acid in the polymer, viscous or solid materials having different degradation rate can be produced. The formulations can be either injected or placed as a solid device directly into the periodontal pocket. Tetracycline-free base incorporated into these materials was released within 10-14 days depending on polymer structure. Increase in lactic acid content in the polymer tended to increase the drug release rate and to reduce the initial lag time. Tetracycline release from such bioerodible delivery system occurs predominantly by surface erosion of the polymeric matrix, leading to kinetics which can be zero order. This periodontal drug delivery system is designed to be used as an adjunct in the treatment of periodontal diseases. Clinical studies are currently in progress.

Biocompatible Materials↗
PubMed2001

Onset of accumulation of PrPres in murine ME7 scrapie in relation to pathological and PrP immunohistochemical changes.

In a murine scrapie model, three different methods (immunohistochemistry, Western blotting and histoblotting) for determining disease-specific PrP accumulation were compared. The incubation period of ME7 scrapie in the F1 cross of C57 BL and VM/Dk mice is about 230 days. Mice show hippocampal neuronal loss from 160-180 days post-inoculation (dpi), CA1 neuron dendritic spine atrophy at 126 dpi, and axon terminal degeneration and synaptic loss from 84-98 dpi. Infectivity titres of at least 100 are present from 40 dpi. PrP was detected immunohistochemically at 60 dpi in the hippocampus and in the thalamus. Thus, PrP accumulation in the hippocampus precedes even the earliest neurodegenerative changes. Low amounts of PrP immunolabelling were found between 60 dpi and 126 dpi, after which the intensity increased markedly. The histoblot method detected PrPres in one of four mice at 100 dpi. Western blotting of whole brains first identified the PrPres at 80 dpi. Thus, in our hands, the most sensitive method for detecting disease-specific accumulations of PrP was immunohistochemical examination. However, immunohistochemical methods are unable to distinguish the normal and abnormal isoforms of PrP. It is therefore possible that the initial accumulation of PrP takes place as PrPsen and that the translation of PrPsen to PrPres does not take place until the later stages of the disease process. The accumulation of disease-specific PrP lags behind the development of infectivity titres. The relative rates of increase of infectivity titre and PrP accumulation are different, suggesting that these parameters may be measures of different biological events.

Animals↗
PubMed2001

A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model.

BACKGROUND: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. METHODS: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. RESULTS: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. CONCLUSIONS: The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.

Adolescent↗
PubMed2001

Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model.

BACKGROUND: The pharmacology of propofol infusions administered for long-term sedation of intensive care unit (ICU) patients has not been fully characterized. The aim of the study was to develop propofol dosing guidelines for ICU sedation based on an integrated pharmacokinetic-pharmacodynamic model of propofol infusions in ICU patients. METHODS: With Institutional Review Board approval, 30 adult male medical and surgical ICU patients were given target-controlled infusions of propofol for sedation, adjusted to maintain a Ramsay sedation scale score of 2-5. Propofol administration in the first 20 subjects was based on a previously derived pharmacokinetic model for propofol. The last 10 subjects were given propofol based on a pharmacokinetic model derived from the first 20 subjects. Plasma propofol concentrations were measured, together with sedation score. Population pharmacokinetic and pharmacodynamic parameters were estimated by means of nonlinear regression analysis in the first 20 subjects, then prospectively tested in the last 10 subjects. An integrated pharmacokinetic-pharmacodynamic model was used to construct dosing regimens for light and deep sedation with propofol in ICU patients. RESULTS: The pharmacokinetics of propofol were described by a three-compartment model with lean body mass and fat body mass as covariates. The pharmacodynamics of propofol were described by a sigmoid model, relating the probability of sedation to plasma propofol concentration. The pharmacodynamic model for propofol predicted light and deep levels of sedation with 73% accuracy. Plasma propofol concentrations corresponding to the probability modes for sedation scores of 2, 3, 4, and 5 were 0.25, 0.6, 1.0, and 2.0 microg/ml. Predicted emergence times in a typical subject after 24 h, 72 h, 7 days, and 14 days of light sedation (sedation score = 3 --> 2) with propofol were 13, 34, 198, and 203 min, respectively. Corresponding emergence times from deep sedation (sedation score = 5 --> 2) with propofol were 25, 59, 71, and 74 h. CONCLUSIONS: Emergence time from sedation with propofol in ICU patients varies with the depth of sedation, the duration of sedation, and the patient's body habitus. Maintaining a light level of sedation ensures a rapid emergence from sedation with long-term propofol administration.

Adult↗
PubMed2001

Understanding the bariatric client and providing a safe hospital environment.

Mobility is a basic human need that, when not met, leads to a cascade of physical problems. Meeting the challenge of safe mobility for bariatric patients is a concern for many healthcare institutions. More than 20% of the adult population now has a body mass index equal to or greater than 30 and are classified as obese. Obesity is associated with many well-known health risks, including heart disease, metabolic disorders, and cancer. Nurses should be aware of these health risks, the interplay between mobility and health risks, and the national guidelines for treating the obese patient population. This article presents an overview of national guidelines for identifying, evaluating, and treating bariatric patients and identifies issues that create challenges to providing a safe environment for mobility among hospitalized obese patients.

Adult↗