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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 271 records · Page 15Linked to original sources
PubMed1998

Lessons to be learned: a case study approach. An unusual case of alveolar deposition from swallowing metallic mercury in an attempt at self-poisoning.

The authors report a case of deliberate self-poisoning in a drug addict who swallowed elemental mercury: in so doing he inadvertently acquired a permanent diffuse deposition of mercury particles throughout both lung fields. Swallowed mercury should be relatively harmless in small quantity but the high specific gravity and free flowing properties of elemental mercury allowed it to overcome the normal swallowing pathways--such that some of it passed into the bronchial tree instead of passing harmlessly through the gut. In that site its significant vapour pressure, together with its potential for oxidation to inorganic mercury--which may, in turn, be absorbed across the alveolar membrane, gives high potential for mercury poisoning.

Adult↗
PubMed1998

A lasting public health response to an outbreak of HIV infection in a Scottish prison?

Between April and June 1993, 8 cases of acute clinical hepatitis B infection and 2 seroconversions to HIV infection were detected among drug injecting inmates of HM Prison Glenochil in Scotland. To prevent the further spread of infection, an initiative which involved counselling and voluntary attributable HIV testing was conducted over a 10-day period commencing at the end of June. A team of 18 counsellors and phlebotomists was brought together rapidly as part of a unique organizational exercise in the field of public health. Fourteen cases of HIV infection were identified of which 13 were almost certainly infected in Glenochil. Following the exercise, a range of harm reduction measures for injecting prisoners was introduced; these included the availability of hepatitis B vaccine, provision of bleach tablets which could be used to clean injecting equipment, a methadone detoxification programme, increased training for prison officers and improved access to drug and harm minimization counselling for inmates. By mid-1996 all these measures had been sustained and several could be found in many other prisons throughout Scotland. Follow-up investigations showed no evidence of epidemic spread of HIV during the 12 months after the initiative. While the frequency of injecting and needle/syringe sharing may have decreased over the last 3 years, these activities are still being reported and it is highly likely that transmissions of bloodborne infections, in particular hepatitis C, continue to occur. The surveillance and prevention of infections associated with injecting drug use in the prison setting remain a high public health priority.

Disease Outbreaks↗
PubMed1998

The multistep process of homotypic neutrophil aggregation: a review of the molecules and effects of hydrodynamics.

Homotypic adhesion of neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes are supported by L-selectin and beta 2-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand the hydrodynamic stresses. Using cone and plate viscometry to apply a uniform linear shear field to suspensions of neutrophils and flow cytometry to quantitate the size distribution of aggregates formed over the time course of formyl peptide stimulation, we conducted a detailed examination of the affect of shear rate and shear stress on the kinetics of cell aggregation. The efficiency of aggregate formation was fit from a mathematical model based on Smoluchowski's two-body collision theory. Over a range of venular shear rates (400-800 s-1), approximately 90% of the single cells are recruited into aggregates ranging from doublets to grouping larger than sextuplets. Adhesion efficiency fit to the kinetics of aggregation increased with shear rate from approximately 20% at 100 s-1 to a maximum level of approximately 80% at 400 s-1. This increase to peak adhesion efficiency was dependent on L-selectin and beta 2-integrin, and was resistant to shear stress up to approximately 7 dyn/cm2. When L-selectin was blocked with antibody, beta 2-integrin (CD11a,b) supported adhesion at low shear rates (< 400 s-1). Aggregates formed over the rapid phase of aggregation remain intact and resistant to shear up to 120 s. At the end of this plateau phase of stability, aggregates spontaneously dissociate back to singlets. The rate of cell disaggregation is linearly proportional to the applied shear rate. The binding kinetics of selectin and integrin appear to be optimized to function within discrete ranges of shear rate and stress, providing an intrinsic mechanism for the transition from neutrophil tethering to firm but reversible adhesion.

Animals↗
PubMed1998

Impact of the prehospital trauma life support programme in Trinidad and Tobago.

The impact of the Prehospital Trauma Life Support (PHTLS) programme, introduced in Trinidad and Tobago in 1992, was assessed by questionnaires completed by 26 medical personnel (MP); 71 ambulance personnel (AP); and 50 non ambulance paramedical personnel (NAP). Of the 23 MP, 45 AP and 38 NAP who were aware of the programme, 19 (82.6%) MP, 40 (88.9%) AP and 25 (65.8%) NAP were able to differentiate personnel that had taken the PHTLS programme based on their performance. 32 (71.1%) of the AP were PHTLS trained. 24 (53.3%) and 4 (9%) of the AP identified poor equipment and poor supervision, respectively, as reasons for difficulty in applying PHTLS principles. Improvements observed among those completing the PHTLS programme were: improved resuscitation techniques by 20 (86.9%) MP, 38 (84.4%) AP and 27 (71.1%) NAP; better vital signs recording by 8 (34.8%) MP, 27 (60%) AP and 8 (21.1%) NAP; improved immobilization by 23 (100%) MP, 40 (88.9%) AP and 33 (86.8%) NAP; better haemorrhage control by 22 (95.6%) MP, 40 (88.9%) AP and 24 (63.2%) NAP; appropriate splinting of fractures by 23 (100%) MP, 40 (88.9%) AP and 32 (84.2%) NAP; and increased utilization of oxygen by 15 (65.2%) MP, 31 (68.9%) AP and 21 (55.3%) NAP. 32 (71.1%) AP with PHTLS training indicated improvement in their ability to resuscitate and transport trauma victims, with 42 (93.3%) reporting improvement in overall prehospital care. Medical, paramedical and ambulance personnel all perceive a significant positive impact of PHTLS training on prehospital trauma care. Although improvements in supervision, documentation and equipment are still required, improved trauma resuscitative techniques after PHTLS training should improve trauma patient outcome in Trinidad and Tobago.

Education, Continuing↗
PubMed1998

The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta.

The role of dual energy x-ray absorptiometry (DEXA) in the evaluation of the pediatric patient with multiple fractures has not been well established. We retrospectively examined the medical records of 45 patients who had presented to our institution with multiple fractures of unknown cause, who were not known to have osteogenesis imperfecta, and who had obtained DEXA as part of their evaluation. Of these, 26 patients had sufficient clinical data for inclusion in this study. Patients underwent DEXA of the anteroposterior spine and whole body. A z score was calculated to normalize the DEXA values for age. The diagnosis of osteogenesis imperfecta was correlated with the outcome of each DEXA scan to assess the validity of DEXA as a diagnostic tool. The DEXA of the anteroposterior spine had the highest sensitivity at 91.7%, while DEXA of the whole body had the highest specificity at 100.0%. Decreased bone mineral density may be associated with osteogenesis imperfecta, and DEXA is helpful in detecting low bone mineral density that may be missed on plain radiographs of children with milder forms of osteogenesis imperfecta.

Absorptiometry, Photon↗
PubMed1998

Neuropsychologic aspects of multiple sclerosis.

The psychological well being of the patient and the patient's entire family is critically important to successful rehabilitation of individuals with multiple sclerosis (MS). This article deals with the psychotherapeutic management and problems faced by the person with MS, including fatigue, chronic pain, stressful life events, and cognitive defects.

Attitude to Health↗
PubMed1998

The influence of stereoisomerism on the pharmacokinetics of Tc radiopharmaceuticals.

The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development.

Humans↗
PubMed1997

Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice.

Dietary calorie restriction extends both mean and maximum life span and retards age-related diseases, including eye lens cataract in Emory mice. The beneficial effects of calorie restriction have been hypothesized to reflect enhanced tissue antioxidant capacity. As a test of this hypothesis, we reared male and female Emory mice on control (C) or 40% calorie-restricted (R) diets. We then determined activities of total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) in eye lens, liver and kidney of young (4.5 or 6 months), mature (11 or 12 months) and old (22 months) animals. Effects of diet, age and sex were evaluated by multi-factor ANOVA. Only kidney GR activities (mean +/- S.E.M.) were significantly enhanced with the R diet (R, 61 +/- 2 vs. C, 54 +/- 3 U/mg protein; P = 0.03). More frequently, we noted reduced antioxidant enzyme activity in R as compared with C animals, including reduced activities of T-SOD in lens, liver and kidney, Cu/Zn-SOD in liver and kidney, liver Mn-SOD and liver CAT (P < 0.05). Effects of age on antioxidant enzyme activity in C mice included age-dependent decreases in lens and kidney CAT and in liver Mn-SOD. There was also an age-dependent increases in liver and kidney Cu/Zn-SOD and liver GR. None of these age-dependent alterations in antioxidant enzyme function were attenuated in tissues of mice fed the R diet. Values for liver CAT were significantly lower in females than in males (P = 0.05). These results indicate that antioxidant enzyme activities in Emory mouse tissues are influenced by diet, age and sex. However, it is unlikely that increased lifespan and attenuation of cataract (and perhaps other age-dependent debilities), which are associated with the R diet in the Emory mouse, are due to enhanced antioxidant enzyme capabilities.

Age Factors↗
PubMed1997

Macroscopic orientation of natural and model membranes for structural studies.

One approach for obtaining high-resolution structural and functional information for biomembranes and their proteins is by static solid-state NMR of oriented systems. Here, a general procedure to align fully functional biological membranes containing large membrane proteins (Mr >30,000) is described. The method, based on the isopotential spin-dry ultracentrifugation technique, relies on the centrifugation of membrane fragments onto a support with simultaneous, or subsequent, partial evaporation of the solvent which aids alignment. The quality of orientation, as shown by the mosaic spread of the samples, was monitored by static solid-state 31P NMR for the phospholipids and by 2H NMR for a deuterated retinal in bovine rhodopsin. The generality of this method is demonstrated with three different membranes containing bovine rhodopsin in reconstituted bilayers, natural membranes with the red cell anion exchange transport protein in erythrocytes, band 3, and the nicotinic acetylcholine receptor.

Animals↗
PubMed1997

Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress.

Upon oxidative stress cells show an increase in the oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio with a concomitant decrease in activity of the ubiquitinylation pathway. Because most of the enzymes involved in the attachment of ubiquitin to substrate proteins contain active site sulfhydryls that might be covalently modified (thiolated) upon enhancement of GSSG levels (glutathiolation), it appeared plausible that glutathiolation might alter ubiquitinylation rates upon cellular oxidative stress. This hypothesis was explored using intact retina and retinal pigment epithelial (RPE) cell models. Exposure of intact bovine retina and RPE cells to H2O2 (0.1-1.7 micromol/mg) resulted in a dose-dependent increase in the GSSG:GSH ratio and coincident dose-dependent reductions in the levels of endogenous ubiquitin-activating enzyme (E1)-ubiquitin thiol esters and endogenous protein-ubiquitin conjugates and in the ability to form de novo retinal protein-125I-labeled ubiquitin conjugates. Oxidant-induced decrements in ubiquitin conjugates were associated with 60-80% reductions in E1 and ubiquitin-conjugating enzyme (E2) activities as measured by formation of ubiquitin thiol esters. When GSH levels in RPE cells recovered to preoxidation levels following H2O2 removal, endogenous E1 activity and protein-ubiquitin conjugates were restored. Evidence that S thiolation of E1 and E2 enzymes is the biochemical link between cellular redox state and E1/E2 activities includes: (i) 5-fold increases in levels of immunoprecipitable, dithiothreitol-labile 35S-E1 adducts in metabolically labeled, H2O2-treated, RPE cells; (ii) diminished formation of E1- and E2-125I-labeled ubiquitin thiol esters, oligomerization of E225K, and coincident reductions in protein-125I-labeled ubiquitin conjugates in supernatants from nonstressed retinas upon addition of levels of GSSG equivalent to levels measured in oxidatively stressed retinas; and (iii) partial restoration of E1 and E2 activities and levels of protein-125I-labeled ubiquitin conjugates in supernatants from H2O2-treated retinas when GSSG:GSH ratios were restored to preoxidation levels by the addition of physiological levels of GSH. These data suggest that the cellular redox status modulates protein ubiquitinylation via reversible S thiolation of E1 and E2 enzymes, presumably by glutathione.

Animals↗
PubMed1997

Activity of ubiquitin-dependent pathway in response to oxidative stress. Ubiquitin-activating enzyme is transiently up-regulated.

Relations between the ubiquitin pathway and cellular stress have been noted, but data regarding responses of the ubiquitin pathway to oxidative stress are scanty. This paper documents the response of this pathway to oxidative stress in lens cells. A brief exposure of lens epithelial cells to physiologically relevant levels of H2O2 induces a transient increase in activity of the ubiquitin-dependent pathway. Ubiquitin conjugation activity was maximal and increased 3. 5-9.2-fold over the activity noted in untreated cells by 4 h after removal of H2O2. By 24 h after removal of H2O2, ubiquitin conjugation activity returned to the level noted in untreated cells. In parallel to the changes in ubiquitin conjugation activity, the activity of ubiquitin-activating enzyme (E1), as determined by thiol ester formation, increased 2-6.7-fold during recovery from oxidation. Addition of exogenous E1 resulted in an increase in ubiquitin conjugation activity and in the levels of ubiquitin carrier protein (E2)-ubiquitin thiol esters in both the untreated cells and the H2O2-treated cells. These data suggest that E1 is the rate-limiting enzyme in the ubiquitin conjugation process and that the increases in ubiquitin conjugation activity which are induced upon recovery from oxidation are primarily due to increased E1 activity. The oxidation- and recovery-induced up-regulation of E1 activity is primarily due to post-synthetic events. Substrate availability and up-regulation of E2 activities also appear to be related to the enhancement in ubiquitinylation upon recovery from oxidative stress. The oxidation-induced increases in ubiquitin conjugation activity were associated with an increase in intracellular proteolysis, suggesting that the transient increase in ubiquitinylation noted upon recovery from oxidative stress may play a role in removal of damaged proteins from the cells.

Adenosine Triphosphate↗
PubMed1997

Fusimotor influence on jaw muscle spindle activity during swallowing-related movements in the cat.

1. The activity patterns of muscle spindle afferents in jaw-closer muscles were studied during reflex swallowing movements in anaesthetized cats. Simultaneous records were made of the electromyogram (EMG) in masseter and anterior digastric muscles and of the unloaded jaw movements. The underlying patterns of fusimotor activity were deduced by comparing afferent discharges occurring during active swallowing with those occurring when exactly the same movements were imposed passively. The interpretation of spindle behaviour was greatly facilitated by characterizing the afferents according to the evidence for their contact with the various intrafusal muscle fibres, derived from testing with succinylcholine. It was also valuable to have two different types of afferent recorded simultaneously. 2. There was clear evidence of fusimotor activity occurring during active jaw closing so as to oppose the spindle silencing. This effect was most marked in b2c-type afferents (probably secondaries) and was therefore attributed to a modulation of static fusimotor discharge approximately in parallel with alpha-activity. 3. Afferents with evidence of bag1 fibre contacts (primaries) showed much greater sensitivity to muscle lengthening during active movement than when the movement was imposed. This difference was exaggerated when anaesthesia was deepened for the passive movements. This was interpreted as evidence for a higher level of dynamic fusimotor activity maintained during active movements than at rest. 4. The results support the view that for a variety of active jaw movements, static fusimotor neurone firing is modulated roughly in parallel with alpha-activity but leading it so as to counteract spindle unloading. Dynamic fusimotor neurone firing appears to be set at a raised level during active movements. Anaesthesia appears to depress activity in the alpha-motoneurones more than in gamma-motoneurones.

Afferent Pathways↗
PubMed1997

Intra- and interobserver variability of MRI prostate volume measurements.

BACKGROUND: The Early Intervention Study, a placebo-controlled clinical trial, enrolled approximately 200 patients between age 45-65 years who had mild symptoms associated with early benign hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging (MRI) and read by the local radiologist, who was blinded to the treatment group but not to the sequence of MRI scans. In order to ascertain whether knowledge of the sequence of the MRI scans by the local radiologist was introducing bias in prostate volume changes, a single radiologist was selected to reread all MRI scans at the end of the study. METHODS: Each film was masked as to patient identity, study drug, and date. A new randomization schedule was prepared to blind the single reader to both sequence and treatment. The two sets of readings were compared. RESULTS: Accuracy was dramatically improved when defined as percentage of patients with a 20% or more decrease in prostate volume, from 14% to 0% in placebo patients, and from 38% to 29% in finasteride patients. The variability was significantly reduced (by 50%) when read by a single observer [1]. CONCLUSIONS: A single reader, blinded to time sequence as well as to therapy, improves the accuracy and precision of the measurements when compared to multiple readers, blinded only to drug therapy.

Aged↗
PubMed1997

Regulation of NF-kappaB and HIV-1 LTR activity in mouse L cells by ultraviolet radiation: LTR trans-activation in a nonirradiated genome in heterokaryons.

A mouse model system for studying the effect of ultraviolet (uv) radiation on reporter gene expression directed by the human immunodeficiency virus type 1 long-terminal repeat (HIV-LTR) has been developed to address the signals required for LTR trans-activation in cells with the reporter gene stably integrated into the genome. In a stable mouse L cell clone, L-15, NF-kappaB DNA binding activity induced by uv-C (254 nm) but not by tumor necrosis factor-alpha (TNF-alpha) or 12-O-tetra-decanoylphorbol-13-acetate (TPA) correlated with the stimulation of HIV-LTR-directed chloramphenicol acetyltransferase (CAT) activity; uv-C was more effective than uv-B (312 nm), while uv-A (365 nm) had little effect on CAT activity. Inducers of oxidative stress, such as H2O2 treatment up to 200 microM or ionizing radiation up to 20 Gy, also had little effect on CAT expression. Pyrrolidine dithiocarbamate (PDTC) inhibited NF-kappaB DNA binding and stimulation of CAT activity by uv-C in a dose-dependent manner. Unexpectedly, PDTC induced NF-kappaB DNA binding that was additive with the response with TNF. In an effort to separate uv irradiation and uv-induced DNA damage from transactivation of the HIV-LTR we devised a heterokaryon system. The fusion of uv-irradiated human fibroblasts with a mouse L cell clone containing the HIV-LTR-directed lacZ gene resulted in the activation of lacZ activity that was detected in heterokaryons at the single-cell level. These data suggest that uv-induced DNA damage in the chromosomal DNA containing the reporter gene cannot explain activation of the HIV-LTR. This finding demonstrates LTR trans-activation in a nonirradiated genome.

Animals↗
PubMed1997

Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment.

OBJECTIVE: To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). METHODS: Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. RESULTS: Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. CONCLUSION: Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

Adult↗