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Biomedical subjects

D Taylor

Publications and source records attributed to D Taylor.

At least 55 records · Page 3Linked to original sources
PubMed2003

Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis.

OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.

Arthritis, Rheumatoid↗
PubMed2003

Hypoalbuminaemia in critically ill children: incidence, prognosis, and influence on the anion gap.

AIMS: Hypoalbuminaemia has significance in adult critical illness as an independent predictor of mortality. In addition, the anion gap is predominantly due to the negative charge of albumin, thus hypoalbuminaemia may lead to its underestimation. We examine this phenomenon in critically ill children, documenting the incidence, early evolution, and prognosis of hypoalbuminaemia (<33 g/l), and quantify its influence on the anion gap. METHODS: Prospective descriptive study of 134 critically ill children in the paediatric intensive care unit (ICU). Paired arterial blood samples were taken at ICU admission and 24 hours later, from which blood gases, electrolytes, and albumin were measured. The anion gap (including potassium) was calculated and then corrected for albumin using Figge's formula. RESULTS: The incidence of admission hypoalbuminaemia was 57%, increasing to 76% at 24 hours. Neither admission hypoalbuminaemia, nor extreme hypoalbuminaemia (<20 g/l) predicted mortality; however, there was an association with increased median ICU stay (4.9 v 3.6 days). After correction for albumin the incidence of a raised anion gap (>18 mEq/l) increased from 28% to 44% in all samples (n = 263); this discrepancy was more pronounced in the 103 samples with metabolic acidosis (38% v 73%). Correction produced an average increase in the anion gap of 2.7 mEq/l (mean bias), with limits of agreement of +/-3.7 mEq/l. CONCLUSION: Admission hypoalbuminaemia is common in critical illness, but is not an independent predictor of mortality. However, failure to correct the anion gap for albumin may underestimate the true anion gap, producing error in the interpretation of acid-base abnormalities. This may have treatment implications.

Acid-Base Imbalance↗
PubMed2003

Morphological and populational characteristics of hemocytes of Ornithodoros moubata nymphs during the ecdysial phase.

The ultrastructure and characteristics of hemocytes of argasid tick species, Ornithodoros moubata, during the ecdysdial phase are herein presented. Hemocyte classes/populations characterized based on their affinity with Giemsa stain and ultrastructural differences comprised the prohemocytes, nongranular cells (Nc), eosinophilic granular cells (Ec), basophilic granular cells (Bc), and unidentified cells. Significant changes/shift in the ratio of hemocyte classes/population was apparent in ticks before and after the ecdysial phase. The granule-scant basophilic granular cells (sBc) constituted the most abundant hemocyte population in the ecdysial phase. Nymphs in ecdysis showed increases in Nc and sBc and decrease in Ec, a phenomenon that was reversed in unengorged nymphs and adults ticks. The significant increase in total Bc population in ecdysis relative to nonengorged ticks clearly point to blastogenesis of Bc taking place during the ecdysial phase and Bc's important role in the process of tissue remodeling.

Animals↗
PubMed2002

Longitudinal study of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme.

PURPOSE: To evaluate the long-term outcome of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme. METHOD: The cohort comprised of diabetic patients from nine market town General Practices around Exeter who first attended the diabetic retinopathy screening programme in 1992. Screening was carried out by a combination of dilated fundoscopy by a screening technician and a single 45 degrees Polaroid photograph of each eye. The prevalence of diabetic retinopathy at the baseline, the incidence of sight threatening diabetic retinopathy (STDR) in the next two rounds of screenings, and the long-term visual outcome are described. RESULTS: The cohort consisted of 775 patients (104 Type I, 517 Type II non-insulin-requiring and 154 Type II insulin-requiring). The mean age was 72.1 years (15-100), with mean disease duration of 13.0 years (1-79). Baseline prevalence was as follows: background retinopathy: 21.4%, proliferative: 2.8%, clinically significant macular oedema: 6.1%. The incidence of proliferative disease was 2.20% and 2.25% respectively in the next two rounds of screening (P > 0.05, chi2 test). The incidence of clinically significant macular oedema was also constant over next two rounds of screening, at 4.79% and 5.18% respectively (P > 0.05, chi2 test). Ninety-five (12.3%) patients were deceased and a further 179 (23%) patients were lost to follow-up by the third round. Only two patients with newly diagnosed STDR suffered deterioration of visual acuity to 6/60 or worse as a result of diabetic retinopathy. CONCLUSION: The incidence of STDR remained constant throughout the period of screening, reflecting the chronic progressive nature of the disease. Significant numbers of patients were lost to follow-up. Screening seemed effective in preserving vision in those patients with newly diagnosed STDR.

Adolescent↗
PubMed2002

Antibacterial peptide defensin is involved in midgut immunity of the soft tick, Ornithodoros moubata.

Two defensin genes A and B were previously demonstrated to be up-regulated by blood feeding in the soft tick, Ornithodoros moubata [Nakajima et al. (2001) Two isoforms of a member of the arthropod defensin family from the soft tick, Ornithodoros moubata (Acari: Argasidae). Insect Biochem Mol Biol 31: 747-751]. In this study, two defensin isoforms C and D similar to defensins A and B were newly cloned. A total of four defensins have been identified in O. moubata. All four Ornithodoros defensins are coded as prepro-defensins. Ornithodoros defensin genes consist of four exons and three introns, an organization reported in mussel defensins but not insect defensins. Ornithodoros defensin C and D genes are predominantly expressed in the midgut and up-regulated in response to blood feeding. The mature peptide of the previously cloned Ornithodoros defensin A was purified from the midgut lumen, indicating defensin is secreted into the midgut. These findings confirm the involvement of Ornithodoros defensin in midgut immunity.

Amino Acid Sequence↗
PubMed2002

Bone adaptation to load: microdamage as a stimulus for bone remodelling.

Mechanical loading in the proximal radius was increased by ulnar osteotomy (Group O), altered by Steinmann pinning (Group P) or unaltered in sham operated controls (Group C) in skeletally mature female sheep, aged 2-4 years. A series of intravenous fluorochromes were given to label bone formation and fuchsin-stained microdamage assessed at intervals of up to 24 weeks. Microcracks were present in all groups and were found in the original cortex near the periosteal surface. No microcracks were found in the new, fibrolamellar bone laid down at periosteal or endosteal surfaces. Mean microcrack length (49 microm, SD 10 microm) did not differ between groups or overtime. Microcrack numerical and surface densities and resorption cavity density peaked in all groups at 6 weeks, consistent with a regional acceleratory phenomenon (RAP), but the peaks were significantly greater in Group O. The density of refilling or secondary osteons peaked at 10 weeks and the mean time required for the formation of an osteon was 7.51 +/- 0.59 weeks. Fatigue-induced microdamage is normally present in bone and is increased due to repetitive loading of the mechanically overloaded radius. The location and timing of microcracks, resorption cavities and secondary osteons are consistent with the activation-resorption-formation remodelling cycle and suggest that microdamage is a stimulus for bone remodelling.

Analysis of Variance↗
PubMed2002

Three-dimensional reconstruction of Haversian systems in ovine compact bone.

Haversian systems or secondary osteons are an integral component of compact bone. However, as their exact shape is debatable, this study describes a technique to view their morphology in three dimensions. Bone remodeling in adult ovine long bones was labelled at intervals using a series of chelating fluorochromes. A series of longitudinal sections were cut at 25 microm intervals through blocks of the distal radius embedded in methylmethacrylate using a sledge macrotome. The chelating agents were used as markers of bone formation in the study of bone growth and osteon morphology. The two-dimensional image of each section was examined using an epifluorescence microscope. Images were transferred to a PC via a CCD low light colour video camera. Surface reference points were noted on each of the sections and, using computer software, a three-dimensional image of a refilling labelled osteon was reconstructed and its dimensions measured. Haversian systems may have a gentle spiral course along the longitudinal axis of the bone. They intertwine with adjacent osteons and give multiple branches along their course producing a complex pattern of organization. The mean labelled length and diameter of the osteons was 1.4 + 1 mm and 145 + 0.42 microm [Mean + S.D], respectively.

Animals↗
PubMed2002

Options for pharmacological management of obesity in patients treated with atypical antipsychotics.

Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.

Amantadine↗
PubMed2002

A comparison of three scoring systems for mortality risk among retrieved intensive care patients.

AIMS: To assess the impact of two paediatric intensive care unit retrieval teams on the performance of three mortality risk scoring systems: pre-ICU PRISM, PIM, and PRISM II. METHODS: A total of 928 critically ill children retrieved for intensive care from district general hospitals in the south east of England (crude mortality 7.8%) were studied. RESULTS: Risk stratification was similar between the two retrieval teams for scores utilising data primarily prior to ICU admission (pre-ICU PRISM, PIM), despite differences in case mix. The fewer variables required for calculation of PIM resulted in complete data collection in 88% of patients, compared to pre-ICU PRISM (24%) and PRISM II (60%). Overall, all scoring systems discriminated well between survival and non-survival (area under receiver operating characteristic curve 0.83-0.87), with no differences between the two hospitals. There was a tendency towards better discrimination in all scores for children compared to infants and neonates, and a poor discrimination for respiratory disease using pre-ICU PRISM and PRISM II but not PIM. All showed suboptimal calibration, primarily as a consequence of mortality over prediction among the medium (10-30%) mortality risk bands. CONCLUSIONS: PIM appears to offer advantages over the other two scores in terms of being less affected by the retrieval process and easier to collect. Recalibration of all scoring systems is needed.

Child↗
PubMed2002

Vertical water distribution during the drying of polymer films cast from aqueous emulsions.

We present a systematic study of the vertical uniformity of water distribution during the drying of waterborne colloidal films, testing the predictions of a Peclet number Pe defined for this system. Pe indicates the relative contributions of water evaporation and Brownian diffusion in determining the concentration profile in the vertical direction ( i.e. normal to the substrate). When Pe < 1, the water concentration in films cast from an alkyd emulsion is found via magnetic-resonance profiling to be uniform with depth, which is consistent with expectations. When Pe > 1, a gradient in the water concentration develops, with less water near the interface with air. The water profiles reveal that the alkyd particles do not coalesce immediately upon contact in close-packing. At later times, a concentrated surface layer develops, but particles are not coalesced in this layer to form a continuous "skin", but rather the structure is likely to be that of a biliquid foam.

Journal Article↗
PubMed2002

Effects of 10 mg and 15 mg oral procyclidine on critical flicker fusion threshold and cardiac functioning in healthy human subjects.

The critical flicker fusion threshold (CFFT) is thought to index alertness and cortical arousal. Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in schizophrenia. This study examined the effects of clinically relevant doses of oral procyclidine administration on CFFT and heart rate in two separate experiments (Experiment 1, drug dose: 10 mg, n = 16; Experiment 2, drug dose: 15 mg, n = 12) involving healthy subjects using a double-blind, placebo-controlled, cross-over design. 10 mg procyclidine had no significant effect on CFFT, heart rate or self-ratings of mood, but the 15 mg dose significantly lowered CFFT at 1 h and 2 h after procyclidine administration, increased drowsiness ratings and produced a drop in heart rate. The effects observed in this study may have implications for treatment compliance of schizophrenic patients, choice of antipsychotics, prescribing to patients with heart disease and monitoring of cardiac function under treatment. Further investigations are required to quantify the effects of procyclidine on CFFT and cardiac function in patients with schizophrenia.

Adult↗
PubMed2002

Caspase activity and expression of cell death genes during development of human preimplantation embryos.

It has been observed that apoptosis occurs in human blastocysts. In other types of cell, the characteristic morphological changes seen in apoptotic cells are executed by caspases, which are regulated by the BCL-2 family of proteins. This study investigated whether these components of the apoptotic cascade are present throughout human preimplantation development. Developing and arrested two pronucleate embryos at all stages were incubated with a fluorescently tagged caspase inhibitor that binds only to active caspases, fixed, counterstained with 4,6-diamidino-2-phenylindole (DAPI) to assess nuclear morphology and examined using confocal microscopy. Active caspases were detected only after compaction, at the morula and blastocyst stages, and were frequently associated with apoptotic nuclei. Occasional labelling was seen in arrested embryos. Expression of proapoptotic BAX and BAD and anti-apoptotic BCL-2 was examined in single embryos using RT-PCR and immunohistochemistry. BAX and BCL-2 mRNAs were expressed throughout development, whereas BAD mRNA was expressed mainly after compaction. Simultaneous expression of BAX and BCL-2 proteins within individual embryos was confirmed using immunohistochemistry. The onset of caspase activity and BAD expression after compaction correlates with the previously reported appearance of apoptotic nuclei. As in other types of cell, human embryos express common molecular components of the apoptotic cascade, although apoptosis appears to be suppressed before compaction and differentiation.

Apoptosis↗
PubMed2002

Measuring consultation skills in primary care in England: evaluation and development of content of the MAAS scale.

BACKGROUND: Consultation skills are essential for general practice. Tools for measuring consultation skills in everyday practice are not well developed AIM: To examine and develop the content validity of the MAAS History-taking and Advice Checklist GP (MAAS-GP) tool which is used in The Netherlands for testing consultation skills, with simulated patients in United Kingdom general practice from the perspectives of both general practitioners and patients. DESIGN OF STUDY: Qualitative research using semi-structured interviews. SETTING: Alternate patients attending seven general practices in the north west of England. METHOD: Thematic analysis of the contents of patient and GP interviews, and of focus groups, mapping key themes to the MAAS-GP. RESULTS: There was strong agreement between patients and GPs on issues mapping to 46 out of 68 items of the MAAS-GP. Eight further MAAS-GP items were linked to issues only raised by patients and four to issues raised only by GPs. The remaining 10 items could not be related to issues raised by either. All of the issues raised by GPs could be mapped but 27 patient items could not. These were included in a revised checklist, the Liverpool MAAS (LIV-MAAS). CONCLUSION: the revised tool seems to have content validity in measuring consultation skills. Measurement of its relability is now required.

Adult↗
PubMed2001

Two isoforms of a member of the arthropod defensin family from the soft tick, Ornithodoros moubata (Acari: Argasidae).

We previously purified and determined the partial amino acid sequence of a 4 kDa peptide having high homology with scorpion defensin from the hemolymph of adult fed female soft ticks, Ornithodoros moubata. In this study, the full length sequences of two defensin isoforms were obtained. Deduced amino acid sequences reveal a precursor protein of 73 amino acid residues with a mature portion consisting of 37 amino acid residues. This mature peptide contains six cysteine residues conserved in the same location as other invertebrate defensins. Phylogenetic analysis reveals that Ornithodoros defensin is most closely related to scorpion defensin and other more ancient arthropods. Ornithodoros defensin mRNA is constitutively expressed and up-regulated by blood-feeding and bacterial injection. Ornithodoros defensin gene expression occurs mainly in the midgut. This is the first report of the cloning and gene expression of an antibacterial peptide from the Acari.

Amino Acid Sequence↗
PubMed2001

Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2.

Regulation of the actin-activated ATPase of smooth muscle myosin II is known to involve an interaction between the two heads that is controlled by phosphorylation of the regulatory light chain. However, the three-dimensional structure of this inactivated form has been unknown. We have used a lipid monolayer to obtain two-dimensional crystalline arrays of the unphosphorylated inactive form of smooth muscle heavy meromyosin suitable for structural studies by electron cryomicroscopy of unstained, frozen-hydrated specimens. The three-dimensional structure reveals an asymmetric interaction between the two myosin heads. The ATPase activity of one head is sterically "blocked" because part of its actin-binding interface is positioned onto the converter domain of the second head. ATPase activity of the second head, which can bind actin, appears to be inhibited through stabilization of converter domain movements needed to release phosphate and achieve strong actin binding. When the subfragment 2 domain of heavy meromyosin is oriented as it would be in an actomyosin filament lattice, the position of the heads is very different from that needed to bind actin, suggesting an additional contribution to ATPase inhibition in situ.

Animals↗