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Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 55 records · Page 3Linked to original sources
PubMed2004

Outcomes in verteporfin photodynamic therapy for choroidal neovascularisation--'beyond the TAP study'.

AIMS: To report on the clinical efficacy of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularisation (CNV) in an NHS setting and to compare treatment rates and outcomes with those in the published literature. PATIENTS AND METHODS: Patients with a visual acuity of 6/60 or better Snellen equivalent and predominantly classic or classic/no occult CNV within 200 microm of the centre of the fovea were enrolled and followed for a minimum of 12 months. Assessment at baseline and all follow-up visits comprised refraction protocol logMAR visual acuity, contrast sensitivity, and stereoscopic fluorescein angiography. RESULTS: A total of 170 eyes of 159 patients were enrolled with CNV due to: 147 age-related macular degeneration (AMD) (90 classic/no occult, 21 recurrent after confluent laser, 36 predominantly classic with occult), 10 pathological myopia, and 13 others. Response to treatment (loss of < 15 letters) at 12 months was 73% overall, 76% in AMD, 70% in classic/no occult, and 89% in predominantly classic. The mean number of treatments in the first year was 2.7. Contrast sensitivity was unchanged. CONCLUSIONS: Verteporfin PDT delivered in a NHS setting can be at least as effective as and requires fewer treatments than reported in the literature.

Choroidal Neovascularization↗
PubMed2004

Fatal fulminant myocarditis caused by disseminated mucormycosis.

Acute fulminant myocarditis is a critical clinical condition with sudden onset of severe congestive heart failure followed by severe haemodynamic deterioration. Instituting early left ventricular support may improve outcome and result in better long term survival. The case of an immunocompromised patient who developed acute fulminant myocarditis in the setting of disseminated mucormycosis is presented.

Acute Disease↗
PubMed2003

Measurements of GnE/GnM from the 2H(e-->,en-->)1H Reaction to Q2=1.45 (GeV/c)2.

We report new measurements of the ratio of the electric form factor to the magnetic form factor of the neutron, G(n)(E)/G(n)(M), obtained via recoil polarimetry from the quasielastic 2H(e-->,e(')n-->)1H reaction at Q2 values of 0.45, 1.13, and 1.45 (GeV/c)(2) with relative statistical uncertainties of 7.6% and 8.4% at the two higher Q2 points, which points have never been achieved in polarization measurements.

Journal Article↗
PubMed2003

Polymer design for corneal epithelial tissue adhesion: pore density.

A porous polymer is required to sustain corneal epithelial tissue on the anterior surface of an implantable contact lens (corneal onlay). Porosity creates topography on the polymer surface and, if defined, this can be manipulated to elicit a particular tissue response. Previous work identified pores of 100-nm diameter to be the critical size of a discontinuity in a polymer surface to facilitate the migration, stratification, and sustained adhesion of corneal epithelial tissue. Now we address the issue of pore density. Corneal epithelial tissue was grown for 21 days on nonporous polycarbonate and polycarbonate track-etched with pores 100-nm diameter with pore densities ranging from 0.27 and 14.4% of the total polymer surface area. Histology was used to score epithelial structure, and electron microscopy was used to quantitate the formation of adhesive structures (basal lamina and hemidesmosomes) at the tissue-polymer interface. Data showed that epithelial tissue stratified and epithelial adhesive structures formed on polycarbonate surfaces with pore densities between 0.52 and 14.4% inclusive. This means that epithelial tissue can be maintained on a polymer where up to 14.4% of the surface is dedicated to small discontinuities in the form of pores 100-nm diameter. These figures can be used to specify the design of a polymer for applications requiring epithelial cover.

Animals↗
PubMed2003

A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.

Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.

Administration, Oral↗
PubMed2003

Observer variation in the detection of colorectal neoplasia on double-contrast barium enema: implications for colorectal cancer screening and training.

AIM: To assess inter-observer error for the diagnosis of neoplasia on double contrast barium enema (DCBE) in the light of claims that no additional interpretative training would be needed for implementation in a national screening programme. MATERIALS AND METHODS: 10 experts, 10 consultants, and 10 experienced trainees each reported 20 DCBE studies, of which two showed cancer, three showed large polyps, four showed small polyps, and 12 were normal. Inter-observer variation was compared using odds ratios with the trainee group as reference (baseline group). RESULTS: Experts were significantly more likely to correctly identify neoplasia on DCBE than trainees. The odds of a correct diagnosis for experts were 2.79 (95% CI 2.04, 3.81) for cancer, 2.36 (1.88, 2.97) for large polyps, and 3.50 (1.98, 6.18) for small polyps. While consultants were more likely to correctly diagnose a large polyp than trainees, 1.45 (1.15, 1.84), there was no significant difference between these two groups for the correct diagnosis of either cancer, 1.24 (0.52, 2.96), or small polyps, 1.26 (0.83, 1.90). A cancer was missed by 6 (60%) experts, 9 (90%) consultants, and 8 (80%) trainees. Large polyps were missed by 4 (40%) experts, 5 (50%) consultants, and 6 (60%) trainees. There was no significant difference between any group when false positive diagnoses were considered. CONCLUSIONS: There is considerable inter-observer perceptive error for the diagnosis of neoplasia on DCBE. Experts performed significantly better than other observers but the overall standard of performance was poor, even amongst experts.

Aged↗
PubMed2003

Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride.

OBJECTIVES: The Symptom Management After Reducing Therapy (SMART-1) study examined the combination of the dual action 5alpha-reductase inhibitor (5ARI) dutasteride, and alpha(1)-blocker tamsulosin, followed by withdrawal of tamsulosin in men with symptomatic BPH. METHODS: 327 BPH patients were randomised to 0.5mg dutasteride and 0.4 mg tamsulosin for 36 weeks (DT36) or 0.5 mg dutasteride and 0.4 mg tamsulosin for 24 weeks followed by dutasteride and tamsulosin matched placebo for the remaining 12 weeks (DT24+D12). Patients' assessment of their symptoms, IPSS at weeks 24, 30, and drug safety were evaluated. RESULTS: 77% of DT24+D12 patients felt the same/better at week 30 compared with week 24 (changes in IPSS were consistent with this finding). Of those subjects with an IPSS <20 who changed to dutasteride monotherapy at week 24, 84% switched without a noticeable deterioration in their symptoms. In the 27% of men with severe baseline symptoms (IPSS >or=20) who had withdrawal of tamsulosin therapy at week 24, 42.5% reported a worsening of their symptoms compared with 14% in the DT36 group. The regimens were well tolerated. CONCLUSIONS: Dutasteride can be used in a 24-week combination with tamsulosin, to achieve rapid onset of symptom relief in patients at risk of underlying disease progression. This symptom relief is maintained in the majority of patients after the alpha(1)-blocker is removed from the combination. Patients with severe symptoms may benefit from longer-term combination therapy.

Adrenergic alpha-Antagonists↗
PubMed2003

Low back pain in schoolchildren: the role of mechanical and psychosocial factors.

BACKGROUND: Low back pain (LBP) in schoolchildren with no apparent clinical cause is known to be a common problem, but considerably less is understood regarding the aetiology of such pain. AIM: To assess the role of both mechanical and psychosocial factors (including emotional and behavioural problems and other somatic pain complaints) in childhood LBP. METHODS: A cross sectional study was carried out in a population of 1446 schoolchildren aged 11-14 years. Information on these potential risk factors for LBP was sought using a self complete questionnaire and a five day bag weight diary. RESULTS: Mechanical factors such as physical activity and school bag weight were not associated with LBP. However, strong associations with LBP were observed for emotional problems, conduct problems, troublesome headaches, abdominal pain, sore throats, and daytime tiredness. CONCLUSION: Results suggest that psychosocial factors rather than mechanical factors are more important in LBP occurring in young populations and could possibly be a reflection of distress in schoolchildren.

Abdominal Pain↗
PubMed2003

Functionality of the spindle checkpoint during the first meiotic division of mammalian oocytes.

The spindle checkpoint ensures accurate chromosome segregation by delaying anaphase until all chromosomes are correctly aligned on the microtubule spindle. Although this mechanism is conserved throughout eukaryotic evolution, it is unclear whether it operates during meiosis in female mammals. The results of the present study show that in mouse oocytes spindle alterations prevent both chromosome segregation and MPF (M phase promoting factor) inactivation during the first meiotic M phase. Moreover, the spindle checkpoint component budding uninhibited by benzimidazole 1 (BUB1) localizes to kinetochores and is phosphorylated until anaphase of both meiotic M phases. Both localization and phosphorylation are similar to those observed in oocytes at microtubule depolymerization. In addition, the kinetochore localization and phosphorylation of BUB1 do not depend on the MOS/.../MAPK pathway. These data indicate that the spindle checkpoint is probably active during meiotic maturation in mouse oocytes. BUB1 remains associated with kinetochores and is phosphorylated during the metaphase arrest of the second meiotic M phase, indicating that this protein may also play a role in the natural metaphase II arrest in mammalian oocytes.

Animals↗
PubMed2002

Perinatal factors affecting survival and survival without disability of extreme premature infants at two years of age.

OBJECTIVE: To study obstetrical factors leading to very preterm delivery (between 24 and 28 weeks) and to relate these factors to neonatal outcome and psychomotor development at two years. STUDY DESIGN: Among 144 infants born alive before 28 weeks of gestation at a single perinatal center between January 1993 and December 1996, we analyzed the influence on neonatal outcome and on psychomotor development at 24 months of a variety of perinatal and neonatal factors. Psychomotor development at two years was classified as: normal, borderline, or moderately or severely handicapped. RESULTS: During the study period, 114 women delivered live infants before 28 weeks' gestation: 87 singletons, 25 sets of twins, 1 set of triplets and 1 set of quadruplets. All 144 live-born infants received neonatal resuscitation: 50 died before discharge. At two years of age, 6 of the 94 survivors were lost to follow-up. Assessments of the psychomotor development of the other 88 was normal for 52%; borderline for 20%, moderately handicapped for 20%, and severely handicapped for 8%. Multivariate analysis found that two factors affected survival: birthweight and fetal heart rate. (The 42% of infants with a birthweight below 700 g survived versus 83% above 900 g, P<0.001, OR=5.2, 95% CI (confidence interval) [2.4-11.2].) CONCLUSION: These data show the influence of perinatal factors on the outcome of very preterm infants; birthweight and fetal heart rate are strongly correlated with survival. Gestational age is a good predictor of psychomotor development at two years.

Birth Weight↗
PubMed2002

Absence of functional insulin receptor substrate-3 (IRS-3) gene in humans.

AIM/HYPOTHESIS: Insulin receptor substrate (IRS) proteins play important roles in insulin action and pancreatic beta-cell function. At least four mammalian IRS molecules have been identified. Although genes and cDNAs encoding human IRS-1, IRS-2, and IRS-4 have been cloned, IRS-3 has been identified only in rodents. Thus, we have attempted to clone the human IRS-3 gene. METHODS: Insulin-stimulated rat or human adipocytes were subjected to Western blot analysis to assess IRS-3 tyrosine phosphorylation. Human liver and adipose cDNA libraries were screened in an effort to clone IRS-3 cDNA. A PCR-based approach was designed to amplify IRS-3 cDNA. Reverse transcription PCR was carried out using mRNA from adipose tissue, liver, and skeletal muscle as templates in combination with an in silico screen using mouse IRS-1, IRS-2 and IRS-3 in a tblastn search of the draft public human genome. RESULTS: In human adipocytes we did not detect a M(r) 60 000 phosphoprotein corresponding to IRS-3, whereas in rat adipocytes IRS-3 protein and insulin-stimulated tyrosine phosphorylation was readily observed. None of the molecular approaches provided evidence for a functional IRS-3gene in human tissue. Two deletions in human IRS-3 gene were identified using bioinformatics. The human IRS-3 gene product is predicted to lack a phosphotyrosine binding domain and also the sequence corresponding amino acid 353-407 of murine IRS-3. The contiguous sequence of genomic DNA between these two homologous regions does not have the coding information for human IRS-3. CONCLUSION/INTERPRETATION: In silico screening of the human IRS-3 genome region, combined with further biological and molecular validation, provides evidence against a functional IRS-3 in humans.

Adipocytes↗
PubMed2002

Preparation and characterization of dealuminated metakaolin and its use in the transformation of waste plastics to aromatic hydrocarbons.

Acid activated metakaolins (AAMKs) have been prepared by calcination of the natural clay at 600 degrees C to provide a metakolin which was then leached at 80 degrees C for 3 h using 1M, 2M, 3M, and 6M HCl. These materials were characterized and their ability to transform the off gases from HDPE decomposition into useful aromatic species was evaluated. The amount of adsorbed water and the number of acid sites increased with the severity of acid treatment. Variable temperature DRIFTS spectroscopy of pyridine treated samples revealed that both Brønsted and Lewis acid centers were present until 425 degrees C. Pyridine bonded to the Lewis acid centers was more thermally stable. The AAMKs were all selective to the production of toluene with respectable, but lesser, amounts of xylenes and trimethylbenzenes. This selectivity contrasts with that of acid leached and pillared smectites which are selective toward trimethylbenzene.

Journal Article↗
PubMed2002

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor.

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

Adenocarcinoma↗
PubMed2002

S100A4 (p9Ka) protein in colon carcinoma and liver metastases: association with carcinoma cells and T-lymphocytes.

The presence of the EF-hand-calcium-binding protein S100A4 in the carcinoma cells of the primary tumour is associated with a shorter survival time of a group of breast cancer patients. In colon cancer, primary tumours as well as metastases to the liver can be studied. Here we show, using quantitative PCR applied to RNA from 24 normal colon, four liver tissues, 24 colon carcinoma specimens, and 24 livers containing colonic carcinoma metastases, that the level of S100A4 mRNA was significantly higher in the carcinomas compared to normal specimens (Mann-Whitney U-test, P=0.05), and in liver metastases compared to carcinoma specimens (P=0.039). The latter comparison included seven liver metastases and their matched primary carcinomas (P<0.001) from the same patient. In situ hybridization and immunocytochemistry techniques have localized S100A4 to both carcinoma cells and lymphocytes in the malignant specimens. The percentage of specimens stained for S100A4 in the epithelial cells is significantly higher for those isolated from carcinomas and metastases than from the corresponding normal tissue, and from metastases than from corresponding carcinoma (Fisher Exact text, P<0.0016, P=0.04, respectively). In most specimens, S100A4 is present in clusters of T lymphocytes and this distribution is also found in the lymphoid, uninflamed appendix.

Adenoma↗
PubMed2002

Long-term stability of a coronary stent coating post-implantation.

A coronary stent possessing a phosphorylcholine-based polymer coating was removed from a human patient 6 months after implantation and analyzed for the presence of the coating. An atomic force microscopy (AFM) technique has been employed to scrape away several 10- micro m(2) areas on the struts of the explanted stent. Scanning-electron microscopy (SEM) and tapping-mode AFM confirmed a surface coating had been removed in each case. Cross-sectional analysis and force-of-removal measurements showed that both coating depth and hardness were characteristic of that for the phosphorylcholine- (PC-) based coating prior to implantation. AFM amplitude-phase and distance curves from the explanted stent were comparable to those obtained when an unused stent was analyzed. Furthermore, laser ablation high-resolution inductively coupled-plasma mass spectometery (LA-HR-ICP-MS) was used to detect the low level of silicon present in the PC coating after explantation. The results from these techniques confirm that the stent coating is the original PC polymer and is not of biological origin, and support the long-term stability of the coating in vivo.

Aged↗
PubMed2002

Penetration of engineered antibody fragments into the eye.

Antibodies are powerful immunotherapeutic agents but their use for treating ocular disorders is limited by their poor penetration into the eye. We hypothesized that antibody fragments of relatively small size might penetrate the cornea more readily. Monovalent single chain variable region (scFv) antibody fragments and divalent miniantibodies were engineered from existing monoclonal antibodies, expressed in a bacterial expression system, and purified by metal ion affinity chromatography. Corneoscleral preparations from normal pig and cat eyes were mounted in a corneal perfusion chamber. Intact antibodies and antibody fragments were applied topically to the anterior corneal surface over 12-h periods, and samples were collected from the artificial anterior chamber. Similar experiments were performed with whole enucleated pig and human eyes. Penetration of antibodies and fragments was quantified by high-sensitivity flow cytometry on appropriate target cells. Both monovalent scFv and divalent miniantibody fragments (but not whole immunoglobulin molecules) passed through de-epithelialized and intact corneas after topical administration, and could be detected by antigen binding. Addition of 0.5% sodium caprate facilitated penetration through intact corneas. Topically-applied scFv was found to penetrate into the anterior chamber fluid of rabbit eyes in vivo. The engineered fragments were stable and resistant to ocular proteases. Monovalent and divalent antibody constructs of molecular weight 28 kD and 67 kD, respectively, can penetrate through intact corneas into the anterior chamber, with retention of appropriate antigen-binding activity. Such constructs may form novel therapeutic agents for topical ophthalmic use.

Animals↗