Biomedical subjects

K E Wilson

Publications and source records attributed to K E Wilson.

At least 19 recordsLinked to original sources

PubMed2006

A comparison of oral midazolam and nitrous oxide sedation for dental extractions in children.

The aim of the study was to compare oral midazolam and inhaled nitrous oxide as sedative agents during the management of children aged 5-10 years presenting for extraction of primary teeth under local anaesthetic. Subjects required two visits for the extraction of four primary teeth, one in each quadrant of the mouth, and were randomly allocated to be given nitrous oxide 30% in oxygen or oral midazolam 0.3 mg.kg(-1) at the first visit, the other technique being used at the second visit. Vital signs, sedation levels and behavioural scores were recorded, and postoperative recall and satisfaction were reported by the patients. Thirty-five children, with a mean [range] age of 7.4 [5-10] years, completed the treatment. The mean dose of oral midazolam given was 8.6 [3.3-16.5] mg. The mean times taken to achieve the maximum level of sedation for midazolam and nitrous oxide sedation were 15.9 [2-30] min and 6.8 [2-10] min, respectively. Physiological parameters remained within acceptable clinical limits for both types of sedation. Oral midazolam was considered acceptable by 59% and was preferred by 36%. Oral midazolam sedation in 5 to 10-year-old children was shown to be as safe and effective as nitrous oxide in oxygen sedation for extraction of primary teeth but would not be the method of choice for all patients.

Administration, Oral↗

PubMed2004

SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies.

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.

Adult↗

PubMed2004

A survey of the opinions of consultant anaesthetists in Scotland of sedation carried out by dentists.

OBJECTIVES: To elicit the attitudes and opinions of consultant anaesthetists working in Scotland, with regard to conscious sedation carried out by dental practitioners. METHOD: A questionnaire was designed to gauge opinion of consultant anaesthetists in Scotland on the practice of conscious sedation by dentists. The questionnaire was sent to 353 consultant anaesthetists working in 49 hospitals within the 15 health boards in Scotland. RESULTS: Of the 366 questionnaires sent, 249 were returned of which 235 were valid. This gave a response rate of 64%. In general, those questioned felt that the provision of sedation in a hospital setting was more appropriate than in general dental practice. A majority (65%) thought that it was unrealistic for anaesthetists to provide all sedation for dental treatment, although many (58%) felt that anaesthetists should take more responsibility in this area. Again, a majority (60%) agreed that dentists should be trained to use sedation techniques for their patients but a significant number (63%) disagreed with the practice of operator/sedationist. CONCLUSION: It is of concern to the dental profession that a significant number of anaesthetists do not feel that it is appropriate for dentists to be administering even the most simple methods of sedation. At present there are no clear, recognised guidelines as to the level of formal training required for the practice of conscious sedation by dentists. It is in the interests of the dental profession and the public to ensure that those choosing to practice sedation do so safely by following recognised guidelines in the training and practice of sedation.

Anesthesia Department, Hospital↗

PubMed2004

High throughput approaches in neuroscience.

Traditional approaches to understanding biological problems are now being advanced with the use of high throughput technologies, which analyse multiple samples simultaneously, or thousands of analytes in a single sample. The application of these technologies in neurochemistry and neuroscience is beginning to be explored and is assisting in the development of new models of drug action, neuroanatomical investigations, and in identifying molecular pathways involved in neurological and psychiatric disease. Tools such as microarray-based gene expression profiling and 2D and multidimensional proteomic methods are uncovering functional components to a wide variety of neuroscience paradigms and the application of these technologies is set to become standard in analysis.

Animals↗

PubMed2004

Functional genomics and proteomics: application in neurosciences.

The sequencing of the complete genome for many organisms, including man, has opened the door to the systematic understanding of how complex structures such as the brain integrate and function, not only in health but also in disease. This blueprint, however, means that the piecemeal analysis regimes of the past are being rapidly superseded by new methods that analyse not just tens of genes or proteins at any one time, but thousands, if not the entire repertoire of a cell population or tissue under investigation. Using the most appropriate method of analysis to maximise the available data therefore becomes vital if a complete picture is to be obtained of how a system or individual cell is affected by a treatment or disease. This review examines what methods are currently available for the large scale analysis of gene and protein expression, and what are their limitations.

Brain↗

PubMed2003

Randomized, controlled, cross-over clinical trial comparing intravenous midazolam sedation with nitrous oxide sedation in children undergoing dental extractions.

BACKGROUND: The use of benzodiazepines for paediatric dental sedation has received limited attention with regard to research into clinical effectiveness. A study was therefore designed to investigate the use of midazolam, for i.v. sedation in paediatric dental patients. METHOD: The aim of the study was to assess the effectiveness of i.v. midazolam in a randomized, controlled, cross-over trial. Children aged 12-16 yr (ASA I and II), requiring two appointments for equivalent but contralateral dental extractions for orthodontic purposes, were recruited. Conscious sedation with either i.v. midazolam titrated at 0.5 mg x min(-1), to a maximum of 5 mg, or nitrous oxide/oxygen titrated to 30%/70% inhalation sedation was used at the first visit, the alternative being used at the second visit. Vital signs including blood pressure, arterial oxygen saturation and ventilatory frequency, as well as sedation levels and behavioural scores, were recorded every 2 min. RESULTS: Forty patients, mean age 13.2 yr (range 12-16 yr), participated in the trial. A mean dose of midazolam 2.8 mg was administered in the test group. The median time to the maximum level of sedation was 8 min for midazolam compared with 6 min for nitrous oxide (P<0.001). Vital signs for both treatments were comparable and within acceptable clinical limits and communication with the patient was maintained at all times. The median (range) lowest arterial oxygen saturation level recorded for midazolam was 97 (91-99)% compared with 97 (92-100)% for nitrous oxide. The mean (range) recovery time for midazolam was 51.6 (39-65) min and 23.3 (20-34) min for nitrous oxide (P<0.0001). Fifty-one per cent said they preferred i.v. midazolam, 38% preferred nitrous oxide, and 11% had no preference. CONCLUSION: I.V. midazolam sedation (0.5 mg x min(-1) to a maximum of 5 mg) appears to be as effective as nitrous oxide sedation in 12-16-yr-old healthy paediatric dental patients.

Adolescent↗

PubMed2002

A study of the effectiveness of oral midazolam sedation for orthodontic extraction of permanent teeth in children: a prospective, randomised, controlled, crossover trial.

OBJECTIVES: To assess the safety, effectiveness and acceptability of o:ral midazolam sedation for orthodontic extraction of permanent teeth in children. DESIGN: A prospective, randomised, controlled, crossover trial. METHODS: A total of 26 children aged 10-16 (ASA I), referred for orthodontic extraction of premolar or canine teeth under sedation, were included in the study. Each child required two treatment sessions for the extraction of equivalent teeth on opposite sides of the mouth. Each subject was sedated with either ora midazolam (0.5 mg/kg) or nitrous oxide and oxygen (30%/70%) at the first visit and the alternative form at the second visit. At each visit two teeth were extracted, one upper and one lower. Heart rate, arterial oxygen saturation, respiration rate, sedation and behavioural scores were recorded every five minutes. Overall behaviour, patient acceptance and patient satisfaction were recorded at the end of treatment. RESULTS: Of the 26 children included in the study there were 12 males and 14 females. The mean age was 12.5 years. The mean heart rate and respiratory rate for both groups were similar and within acceptable clinical limits. The lowest mean arterial oxygen saturation levels for nitrous oxide and midazolam sedation were 97.7% and 95.0% respectively. Although midazolam caused greater oxygen desaturation, the range (91%-100%) was within safe limits for conscious sedation. The mean level of sedation was greater in the midazolam group compared with the nitrous oxide group and all but one case completed treatment. A total of 23 patients (88%) said they would be prepared to have ora midazolam sedation again and 17 (65%) actually preferred oral midazolam to nitrous oxide sedation. CONCLUSION: Oral midazolam (0.5mg/kg) appears to be a safe and acceptable form of sedation for 10-16 year old paediatric dental patients.

Administration, Oral↗

PubMed2002

A randomised, controlled, crossover trial of oral midazolam and nitrous oxide for paediatric dental sedation.

A randomised, controlled, crossover trial was designed to assess the safety and effectiveness of oral midazolam sedation for orthodontic extractions. Forty-six ASA physical status I children aged 10-16 years were recruited. Each child required two treatment sessions. Sedation with either oral midazolam 0.5 mg.kg-1 or nitrous oxide in oxygen was used at the first visit, the alternative being used at the second visit. Blood pressure, heart rate, arterial oxygen saturation, and sedation and behavioural scores were recorded every 5 min. Anxiety levels and postoperative satisfaction were also recorded. Blood pressure, heart rate and arterial oxygen saturation in both groups were similar and within acceptable clinical limits. The median [range] lowest arterial oxygen saturation levels for subjects in the midazolam and nitrous oxide groups were 95 [90-100]% and 98 [93-100]%, respectively. The median [range] time to the maximum level of sedation in the midazolam group was 20 [5-65] min compared with 5 [5-10] min in the nitrous oxide group (p < 0.001). The median [range] duration of treatment was similar in both groups (midazolam group: 10 [5-30] min, nitrous oxide group: 10 [5-25] min). Seventy-four per cent of subjects were prepared to have oral midazolam sedation again, 54% preferring it. Oral midazolam appears to be a safe and acceptable form of sedation for 10-16-year-old paediatric dental patients.

Adolescent↗

PubMed2002

Bordetella pertussis isolates with a heterogeneous phenotype for erythromycin resistance.

Erythromycin is currently being used for both prophylaxis and treatment of pertussis infections. Erythromycin resistance was first recognized in Bordetella pertussis in Arizona in 1994, and since then, three additional resistant isolates have been identified in the United States. To better assess the potential public health impact of erythromycin-resistant B. pertussis, we used the disk diffusion assay to evaluate the frequency of erythromycin resistance among 1,030 recently circulating U.S. isolates and found the rate of occurrence to be <1%. We also describe a novel heterogeneous phenotype, with erythromycin-resistant colonies appearing only after a 7-day incubation period. To optimize patient management, we recommend that clinicians be alert to potential treatment failures and that laboratorians use a 7-day incubation period when screening for resistance. Our ongoing national surveillance will continue to monitor for resistant B. pertussis isolates and their potential association with changing pertussis epidemiology.

Anti-Bacterial Agents↗

PubMed2001

Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum.

AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.

Animals↗

PubMed2001

Rheumatoid arthritis synovial T cells regulate transcription of several genes associated with antigen-induced anergy.

Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis whose pathogenesis may involve autoimmune mechanisms. Anergy is a state of T-cell nonresponsiveness characterized by downregulated IL-2 production. Paradoxically, RA T cells are hyporesponsive and proliferate poorly to antigens and mitogens, thus sharing some characteristics with anergic T cells. We analyzed the molecular basis of anergy in cloned human CD4+ T cells using differential display RT-PCR and subsequently examined the levels of differentially expressed transcripts in RA and, as control, reactive arthritis (ReA) synovium. Several transcriptional events were common to anergic T cells and RA synovium. These included downregulation of CALMODULIN:, which is critical to T-cell activation, and of cellular apoptosis susceptibility protein, which may mediate resistance to apoptosis in RA. Transcription of CALMODULIN: in RA synovium was less than 1% of that in ReA and was lower in RA synovial fluid mononuclear cells than in paired PBMCs. Following anti-TNF-alpha therapy in vivo, RA PBMC CALMODULIN: transcripts increased five- to tenfold. Pharmacological calmodulin blockade in vitro impaired antigen-specific proliferation. These data provide a link between reduced CALMODULIN: transcription and impaired T-cell responsiveness in RA. The identification of transcriptional changes common to anergic and RA synovial T cells should help interpret some of the characteristic RA cellular defects.

Antigens↗

PubMed2001

Effects of ultraviolet-A exposure on ultraviolet-B-induced accumulation of specific flavonoids in Brassica napus.

Many plant species are able to acclimate to changes in ultraviolet-B radiation (UVB) (290-320 nm) exposure. Due to the wide range of targets of UVB, plants have evolved diverse repair and protection mechanisms. These include increased biosynthesis of UVB screening compounds, elevated antioxidant activity and increased rates of DNA repair. We have shown previously that Brassica napus L. cv Topas plants can acclimate quite effectively to environmentally relevant increases in UVB through the accumulation of specific flavonoids in the leaf epidermis. However, B. napus was found to lose other flavonoids when plants are exposed to ultraviolet-A radiation (UVA) (320-400 nm) and/or UVB (Wilson et al. [1998] Photochem. Photobiol. 67, 547-553). In this study we demonstrate that the levels of all the extractable flavonoids in the leaves of B. napus plants are decreased in a dose-dependent manner in response to UVA exposure. Additionally, the accumulation of the extractable flavonoids was examined following a shift from photosynthetically active radiation (PAR) + UVA to PAR + UVB to assess if preexposure to UVA affected UVB-induced flavonoid accumulation. UVA preexposures were found to impede UVB-induced accumulation of some flavonoids. This down regulation was particularly evident for quercetin-3-O-sophoroside and quercetin-3-O-sophoroside-7-O-glucoside, which is interesting because quercetins have been demonstrated to be induced by UVB and correlated with UVB tolerance in some plant species. The photobiological nature of these UVA-mediated effects on flavonoid accumulation implies complex interactions between UVA and UVB responses.

Acclimatization↗

PubMed2000

The role of growth rate, redox-state of the plastoquinone pool and the trans-thylakoid deltapH in photoacclimation of Chlorella vulgaris to growth irradiance and temperature.

The long-term photoacclimation of Chlorella vulgaris Beijer (UTEX 265) to growth irradiance and growth temperature under ambient CO2 conditions was examined. While cultures grew at a faster rate at 27 than at 5 degrees C, growth rates appeared to be independent of irradiance. Decreases in light-harvesting polypeptide accumulation, increases in xanthophyll pool size and changes in the epoxidation state of the xanthophyll cycle pigments were correlated linearly with increases in the relative reduction state of QA, the primary quinone receptor of photosystem II, when estimated as 1-qP under steady-state growth conditions. However, we show that there is also a specific temperature-dependent component, in addition to the redox-state of the QA, involved in regulating the content and composition of light-harvesting complex II of C. vulgaris. In contrast, modulation of the epoxidation state of the xanthophyll pool in response to increased 1-qP in cells grown at 5 degrees C was indistinguishable from that of cells grown at 27 degrees C, indicating that light and temperature interact in a similar way to regulate xanthophyll cycle activity in C. vulgaris. Because C. vulgaris exhibited a low-light phenotype in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), but a high-light phenotype upon addition of 2,5-dibromo-6-isopropyl-3-methyl-1,4-benzoquinone, we conclude that the plastoquinone pool acts as a sensor regulating the accumulation of light-harvesting polypeptides in C. vulgaris. However, concomitant measurements of non-photochemical fluorescence quenching (qN) and the epoxidation state of the xanthophyll pool appear to indicate that, in addition to the redox-state of the plastoquinone pool, the trans-thylakoid deltapH may also contribute to sensing changes in irradiance and temperature that would lead to over-excitation of the photosynthetic apparatus. We suggest that sink capacity as reflected in photosynthate utilization and cell growth ultimately regulate photoacclimation in C. vulgaris.

Adaptation, Physiological↗

PubMed2000

A prospective randomised controlled study of patient-controlled propofol sedation in phobic dental patients.

The safety and effectiveness of patient-controlled propofol sedation was prospectively assessed in 18 healthy, phobic dental patients. Using a randomised, crossover design each patient received two sessions of equivalent dental treatment under patient-controlled or clinician-controlled propofol sedation. The patient-controlled technique used 29.8% less drug (time-weighted dose) than the clinician-controlled method (p = 0.011). There was a high correlation between number of demands and number of doses actually infused during the patient-controlled technique (r = 0.99, p < 0. 001). Clinically, the level of sedation was lighter and the degree of operator satisfaction was higher with patient-controlled sedation. Blood pressure and arterial oxygen saturation showed minimal changes and remained within normal ranges during both techniques. Patient-controlled sedation produced a greater reduction in dental and general anxiety compared with clinician-controlled sedation, but the difference did not reach statistical significance. Three times the number of patients expressed a preference for the patient-controlled, compared with the clinician-controlled, technique. Patient-controlled sedation provides safe and acceptable intra-operative anxiolysis for phobic dental patients, but with reduced propofol dosage.

Adult↗

PubMed1999

Beta 1 integrin- and proteoglycan-mediated stimulation of T lymphoma cell adhesion and mitogen-activated protein kinase signaling by thrombospondin-1 and thrombospondin-1 peptides.

Cell-cell and cell-matrix interactions play important regulatory roles in lymphocyte homeostasis. Thrombospondin-1 (TSP1) is a matricellular protein that differentially promotes the adhesion of resting and activated T cells. In this work, we show that adhesion of Jurkat T cells on substrates coated with TSP1 or TSP1-derived peptides is mediated by beta 1 integrins, CD47, and heparan sulfate proteoglycans. Interactions with TSP1 or TSP1 peptides stimulated CD3-induced Ras activation and tyrosine phosphorylation of several T cell proteins. The signals from TSP1 and its derived peptides differentially synergized with activation of the TCR to induce phosphorylation of linker for activation of T cells (LAT) and extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase, and p38 kinases. The phosphorylation of ERK in the presence of full-length TSP1 was transient and dependent on a beta 1 integrin receptor. Interestingly, peptides derived from the type 1 repeats of TSP1 and a CD47-binding peptide from the carboxyl-terminal domain of TSP1 also stimulated mitogen-activated protein (MAP) kinase phosphorylation. Moreover, the TSP1 heparin-binding peptide synergized with Ab-ligated TCR to transduce signals to the nucleus, detected by activation of AP-1- and Elk-dependent transcription. This TSP1 peptide-dependent activation of AP-1 was inhibited by both heparin and the MAP/ERK kinase inhibitor PD98059, providing a functional link between adhesion molecule interaction and nuclear transactivation events via the MAP kinase pathways. These findings have implications for the role of extracellular TSP1 and TSP1 fragments in the regulation of T cell function during hemostasis, wound repair, and other inflammatory responses.

Amino Acid Sequence↗

PubMed1999

Regulation and function of the extracellular matrix protein tenascin-C in ovarian cancer cell lines.

The extracellular matrix glycoprotein tenascin-C (TN) is overexpressed in the stroma of malignant ovarian tumours particularly at the interface between epithelia and stroma leading to suggestions that it may be involved in the process of invasion (Wilson et al (1996) Br J Cancer 74: 999-1004). To define regulation of TN further and investigate its function in ovarian cancer, a range of cell line models were studied. Concentrations of secreted TN in media from cultures of ovarian fibroblast cell lines were at least 100-fold greater than from carcinoma cell lines. Evidence for paracrine regulation of TN secretion was obtained by co-culture of carcinoma cells with fibroblast cells wherein secretion into the media was greater than from fibroblasts alone. Transforming growth factor (TGF)-beta1, insulin-like growth factor (IGF)-II and progesterone all stimulated TN secretion while human choriogonadotropin (hCG), follicle-stimulating hormone (FSH) and gamma-interferon inhibited secretion. TGF-beta1 produced the greatest stimulation of TN in cultured fibroblasts and its co-expression with TN was examined in primary ovarian tumours. There was a significant association between the presence of moderate-strong expression of TN and TGF-beta1. Evidence for TN having a functional role in ovarian carcinoma was obtained from adhesion and migration assays. The PE01, PE04, SKOV-3 and 59M cell lines all demonstrated marked adhesion to plastic coated with TN relative to the control protein bovine serum albumin (BSA) and expressed alpha2beta1 and alpha3beta1 integrins. The SKOV-3 cell line migrated more rapidly through TN than through BSA indicating that TN can facilitate migration of ovarian carcinoma cells.

Animals↗

PubMed1998

Organometallic flavonoid derivatives as spectroscopic probes.

Derivatives of naringenin have been synthesized with organometalcarbonyl reporting groups for IR spectroscopy attached at C-2, C-3', or C-6, and the products have been tested for the induction of nod gene expression using a Rhizobium leguminosarum strain which contains the Escherichia coli lacZ (beta-galactosidase) gene fused to nodABC. Derivatives with an OMe substituent within the reporting group moiety showed residual gene induction activity.

Escherichia coli↗

PubMed1998

Advantages of impact testing over hardness testing in determining physical integrity of tablets.

An investigation of four different tablet strength tests was carried out on four different placebo formulations (differing in Avicel: Pharmatose ratios). The results analysis compared fatigue failure, work of failure, and impact failure to diametrical compression measurements (hardness). The impact results clearly show how different formulations can have the same hardness, yet their impact resistance can vary by as much as 200%. The impact test used in this work and other tests described are useful in tablet development to understand, compare, and mitigate tablet breakage during subsequent unit operations.

Cellulose↗