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Biomedical subjects

M Thornhill

Publications and source records attributed to M Thornhill.

15 recordsLinked to original sources
PubMed2003

Association of specific interleukin 1 gene cluster polymorphisms with increased susceptibility for Behcet's disease.

OBJECTIVE: The aim of this study was to investigate if the inheritance of specific polymorphisms of interleukin 1 (IL-1) A, IL-1B and IL-1 receptor antagonist (IL-1RN) genes could affect the susceptibility to Behçet's disease (BD). METHODS: A total of 132 BD patients and 105 healthy controls were genotyped for IL-1A -889, IL-1B -511, -35, +5810, +5887, and IL-1RN +8006, +8061, +9589, +11,100 single nucleotide polymorphisms, and IL-1RN 86-bp variable number of tandem repeat polymorphism. chi 2-analysis was used to compare the allele and genotype frequencies of the cases and controls. IL-1A and IL-1B haplotypes were reconstructed using the Phase program. RESULTS: Inheritance of the C allele of the IL-1A -889 polymorphism was associated with BD (OR=2.0, P=0.01) and inheritance of the IL-1A -889C/IL-1B +5887T haplotype was identified as an increased risk for BD. The IL-1A -889 and IL-1B +5887 CC/TT combined genotype was significantly more observed in BD cases than in controls (57.5 vs 38.1%, OR=2.2, P=0.003). No association with BD was found for other investigated polymorphisms in the IL-1B and IL-1RN genes. CONCLUSION: Susceptibility to BD is increased in individuals carrying both the IL-1A -889C and IL-1B +5887T haplotype. Individuals who are both homozygous CC at IL-1A -889 and TT at IL-1B +5887 appear to have twice the risk of developing BD as individuals having other IL-1A -889/IL-1B +5887 genotypes.

Behcet Syndrome↗
PubMed2003

Borderline nuclear change in cervical smears: five-year follow-up.

Borderline nuclear changes (BNC) account for 5-20% of cervical smears, and their outcome is unpredictable. Current management involves repeat smears at 6-mo intervals, for a further 12 mo with referral for colposcopy, if the changes persist. Given the uncertainty surrounding the natural history of BNC and the claim that many patients are further investigated unnecessarily and potentially "overtreated," the aim of this study was to determine the outcome for patients with a diagnosis of BNC to define whether the management protocol is appropriate for this patient group in our laboratory. A total of 808 patients with BNC were followed up. There was a 4.05% progression to high-grade dyskaryosis, and most of these were detected within the first year of follow-up. This at least justifies the early and intense follow-up of this patient group until a reliable "triage tool" is adopted to pre-select those patients with BNC who will progress or revert to negative.

Cell Nucleus↗
PubMed2002

Comparative study: conventional cervical and ThinPrep Pap tests in a routine clinical setting.

The conventional Papanicolaou smear is associated with variable false positive and false negative rates, difficulties with interpretation and high unsatisfactory and suboptimal rates. Newer fluid-based methods such as the ThinPrep 2000 system (Cytyc Corp., Boxborough, MA) are said to overcome these difficulties. The aim of this study was to compare the conventional smear with the ThinPrep method in a busy, routine cytology screening laboratory setting. One thousand split samples were evaluated. Using ThinPrep, the results showed an increased sensitivity and a dramatic improvement in specimen adequacy, with a combined 17.2% reduction in 'unsatisfactory' and 'suboptimal' reports. Screening time per slide was also reduced to 3-4 min. In conclusion, we report an increase in sensitivity, a reduction in screening time and a dramatic improvement in specimen adequacy with the ThinPrep method.

Cell Nucleus↗
PubMed2000

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus is a chronic autoimmune disease of unknown aetiology that affects the inner surface of the mouth. The symptomatic forms are painful,tend to worsen with age and with remissions being rare. Current treatment is palliative and not curative, many topical and systemic agents have been tried with little hard evidence for efficacy. OBJECTIVES: To assess the effectiveness and safety of any form of palliative therapy against placebo for the treatment of symptomatic oral lichen planus. SEARCH STRATEGY: Electronic databases, handsearching of conference proceedings and specific journals, researchers in the field, drug manufacturers. SELECTION CRITERIA: Any placebo-controlled trial of palliative therapy for symptomatic oral lichen planus, using a randomised or quasi-randomised design that measured changes in symptoms and/or clinical signs. DATA COLLECTION AND ANALYSIS: Change in symptoms (pain, discomfort) and clinical signs (visual impression, lesion measurements) at the end of therapy. Odds ratio of improvement vs no improvement for each trial outcome and pooling where appropriate. MAIN RESULTS: A total of nine RCTs were identified. The nine interventions were grouped into four separate classes (cyclosporines, retinoids, steroids and phototherapy) for comparison. No therapy was replicated exactly, the closest replication involved two trials using high and low dose cyclosporine mouthwash. Only trials recording the same outcomes in each therapeutic class were pooled. The largest number of pooled trials was three. Large odds ratios with very wide confidence intervals indicating a statistically significant treatment benefit were seen in all trials. However this has to be tempered by considerations of the small study sizes, the lack of replication, the difficulty in measuring outcome changes and the very high likelihood of publication bias. Only systemic agents were associated with treatment toxicities, all other side-effects were mild and mainly limited to local mucosal reactions. REVIEWER'S CONCLUSIONS: The review provides only weak evidence for the superiority of the assessed interventions over placebo for palliation of symptomatic OLP. The results highlight the need for larger placebo-controlled RCTs with more carefully selected and standardised outcome measures before between-treatment comparisons can be properly interpreted.

Cyclosporins↗
PubMed2000

An open clinical trial of sulphamethoxypyridazine in the treatment of mucous membrane pemphigoid.

Twenty-five patients with mucous membrane pemphigoid (MMP), whose oral lesions were unresponsive to topical steroid treatment, were treated with 1 g daily of sulphamethoxypyridazine (SMXP), a long-acting sulphonamide antibiotic, in an open prospective clinical trial. Lesion severity was assessed objectively in a semiquantitative fashion before treatment and after 14 weeks of treatment. The patient's subjective assessment of the associated pain or discomfort, using a visual analogue scale, was also recorded at these times. Three patients (12%) were withdrawn from the study owing to side-effects or complications, one due to an allergic reaction, the other two because of significant haemolysis. For the remainder there was a significant improvement in the mean objective clinical scores for desquamative gingivitis, other oral lesions, conjunctival inflammation, nasal, vulvovaginal and skin involvement, after 14 weeks treatment with SMXP (all P < 0.001, except skin P < 0. 01). Only conjunctival scarring showed no improvement. In addition, there was a significant improvement (P < 0.001) in the pain scores for the mouth, eyes, nose, vulvovaginal region and skin. The results indicate that with appropriate monitoring SMXP is an effective treatment for MMP and compares favourably with other systemic agents used in the management of this condition.

Aged↗
PubMed1998

Client perceptions of a rural-based cardiac rehabilitation program: a grounded theory approach.

A grounded theory approach was used in an attempt to generate theory about client perceptions and experiences of a cardiac rehabilitation program conducted in a rural community. A series of interviews was conducted with a selection of people who had experienced a life-threatening cardiac event. The cohort was divided into two groups: those who attended a cardiac rehabilitation program and those who did not. The findings, though not generalisable, allowed the generation of a number of theories (which may come to be the genesis of future research) regarding the differences in the physiological, psychological, sociological and vocational well-being between the groups. The findings also suggested that location of the program, the times it was conducted, and the communication skills of significant healthcare workers who recruited participants were important factors affecting attendance.

Aged↗
PubMed1995

DNA quantification is technically feasible and of value in cervical smear samples: possible applications for determination of progression in low grade dyskaryosis.

This study evaluates the feasibility of DNA analysis of cervical intraepithelial neoplasia III (CIN III) lesions on cervical smear and formalin-fixed paraffin-embedded tissue (FFPET) blocks with a view to extending this type of analysis to milder grades of dyskaryosis. DNA ploidy was determined by image analysis using a CAS 200 Image Analyser. Seventeen patients with a diagnosis of CIN III were studied. Results show that all smear and tissue samples were non-diploid with nine aneuploid and eight tetraploid lesions. In 6/7 patients whose smears and corresponding biopsies were examined there was complete agreement as to the DNA profile. We conclude that DNA quantification is technically feasible in archival, routinely prepared cervical smears. This technique should now be applied to CINI and CINII cervical smears to determine if it is of value in identifying those lesions that will progress to CIN III. This study is particularly timely with the possibility in the near future of estimation of ploidy by image analysis using instruments such as the Highly Optimized Microscope Environment (HOME) system.

Aneuploidy↗
PubMed1991

The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity.

Endothelial cell adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-regulated cell surface molecules involved in leukocyte adhesion. We have studied two forms of cutaneous inflammation to investigate in vivo the kinetics of adhesion molecule expression in relation to tissue accumulation of leukocytes. Immunohistology was performed on skin biopsies taken from human volunteers at 1, 6, 24, 72 h, and 1 week after two minimal erythema doses (MED) of ultraviolet B (UV-B) or intra-cutaneous tuberculin-purified protein derivative (PPD) (10-100 U). ELAM-1 expression on vascular endothelium and polymorphonuclear leukocyte infiltration were first observed at 6 h and maximal at 24 h after both UV-B and PPD. At 72 h and 1 week, however, endothelial ELAM-1 was more strongly expressed in PPD biopsies. VCAM-1 was minimally expressed in control skin, and was induced above background levels on endothelium, on some perivascular cells, and on stellate-shaped cells in the upper dermis at 24 h after injection of PPD; it was maintained up to 1 week. In contrast, no induction of VCAM-1 was seen following challenge with either 2 or 8 MED UV-B. Following PPD, but not UV-B, there was marked induction of ICAM-1 expression on basal keratinocytes. In these biopsies, the inflammation induced in response to PPD therefore differed from UV-B-induced inflammation in showing prolonged expression of endothelial ELAM-1, induction of VCAM-1 on endothelium and other cells, and induction of keratinocyte ICAM-1. These differences may result from differences in the cytokines released and may in turn be responsible for the differences in the nature of the leukocytic infiltration during the two types of inflammatory response.

Cell Adhesion↗
PubMed1990

Review of an Irish cervical smear service.

Cervical cytology material from 5,815 women who presented to General Practitioners throughout Ireland for routine cervical smears were referred to our Pathology Laboratory. The smears were reviewed retrospectively in order to report on the incidence of dyskaryosis and other abnormalities diagnosed on cervical cytology. Evidence of dyskaryosis was found in a total of 2.2% and "borderline" changes in a total of 0.3% of smears. Cytology and subsequent histology were compared in cases of significant cervical intraepithelial neoplasia. Comparison in cases of moderate and severe dyskaryosis showed precise correlation between the diagnosis of cervical intraepithelial neoplasia on biopsy and its prediction on cytology in 30 of 33 cases. Over a third of women screened were in their 4th decade and the highest incidence of dyskaryosis was in this age group. Only 10% of those screened were 50 years or over and a third were aged 40 years and over. These facts are of relevance with regard to the problem of targeting the population at risk in the long term planning of routine cytology screening services in this country.

Adolescent↗
PubMed1989

Pharmacokinetics of sufentanil in neurosurgical patients undergoing hyperventilation.

The pharmacokinetics of sufentanil were determined in 11 hypocapnic (arterial PCO2 2.9-3.7 kPa) and seven normocapnic (arterial PCO2 5.3-6.0 kPa) neurosurgical patients. Following a single i.v. bolus of sufentanil 4 micrograms kg-1, multiple arterial samples were obtained at timed intervals and plasma concentration of sufentanil was measured by radioimmunoassay. Calculation of the pharmacokinetic parameters from the derived compartmental models demonstrated an increased total volume of distribution of sufentanil in hypocapnic patients (mean 5427 (SD 1866) ml kg-1 v. 3518 (1097) ml kg-1; P less than 0.05) in the control patients and a more prolonged elimination half-life (232 (60) min v. 143 (51) min; P less than 0.01). The increased distribution of sufentanil with hyperventilation was probably caused by an increased proportion of opioid in the nonionized state.

Adult↗
PubMed1989

Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1-deficient cell line.

In order to investigate the role of lymphocyte function-associated antigen 1 (LFA-1) in lymphocyte adhesion to endothelial cells (EC), we have studied the adhesion of a LFA-1-deficient lymphoblastoid cell line, ICH-KM, which has < 10% of the cell surface LFA-1 expressed on a normal lymphoblastoid cell line, ICH-BJ. The adhesion of ICH-KM cells to unstimulated EC was 49.9 +/- 8.6% (mean +/- SD) that of ICH-BJ cells. Moreover, phorbol ester-stimulated ICH-KM cells showed a considerably weaker increase in adhesion to unstimulated EC compared with ICH-BJ cells (mean +/- SD increase in percentage adhesion, 3.8 +/- 2.3 compared with 18.5 +/- 8.0; P<0.025). In contrast, there was no significant difference between the enhanced adhesion of ICH-KM cells and ICH-BJ cells to interleukin-1 (IL-1)-stimulated EC. Thus ICH-KM cells showed a 22.7 +/- 11.0 (mean +/- SD) increase in percentage adhesion to IL-1-stimulated EC compared with the 24.8 +/- 8.5 increase in percentage adhesion of ICH-BJ cells. Anti-LFA-1 monoclonal antibodies had no effect on the enhanced adhesion of ICH-KM and ICH-BJ cells to IL-1-stimulated EC but abolished the differences in adhesion between the two cell lines. The study therefore indicates that although a major part of unstimulated and phorbol ester-stimulated lymphocyte-EC adhesion is dependent upon LFA-1, the enhanced adhesion due to stimulation of EC with IL-1 is not dependent upon this molecule. The data therefore supports the existence of cytokine-inducible LFA-1-independent adhesion molecules for lymphocytes on EC.

Antibodies, Monoclonal↗
PubMed1983

Development of selected neurological skills.

The development of several selected neurological skills in 592 children, ages 3 to 6 years 11 months, were studied. The sequence in the development of these skills included the ability to point up and down, to keep the arms extended, pointing back, to open and close a safety pin, pointing front, figure identification, single finger identification, and right-left concept developing shortly after the others. Clinical implications of these findings have not been evaluated in this study.

Brain Damage, Chronic↗