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Biomedical subjects

D McNaughton

Publications and source records attributed to D McNaughton.

18 recordsLinked to original sources

A Fourier transform infrared microspectroscopic imaging investigation into an animal model exhibiting glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly malignant human brain tumour for which no cure is available at present. Numerous clinical studies as well as animal experiments are under way with the goal being to understand tumour biology and develop potential therapeutic approaches. C6 cell glioma in the adult rat is a frequently used and well accepted animal model for the malignant human glial tumour. By combining standard analytical methods such as histology and immunohistochemistry with Fourier Transform Infrared (FTIR) microspectroscopic imaging and multivariate statistical approaches, we are developing a novel approach to tumour diagnosis which allows us to obtain information about the structure and composition of tumour tissues that could not be obtained easily with either method alone. We have used a "Stingray" FTIR imaging spectrometer to analyse and compare the compositions of coronal brain tissue sections of a tumour-bearing animal and those from a healthy animal. We have found that the tumour tissue has a characteristic chemical signature, which distinguishes it from tumour-free brain tissue. The physical-chemical differences, determined by image and spectral comparison are consistent with changes in total protein absorbance, phosphodiester absorbance and physical dispersive artefacts. The results indicate that FTIR imaging analysis could become a valuable analytic method in brain tumour research and possibly in the diagnosis of human brain tumours.

Animals↗

Fourier transform infrared (FTIR) spectral mapping of the cervical transformation zone, and dysplastic squamous epithelium.

OBJECTIVES: This paper is aimed at establishing infrared spectral patterns for the different tissue types found in, and for different stages of disease of squamous cervical epithelium. Methods for the unsupervised distinction of these tissue types are discussed. METHODS: Fourier transform infrared (FTIR) maps of the squamous and glandular cervical epithelium, and of the cervical transformation zone, were obtained and analyzed by multivariate unsupervised hierarchical cluster methods. The resulting clusters are correlated to the corresponding stained histopathological features in the tissue sections. RESULTS: Multivariate statistical analysis of FTIR spectra collected for tissue sections permit an unsupervised method of distinguishing tissue types, and of differentiating between normal and diseased tissue. By analyzing different spectral windows and comparing the results with histology, we found the amide I and II region (1740-1470 cm(-1)) to be very important in correlating anatomical and histopathological features in tissue to spectral clusters. Since an unsupervised, rather than a diagnostic, algorithm was used in these efforts, no statistical analysis of false-positive/false-negative results is reported at this time. CONCLUSIONS: The combination of FTIR micro-spectroscopy and multivariate spectral processing provides important insights into the fundamental spectral signatures of individual cells and consequently shows potential as a diagnostic tool for cervical cancer.

Cell Transformation, Neoplastic↗

Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study.

OBJECTIVE: To examine whether allopurinol is associated with any alteration in mortality and hospitalisations in patients with chronic heart failure (CHF). This hypothesis is based on previous data that a high urate concentration is independently associated with mortality with a risk ratio of 4.23 in CHF. DESIGN: Retrospective cohort study. SETTING: Medicines Monitoring Unit, Ninewells Hospital, Dundee, UK. PATIENTS: 1760 CHF patients divided into four groups: those on no allopurinol, those on long term low dose allopurinol, those on short term low dose allopurinol, and those on long term high dose allopurinol. MAIN OUTCOME MEASURES: Total mortality, cardiovascular mortality, cardiovascular hospitalisations, cardiovascular mortality or hospitalisations. RESULTS: Long term low dose allopurinol was associated with a significant worsening in mortality over those who never received allopurinol (relative risk 2.04, 95% confidence interval (CI) 1.48 to 2.81). This may be because low dose allopurinol is insufficient to negate the adverse effect of a high urate concentration. However, long term high dose (> or = 300 mg/day) allopurinol was associated with a significantly better mortality than longstanding low dose allopurinol (relative risk 0.59, 95% CI 0.37 to 0.95). This may mean that high dose allopurinol can fully negate the adverse effect of urate and return the mortality to normal. CONCLUSIONS: Long term high dose allopurinol may be associated with a better mortality than long term low dose allopurinol in patients with CHF because of a dose related beneficial effect of allopurinol against the well described adverse effect of urate. Further work is required to substantiate or refute this finding.

Aged↗

Micro-Raman characterisation of the R to T state transition of haemoglobin within a single living erythrocyte.

We present the first recorded Raman spectra of haemoglobin in both the R and T states from within a single living erythrocyte using 632.8 nm excitation. Bands characteristic of low spin haems are observed in oxygenated and carboxylated erythrocytes at approx. 1636 (nu(10)), 1562-1565 (nu(2)), 1250-1245 cm(-1) (nu(13)) and 1226-1224 cm(-1) (nu(5)+nu(8)). The spectra of deoxygenated and methaemoglobin erythrocytes have characteristic high spin bands at approx. 1610-1606 cm(-1) (nu(10)), 1582-1580 (nu(37)), 1547-1544 (nu(11)), 1230-1220 cm(-1) (nu(13)) and 1215-1210 cm(-1) (nu(5)+nu(8)). Bands at 1172 (nu(30)), 976 (nu(45)) and 672 (nu(7)) cm(-1) appear to be enhanced at 632.8 nm in low spin haems. The oxidation state marker band (nu(4)) at 1364-1366 cm(-1) appeared invariant within this domain in all single cells and conditions investigated contrary to other resonance Raman studies on haem isolates. The information gained by in vivo single erythrocyte molecular analysis has important ramifications to the understanding of fundamental physiological processes and may have applications in the diagnosis and treatment of red blood cell disorders.

Erythrocytes↗

Pharmacoepidemiological research at the Medicines Monitoring Unit, Scotland: data protection and confidentiality.

The Medicines Monitoring Unit (MEMO) is a University-based organization that uses record-linkage techniques to construct an observational database for the population of Tayside, Scotland (approximately 400,000 people). This contains healthcare data indexed by a unique identifier, including data on all prescriptions dispensed, which facilitates pharmacoepidemiological (and other) research. It has hitherto been possible to carry out drug safety studies in the entire population, with access to original medical records of patients where necessary, that have satisfied ethical concerns and confidentiality legislation. However, the recent UK Data Protection Act 1998 (which enforces the 1995 European Directive on Data Protection) has important implications for MEMO's research. The Act has necessitated changes to the way in which research studies are carried out, with MEMO's objective being to ensure that research can continue while protecting the rights and privacy of individual patients. This involves anonymization of data, seeking specific ethical approval for research studies and obtaining relevant permissions from 'Caldicott Guardians', as described in this article.

Bioethics↗

The High-Resolution FTIR Spectrum and Equilibrium Structure of Chloro(sulphido)boron.

The FTIR spectrum of chloro(sulphido)boron, Cl-B&bond;S, has been recorded at 0.0035 cm(-1) resolution. The nu(3) bands of the isotopomers (35)Cl(11)B(32)S, (37)Cl(11)B(32)S, (35)Cl(11)B(34)S, (37)Cl(11)B(34)S, (35)Cl(10)B(32)S, (37)Cl(10)B(32)S, and (35)Cl(10)B(34)S have been analyzed to yield effective rotational and centrifugal distortion constants for the ground and a number of excited vibrational states. For the (35)Cl(11)B(32)S isotopomer the nu(1) band has also been analyzed. The rotational constants have been used to determine equilibrium bond lengths of 168.42(8) and 160.14(8) pm for the Cl-B and B-S bonds, respectively. Copyright 2000 Academic Press.

Journal Article↗

Fourier-transform infrared spectroscopy as a tool for detecting early lymphocyte activation: a new approach to histocompatibility matching.

Fourier transform infrared (FT-IR) spectroscopy due to its speed and sensitivity is becoming an increasingly powerful tool in the study of cell composition. We outline the potential of FT-IR microspectroscopy in monitoring mitogenic and cell mediated lymphocyte activation. We demonstrate the potential of FT-IR spectroscopy in histocompatibility testing by showing that significant spectral differences (p < 0.001, for the mean integrated intensity of phosphodiester band located in the 1142-996 cm(-1) region) exist between lymphocyte cocultures from pairs of HLA matched and mismatched volunteers after only 90 min of incubation. The preliminary results indicate that early spectral changes measured are due to HLA differences between individuals, although the relative contribution of class I and class II differences has yet to be determined. FT-IR spectroscopy represents a novel approach to histocompatibility matching and the rapidity and sensitivity of the technique indicates a potential role in matching protocols for clinical use, particularly in allogeneic bone marrow transplantation.

Analysis of Variance↗

Quantitative determination of the biodegradable polymer Poly(beta-hydroxybutyrate) in a recombinant Escherichia coli strain by use of mid-infrared spectroscopy and multivariative statistics.

Fourier transform infrared (FTIR) spectroscopy in combination with the partial least squares (PLS) multivariative statistical technique was used for quantitative analysis of the poly(beta-hydroxybutyrate) (PHB) contents of bacterial cells. A total of 237 replicate spectra from 34 samples were obtained together with gas chromatography-determined reference PHB contents. Using the PLS regression, we were able to relate the infrared spectra to the reference PHB contents, and the correlation coefficient between the measured and predicted values for the optimal model with a standard error of prediction of 1.49% PHB was 0.988. With this technique, there are no solvent requirements, sample preparation is minimal and simple, and analysis time is greatly reduced; our results demonstrate the potential of FTIR spectroscopy as an alternative to the conventional methods used for analysis of PHB in bacterial cells.

Biodegradation, Environmental↗

The High-Resolution FTIR Far-Infrared Spectrum of Formamide.

The far-infrared spectrum of formamide (HCONH2) has been recorded at high resolution and over 9000 vibration-rotation lines assigned. Molecular parameters from the rovibrational analyses of the unperturbed 12(1)0 out-of-plane vibration band have been obtained for the ground state and the excited state. An analysis of the complicated resonance system between the 9(1)0, 11(1)0, and 12(2)0 bands has also been carried out. The mid-infrared spectrum of formamide has been recorded at low resolution and assignments for the fundamental, combination, and overtone bands in this region are given. The Large Amplitude Motion (LAM) of the out-of-plane mode has been reanalyzed using the new parameter set. Copyright 1999 Academic Press.

Journal Article↗

The High-Resolution FTIR Far-Infrared Spectrum of Vinylamine.

The infrared spectrum of vinylamine, generated by pyrolysis of cyclobutylamine, has been investigated at low and high resolution. The rovibrational structure of the far infrared spectrum (0.002 cm(-1)) has been analyzed, and effective rotational and centrifugal distortion constants have been derived for eight vibration-rotation bands in the region 250-750 cm(-1). The rovibrational structure of two further bands has been assigned using combination differences, and some conclusions have been drawn about the vibrational energy levels involved. With the large amount of new data it is possible to achieve a vibrational analysis of the far infrared region, but not to totally exclude an alternative assignment. Copyright 1999 Academic Press.

Journal Article↗

FTIR microspectroscopic study of cell types and potential confounding variables in screening for cervical malignancies.

FTIR microscopy was applied to the analysis of cell types and other variables present in Pap smears to ascertain the limitations of infrared spectroscopy in the diagnosis of cervical cancer and dysplasia. It was found that leukocytes, and in particular lymphocytes, have spectral features in the phosphodiester region (1300-900 cm[-1]) suggestive of what has previously been described as changes indicative of malignancy. Endocervical cells and fibroblasts have similar spectral features to HeLa cells and consequently could also confound diagnosis. The use of ethanol as a fixative and dehydrating agent results in retention of glycogen in cervical cell types and thus minimizes spectral changes in the glycogen region due to sampling technique. Spectra of seminal fluids exhibit strong bands in the phosphodiester/carbohydrate region; however, sperm contamination should be easily detectable by the presence of a distinctive doublet at 981/968 cm(-1). Erythrocyte spectra exhibit a reduction in glycogen band intensity, but can be discerned by a relatively low-intensity nu(s) PO2- band. Endocervical mucin spectra exhibit a reduction in glycogen bands and a very pronounced nu(s) PO2- band, which is similar in intensity to the corresponding band in HeLa cells. Thrombocytes have strong bands in the phosphodiester region, but thrombocytes can be discerned from other cell types by the presence of two small broad bands at 980 and 935 cm(-1). Candida albicans is characterized by strong bands in the polysaccharide region which could potentially obscure diagnostic bands if C. albicans is present in large numbers. Spectra of bacteria common to the female genital tract, in general, also have strong absorptions in the polysaccharide region; however, bacterial contamination is usually minimal and would not be expected to obscure cervical cell spectra. Nylon threads and bristles from cervical sampling implements produce characteristic IR profiles which allow for easy identification. Given the number of potential confounding variables associated with cervical cytology, a multivariate statistical or neural network analysis would appear to be necessary before the implementation of FTIR technology in clinical laboratories.

Biopsy↗

High-Resolution Fourier Transform Infrared Spectroscopy of Nitrosyl Fluoride

The high-resolution FTIR spectrum of FNO has been recorded and the rovibrational structure of the essentially unperturbed nu3, 2nu3, and nu1 + nu3 cold bands and the 2nu3 <-- nu3, nu2 + nu3 <-- nu3, and nu1 + nu2 + nu3 <-- nu3 hot bands has been analyzed. The perturbed bands nu1 and nu1 + nu2 have been assigned and the data analyzed by fitting the transitions with the dark states nu2 + 2nu3 and 2nu2 + 2nu3. Parameters for both light and dark states together with Coriolis coupling parameters have been determined. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

Infrared microspectroscopy and artificial neural networks in the diagnosis of cervical cancer.

Infrared spectra of 88 normal and 32 abnormal (mild to severe dysplasia) cervical smear samples were used as a databank to investigate the usefulness of artificial neural networks (ANN) in the diagnosis of cervical smears. The spectra were first reduced, using principal component analysis (PCA), to seven wavenumber components that are the major contributors to the variance. A number of different ANN architectures were investigated that could differentiate between normal and abnormal cervical smears. Although the ANNs were trained to differentiate only normal from abnormal smears, the results using an independent test data set indicated that within the abnormal category mild dysplasia could be distinguished from severe dysplasia. The results using this restricted data set indicate that neural networks coupled to infrared microspectroscopy could provide an alternative automated means of screening for cervical cancer.

Female↗

The High-Resolution FTIR Spectrum of Jet-Cooled CH3CF2Cl

The infrared spectrum of HCFC-142b, CH3CF2Cl, has been recorded at high and low resolution using a supersonic jet-FTIR spectrometer system. Molecular parameters for a number of vibrational states have been obtained from rovibrational analyses of the C-type bands nu14 (1192 cm-1) and nu15 (967 cm-1), the A-type band nu7 (905 cm-1), and the B-type bands nu5 (1234 cm-1) and nu7 + nu11 (1215 cm-1). A rotational temperature of ca. 50 K in the jet expansion has been estimated from a comparison of the experimental spectrum with band simulations calculated using the resultant molecular constants. Copyright 1997Academic Press

Journal Article↗

The effect of five proofreading conditions on the spelling performance of college students with learning disabilities.

This study investigated the effect of five proofreading conditions on the spelling performance of 12 college students with learning disabilities on a composition activity. The proofreading conditions investigated were handwriting with no additional assistance, handwriting with a conventional print dictionary, handwriting with a handheld spelling checker, word processing with no additional assistance, and word processing with an integrated spelling checker. A repeated measures ANOVA was used to analyze the results, with proofreading condition used as a within-participants factor. Except for handwriting alone, all of the techniques resulted in significant reductions in the number of spelling errors in the students' written work; however, none of the techniques enabled the students to produce compositions with a mean level of spelling accuracy comparable to that of their nondisabled peers.

Achievement↗