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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

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

Familial motor neurone disease with dementia: phenotypic variation and cerebellar pathology.

OBJECTIVES: To characterise the neuropathological phenotypes of two affected individuals from a family with an unusual clinical phenotype resembling motor neurone disease and dementia. METHODS: Histological sections of cerebral cortex, basal ganglia, brain stem, cerebellum, and spinal cord were stained with haematoxylin-eosin, luxol fast blue, silver stains, anti-tau, anti-ubiquitin, anti-alpha-synuclein, and anti-neurofilament. RESULTS: Numerous ubiquitin positive, tau and alpha-synuclein negative intraneuronal inclusions were present in the cerebral cortex (particularly within the dentate gyrus), cerebellar cortex, brain stem, and spinal cord. The cerebellar ubiquitinated inclusions were located in the proximal dendrite of the Purkinje cells. Loss of Purkinje cells and occasional silver and neurofilament positive axonal swellings (torpedoes) were also seen within the cerebellar cortex. The main difference between the two cases was the severity of the spinal cord involvement: no significant pathology was present within one, but obvious motor neurone disease within the other. CONCLUSIONS: The clinical and neuropathological findings in this family are best described as an example of familial motor neurone disease with dementia. Intraneuronal ubiquitin inclusions together with agyrophilic, neurofilament positive torpedoes were present within the cerebellar cortex, both previously unrecognised findings in this group of diseases.

Adult↗
PubMed2003

Cardiovascular effects of donepezil in patients with dementia.

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer's disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

Aged↗
PubMed2002

Comparison of semi-automated image analysis and manual methods for tissue quantification in pancreatic carcinoma.

Objective measurements of tissue area during histological examination of carcinoma can yield valuable prognostic information. However, such measurements are not made routinely because the current manual approach is time consuming and subject to large statistical sampling error. In this paper, a semi-automated image analysis method for measuring tissue area in histological samples is applied to the measurement of stromal tissue, cell cytoplasm and lumen in samples of pancreatic carcinoma and compared with the standard manual point counting method. Histological samples from 26 cases of pancreatic carcinoma were stained using the sirius red, light-green method. Images from each sample were captured using two magnifications. Image segmentation based on colour cluster analysis was used to subdivide each image into representative colours which were classified manually into one of three tissue components. Area measurements made using this technique were compared to corresponding manual measurements and used to establish the comparative accuracy of the semi-automated image analysis technique, with a quality assurance study to measure the repeatability of the new technique. For both magnifications and for each tissue component, the quality assurance study showed that the semi-automated image analysis algorithm had better repeatability than its manual equivalent. No significant bias was detected between the measurement techniques for any of the comparisons made using the 26 cases of pancreatic carcinoma. The ratio of manual to semi-automatic repeatability errors varied from 2.0 to 3.6. Point counting would need to be increased to be between 400 and 1400 points to achieve the same repeatability as for the semi-automated technique. The results demonstrate that semi-automated image analysis is suitable for measuring tissue fractions in histological samples prepared with coloured stains and is a practical alternative to manual point counting.

Algorithms↗
PubMed2002

Anomalous relationship of the spinal accessory nerve to the internal jugular vein.

A patient with an early cancer of the tongue and undergoing a staging neck dissection was noted to have an anomalous relationship of the internal jugular vein and spinal accessory nerve. At the upper end of the dissection (level II, Memorial Sloan-Kettering classification), the internal jugular vein was observed to divide above and reconstitute below the spinal accessory nerve. Although apparently not previously described in the literature, this finding may be encountered by other surgeons who operate in this area, and it is important that these anatomical variations are borne in mind to prevent inadvertent injury.

Accessory Nerve↗
PubMed2002

Systematic comparison of different algorithms for apnoea detection based on electrocardiogram recordings.

Sleep apnoea is a common disorder that is usually diagnosed through expensive studies conducted in sleep laboratories. Sleep apnoea is accompanied by a characteristic cyclic variation in heart rate or other changes in the waveform of the electrocardiogram (ECG). If sleep apnoea could be diagnosed using only the ECG, it could be possible to diagnose sleep apnoea automatically and inexpensively from ECG recordings acquired in the patient's home. This study had two parts. The first was to assess the ability of an overnight ECG recording to distinguish between patients with and without apnoea. The second was to assess whether the ECG could detect apnoea during each minute of the recording. An expert, who used additional physiological signals, assessed each of the recordings for apnoea. Research groups were invited to access data via the world-wide web and submit algorithm results to an international challenge linked to a conference. A training set of 35 recordings was made available for algorithm development, and results from a test set of 35 different recordings were made available for independent scoring. Thirteen algorithms were compared. The best algorithms made use of frequency-domain features to estimate changes in heart rate and the effect of respiration on the ECG waveform. Four of these algorithms achieved perfect scores of 100% in the first part of the study, and two achieved an accuracy of over 90% in the second part of the study.

Algorithms↗
PubMed2002

Developing a quality scoring system for epidemiological surveys of genetic disorders.

A prototype database of published articles containing data on the frequency of human inherited disorders has been developed for use in clinical contexts, in medical research, for epidemiological studies, and in the planning of genetic services. It can be accessed at http://www.uwcm.ac.uk/uwcm/mg/fidd/. The information available in the literature comes from a wide range of publications, not all can be described primarily as epidemiological surveys. A preliminary assessment indicated that the quality of published articles was highly variable. Very few published articles describe quality-scoring systems for epidemiological surveys in general. We have developed a new scoring system to assess the quality of published articles on genetic disease frequency based on five main criteria and nine component scores. We carried out a first pilot study, to test its feasibility, usefulness and reproducibility. Eleven assessors scored six papers on the epidemiology of Huntington disease. As a result of these findings, we modified the scoring system to define each component more clearly. This was then evaluated in a second pilot study, which utilized six assessors to score 20 papers. The consensus between assessors remained relatively poor. We feel that while it may be possible to improve the scoring system further, the degree of improvement attainable may be limited by the poor standards of content and presentation of published surveys, which led to confusion and uncertainty by assessors. This pilot exercise has shown the need to raise the awareness of researchers and clinicians about the basic quality standards to be required of epidemiological genetic surveys.

Epidemiologic Research Design↗
PubMed2002

Age-related changes in peripheral pulse timing characteristics at the ears, fingers and toes.

It is accepted that older subjects have increasing arterial stiffness, which results in increasingly faster pulse transmission to the periphery. However, this age association is less clear in younger subjects and for different peripheral measurement sites. The aims of this study were to determine the association between age and pulse timing characteristics over a five decade age range at the ears, fingers and toes, and to compare these with any additional effects associated with differences in subject height, systolic blood pressure and heart rate. Photoplethysmography pulse wave-forms were recorded noninvasively from the right and left sides at the ears, fingers and toes of 116 normal healthy human subjects. Their median age was 42 years (range 13-72 years). Systolic blood pressure, height and heart rate were also measured. Pulse transit times (PTTs) were determined and referenced to the electrocardiogram R wave. The results revealed that age was the strongest contributor to PTT differences at all sites (P<0.0001). The decrease with ageing was greatest at the toes: -1.6, -0.6, -0.4 ms/year for the toes, fingers, and ears, respectively. Changes for the right and left body sides at each level were highly similar. Blood pressure was also an important contributor to PTT at all sites (P<0.0001); -1.0, -0.4, -0.3 ms/mm Hg, respectively, with approximately half of the effect explained by age. Height was significantly and independently related to PTT at the fingers and toes (P<0.0001); +1.1, +0.7 ms/cm, respectively. The fraction of PTT variability explained by these relationships was 0.65, 0.48, 0.26 for the toes, fingers and ears, respectively (P<0.0001). Finally, we concluded that the age effect decreased linearly from the second to the seventh decades, demonstrating that the effect of changes in arterial stiffness can be detected noninvasively from an early age at three main peripheral sites. Age is the dominant factor in contributing to PTT, and is greatest at the toes, followed by the fingers and then the ears.

Adolescent↗
PubMed2002

The novel tumour suppressor gene ING1 is overexpressed in human melanoma cell lines.

BACKGROUND: Epidemiological evidence indicates that exposure to ultraviolet (UV) radiation is directly linked to the increase of both incidence and mortality of melanoma. However, the genetic changes caused by UV radiation that lead to melanoma formation remain poorly understood. Recently, a potential tumour suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and induce apoptosis in the presence of p53. We have demonstrated that the expression of ING1 is induced after UV irradiation and that ING1 enhances the repair of UV-damaged DNA. OBJECTIVES: To investigate if ING1 plays a role in melanoma formation. METHODS: We examined p33ING1 expression levels in 14 melanoma cell lines. RESULTS: We found that p33ING1 is overexpressed at both mRNA and protein levels in melanoma cell lines compared with normal melanocytes. Single-strand conformation polymorphism (SSCP) analysis showed band shifting in two melanoma cell lines. DNA sequencing confirmed that there were nucleotide alterations in the ING1 gene in Sk-mel-24 and Sk-mel-110 cell lines. Two silent nucleotide alterations in exon 1a were detected in Sk-mel-110. In Sk-mel-24, the A-->G nucleotide alteration at codon 260 resulted in an amino acid change from Asn to Ser, while seven other nucleotide alterations were silent. To determine if the silent nucleotide alterations in these two melanoma cell lines were due to polymorphism, SSCP analysis of ING1 gene was performed in 25 healthy volunteers. No band shift was observed in the SSCP analysis, suggesting that the nucleotide alterations in the melanoma cell lines are unlikely to be due to polymorphism. CONCLUSIONS: Taken together, our data demonstrate that ING1 is overexpressed, but infrequently mutated, in melanoma cell lines.

Cell Cycle Proteins↗
PubMed2002

Epitope affinity chromatography and biophysical studies of monoclonal antibodies and recombinant antibody fragments.

Peptide epitope affinity chromatography is a powerful technique for the purification of antibodies. This study aims to demonstrate the versatility of the technique and to show how biophysical techniques such as circular dichroism (CD) and fluorescence quenching (FQ) can aid the rational design of affinity ligands and characterization of antibody-based reagents. The performance of a number of peptide ligands for the purification of a range of different antibodies and recombinant fragments is investigated by automated fast-protein liquid chromatography. Purified products are analyzed for purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. They are then radiolabelled and the immunoreactivity is determined. Ligands are analyzed for secondary structural characteristics by CD and for binding affinity by FQ. Finally, a study is performed to investigate the thermal stability of a recombinant antibody fragment by CD analysis. It is found that simple ligand modifications such as the introduction of a C-terminal cysteine residue can improve purification performance. The FQ studies show that the modified peptide has a higher affinity for antibody. The CD analysis shows that it has a tendency to dimerize because of the formation of disulfide bonds. The versatility of epitope affinity is demonstrated through the purification of a recombinant diabody (dbFv) and by the use of a separate peptide matrix for the purification of an unrelated antibody. All studies result in antibody preparations of high purity and immunoreactivity. The CD analysis of the dbFv shows that it is denatured at 37 degrees C and is therefore unsuitable as a targeting reagent for use in humans in its present form. It is concluded that epitope affinity chromatography coupled with biophysical analyses plays an important role in the production and characterization of antibody-based reagents for targeted diagnosis and therapy of human diseases.

Amino Acid Sequence↗
PubMed2002

Clinical photographs--the gold standard.

This survey was carried out to allow a minimum data set required for intra- and extra-oral photographs to be established. In 1999 a questionnaire was sent to members of the Angle Society of Europe to establish their current clinical practice with regard to extra- and intra-oral photography. The Angle Society was chosen because of their stated commitment to a high standard of record keeping and of clinical care. Results showed that a full series of extra- and intra-oral photographs were taken both before and after treatment, as well as stage photographs during treatment on many cases. The need for each of these photographs will be discussed in some detail, and recommendations will be made as to what would be considered the Gold standard before, during, and after a course of orthodontic treatment.

Attitude of Health Personnel↗
PubMed2002

Manipulation of digital photographs.

This article provides simple details of what to do with digital images once they have been captured. Inspection of the images as 'thumbnails' using Exif viewer is described, as well as zooming in to check detail contained on the images. Storage of every orthodontic patient using the popular programme, Dentofacial Showcase is described in some detail. For more formal verbal presentations or written material intended for display Microsoft Powerpoint is the programme of choice. Transfer of the images between the three programmes is described in detail, as well as recommended layouts for written and verbal presentations.

Dental Records↗
PubMed2001

Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10.

Limited response to idiotype vaccination in patients with myeloma suggests that there is a need to develop better immunotherapy strategies. It has been determined that the number of high-potency CMRF44+CD14-CD19- dendritic cells (DCs) in the blood of patients with myeloma (range, 0.03%-0.8% of mononuclear cells [MNCs]; n = 26) was not significantly different from that in controls (range, 0.05%-0.8% of MNCs; n = 13). Expression of the costimulatory molecules CD80 and CD86 on DCs from these patients (mean, 29%+/-17% of MNCs and 85%+/-10% of MNCs, respectively) was also normal (mean, 29%+/-17% and 86%+/-16% of MNCs, respectively). Up-regulation of CD80 expression in response to stimulation by human huCD40LT + interleukin (IL)-2 was significantly reduced on the DCs of patients with myeloma during stable disease (n = 9) and was absent during progressive stages (n = 7) of disease. Similar effects were seen on B cells but not on monocytes of the same group of patients. CD86 expression on DCs was high before (86%) and after (89%) stimulation. Inhibition of CD80 up-regulation was neutralized by either anti-transforming growth factor (TGF)-beta1 or anti-IL-10. Up-regulation of CD80 on DCs of controls was inhibited by rTGF-beta1 in a dose-dependent manner. Serum TGF-beta1 and IL-10 levels were normal in most patients studied. Cytoplasmic TGF-beta1 was increased in plasma cells during progressive disease. Thus patients with myeloma have normal numbers of DCs, but CD80 expression may fail to be up-regulated in the presence of huCD40LT because of tumor-derived TGF-beta1 or IL-10. Autologous high-potency DCs may have to be tested for CD80 up-regulation and biologically modified ex vivo before idiotype priming for immunotherapy.

Antibodies, Monoclonal↗
PubMed2001

Generation and refinement of peptide mimetic ligands for paratope-specific purification of monoclonal antibodies.

Paratope-specific purification of antibodies has distinct advantages over conventional methods of antibody purification with respect to its capacity to isolate product of high purity and immunoreactivity. The present report addresses the problems of identifying peptide ligands for the purification of antibodies reactive with nonprotein antigens. Using an anti-steroid antibody as the model, a lead sequence that bound antibody was identified from a peptide phage display library. The minimum binding unit in this sequence was deduced using a series of truncated peptides synthesized on the heads of polyethylene pins. Replacement Net analysis of the minimum binding unit identified peptides with increased affinity for the antibody. The affinity-matured peptide mimotope bound antibody in solution. By molecular modeling the peptide was superimposable onto estrone-3-glucuronide localized in the crystal structure of the antibody binding pocket. In order to resolve problems of presentation posed by the reversal of orientation of the peptide on the affinity matrix compared with the pins, the mimotope peptide was synthesized in reverse sequence using d-amino acids. The resulting affinity matrix was effective for the purification of antibody. Eluted product demonstrated molecular homogeneity and high immunoreactivity. It is concluded that the combination of biological and chemical library techniques described provides a method for the generation and affinity maturation of mimotopes for antibodies against nonprotein antigens.

Animals↗
PubMed2001

The repeatability of superovulatory response and embryo recovery in sheep.

Over an 8-year period, a total of 328 Scottish Blackface donor ewes were involved in a MOET program. They were synchronized with fluorogestone acetate sponges and superovulated with ovine FSH. After the onset of estrus, ewes were hand-mated and laparoscopic artificial insemination was performed with fresh semen 44-46 h after sponge removal. Embryos were recovered semi-laparoscopically on either Day 5 or Day 6 after insemination. Of the 328 donor ewes used, 222 ewes were supervoulated only once, while the remaining ewes were superovulated either twice (73 ewes), 3 times (26 ewes) or 4 times (7 ewes) at yearly intervals to generate a maximum of 474 records for subsequent analysis. There was no significant change in either mean ovulation rate or the mean number of embryos recovered per donor ewe at successive treatments. However, significant (P < 0.05 at least) effects of both year and donor ewe age existed for superovulatory response and number of embryos recovered, though only the effect of year was significant (P < 0.001) for percentage embryo recovery. Repeatability was significant (P < 0.05 at least) for both superovulatory response (r = 0.55, s.e. 0.055) and number of embryos recovered (r = 0.38, SE 0.074), but not for percentage embryo recovery (r = 0.04, SE 0.102).

Age Factors↗
PubMed2001

Prospective study of morbidity after tonsillectomy in children.

Post-operative morbidity was prospectively studied in 384 children after tonsillectomy or adenotonsillectomy, using visual analogue scores to record symptom levels, and questionnaires to monitor satisfaction scores from the children and their families. Assessments were performed between the 7th and 14th day post-operatively. Two hundred children were assessed before the introduction of a pre-admission programme which consisted of an instructional videotape session in the ward and an advice booklet. Department practice was also changed to provide a bottle of paracetamol on discharge routinely for each child. Following these changes in practice a further 184 children were assessed. The provision of relatively simple measures in the programme increased parental satisfaction rates (P<0.05) and reduced GP contact rates (35--17%, P<0.05) post-operatively. The actual levels of morbidity were unchanged despite the provision of analgesia.

Acetaminophen↗