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Biomedical subjects

R Scott

Publications and source records attributed to R Scott.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cadmium concentrations in human kidney in the UK: 1978-1993.

Almost 2700 samples of human renal cortex have been collected from throughout the UK over a 16 year period from 1978 to 1993. The mean Cd concentration was 19 micrograms g-1 and the median 16 micrograms g-1. Smokers were, on average, about 5 micrograms g-1 higher than non-smokers. Cd increased from low concentration in the young to a maximum of 23 micrograms g-1 in middle age followed by a decrease in old age. Subjects who had died of renal disease had lower Cd concentrations. Geographical variations in the UK are small and the concentrations appear to be static over the 16 year period. Some 3.9% of the population had Cd concentrations > 50 micrograms g-1, the critical level at which beta 2-microglobulin appears in urine.

Adolescent↗
PubMed1999

Surgical complications of functional neurosurgery treating movement disorders: results with anatomical localisation.

Thalamic and pallidal lesions can alleviate movement disorders, but to achieve this safely and efficaciously requires accurate target localization. We report the surgical complications encountered using an anatomical localization technique to create 121 thalamic and pallidal lesions in 79 consecutive patients over a 3 year period. There was no perioperative mortality, although there was one late death indirectly related to surgery. The risk of haemorrhage was 3.3% per lesion made. Anatomical localization offers a relatively safe way of identifying targets for functional neurosurgery, with complication rates which compare favourably with the published literature. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Rapid visualization of metaphase chromosomes in single human blastomeres after fusion with in-vitro matured bovine eggs.

The present study was aimed to facilitate karyotyping of human blastomeres using the metaphase-inducing factors present in unfertilized eggs. A rapid technique for karyotyping would have wide application in the field of preimplantation genetic diagnosis. When cryopreserved in-vitro matured bovine oocytes were fused with human blastomeres, the transferred human nuclei were forced into metaphase within a few hours. Eighty-seven human blastomeres from abnormal or arrested embryos were fused with bovine oocytes in a preclinical study. Fusion efficiency was 100%. In 21 of the hybrid cells, no trace of human chromatin was found. Of the remaining 66, 64 (97%) yielded chromosomes suitable for analysis. The method was used to karyotype embryos from two patients with maternal translocations. One embryo which was judged to be karyotypically normal was replaced in the first patient, resulting in one pregnancy with a normal fetus. None of the second patient's embryos was diagnosed as normal, and hence none was transferred. The results of the present study demonstrated that the ooplasmic factors which induce and maintain metaphase in bovine oocytes can force transferred human blastomere nuclei into premature metaphase, providing the basis for a rapid method of karyotyping blastomeres from preimplantation embryos and, by implication, cells from other sources.

Adult↗
PubMed1999

Positive outcome after preimplantation diagnosis of aneuploidy in human embryos.

usromosomal abnormalities are responsible for a great deal of embryo wastage, which is reflected, at least partially, in decreased implantation and increased miscarriage in older women. To address this problem the transfer of only chromosomally normal embryos previously selected by preimplantation genetic diagnosis (PGD) has been proposed. We designed a multi-centre in-vitro fertilization (IVF) study to compare controls and a test group that underwent embryo biopsy and PGD for aneuploidy. Patients were matched retrospectively, but blindly, for average maternal age, number of previous IVF cycles, duration of stimulation, oestradiol concentrations on day +1, and average mature follicles. All these parameters were similar in test and control groups. Only embryos classified as normal for those chromosomes were transferred after PGD. The results showed that the rates of fetal heart beat (FHB)/embryo transferred between the control and test groups were similar. However, spontaneous abortions, measured as FHB aborted/FHB detected, decreased after PGD (P < 0.05), and ongoing pregnancies and delivered babies increased (P < 0.05) in the PGD group of patients. Two conclusions were obtained: (i) PGD of aneuploidy reduced embryo loss after implantation; (ii) implantation rates were not significantly improved, but the proportion of ongoing and delivered babies was increased.

Aneuploidy↗
PubMed1999

Evidence of a role for Ki-Ras in the stimulated proliferation of renal fibroblasts.

Progressive renal fibrosis is driven by a range of cytokines that act via membrane receptors and intracellular signaling cascades to evoke gene transcription events and related responses. The Ras family of GTPases has been implicated in many of these signaling cascades in model systems such as 3T3 fibroblasts. However, the roleof the specific Ras isoforms Ki, Ha, and N in the stimulation of renal fibroblasts has not been defined. In this study, Ras has been inhibited in primate renal fibroblasts (vero cells) using specific phosphorothioate oligodeoxynucleotides (oligos) targeting the three isoforms. Lipofectin transfection with 200 to 400 nM Ki-Ras oligo inhibited the epidermal growth factor- and fibroblast growth factor-stimulated proliferation of vero cells by 25 to 35% with a lesser effect on serum-stimulated growth. Oligos against Ha-Ras and N-Ras were inactive with respect to control oligo. Total cellular Ras protein (estimated by Western blotting) was reduced by 60 to 90% 24 h after transfection with Ki-Ras oligo. N-Ras, Ha-Ras, and control oligos were inactive. Total Ras synthesis over 4 h measured using [35S]-cys/met pulse chase was reduced by approximately 70% by Ki-Ras oligo and not altered by other oligos. The fractional prenylation of Ras was quantified from the discrete bands on polyacrylamide gel electrophoresis and was increased by the Ki-Ras oligo alone. These data demonstrate that these renal fibroblasts predominantly express the Ki isoform of Ras and that this GTPase plays a role in the stimulated proliferation of these cells. Ras GTPases may be a target for the inhibition of processes leading to renal fibrosis.

Base Sequence↗
PubMed1999

Voices, Opportunities & Choices Employment Club: transforming sheltered workshops using an affirmative business approach. The VOCEC Board of Directors.

Voices, Opportunities & Choices Employment Club (VOCEC) is a non-profit "umbrella" corporation that facilitates the development of affirmative businesses to create jobs for consumers of mental health services. To date, 5 independent businesses have been developed by transforming the resources of sheltered workshops within Kingston Psychiatric Hospital and 2 businesses have been established in collaboration with a local public library. This paper provides a description of VOCEC, including an overview of the affirmative business approach, the structure of the organization, and the process of business development. Personal reflections provide insights into the experiences of consumers, staff, and Board members associated with the corporation.

Community Participation↗
PubMed1998

Effects of over- and under-expression of Cu,Zn-superoxide dismutase on the toxicity of glutamate analogs in transgenic mouse striatum.

Considerable evidence suggests that reactive oxygen species mediate the neurotoxic effects of ionotropic glutamate receptor activation. Accordingly, we have examined neuronal degeneration resulting from intrastriatal injection of quinolinic acid, an NMDA receptor agonist, and kainic acid in gene targeted and transgenic mice that under- or over-express copper, zinc superoxide dismutase (Cu,Zn-SOD; SOD-1). Elevated SOD-1 activity significantly protects against quinolinic acid and kainic acid neurotoxicity in the mouse striatum whereas reduced activity appears to potentiate neurotoxicity. Thus a 'gene-dose' effect of SOD-1 has been demonstrated with regard to excitotoxic mechanisms.

Animals↗
PubMed1998

Convergence characteristics of two algorithms in non-linear stimulus artefact cancellation for electrically evoked potential enhancement.

Somatosensory evoked potentials (SEPs) are a sub-class of evoked potentials (EPs) that are very useful in diagnosing various neuromuscular disorders and in spinal cord and peripheral-nerve monitoring. Most often, the measurements of these signals are contaminated by stimulus-evoked artefact. Conventional stimulus-artifact (SA) reduction schemes are primarily hardware-based and rely on some form of input blanking during the SA phase. This procedure can result in partial SEP loss if the tail of the SA interferes with the SEP. Adaptive filters offer an attractive solution to this problem by iteratively reducing the SA waveform while leaving the SEP intact. Owing to the inherent non-linearities in the SA generation system, non-linear adaptive filters (NAFs) are most suitable. SA reduction using NAFs based on truncated second-order Volterra expansion series is investigated. The focus is on the performance of two main adaptation algorithms, the least mean square (LMS) and recursive least squares (RLS) algorithms, in the context of non-linear adaptive filtering. A comparison between the convergence and performance characteristics of these two algorithms is made by processing both simulated and experimental SA data. It is found that, in high artefact-to-noise ratio (ANR) SA cancellation, owing to the large eigenvalue spreads, the RLS-based NAF is more efficient than the LMS-based NAF. However, in low-ANR scenarios, the RLS- and LMS-based NAFs exhibit similar convergence properties, and the computational simplicity of the LMS-based NAFs makes them the preferred option.

Electric Stimulation↗
PubMed1998

First pregnancies after preconception diagnosis of translocations of maternal origin.

OBJECTIVE: To develop an approach to preimplantation diagnosis of translocations that would not require the use of specific DNA probes for each translocation type. DESIGN: Retrospective analysis. SETTING: Clinic. PATIENT(S): Two patients with 45XX,der(13;14)(q10;q10) karyotypes and one patient with a 46XX,t(4;14)(p15;q24) karyotype. INTERVENTION(S): Based on the observation that first polar body chromosomes remain at the metaphase stage for a few hours after oocyte retrieval, fluorescence in situ hybridization with chromosome-painting probes was used to perform preconception genetic diagnosis of translocation of maternal origin. MAIN OUTCOME MEASURE(S): Oocyte FISH analysis. RESULT(S): A total of 31 mature oocytes were produced, and results were obtained in 23 first polar bodies. After IVF-ET, all three patients became pregnant, preconception diagnoses being confirmed by prenatal diagnosis or birth. CONCLUSION(S): Preconception diagnosis of translocations may reduce significantly the risk of chromosomally unbalanced offspring and pregnancy loss. This method is simpler than previous approaches because the need to develop specific DNA probes for each translocation type is avoided.

Adult↗
PubMed1998

Type 1 diabetes in insulin-treated adult-onset diabetic subjects.

The frequency of autoimmune features was compared in adult-onset diabetic subjects either requiring insulin treatment within 12 months of diagnosis or progressing to insulin therapy after a latency of at least 5 years. Adult-onset insulin-treated diabetic subjects were sampled from the population-based Canterbury Diabetes Registry (n = 1580). There were 237 (15%) registrants who met the study criteria of age < 75 years at 1 January 1993, age at diagnosis of diabetes > or = 45 years and duration of diabetes between 5 and 15 years; 101 subjects commenced insulin 5-15 years after diagnosis (group 1) and 80 subjects commenced insulin within 1 year of diagnosis (group 2). C-peptide levels, islet cell antibodies (ICA) and antibodies against glutamic acid decarboxylase (anti-GAD) were determined in all individuals from group 1 (n = 27) and group 2 (n = 23) who agreed to be recruited to the study. The group 1 and group 2 samples did not differ significantly in their demographic characteristics, nor were they different from the two groups from which they were drawn (mean age, 64.2 years; age at diagnosis, 53.5 years; duration of diabetes, 10.7 years; body mass index, 28.6 kg/m2). Overall, 12 of the 50 (24%) study subjects tested positive for anti-GAD; 43% (10) of group 2 subjects were anti-GAD positive compared with only 7.4% (2) of group 1 subjects (P < 0.01). Postprandial C-peptide levels were significantly lower in group 2 subjects compared with group 1 subjects (627 vs 1124 pM, P < 0.05). All subjects were ICA negative. These observations suggest that autoimmune destruction of beta-cells explains early requirement for insulin in adult-onset diabetes.

Age of Onset↗
PubMed1998

Spontaneous abortions are reduced after preconception diagnosis of translocations.

PURPOSE: Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11). METHODS: The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added. RESULTS: A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%). CONCLUSIONS: With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1998

Is the timing of post-vasectomy seminal analysis important?

OBJECTIVE: To review the practice in two hospitals with differing protocols in the timing of seminal analysis after vasectomy. PATIENTS AND METHODS: The results from 245 vasectomies carried out at Hospital A, where semen was assessed 3 months after vasectomy, were reviewed and compared with those from 100 consecutive vasectomies at Hospital B, where semen was assessed 6 months after vasectomy. The results of seminal analysis at Hospital A were also audited after changing to the 6-month protocol. The patients' preferences for the timing of seminal analysis were also obtained. RESULTS: Of the 245 patients at Hospital A, 58 (24%) failed to provide samples, leaving 187 (76%) for evaluation; 528 samples were examined (mean 2.8 per patient, range 1-13). The first sample was positive in 36 (19.3%) and the second positive in 10 (5.3%), the first being negative. Four (2%) patients had persistent spermatozoa at 6 months, one subsequently undergoing exploration. Thirty-one (17%) patients provided further samples despite providing two consecutive clear ones. At Hospital B, 24 (24%) patients failed to provide samples; 10 (13%) patients had persistent spermatozoa at 6 months and live spermatozoa were detected in one patient's samples. All eventually produced clear samples, with none requiring exploration. After changing the protocol, 87 vasectomies were performed, with 18 (21%) patients failing to provide samples; seven (10%) of the samples collected showed occasional nonmotile spermatozoa at 6 months in either the first, second or both samples, with all samples clear by 8 months after vasectomy. CONCLUSIONS: The complete disappearance of spermatozoa after vasectomy takes longer than is generally believed and we therefore suggest that given adequate counselling, seminal analysis 6 months after vasectomy is cost-effective and in the patient's interest.

Humans↗
PubMed1998

The effect of oral selenium supplementation on human sperm motility.

OBJECTIVES: To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility. PATIENTS AND METHODS: Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility. RESULTS: Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group. CONCLUSION: This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.

Adult↗
PubMed1998

The pallidotomy debate.

It has been suggested that image-guidance and macro-stimulation alone are not sufficiently accurate to result in safe and effective lesion localization in pallidotomy for Parkinson's disease when compared with micro-electrode recording. This review analyses the data in the series published to date, and compares the safety and efficacy of the two techniques, finding no evidence to support this claim. In addition, evidence regarding the necessary accuracy of lesion placement is reviewed.

Brain Mapping↗
PubMed1998

Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson's disease. A consecutive series of eight simultaneous bilateral and twelve unilateral procedures.

Intellectual, psychological and functional outcomes were evaluated in a consecutive series of 20 Parkinsonian patients who had unilateral (UPVP) or simultaneous bilateral posteroventral pallidotomy (BPVP) using Image Fusion and Stereoplan (Radionics Inc., Boston, Mass., USA) with stimulation for lesion localization. Comprehensive baseline and 3-month postoperative neuropsychological and neurological assessment protocols were administered together with questionnaire measures of functional disability, quality of life and psychological symptomatology. Changes in patients' clinical presentation and scores on psychometric tests, questionnaires and observational rating scales were then examined. We observed no new neuropsychiatric sequelae directly related to pallidotomy. Cognitive sequelae were restricted to selective reductions in categorical verbal fluency following UPVP (P < 0.001) and BPVP (P < 0.01) and a reduction in phonemic verbal fluency following BPVP (P < 0.01); these changes were not reported subjectively. A fall in diadochokinetic rates (P < 0.01) and some subjective reports of a worsening in pre-existing dysarthria, hypophonia and hypersalivation/drooling following BPVP also suggested changes in speech motor apparatus; however, these changes did not have significant functional consequences. There was one case of more generalized cognitive impairment following BPVP. We also observed significant symptomatic improvement on neurological rating scales; following UPVP, Total Unified Parkinson's Disease Rating Scale (UPDRS) scores improved by 27% (P < 0.01) and following BPVP the improvement was 53% (P < 0.05). Patients' perceptions of reduced postoperative functional disability and improvements in 'quality of life' also achieved statistical significance on a number of both physical and psychosocial questionnaire subscales.

Activities of Daily Living↗