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Biomedical subjects

D Thomson

Publications and source records attributed to D Thomson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status.

STUDY OBJECTIVE: To determine whether inclusion of a leukocyte specific filter into the extracorporeal circuit during aortocoronary bypass surgery alters postoperative cardiopulmonary function. DESIGN: Randomized, double-blinded control trial. SETTING: Tertiary care hospital. PATIENTS: Convenience sampling of patients undergoing elective aortocoronary bypass between October 1992 and June 1993. INTERVENTIONS: A total of 32 patients were randomized to a leukocyte specific filter (n = 16) or to a standard blood filter (n = 16) during the surgical procedure. MEASUREMENTS AND RESULTS: White blood cell count in the standard filter group (12.2 +/- 3.6 10(9)/L) was higher (p = 0.047) than in the leukocyte filter group (9.9 +/- 2.6 10(9)/L) at 4 h postoperatively but counts were similar (p = 0.063) at 24 h (10.8 +/- 2.7 vs 8.9 +/- 2.6 10(9)/L, respectively). Leukocyte activation assessed by chemiluminescence was similar between groups at all measurement periods. We noted transient improvements (p < 0.05) in intrapulmonary shunt (19 +/- 50% vs 24 +/- 9%) and mean blood pressure (85 +/- 8 vs 76 +/- 9 mm Hg, respectively) in the leukocyte filter group compared with the standard filter group, respectively. Otherwise there were no differences noted between groups. CONCLUSIONS: Inclusion of a leukocyte filter during cardiopulmonary bypass caused transient cardiorespiratory improvement that was lost within 24 h and did not offer any significant clinical benefits.

Aged↗
PubMed1995

Single-step protocol for preparation of plant tissue for analysis by PCR.

PCR has many applications in the isolation and analysis of plant DNA. The influence of salt and EDTA concentration, pH, incubation time and temperature on the preparation of plant material for PCR was evaluated. A general single-step method was developed in which a small amount of plant tissue was heated in a simple solution. The DNA in the supernatant was found to be suitable for most PCR applications including arbitrarily primed PCR (random-amplified polymorphic DNA) and PCR with specific primers for both single- and multiple-copy genes. The technique is much simpler than those generally used for plant DNA preparation and was successful with tissues from a wide range of species.

Base Sequence↗
PubMed1994

Preoptic/anterior hypothalamic warming increases EEG delta frequency activity within non-rapid eye movement sleep.

The effects of mild POAH warming and cooling on EEG frequency patterns within sustained periods of NREM sleep were examined. EEG spectral power analysis showed that POAH warming increased delta (0.5-4.0 Hz) activity, but had no effect on theta or sigma frequencies. Delta power was also increased during a 1 h recovery period, following warming. POAH cooling had no EEG effects. Since delta power is thought to be an index of sleep depth, our findings suggest that POAH thermoregulatory mechanisms participate in the regulation of the depth of NREM sleep.

Animals↗
PubMed1994

Expression of tissue kallikrein in human kidney.

1. We studied the distribution of human tissue kallikrein mRNA in normal and diseased kidney, using in situ hybridization, together with immunohistochemical localization of renal kallikrein protein. Materials studied were (a) normal tissue from kidneys removed because of localized renal carcinoma, (b) kidneys removed because of post-traumatic haemorrhage and (c) renal biopsy specimens from patients with membranous glomerulonephritis and nephrotic syndrome. 2. A 1.35 kb EcoRI fragment of human tissue kallikrein cDNA was labelled with [32P]dCTP using the random-primer technique, and used for in situ hybridization. A specific rabbit antibody to active human urinary kallikrein was employed for immunocytochemistry, using a peroxidase-antiperoxidase method. 3. By in situ hybridization, no tissue kallikrein gene expression was seen in the carcinoma nephrectomy specimens. Positive expression was seen in the trauma nephrectomy tissue, and in four of five nephrotic syndrome biopsies. In all kidneys, expression was confined to the renal cortex. The dominant site of gene expression was the distal tubule. Apart from one area of positive signal related to an epithelial cell of Bowman's capsule, expression was not observed in glomeruli. Expression was also seen in the walls of large- and medium-sized blood vessels. 4. By immunohistochemistry, the dominant site of immunoreactivity was the distal tubule. Dense staining was also seen in granular peripolar cells and in isolated parietal epithelial cells close to the vascular pole. Isolated immunoreactive cells were seen in the media of large- and medium-sized arteries. 5. The tissue kallikrein gene in the kidney may not be constitutively expressed, but is expressed in response to physiological or pathological stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Repeated episodes of myocardial ischaemia during combined thoracic epidural-isoflurane anaesthesia.

A patient with a history of coronary artery diseases developed new ST segment depressions in the ECG registration during a low dose (0.7%) isoflurane anaesthesia that was combined with a continuous thoracic epidural analgesia. Simultaneously a small decrease in mean arterial blood pressure (MAP) was noted. During the next 5 min these changes were followed by a severe drop in MAP (from 88 to 60 mmHg) and in cardiac output from 5.5 to 3.2 L/min. When isoflurane was discontinued both the ECG and the cardiovascular changes returned to the previous condition. Later, when 0.5% isoflurane was restarted, the ECG changes reappeared within ten min, but disappeared once again when isoflurane administration was discontinued. Thus, this patient had repeated episodes of myocardial ischaemia which were associated with the use of low dose isoflurane. Although isoflurane-induced "coronary steal" may appear as a likely cause of these ischaemic episodes, it is possible that the thoracic epidural had synergistic action and rendered the patient exceptionally sensitive to minor changes in perfusion pressure.

Anesthesia, Epidural↗
PubMed1994

Neutrophil-mediated acute lung injury after extracorporeal perfusion.

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Animals↗
PubMed1993

Analysis of the anti-p53 antibody response in cancer patients.

Mutations in the p53 tumor suppressor gene giving rise to mutant p53 proteins are among the most common genetic alterations associated with tumor cells. Mutant p53 gene products lose the wild type ability to suppress transformation in vitro or regulate cellular gene transcription. Mutant and wild type p53 protein conformations differ and mutant p53 is often present at high levels in the tumor cell relative to the low levels found in normal cells. Despite the major advances made to characterize the structure and biology of mutant and wild type p53, the humoral immune response against mutant p53s remains to be clearly defined. In the present study we have examined the anti-p53 response from cancer patients against the native and denatured state of mutant and wild type p53. Western blot analysis, immunoprecipitation analysis, and dilution analysis demonstrate that the anti-p53 sera recognize both wild type and mutant p53 conformational and denaturation resistant epitopes. There was no evidence that the mutant p53 molecules contain dominant antigenic epitopes which are not present on the wild type p53 protein. We also demonstrate that patients with ovarian cancer are also among those which can produce anti-p53 antibodies.

Antibodies, Neoplasm↗
PubMed1993

Selective increases in non-rapid eye movement sleep following whole body heating in rats.

Afternoon body heating has been reported to increase amounts of slow wave sleep (SWS) during the subsequent night in humans. This delayed effect of body heating on SWS has not been previously studied in laboratory animals. We examined the effect of whole body heating during the last 4 h of the light period on sleep and brain temperature (Tbr) during the subsequent twelve hour period in rats. Whole body heating was accomplished by elevating ambient temperature, typically to 33-35 degrees C, which increased Tbr to 40 +/- 0.5 degrees C. This condition was compared to a sleep-matched control condition, a sleep-deprived control condition and to a baseline condition. Following heating, non-rapid eye movement sleep 2 (NREMS2 or deep NREMS) was significantly increased during the first 2 h of the recovery period compared with baseline and sleep-matched control conditions and during the first hour compared with the totally sleep-deprived condition. NREMS1 was not significantly changed by heating. Rapid eye movement sleep was not different following heating compared to the sleep-matched and sleep-deprived control conditions but was significantly increased during the first hour of the recovery period following heating compared to baseline. Tbr was significantly lower for the first 5 h and the 7th h following heating compared to all three other conditions. Possible relationships between the regulation of sleep and temperature are discussed.

Animals↗
PubMed1993

Neurotoxicity of peptide analogues of the transactivating protein tat from Maedi-Visna virus and human immunodeficiency virus.

Infection by lentiviruses such as human immunodeficiency virus, Maedi-Visna virus and Caprine Arthritis Encephalitis Virus, is associated with a variety of neurological syndromes, but the mechanism by which the damage occurs to the nervous system is not known. The viruses do not infect neurons and so the neurotoxic actions must be mediated indirectly. Here we applied synthetic peptide analogues derived from basic regions of Maedi-Visna virus and human immunodeficiency virus transactivating protein, tat, to rat brain in vivo and found them to be potent neurotoxins. The toxicity of the Maedi-Visna virus peptide was demonstrated to be reduced by blockade of nitric oxide synthase and of N-methyl-D-aspartate channel opening. These experiments suggest that peptides derived from lentiviral tat may share a common neurotoxic action.

Amino Acid Oxidoreductases↗
PubMed1993

Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic malignant melanoma.

In a multi-centre randomised clinical trial comparing dacarbazine (DTIC) plus recombinant interferon-alfa2a (IFN) versus DTIC alone for patients with metastatic malignant melanoma, aspects of quality of life (QL) were measured prospectively by patients using linear analogue self assessment (LASA) scales including the GLQ-8 and by doctors using Spitzer's QL Index. QL scores and performance status at the time of randomisation were available for 152 of 170 eligible patients. These scores carried significant prognostic information. In univariate analyses, Spitzer QL Index assessed by the doctor and LASA scores for physical wellbeing (PWB), mood, pain, appetite, nausea and vomiting, GLQ-8 total and overall QL were significant (P < 0.01) predictors of subsequent survival. QL Index and LASA scales for mood, appetite, and overall QL remained independently significant (all P < 0.05) in multivariate models allowing for significant prognostic factors other than QL (liver metastases and performance status). These findings closely parallel those in patients with metastatic breast cancer. They add further validity to the QL Index and LASA scores, provide the first evidence of the prognostic significance of the GLQ-8, and argue strongly for the routine assessment of QL in future therapy trials.

Adult↗
PubMed1993

Peptide stability in drug development. II. Effect of single amino acid substitution and glycosylation on peptide reactivity in human serum.

The determination of peptide stability in human serum (HS) or plasma constitutes a powerful screening assay for eliminating unstable peptides from further development. Herein we report on the stability in HS of several major histocompatibility complex (MHC)-binding peptides. Some of these peptides are in development for the novel treatment of selected autoimmune disorders such as rheumatoid arthritis and insulin-dependent diabetes. For most of the l-amino acid peptides studied, the predominant degradation mechanism is exopeptidase-catalyzed cleavage. Peptides that were protected by d-amino acids at both termini were found to be more stable than predicted, based on additivity of single substitutions. In addition, N-acetylglucosamine glycopeptides were significantly stabilized, even when the glycosylation site was several amino acids from the predominant site(s) of cleavage. This indicates that long-range stabilization is possible, and likely due to altered peptide conformation. Finally, the effect of single amino acid substitutions on peptide stability in HS was determined using a model set of poly-Ala peptides which were protected from exopeptidase cleavage, allowing the study of endopeptidase cleavage pathways.

Acetylglucosamine↗
PubMed1993

Evaluation of a computerized assessment package for general practitioner trainees.

A computerized assessment package for general practitioner trainees has been developed in order to measure the impact of teaching during the trainee year and to help identify areas of possible weakness in the knowledge base of trainees. The programme consists of an electronic questionnaire asking for background educational details, confidence rating scales, 60 multiple choice questions divided into 11 educational areas and a patient management problem to add variety and interest and to test decision making skills. A printout is produced at the end of the test summarizing the trainee's results and comparing these with the previous cohort of trainees. The programme was designed to be interesting and stimulating to the trainee by using colour and graphics, ensuring it was easy to use and providing instant feedback of results in comparison with their peer group. It was also designed to require the minimum intervention by trainers. Three sets of 70 trainees undertook the test in consecutive years with each trainee completing the assessment twice, once at the beginning of the trainee year and again towards the end of the year. In addition, a group of trainees completed a manual questionnaire asking them to rate certain aspects of the test. The results of the assessments showed a significant increase in knowledge in nearly all topic areas between the first and second tests. In general, the trainees' response to the test was positive with 63% stating it was useful in pinpointing areas of possible knowledge deficiency. The computer package described has been shown to be an effective and acceptable method for some aspects of trainee assessment.

Adult↗
PubMed1992

Problem drug use in a central London general practice.

OBJECTIVE: To describe the profile of problem drug users presenting in general practice and to determine whether they can be cared for in general practice. DESIGN: Study of consultations by problem drug users. SETTING: Central London general practice. SUBJECTS: 150 problem drug users presenting over two years. MAIN OUTCOME MEASURES: Stopping drug use, alterations in lifestyle, obtaining paid work, and stopping drug related crime. RESULTS: Of the 150 patients, 111 were men and 39 women, and 106 were unemployed. 121 patients used heroin, 112 of whom injected. 145 patients accepted a methadone reduction programme and 81 completed it. A further 25 were stabilised on reducing doses of methadone, until places became available for them as inpatients at drug dependency units or rehabilitation projects. CONCLUSION: Withdrawal programmes for patients who misuse drugs can be successfully managed in general practice.

Family Practice↗
PubMed1992

MHC interaction and T cell recognition of carbohydrates and glycopeptides.

The T cell independence of complex polysaccharide Ag has suggested the possibility that carbohydrates may be incapable of T cell recognition because of a failure to interact with MHC restriction elements and/or a failure of MHC/carbohydrate complexes to interact with and be recognized by Ag-specific TCR. We have used two approaches to obtain information about T cell recognition of carbohydrate. First, we have determined the capacity of a series of oligosaccharides and glycolipids to bind a murine class II MHC molecule, IAd. No significant binding was observed with the 26 compounds tested, but the limitation to these studies was that there was a relatively limited collection of synthetic carbohydrate and glycolipid structures of limited complexity available for analysis. The second approach involved the study of the effect of glycosylation of a known peptide T cell epitope (OVA 323-339) on MHC binding of the peptide and on T cell recognition. Three patterns of effects were observed: 1) no effect on either binding or T cell recognition. This pattern was observed when the carbohydrate was located at residues removed from the core MHC-binding region. When the carbohydrate was located within the core MHC-binding regions, either 2) glycosylation destroyed both MHC binding and T cell recognition; or 3) glycosylation did not ablate MHC binding or T cell recognition. In this latter instance, there was evidence to indicate that the carbohydrate moiety was an important part of the antigenic determinant recognized by T cells.

Animals↗
PubMed1992

Inhibitory effects of glyceryl trinitrate on alpha-adrenoceptor mediated contraction in the human internal mammary artery.

1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta-adrenoceptor mediated relaxation and that alpha-adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha-adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA--coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40-90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/- 0.06 -log M) and 20-90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/- 0.16 -log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8-38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9-39.3% (P greater than 0.05). The alpha 1-adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗