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Biomedical subjects

R J Davidson

Publications and source records attributed to R J Davidson.

At least 127 records · Page 7Linked to original sources

Influence of cyclosporin A on growth of an acute T-cell leukaemia in PVG rats.

Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T-cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immunocytochemical analysis) to have a mature, T-helper-cell phenotype, i.e., OX-19 (CD5) +/- , W3/25 (CD4)+, OX44+, MHC-class I+, OX-26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 X 10(3) viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host "reactive" cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA-treated leukaemic animals, there was biochemical evidence of synergistic impairment of glomerular and tubular function.

Animals↗

Changes in red cell density and related indices in response to distance running.

The red cell population in peripheral venous blood was characterised in 7 young males before and up to 16 days after a 21.1 km road race. There was a 1.9 +/- 2.4% (mean +/- SD) reduction in plasma volume immediately post race (p less than 0.05), an increase in serum osmolality from 277 +/- 4 mOsm.kg-1 to 291 +/- 14 mOsm.kg-1 (p less than 0.05) and a reduction in red cell water (64.4 +/- 0.3% to 63.4 +/- 0.4%, p less than 0.001). The latter was consistent with alterations in the manually derived MCV and MCHC values although the same Coulter derived values were unaltered. A concomitant increase in median red cell density in whole blood (1.1045 +/- 0.0009 g.ml-1 pre race to 1.1057 +/- 0.012 g.ml-1 immediate post race, p less than 0.05) was recorded by centrifugation through phthalate esters of different density. The changes in creatine content of the red cells suggested that during the race younger cells were released into the circulation but that 24 h to 72 h after the race the mean red cell age had increased. Similarly, fractionation of the red cells on discontinuous Percoll density gradients indicated that the cell population was significantly denser in all post race samples up to 72 h but had normalized by a 16 day sample; the osmotic fragility was similarly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Iron deficiency in pernicious anaemia: a neglected diagnosis.

In 114 patients (52 males and 62 females) with long-standing pernicious anaemia, hypoferritinaemia was found in 27 (23.7%) and hypochromic microcytic anaemia in 19 (16.6%). Our findings indicate that iron deficiency is a common yet neglected complication of long-standing pernicious anaemia and warrants greater diagnostic and therapeutic attention.

Aged↗

EEG measures of cerebral asymmetry: conceptual and methodological issues.

An overview of the use of EEG to assess hemispheric differences in cognitive and affective processes is presented. Some of the advantages of using EEG to assess asymmetric hemispheric differences in the study of complex mental activity are described. Following this brief introduction, two conceptual issues which are central to studies of EEG asymmetries are introduced: (1) the distinction between hemispheric specialization and activation, and (2) the importance of rostral-caudal differences for the understanding of both specialization and activation. Three methodological issues in the use of EEG to assess hemispheric differences are then presented: (1) the use of asymmetry metrics, (2) muscle artifact, and (3) appropriate reference electrode location. Finally, some empirical examples of using EEG to assess affective and cognitive processes which illustrate these conceptual and methodological issues are described.

Affect↗

Faecal blood loss in response to exercise.

Recently qualitative tests have indicated that gastrointestinal bleeding during exercise may be an important contributory factor in sports anaemia. In six healthy men who walked 37 km on four consecutive days faecal haemoglobin content remained normal (reference range 0.10-2.53 mg/g faeces) with no significant differences between values. In 28 marathon runners who refrained from taking drugs or food containing blood the median faecal haemoglobin content increased by 0.42 mg/g faeces (95% confidence interval 0.12 to 0.83 mg/g) from 1.06 (0.86 to 1.31) mg/g before the race. In 13 runners who had taken drugs before the race the corresponding increase in the median faecal haemoglobin content was 0.87 (-0.03 to 2.20) mg/g from the value before the race of 0.93 (0.46 to 1.55) mg/g. Prolonged walking had no effect on gastrointestinal blood loss. Intense endurance exercise in the form of marathon running induced a significant but clinically unimportant increase. This may be exaggerated by the ingestion of drugs and assume importance in causing iron deficiency and sports anaemia. The use of drugs, particularly analgesics, by marathon runners should be actively discouraged.

Adult↗

Ratings of emotion in faces are influenced by the visual field to which stimuli are presented.

This experiment was designed to assess the differential impact of initially presenting affective information to the left versus right hemisphere on both the perception of and response to the input. Nineteen right-handed subjects were presented with faces expressing happiness and sadness. Each face was presented twice to each visual field for an 8-sec duration. The electro-oculogram (EOG) was monitored and fed back to subjects to train them to keep their eyes focused on the central fixation point as well as to eliminate trials confounded by eye movement artifact. Following each slide presentation, subjects rated the intensity of the emotional expression depicted in the face and their emotional reaction to the face on a series of 7-point rating scales. Subjects reported perceiving more happiness in response to stimuli initially presented to the left hemisphere (right visual field) compared to presentations of the identical faces to the right hemisphere (left visual field). This effect was predominantly a function of ratings on sad faces. A similar, albeit less robust, effect was found on self-ratings of happiness (the degree to which the face elicited the emotion in the viewer). These data challenge the view that the right hemisphere is uniquely involved in all emotional behavior. The implications of these findings for theories concerning the lateralization of emotional behavior are discussed.

Adult↗

Hematological changes associated with marathon running.

Coulter profiles with differential white cell counts, serum ferritin, and haptoglobin levels were determined in venous blood samples obtained from 90 males (M) and 25 females (F) immediately before and after completion of a competitive marathon (42.2 km) race. In an additional 20 male runners, the same measurements were performed serially during the 24 h following their completion of the race. In the pre-race samples from 90 M and 25 F, hypoferritinemia was present in 4/22 M and 1 F found to be mildly anemic. Neutropenia was detected in 4 M and 3 F and mild thrombocytopenia in 2 M. Haptoglobin levels were normal in all the female runners but reduced (less than 0.3 g/l) in 6 M. All post-race samples (88 M and 25 F) were characterized by a reactive neutrophilia and thrombocytosis including those with pre-race neutropenia or thrombocytopenia. An unexpected and incompletely explained sex difference in packed cell volume (PCV) response was observed. In males, the mean PCV increased from 0.425 +/- 0.021 to 0.444 +/- 0.028 (P less than 0.0001) whereas in females it decreased from 0.437 +/- 0.029 to 0.423 +/- 0.036 (P less than 0.05). In the post-race samples, anhaptoglobinemia was found in 13/88 M and 4/25 F. In the 20 male runners studied serially for 24 h after the race, the major changes involved a progressive increase in mean plasma volume (17.4% +/- 12.2% at 24 h) compared with the pre-race value, a progressive and significant increase in MCH and MCHC probably indicating a loss in red cell water and the gradual reversion of the reactive neutrophilia and thrombocytosis to basal levels.

Adult↗

Taste-elicited changes in facial signs of emotion and the asymmetry of brain electrical activity in human newborns.

Recent evidence suggests that frontal brain electrical activity reveals asymmetries in activation in response to positive vs negative affective stimuli. This study was designed to evaluate whether this asymmetry is present at birth. Newborn infants were presented with water followed by a sucrose solution and then by a citric acid solution. Facial expression was videotaped during the presentation of the liquids and EEG was recorded from the frontal and parietal scalp regions on the left and right side. Usable EEG data were obtained from 16 newborn infants in response to these taste conditions. Videotaping of facial expression in response to these stimuli indicated the presence of disgust during both water (the first taste introduced) and citric acid. EEG was Fourier Transformed and power in the 1-3, 3-6 and 6-12 Hz bands was computed. The findings revealed that the water condition produced reductions in right-hemisphere power in the two higher frequency bands in both the scalp regions compared with the other two conditions. The sucrose condition produced greater relative left-sided activation in both regions compared with the water condition. These data, in conjunction with our previous findings of asymmetries in 10-month-old infants, indicate that stimulus-elicited affective asymmetries in brain electrical activity are present at birth.

Citrates↗

Inhibition of drug-induced eosinophilia by cyclosporin A.

Administration of cyclophosphamide to Sprague-Dawley rats 2 days before immunization with ovalbumin in complete Freund's adjuvant resulted in a striking blood, bone marrow, and tissue eosinophilia. The number of circulating eosinophils reached a maximum (50-fold increase above normal) 2 weeks after immunization, and eosinophils were also prominent in bone marrow, lymph nodes (paracortical areas), spleen (white and red pulp), and liver. The eosinophilia could be inhibited by daily oral administration of cyclosporin A (CsA), although its effect was dependent both on the duration of treatment and on the dosage of CsA. A similar, inhibitory action of CsA was demonstrated with respect to methotrexate-induced eosinophilia. This experimental model may prove useful in the study of factors regulating eosinophil production and in examining the prospective value of CsA in the treatment of conditions where eosinophils play a central role.

Animals↗

Haematological changes due to triathlon competition.

A twelve parameter blood cell profile has been measured in 6 subjects before and after each phase of triathlon event. This involved 29 miles cycling, 12 miles running and finally 18.5 miles canoeing. There was a significant decrease in plasma volume (8.7% +/- 3.1%, p less than 0.001) following the first phase (cycling); this decrease was sustained to the end of the event. A substantial increase in the number of circulating leukocytes after cycling (84 +/- 58%) and running (255 +/- 83% of pre-event value) was observed. There was no further leucocyte increment after the canoeing stage which may indicate that the circulating concentration of these cells was maximal after running. Fluid shifts following the postural alteration accompanying the different types of exercise and subject variability may have masked any subtle changes in the red cell parameters.

Adult↗

A comparative toxicological study of cyclosporine and Nva2-cyclosporine in Sprague-Dawley rats.

Adult, male Sprague-Dawley rats were given 50 mg/kg cyclosporine (CsA), cyclosporine G (nor-valine2-cyclosporine [CsG], or drug vehicle by orogastric intubation every 24 hr for 14 days. Both drugs profoundly suppressed humoral immune responses. Similar trough whole-blood cyclosporine levels were recorded in each group at days 7 and 14. In CsA-treated animals, significant lymphopenia was evident on day 14, together with monocytosis and neutrophilia. Only the monocytosis was seen in the CsG group. CsA and CsG both caused significant impairment of renal function by day 7, although at this time the effect was less marked with CsG. In both drug-treated groups, there was evidence of further deterioration in glomerular filtration rate (GFR) by day 14. A significant rise in enzymuria was also recorded in each group. Typical cyclosporine-induced proximal straight tubular cell vacuolation was evident in four of the eight rats given CsG and in three of seven CsA-treated animals. Liver function was also significantly impaired in both CsA and CsG groups. These data show that, at the selected dose, CsG shares the nephrotoxic and hepatotoxic properties of CsA. The extent to which these effects of CsG are dose-related and the true clinical potential of this cyclosporine analogue have yet to be evaluated.

Animals↗

Alterations in erythrocytes in hyperosmolar diabetic decompensation: a pathophysiological basis for impaired blood flow and for an improved design of fluid therapy.

In a study of 10 diabetic patients, each of whom was in a severely decompensated state, notable alteration of blood flow properties was observed in those six patients who were hyperosmolar. In this form of diabetic decompensation, whole blood filtration was distinctly impaired. The additional impairment was shown to be due to an accumulation of solute within the erythrocytes occurring as a consequence of hyperosmolarity. The alterations in erythrocytes were revealed by Coulter blood count abnormalities and confirmed by osmotic fragility studies. When biochemical improvement was achieved in these patients, rapid resolution of the erythrocyte abnormalities occurred. Microvascular ischaemia due to such erythrocyte alterations may be a possible explanation for the characteristic cerebral disturbances of the hyperosmolar diabetic state. Altered blood flow properties would also promote vascular thrombosis, a common terminal event in the hyperosmolar non-ketotic syndrome with associated 50 per cent mortality. An improved design of the insulin and fluid replacement therapy for patients in hyperosmolar diabetic coma might be based on the findings of these and further studies.

Adolescent↗