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Biomedical subjects

S Cox

Publications and source records attributed to S Cox.

At least 145 records · Page 8Linked to original sources

Influence of repeated administration of cimetidine on the pharmacokinetics and pharmacodynamics of adinazolam in healthy subjects.

Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration. Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments. Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life. The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine. Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.

Adult↗

Acute effects of aerobic exercise on mood.

Thirty-two female students participated in a single-session experiment during which they carried out two 8-min trials of high-intensity exercise and two 8-min trials of low-intensity exercise. One high- and one low-exercise trial were accompanied by music; the other two trials were accompanied by metronome. Mood was assessed with a modification of the Profile of Mood States before and immediately after each trial. The purpose of the experiment was disguised to reduce the influence of subject expectations on mood responses. Participants were divided into fit and unfit groups based on heart rate responses during high-exercise trials. Overall, high-intensity exercise led to increases in tension/anxiety and fatigue, whereas positive mood changes (vigor and exhilaration) were seen following low-intensity exercise only. No group differences in mood responses were observed. Explanations of these results are considered in light of other literature concerning the acute effects of exercise on mood.

Adolescent↗

Carbamazepine plasma concentration. Relationship to cognitive impairment.

Neuropsychological function was assessed before and after carbamazepine monotherapy in children with newly diagnosed complex partial epilepsy. Simultaneous video-electroencephalographic monitoring examined the influence of subclinical abnormal electrical discharges on performance. Total and unbound plasma carbamazepine concentrations were examined in relation to changes in performance at low (carbamazepine level, less than or equal to 32 mumol/L [less than or equal to 7.5 mg/L]) and moderate (carbamazepine level, greater than 34 mumol/L [greater than 8.0 mg/L]) drug levels. The data suggest a mild beneficial effect of carbamazepine on speeded eye-hand coordination and, at low drug levels, more rapid processing of items in memory. Efficiency of learning new information and memory-scanning rate displayed a concentration-dependent relationship with carbamazepine level, with poor performance significantly associated with higher carbamazepine plasma concentrations. Carbamazepine free levels were equivalent to total levels in predicting cognitive side effects.

Carbamazepine↗

The effects of interferons on the activity of alpha-glycerolphosphate dehydrogenase in benign prostatic hyperplasia cells in primary culture.

Human benign prostatic hyperplasia (BPH) tissues were obtained from patients undergoing transurethral resection of the prostate and viable cells from these were successfully maintained in primary cultures grown on collagen gel. The prostatic origin of the cells was confirmed by the measurement of prostate specific acid phosphatase and by scanning and transmission electron microscopy before and after immunostaining with human prostate specific antigen-antibody. The cell cultures were treated with various interferons (IFNs), both in the presence and absence of testosterone propionate (TP), for 72 hours and the activities of seven enzymes of carbohydrate metabolism were estimated in the cytosolic fraction of the cells. Treatment with TP induced a significant decrease in the activity of alpha-glycerolphosphate dehydrogenase (alpha-GPDH). Using this enzyme activity as a marker, the effects of various types of IFNs were investigated. IFN-alpha (wellferon) increased the activity of the enzyme both in the presence of one microgram./ml. of TP and in its absence whereas IFN-gamma inhibited the activity under similar conditions. The effect of treatment with IFN-beta in the presence of TP was biphasic in that there was an increase in the activity of the enzyme at the lowest concentration while at higher concentrations an inhibition of enzymic activity was observed. In the absence of TP IFN-beta inhibited the activity. The significance of these findings in terms of the clinical usefulness of IFNs is discussed and it is postulated that IFN-alpha (wellferon) might be effective in the treatment of metastatic carcinoma of the prostate in selected patients.

Cells, Cultured↗

Nitroprusside abolishes the deleterious effects of surface cooling-induced hypothermia on immature pigs with ventricular septal defects.

The efficacy of systemic hypothermia in combination with cardiopulmonary bypass for the repair of congenital cardiac malformations is established. Surface cooling in infants with ventricular septal defects as a prebypass adjunct has been associated with visceral ischemic complications. Surface cooling in infant pigs with ventricular septal defects results in increased systemic vascular resistance and unchanged pulmonary vascular resistance with increased left-to-right shunting and a maldistribution of blood flow away from the viscera and kidneys. This study was to determine whether nitroprusside ameliorates the deleterious effects of increased systemic vascular resistance during hypothermia in infant pigs with ventricular septal defects. Nine neonatal pigs (4 weeks, 4 kg) had experimental ventricular septal defects resulting in a 2.3 +/- 0.3: 1 shunt. Systemic and pulmonary vascular resistances were determined by the flow probe and microsphere techniques. Systemic and pulmonary blood flow distributions were measured by the microsphere technique. Left-to-right shunt ratios were determined by oximetry, flow probe, and microsphere. The pigs were cooled to 28 degrees C and measurements were made at 37 degrees, 32 degrees, and 28 degrees C. We found that nitroprusside abolishes the deleterious effects of surface cooling by blocking the rise of systemic vascular resistance without significant changes in aortic pressure. As a result, the animals maintained control pulmonary-to-systemic flow levels and maintained control levels of oxygen delivery while showing a decline in oxygen consumption. Additionally, the vasodilatory effect allowed the animals to cool twice as fast as animals without nitroprusside. Regional blood flow distribution as percent cardiac output and absolute tissue flow were protected during surface cooling. This technique may have a role in cardiac operations on infants with left-to-right shunts.

Animals↗

Study of the histochemical changes in mucus from normal and tumour bearing mucosa in patients with colorectal cancer.

The prognosis in colorectal cancer is related to the stage of the tumour. Thus, early detection of developing tumours will significantly improve the overall prognosis. This study assessed the histochemical changes in mucus from normal and tumour bearing mucosa to determine possible premalignant changes. Eighty patients with colorectal cancer and ten normal subjects were studied. Biopsies were taken from the tumour and from adjacent 'normal' mucosa and from both resection edges. Sections were stained with high iron diamine-alcian blue to distinguish sulphated from sialomucins. All normal mucosal biopsies showed a predominantly sulphated mucin pattern. By contrast, all 70 tumour mucosal biopsies showed a marked sialomucin staining. In transitional mucosa adjacent to the tumour, 30 patients showed marked increase in sialomucin (2+), 42 a moderate increase (+) and the remaining eight a normal pattern (-ve). Twenty-one (15%) patients had increased sialomucin at either surgical resection margins, all of whom had similar changes adjacent to the tumour, suggesting a wide field change in the mucus pattern. Since these changes in mucus are associated with malignant transformation then estimation of mucus pattern may give early prediction of malignant change in patients at risk of developing primary or recurrent carcinoma.

Adult↗

The nature and assessment of general well-being.

Data on self-reported symptoms of ill-health were collected from 1500 respondents, and factor analysed. The results of this analysis suggested a two factor orthogonal model of well-being: one factor reflecting fatigue, emotional fragility and confusion (worn-out) and the other tension, anxiety and agitation (up-tight). The reliability and validity of the model were tested and appeared acceptable, and scales were constructed for the assessment of the two factors. It is suggested that the model and the associated scales could offer new information in studies of occupational stress and health.

Data Collection↗

Enumeration of thioguanine-resistant lymphocytes using autoradiography.

Strauss and Albertini (1979) proposed a method whereby the frequency of thioguanine-resistant lymphocytes could be measured by an autoradiographic technique and suggested that it would provide a measure of in vivo mutation frequency. A number of variables influencing the method were studied and concentration of thioguanine and duration of assay found to be particularly important. The modified method finally arrived at involved culture of PHA-stimulated lymphocytes for 64 h in the presence of 40 microgram/ml of thioguanine, lysis of cells with Nonidet and collection of nuclei on Nucleopore membranes. The frequency of TG-resistant cells was 1.5 x 10(-6) - 1.7 x 10(-5) in young adults and it showed an increase with age. The technique was also adapted for use with continuously cultured lymphocytes, by using a concentration of 60 microgram/ml of thioguanine and an incubation time of 72 h. The frequency of TG-resistant continuously cultured cells was less than 10(-6) - 2 x 10(-5). Consideration of the effect of different variables on the assay suggested that the above estimates for TG-resistant lymphocytes were more valid than the previously published substantially higher estimates.

Autoradiography↗

Human lymphocytes resistant to 6-thioguanine increase with age.

Using an autoradiographic technique we determined the number of circulating lymphocytes that were resistant to 6-thioguanine and which were presumably mutants at the hypoxanthine--guanine phosphoribosyl transferase locus. The number in normal individuals was found to increase exponentially with age. The data suggest a relationship between mutagenesis and ageing, perhaps by way of a decline with age in the fidelity of DNA replication or repair.

Adolescent↗

Mechanisms of uptake and the fate of serum proteins and horseradish peroxidase in cultured human glioma cells. A light- and electron-immunocytochemical study.

Previous studies have shown that serum proteins are taken up from extracellular oedema fluid by reactive astrocytes and by tumour astrocytes. The present investigation was designed to define the mechanism of this protein uptake. Two or 3-week-old explant cultures from 26 astrocytic gliomas, one anaplastic ependymoma, and five non-glial intracranial tumours were treated with either human IgG (12 mg/ml), human serum albumin, (44 mg/ml) or horseradish peroxidase (0.1--4.0 mg/ml) for 4--24 h. Human IgG and albumin were subsequently detected in cultured cells by the indirect peroxidase-antiperoxidase (PAP) method for light microscopy or by direct peroxidase conjugate technique for electron microscopy. Horseradish peroxidase activity was localised by treatment with diaminobenzidine and hydrogen peroxide. Results of the study show that human serum proteins and horseradish peroxidase are taken up by tumour astrocytes and ependymal cells, and by macrophages, but not by non-glial tumour cells nor by mesenchymal elements in the glioma cultures. Electron immunocytochemistry suggests that the serum proteins are taken up by smooth walled micropinocytic vesicles (approximately 80 nm in diameter) which fuse to form larger endocytic vesicles (200--300 nm); these vacuoles in turn fuse with secondary lysosomes to form cytoplasmic bodies 1.2--3 mum in diameter.

Adolescent↗