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Biomedical subjects

T Murray

Publications and source records attributed to T Murray.

At least 73 records · Page 4Linked to original sources
PubMed1990

Cardiovascular response to isokinetic endurance exercise testing.

The purpose of this study was to compare specific cardiovascular responses; maximal heart rate (MHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the calculated pressure rate product (PRP) [SPB X HR X 10(-2)] achieved during a Cybex+ isokinetic endurance test to those generated during a maximal graded exercise test (GXT). Nine untrained college females underwent a Bruce GXT and a maximal effort Cybex knee endurance test. Independent t-tests were used to analyze the differences between the means for MHR, SPB, DBP, and PRP elicited during both tests. There was no significant difference (p less than 0.01) between SBP and DBP means elicited during either test. MHR was significantly higher on the GXT with Cybex values ranging from 71 to 88% of GXT values. PRP was significantly lower during Cybex exercise but ranged from 58 to 102% of maximal GXT values. The results of this study demonstrate the high demands that a Cybex endurance test places on the cardiovascular system of this healthy population and also emphasize the need to carefully evaluate and monitor these parameters for clients of all ages and diagnoses.

Adult↗
PubMed1989

A comparative study of the relative sensitivity and specificity of radiolabelled monoclonal antibody and computerised tomography in the detection of sites of disease in human malignant melanoma.

A monoclonal antibody raised against the high molecular weight melanoma antigen was labelled with indium-111 and injected intravenously into 25 patients with malignant melanoma. The results obtained from images at 24 and 96 h post i.v. administration of the antibody were compared with results obtained from computerised tomography studies with regard to detection of previously unrecognised sites of metastatic disease and apparent false positive localisation. Detailed study of the patients' clinical condition and detection rates using the two methods suggest that both methods detect approximately 80% of clinically and pathologically confirmed metastases. Of 62 known metastases, the antibody detected 50 (81%), with 17 false positive results. False negatives were most common in the lung. In eight patients the two methods were considered of equal value, in 10 the monoclonal gave a greater amount of clinically relevant information, and in seven the CT was superior. In three patients clinically significant metastatic lesions were detected by the radiolabelled monoclonal and had not been previously recognised either by CT scanning or on clinical grounds. No patients had any adverse reaction to the antibody and in the course of our study the dose of antibody was reduced from 20 mg to 200 micrograms with no apparent loss of sensitivity. In at least two patients uptake of the labelled monoclonal into tumour sites would have been adequate for effective targeted radiotherapy.

Antibodies, Monoclonal↗
PubMed1989

The cytostatic effects of alpha-interferon may be mediated by transforming growth factor-beta.

There is some evidence to suggest that transforming growth factor-beta (TGF-beta) mediates the cytostatic effects of the anti-oestrogen tamoxifen. In this study we have demonstrated that alpha-interferon has a significant anti-proliferative effect on the oestrogen receptor-positive human breast cancer cell line ZR-75. There is decreased phenotypic expression of the oestrogen receptors (to about 30% of control values) and increased TGF-beta mRNA. Under the growth conditions used here, ZR-75 cells had approximately 5800 TGF-beta binding sites per cell, with an apparent dissociation constant of 70 pm, and we have shown that the anti-proliferative effects of alpha-interferon can be reduced by 60% by co-treating the cells with a TGF-beta polyclonal antibody. The cytostatic effects of alpha-interferon may therefore be mediated by TGF-beta in this human breast cancer cell line.

Antibodies↗
PubMed1989

Training responses of plasma beta-endorphin, adrenocorticotropin, and cortisol.

The purpose of this study was to examine the effects of three different run training programs on plasma responses of beta-endorphin (beta-EP), adrenocorticotropin (ACTH), and cortisol to maximal treadmill exercise. Subjects were randomly assigned to one of three training groups: sprint intervals (SI) (N = 8), endurance (E) (N = 10), or combination (C) (N = 7). Training was monitored for 10 wk, and maximal treadmill exercise tests were administered pre-training and after 2, 4, 6, 8, and 10 wk of training. Blood samples were obtained (pre-training and after 10 wk) before, immediately after, and 5 and 15 min following the maximal exercise tests. All groups significantly (P less than 0.05) increased maximal oxygen consumption values at 8 and 10 wk of the training period. Significant exercise-induced increase in plasma beta-EP, ACTH, cortisol, and blood lactate were observed for both pre- and post-training tests in all training groups. The SI group demonstrated significant post-training increases in beta-EP, ACTH, cortisol, and 5 min post-exercise blood lactate concentrations in response to maximal exercise. No training-induced hormonal changes were observed for the E group. While exercise-induced increases were observed, the C group exhibited significant post-training reductions in plasma responses of beta-EP, ACTH, and blood lactate concentrations in response to maximal exercise. Still, resting and post-exercise increases in plasma cortisol concentrations were significantly higher in magnitude in the post-training test. Lactate was significantly correlated with beta-EP (r = 0.72), ACTH (r = 0.70), and cortisol (r = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

A tumour spheroid model for antibody-targeted therapy of micrometastases.

Human neuroblastoma cells grown as tumour spheroids were briefly incubated with a conjugate of 131I and an anti-human neuroectodermal monoclonal antibody UJ13A. Unbound 131I was removed by washing and the spheroids observed in culture conditions for up to 4 weeks. Spheroid response to irradiation was evaluated as time to reach 10x treatment volume and proportion of spheroids sterilised. Spheroid growth was found to be affected by both the activity of 131I-UJ13A and the duration of the incubation. Na[131I], 131I-HSA, 131I labelled non-specific antibody and unlabelled antibody were found to be relatively ineffective compared to 131I-UJ13A. The tumour spheroid model has applications in the evaluation of antibodies or antibody fragments and different radionuclides which may be considered for radioimmunotherapy of micrometastases.

Antibodies, Monoclonal↗
PubMed1988

Automated radiopharmaceutical dispensing.

An automated workstation, developed for clinical biochemistry, has been evaluated for potential use in preparing radiopharmaceuticals. It was found that substantial modifications, both hardware and software, would be required but the approach seemed feasible.

Equipment Design↗
PubMed1988

Immunoscintigraphy of human ovarian cancer xenografts using a radiolabelled monoclonal antibody to human pregnancy serum-derived immune complexes.

The in vivo imaging of xenografted human ovarian cancer in nude mice with a specific and control radiolabelled monoclonal antibody (MoAb) is described. The specific MoAb was previously raised by immunizing mice with immune complexes derived from late human pregnancy serum. In the first group of mice the specific MoAb 131I-5E3 F(ab')2 was injected, while a second group received equivalent amounts of a control MoAb 131I-UJ13A F(ab')2. The mice were imaged at various times up to a maximum of 2 weeks using a gamma camera, and the tumour to non-tumour (T/NT) ratio was recorded for each group. The T/NT ratio rose to 2.02 in the specific group, while the corresponding ratio in the control group was 0.70. In addition, the count rate in the tumour and non-tumour regions was determined on each imaging occasion. Biological half-lives of the divalent fragments of 5E3 and UJ13A in the tumour were 7.53 days and 0.62 days, respectively. Following sacrifice, the tumours were excised and counted relative to the rest of the animal, and the T/NT ratio was calculated. In vitro results were in direct agreement with those recorded in vivo using the gamma camera. From the results it would appear that the divalent fragment of 5E3, which has been raised to immune complexes derived from late human pregnancy serum, is specific for human ovarian tumour xenografts in the nude mouse model.

Animals↗
PubMed1987

Enhanced oral bioavailability of meptazinol in cirrhosis.

Kinetic analysis was carried out after single intravenous (25 mg) and oral (200 mg) doses of the novel partial opioid agonist meptazinol (Meptid) in patients with non-cirrhotic liver disease (NCLD) and biopsy proven cirrhosis. Comparison was made with a group of patients with normal hepatic function. Elimination half-lives after the intravenous dose were slightly prolonged in the cirrhotics (n = 10; 4.2 +/- 0.6 h) compared with the control (n = 8; 2.7 +/- 0.2 h: p less than 0.05) and NCLD (n = 8; 3.2 +/- 0.5 h) groups. There was no significant difference in meptazinol plasma clearance between the groups (cirrhotics = 72 +/- 8 l/h; NCLD = 89 +/- 9 l/h; control = 83 +/- 10 l/h). After the oral dose, seven of 15 cirrhotic patients vomited but only one patient in each of the other groups was unable to tolerate the drug (p = 0.06). This may be explained by very much higher peak meptazinol concentrations in the cirrhotic (n = 8; 184 +/- 37 ng/ml, p less than 0.01) and NCLD (n = 8; 131 +/- 38 ng/ml, p less than 0.05) patients than those of the controls (n = 7; 53 +/- 12 ng/ml) reflecting a mean four-fold and two-fold increase in oral bioavailability respectively (cirrhotics: n = 8; 27.9 +/- 5.3%: p less than 0.001; NCLD: n = 7; 13.7 +/- 3.9% p less than 0.05; controls: n = 7; 6.5 +/- 1.3%). There was no evidence of accumulation after chronic dosing with 200 mg meptazinol four times daily for 13 doses in seven control, seven NCLD and six cirrhotic patients. There were no detectable differences in psychomotor function measured objectively using the Leeds Psychomotor Tester of subjectively by linear analogue scoring between the groups in all three parts of the study. The oral use of meptazinol in patients with chronic liver disease is associated more with the development of nausea and vomiting rather than excessive sedation. These data suggest that dosage reduction in cirrhotic patients is advisable particularly if the drug is taken by mouth.

Administration, Oral↗
PubMed1986

Formation of labelled colloid in 99Tcm-DMSA due to the presence of bactericidal fluid.

The possibility that traces of bactericidal fluid in 99Tcm-DMSA could lead to the formation of labelled colloid, was explored. In vitro investigations were undertaken using ultracentrifugation techniques and photon correlation spectroscopy. The latter showed that both contaminated and uncontaminated DMSA contained colloidal (or particulate) material. However the presence of 10 microliters bactericidal fluid as contaminant was shown by ultracentrifugation to result in labelling of this colloidal material when 99Tcm was added to DMSA. Studies in a normal volunteer confirmed the results of the in vitro studies, in that significant liver and spleen uptake was observed after the administration of contaminated 99Tcm-DMSA.

Anti-Infective Agents, Local↗
PubMed1986

Formation of large particles in a 99Tcm-tin colloid preparation.

The effect of prolonged continuous movement on particle size within a 99Tcm-tin colloid preparation was investigated, making use of photon correlation spectroscopy for size estimation. No increase in particle size was found when the preparation was left undisturbed for up to 7 h, the mean (+/- S.D.) size being found to be 239 +/- 24 nm. When the preparation was placed in a laboratory rotator for the same period of time, there was a gradual increase in mean particle size to 404 +/- 127 nm. The increase in size was much greater, however, after 7 h of continuous agitation in a laboratory shaker, a mean value of 2260 +/- 746 nm being observed. An antimony sulphide colloid was subjected to continuous agitation for the same period of time but there was no evidence of aggregation. It is supposed that continuous movement of reconstituted 99Tcm-tin colloid, leading to a marked increase in particle size, may explain occasional instances of significant lung intake.

Humans↗
PubMed1986

Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.

Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.

Adult↗
PubMed1985

Bone mineral content in idiopathic calcium nephrolithiasis.

The calcium content of the central one third of the skeleton was measured using neutron activation analysis in 109 patients with idiopathic calcium nephrolithiasis. The bone mineral content (calcium bone index or CaBI, corrected for body size) was significantly decreased by 5.2% in 20- to 60-year-old patients with calcium nephrolithiasis (p less than 0.01). Under age 50 the decrease was more marked in 64 males (7.1%; p less than 0.02) than in 21 females (4.1%; p = NS). There was a significant negative correlation of CaBI with fasting urine calcium/creatinine ratio (r = 0.39; p less than 0.01), but no correlation with age or indices of parathyroid function. The decrease in bone mineral content did not appear to be progressive. The decrease in CaBI indicates negative calcium balance, either in the past or at present, in patients with calcium nephrolithiasis and does not favour increased intestinal absorption as a primary cause. The lack of correlation of CaBI with parameters of parathyroid function does not support a primary renal loss of calcium. The results suggest that increased bone turnover may be an important component of disordered calcium metabolism in patients with calcium nephrolithiasis.

Adult↗
PubMed1984

Hemodynamic effects of oral smokeless tobacco in dogs and young adults.

Oral smokeless tobacco (snuff) is increasingly used among the young male population. To determine cardiovascular effects of an oral smokeless tobacco product, 10 anesthetized dogs were instrumented to measure blood pressure, heart rate, left ventricular end diastolic pressure, and circumflex coronary, renal, and femoral flows. After a 5-min baseline, a 2.5-g, approximately 1.2% nicotine bolus dose was placed in the buccal space, and measurements were made for 20 min. Significant increases were seen in heart rate, blood pressure, left ventricular pressure, left ventricular end diastolic pressure, and left ventricular dP/dt. Significant decreases in flow were noted in the coronary circumflex, renal, and femoral arteries. The flow reduction was thought to have been mediated by an alpha-adrenergic mechanism. Additionally, 20 human males, mean age 20 years, without nicotine exposure for 72 hr, were given a 2.5-g dose of the same oral smokeless product. From baseline to 20 min, heart rate increased from 69 to 88 beats/min (P less than 0.05), blood pressure from 118/72 to 126/78 mm Hg (P less than 0.05). Thus, oral smokeless tobacco use can produce significant hemodynamic changes in both dogs and normal humans.

Administration, Oral↗
PubMed1984

Effects of cimetidine on carbamazepine auto- and hetero-induction in man.

The effect of cimetidine (CMT; 400 mg twice daily) and matching placebo on the enzyme-inducing properties of carbamazepine (CBZ; 200 mg at night for 15 days) was studied in seven healthy male volunteers. CMT alone had no significant effect on antipyrine kinetics, urinary 6 beta-hydroxycortisol excretion or leucocyte delta-aminolaevulinic acid synthase (ALA.S) activity. CBZ increased leucocyte ALA.S activity by 204% following 1 week's treatment (P less than 0.001). Thereafter, ALA.S activity fell despite continued CBZ administration. Concomitant CMT did not influence this response. Antipyrine clearance and urinary 6 beta-hydroxycortisol excretion were both increased by CBZ after 2 weeks' treatment (P less than 0.01). CMT blocked CBZ induction of antipyrine metabolism but the rise in urinary 6 beta-hydroxycortisol excretion was unaffected. Plasma CBZ concentrations 10, 14 and 18 h following the 8th and 15th doses were higher when CMT was taken concurrently (P less than 0.05). CBZ half-life fell by 36% and clearance rose by 29% (both P less than 0.001) with placebo and by 10% and 7% (both NS) when CMT was taken concurrently. CMT inhibits CBZ auto- and hetero-induction in man. Epileptic patients receiving CBZ chronically may be at risk of toxicity if CMT is also prescribed.

5-Aminolevulinate Synthetase↗