Search PubMed⌕ Search

Biomedical subjects

R G Morris

Publications and source records attributed to R G Morris.

At least 199 records · Page 11Linked to original sources
PubMed1988

Renal clearance and protein binding of melphalan in patients with cancer.

The renal clearance of melphalan and the fraction unbound in plasma were determined after intravenous infusion of 5 mg/m2 over 5 min in nine patients with cancer to obtain information regarding the mechanism of renal handling of melphalan. Four of the patients underwent bone marrow transplantation and also received an IV dose of 220 mg/m2. Total melphalan clearance after the 5 mg/m2 dose ranged from 66.0 to 272 ml/min per m2; the percentage of the dose excreted unchanged in urine, from 2.5% to 92.8%; renal clearance, from 4.1 to 188 ml/min per m2; the fraction unbound in plasma, from 0.0598 to 0.460; and t1/2 beta, from 39.4 to 84.3 min. Unbound melphalan clearance and renal clearance calculated from the unbound fraction in plasma for each patient ranged from 441 to 3356 ml/min per m2 and 15 to 961 ml/min per m2 respectively and were not related to serum albumin, serum creatinine or creatinine clearance. The percentage of the dose excreted and melphalan renal clearance were not related to urine flow. There was evidence of active secretion of melphalan in the kidney an possible reabsorption. There were no significant paired differences in melphalan disposition between the high- and low-dose studies. Highly variable renal clearance involving active secretion may contribute in part to large interpatient differences in the total plasma clearance of melphalan in patients with cancer.

Adult↗
PubMed1988

Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat.

Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.

2-Amino-5-phosphonovalerate↗
PubMed1988

The effect of renal and hepatic impairment and of spironolactone on digoxin immunoassays.

The effect of renal and/or hepatic dysfunction, and of concomitant spironolactone therapy, on seven commercial digoxin assays was evaluated in 45 patients taking both these drugs, and a comparison made with the digoxin concentrations measured using the same assays in 30 patients taking digoxin in the absence of spironolactone. The study showed that increasing renal dysfunction resulted in increasing inaccuracy in assay results with the methods tested. The influence of concomitant spironolactone was to produce a further distortion, which was shown to be additive in patients with impaired renal and/or liver function. The results highlight the unresolved specificity problems which persist in many, if not all, of the immunoassays currently offered to clinical laboratories which, if not recognised, could significantly influence digoxin therapy and patient management.

Aged↗
PubMed1988

Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis.

The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation.

Animals↗
PubMed1988

Primary and working memory functioning in Alzheimer-type dementia.

This paper reviews recent neuropsychological studies of primary-memory functioning in early Alzheimer-type dementia (AD) with specific reference to recent research on working memory. The deficits in primary memory follow a fairly distinct pattern with a comparatively unimpaired recency effect in free recall, a moderate impairment in memory span, and a more substantial impairment in short-term retention following distraction. The nature of these deficits is considered in relation to the Working Memory Model (Baddeley & Hitch, 1974). It is suggested that the Articulatory Loop System is functioning normally but that there is an impairment in the control processes of working memory.

Alzheimer Disease↗
PubMed1988

A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease.

Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.

Alzheimer Disease↗
PubMed1988

Phenytoin and phenobarbital assayed by the ACCULEVEL method compared with EMIT in an outpatient clinic setting.

The ACCULEVEL (Syntex) therapeutic drug assay technique was evaluated for phenytoin and phenobarbital in 30 patients with epilepsy who attended a neurology outpatient clinic. This finger-prick whole blood method is calibrated by the manufacturer to give assay results equivalent to plasma drug concentration. The results were compared with EMIT (Syva) technique measurements on the plasma from venous blood drawn simultaneously. The results presented show regression lines of y = 0.91x + 10.8, (r2 = 0.92) and y = 0.97x + 5.01, (r2 = 0.77) for phenytoin and phenobarbital (microM), respectively, when the ACCULEVEL finger-prick blood assay was compared with the EMIT venous plasma assay. Acceptable precision and accuracy data are presented for replicated ACCULEVEL assays. The ACCULEVEL method was found to be reliable when performed by a laboratory technician and provides a very convenient quantitative drug assay that could easily be performed by a variety of individuals at a site remote from laboratory facilities.

Humans↗
PubMed1988

The relationship between marital intimacy, perceived strain and depression in spouse caregivers of dementia sufferers.

This study explored the quality of marital relationship between dementia sufferers and their spouse caregivers. It assessed the quality of the relationship (level of intimacy) prior to the onset of dementia and also at the time of the study. Caregivers who experienced lower levels of marital intimacy, both currently and before the onset of dementia, were found to have higher levels of perceived strain and depression. The decline in intimacy following the onset of dementia was estimated from the difference between the levels of past and present intimacy. Caregivers who experienced a greater loss of intimacy had a higher level of depression, but did not show evidence of increased perceived strain. It is speculated that a poor premorbid relationship makes caregiving more stressful because of a greater difficulty in performing the caregiving role. In addition, it is suggested that a poor premorbid relationship or high loss of intimacy acts as a vulnerability factor, predisposing the caregiver to depression.

Aged↗
PubMed1988

Planning and spatial working memory in Parkinson's disease.

The higher level cognitive function of planning was studied in a group of medicated Parkinson's disease patients and a group of matched control subjects, using a computerised version of Shallice's Tower of London task. Baseline measurement of the ability to execute a given plan of action, to generate low level strategies required for efficient searching, and spatial working memory capacity, all of which contribute to performance on the planning task, established that the Parkinson's disease group was unimpaired on any of these measures. On the Tower of London task, the Parkinson's disease group was also unimpaired in terms of the average number of moves required to solve a problem. However, a specific planning deficit was evident when "thinking" times were analysed, and this was after the confounding influence of motor initiation and execution times had been carefully extracted from total performance times. This finding is discussed in relation to putative functions of the frontal lobes and basal ganglia, and an attention-switching hypothesis is developed to account for it.

Aged↗
PubMed1988

Metabolism of exogenous noradrenaline in constricted and in distended rabbit ear arteries.

(1) The metabolism of extraluminal and of intraluminal 3H-noradrenaline (3H-NA; 0.18 mumol/l) was examined in arteries from reserpine-pretreated rabbits. The arteries were perfused in Ca medium (a) in the absence of prazosin to permit constriction to occur, (b) in the presence of prazosin, and (c) at a high intraluminal pressure (110 mm Hg; prazosin present) in order to distend the vessel. (2) The constrictor activity of the extraluminal NA was extremely weak, and antagonism by prazosin was not associated with a change in metabolite formation. The only change accompanying distension was a small (24%) increase in 3,4-dihydroxyphenylethylene glycol (DOPEG) formation. (3) The constrictor activity of intraluminal NA was much stronger than that of extraluminal NA. Antagonism of constriction by prazosin was accompanied by a 5-fold increase in DOPEG formation and a 2-fold increase in normetanephrine (NMN) formation. Distension resulted in a further 3-fold increase in DOPEG formation, but had little effect on NMN formation. (4) Since DOPEG is neuronal in origin, it is suggested that the changes in DOPEG formation in point 3 above reflect changes in the rate at which the intraluminal NA diffuses into the region of the sympathetic nerve terminals. In support of this suggestion, (a) distension was without effect when DOPEG formation was related to the vascular dimensions which determine rate of diffusion of NA, instead of to vascular mass, and (b) effects of constriction and distension on the rate of diffusion of intraluminal 14C-sorbitol across the artery wall paralleled their effects on DOPEG formation. (5) The effects of constriction on NMN formation in point 3 are attributed to diminished uptake2 (on which NMN formation depends) in the contracted smooth muscle, in association with tendencies for both NMN formation, and contractile activity, to be localized to the region of the vessel wall closest to the surface of entry of the NA. (6) Diffusion coefficients of 14C-sorbitol were estimated. The estimates indicate that (a) the changes in vascular dimensions are the prime determinants of rates of diffusion, (b) diffusivity is decreased when the vessel constricts, and (c) there may be bulk flow of the intraluminal medium into the vessel wall when it is distended by a high intraluminal pressure.

Animals↗
PubMed1988

Influence of uptake1 and uptake2 on the relationship between diffusion and metabolism of noradrenaline in the perfused rabbit ear artery.

3H-metabolite effluxes from each surface of the perfused rabbit ear artery were measured during a 30-min period of application of 3H-(-)-noradrenaline (NA) to the intimal surface, the adventitial surface, and both surfaces simultaneously. The arteries were from reserpine-treated rabbits and were perfused in Ca-free medium containing prazosin to prevent the constrictor activity of NA. During intimal application, 3H-normetanephrine (NMN) was the principal metabolite. Effects of hydrocortisone, and of cocaine, indicated that (a) 3H-NMN was derived largely via uptake2, (b) 3H-3,4-dihydroxyphenylethylene glycol (DOPEG) was derived largely via uptake1, and (c) uptake2 limited access of the NA to sites of uptake1. During adventitial application, 3H-DOPEG was the principal metabolite. Effects of cocaine and hydrocortisone indicated that (a) 3H-DOPEG was derived largely via uptake1, (b) 3H-NMN was only partly derived via uptake2, and (c) uptake1 limited access of the NA to sites of uptake2. When 3H-NA entered both surfaces simultaneously, the effluxes of the deaminated catechols were identical to those prevailing during adventitial entry of the amine. In contrast, the effluxes of NMN corresponded more closely to the sum of those prevailing during entry via each surface separately. It is suggested that, in the perfused artery, regional differences in the diffusivity of NA between the adventitia and media are primarily responsible for the marked influence which the surface of entry exerts on exogenous NA metabolism.

Animals↗
PubMed1988

Factors affecting the emotional wellbeing of the caregivers of dementia sufferers.

Recent research on the factors that mediate the emotional wellbeing of the caregivers of dementia sufferers is reviewed. The roles of such factors as the caregiver's attributional style and coping strategies, the caregiver's relationship with the dementia sufferer, and levels of formal and informal support are discussed with reference to identifying those caregivers who are particularly vulnerable to emotional disorder or strain.

Adaptation, Psychological↗
PubMed1987

Pharmacokinetics of trimetrexate administered by five-day continuous infusion to patients with advanced cancer.

The disposition of the methotrexate analogue trimetrexate (TMTX, NSC 352122; 2,4-diammino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]qui nazoline) was determined in a Phase I study in 16 patients with refractory or relapsing cancer. The drug was administered by continuous 5-day infusion at doses of 5 to 60 mg/m2/120 h (1-12 mg/m2 daily for 5 days). Plasma and urine collections were made during and after infusion and TMTX levels were quantitated by a specific and sensitive high-performance liquid chromatographic assay. Estimates of pharmacokinetic parameters were similar when determined by either compartmental or noncompartmental methods. There were no significant differences in parameters between the first and second courses of treatment to 10 of the patients. Significant linear relations between TMTX dose and the area under curve of plasma TMTX (r2 = 0.858, P = 0.0001) and the steady-state TMTX plasma level (r2 = 0.764, P = 0.0001) were established. Total TMTX clearance was 30.4 +/- 7.6 (SD) ml/min/m2, renal clearance 7.80 +/- 3.9 ml/min/m2, nonrenal clearance 23.2 +/- 7.1 ml/min/m2, volume of distribution 32.8 +/- 16.6 liters/m2, and terminal half-life 13.4 +/- 7.0 h. The percentage of the trimetrexate dose excreted unchanged in urine ranged from 8.4 to 40.7% (mean, 24.9 +/- 9.2%) and was related to creatinine clearance (r2 = 0.312, P = 0.010). Trimetrexate renal clearance was also related to urine flow (r2 = 0.330, P = 0.008). Trimetrexate pharmacokinetics was linear over the dose range 5 to 60 mg/m2 when given by 5-day continuous infusion to patients but there was evidence of urine flow-dependent renal clearance which requires further examination.

Adult↗
PubMed1987

Effect of L-leucine on oral melphalan kinetics in patients.

Melphalan uptake in the intestine has recently been shown to be an energy-dependent process which is affected by metabolic inhibitors. It is therefore theoretically possible that amino acids in food could reduce melphalan absorption by competing for uptake at the sites of absorption in the intestine. Since L-leucine has been shown to be the most potent inhibitor of melphalan transport into cells in vitro, this amino acid was chosen for the present study in patients. Oral melphalan (4.5 +/- 0.5 mg/m2) was given to ten fasting patients with and without a 2-g oral dose of L-leucine on separate randomized occasions at least 1 week apart. Melphalan plasma levels were measured by high-performance liquid chromatography (HPLC) for 5-h after dosing. L-Leucine plasma levels were measured by HPLC before and at 1 h after dosing. The area under the curve for melphalan was lower in seven of the patients after L-leucine. Plasma L-leucine levels 1 h after melphalan administration were 15.4 +/- 3.7 micrograms/ml fasting and 35.4 +/- 5.2 micrograms/ml after L-leucine. The results indicate that L-leucine can reduce plasma melphalan levels in some patients, probably through a reduction in absorption of the drug from the gastrointestinal tract. However, the effect, like that of food, is highly variable.

Administration, Oral↗
PubMed1987

Articulatory rehearsal in Alzheimer type dementia.

This study investigated the relationship between articulation rate and memory span in a sample of 21 patients with early Alzheimer type dementia (AD), comparing their performance with 21 matched controls. Memory span was measured using auditorily and visually presented digits. The AD patients were moderately impaired in both conditions. Articulation rate was measured either by requiring subjects to read lists of random digits or repeatedly count from 1 to 10. The AD patients were able to read the digits as fast as the controls but were slower in the counting task. The measures of memory span and articulation rate correlated significantly for the controls but not for the AD patients, indicating that the normal association between articulation and memory span is disrupted. These results are discussed in relation to previous results and suggest that articulatory rehearsal processes in primary memory are unimpaired at the early stages of AD.

Aged↗
PubMed1987

Chlordiazepoxide, an anxiolytic benzodiazepine, impairs place navigation in rats.

There are separate proposals that the hippocampus is involved in 'spatial memory' and in the control of 'anxiety'. Despite a larger number of common effects of anxiolytic drugs and hippocampal lesions, no effect of anxiolytic drugs has yet been reported in those spatial tasks which are particularly sensitive to the effects of hippocampal lesions. The present study addresses this issue. Separate groups of rats were treated, i.p., with 5 mg/kg chlordiazepoxide (an anxiolytic benzodiazepine), 1 mg/kg scopolamine (a muscarinic antagonist which has previously been shown to impair spatial learning) and a saline placebo. They were then trained to find a platform which was hidden in a constant location just under the surface of opaque water in a swimming pool. Separate groups of rats were trained with 4 trials per day and with 1 trial per day. Number of trials per day did not significantly influence the effects of the drugs. Chlordiazepoxide and scopolamine produced similar degrees of impairment in spatial learning to each other--but less impairment than has previously been reported with hippocampal lesions. The effectiveness of the anxiolytic drug chlordiazepoxide in the swimming pool, a specifically spatial task, suggests that the opposing concepts of 'spatial memory' and 'anxiety' which have been used previously to describe hippocampal function may represent different aspects of a unitary concept.

Animals↗