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Biomedical subjects

M J Morris

Publications and source records attributed to M J Morris.

At least 73 records · Page 4Linked to original sources
PubMed1993

Determination of the HMG-CoA reductase inhibitors simvastatin, lovastatin, and pravastatin in plasma by gas chromatography/chemical ionization mass spectrometry.

A general method for the assay of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors lovastatin, pravastatin, and simvastatin in plasma has been developed and validated. The analytes are isolated from plasma by a solid-phase extraction procedure which separates the lactone and acid forms of the drugs. The lactone is converted to the acid form, which is subsequently derivatized by pentafluorobenzylation of the carboxyl group, and trimethylsilylation of the hydroxyl functions. Derivatized samples of intrinsic and converted acid are assayed by gas chromatography/mass spectrometry using negative chemical ionization mass spectrometry. The method has sufficient sensitivity, precision, accuracy, and selectivity for the analysis of clinical samples containing the drugs administered at therapeutic doses. The method thus permits determination of both the lactone and hydroxy acid forms of lovastatin and simvastatin, and is also applicable to the assay of pravastatin.

Anticholesteremic Agents↗
PubMed1993

The role of skin nociceptive afferent nerves in blister healing.

Because sensory neuropeptides improve survival of critical skin and muscle flaps in rats, skin nociceptive sensory nerve function in blister healing was examined. Sensory nerve ablation by unilateral hindlimb denervation or cutaneous axon reflex enhancement by 14 days systemic nicotine treatment (5 mg kg-1 day-1) decreased and increased, respectively, peripheral motor functions of nociceptive (peptidergic) skin nerves. Effects on nociception were measured by a radiant heat tail-flick test. Axon reflex flares were evoked by transdermal iontophoresis of acetylcholine or noxious electrical stimulation under pentobarbitone 40 mg kg-1 anaesthesia. Resultant changes in cutaneous microvascular blood flux were measured non-invasively by laser Doppler flowmetry. In nicotine-treated rats compared with placebo-treated controls, acetylcholine-evoked axon reflex flare was enhanced by 240% (p < 0.01) without enhancement of electrically evoked flare. Thus, nicotine-sensitized nociceptors show stimulus specificity in their enhancement of neurogenic flare responses. No significant changes were seen in other endothelial-dependent or smooth muscle-dependent microvascular dilator responses. Nicotine-treated rats had prolonged tail-flick withdrawal latencies to noxious radiant heat stimuli compared with placebo-treated controls (p < 0.05), suggesting an antinociceptive or analgesic effect of nicotine-treatment. Neurogenic effects on wound healing rate were assessed by measuring the dimensions of standardized blisters twice daily. The blisters were raised on hindpaw glabrous skin using a constant weight and diameter of compressed dry ice pellet applied for 30 secs at constant force. Dry-ice blisters raised on the hindpaw 14 days post-denervation were significantly slower to heal completely (42 days) than controls (30 days: P < 0.05) and the surrounding inflammation was reduced. By contrast, nicotine-treated rats showed more rapid blister healing (25 days) than controls (30 days), seen only in the later phase after day 15. Finally, resting substance P release from blisters, after direct cutaneous nerve stimulation, appears to be enhanced in nicotine-treated rats. Thus nociceptive innervation appears critical for inflammation and rapid healing of blisters in rat skin. The data signal a possible important role for neuropeptides in these processes and question the function of nicotinic receptors on sensory nerves.

Animals↗
PubMed1992

In vivo and in vitro effects of isradipine on cytosolic Ca2+ concentration in erythrocytes from spontaneously hypertensive rats.

Cytosolic Ca2+ concentration ([Ca2+]i) was investigated in erythrocytes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY), after an acute treatment with the Ca2+ antagonist isradipine. Blood samples were obtained from conscious rats and [Ca2+]i measured with fura-2. The [Ca2+]i was higher in SHR than in WKY erythrocytes (P < .05). Isradipine administration had no effect on WKY [Ca2+]i, but reduced that of SHR to WKY levels after 1 h. In vitro, isradipine dose-dependently decreased [Ca2+]i only in SHR (P = .006). The reduction by isradipine of the elevated [Ca2+]i in SHR suggests the presence of a greater dihydropyridine-sensitive Ca2+ influx in the SHR erythrocyte.

Animals↗
PubMed1991

Determination of MK-287, a new platelet-activating factor antagonist, in plasma and serum by gas chromatography chemical ionization mass spectrometry.

MK-287 is a novel platelet-activating factor antagonist. A sensitive and specific gas chromatographic/mass spectrometric assay has been developed for the determination of the drug in serum and plasma. The assay utilizes an extraction with methyl-t-butyl ether and subsequent trimethylsilylation of the hydroxyl function. The gas chromatographic/mass spectrometric determinations are carried out with temperature-programmed capillary gas chromatography and ammonia negative chemical ionization mass spectrometry. The method has sufficient sensitivity, precision, accuracy and selectivity for the analysis of drug concentrations in clinical samples.

Furans↗
PubMed1991

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Peak flow measurement as a screening test for restrictive pulmonary disorders.

We tested whether measurement of peak flow was useful in determining the presence and severity of restrictive pulmonary disorders in addition to its recognized use in the diagnosis and management of airflow obstruction. In 102 patients with various causes of restriction of lung volumes, we found that peak expiratory flow correlated well with forced vital capacity. As a diagnostic test it was useful in restrictive disorders, except in fibrosing alveolitis where it consistently failed to detect abnormality.

Forced Expiratory Flow Rates↗
PubMed1990

Diltiazem and atenolol in essential hypertension: additivity of effects on blood pressure and cardiac conduction with combination therapy.

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Atenolol↗
PubMed1990

Effects of neuropeptide Y on cardiac performance and renal blood flow in conscious normotensive and renal hypertensive rabbits.

The effects of neuropeptide Y (NPY, 10 micrograms/kg bolus iv) on cardiac output, renal blood flow and myocardial contractility were determined in intact renal hypertensive and normotensive rabbits instrumented with ultrasonic flow transducers or left ventricular catheters. The basal plasma concentration of NPY-like immunoreactivity in arterial blood was greater in the hypertensive rabbits (4.2 +/- 0.7 micrograms/l) than in normotensive animals (2.2 +/- 0.4 micrograms/l, p less than 0.05). There were similar moderate increases in arterial blood pressure and total peripheral resistance following NPY, but a small NPY-induced reduction in cardiac output in normotensive rabbits was not seen in hypertensive animals. Resting peak left ventricular dP/dt (an index of myocardial contractility) was higher in hypertensive rabbits (7397 +/- 619 vs 5551 +/- 342 mmHg/sec, p less than 0.05), but there was no significant difference between the maximum NPY-induced falls in peak dP/dt. NPY produced significant peak reductions in renal blood flow in both hypertensive (from 2.5 +/- 0.2 to 1.2 +/- 0.2 kHz, p less than 0.05) and in normotensive rabbit groups (from 2.2 +/- 0.1 to 0.3 +/- 0.1 kHz, p less than 0.05), but the fall in renal blood flow and the corresponding rise in renovascular resistance were smaller in the hypertensive animals (p less than 0.05). The cause of this apparent decrease in renovascular reactivity in the renal hypertensive model was not determined.

Animals↗
PubMed1990

Breathing muscle activity during expiration in patients with chronic airflow obstruction.

During quiet ventilation in 10 patients with severe chronic airflow obstruction (AFO) there were large tidal swings of pleural pressure, 15.8 +/- 5.1 cmH2O, with high negative pressures achieved, 15.2 +/- 5.2 cmH2O. The pattern of pleural pressure mirrored that of tidal expiratory flow with a rapid rise to maximum of pleural pressure and flow at the beginning of expiration, a slow decline of both throughout most of expiration, and just before the onset of inspiration at flow reversal, a sharp fall in pleural pressure and expiratory flow. The shape of expiratory flow and pleural pressure tracings and the pattern of EMG recordings are compatible with loss of post-inspiratory muscle braking of flow. The generally negative pleural pressure and the EMG silence during expiration indicated relaxation of expiratory muscles throughout expiration. Extrapolation of the tidal expiratory flow curve to zero, and calculation of the area under the extrapolated curve showed the volume of dynamic hyperinflation to be a small proportion of the total increase in functional residual capacity above the predicted value in these patients.

Adult↗
PubMed1990

Antigenic assay for protein C determination in horses.

An antigenic assay was developed for determination of protein C in horses. Protein C, a natural, vitamin K-dependent anticoagulant component in blood, was isolated from equine plasma, a specific antibody was produced in goats, and a rocket electroimmunophoresis assay was established. Tests were performed to verify the identity of the isolated protein C and to determine the purity of the antibody. Protein C antigen was measured in plasma from 34 clinically normal horses, and values were compared with amidolytic function values. The mean (+/- SD) values for the 2 test methods were similar (antigen content, 104.5 +/- 13.8%; amidolytic activity, 104.6 +/- 17.5%), but the correlation coefficient was 0.1. Four horses given Na coumarin had markedly decreased plasma protein C amidolytic activity and minimal decrease in protein C antigen content.

Animals↗
PubMed1989

Problems in genetic prediction for Huntington's disease.

Experience with nearly 300 applicants for predictive testing for Huntington's disease has shown that apart from the expected problems such as those related to third-party interests and the effects of an adverse test result, there were several less foreseen difficulties. These included the finding that some applicants were already clinically affected, requests for testing of minors, unintentional risk alteration for relatives, and the use of research samples for service purposes. More of the problems involved clinical and counselling aspects rather than laboratory procedures.

Adolescent↗
PubMed1989

Structure of the human CR1 gene. Molecular basis of the structural and quantitative polymorphisms and identification of a new CR1-like allele.

Structural and quantitative polymorphisms have been described in human CR1. In the former, the S allotype is larger than the F allotype by 40-50 kD, the size of a long homologous repeat (LHR). In the latter, homozygotes for a 7.4-kb Hind III fragment express fourfold more CR1 per erythrocyte than do homozygotes for the allelic 6.9-kb restriction fragment. The basis for these genomic polymorphisms has been determined by restriction mapping the entire S allele and part of the F allele. The S allele is 158 kb and contains 5 LHRs of 20-30 kb, designated -A, -B/A, -B, -C, and -D, respectively, 5' to 3'. Extensive homology was found among the LHRs in their restriction maps, exon organization, and the coding and noncoding sequences. The presence of LHR-B/A in the S allele but not in the F allele accounts for the longer transcripts and polypeptide associated with the former allotype. At least 42 exons are present in the S allele, with distinct exons for the leader sequence, the transmembrane and cytoplasmic regions and most of the SCRs comprising the extracellular portion of CR1. Consistent with the mapping of the ligand binding site to the first two SCRs in each LHR, the second SCRs in LHR-A, -B/A, -B, and -C are encoded by two exons, reflecting a specialized function for this unit. The allelic 7.4/6.9-kb Hind III fragments extend from the 3' region of LHR-C to LHR-D. The 6.9-kb restriction fragment is the result of a new Hind III site generated by a single base change in the intron between the exons encoding the second SCR of LHR-D. A second cluster of genomic clones has been identified by hybridization to CR1 probes. Although they contain regions of hybridization to the cDNA and genomic probes derived from CR1, these cannot be overlapped with the structural gene owing to their distinct restriction maps. Three genomic polymorphisms previously identified by CR1 cDNA probes map to this region. These additional clones may represent part of a duplicated allele located nearby within the CR1 locus.

Alleles↗
PubMed1989

Neuropeptide Y-like immunoreactivity of plasma during hypoglycaemia in man.

Previous studies have demonstrated that plasma Neuropeptide Y-like immunoreactivity (NPY-LI) increases after activation of sympathetic nerves. To test the hypothesis that the adrenal medulla may also be a significant source of circulating plasma NPY-LI and to determine if NPY is co-released with adrenal catecholamines, we have measured the peripheral venous concentrations of NPY-LI, adrenaline and noradrenaline in six patients, before and after induction of hypoglycaemia as part of pituitary function tests that also tested gonadotrophin and thyroid stimulating hormone release. The plasma adrenaline concentration was increased approximately 15 times (p less than 0.05) relative to baseline at 30 mins and remained elevated for the 90 minutes of the study. The plasma concentration of both noradrenaline and NPY-LI remained unchanged. These results failed to demonstrate an increase in the amount of NPY-LI released into the plasma during stimulation of the adrenal medulla with hypoglycaemic stress in man. They do not support significant co-release of NPY with adrenaline from the adrenal medulla in man, nor a physiological role for NPY as an adrenal hormone in human subjects in this situation.

Adult↗
PubMed1988

Red blood cell ionized calcium concentration in spontaneous hypertension: modulation in vivo by the calcium antagonist PN 200.110.

1. Altered calcium regulation has been observed in experimental and human hypertension. In this study erythrocyte (RBC) intracellular calcium concentration ([Ca2+]i) was compared in conscious spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) at rest and after injection of the dihydropyridine calcium antagonist PN 200.110. 2. Resting [Ca2+]i was similar in SHR and WKY. 3. PN 200.110 administration induced a rapid decrease in blood pressure in SHR and WKY. Five minutes after the injection no change in [Ca2+]i was observed; at 1 h [Ca2+]i was significantly decreased in SHR, but not in WKY. 4. These results suggest that the mutual adaptation of the rate of calcium influx through calcium channels and the activity of the calcium extruding pump differ between WKY and SHR.

Animals↗