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Biomedical subjects

J L Morris

Publications and source records attributed to J L Morris.

At least 19 recordsLinked to original sources
PubMed1996

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Activities of Daily Living↗
PubMed1995

ISIS-4.

Explore the source record for details and available documents.

Humans↗
PubMed1995

Peptides as neurotransmitters in vascular autonomic neurons.

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation ( > 2-5Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases medicated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.

Animals↗
PubMed1995

Nitrates in myocardial infarction: influence on infarct size, reperfusion, and ventricular remodelling.

OBJECTIVE: To assess the possible benefits of intravenous isosorbide dinitrate in acute myocardial infarction and oral isosorbide mononitrate in subacute myocardial infarction. METHODS: 316 patients presenting with acute myocardial infarction were entered into double blind placebo controlled clinical trials assessing infarct size by enzyme release, ventricular size and function by echocardiography, reperfusion by continuous 12 lead ST segment monitoring and late potentials by high resolution electrocardiography. RESULTS: 301 patients, of whom 292 (97%) received thrombolytic treatment, were randomised on admission to intravenous isosorbide dinitrate or placebo. Overall, there was no significant effect of treatment on infarct size, ST segment resolution, ventricular remodelling, or late potentials at day 3. A trend was observed towards a reduction in infarct size in patients with non-Q wave infarction treated with isosorbide dinitrate. Heterogeneity of nitrate effect was observed in relation to the degree of ST segment elevation on presentation with a clear benefit of isosorbide dinitrate in patients with moderate ST segment elevation (472 U/l v 704 U/l, P = 0.003) and a trend towards a deleterious effect in patients with marked ST segment elevation (1152 U/l v 1058 U/l, P = 0.2). ST segment re-elevation was more common among patients receiving nitrate treatment than in those assigned to placebo (29 v 16, P < 0.05). Some 160 patients underwent a further randomisation to sustained release isosorbide mononitrate or placebo on day 3. Echocardiographic volumes after 6 weeks of treatment were similar in the two groups. CONCLUSIONS: No benefit was observed with administration of nitrates in the treatment groups as a whole for either acute or subacute infarction. There was, however, evidence of heterogeneity of effect in the different subgroups of acute infarction, and the possibility that nitrates may have differing actions in different groups of patients should be considered.

Aged↗
PubMed1995

Roles of peptides and other substances in cotransmission from vascular autonomic and sensory neurons.

Blood vessels may be innervated by up to three major classes of neurons: sympathetic vasoconstrictor neurons; sympathetic or parasympathetic vasodilator neurons; and peripheral fibres of small diameter sensory neurons, which can mediate vasodilation. Most vascular neurons utilise multiple transmitters, including neuropeptides and small nonpeptides such as ATP or nitric oxide, often in addition to noradrenaline or acetylcholine. Subpopulations of each major class of vascular neurons innervating different vascular segments may contain different combinations of neurotransmitters. Furthermore, the same population of neurons can release different cotransmitters in response to different patterns of stimulation. In general, peptides mediate slower and more long lasting changes in vascular resistance than do nonpeptides. Thus, autonomic and sensory neurons are well adapted to produce qualitatively different vascular effects in response to different types of afferent input. The major challenge for the future is to develop new antagonists for many of the substances colocalised in vascular neurons, particularly neuropeptides. These agents will allow us to precisely determine the relative roles of multiple cotransmitters, and are likely to provide therapeutic agents that can be targeted to specific regions of the vasculature.

Animals↗
PubMed1995

Nitrates in myocardial infarction: a current perspective.

In addition to well-established roles in the management of stable angina, unstable angina and heart failure, nitrates are widely used in the management of acute infarction and the subacute period of recovery after infarction. A meta-analysis suggested that intravenous nitrate therapy in acute infarction reduced mortality by 35%. Subsequently, two recently reported 'mega' trials, GISSI-3 and ISIS-4, addressed the role of nitrates during and after infarction. The results of the mega trials have failed to substantiate a statistically significant benefit for nitrates. The contrast between the promising results of the meta-analysis and the disappointing results of the mega trials raises a number of issues considered in this paper. The role of nitrates in acute myocardial infarction remains unclear. The mega trials do offer some suggestive evidence of an early benefit of nitrate therapy. If any benefit does exist, it must be much smaller than the 35% reduction in mortality suggested by the meta-analysis. Further trials are required to assess the possibility of an early acute benefit. Any benefits will probably apply only to subgroups of infarcts.

Female↗
PubMed1994

Selective constriction of small cutaneous arteries by NPY matches distribution of NPY in sympathetic axons.

This study has begun to investigate some functional implications of the differential localization of neuropeptide Y (NPY) in sympathetic neurons supplying different arterial segments in the cutaneous circulation of the guinea-pig ear. Responses of the main ear artery to exogenous NPY and norepinephrine (NE) were examined in vitro by measuring isometric tension. Responses of smaller arterial vessels to application of exogenous NPY or NE to the adventitial surface were examined in anaesthetized, ventilated guinea-pigs, by measuring changes in internal vessel diameter using video microscopy. Some arterial segments subsequently were examined for the presence of immunoreactivity (IR) to tyrosine hydroxylase (TH) and NPY. NPY (1 nM-10 microM) contracted the main ear artery (EC50 = 10 nM; max. contraction = 30% KCl), and 1 nM NPY produced slight potentiation of contractions produced by NE. In vivo, local applications of NPY (1-10 microM) constricted only a subpopulation of arterial vessels (23 of 41). All vessels constricted by NPY were innervated by axons containing IR to both TH and NPY, and as a population, were more proximal in the arterial tree (branch orders 3 to 6) than were vessels insensitive to NPY (branch orders 4 to 8). Most vessels insensitive to NPY were arterioles and arterio-venous anastomoses < 40 microns in diameter, which were innervated by axons containing TH-IR but not NPY-IR. In contrast, local application of NE (1-30 microM) constricted all vessels examined in vivo. When present, NPY constrictions had a longer latency (15-45 s) and duration (3-4 min) than NE constrictions of the same vessel segments. In vivo, NPY sometimes potentiated the peak amplitude of NE constrictions (2 of 7 vessels), but only in vessels where NPY also produced direct constriction. These results reveal an excellent correlation between the localization of NPY in sympathetic axons, and the location of postsynaptic NPY receptors throughout the cutaneous arterial system. Any NPY released in response to strong activation of cutaneous sympathetic neurons is likely to act preferentially on the proximal cutaneous arteries, and to lead to a more prolonged constriction of these arteries than of more distal arterioles and arterio-venous anastomoses.

Adrenergic Fibers↗
PubMed1994

Comparison of the NPY receptors mediating vasoconstriction of the guinea-pig uterine artery and thoracic vena cava using a range of NPY analogues.

The ability of analogues of neuropeptide Y (NPY) to produce direct vasoconstriction, or to antagonize NPY constrictions, was examined in isolated segments of the thoracic vena cava and the uterine artery of guinea-pigs, where NPY mediates a slow phase of sympathetic vasoconstriction. [Leu31,Pro34]NPY, NPY(13-36) and NPY(18-36) all contracted the uterine artery and the vena cava. Contractions produced by [Leu31,Pro34]NPY were similar in time course to those produced by porcine NPY (pNPY), although contractions produced by NPY(13-36) or NPY(18-36) typically were slower than pNPY contractions. In both vessels the order of potency of the agonists was pNPY > or = [Leu31,Pro34]NPY > NPY(13-36) > NPY(18-36). High concentrations (10(-5)mol.l-1) of pNPY or [Leu31,Pro34]NPY produced desensitization of contractions of the uterine artery produced by NPY(13-36). The reported NPY receptor antagonists, PYX-1 and PYX-2 (5 x 10(-6)mol.l-1), slightly reduced (by 21-47%) the magnitude of constrictions produced by exogenous pNPY (1-3 x 10(-8) mol.l-1) in both the uterine artery and the vena cava. These results show that the NPY receptors mediating slow sympathetic vasoconstriction of both the uterine artery and the vena cava are likely to be predominantly Y1 receptors, despite differences between the adrenoceptors mediating sympathetic responses in the two blood vessels.

Animals↗
PubMed1994

Roles of noradrenaline and ATP in sympathetic vasoconstriction of the guinea-pig main ear artery.

This study has investigated the roles of noradrenaline (NA) and adenosine 5'-triphosphate (ATP) in sympathetic vasoconstriction of the main ear artery from guinea-pigs. A range of agents which interact with adrenoceptors or purinoceptors was tested on contractions produced by exogenous NA or ATP, and on contractions produced by transmural stimulation of sympathetic axons. Contractions produced by NA were antagonized competitively by prazosin (Schild plot slope 0.88 +/- 0.13, not significantly different from 1.0). Dihydroergotamine (10 microM) produced significant depression of contractions produced by all concentrations of NA. Yohimbine (1 microM) caused a small rightward shift in the NA concentration-response curves (0.34 log units), whereas propranolol had no effect. alpha,beta,m-ATP (6 microM) enhanced contractions produced by low concentrations of NA (0.1-1 microM), whereas suramin (30 microM) produced a slight depression in the maximum NA-induced contraction in all experiments. Contractions produced by ATP (0.1 mM) were greatly reduced by suramin (30 microM; 59% reduction) and by alpha,beta,m-ATP (6 microM); 96% reduction), and were slightly depressed by dihydroergotamine (10 microM; 12% reduction). Transmural electrical stimulation with trains of 200-300 pulses produced contractions which were rapid in onset and recovery, and sometimes were biphasic. Contractions at both 5 Hz and 20 Hz were reduced by 50-70% after treatment with prazosin (0.1-1 microM). The remaining contractions were enhanced significantly by yohimbine (1 microM), were reduced very slightly by dihydroergotamine, and were largely abolished by guanethidine (1 microM). alpha,beta,m-ATP (1-100 microM) alone often enhanced neurogenic contractions (by 100-200%), whereas suramin (30 microM) alone reduced contractions by 48%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Multiple populations of neuropeptide-containing intrinsic neurons in the guinea-pig heart.

Recent studies of autonomic ganglia have shown that specific combinations of neuropeptides and other potential neurotransmitters distinguish different functional types of neurons. In the present paper the patterns of coexistence of neurochemicals in guinea-pig cardiac ganglion cells was examined, using multiple-labelling immunohistochemistry. Many neurons were found to contain somatostatin immunoreactivity with various combinations of immunoreactivity for dynorphin B, substance P, neuropeptide Y and nitric oxide synthase. There were several small populations of neurons without somatostatin immunoreactivity, which contained combinations of immunoreactivity for vasoactive intestinal peptide, neuropeptide Y, dynorphin B, substance P and nitric oxide synthase. Possible synaptic inputs to these populations of ganglion cells were identified using multiple-labelling immunohistochemistry combined with long-term organ culture. These experiments demonstrated that cardiac ganglia contain prominent pericellular baskets of varicose nerve terminals of sympathetic and sensory origin. In addition, populations of intrinsic intraganglionic nerve terminals were identified which were immunoreactive for vasoactive intestinal peptide, neuropeptide Y or both peptides. These terminals presumably originate from intrinsic neurons, with the same combinations of neuropeptides, located in other cardiac ganglia. These results have demonstrated that there are diverse populations of cardiac ganglion cells in the guinea-pig and that some of these neurons may act as interneurons within the intrinsic cardiac plexuses. Therefore it is highly likely that vagal transmission in the heart is modified by sympathetic, sensory and intrinsic neurons and that cardiac ganglia are complex integrators of convergent neuronal activity rather than simple relays.

Animals↗
PubMed1994

Blockade of noradrenaline-induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea-pig ears.

1. The study has examined the receptors mediating constriction produced by brief local application of noradrenaline (NA) to cutaneous arteries and arterioles in the ear vasculature of anaesthetized guinea-pigs. The innervation of the corresponding vascular segments has been examined immunohistochemically at the conclusion of the pharmacological experiments. 2. Small arteries of branch order 4 (4 degrees, 40-110 microns internal diameter) were more sensitive to the vasoconstrictor action of NA than were more proximal arteries of branch order 3 (3 degrees, 60-150 microns internal diameter), or more distal arteries and arterioles of branch orders 5 to 7 (5 degrees-7 degrees, 18-85 microns internal diameter). This higher sensitivity of 4 degrees arteries was maintained after blockade of neuronal uptake with desipramine (1 microM), and after blockade of beta-adrenoceptors with propranolol (1 microM). 3. NA-induced vasoconstrictions of distal arterioles (5 degrees-7 degrees) were abolished or greatly reduced by yohimbine (1 microM). The blockade by yohimbine decreased progressively with increasing vessel diameter of proximal arteries, while the blockade by prazosin (1 microM) increased progressively in arteries > 40 microns diameter. 4. In 3 degrees and 4 degrees arteries, a substantial component (approximately 50%) of NA-induced vasoconstrictions remained after combined treatment with yohimbine and prazosin, in the presence or absence of desipramine. These constrictions were not further reduced by benextramine (1-10 microM), but were abolished by dihydroergotamine (1-10 microM). Constrictions induced by ATP (0.1-1 mM) were not affected by dihydroergotamine. 5. 5-Hydroxytryptamine (3-100 microM) had a variable effect on 3 degree and 4 degree arteries including: concentration dependent constrictions (n = 3); small constrictions at some concentrations, and dilatations or no change in diameter at other concentrations (n = 6); concentration-dependent dilatations only (n = 3). The 5-HT2 receptor antagonist, ketanserin (0.1-0.3 micro M), did not affect NA-induced constrictions.6. In 16 arterial segments ranging from 3 degree arteries to 60 arterioles, there was a significant correlation between the presence of neuropeptide Y-immunoreactive (NPY-IR) sympathetic axons and the degree of blockade of NA-induced constrictions by yohimbine, prazosin and dihydroergotamine.7. These results demonstrate marked differences in the postsynaptic adrenoceptors mediating vasoconstriction to a bolus of NA applied briefly to the adventitial surface of different segments of the cutaneous vasculature of the guinea-pig ear. Furthermore, the presence or absence of adrenoceptors sensitive to blockade by yohimbine or prazosin is related to the proportion of sympathetic axons innervating each vascular segment which contain NPY-IR.

Animals↗
PubMed1994

Activation of the human immunodeficiency virus long terminal repeat by abrasion of the skin in transgenic mice.

Mechanical wounding was shown to activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in the skin of transgenic mice. Both noninvasive rubbing and scratching of the skin resulted in a range of 4- to 44-fold increased levels of luciferase reporter gene activities when assayed 24-48 h after wounding. Moreover, long-term noninvasive rubbing each day for 17 days resulted in similar increased levels of luciferase activity. Experiments were done to determine whether the HIV-1 LTR-luciferase transgene might be activated when pups were nursed on the mammary tissues of transgenic mice. Luciferase reporter gene activity in mammary glands skin following nursing was significantly higher than in skin from non-pregnant transgenic mice or transgenic mice 20 days post-conception, which suggests that the natural abrasive action of nursing resulted in activation of the LTR. These results may have implications for sexual transmission and maternal-to-infant transmission of HIV-1.

Animals↗
PubMed1994

A conceptual look at rearfoot motion.

A conceptual look at rearfoot motion and the interaction of the axes of the rearfoot is presented. The importance of midtarsal joint stability is discussed, and a question is raised as to what creates stability in the midtarsal joint. Finally, the nature of orthosis function and the effect these devices have on the midtarsal joint for stability and function are discussed.

Biomechanical Phenomena↗
PubMed1994

New techniques to establish the subtalar joint's functional axis.

A new technique to establish the functional subtalar joint axis in live models is presented. Previous studies had a poor reference to the body planes because they relied on cadaver bone models and were not referenced to actual live function. The lower value for the function axis is due to the response of the midtarsal joint and forefoot to loading and ground reactive forces. The techniques were applied to the clinical setting by establishing a reference line on lateral RCSP radiographs and calculating the actual axis to this reference line. The axis deviated from the reference line by a small range (4 degrees) and can be corrected by reference to the calcaneal inclination angle for high or low angular differences. This simple technique can be used clinically to determine axial changes that may be required for surgical procedures and for evaluating the effect of orthosis control.

Adolescent↗
PubMed1993

Levodopa improves spatial contrast sensitivity in Parkinson's disease.

OBJECTIVE: To study the effect of levodopa on the visual contrast sensitivity of patients with Parkinson's disease. DESIGN: Contrast sensitivity of patients was measured before and after levodopa administration. Patient contrast sensitivity was compared with that of normal controls by repeated-measures analyses of variance. SETTING: Parkinson's disease research center associated with private neurology practice. PATIENTS: Fifteen patients with idiopathic Parkinson's disease (eight men, seven women; mean age, 71.8 years) and 22 normal controls (10 men, 12 women; mean age, 68.0 years) volunteered for the study. INTERVENTION: Levodopa/carbidopa (Sinemet). MAIN OUTCOME MEASURE: Change in contrast sensitivity of parkinsonian patients. RESULTS: Following levodopa treatment, the contrast sensitivity of parkinsonian patients improved significantly at the three lowest spatial frequencies tested (0.4, 1, and 2 cycles per degree). CONCLUSIONS: Levodopa improves low-frequency contrast sensitivity in parkinsonian patients. Initially deficient contrast sensitivity in such patients may be restored to near normal levels by levodopa therapy.

Aged↗
PubMed1993

Co-transmission from autonomic vasodilator neurons supplying the guinea pig uterine artery.

This study set out to identify the neurotransmitters involved in autonomic vasodilatation of the guinea pig uterine artery. Non-noradrenergic, paracervical neurons supplying this artery contain at least four neuropeptides: vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), dynorphin A (1-17) and somatostatin, probably in addition to acetylcholine. Transmural nerve stimulation of arterial segments precontracted with phenylephrine (3 x 10(-7) mol l-1 and treated with guanethidine (10(-6) mol l-1), produced relaxations which varied in form with the frequency of stimulation and the length of the pulse train. The relaxations were monophasic at low frequencies (< 2 Hz), and were biphasic at higher frequencies (> 5 Hz) and with longer pulse trains (> 50 pulses). Neither phase of the relaxations was reduced by hyoscine (10(-6) mol l-1), or by removal of the endothelium. The faster phase of the relaxations was selectively reduced (by 61%) during treatment with L-nitro-arginine methyl ester (L-NAME; up to 3 x 10(-5) mol l-1). This reduction was reversed by an excess of L-arginine, indicating that the fast relaxation was mediated by nitric oxide, possibly acting as a neurotransmitter. The slower phase of the neurogenic relaxation was preferentially reduced (by 43%) by the endopeptidase, trypsin (1-3 micrograms.ml-1). As VIP is the only currently identified peptide present in the paracervical neurons which causes vasodilatation, it is likely that VIP, or a closely-related peptide, is the transmitter responsible for the slow relaxation. Acetylcholine and an opioid peptide also seem to be released from the vasodilator neurons, but their effects were small, and may have been restricted to pre-synaptic sites. The slower neurogenic relaxations were inhibited by exogenous neuropeptide Y (68% reduction in amplitude), and were slightly potentiated by somatostatin (21% increase in amplitude). Therefore, endogenous stores of these peptides may also contribute to the sum effect of stimulating the paracervical vasodilator neurons. In conclusion, many different substances may act as autonomic co-transmitters from these pelvic vasodilator neurons.

Animals↗
PubMed1993

Effects of in vitro ethanol and fetal ethanol exposure on glutathione stimulation of N-methyl-D-aspartate receptor function.

The present studies investigated the effects of glutathione (GSH; gamma-glutamylcysteinylglycine) and its oxidized form (GSSG) on neuronal N-methyl-D-aspartate (NMDA) receptor activation in both acute and chronic preparations of ethanol exposure. It was demonstrated using fura-2-loaded dissociated brain cells from newborn rat pups that both GSH and GSSG (0-4 mM) produced concentration-dependent increases in intracellular calcium similar to those produced by NMDA and other agonists of the NMDA receptor. GSH-stimulated calcium entry was not inhibited by low intoxicating concentrations of ethanol, which contrasts with ethanol's typical inhibitory effect on NMDA-stimulated receptor activation. Behavioral studies in adult rats demonstrated that ethanol-induced sleep times were significantly decreased when 10 microliters of GSSG (20 mM) were administered intracerebroventricularly approximately 5 min before an intraperitoneal injection of 20% (w/v) ethanol (3 g/kg). These findings suggest that the less potent effect of ethanol on GSH-stimulated calcium entry as well as the reduction in ethanol-induced sleep times may be related to the presence of glycine in the peptide. The glycine found in GSH may activate the glycine site and block or reduce ethanol's action on this site. It appears that although GSH may play an important role in the activation of the NMDA receptor, this action does not involve a process that is sensitive to acute ethanol exposure. In contrast, when rat pups were chronically exposed to ethanol via prenatal exposure before the fura-2 preparation, increases in NMDA- and GSH-stimulated calcium entry were significantly decreased relative to those in pair-fed and ad libitum-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗