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Biomedical subjects

C J Fowler

Publications and source records attributed to C J Fowler.

At least 199 records · Page 11Linked to original sources
PubMed1989

The value of urethral sphincter electromyography in the differential diagnosis of parkinsonism.

A series of 54 patients presenting with parkinsonism underwent clinical assessment and urethral sphincter electromyography (EMG). After clinical assessment, 26 were thought to be suffering from probable multiple system atrophy (MSA), 15 were thought to have possible MSA and 13 were diagnosed as having probable idiopathic Parkinson's disease (IPD). Of those with probable MSA, 16 were found to have an abnormal urethral sphincter EMG. In the group with possible MSA, only 5 patients had an abnormal EMG while in the group with probable IPD, only 1 patient had an abnormal EMG. It was concluded that urethral sphincter electromyography provides a useful method of distinguishing between idiopathic Parkinson's disease and multiple system atrophy. It also provides a means of identifying those patients with parkinsonism whose incontinence may well be worsened, or in whom incontinence may develop following lower urinary tract surgery.

Aged↗
PubMed1989

Enhancement by potassium of carbachol-stimulated inositol phospholipid breakdown in rat cerebral cortical miniprisms: comparison with other depolarising agents.

Increasing the [K+] in the assay medium from 5.7 to 17.8 mM produces a large enhancement of the inositol phospholipid breakdown response to the muscarinic agonist carbachol in rat cerebral cortical miniprisms, with minor effects on basal inositol phospholipid breakdown. This effect is also found with Rb+. The enhancement by a raised [K+] is not accompanied by a change in the composition of the labelled polyphosphoinositides. The carbachol-stimulated inositol phospholipid breakdown at 17.8 and 42.7 mM K+ was antagonised by veratrine (5-80 microM), 4-aminopyridine (5 mM), and tetraethylammonium (20 mM). These compounds, however, also inhibited the binding of [3H]quinuclidinyl benzilate to cortical membranes. BRL 34915 (0.2-20 microM) was without significant effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+.Mg2+ (10 mM) considerably reduced the carbachol-stimulated inositol phospholipid breakdown at 17.8, but not 42.7, mM K+. Inositol phospholipid breakdown was also stimulated, albeit to a small extent, by L-glutamate (100-3,000 microM) and quisqualate (1-100 microM), with the stimulation being additive to that produced by carbachol at both 5.7 and 17.8 mM K+. N-Methyl-D-aspartate (10-1,000 microM in Mg2+-free medium) had no significant effect on basal inositol phospholipid breakdown and had little or no effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+. It is concluded that it may not be correct to ascribe wholly the enhancement by K+ of carbachol-stimulated inositol phospholipid breakdown to the tissue-depolarising actions of this ion and that other actions of K+ may be involved.

Amino Acids↗
PubMed1989

Comparison of intra- and extrasynaptosomal monoamine oxidase-A and -B activities in the striatum and frontal cortex of two mice strains with different sensitivities to the neurotoxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Conditions for the assay of the intra- and extrasynaptosomal rates of deamination of dopamine and noradrenaline by the two forms of monoamine oxidase (MAO) have been determined in striatal and frontal cortical homogenates, respectively, from C57 BL/6 mice. The activities obtained were compared with the corresponding activities found for NMRI mice, a strain less sensitive to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) than the C57 BL/6 strain. In both strains, the intra- and extrasynaptosomal deamination of dopamine in the striatal homogenates was brought about predominantly by MAO-A. No significant differences between the two strains were found for the intra- or extrasynaptosomal MAO-A or -B activities towards dopamine in striatal homogenates. On the other hand, the striatal dopamine concentrations were higher in the C57 BL/6 mice than in the NMRI mice. The concentrations of the dopamine metabolites DOPAC and HVA were similarly higher, suggesting that the rate of turnover of dopamine is the same for the two strains. In frontal cortical homogenates, MAO-A predominated in the deamination of noradrenaline both intra- and extrasynaptosomally. The extrasynaptosomal rates of deamination of noradrenaline were similar in the two mice strains, whereas the intrasynaptosomal MAO-A activity was significantly higher for the C57 BL/6 mice. These results concur with and extend to the noradrenergic system the conclusion previously made by Jossan et al. (1987) for the dopaminergic system that although MAO-B activity is necessary for expression of MPTP neurotoxicity, it is not the rate-limiting step for the development of the neurotoxic effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Comparison of the effects of the novel antipsychotic agent remoxipride on dopamine and noradrenaline turnover in the rat brain.

The ex vivo effects of the antipsychotic dopamine receptor antagonist remoxipride on dopamine and noradrenaline turnover in the rat brain have been compared. Remoxipride (5-125 mumol/kg intraperitoneally) produced large increases in striatal DOPAC and HVA concentrations with only maginal effects on striatal, hippocampal and hypothalamic MHPG concentrations. Both remoxipride (5.6 mumol/kg intraperitoneally) and haloperidol (0.23 mumol/kg intraperitoneally) increased the rate of striatal dopamine disappearance following inhibition of tyrosine hydroxylase by H 44/68 without corresponding effect on hypothalamic and frontal cortical noradrenaline disappearance. It is concluded that at doses of remoxipride producing compensatory increases in dopamine turnover, there is little or no effect on noradrenaline turnover, confirming the in vitro dopamine:noradrenaline selectivity of this compound.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The extent of small fibre sensory neuropathy in diabetics with plantar foot ulceration.

Thresholds for cutaneous warming and cooling stimuli were measured in 20 diabetics with neuropathic foot ulcers. All patients had a profound disturbance of sensory perception in the ulcerated foot with complete loss of perception of warming; thresholds for vibration and cooling were highly abnormal in all but two patients. Measurements of thermal threshold were made on both feet in 10 patients: warming was lost bilaterally in all, and cooling was bilaterally absent in six. There was no clear pattern of sensory loss in those diabetics with unilateral foot ulceration to suggest that sensory impairment was the determining factor for the development of a plantar ulcer. Measurements of thermal thresholds were made at additional sites in 13 patients and although the most marked abnormalities of sensation were always found in the feet, in some severe neuropaths, abnormal thresholds on the hand and even the face were demonstrated. Thresholds for warming were invariably more abnormal than thresholds for cooling. The diabetics with neuropathic ulceration in this study all had severe generalised peripheral nerve disease involving large myelinated as well as both small myelinated and unmyelinated sensory fibres. The quantitative evidence on the distribution of sensory loss for thermal sensations supports the hypothesis that the neuropathic process affecting the small myelinated and unmyelinated fibres is length dependent.

Adult↗
PubMed1988

Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome?

A potential association between abnormal electromyographic activity--that is, decelerating bursts and complex repetitive discharges--of the urethral sphincter and difficulty in voiding was examined in 57 women with urinary retention. Abnormal electromyographic activity was found in 33. Ultrasonography of the ovaries in 22 of the 33 women showed that 14 had polycystic ovaries. Of the other eight women, two had had oophorectomies, one had shrunken ovaries and ovarian failure, and one had previously undergone oophorectomy and the other ovary could not be seen; in one neither ovary could be seen, and three had ovaries of normal appearance, although two of these women were taking the contraceptive pill. Thirteen of the group had endocrine symptoms and signs characteristic of the polycystic ovary syndrome. Videocystometrography in 17 of the women who were examined by ultrasonography showed low flow rates and high residual volumes of urine after micturition in 12 women who could void, the other five having chronic urinary retention. A speculative hypothesis for the observed association of impaired voiding, abnormal electromyographic activity of the urinary sphincter, and polycystic ovaries is advanced, based on the relative progesterone deficiency that characterises the polycystic ovary syndrome. Progesterone stabilises membranes, and its depletion might permit ephaptic transmission of impulses between muscle fibres in the muscle of the urethral sphincter, giving rise to the abnormal electromyographic activity. This may impair relaxation of the sphincter, resulting in low flow rates of urine, incomplete emptying of the bladder, and, finally, urinary retention.

Adult↗
PubMed1988

Comparison of the effects of haloperidol, remoxipride and raclopride on "pre"- and postsynaptic dopamine receptors in the rat brain.

The ability of the dopamine receptor antagonists haloperidol, raclopride and remoxipride to prevent the B-HT 920-induced decrease in striatal and limbic L-DOPA accumulation in gamma-butyrolactone (GBL)- and NSD 1015-treated rats (termed 'GBL-reversal') was used to define the effects of these compounds on "presynaptic" dopamine receptors. The doses of the dopamine antagonists producing antagonism of GBL-reversal were in each case roughly similar to the doses required to increase dopamine turnover in striatal and limbic areas. The potencies of haloperidol, raclopride and remoxipride in the GBL model were compared with their potencies in behavioural models for postsynaptic dopamine receptors. Haloperidol produced antagonism of GBL-reversal over a similar dose range to that required for antagonism of apomorphine-induced hyperactivity and stereotypy syndromes. Raclopride was effective in the order of potency: antagonism of apomorphine-induced hyperactivity greater than antagonism of GBL-reversal greater than antagonism of apomorphine-induced stereotypy. For remoxipride, the dose-response curve for antagonism of GBL-reversal was superimposable over that for antagonism of apomorphine-induced stereotypies, with an ED50 value about 12 times higher than that for antagonism of apomorphine-induced hyperactivity. Thus, the relative potencies of dopamine receptor antagonists at "pre-" and postsynaptic dopamine receptors vary considerably from compound to compound.

Adrenergic alpha-Agonists↗
PubMed1988

Adrenergic, serotoninergic, histaminergic, and imipramine binding sites in post-mortal human cerebral microvessel preparations.

Cerebral microvessels were prepared from fresh and frozen human brain samples obtained from autopsy cases. Structural integrity and purity of the microvessels were confirmed by light and electron microscopy, and by measurement of the enzymatic marker gamma-glutamyltranspeptidase. Similar morphological and enzymatic characteristics were found for the microvessels prepared from fresh and frozen brain samples. Radioligand binding experiments indicated the presence both in the "fresh" and "frozen" microvessel preparations of specific alpha 1-, alpha 2-, and beta-adrenergic, histamine H1, serotonin S1 and imipramine binding sites, although the density of beta-adrenergic and histamine H1 specific binding sites were lower in the frozen samples than in the fresh samples. Low levels of specific binding to muscarinic, GABAergic and serotonin S2 sites (with respect to the specific binding densities in the crude homogenates) were found in the microvessel preparations.

Adult↗
PubMed1988

Norepinephrine-stimulated inositol phospholipid breakdown in the rat cerebral cortex following serotoninergic lesion.

Norepinephrine (NE)-stimulated inositol phospholipid hydrolysis ("PI breakdown") in rat cerebral cortical miniprisms was used as a measure of alpha 1-adrenoceptor function following serotonin and/or NE depletion. The use of ascorbic acid to prevent autooxidation of the NE during the PI breakdown assay was found to be warranted. Treatment of rats with 5,7-dihydroxytryptamine and DSP4 produced selective depletions of serotonin (79-95%) and NE (69-85%), respectively, in cortical and hippocampal brain regions. The degree of cortical NE-stimulated PI breakdown in the lesioned animals was not significantly different from that in the control animals, suggesting that under the conditions used, serotonin and NE depletion do not lead to a changed sensitivity of alpha 1-adrenoceptors coupled to PI breakdown in the rat cortex.

5,7-Dihydroxytryptamine↗
PubMed1988

The value of testing for unmyelinated fibre, sensory neuropathy in diabetic impotence.

Measurement of thermal thresholds provides a means of assessing neurological deficit and in particular of recognising a neuropathic process affecting unmyelinated and small myelinated fibres of the peripheral nerve. These groups of fibres cannot be tested by nerve conduction studies but are particularly susceptible to disease in diabetes. Thresholds for thermal sensation on the sole of the foot were measured in 33 men presenting with erectile dysfunction. All 15 men with erectile dysfunction, which had been considered on clinical grounds to be neuropathic, had abnormal thermal thresholds. Diabetics with non-neuropathic erectile dysfunction had normal results. Whereas tests of unmyelinated sensory fibre function were abnormal in all those with neuropathic erectile dysfunction, electrophysiological measurement of the bulbocavernosus reflex was normal in five of nine men with diabetic neuropathic impotence.

Adult↗
PubMed1988

Increased duration of dopamine receptor antagonist-induced effects on both behaviour and striatal dopamine turnover by repeated testing in rats.

The present results show that the effects on striatal dopamine (DA) turnover of a single dose of the DA receptor antagonists haloperidol or raclopride in the rat, are dependent on the activity level of the animal during treatment. Thus, animals tested for treadmill locomotion 30 and 60 min. after injection display an increased striatal DA turnover at 90 or 120 min. (raclopride and haloperidol, respectively) compared with control animals which were administered the same dose of the DA antagonist, but which did not have the treadmill tests. The relevance of these findings with respect to individual differences in clinical response and occurrence of side effects as well as the reported difficulties in obtaining good correlations between plasma levels and clinical response with DA-receptor blocking antipsychotic drugs are discussed.

Animals↗
PubMed1988

Dopamine and apomorphine do not modulate the uptake of [3H]D-aspartate in the rat striatum in-vitro.

Sodium-dependent [3H]D-aspartate uptake was measured in rat striatal homogenates. The uptake was inhibited by both L- and D-glutamate, with IC50 values of 5.6 and 224 microM, respectively. Dopamine (10(-7)-10(-4) M), apomorphine (10(-7) M), sulpiride (10(-6) M) or a combination of dopamine and sulpiride were found not to affect the observed uptake of [3H]D-aspartate. Thus, the in-vitro dopaminergic modulation of high affinity glutamate uptake reported in the literature is not found when [3H]D-aspartate is used instead of [3H]L-glutamate.

Animals↗
PubMed1988

Peripheral neuropathy complicating pancreatitis and major pancreatic surgery.

Four cases of a polyneuropathy associated with pancreatitis and pancreatic pseudocyst formation are reported. Electrophysiological investigation showed the peripheral neuropathy to be predominantly axonal in type. These patients were all seriously ill and many factors may have been involved in the pathogenesis of their neuropathy. They had all received parenteral nutrition and multiple drug therapy including metronidazole, and all had severe sepsis. There was evidence that insufficient vitamin replacement had been given during total parenteral nutrition. It was not possible to decide whether the polyneuropathy resulted from the summation of these factors, is similar to what has been called the polyneuropathy of the critically ill, or is a new association with pancreatic disease.

Acute Disease↗
PubMed1988

The conduction velocities of peripheral nerve fibres conveying sensations of warming and cooling.

With the current practice of measuring thresholds for warming and cooling separately, the question of the exact nature of afferents subserving these sensations assumes new importance. Experiments to measure reaction times to warming and cooling stimuli at two sites on the lower limb are described. The conduction velocity for each sensation was estimated from the conduction distance and conduction time in the limb. The estimated mean conduction velocity for warming was 0.5, SD 0.2 m/s and cooling 2.1, SD 0.8 m/s. These figures confirm that the sensation of warming is conveyed in unmyelinated and cooling in small myelinated peripheral nerve fibres.

Adult↗
PubMed1987

Impaired performance of rats in the Morris swim-maize test late in abstinence following long-term sodium barbital treatment.

Rats were tested for place learning in the Morris swim maze on days 110-114 of abstinence following 48 weeks of treatment with sodium barbital. A retarded acquisition of the swim-maze task, that could not be ascribed to motor impairments, was found in the barbital-treated rats. There was a significant difference in brain weight, but there were no significant differences between the control and barbital-treated rats in the frontal cortical concentrations of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), nor in the intra- and extrasynaptosomal activities of cerebral cortical monoamine oxidase towards NA and 5-HT. Postsynaptically, neither the cerebral cortical inositol phospholipid breakdown responses to carbachol and NA (mediated by muscarinic and alpha 1-adrenergic receptors, respectively), nor the striatal and cortical densities of muscarinic receptors labelled by [3H]quinuclidinyl benzilate [( 3H]QNB) were found significantly to be altered in the barbital-treated rats. A strong correlation between the density of striatal and cortical [3H]QNB binding sites was seen for the barbital-treated (r = 0.91) but not for the control (r = -0.05) rats. It is suggested that the deficit in performance of the barbital-treated rats in the Morris maze may be related to a cholinergic dysfunction.

Animals↗
PubMed1987

Suppression of exploratory locomotor activity and increase in dopamine turnover following the local application of cis-flupenthixol into limbic projection areas of the rat striatum.

Recent neuroanatomical tracer studies have demonstrated the topography of 'limbic' (A10) projections into the striatum of the rat (see Introduction). The target areas include the nucleus accumbens and the ventromedial part of the neostriatum, whereas the dorsolateral part of the neostriatum does not receive such afferents. Taking this topography into account, the present results show that local application of cis-flupenthixol (10-40 micrograms/side) into the nucleus accumbens or the ventromedial, but not the dorsolateral, neostriatum produces suppression of exploratory locomotor activity in the rat. trans-Flupenthixol (40 micrograms/side) was completely ineffective when locally applied into the nucleus accumbens. Measurements of the concentrations of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) at the site of injection, and in neighboring areas at different times after cis-flupenthixol administration, indicated that there was little or no diffusion of the drug from the injection sites. Much higher concentrations of DOPAC and HVA in a given area were found after systemic administration of cis-flupenthixol as compared with local application of the drug to the same area.

3,4-Dihydroxyphenylacetic Acid↗