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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 199 records · Page 11Linked to original sources

The action of Avermectin (MK 936) on identified central neurones from Helix and its interaction with acetylcholine and gamma-aminobutyric acid (GABA) responses.

Intracellular recordings were made from identified neurones in the suboesophageal ganglionic mass of the snail, Helix aspersa. Avermectin, MK 936, 0.01-1.0 microM, induced an outward current in certain neurones. The size of this current varied from one cell type to another. This direct effect of Avermectin occurred irrespective of whether the neurones were sensitive to GABA or not and was generally irreversible. Avermectin, 0.1 microM, reduced the chloride mediated inhibitory GABA response and potentiated the largely sodium mediated excitatory GABA response. Avermectin, 0.1 microM, reduced the chloride mediated acetylcholine inhibitory response and potentiated the sodium mediated excitatory acetylcholine response. In neurones which showed a biphasic response to acetylcholine, Avermectin enhanced the excitatory and depressed the inhibitory component. It is concluded that Avermectin can interact with chloride ionophores to induce an outward current and can reduce chloride mediated responses associated with acetylcholine and GABA.

Acetylcholine↗

Colposcopic assessment of the lower genital tract in female renal transplant recipients.

The incidence of epithelial or cutaneous abnormality of the lower genital tract was studied colposcopically in 31 women aged 35 (SD9) years on renal replacement therapy for one to 184 months (mean 73 months). Twenty-four women had a renal transplant and had received immunosuppressive therapy for two to 173 months (mean 61 months). Seven women (two with failed transplants) were on home hemodialysis (one to 48 months, mean 19 months) awaiting transplantation. In 22 women (17 transplant and 5 dialysis patients) no abnormality was found. One hemodialysis patient had an extensive area of vulval intra-epithelial neoplasia. Five transplant recipients had evidence of genital papilloma virus (HPV) infection. No patient had cervical intra-epithelial neoplasia or invasive genital tract malignancy. The high incidence of HPV-associated lesions in this group, and the increasing evidence that HPV changes may predispose to cervical neoplasia suggest that this high risk group require regular gynecological assessment.

Adult↗

Alcohol enhances vitamin C excretion in the urine.

Urinary ascorbic acid excretion was measured on four consecutive days in 9 normal male volunteers for 4 hr before and after drinking nothing (control), 0.58 g alcohol/kg body wt as whisky or lager or water (11./70 kg body wt). The normal reduction in ascorbic acid excretion under control conditions was abolished by drinking water. Alcohol in either form produced a 47% increase in urinary ascorbic acid excretion. A similar ascorbiuresis in chronic alcoholics would be an additional factor in the causation of vitamin C deficiency in these patients.

Adult↗

Effect of oral penbutolol on renal haemodynamics of hypertensive patients with renal insufficiency.

Acute or chronic administration of most beta-adrenoreceptor blocking drugs is associated with a fall in renal blood flow and glomerular filtration rate. In patients with renal insufficiency this effect on renal function may be clinically important. Penbutolol is a non-cardioselective, pure laevo, beta-blocker with intrinsic sympathomimetic activity. Previous studies have suggested that penbutolol may increase the glomerular filtration rate. In this study eight hypertensive patients with renal insufficiency were studied during a three-week placebo period and then for four weeks while taking penbutolol in a dose of 40 or 80 mg daily. Penbutolol produced a fall in the pulse rate in all eight patients. Five of the eight patients had a fall in their supine and standing blood pressure. Effective renal plasma flow and glomerular filtration rate did not change significantly. In seven of the eight patients there was a fall in the calculated renal vascular resistance but the mean fall did not reach statistical significance. Penbutolol appears to be an effective beta-blocker and one that could be used appropriately in patients with renal insufficiency.

Adult↗

The antagonism of acetylcholine excitatory and inhibitory responses of Helix central neurones, by some neuromuscular blocking drugs.

Intracellular recordings were made from identified central neurones of the snail Helix aspersa. The antagonism of acetylcholine excitatory and inhibitory responses by d-tubocurarine, HS818 and HS626 was investigated. d-Tubocurarine was equipotent against both the inhibitory and excitatory responses, while HS626 and HS818 were of similar potency to d-tubocurarine in antagonising acetylcholine excitation but were approximately one order of magnitude less potent in antagonising the inhibitory response.

Acetylcholine↗

Radionuclide perfusion scans in the assessment of acute renal transplant rejection.

Acute renal transplant rejection is a diagnostic and management problem. In the oliguric patient clinical evaluation and biochemical tests are less helpful than in those with a functioning graft. The perfusion index derived from a 99mTc-diethylenetriamine penta-acetic acid scan may be a more reliable marker of acute rejection. We studied 20 consecutive renal transplant recipients with serial radionuclide imaging to assess the usefulness of the perfusion index. Seventy-two of 74 episodes of acute rejection were evaluated. Thirty-three (46%) episodes were predicted or supported by a change in the perfusion index. In the non-functioning transplant, 12 of 15 (80%) acute rejection episodes were predicted or supported. A scan obtained the day after transplantation confirmed graft artery patency in all patients. The perfusion index is a useful diagnostic test for the diagnosis and management of acute rejection, particularly in the non-functioning transplanted kidney.

Graft Rejection↗

Actions of the molluscan neuropeptide FMRF-amide on neurones in the suboesophageal ganglia of the snail Helix aspersa.

The effects of the molluscan neuropeptide FMRF-amide were tested on several neurones in the suboesophageal ganglia of the snail Helix aspersa. Almost all neurones tested responded to the peptide, some being hyperpolarized (H response) and others depolarized (D response). The H response is due primarily to an inward potassium current and may be blocked in 20 microM 4-aminopyridine. The hyperpolarizing actions of FMRF-amide and dopamine may be separated by ergometrine which blocks the response to dopamine but not to FMRF-amide. The D response is due mainly to an inward sodium current but this is not blocked by d-tubocurarine, morphine or TTX. It appears to be mediated by a distinct receptor/ionophore as excitation by ACh and 5-HT are both antagonized by d-tubocurarine. The Leu2-substituted analogue FLRF-amide was found to produce similar H responses to FMRF-amide, but was much less potent at producing D responses. It did, however, produce cross-desensitization of the D response to FMRF-amide, suggesting that it does bind to the FMRF-amide receptor.

Animals↗

The action of cholinomimetic and cholinolytic agents, hemicholinium-3 and alpha- and beta-bungarotoxin on the body wall muscle of the earthworm, Lumbricus terrestris.

Strips of muscle, approximately 12 segments in length, were prepared from the body wall of the earthworm, Lumbricus terrestris, from which the nerve cord and viscera had been removed. Contractions to electrical stimulation and acetylcholine agonists were recorded using an isometric transducer. A range of nicotinic and muscarinic agonists and antagonists were tested on this preparation and the results indicate that the acetylcholine receptor on this muscle cannot be classified as either nicotinic or muscarinic. Hemicholinium-3 abolished electrically induced muscle twitches at concentrations which had no effect on the acetylcholine response. Alpha-Bungarotoxin blocked the responses to both electrical stimulation and acetylcholine while beta-bungarotoxin blocked the contractions induced by electrical stimulation but potentiated the acetylcholine contraction.

Acetylcholine↗

Central effects of nicotinamide and inosine which are not mediated through benzodiazepine receptors.

The actions of nicotinamide and inosine were investigated on rat cerebellar Purkinje cells using ionophoretic and extracellular recording techniques. Ionophoretic application of nicotinamide or inosine showed that they were potent inhibitors of Purkinje cell firing. This inhibition differed from that induced by benzodiazepines in that it was not reversed by the GABA antagonists bicuculline methiodide and picrotoxin. RO 15-1788, the specific benzodiazepine antagonist, did not reverse the effects of nicotinamide. Chlordiazepoxide has been shown to increase significantly social interaction between pairs of male rats and this increase can be reversed by RO 15-1788, 20 mg kg-1 i.p. Nicotinamide also caused a small increase in social interaction but this effect was not reversed by the benzodiazepine antagonist. Inosine did not increase social interaction. [3H]-flunitrazepam binding studies showed that nicotinamide and inosine have only low affinities for the benzodiazepine binding site. These results suggest that while nicotinamide may exert some neuronal depressant and anxiolytic activity, its site of action appears not to be associated with the benzodiazepine receptor site. Similarly, inosine exerts a neuronal depressant effect dissimilar from that of benzodiazepines.

Action Potentials↗

Spontaneous hemorrhage of the kidney.

A young hypertensive man with hypertensive nephrosclerosis presented with an acute abdominal emergency due to a spontaneous renal hemorrhage. Investigations demonstrated a large left perinephric hematoma. This was managed conservatively. With control of his hypertension, renal function has remained stable.

Adult↗

Is there a place in the United Kingdom for intensive antacid treatment for chronic peptic ulceration?

Sixty nine patients with chronic duodenal or juxtapyloric ulceration were studied in a prospective double blind randomised trial to compare the efficacy of antacid and placebo at high (30 ml seven times daily) and low (10 ml as required) doses. After four weeks ulcers had healed in 12 out of 18 patients (67%) receiving "low dose" antacid compared with in six out of 17 patients (35%) receiving low dose placebo; ulcers had also healed in six out of 19 patients (32%) receiving "high dose" antacid compared with in two out of 15 patients (13%) receiving high dose placebo. Overall, the effect of antacid was superior to that of placebo in healing ulcers (p less than 0.05) and the effect of low dose treatment was superior to that of high dose treatment (p less than 0.01). There were no significant differences between antacid and placebo at eight weeks. Antacid was better than placebo in relieving pain, but the difference was not significant. Poor compliance and high incidence of diarrhoea made high dose antacid an impractical treatment. Low dose antacid was associated with a significantly better rate of healing than high dose antacid and was far better tolerated. This low dosage of antacid should be considered to be an active treatment in trials of ulcer healing.

Adolescent↗

The action of gamma-aminobutyric acid (GABA) and ethylenediamine (EDA) on Limulus and Helix central neurones and rat cerebellar and sympathetic ganglion neurones.

Intracellular recordings were made from central Limulus and Helix neurones and extracellular recordings from rat cerebellar Purkinje cells and sympathetic ganglia. The actions of gamma-aminobutyric acid (GABA) and ethylenediamine (EDA) and related analogues on these preparations were investigated. On Limulus neurones inhibited by GABA, EDA and piperazine were 81 and 186 times respectively less potent than GABA. Both the GABA and EDA events were chloride mediated, having similar reversal potentials and were reversibly antagonised by picrotoxinin. The EDA response persisted in high magnesium Ringer. On Helix neurones inhibited by GABA, EDA was 92 times less potent while on neurones excited by GABA, EDA was 9.25 times less potent. The other analogues tested had little or no GABA-like effect on either preparation. On rat cerebellar Purkinje cells, EDA was equipotent with GABA and both compounds were antagonised by bicuculline. Flurazepam only potentiated the action of EDA on 3 out of 23 cells tested while the GABA response of all 23 cells was potentiated by the benzodiazepine. Diaminopropionic acid was a weak inhibitor of cerebellar Purkinje cell firing but flurazepam potentiated this response in 6 out of 10 cells tested. On rat cervical ganglion neurones, EDA was half the potency of GABA and likewise the other analogues were less potent than GABA as depolarising agents. Incubation with glutamic acid decarboxylase inhibitors had no effect on the EDA response. Cross desensitisation between GABA and EDA was demonstrated using the ganglion preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗