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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 109 records · Page 6Linked to original sources
PubMed1995

Cholesterol precursor concentration in plasma from patients with chronic renal failure or kidney grafts.

Plasma lathosterol concentration which is an index of cholesterol synthesis rate was measured in 36 patients with chronic renal failure (CRF) including 13 who were dialysis independent, 12 receiving hemodialysis and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients and 27 healthy control subjects. Concentrations of plasma lathosterol were significantly (ANOVA p = 0.03) lower in all categories of renal patients excepting those treated by CAPD, compared with control values. In normolipidemic subjects (cholesterol < or = 6.50 mmol/l and triglycerides < or = 2.0 mmol/l) plasma lathosterol levels in hemodialysis patients and renal transplant recipients were still significantly (ANOVA p = 0.02) lower than control values. In transplant recipients, the plasma lathosterol/cholesterol ratio was significantly (p = 0.02) lower than those treated with azathioprine and prednisone compared with those treated with these drugs and cyclosporin. Significant (p < 0.001) positive correlations were recorded between plasma lathosterol concentration and plasma levels of apolipoprotein B (apoB) and very low density lipoprotein (VLDL) lipids in the renal patients. These data suggest that the rate of cholesterol synthesis may be low in undialysed and hemodialysed patients with CRF and in renal transplant recipients, particularly those treated with double therapy, and may be linked to the metabolism of apoB and VLDL.

Adolescent↗
PubMed1995

Relationship between visual acuity and observation distance.

The visual acuities of 17 young emmetropes and corrected ametropes were measured over the range of 7.5-0.19 m using a Bailey-Lovie chart. Accommodation stimulus-response measures were also taken over this range using retinoscopy to establish whether variations in visual acuity with observation distance could be attributed to accommodation behaviour. Tonic accommodation was recorded using the Canon R1 autorefractor and was compared with visual acuity and stimulus-response results. In general, visual acuity was found to be dependent on stimulus distance, being significantly reduced for most observers for the closest targets. There were three categories of observer performance for visual acuity as a function of observation distance; one group showing no change in visual acuity with distance, a second showing a flat function for distances 7.55-0.5 m, and then a decrease in visual acuity for shorter distances; and a third category that showed a maximum visual acuity in the 1.2-1.6 m region. This behaviour was unrelated to individual stimulus-response characteristics and there was no significant relationship between tonic accommodation and the distance where acuity was best for the third category observers.

Accommodation, Ocular↗
PubMed1995

Successful self-care home dialysis in the elderly: a single center's experience.

OBJECTIVE: This study was designed to prospectively review our experience with self-care home dialysis in the 60-years-and-older age group since the commencement of continuous ambulatory peritoneal dialysis (CAPD) in our center in 1989. DESIGN: Data on mortality, morbidity, dialysis technique and complications, quality of life, and rehabilitation were collected prospectively. SETTING: A regional dialysis unit providing full renal replacement services for a population of 292,000. PATIENTS: Twenty-five patients (16 male) with an average age of 64.4 years (range: 58.25 - 76.5 years) at commencement of dialysis. RESULTS: All patients were on self-care home dialysis. Patient survival rates were comparable with the national average at 12 months (90% vs 89%) and two years (84% vs 80%). Dialysis therapy was well tolerated and technique survival rates were comparable for both hemodialysis and CAPD. There was a very low peritonitis rate of 1 episode per 28.5 patient-months. CONCLUSIONS: Self-care home dialysis is a viable therapeutic option with a high degree of technique success and a good quality of life in the older population.

Aged↗
PubMed1995

Cell cholesterol transport to plasma in blood from patients with renal failure or a kidney transplant.

Accumulation and distribution of cell cholesterol in plasma lipoproteins of incubated blood was examined in 36 patients with chronic renal failure including 13 who were dialysis-independent, 12 on haemodialysis, and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients, and 8 healthy controls. In addition, transport of cholesterol between red blood cells and high-density lipoprotein subfraction 3 (HDL3) isolated from a subgroup of patients with chronic renal failure was determined. Significantly less cell cholesterol appeared in plasma (P < 0.002) and HDL (P = 0.03), the main recipient of cell cholesterol, in patients with chronic renal failure compared with healthy subjects. Corresponding values in blood from renal transplant recipients were similar to controls. In patients with chronic renal failure, plasma HDL3 cholesterol levels (P < 0.02), HDL3 phospholipid content (P < 0.001) and net transport of red cell cholesterol to isolated HDL3 (P < 0.001) were significantly lower compared with controls. The data suggest that in patients with chronic renal failure, low levels of plasma HDL3 of abnormal composition may restrict the incorporation of cell cholesterol into the antiatherogenic HDL fraction potentially leading to inefficient transport of cholesterol from peripheral tissues and the development of atherosclerosis. These abnormalities appear to be reversed by renal transplantation.

Adolescent↗
PubMed1995

The pharynx of the nematode Ascaris suum: structure and function.

The pharyngeal muscle of nematodes consists of a syncytium of radial muscle whereby feeding occurs by the process of pharyngeal pumping. It is believed that the pumping behaviour of the pharynx may be partly controlled by the enteric nervous system (ENS), a component of the nematode nervous system which is associated predominantly with the pharynx. The distribution of serotoninergic and peptidergic (especially SALMF-amide-like) immunostaining is widespread in the ENS of Ascaris, being localized within the lateral and dorsal pharyngeal nerve tracts, the pharyngeal commissures, the nerve plexuses and associated nerve cells and fibres. Immunostaining for serotonin (5-HT) was only localized within the ENS. This paper also describes a method to enable in vitro pharmacological studies on the Ascaris pharynx. The effects of "classical" neurotransmitters and native nematode peptides on pharyngeal pumping behaviour in Ascaris have been investigated. The function of the pharynx in Ascaris is discussed.

Amino Acid Sequence↗
PubMed1994

Different functional effect of Ro 15-4513 and Ro 19-4603 on synaptic responses of Purkinje cells in the rat cerebellar slice.

Modulation of GABA-mediated neurotransmissions by Ro 15-4513 in cerebellar slices was assessed following stimulation of the parallel fibre input, which, in this preparation, preferentially activates the inhibitory interneurones innervating Purkinje cells. Peristimulus-time histogram analysis of inhibitory responses of spontaneously-active Purkinje cells showed only a decrease in the duration of inhibition induced by Ro 19-4603. This is consistent with inverse agonism on the BZ1 receptors associated with postsynaptic GABAA receptors on Purkinje cells. 1 microM Ro 15-4513 induced a similar response but 100 nM Ro 15-4513 induced a biphasic response, with an increase in duration of inhibition preceding the decrease during continued perfusion of the compound. At lower concentrations of Ro 15-4513 the increase in inhibition predominated, the minimal effective concentration being 10 pM. 1 microM flumazenil blocked both components of this response to 100 nM Ro 15-4513, but at 100 nM flumazenil only blocked the decrease in inhibition. The ability of Ro 15-4513 but not Ro 19-4603 to enhance inhibition and its relative insensitivity to 100 nM flumazenil, parallel the affinities of these compounds for diazepam-insensitive (DI) binding sites in the cerebellum. These data suggest that the enhancement of inhibition induced by Ro 15-4513 results from its inverse agonist activity on DI receptors causing disinhibition of both granule cells and their parallel fibres and increased sensitivity to the electrical stimuli inducing activation of the inhibitory interneurones innervating Purkinje cells.

Animals↗
PubMed1994

A randomised controlled trial of a dietary advice program for relatives of heart attack victims.

OBJECTIVE: To compare two interventions for reducing dietary fat intake in first degree relatives of recent heart attack victims. DESIGN: A randomised controlled trial comparing a low cost mail-out advice program; referral to a general practitioner (GP); and no intervention (control group). PARTICIPANTS: Adult children or siblings, aged less than 70 years, of survivors of definite or suspected heart attack who had been admitted to hospitals in the Lower Hunter Region of New South Wales. MAIN OUTCOME MEASURES: Dietary fat intake (evaluated with a validated short questionnaire) and measurement of blood cholesterol levels at six months. RESULTS: Of the 342 relatives who participated (36% of those invited), 109, 120 and 113, respectively, were randomly assigned to receive a mail-out intervention, advice from their GP or to be part of a control group. The six-month follow-up questionnaire was completed by only 59% of those in the mail-out intervention group compared with 71% of the GP group and 77% of the control group. Younger participants, cigarette smokers and children (compared with siblings) were less likely to return a follow-up questionnaire. The mail-out group showed a statistically significant 20% reduction in self-reported dietary fat intake, but this was not seen in either the GP group or the controls. The low response rate meant the study had insufficient power to detect hypothesised changes in blood cholesterol. CONCLUSION: Because of the poor response rate and possible biases from a differential response to follow-up, we conclude that this low intensity intervention for relatives of people with recent heart attack produces only a modest improvement in reported dietary fat intake. Alternative strategies may be more effective in reducing the risk of heart disease.

Adult↗
PubMed1994

Actions of Fusinus FMRFamide-related peptides on the identified central neurones of the snail, Helix aspersa.

The actions of Fusinus FMRFamide-related peptides, that is FMRFamide, FLRFamide, GSLFRFamide, SSLFRFamide, the analogue, GSFFRFamide, and the fragments, LFRFamide and RFamide, were examined on the F1, F2 and F5 neurones of Helix aspersa. All Fusinus peptides exhibit an inhibitory effect on F1 and F5 neurone. On F2 neurone, FMRFamide and FLRFamide exhibit an excitatory effect but GSLFRFamide and SSLFRFamide exhibit an inhibition. The fragment, LFRFamide, is 10-times less potent than GSLFRFamide. GSFFRFamide and RFamide are inactive on F1, F2 and F5 neurone. This evidence indicates that the fragment, LFRFamide, is crucial for the biological activity of Fusinus hexapeptides. The inhibition induced by Fusinus hexapeptides had a reversal potential around -75/-80 mV. It was potentiated in K(+)-free saline, partially abolished either in 10 mM TEA or in 10 mM Co2+ saline and completely abolished in 500 microM 4-AP saline. This evidence indicates that there are multiple K+ channels which are activated by Fusinus hexapeptides and that the IA is more susceptible than IK and IKCa to these peptides.

Acetylcholine↗
PubMed1994

Altered free calcium transients in pig kidney cells (LLC-PK1) cultured with penicillin/streptomycin.

The effect of a conventional antibiotic (penicillin/streptomycin) mixture on the widely used kidney epithelial cell line, LLC-PK1, was investigated by measuring growth and intracellular free calcium. Free calcium concentration was the same in cells cultured for 3 to 7 wk with ("plus") and without ("minus") antibiotics both at rest and when challenged with high (14 mM) external calcium. When exposed to vasopressin, minus cells exhibited significantly smaller calcium transients than plus cells. A similar difference existed for transients elicited by a calcium ionophore, 4-br-A23187. After longer periods of culture (> 20 wk), minus cells grew slower than plus cells but on reaching confluence (minus cells took 1 day longer) the morphologies and viabilities were indistinguishable. The finding that culture with penicillin/streptomycin reversibly modified some properties of LLC-PK1 cells, at least partly through altered calcium homeostasis, is of importance for workers using this cell model to study drug effects and raises the general possibility of similar effects on other cultured cells.

Animals↗
PubMed1994

Plasma cholesteryl ester transfer in patients with non-insulin dependent diabetes mellitus.

Plasma newly synthesised cholesteryl ester transfer (NCET) rates from high density lipoproteins (HDL) to very low density lipoproteins (VLDL) and low density lipoproteins lipoproteins (LDL) were measured in 26 patients with non-insulin dependent diabetes mellitus (NIDDM), 26 healthy subjects with closely matching plasma triglyceride (TG) levels and 10 normolipidaemic healthy individuals. In addition, insulin mediated glucose uptake was measured in the NIDDM patients and the normolipidaemic subjects. Rates of NCET were significantly (P < 0.05) elevated in NIDDM patients compared with healthy normolipidaemic individuals but were similar to rates in healthy subjects with closely matching TG levels. In all groups of subjects plasma NCET was significantly (P < 0.001) correlated with plasma TG concentration. In NIDDM patients correlations between NCET and plasma glucose (r = 0.489, P = 0.011) independently of plasma TG levels, and glycated haemoglobin levels (r = 0.430, P = 0.028) were also recorded. Insulin mediated glucose uptake was unrelated to plasma NCET rates in the study. These data suggest that in NIDDM patients under good diabetic control elevated plasma NCET rates are mainly due to hypertriglyceridaemia and a specific and possibly stimulatory effect of diabetes on these rates may be seen only in patients with poorly controlled diabetes.

Adult↗
PubMed1994

The effect of acute hyperinsulinemia on plasma cholesteryl ester transfer protein activity in patients with non-insulin-dependent diabetes mellitus and healthy subjects.

The effect of acute hyperinsulinemia on plasma cholesteryl ester (CE) transfer protein (CETP) activity was determined in 11 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy subjects. Plasma CETP activity was reduced significantly in NIDDM patients (-37 +/- 59 nmol/mL/h, P < .05) but not in healthy subjects (-7 +/- 37 nmol/mL/h) during insulin infusion. Saline infusion did not alter plasma CETP activity significantly. The change in plasma CETP activity was correlated significantly with the baseline plasma triglyceride (TG) concentration (r = -.523, n = 21, P = .01) and marginally with the concomitant decrease in these levels with acute hyperinsulinemia (r = .413, n = 21, P = .06) in NIDDM patients and healthy subjects combined. These data indicate that acute hyperinsulinemia reduces plasma CETP activity and probably plasma CETP concentration in NIDDM patients, and suggest coordinated regulation of CETP levels and TG metabolism by insulin.

Adult↗
PubMed1994

The effects of RU 33965 and RU 34030, two new 3-cyclopropyl carbonyl imidazobenzodiazepines, on GABAA receptor-mediated synaptic transmission in cerebellar slices in the rat.

1. Two 3-cyclopropyl carbonyl imidazobenzodiazepines, RU 33965 and RU 34030, were tested for their ability to modulate GABAA synaptic transmission in rat cerebellar slices. The action of the full benzodiazepine agonist RU 32007 and the inverse agonist Ro19-4603 were tested for comparison. 2. Extracellular recordings were made from the Purkinje cell layer of the cerebellar slices and inhibition induced by just threshold electrical stimulation of the parallel fibres was bicuculline sensitive. 3. The major effect of RU 32007 when examined at 100 nM and 1 microM was to increase the GABAA mediated inhibition in the slice. 4. In contrast the major effect of the inverse agonist Ro19-4603 was to reduce the period of inhibition. 5. RU 33965 and RU 34030 at 10 and 1 microM respectively either had little effect on GABAA mediated inhibition or decreased it slightly. 6. RU 34030, 1 microM, abolished the agonist effect of RU 32007, 1 microM. 7. The effects of RU 32007 and Ro19-4603 were abolished by the benzodiazepine antagonist flumazenil. 8. It is concluded that both RU 33965 and RU 34030 have marginal inverse agonist properties.

Animals↗
PubMed1994

A nematode FMRFamide-like peptide, SDPNFLRFamide (PF1), relaxes the dorsal muscle strip preparation of Ascaris suum.

PF1 (SDPNFLRFamide) is a FMRFamide-like peptide extracted from the free-living nematode Panagrellus redivivus. Here we show that this peptide causes a hyperpolarization of somatic muscle cells of the parasitic nematode Ascaris suum and a relaxation of the somatic muscle strip preparation. We have assessed whether or not the relaxation of Ascaris dorsal muscle strip by PF1 is due to (i) inhibition of the release of the excitatory neuromuscular junction transmitter acetylcholine (ACh), (ii) potentiation of the release of the inhibitory neuromuscular junction transmitter gamma-aminobutyric acid (GABA) or (iii) a direct inhibitory action of the peptide on the muscle cells. Under the experimental conditions described here, tonic ACh release does not seem to be involved in determining the resting membrane potential or resting tone of the Ascaris dorsal muscle strip and thus inhibition of tonic ACh release is unlikely to explain the relaxation elicited by the peptide. Furthermore, PF1 (100 nM-1 microM) inhibited the contraction of the muscle strip elicited by bath application of ACh, suggesting either a direct inhibitory action of the peptide on the muscle cells or a potentiation of GABA release. In electrophysiological experiments, the reversal potential for the PF1 hyperpolarization was not the same as that for GABA. Thus, PF1 hyperpolarizes Ascaris muscle by a mechanism that does not involve stimulation of GABA release from inhibitory pre-synaptic terminals.

Acetylcholine↗
PubMed1994

Characterization of identifiable neurones in the head ganglia of the parasitic nematode Ascaris suum: a comparison with central neurones of Caenorhabditis elegans.

Intracellular recordings have been made from neurones in the head ganglia of Ascaris. The neurones had low resting membrane potentials of -21 +/- 9 mV (n = 78) and a relatively high input resistance (e.g. 25 M omega for a 100 microns cell). In all cases the intracellular location of the recording electrode was verified by injection of the fluorescent marker, 5,6-carboxyfluorescein (CBXF). To ascertain whether or not the low membrane potential was due to impalement damage, the same neurone was recorded from using two microelectrodes. The membrane potential following the first impalement by a 20 M omega 3 M KCl electrode was -38 mV and following the second impalement by a 80 M omega CBXF (for subsequent intracellular labelling) electrode was decreased to -34 mV. Input resistance of these cells was estimated using both single and two electrode intracellular recording techniques and in both cases yielded a relatively high value for the size of cell (e.g. 25 M omega for a 100 microns cell). Neurones labelled by intracellular injection of the fluorescent marker 5,6-carboxyfluorescein were morphologically simple and lacked extensive arborizations. The dorsal ganglion is a discrete structure consisting of only 3 neurones. Here we compare the morphological properties of these neurones to those described in the dorsal ganglion of Caenorhabditis elegans. The whole mount preparation of Ascaris ganglia thus provides a useful model to study the functional properties of neurones in nematode central nervous system and presents the possibility to assess central sites of action for anthelmintics.

Animals↗
PubMed1994

Cholesteryl ester transfer in patients with renal failure or renal transplants.

Plasma newly-synthesized cholesteryl ester transfer (NCET) rate and concentrations of lipids, lipoproteins and apolipoproteins A1 and B were measured in chronic renal failure patients (dialysis independent and dialysis dependent), patients with a functioning renal transplant and in healthy control subjects with comparable ages and plasma triglycerides. Plasma NCET rates and apoB concentrations were significantly higher in patients treated by continuous ambulatory peritoneal dialysis (CAPD) compared with controls. In normolipidemic subjects (cholesterol < 6.5 mmol/liter, triglycerides < 2.0 mmol/liter), plasma NCET rates did not differ significantly from rates in the corresponding control subjects. In hyperlipidemic subjects, plasma NCET rates were significantly higher than rates in the normolipidemic subgroup. Plasma NCET rates were correlated closely with plasma apoB levels in all renal patients combined (r = 0.754, N = 53, P < 0.001) and with plasma cholesteryl ester mass transfer (r = 0.853, N = 13, P < 0.001). We conclude that, in the absence of hyperlipidemia, plasma NCET rate is normal in patients with chronic renal failure irrespective of the treatment for uremia, and when hyperlipidemia is present NCET rates are raised and may contribute to elevated levels of the proatherogenic apoB-containing lipoproteins.

Adolescent↗
PubMed1994

Plasma natriuretic peptides and cardiac volume during acute changes in intravascular volume in haemodialysis patients.

1. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP) were measured, along with left and right atrial and left ventricular volumes, in eight patients with chronic renal failure before and after the removal of 2.1 +/- 0.61 of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l saline) to restore body weight plus 0.5 kg. 2. Baseline levels of ANP (46.0 +/- 7.5 pmol/l) and BNP (22.0 +/- 4.4 pmol/l) were elevated above normal. There was a significant reduction in plasma ANP (26.5 +/- 4.7 pmol/l, P < 0.05) and BNP (19.1 +/- 4.9 pmol/l, P < 0.05)) following ultrafiltration. Changes in plasma ANP during ultrafiltration correlated significantly with changes in left atrial volume (r = 0.643, P < 0.05). 3. During volume repletion there was an exaggerated release of ANP (mean level post repletion 71.3 +/- 20.8 pmol/l) which was not paralleled by changes in BNP. Changes in BNP were small, showing no correlation with atrial or ventricular volumes during either ultrafiltration or volume repletion. 4. These findings indicate that in chronic renal failure without left ventricular dysfunction, moderate acute changes in volume status elict only small immediate responses in plasma BNP. Changes in plasma ANP are greater than BNP and more responsive to changes in left atrial volume.

Adolescent↗
PubMed1994

Multiple pancreatic abscesses due to Candida albicans following ERCP.

A report is presented of a patient who developed multiple abscesses of the pancreas due to Candida albicans following an Endoscopic retrograde chole-pancreatography (ERCP) for acute pancreatitis. He was not immunocompromised, debilitated and had not had recent surgery. There was complete radiological and clinical resolution of the abscess on prolonged treatment with amphotericin alone. Only a few cases of candidal abscess of the pancreas have been reported, none of them having occurred after an ERCP.

Abscess↗