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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 91 records · Page 5Linked to original sources
PubMed1995

Necrotising fasciitis: a single centre's experience.

AIMS: Necrotising fasciitis is a rare but serious soft tissue infection with high morbidity and mortality. We wished to review our 5 year experience with this condition 1989-94. In addition, in light of recent interest in the association between necrotising fasciitis and nonsteroidal antiinflammatory drugs, we wished to determine the incidence of NSAID use in our necrotising fasciitis patients. METHODS: A review of all Dunedin Hospital cases of necrotising fasciitis between January 1989-June 1994 was undertaken. Subsequently all specialists involved in treating the patients audited the notes, particularly regarding clinical presentation, complications, treatment, outcome and concomitant use of NSAIDs was also recorded. RESULTS: There have been seven patients (4 males) with a mortality rate of 43%. Survival was associated with early diagnosis, rapid and intensive medical and surgical intervention, and possibly the early use of haemofiltration. Five of the seven patients had ingested nonsteroidal antiinflammatory drugs (NSAID) prior to their presentation which may have potentiated the severity of the endotoxic shock. CONCLUSION: Necrotising fasciitis remains a potentially lethal disease but early management and aggressive treatment improves outcome. A high index of suspicion, avoidance of NSAIDs, and aggressive multidisciplinary team management of these patients offers the best chance of survival in necrotising fasciitis.

Adult↗
PubMed1995

Actions of a small cardioactive peptide from Mytilus, APNFLAYPRLamide, on central neurones of Helix aspersa.

1. Mytilus small cardioactive peptide (SCP) was originally isolated from the anterior byssus retractor muscle of Mytilus edulis, with a primary structure, APNFLAYPRLamide. The mechanisms of action of this peptide were examined on identified central neurones of the snail, Helix aspersa, using intracellular recordings and a two electrode voltage clamp. 2. 50 microM APNFLAYPRLamide could elicit a long term excitation on F2 neurones, in normal saline, Na(+)-free saline, Ca(2+)-free saline or in 10 mM Co2+ saline. This indicates that the excitatory effect of APNFLAYPRLamide involved an increase in membrane conductance to both Na+ and Ca2+. 3. 10 microM APNFLAYPRLamide potentiated the Ca2+ inward current of F2 neurones while reversibly reducing the ACh-induced membrane current of these neurones. Forskolin had identical effects to those of APNFLAYPRLamide. This indicates that the action of APNFLAYPRLamide may be through a second messenger. In contrast APNFLAYPRLamide potentiated a cholinergic EPSP evoked in F2 neurones. 4. YPRLamide was inactive even at higher concentrations, for example, 100 microM, while LAYPRLamide exhibited activity but with a lower potency. This indicates that LAYPRLamide is the minimum structure required for activating this class of SCP-like peptide receptor. However, the mode of action of APNFLAYPRLamide on the Na+ current of F2 neurones requires further investigation.

Acetylcholine↗
PubMed1995

Inhibitory action of SKPYMRFamide on acetylcholine receptors of Helix aspersa neurons: role of second messengers.

1. SKPYMRFamide, a novel FMRFamide-like endogenous peptide reversibly decreases excitatory responses (depolarization and inward current) evoked by local ionophoretic application of acetylcholine (ACh) onto the soma of identified neurons F1, F2, F4 and F5/6 of the land snail, Helix aspersa. 2. Threshold concentrations of SKPYMRFamide for an inhibitory action on ACh-induced responses are 0.5-1 mumoll-1. This modulatory action of peptide is dose- and time-dependent. 3. It is concluded that SKPYMRFamide inhibits ACh receptors through activation of specific binding sites on the plasma membrane. 4. The possible role of different second messengers in the modulatory influence of SKPYMRFamide on ACh receptors was tested using 13 modulators of different second messenger systems. 5. The results indicate that SKPYMRFamide may inhibit ACh receptors through activation of one or more of the following systems: phospholipases C, A2, NO-synthase, soluble guanylate cyclase and lipoxygenases which elevate basal intracellulal levels of NO, cGMP, arachidonic acid, acyclic eicosanoids, inositol-1,4,5-trisphosphate (I(1,4,5)P3), I(1,4,5)P3-dependent Ca(2+)-mobilization followed by activation of calmodulin and Ca2+/calmodulin-dependent protein kinase II. Protein kinases A, C and cyclic eicosanoids do not appear to participate in modulatory action of SKPYMRFamide.

Acetylcholine↗
PubMed1995

The effect of the nematode peptides SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2) on synaptic transmission in the parasitic nematode Ascaris suum.

The action of two peptides isolated from the nematode Panagrellus redivivus, PF1 (SDPNFLRFamide) and PF2 (SADPNFLRFamide) have been studied on synaptic transmission in the motornervous system of the parasitic nematode Ascaris suum. Intracellular recordings were made from Ascaris somatic muscle cells and excitatory junction potentials (EJPs) elicited by stimulation of the ventral nerve cord. The EJPs were cholinergic as they were blocked by the Ascaris nicotinic receptor antagonist, benzoquinonium. PF1 caused a slow hyperpolarization, similar to the action of this peptide first reported by Bowman, Geary & Thompson (1990) and further characterized by Franks et al. (1994). The hyperpolarization was accompanied by a marked decrease in the amplitude of the EJPs with an EC50 of 311 +/- 30 nM (n = 5). This inhibition is unlikely to be due to a post-synaptic site of action of the peptide as the muscle cell input conductance was not significantly altered by PF1 and furthermore the response to bath-applied acetylcholine was not inhibited by PF1 at concentrations up to 10 microM (n = 6). PF2 also inhibited the EJPs in a similar manner to PF1. These studies indicate that both of the peptides isolated from the free-living nematode Panagrellus redivivus have biological activity in the parasitic nematode Ascaris suum. PF1 and PF2 have inhibitory actions in contrast to the predominantly excitatory actions of the Ascaris endogenous peptides AF1 (KNEFIRFamide) and AF2 (KHEYLRFamide). The potent actions of the Panagrellus neuropeptides PF1 and PF2 in Ascaris suggest that peptides with a similar or identical sequence may also occur in Ascaris and have an inhibitory role in the motornervous system.

Acetylcholine↗
PubMed1995

Histochemical mapping of NADPH diaphorase in the nervous system of the parasitic nematode Ascaris suum.

NADPH diaphorase has recently been discovered to be responsible for neuronal nitric oxide (NO) synthase activity in mammals. It thus serves as a histochemical marker for the localization of NO synthase in the nervous system. The histochemical technique was used to map out potential NO-producing neurones in the nervous system of the parasitic nematode, Ascaris suum. Positive staining for NADPH diaphorase was present in various parts of the central nervous system, in particular within selective cell bodies and fibres in the ventral ganglion, the retrovesicular ganglion, ventral and dorsal cords and sublateral lines. Intense staining was also present in the motorneurone commissures, indicating a potential role for NO as a neurotransmitter at the neuromuscular junction. NADPH disphorase-positive neurones were not confined to the central nervous system. Selective staining was also present in the enteric nervous system, in particular the pharynx and in the peripheral nervous system innervating the sensory organs.

Animals↗
PubMed1995

The FMRFamide-like neuropeptide AF2 is present in the parasitic nematode Haemonchus contortus.

Peptides belonging to the FMRFamide family are widely distributed amongst invertebrates. We report here on the isolation of the FMRFamide neuropeptide AF2 (Lys-His-Glu-Tyr-Leu-Arg-Phe-NH2) from the parasitic nematode Haemonchus contortus. Immunocytochemical techniques showed that FMRFamide-like material was distributed in several regions of these organisms including nerve cords and cell bodies of the central nervous system. AF2 was isolated using a method that employed 6 steps of reverse-phase HPLC. The concentration of AF2 in this organism was approximately 30 pmol/g of nematode.

Amino Acid Sequence↗
PubMed1995

The effects of the nematode peptide, KHEYLRFamide (AF2), on the somatic musculature of the parasitic nematode Ascaris suum.

AF2 is an endogenous RFamide-like peptide from the parasitic nematode Ascaris suum. The potent stimulatory effects of this peptide on the somatic musculature of Ascaris strongly suggest that it may have an important role in the motornervous system. Here we have investigated the possibility that AF2 may elicit a stimulatory action on Ascaris muscle by potentiating the actions of the excitatory cholinergic motonervous system either pre-synaptically, post-synaptically or both. In in vitro pharmacological experiments AF2 produced a dose-dependent increase in the frequency and amplitude of spontaneous contractions of Ascaris muscle strip which lasted for more than 1 h after a 3 min application of AF2 (10 nM-10 microM; N = 7). In addition, AF2 (100 nM) potentiated the contraction elicited by ACh by 43 +/- 9% (P < 0.01; N = 8). In electrophysiological recordings from muscle cells, AF2 (10-100 nM; N = 10) potentiated the amplitude of EJPs (excitatory junction potentials). For 100 nM AF2, the potentiation of the EJP was 218 +/- 48% (N = 7; P < 0.01). This effect reversed after a wash of 10 min. AF2 did not potentiate the depolarization of the muscle cell elicited by bath applied ACh. These latter two observations are consistent with a presynpatic action of AF2. AF2 (10-100 nM) generated spontaneous muscle cell action potentials in previously quiescent cells. This effect took more than 1 h to wash out. These observations are discussed in terms of the paralysis of Ascaris that is elicited by AF2.

Acetylcholine↗
PubMed1995

The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum.

The pharyngeal component of the enteric nervous system of the parasitic nematode, Ascaris suum exhibits immunoreactivity for serotonin (5-hydroxytryptamine or 5-HT) and for FMRFamide-like peptides. This paper describes the application of an in vitro pharmacological approach to investigate the functional role of 5-HT and FMRFamide-like peptides. The pharyngeal pumping behaviour of Ascaris suum was monitored using a modified pressure transducer system which measures pharyngeal pressure changes and therefore pumping. The pharynx did not contract spontaneously; however, 5-HT (10-1000 microM) stimulated pumping at a frequency of 0.5 Hz. FMRFamide had no apparent effect on pharyngeal pumping. The native nematode FMRFamide-related peptide (FaRP), KSAYMRFamide inhibited the pumping elicited by 5-HT. The duration of inhibition was dose-dependent (0.1-1000 nM) with a threshold of 0.1 nM. In 4 preparations, the inhibition of the pharyngeal muscle was preceded by an initial excitation and increase in the amplitude of pharyngeal pressure changes. The pharynx is involved in various nematode processes, including feeding, regulation of hydrostatic pressure and excretion. The role of 5-HT and KSAYMRFamide in the pharyngeal function of nematodes is discussed.

Amino Acid Sequence↗
PubMed1995

Oxidation of low density lipoproteins from patients with renal failure or renal transplants.

Peroxidation of low density lipoproteins (LDL) may be involved in the development of atherosclerosis which is prevalent in patients with chronic renal failure and renal transplant recipients. We determined the copper ion catalyzed oxidation in vitro, vitamin E content, and chemical and fatty acid composition of LDL isolated from 38 patients with renal disease and 15 healthy subjects. Also the acute effect of hemodialysis treatment on LDL oxidation variables was tested. The lag time in conjugated diene formation during oxidation was significantly (P = 0.011) shorter in LDL from renal transplant recipients (66 min, N = 18) mainly due to significantly (P < 0.05) shorter times in women (47 min, N = 7), compared with healthy subjects (83 min, N = 15), patients on hemodialysis (91 min, N = 13) and patients treated by continuous ambulatory peritoneal dialysis (CAPD) (82 min, N = 7). The maximum rate and the extent of LDL oxidation were significantly (P < 0.01) lower in all patients with renal disease compared with healthy subjects. The triglyceride content of LDL was significantly (P < 0.001) higher in women with kidney grafts (7.3%) compared with levels in the corresponding men (5.3%) and healthy women (5.0%), and was correlated significantly with the lag time in LDL oxidation in renal transplant recipients (Spearmans r = -0.502, P = 0.034). The percentage oleic acid in LDL was significantly higher (P = 0.002) and the percentage linoleic acid was significantly lower (P = 0.046) in patients with renal disease, and may largely account for their lower rates and extent of LDL oxidation. Levels of the LDL oxidation variables and organic lipid peroxide content of LDL were not significantly different before and after hemodialysis and 24 hours later. These results suggest that LDL from women with renal transplants may be abnormally susceptible to oxidation possibly due to increased triglyceride content.

Adult↗
PubMed1995

Prolonged bleeding time during ciprofloxacin therapy.

Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and other gastrointestinal symptoms; skin and musculoskeletal side effects may also occur. No bleeding abnormalities or alteration in coagulation have been documented. We report a case where ciprofloxacin appeared to contribute to an idiosyncratic prolongation of bleeding time although a rechallenge 8 months later did not reproduce the effect. Moreover, subsequent investigation of the influence of ciprofloxacin on bleeding parameters in 10 healthy volunteers demonstrated no alterations in bleeding parameters.

Administration, Oral↗
PubMed1995

Fluconazole infused via a nephrostomy tube: a novel and effective route of delivery.

Fluconazole is an effective oral or intravenous anti-fungal agent. It undergoes little or no metabolism with 70-80% of the drug excreted unchanged in the urine. There is no readily available information on its effectiveness in treating fungal urinary tract infections in the presence of chronic renal failure. We report a case of chronic renal failure with ureteric obstruction complicated by infection with Candida albicans that was successfully treated by the infusion of fluconazole via a nephrostomy tube. There were no complications related to the use of fluconazole.

Aged↗
PubMed1995

The effects of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects.

BACKGROUND: There are conflicting reports about the effects of ACE inhibitors (ACEI) on insulin sensitivity and glycaemic control. Most studies have used a standard high dose of an ACEI but there have been no studies reported to establish whether any changes in glycaemic control or insulin sensitivity associated with ACEI are dose-related. AIM: To examine the effect of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects. METHODS: The effects of increasing doses of enalapril on insulin sensitivity in ten normotensive non-insulin dependent diabetic subjects were measured, using the hyperinsulinaemic isoglycaemic clamp technique. Following a baseline study, enalapril was commenced at 5 mg daily and increased to 10 mg daily then 20 mg daily at 14 day intervals. Repeat studies were undertaken after 14 days at each dosage. RESULTS: There was a significant dose-related reduction of systolic blood pressure with enalapril. In contrast enalapril at 5-20 mg daily produced no significant changes in insulin mediated glucose uptake (M-value) or insulin sensitivity index (ISI). CONCLUSIONS: These findings indicate that in this insulin resistant population of normotensive non-insulin dependent diabetics, angiotensin converting enzyme inhibition with enalapril has no significant effect on insulin mediated glucose uptake.

Aged↗
PubMed1995

Metabolism of quinine in man: identification of a major metabolite, and effects of smoking and rifampicin pretreatment.

Our previous studies have shown that cigarette smoking and rifampicin pretreatment enhance the elimination of quinine, metabolism assumed, by analogy with quinidine, to be carried out by CYP3A (P450IIIA). This finding is unexpected since it has been shown that smoking induces the CYP1A rather than the CYP3A enzyme family, suggesting that the metabolism of quinine may be catalysed by CYP1A. Therefore, we conducted this study to identify possible quinine metabolites in human urine and to determine which metabolic pathway is induced by cigarette smoking and rifampicin pretreatment. A specific HPLC procedure was employed to identify metabolites of quinine in urine samples collected from healthy volunteers after an oral dose of 600 mg quinine sulphate. The results showed that there were at least seven possible metabolites of quinine detected in human urine. Three of these were identified as 2'-oxoquininone, quinine glucuronide and 3-hydroxyquinine. The 3-hydroxyquinine appeared to be a major metabolite of quinine in urine samples from every subject who took an oral dose of quinine. Although cigarette smoking and rifampicin pretreatment were shown to cause a marked increase in the elimination of quinine there were no significant changes in the formation of 3-hydroxyquinine as measured in the urine samples. This suggests that the effects of smoking and rifampicin are more complicated than we expected and require further investigation.

Antimalarials↗
PubMed1995

Hepatic function in workers occupationally exposed to carbon tetrachloride.

OBJECTIVES: To identify any differences in hepatic function between workers exposed to carbon tetrachloride and controls, and to identify the best variable with which to examine any effects. METHODS: In a cross sectional study of hepatic function in workers occupationally exposed to carbon tetrachloride, 135 exposed employees were compared with 276 non-exposed controls. The exposed group was taken from three sites in the north west of England and the control group included non-exposed workers from one of these sites and another site located nearby. Demographic and alcohol consumption data were collected from both groups by questionnaire. Each member of the study group was allotted a notional estimated exposure to carbon tetrachloride, calculated from historic personal monitoring data and job category. A fasting sample of blood was taken from all participants and analysed for a variety of biochemical and haematological variables. The techniques of univariate and multivariate analysis of variance were used to investigate the effect on biochemical and haematological indices of a range of factors. RESULTS: Multivariate analysis of variance of four core liver function variables, alanine transaminase, aspartate transaminase, alkaline phosphatase, and gamma-glutamyl transferase, showed a significant difference between exposed and non-exposed workers. The univariate analyses identified increases in only alkaline phosphatase and gamma-glutamyl transferase within the exposed group and these did not show a significant dose-response relation. Univariate analysis of variance did show effects of alcohol and age on several variables. Significant differences between exposed and control groups for three haematological variables, haemoglobin, packed cell volume, and red blood count, were thought not to be due to the effects of exposure. Clinical review of exposed subjects with abnormal results did not show clinically evident disease that could have been associated with exposure to carbon tetrachloride. Also, a follow up study conducted three years after the cross sectional study at the site with highest exposures to carbon tetrachloride showed no evidence of any further changes in liver function variables. CONCLUSIONS: The most sensitive statistical methods have shown significant differences in the liver function variables measured between people exposed to carbon tetrachloride and the control group. The interpretation of the data collected was that these differences may be due to exposure to carbon tetrachloride but this was not clearly shown. Furthermore, the changes found have not given rise to any clinical disease.

Adult↗
PubMed1995

Reversible erythrocytosis in a patient with a hydronephrotic horseshoe kidney.

A 33-year-old man with dystrophia myotonica presented with erythrocytosis and an increased plasma erythropoietin concentration. Investigations showed a horseshoe kidney, one moiety of which was grossly hydronephrotic. Fluid aspirated from the latter had a similar erythropoietin concentration to that in plasma. Following partial nephrectomy, the hematocrit and plasma erythropoietin concentration returned to normal.

Adult↗
PubMed1995

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking.

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.

Acetylglucosamine↗