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Biomedical subjects

J E Tattersall

Publications and source records attributed to J E Tattersall.

At least 19 recordsLinked to original sources
PubMed2001

Effects of low intensity radiofrequency electromagnetic fields on electrical activity in rat hippocampal slices.

Slices of rat hippocampus were exposed to 700 MHz continuous wave radiofrequency (RF) fields (25.2-71.0 V m(-1), 5-15 min exposure) in a stripline waveguide. At low field intensities, the predominant effect on the electrically evoked field potential in CA1 was a potentiation of the amplitude of the population spike by up to 20%, but higher intensity fields could produce either increases or decreases of up to 120 and 80%, respectively, in the amplitude of the population spike. To eliminate the possibility of RF-induced artefacts due to the metal stimulating electrode, the effect of RF exposure on spontaneous epileptiform activity induced in CA3 by 4-aminopyridine (50-100 microM) was investigated. Exposure to RF fields (50.0 V m(-1)) reduced or abolished epileptiform bursting in 36% of slices tested. The maximum field intensity used in these experiments, 71.0 V m(-1), was calculated to produce a specific absorption rate (SAR) of between 0.0016 and 0.0044 W kg(-1) in the slices. Measurements with a Luxtron fibreoptic probe confirmed that there was no detectable temperature change (+/- 0.1 degrees C) during a 15 min exposure to this field intensity. Furthermore, imposed temperature changes of up to 1 degrees C failed to mimic the effects of RF exposure. These results suggest that low-intensity RF fields can modulate the excitability of hippocampal tissue in vitro in the absence of gross thermal effects. The changes in excitability may be consistent with reported behavioural effects of RF fields.

Action Potentials↗
PubMed2001

An improved brain slice model of nerve agent-induced seizure activity.

A brain slice model was developed to investigate the mechanisms of seizure activity induced by soman and the effectiveness of potential anticonvulsant drugs. Unlike previously reported slice studies with nerve agents, this model contains the entorhinal cortex as well as the hippocampus. This allows the study of the spread of seizure discharges within the limbic system and the development of prolonged, sustained discharges that are rarely seen in the simple hippocampal slice preparation. Soman (1 microM) induced a second population spike in the evoked field potential in the CA1 or CA3 region within 15-20 min. In almost all the slices tested, this developed into spontaneous seizure activity within 30-40 min. As well as interictal bursts, many slices also showed longer periods of high-frequency bursting analogous to ictal seizure activity that originated in the entorhinal cortex. This activity appeared similar to that induced by the muscarinic agonist pilocarpine. Both the second population spike and the spontaneous discharges could be blocked by diazepam and by AMPA/kainate antagonists, but not by the NMDA antagonists AP5 and MK-801. This study confirms that the combined hippocampal-entorhinal cortex slice preparation is a suitable model for investigating the origin and propagation of nerve-agent-induced seizures within the limbic system.

Animals↗
PubMed1999

The effect of exercise during haemodialysis on solute removal.

BACKGROUND: Urea rebound results as urea re-equilibrates between intracellular and intravascular compartments post haemodialysis. The mechanism of the rebound is thought to be due to either a reduced diffusion rate or blood flow. It is hypothesized that low blood flow in the skeletal muscles might be responsible. We tested this by studying the effect of exercise during dialysis on the removal of urea, creatinine and potassium. METHODS: Eleven patients (aged 32-78 years) on haemodialysis (4-58 months) were studied on paired dialysis sessions; one with exercise and the other as a control. Patients pedalled on a cycle for 5-20 min at submaximal workload followed by 10 min rest to achieve a total of 60 min exercise. Plasma concentrations of urea, creatinine and potassium were measured pre-, post- and 30-min post dialysis. The post-dialysis rebound (% rebound) and reduction ratios (RR) of the solutes and equilibrated (two-pool) urea Kt/V were calculated for comparison. RESULTS: The rebound of all three solutes was reduced significantly following exercise. The rebound of urea decreased from 12.4 to 10.9% (median, P<0.01 Wilcoxon signed rank test), creatinine from 21.2 to 17.2% (P<0.001) and potassium from 62 to 44% (P<0.05). Kt/V and RR increased significantly as a result: Kt/V urea from 1.00 to 1.15 (P=0.001), RR urea from 0.63 to 0.68 (P<0.001); Kt/V creatinine from 0.71 to 0.84 (P<0.01); and RR creatinine from 0.51 to 0.57 (P<0.05). CONCLUSION: Exercise increased the efficiency of dialysis by reducing the rebound of solutes due to increased perfusion of the skeletal muscles.

Adult↗
PubMed1997

Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro.

Alpha-dendrotoxin (alpha-DTx), a snake venom toxin which blocks several types of fast-activating voltage-dependent potassium channels, induces limbic seizures and neuronal damage when injected into the brain. The mechanisms underlying these convulsant and neuropathological actions are not fully understood. We have studied the effects of alpha-DTx on neurotransmitter release and electrical activity in rat hippocampal brain slices and the role of excitatory amino acid receptors in mediating these actions of the toxin. alpha-DTx increased the basal release of acetylcholine, glutamate, aspartate, and GABA in a concentration-dependent manner and induced epileptiform bursting in the CA1 and CA3 regions of the slice. The increase in neurotransmitter release was evident during the first 4 min after toxin addition, whereas the bursting appeared after a concentration-dependent delay (20-40 min with 250 nM toxin). The N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and MK-801 had no effect on the frequency or amplitude of dendrotoxin-induced epileptiform bursts, but the non-NMDA antagonists CNQX and DNQX abolished bursting in both CA1 and CA3 within 4-6 min. In contrast, the toxin-induced increases in neurotransmitter release were not blocked by DNQX. This study has demonstrated that, following exposure to alpha-DTx, there is a rapid increase in the release of neurotransmitters which precedes the onset of epileptiform bursting in the hippocampus. Since DNQX abolished the bursting but had no effect on the increase in neurotransmitter release, these results suggest that DNQX blocks alpha-DTx-induced epileptiform activity by antagonism of postsynaptic non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1997

Low serum vitamin B12 levels in chronic high-flux haemodialysis patients.

The occurrence of vitamin B12 (B12) deficiency in chronic haemodialysis patients and the need for its supplementation in these patients are still matters of debate. We measured serial predialysis serum B12 levels, at 3- to 6-month intervals, in 67 unselected patients on our high-flux haemodialysis programme. Over a 12-month period, there was a significant fall in serum B12 from 497 +/- 200 (SD) to 391 +/- 131 ng/l (p < 0.001). 22 patients developed subnormal serum B12 levels and were commenced on hydroxocobalamin supplements. We were unable to demonstrate B12 clearance during dialysis using blood side studies. Measurement of B12 in the dialysate showed that 0-4.5 microg B12 was cleared per dialysis. Using these B12 measurements, in vivo B12 clearance was estimated at 9.1 ml/min. Dietary studies on 24 unselected patients showed borderline or low B12 intake in 4 patients. Absorption studies by whole-body counting on 6 patients using 57Co and 58Co showed normal B12 absorption. The same radioisotope studies demonstrated no B12 adsorption to the dialyser membrane. This study demonstrates that low serum B12 levels occur in high-flux haemodialysis patients and that losses during dialysis and dietary deficiency may be contributing factors.

Adsorption↗
PubMed1996

The post-hemodialysis rebound: predicting and quantifying its effect on Kt/V.

Immediately after hemodialysis, the urea concentration rebounds upwards as urea continues to be transferred into the arterial circulation from peripheral body compartments. This rebound takes at least 30 minutes to complete. Hemodialysis is quantified as the Kt/V, calculated prom pre- and post-dialysis urea samples. Unless the post-dialysis sample is taken at least 30 minutes after dialysis, the Kt/V will be overestimated. This overestimation will be relatively greater in short high-efficiency dialyses, which have greater post-dialysis rebounds. We propose a method of correction that uses only the conventional pre- and immediate post-dialysis samples and is based on the physiologically-appropriate patient clearance time (tp). This is the time needed to clear all body compartments when the dialyzer clearance is infinite. The tp can be calculated from the pre-, immediate post- and 30-minute post-dialysis urea concentrations and was 35 minutes (SD 16) in 29 patients undergoing short (149 min) hemodiafiltration and standard (243 min) hemodialysis the following week. There was no significant difference between tp values calculated during the two treatments. Standard Kt/V can be corrected by multiplying by t/(t + tp) and dialysis time should be increased by tp x Kt/V minutes to compensate for the rebound. Despite individual variations in tp, a value of tp = 35 was sufficient to correct Kt/V in all patients. Kt/V corrected in this way agreed with Kt/V calculated using a 60-minute post-dialysis sample (r = 0.856, P < 0.001). The method predicted the 60-minute post-rebound concentration (SE 0.5 mM, r = 0.983, P < 0.001) and the addition of 35 minutes to the treatment time corrected for the rebound in both conventional and short treatments. Similar simple equations corrected the error in V caused by rebound effects.

Adult↗
PubMed1995

Compared toxicity of the potassium channel blockers, apamin and dendrotoxin.

The central toxicities of two potassium ion channel blockers, apamin and alpha-dendrotoxin (DTx), have been compared. Both apamin and dendrotoxin injected intracerebroventricularly produced signs of poisoning, including tremor and ataxia; however, only DTx produced changes in brain electrical activity, with high voltage spikes and epileptiform activity and subsequent brain damage. DTx, but not apamin, increased the amplitude of evoked field potentials and caused repetitive firing of neurones in hippocampal slices. Signs of poisoning following peripheral (intraperitoneal) administration of apamin were similar to those following central administration, including dramatic haemorrhagic effects on the lungs of decedent animals. These results are consistent with dendrotoxin being a centrally-active neurotoxin producing epileptiform activity and brain damage, whilst apamin produces its most significant pathology in the lung, possibly involving a neurogenic mechanism.

Animals↗
PubMed1995

Alkalosis and hypomagnesaemia: unwanted effects of a low-calcium CAPD solution.

We studied 43 CAPD patients for 4 months during the change from a high-calcium dialysis fluid (Baxter PD1) to a low-calcium fluid (Baxter PD4), which also contained low magnesium (0.25 mmol/l) and high lactate concentrations (40 mmol/l). Serum calcium fell significantly as did the incidence of hypercalcaemia, whilst the proportion of patients taking calcium-containing phosphate binders increased. There was a non-significant increase in serum i-PTH levels but the proportion with i-PTH > 150 pg/ml (normal range 10-65 pg/ml) increased significantly. There was a significant fall in serum magnesium level and seven patients developed hypomagnesaemia. Serum bicarbonate increased significantly and progressively and 17 patients were alkalotic at 4 months, five severely (bicarbonate 35-40 mmol/l). One patient developed recurrent episodes of painful subcutaneous and periarticular calcification, which may have been related to the alkalosis. Initial serum bicarbonate levels correlated significantly with dialysis adequacy assessed by daily Kt/V (r = 0.458, P = 0.002). The relationship to adequacy was abolished during the period of use of the high-lactate dialysis fluid. Use of low-magnesium CAPD fluids must be supported by regular monitoring of serum magnesium levels. The high lactate concentration in such fluids may not be appropriate and is potentially hazardous when individualization of dialysis dose demands the use of relatively high exchange volumes. Low serum bicarbonate levels in CAPD patients reflect inadequate dialysis, which use of these fluids serves to mask.

Adult↗
PubMed1994

Maintaining adequacy in CAPD by individualizing the dialysis prescription.

Urea kinetic modelling (UKM) has been proposed as a tool for auditing the adequacy of CAPD and a total fractional daily urea cleared volume (Kt/V) of 0.25 suggested as the minimum adequate level. At the start of CAPD the kidneys contribute significantly to the total clearance and Kt/V often falls below 0.25 as renal function declines. We performed 3-monthly UKM measurements in 56 CAPD patients. These results were used to individualize exchange volume and frequency in an attempt to achieve a Kt/V > 0.25 and compensate for declining renal function in all patients over a study period of 1 year. The mean Kt/V was maintained over 0.29 over the study period. During this time the residual renal component of Kt/V fell significantly from 0.09 (SD +/- 0.07) to 0.06 +/- 0.08 (P < 0.001) while the dialysis component increased significantly from 0.20 +/- 0.05 to 0.24 +/- 0.05 (P < 0.005). This was achieved by increasing the mean daily exchange volume from 8.12 +/- 1.22 to 10.39 +/- 2.68 litres (P < 0.001). After a year, 15 patients had Kt/V < or = 0.25 despite maximum practical exchange volumes. Twelve patients dropped out of the study due to death (4), transplantation (2), and transfer to haemodialysis (6 patients, of whom 4 had frank uraemic toxicity). In most CAPD patients it is possible to compensate for declining renal function by increasing exchange volume, at least over 1 year. However, CAPD was unable to provide Kt/V > 0.25 in 40% of patients, despite individualization of the dialysis prescription.

Body Weight↗
PubMed1993

Kinetic modelling and underdialysis in CAPD patients.

Kinetic analysis was performed in all 58 patients undergoing standard CAPD. The urea distribution volume was estimated from anthropomorphic measurements (Watson formulae). Normalized protein catabolic rate (NPCR), daily protein leak (PL), urea and creatinine Kt/Vs, clearances and peritoneal mass transfer coefficients (Kp) were calculated from measurements on serum, 24-h urine and PD fluid effluent. The mean total (renal+PD) daily creatinine and urea Kt/Vs (KT/V) were 0.31 (range 0.15-0.79) and 0.31 (0.18-0.65). There was no relationship between KT/V and serum urea or Kp. The strongest determinant of the urea KT/V was the residual renal urea clearance (KrU)(R = 0.79, P < 0.001) which decreased with time on dialysis (R = -0.38, P < 0.005). There was a significant correlation between the hospital admissions per year and both the urea and creatinine KT/V and KrU (R = -0.30, -0.32, P < 0.05). Patients with urea KT/V < 0.25 (n = 22) had more hospital admissions/year than those with KT/V > 0.25 (mean of 2.6 versus 1.5, P < 0.05). NPCR correlated with urea KT/V (R = 0.62, P < 0.001) but not with serum albumin or the PL. Patients identified by UKM to be less well dialysed have a lower residual renal function and are more likely to be hospitalized. Undernutrition in CAPD patients appears to be related to underdialysis rather than protein loss.

Creatinine↗
PubMed1993

Haemodialysis recirculation detected by the three-sample method is an artefact.

The efficiency of haemodialysis may be limited by recirculation of blood between venous and arterial needles. Recirculation can be detected directly using a saline dilution method but is most commonly calculated from the urea concentrations of simultaneous samples from venous and arterial lines and a peripheral vein (three-sample method). The methods detect markedly different rates of recirculation in similar study populations. To investigate the possibility that the methods detect different phenomena, we performed both tests on 16 haemodialysis patients at various extracorporeal blood flow rates (Qb). The saline dilution method showed no recirculation in any of the patients, whereas the three-sample method indicated recirculation in all patients. The three-sample method indicated a mean recirculation fraction of 12.5% (SD 6.1) and was not influenced by changing Qb, suggesting that it was not detecting fistula recirculation. The three-sample method detects a solute concentration difference between arterial blood and peripheral blood during dialysis. There appears to be a disequilibrium between a central pool, represented by the arterial sample, and a poorly perfused peripheral pool, relatively isolated from the dialysis process, represented by the peripheral venous sample. The three-sample method for detecting recirculation should be abandoned.

Arteries↗
PubMed1993

Ion channel blockade by oximes and recovery of diaphragm muscle from soman poisoning in vitro.

1. The actions of oximes and related compounds on the nicotinic acetylcholine receptor ion channel at the adult mouse muscle endplate were investigated by use of single-channel recording techniques. The aim of the study was to determine whether the channel-blocking properties of the compounds could contribute to their therapeutic effectiveness against soman poisoning in vitro. 2. Therapeutic effectiveness was assessed in guinea-pig phrenic nerve-hemidiaphragm preparations by measuring the degree of recovery of neuromuscular function produced by the compounds following poisoning by soman. A number of the compounds, including some which lacked the oxime group, produced a significant recovery of neuromuscular function which was unrelated to acetylcholinesterase (AChE) reactivation; this was reversed by washing off the compound, and was therefore attributed to a direct pharmacological action on the muscle. 3. Single channel recordings showed that some of the compounds blocked open nicotinic receptor ion channels in preparations of mouse muscle fibres. The compounds which showed the greatest direct pharmacological actions in diaphragms produce a very fast, flickering blockade of the channels. Several quantitative measures of channel-blocking activity correlated very well with the direct pharmacological action. Furthermore, for two compounds studied in greater detail, the direct action and channel-blocking showed similar concentration-response relationships. 4. The results of this study indicate that the direct pharmacological action of oximes and their analogues against neuromuscular blockade by soman in vitro is due to their channel-blocking activity. The direct action does not correlate well with protection against soman poisoning in vivo, however, which suggests that additional non-reactivating properties of these compounds, at sites other than the neuromuscular junction, may also be important for their therapeutic effectiveness.

Animals↗
PubMed1993

Heparin-free dialysis with an on-line hemodiafiltration system.

In heparin-free hemodialysis, the extracorporeal circuit is frequently flushed with normal saline. We report about an on-line hemodiafiltration (HDF) machine for performing heparin-free dialysis. The circuit is periodically flushed with fluid produced by filtration of the dialysis fluid. Because the fluid is derived from the volumetric dialysate circuit, it causes an equivalent ultrafiltration from the patient, and there is no need to allow for it in the fluid balance calculation. The use of the on-line HDF system in heparin-free dialysis is simple and cheaper than the saline-flush method. Automation of this system is possible and would result in even easier operation.

Equipment Design↗