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Biomedical subjects

J Dempster

Publications and source records attributed to J Dempster.

At least 19 recordsLinked to original sources
PubMed2005

BAHNO surgical specialities: same patients, different practices?

The British Association of Head and Neck Oncologists (BAHNO) is 'a multidisciplinary society for healthcare professionals involved in the study and treatment of head and neck cancer'. Surgical members of this organization are from three specialities (otolaryngology, maxillo-facial and plastic surgery). Although the overall impression is that the management of UK head and neck cancer patients is consensus based, there are appreciable differences in each surgical speciality's practice. Anecdotally, this can lead to variation in the management of very similar patients. To identify some of these variations BAHNO surgeons were surveyed regarding their current head and neck cancer practices from the perspectives of surgical activity and post-operative care. Some unexpected differences were identified, particularly in relation to post-operative care with plastic and maxillo-facial surgeons demonstrating different patterns of high dependency unit (HDU) and intensive care unit (ICU) use for the same patients. The implications for future consensus in the light of these variations are discussed.

Critical Care↗
PubMed2003

Adenoid cystic carcinoma of the nasal septum.

Adenoid cystic carcinoma is a malignant tumour frequently described arising from seromucinous salivary tissue in the major and minor salivary glands. Within the nasal cavity, it is uncommon and usually involves the lateral wall. A rare case of adenoid cystic carcinoma of the nasal septum is presented along with a review of the literature. The presentation and management of this uncommon condition is discussed.

Biopsy, Fine-Needle↗
PubMed2002

Tamoxifen therapy in steroid-resistant Riedels disease.

Riedels thyroiditis is a rare chronic inflammatory disorder characterised by extensive fibrosis of the thyroid gland and sometimes the surrounding tissues. We report a case of Riedels Thyroiditis in a middle aged female presenting with goitre, stridor and dyspnoea. She initially responded to corticosteroid treatment and subsequently to tamoxifen. The rationale for these treatments are discussed.

Anti-Inflammatory Agents↗
PubMed2001

Asthma care by nurse practitioners in the United States.

PURPOSE: To survey nurse practitioners (NPs) in the United States on their level of input to asthma care prior to enrolling in The National Asthma and Respiratory Training Centre (NARTC) specialist asthma education program in the UK. DATA SOURCES: Responses of 134 (66%) of the 202 NPs who self-selected for enrollment in the NARTC program on a preliminary questionnaire. CONCLUSIONS: Nearly all (133 or 99%) currently work with asthmatics and 122 (91%) prescribe asthma drugs. Only 92 (69%) measure peak flow(PF), 84 (63%) check inhaler technique, 76 (57%) teach use of a home PF meter and diary, and 63 (47%) provide written self-management plans on any regular basis. Many have not established follow-up procedures (56 or 42%), or evaluated their asthma management practices (55 or 41%). IMPLICATIONS FOR PRACTICE: Successful asthma management requires correct medication, systematic follow-up, patient education, and self-management. Specialist asthma training should encourage practitioners to combine effective drug usage with a long-term preventative approach.

Asthma↗
PubMed2001

Tamoxifen therapy in steroid resistant Reidel's thyroiditis.

Riedel's thyroiditis is a rare chronic inflammatory disorder characterised by extensive fibrosis of the thyroid gland and sometimes the surrounding tissues. We report a case of Riedel's Thyroiditis in a middle aged female presenting with goitre, stridor and dyspnoea. She initially responded to corticosteroid treatment and subsequently to Tamoxifen. The rationale for these treatments are discussed.

Drug Resistance↗
PubMed2001

Alveolar rhabdomyosarcoma of the parotid gland.

Alveolar rhabdomyosarcoma of the parotid gland is a rare condition. The treatment should involve an aggressive multi-modality approach incorporating surgical removal of the tumour, radiotherapy, and multi-agent chemotherapy. The presentation of this condition along with the most appropriate line of treatment is discussed.

Adult↗
PubMed2000

Regional electrophysiological effects of left ventricular hypertrophy in isolated rabbit hearts under normal and ischaemic conditions.

OBJECTIVES: Left ventricular hypertrophy (LVH) has been reported to produce differential electrophysiological effects in isolated epicardial and endocardial cells. This study aimed to examine regional electrophysiological effects of LVH in normal and ischaemic conditions in the whole heart. METHODS: LVH was secondary to perinephritis-induced hypertension. Monophasic action potential duration (MAPD(90)), effective refractory period (ERP) and conduction delay were measured in paced, isolated working rabbit hearts either at one right ventricular and two left ventricular sites (apical and basal epicardium) or at three left ventricular sites (apical and basal epicardium, apical endocardium). The hearts were subjected to 30 min of regional ischaemia and 15 min of reperfusion. RESULTS: In non-ischaemic conditions, LVH produced uniform prolongation of MAPD(90) and ERP in the left ventricular epicardium, but not in the endocardium. After coronary artery occlusion, LVH significantly increased ischaemia-induced transepicardial dispersion of repolarisation, but not refractoriness. LVH did not affect arrhythmogenesis in either non-ischaemic or ischaemic conditions. CONCLUSIONS: Differential effects of LVH on epicardial and endocardial electrophysiological parameters are also observed in the whole heart. In addition, the sensitivity of hypertrophied myocardium to ischaemia is increased and leads to an increase in ischaemia-induced dispersion of repolarisation. However, neither dispersion of refractoriness nor arrhythmogenesis are affected by LVH in non-ischaemic or ischaemic conditions in this experimental model.

Action Potentials↗
PubMed1998

Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes.

The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit (5-HT3A(b)) heterologously expressed in Xenopus laevis oocytes. At negative holding potentials, bath applied 5-HT (300 nM - 10 microM) evoked a transient, concentration-dependent (EC50 = 1.1+/-0.1 microM), inward current. The response reversed in sign at a holding potential of -2.1+/-1.6 mV. The response to 5-HT was mimicked by the 5-HT3 receptor selective agonists 2-methyl-5-HT (EC50= 4.1+/-0.2 microM), 1-phenylbiguanide (EC50=3.0+/-0.1 microM), 3-chlorophenylbiguanide (EC50 = 140+/-10 nM), 3,5-dichlorophenylbiguanide (EC50 = 14.5+/-0.4 nM) and 2,5-dichlorophenylbiguanide (EC50 = 10.2+/-0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 microM) of 5-HT. Responses evoked by 5-HT at EC50 were blocked by the 5-HT3 receptor selective antagonist ondansetron (IC50=231+/-22 pM) and by the less selective agents (+)-tubocurarine (IC50=31.9+/-0.01 nM) and cocaine (IC50 = 2.1+/-0.2 microM). The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT3A subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT3 receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT3A subunit orthologues.

Algorithms↗
PubMed1997

Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals.

1. The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/ hemidiaphragm preparations. 2. Hexamethonium (200 microM), but not MLA (0.4-2.0 microM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. 3. At low frequencies of stimulation (0.5-2 Hz), hexamethonium (200 microM) and MLA (2.0 microM) increased e.p.c. quantal content by 30-40%. At high frequencies (50-150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. 4. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. 5. At the concentrations studied, MLA and hexamethonium produced a small (10-20%) decrease in the peak amplitude of m.e.p.cs. 6. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca(2+)-activated K(+)-channels. 7. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the alpha-bungarotoxin-insensitive neuronal type.

Acetylcholine↗
PubMed1995

Prejunctional actions of muscle relaxants: synaptic vesicles and transmitter mobilization as sites of action.

1. Nicotinic antagonists such as tubocurarine affect acetylcholine release from motor nerve terminals at the neuromuscular junction. 2. Electrophysiological studies comparing the prejunctional actions of tubocurarine to those of vesamicol and vecuronium have been used to provide an insight into the mechanisms involved in the prejunctional effects of tubocurarine-like compounds. 3. The observed prejunctional actions of tubocurarine can be accounted for by a model in which the compound has two separately identifiable effects on the nerve terminal. At low frequencies of nerve stimulation tubocurarine augments acetylcholine release while at high frequencies of nerve stimulation tubocurarine depresses acetylcholine release. 4. Both of the effects of tubocurarine on acetylcholine release are a consequence of a change in the number of quanta within the nerve terminal immediately available for release upon nerve stimulation. 5. On the basis of our experimental observations, we suggest that the two prejunctional effects of tubocurarine are mediated through two pharmacologically distinct prejunctional nAChRs.

Animals↗
PubMed1994

Nicotinic antagonist-produced frequency-dependent changes in acetylcholine release from rat motor nerve terminals.

1. The frequency (0.5-150 Hz) and calcium dependence (0.5-2.0 mM) of the effects of the nicotinic antagonist tubocurarine (0.2 microM) on acetylcholine (ACh) liberation from motor nerve terminals has been examined using binomial analysis of quantal transmitter release. 2. At an extracellular calcium ion concentration ([Ca2+]o) of 2.0 mM, tubocurarine produced a decrease in the endplate current (EPC) quantal content of approximately 30% at high frequencies of motor nerve stimulation (50-150 Hz). In contrast, at low frequencies of stimulation (0.5-1.0 Hz), tubocurarine enhanced the EPC quantal content by approximately 20%. 3. The enhancement of EPC quantal content produced by tubocurarine at low frequencies of motor nerve stimulation was [Ca2+]o dependent, being abolished when [Ca2+]o was lowered from 2.0 to 0.5 mM. In contrast, the decrease in quantal content produced by tubocurarine at high frequencies of motor nerve stimulation was independent of [Ca2+]o, being approximately 30% at all calcium ion concentrations studied. 4. In direct contrast to tubocurarine, the nicotinic antagonist vecuronium (1.0 microM) produced no increase in EPC quantal content at low frequencies of nerve stimulation. However, at high frequencies of nerve stimulation it decreased EPC quantal content to a similar extent to 0.2 microM tubocurarine. The frequency-dependent decrease in EPC quantal content produced by 1.0 microM vecuronium in 2.0 mM [Ca2+]o was very similar to that seen with 0.2 microM tubocurarine in 0.5 mM [Ca2+]o. 5. Binomial analysis revealed that all the changes in EPC quantal content associated with both nicotinic antagonists were due to changes in the size of the pool of quanta in the nerve terminal available for immediate release with no effect on the probability of release of an individual quantum. 6. The results are interpreted in terms of two separately identifiable prejunctional actions of the nicotinic antagonists, both involving an action at nicotinic ACh receptors situated on the motor nerve terminal. Thus, at high frequencies of motor nerve stimulation tubocurarine and vecuronium produce a [Ca2+]o-independent decrease in ACh release, probably through an inhibitory action on a positive-feedback prejunctional nicotinic autoreceptor closely related to the muscle-type nicotinic ACh autoreceptor. However, at low frequencies of motor nerve stimulation we suggest that tubocurarine, but not vecuronium, produces a [Ca2+]o-dependent increase in ACh release through an action at a negative-feedback prejunctional neuronal-type nicotinic ACh autoreceptor.

Acetylcholine↗
PubMed1993

Electrophysiological analysis of transmission at the skeletal neuromuscular junction.

The review is divided into two sections. The first deals with methods and problems associated with performing electrophysiological experimentation on the skeletal muscle neuromuscular junction. The second section concentrates on the computer analysis of electrophysiological data. In the first section, the various techniques available for producing skeletal muscle paralysis are described. These include the use of pharmacological manipulations, such as an excess of magnesium ions or a competitive postjunctional nicotinic acetylcholine antagonist, physiological manipulations, such as cutting the muscle fibers, and the muscle fiber sodium channel toxin, mu-conotoxin. Also, in this section, a comparison is made of the use of voltage- and current-recording techniques, including descriptions of, and solutions to, the problems associated with membrane capacitance, nonlinear summation, membrane space constant, and electrical and mechanical interference. In the second section, details are given of the types of computer system commonly used for the analysis of electrophysiological data and also the requirements of the data analysis software. The use of computer algorithms for signal detection, signal evaluation, signal averaging, and curve fitting are qualitatively described, along with some of the problems and pitfalls often associated with these methods.

Animals↗
PubMed1990

End-plate ion channel block produced by lincosamide antibiotics and their chemical analogs.

Five lincosamide compounds were studied for their effects on end-plate currents (epcs), miniature end-plate currents and acetylcholine-induced current fluctuations in the garter snake costocutaneous nerve-muscle preparation. At high concentrations, lincomycin and clindamycin reduced epc amplitude, but analysis of driving functions showed that only with clindamycin was this due solely to changes in epc quantal content. The effect of lincomycin on epc amplitude was exaggerated by rapid channel block during the rising phase of the epc. Clindamycin produced currents with a single exponential decay and single Lorentzian noise spectra. All the other compounds produced currents which decayed as the sum of two exponential components. For lincomycin and epilincomycin, noise spectra consisted of two Lorentzian components. For epiclindamycin and deoxylincomycin, although epcs and miniature end-plate currents decayed with two components, it was not possible to separate two components in the noise spectra. A kinetic analysis of ion channel blocking actions showed only small differences between the two pairs of stereoisomers studied. End-plate ion channel blocking and unblocking rate constants did not vary greatly among the compounds but the end-plate ion channel unblocking rate constant values for the two lincomycin stereoisomers were larger than those for the two clindamycin stereoisomers. Deoxylincomycin exhibited properties similar to those of the clindamycins. It was concluded that lipid solubility, not stereochemical conformation, plays the greater role in determining the ion channel blocking properties within the series, particularly that of the rate of dissociation of the compound from end-plate ion channels.

Animals↗
PubMed1989

Umbilical artery velocity waveforms: poor association with small-for-gestational-age babies.

A total of 205 high-risk pregnancies was studied using continuous wave Doppler ultrasound examination of the umbilical artery to investigate the ability of the test to detect small-for-gestational-age (SGA) infants. The waveforms were analysed by calculating a ratio of the peak systolic to end diastolic frequency (A/B ratio). An A/B ratio greater than 95th centile from our derived normal values was classified as abnormal. Three outcome variables were examined: birthweight for gestational age, the standard deviation birthweight score and the ponderal index. Although of the 56 pregnancies with an abnormal Doppler result 34 (61%) were associated with a SGA infant, only 41% of all the SGA infants had an abnormal Doppler result. Alternative measures of growth, the ponderal index and the SD birthweight score, showed that on average the babies in the Doppler abnormal group were smaller than those in the Doppler normal group, but the overlap between the normal and abnormal groups was large. Therefore although Doppler ultrasound appears to identify groups of smaller babies, it does not identify individual pregnancies where the baby will be small at birth.

Blood Flow Velocity↗
PubMed1989

The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques.

1 The characteristics of transmembrane currents evoked by 5-hydroxytryptamine (5-HT) in the neuroblastoma x Chinese hamster brain cell line NCB-20 and neuroblastoma clonal cell line N1E-115 have been studied under voltage-clamp conditions by the whole-cell recording and outside-out membrane patch modes of the patch-clamp technique. 2 In 73% of NCB-20 cells examined (n = 221), and all N1E-115 cells studied (n = 80), 5-HT (10 microM) elicited a transient inward current at negative holding potentials, this being associated with an increase in membrane conductance. In both cell lines responses to 5-HT reversed in sign at a potential of approximately -2 mV and demonstrated inward rectification. 3 The reversal potential of 5-HT-induced currents (E5-HT) recorded from either NCB-20 or N1E-115 cells was unaffected by total replacement of internal K+ by Cs+. In N1E-115 cells, reducing internal K+ concentration from 140 to 20 mM produced a positive shift in E5-HT of approximately 28 mV, whereas reducing external Na+ from 143 to 20 mM was associated with a negative shift in E5-HT of about 37 mV. A large reduction in internal Cl- concentration (from 144 to 6 mM) had little effect on E5-HT. 4 5-HT-induced currents of NCB-20 cells were unaffected by methysergide (1 microM) or ketanserin (1 microM), but were reversibly antagonized by GR38032F (0.1-1.0 nM) with an IC50 of 0.25 nM. GR 38032F (0.3 nM) reduced 5-HT-induced currents in N1E-115 cells to approximately 26% of their control value. 5 On outside-out membrane patches excised from both NCB-20 and N1E-115 cells, 5-HT induced small inward currents which could not be clearly resolved into discrete single channel events. Such responses were: (i) reversibly antagonized by GR 38032F (1 nM) (ii) reversed in sign at 0 mV, and (iii) subject to desensitization. 6 Fluctuation analysis of inward currents evoked by 5-HT (1 microM) in N1E-115 cells suggests that 5-HT gates a channel with a conductance of approximately 310fS. Such a relatively small conductance could readily explain why the response of outside-out membrane patches to 5-HT cannot at present be resolved into clear single channel events.

Cell Membrane↗
PubMed1988

Fetal umbilical artery flow velocity waveforms: prediction of small for gestational age infants and late decelerations in labour.

The relationship between fetal umbilical artery waveform patterns and (a) small for gestational age infants or (b) late fetal heart rate (FHR) decelerations in labour was examined in 205 clinically high-risk pregnancies. All pregnancies were studied using continuous-wave Doppler Ultrasound within 7 days of delivery. Waveforms were analysed by calculating a ratio of peak systolic frequency to end diastolic frequency (A/B ratio). An abnormal Doppler result was defined as being above the 97th centile for gestation from our previously derived normal values. Abnormal Doppler results occurred in only 38% of small for gestational age (SGA) infants and in 70% of those developing late decelerations in labour. Doppler ultrasound is a poor predictor of SGA infants, but may identify a high proportion of cases at risk of developing late FHR decelerations in labour.

Blood Flow Velocity↗
PubMed1988

A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity.

1. The effects of vesamicol (2-(4-phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine storage, and its two optical isomers have been studied on neuromuscular transmission in rat and frog muscle, and on nerve conduction in frog nerve. 2. Racemic vesamicol produced a pre-block augmentation of twitch tension that also occurred in directly-stimulated muscle. This effect is thus at least partially due to an increase in muscle contractility. 3. (-)-Vesamicol was approximately 20 times more potent than (+)-vesamicol in blocking twitches elicited at 1 Hz. This degree of stereoselectivity is similar to that measured for inhibition of acetylcholine uptake by isolated synaptic vesicles. Both enantiomers were equally weak in reducing nerve action potential amplitude in frog nerve. 4. Further studies with the active isomer, (-)-vesamicol, showed that, like that produced by racemic vesamicol, the neuromuscular block was highly frequency-dependent. The block was not reversed by choline or neostigmine, but was partially reversed by 4- or 3,4-aminopyridine. 5. Preliminary electrophysiological studies showed that vesamicol reduced miniature endplate potential amplitude in rapidly-stimulated frog nerve-muscle preparations. Addition of lanthanum ions increased the frequency of miniature endplate potentials and led to the appearance of apparently normal-sized potentials amongst those of reduced amplitude. 6. The results show the close agreement between pharmacological and biochemical observations indicating the suitability of the rat diaphragm as a test model for substances of this nature. The degree of reversibility of the vesamicol-induced neuromuscular block by aminopyridines was unexpected, and it is suggested that in the presence of a drug which greatly increases release, a pool of acetylcholine is capable of being released which is not normally releasable after block of storage by vesamicol. It is also considered possible that the results from the intracellular recording studies may be explained in these terms.

Anesthetics, Local↗