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Biomedical subjects

A M Cairns

Publications and source records attributed to A M Cairns.

At least 19 recordsLinked to original sources

The dental practitioner and child protection in Scotland.

OBJECTIVES: To identify from general dental practitioners: undergraduate and postgraduate training experience in child protection; numbers of suspected cases of child physical abuse; reasons for failing to report suspicious cases of child physical abuse; knowledge of local child protection protocols and procedures for referral. MATERIALS AND METHODS: Postal questionnaires were sent to 500 randomly selected general dental practitioners in Scotland, with a further 200 sent to a random sample of the original 500 to increase response rate. RESULTS: Sixty-one per cent (306) of the original 500 questionnaires, and 35% (69) of the second random mail shot of 200 questionnaires were returned. Only 19% could remember any undergraduate training and 16% had been to a postgraduate lecture or seminar in child protection. Twenty-nine per cent of dentists had seen at least one suspicious case in their career. Only 8% of suspicious cases were referred on to the appropriate authorities. Reasons for failure to refer revealed that 11% were concerned about a negative impact on their practice, 34% feared family violence towards the child, 31% feared violence directed against them, and 48% feared litigation. Only 10% of dentists had been sent a copy of the local child protection guidelines on commencing work and only 15% had seen their Area Child Protection Committee (ACPC) Guidelines via any route. CONCLUSIONS: Due to lack of training or clear guidelines for dentists in Scotland, most practitioners were unsure what to do in the event of a suspicion of child abuse. Twenty-one per cent of dentists had encountered suspicious cases but failed to take any action. Dentists overwhelmingly requested appropriate training. This training should address dental competence in assessment of suspicious indicators and involve dentists in inter-agency child protection training.

Adult↗

Injuries to the head, face, mouth and neck in physically abused children in a community setting.

OBJECTIVES: The aims of the present study were to identify the incidence of orofacial injuries found within a cohort of physically abused children, and examine demographic data surrounding the alleged perpetrator, the location in which the alleged assault occurred, the mechanism of injury and the actual orofacial injury incurred. METHODS: The research took the form of a retrospective study of clinical case records of children with suspected physical abuse from 1 June 1998 to 31 May 2003. Seven hundred and fifty case records were identified and 390 (46.7%) were available for data extraction. RESULTS: Fifty-nine per cent (n = 230) of children had signs of abuse on the head, face or neck. The alleged perpetrator was the mother in 104 cases (26.7%), the father in 100 (25.6%) and mother's partner in 49 other cases (12.6%). More than half (53.3%) of the alleged abuse occurred in the child's home; in 32.3% of cases, the location was not recorded. Other locations included outside in a public place, school and at the home of the alleged abuser. Some 23.4% (n = 54) had been punched or slapped around the head, neck or face, 17.4% (n = 40) had been struck by an object, and 15.2% (n = 35) had allegedly sustained multiple modes of injury. Bruising to the head, neck or face was seen in 95.2% (n = 219) of children, and 32.6% (n = 75) had abrasions; 65.2% (n = 150) of the bruises and 22.9% (n = 53) of the abrasions were on the face. CONCLUSIONS: Fifty-nine per cent of physically abused children in the present cohort had orofacial signs of abuse which would be easily visible to a dental practitioner. The commonest injuries were bruises and abrasions. This concurs with previous reports in the literature and highlights the important role of dental practitioners in the recognition of children who have been abused.

Adolescent↗

Determination of a beta(3)-agonist in human plasma by LC/MS/MS with semi-automated 48-well diatomaceous earth plate.

Methods for the determination of a beta(3)-agonist (A) in human plasma were developed and compared based on high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection using a turbo ion spray (TIS) interface. Drug and internal standard were isolated from plasma by three sample preparation methods, liquid-liquid extraction, Chem Elut cartridges and 48-well diatomaceous earth plates, that successively improved sample throughput for LC/MS/MS. MS/MS detection was performed on a PE Sciex API 365 tandem mass spectrometer operated in positive ion mode and using multiple reaction monitoring (MRM). The precursor/product ion combinations of m/z 625/607 and 653/515 were used to quantify A and internal standard, respectively, after chromatographic separation of the analytes. Using liquid-liquid extraction and Chem Elut cartridges, the assay concentration range was 0.5-100 ng/ml. Using diatomaceous earth plates, the concentration range of the assay was extended to 0.5-200 ng/ml. For all three assays, the statistics for precision and accuracy is comparable. The assay accuracy ranged from 91-107% and intraday precision as measured by the coefficient of variation (CV) ranged 2-10%. The sample throughput was tripled when the diatomaceous earth plate method was compared with the original liquid-liquid extraction method.

Adrenergic beta-3 Receptor Agonists↗

High-performance liquid chromatographic methods for the determination of a new carbapenem antibiotic, L-749,345, in human plasma and urine.

A column-switching, reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of a new carbapenem antibiotic assay using ultraviolet detection has been developed for a new carbapenem antibiotic L-749,345 in human plasma and urine. A plasma sample is centrifuged and then injected onto an extraction column using 25 mM phosphate buffer, pH 6.5. After 3 min, using a column-switching valve, the analyte is back-flushed with 10.5% methanol-phosphate buffer for 3 min onto a Hypersil 5 microm C18 BDS 100x4.6 mm analytical column and then detected by absorbance at 300 nm. The sample preparation and HPLC conditions for the urine assay are similar, except for a longer analytical column 150x4.6 mm. The plasma assay is specific and linear from 0.125 to 50 microg/ml; the urine assay is linear from 1.25 to 100 microg/ml.

Anti-Infective Agents↗

Determination of pilocarpic acid in human plasma by capillary gas chromatography with mass-selective detection.

A novel, highly sensitive method for the determination of pilocarpic acid (PA) in human plasma is described. In addition, the method provides for the conversion of the lactone, pilocarpine (P), to PA so that a total drug presence can be determined. Using novel high-performance liquid chromatographic conditions capable of separating P, isopilocarpine (I-P), PA and isopilocarpic acid (I-PA) from each other and from endogenous plasma impurities, it was confirmed that P exclusively and quantitatively converts to PA in heparinized human plasma during storage. For the determination of PA, the selective extraction of PA from protein-free plasma was accomplished using two different solid-phase extraction (SPE) cartridges in two consecutive SPE steps. After extraction, PA was lactonized with trifluoroacetic acid back to P, and both P and an internal standard were acylated using heptafluorobutyric anhydride (HFBA). The trifluoroacetylated derivatives were monitored using gas chromatography (GC) with mass spectrometric (MS) detection. This procedure allowed the sensitive and reliable determination of PA with a limit of quantification (LOQ) of 1 ng/ml, which could not be achieved using previously described methods. The assay was validated in the concentration range of 1 to 10 ng/ml with an intra-day precision (expressed as the coefficient of variation, C.V.) ranging from 9.9 to 0.5%. Inter-day precision for the quality control standard at 2.5 ng/ml showed a C.V. of 10.2%. Accuracy ranged from 94 to 102%. The assay was used to monitor the maximum systemic exposure to P, administered by the ocular route, in terms of total plasma PA (P and PA).

Gas Chromatography-Mass Spectrometry↗

High-frequency oscillation and centroid frequency of diaphragm EMG during inspiratory loading.

Power spectra were derived from the diaphragm electromyogram (EMG) in anesthetized rabbits subjected to inspiratory resistive loading (IRL) with airway pressure swings of 40-60 cm H2O for 20 min to 2 h. Shifts in the centroid frequencies of the power spectra were found to be associated with the appearance of power spectral peaks in the range of 105-140 Hz, termed high-frequency oscillation, or HFO. Such peaks have been described before in phrenic nerve activity and in the diaphragm EMG. However, these peaks have not previously been connected with the shifts in centroid frequency seen during loaded breathing. Although such changes in frequency content have been taken to indicate fatigue in the diaphragm, we find that HFO can also cause a shift in centroid frequency during loaded breathing, an effect whose relation to fatigue has yet to be established.

Air Pressure↗

Phrenic motoneuron firing rates before, during, and after prolonged inspiratory resistive loading.

Phrenic motoneuron firing rates during brief inspiratory resistive loading (IRL) are high, and nearly all the motoneurons are recruited. Diaphragmatic fatigue has been difficult to demonstrate during IRL. Furthermore, evidence from studies in limb muscles has shown variable motoneuron responses to prolonged high-intensity loads. We studied phrenic motoneuron firing rates before, during, and after prolonged IRL in anesthetized rabbits. Of 117 phrenic axons, only 2 axons were not recruited; 41 axons were silent during unloaded breathing but were recruited at higher loads. Silent axons showed a more rapid increase in firing rate as the load increased. Phrenic motoneuron firing rates increased throughout the period of loading, whereas airway pressure swings did not. After prolonged IRL, higher motoneuron firing rates were needed during brief loads to produce the same airway pressure. No evidence of a decline in motoneuron firing rates was seen at any point. We conclude that the respiratory muscles can be shown to demonstrate physiological responses consistent with fatigue during prolonged IRL, and activation rates are high and remain so throughout this prolonged loading.

Action Potentials↗

Enantioselective high-performance liquid chromatographic determination of omeprazole in human plasma.

A new stereoselective HPLC assay was developed to isolate omeprazole enantiomers from human plasma using C2 solid-phase extraction cartridges and an analogue was used as internal standard. Recoveries of the (+)-isomer were 83.4 and 89.7% at 100 and 250 ng/ml, respectively. Recoveries of the (-)-isomer were 78.4 and 82.8%, respectively. Recovery of the internal standard averaged 77.2%. Direct chiral separation of the enantiomers is achieved on a Resolvosil BSA-7 chiral column (15 cm x 4 mm I.D.) and a matching guard column. The mobile phase is a variable amount of n-propanol (0.05-1.0%) in 0.05 M ammonium phosphate buffer (pH 7.0) and the flow-rate is 1.5 ml/min. Drug absorbance is monitored at 302 nm. Standard curves are linear from 15 to 250 ng/ml for each enantiomer. The coefficients of variation for intra-day precision at each concentration over the range of the standard curve were between 0.98 and 10.87%. The coefficients of variation for inter-day precision for the analyses of omeprazole enantiomers in plasma (30 and 175 ng/ml) were less than 10% over a four month interval.

Chromatography, High Pressure Liquid↗

Differential use-dependent (frequency-dependent) effects in single mammalian axons: data and clinical considerations.

The potential clinical scope of use-dependent block of conduction (UDB) was assessed by studying characteristics of UDB in vitro in individual mammalian axons. Single and repetitive stimulation was applied to rabbit cervical sympathetic and vagus nerves exposed to solutions containing lidocaine 0, 0.3, or 0.6 mmol/l (9.1 or 18.2 mg/dl) at 37 degrees C. Unit responses were recorded in dissected filaments or extracellularly in the vagus nodose ganglion. With lidocaine 0.3 mM, equilibrium conduction block, tested by single shocks, was rare. 40-Hz trains produced a significantly greater increase in latency (slowing of conduction) and a much greater incidence of UDB in the sympathetic units than in myelinated vagus axons of equivalent control conduction velocities or in unmyelinated axons. 10-Hz stimulation did not produce UDB. With lidocaine 0.6 mM, the incidence of equilibrium conduction block was too high among sympathetic axons to assess UDB, and significantly higher than among nonsympathetic myelinated and unmyelinated units. The observations support the hypothesis that the differential block of sympathetics observed clinically with spinal anesthesia may be, at least in part, a use-dependent (frequency-dependent) effect. UDB seems unlikely to contribute to local anesthetic block of pain impulses.

Anesthesia, Spinal↗

Lack of size-related differential sensitivity to equilibrium conduction block among mammalian myelinated axons exposed to lidocaine.

This study sought to evaluate the sensitivity of individual, relatively thick myelinated axons of mammalian nerve to equilibrium conduction block by lidocaine, and to compare this to the incidence of conduction block previously measured in individual thinner myelinated axons. The incidence of conduction block by lidocaine 0.3 and 0.6 mM (8.1-16.2 mg/dl) was determined on 35 individual axons in dissected filaments of rabbit recurrent laryngeal nerve (RLN) in which the control conduction velocity ranged from 28 to 77 m/sec. Thirty-four axons (97%) remained excitable in lidocaine 0.3 mM; 2 axons (6%) remained excitable in lidocaine 0.6 mM. These proportions did not differ significantly (P greater than 0.2) from those in thinner axons of vagus, either in comparisons with previous data from extracellular recordings or with new data from filament recordings. The results imply that differential blocks observed under clinical conditions probably depend on factors other than a size-related difference in the minimal equilibrium blocking concentration among myelinated axons. Equilibrium depression of the amplitude of RLN compound action potentials by lidocaine 0.3 and 0.6 mM was disproportionately great relative to the incidence of equilibrium conduction block in individual axons, confirming that depression of the compound action potential is not a reliable measure of nerve conduction block.

Action Potentials↗

Differential margin of safety of conduction in individual peripheral axons.

The relation between fiber size and safety of conduction was tested in vitro on individual afferent axons of rabbit vagus nerve by lowering the external sodium ion concentration and noting the effect on threshold excitability and conduction velocity. Conduction safety of myelinated axons was found to be independent of fiber size and slightly less than among unmyelinated axons. The results are consistent with previous data from the same model, where blocking concentration and diffusion time of lidocaine to the excitable membrane of individual axons also were independent of myelinated axonal size. The evidence from these single-unit studies implies that the differential blocks of functional modalities observed with spinal and epidural anesthesia probably do not arise from fiber size-related differences in susceptibility to block: possible alternatives are mentioned briefly.

Animals↗

Differential effect of nerve fiber structure on block by local anesthetic.

The incidence of conduction block by lidocaine 0.3 mmol/l (8.1 mg/dl) in several successive lengths of individual afferent axons of rabbit was compared. The conduction velocity of the axons was either "slow," "intermediate" (1.3-4 m/s), or "fast." The "intermediate" group showed a higher incidence of proximal acceleration of conduction (P less than 0.001) and a greater incidence of block (P less than 0.001) than the "slow" and "fast" fiber groups. The results were interpreted as indicating that the fibers of the "intermediate" group had an unmyelinated peripheral and a myelinated proximal length, with a junctional heminodal region that was the seat of the high sensitivity to block. The potential clinical significance of the observation is discussed in terms of the known distribution of heminodes in the peripheral nervous system.

Anesthetics, Local↗

Differential slowing and block of conduction by lidocaine in individual afferent myelinated and unmyelinated axons.

The study of compound action potentials has not succeeded in determining exact limits to differential block of nerve fibers by local anesthetics. Further observations on individual neurons therefore were undertaken. Rabbit vagus nerve and ganglion were superfused in vitro at 37 degrees C, pH 7.4. Activity evoked by stimulating the distal end of the nerve was monitored extracellularly from individual somata by a microelectrode in the ganglion. Lidocaine HCl in steps of 0.2-0.1 mmol/l (0.0005-0.0025 g/dl) was applied to the intervening nerve to identify two concentrations, respectively, just sparing and extinguishing conduction in the axon belonging to the soma, the average being regarded as the blocking concentration. The mean blocking concentrations (mM, +/- SD) for axons conducting at control velocities between 3 and 26 m/s (myelinated axons) was 0.43 +/- 0.15, N = 18, for axons slower than 1.4 m/s (unmyelinated axons) 0.63 +/- 0.14, N = 11, for intermediate velocity axons 0.19 +/- 0.18, N = 7. The differences were significant by Scheffé's multiple comparisons test (P less than 0.01). Although the myelinated axons were blocked by a lower average concentration of lidocaine than unmyelinated axons, they manifested significantly more slowing of conduction before block (P less than 0.001). No relation between blocking concentration or latency increase and conduction velocity (fiber size) was evident within any fiber group.

Animals↗

Diffusional delay in local anesthetic block in vitro.

The diffusion of lidocaine to myelinated and unmyelinated axons was compared on individual afferent fibers of rabbit vagus nerve. The criterion consisted of the time required for more than 95% completion of the asymptotic increase in impulse conduction time produced by a weak, nonblocking concentration of lidocaine. Measurements on sheathed and desheathed nerves for both myelinated and unmyelinated axons detected an apparent but statistically not significant diffusional lag at the perineurial sheath, averaging four minutes in this model; there was no significant difference in the mean time for attainment of criterion in myelinated and unmyelinated axons, which averaged an additional 13 min in both types of fiber. From these observations the authors conclude that lidocaine diffused as readily through the nodal gap to the excitable membrane of the myelinated fiber as through the Schwann cell mesaxon to the unmyelinated fiber. Thus differential diffusion within a nerve seems unlikely to be a contributing factor to clinical differential block.

Anesthetics, Local↗

Differential vulnerability of large and small mammalian myelinated fibers to glucose lack.

The excitability of A fibers of peripheral nerves in vitro is more susceptible to depression by energy lack than is excitability of C fibers. Whether there is also a differential vulnerability between small myelinated A delta fibers that conduct fast pain and large myelinated A beta fibers is unclear. We evaluated the relative abilities of A beta and A delta fibers to withstand energy lack in rabbit vagus nerve by measuring the amplitudes and latencies of the compound action potentials during incubation in glucose-free Ringer's-bicarbonate solution. We also evaluated the reversibility of the effects after returning the nerves to glucose containing solution. We found that A delta fibers are more susceptible to such energy lack and recover from it less completely than A beta fibers.

Action Potentials↗

A new approach to differential peripheral nerve fiber block: Na+,K+-ATPase inhibition.

Differential block of peripheral nerve fibers was attempted in vitro by a new approach based on inhibiting the membrane pump with ouabain. Sequential concentration dependent extinction of the components of the compound action potential was obtained: C extinguished first, A delta next, A beta last. The sequence conforms to expectations based on axonal size. Because pain is mediated by C and A delta fibers, and block of these groups by ouabain was not reversed readily, further investigation of the practicability of the new approach seems warranted.

Action Potentials↗