Biomedical subjects
Publications and source records attributed to M Fitzgerald.
Lyso-PAF was detected after ionophore challenge in the effluent of lungs of guinea-pigs exposed to oxygen and perfused through the pulmonary circulation as well as of control lungs perfused through the airways. Lyso-PAF is probably the inactive metabolite of PAF-acether which could not, itself, be detected in the lung effluents.
The sciatic nerve was sectioned unilaterally in rats and nerve growth factor (NGF) applied locally to the nerve stump for the following 10-14 days using an indwelling osmotic pump. The aim of the experiment was to test whether NGF had any effect on the previously reported neurophysiological and neurochemical events that occur central to a peripheral nerve lesion. The method of application allowed the sciatic nerve on the other side to be used as a control. Primary afferent depolarization fell, as expected, to 13% of its control value after chronic nerve section but if NGF was administered it fell to only 43.5% of control. Chronic nerve section is also known to result in expansion of the receptive fields of deafferented dorsal horn cells. NGF treatment reduced the number of such large receptive fields by 50%. The normal depletion of fluoride resistant acid phosphatase from the cut nerve terminals in the dorsal horn did not occur following NGF treatment. Radioimmunoassay of substance P revealed that the 30% reduction in dorsal horn levels that follows chronic sciatic nerve section did not occur when NGF was applied and that the accompanying 60% decrease in dorsal root ganglion levels was changed to a 64% increase by NGF. The results show that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation.
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Four adult Rhesus monkeys provided 120 teeth for buccal Class V cavities. Twenty-nine were non-exposed controls and 91 were exposed for 3 intervals. All 120 teeth were capped with a hard set Ca(OH)2 medicament, restored with amalgam, 57 evaluated after 1 year and 63 after 2 years. Of the 91 exposed pulps, 45 showed complete healing, 25 showed pulpal inflammation varying from acute to chronic, 12 showed severe pulpal breakdown and abscess formation and 9 were necrotic. No difference was observed in the healing response between the 3 exposure times. New hard tissue formed at, or subjacent to, the medicament in 77 of 91 exposed pulps with a tunnel defect frequently present, running from the medicament interface to the pulp. This study demonstrates that recurring pulp inflammation observed after 1 & 2 year direct pulp capping, is associated with bacterial contamination.
The responses evoked in lumbar dorsal horn cells by both natural and electrical hind-limb skin stimulation were recorded in the spinal cord of rat pups aged 0-15 days under urethane anaesthesia. The input volley was recorded on the L4 dorsal root and consisted of two separate waves from birth. Latency and threshold measurements were consistent with these two waves being immature A (myelinated fibre) waves and C (non-myelinated fibre) waves. On the first 3 days of life background activity of cells in the dorsal horn was low and evoked discharges were sluggish. On electrical stimulation of the skin, neonatal dorsal horn cells frequently responded with only 1 or 2 impulses per input volley with long central delays of up to 20 ms. Synaptic linkage appeared weak and many cells failed to follow stimulation rates of 5 Hz. Natural skin stimulation showed that the majority of cells at days 0-3 responded to pinching the skin only. The development of responses evoked by C fibres in the dorsal horn was delayed compared to that of responses evoked by A fibres. Short and long latency responses corresponding to the early A and late C afferent input volleys could be recorded in the superficial laminae (I, II and III) of the dorsal horn from day 0, but in the deeper laminae only early short latency A responses were evoked until the age of day 7-8. After this time, a long latency C response also appeared and increased in strength with age. Convergence of low and high threshold inputs onto dorsal horn cells was rare at birth but increased gradually over the following two weeks. Receptive field areas, mapped by natural mechanical stimulation of skin, were large at birth and decreased in size with age. At birth the mean receptive field area was 14.2% of the total hind-limb area whereas at day 15 it was 3.6%. This fall in size was particularly marked in cells of the deep dorsal horn. Pinching or brushing the receptive field of many neonatal dorsal horn cells resulted in long-lasting after-discharges (30-90 s) which on days 0-3 could be more pronounced than the initial evoked response. The duration and amplitude of these responses decreased with age. Repetitive electrical skin stimulation of the receptive fields of these cells produced 'wind-up' and prolonged after-discharge. Ipsilateral, contralateral and distant inhibitory components to receptive fields were observed from day 0.(ABSTRACT TRUNCATED AT 400 WORDS)
A consecutive series of 95 3 to 4 year old and 43 7 to 11 year old children attending surgical, and medical outpatient clinics was studied, using questionnaires that measured behavioural deviance and had adequate reliability and validity for screening populations of children. A control group was also studied in the 7 to 11 year old sample. Depressive symptoms in the mothers of the children were determined using the Wakefield depression inventory. There was considerable behavioural deviance in children attending the outpatient clinics; 44% of the 7 to 11 year olds who were surgical outpatients had deviant scores. Thirty two per cent of mothers of medical outpatients had deviant scores on the depression inventory. These findings have relevance for the approach paediatricians take to their outpatients.
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The postnatal development of sensory C fibre function was investigated in neonatal rats aged 1-21 days. From birth, flexor-withdrawal reflexes (measured from the hamstring electromyograph) to pinching and heating the skin of the hindfoot were easily recorded under light anaesthesia and in fact were exaggerated in amplitude and duration compared to adult responses. Flexor reflexes to irritant chemicals, however, were not present until day 10-11 of life. In parallel with this late development of specific chemical sensitivity, neurogenic oedema, a C fibre-mediated inflammatory reaction, also did not occur until day 11. Substance P and fluoride-resistant acid phosphatase histochemistry were used to investigate the neurochemical development of sensory C fibres. Substance P was present in the skin, nerve, dorsal root ganglion and spinal cord from birth and fluoride-resistant acid phosphate within 12 h of birth. The adult neurochemical appearance of C-fibre terminals in the dorsal horn was established in a few days. The results show that despite the apparent early anatomical and neurochemical maturity of C fibres, physiological function is not fully established until the second week of life.
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Vinblastine, a transport blocker, was applied locally to the sciatic nerve in rats. It was found to be a powerful neurotoxin with a dose-dependent action, destroying all afferents at doses of 5 X 10(-4)M, primarily C fibers at intermediate doses of 2.5 X 10(-4)M, and only at a critically low dose of 10(-4)M was a degeneration-free axon transport blockade, lasting for 4 to 5 days, produced. Such transport block failed to alter thermal responsiveness of the rats as measured behaviorally, by the flexor reflex, or by dorsal horn cell responses. It did, however, significantly reduce both the chemical sensitivity of the C afferents and their ability to produce neurogenic edema. This began 24 hr after treatment and lasted 4 to 5 days. Therefore, it is likely that these functions are dependent on the continuous transport of some compound to the axon terminals from the cell body. This low concentration of local vinblastine treatment also resulted in depletion of fluoride-resistant acid phosphatase from C fiber terminals in the dorsal horn of the spinal cord. Transmission from C fibers to second-order neurons in the spinal cord, however, was totally unaffected. Substance P levels in the spinal terminals was largely unaffected, although in 1 of 5 cases there was depletion. It appears, therefore, that some, but not all, retrograde changes in sensory neurons following peripheral nerve damage can be mimicked by blockade of axon transport. The effects following vinblastine treatment are compared to other peripheral nerve manipulations, such as cut, crush, and application of local capsaicin.
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A study was carried out to determine at what stage of development the adult pattern of primary afferent projections to the substantia gelatinosa (SG) is first established. Horseradish peroxidase conjugated wheat-germ agglutinin (WGA-HRP) was applied to cut ends of sciatic nerves at mid-thigh level in adult and neonatal rats aged 1-16 days. The distribution of transganglionically transported label in primary afferent terminals in SG was reconstructed from transverse sections of spinal cord segments L1 to S1. The distinctive U-shaped projection field of the sciatic nerve in SG of the adult was found to exist in miniature form already in the second postnatal day 24 h after WGA-HRP had been applied. The highly specific somatotopic projections of primary afferents to SG are probably established before birth. Any delay in the maturation of functional specificity in the dorsal horn of the neonate cannot be attributed to the absence or disorganization of anatomical projections to SG of primary afferent inputs.
The physiological properties of neurones in the superficial laminae of the dorsal horn of the fourth and fifth lumbar segments of the rat spinal cord have been investigated in decerebrate spinal animals. Both extracellular recordings with platinum-plated tungsten microelectrodes (n = 72) and intracellular recordings with glass microelectrodes (N = 79) were made. Attempts were made to fill cells intracellularly with horseradish peroxidase or Lucifer Yellow. Thirty-seven percent of the intracellularly injected neurones were recovered after histological processing and their cell bodies found to be in lamina 1 or 2 and in the dorsal white matter overlying lamina 1. The dendritic spread of the stained neurones was maximal in the rostrocaudal plane with a restricted mediolateral spread. The physiological properties of the extracellularly recorded units, the intracellularly unidentified units, and the intracellularly stained units were the same. The neurones were characterized by low background activity and all had excitatory receptive fields on the lower limb. Some neurones responded only to low-threshold mechanical stimulation of the skin or only to noxious skin stimulation but the majority of units (58%) were wide-dynamic-range cells responding to both types of stimuli. Receptive field classification was made questionable, however, by the existence of cells (9%) that exhibited a spontaneous shift in the size of their receptive fields and in the type of stimulus that elicited a response. The neurones in the superficial dorsal horn commonly showed a marked inhibition to repeated cutaneous stimuli (27%) or a prolonged afterdischarge followed a single stimulus (20%). Afferent input from the sural nerve was found to be from A and C fibres in both extra-and intracellular recordings. A delta- and C-mediated excitations were most common although convergent inputs from A beta-fibres occurred in 40% of units. No correlation was found between cell structure or distribution of dendritic fields and physiological properties in our small sample of intracellularly stained cells. The morphology of the cells was highly diverse, as were the different receptive fields. There was, however, some correlation between the location of cell bodies and their responses. Neurones responding only to low-threshold stimuli were distributed either in the dorsal white matter or in inner lamina 2. Wide-dynamic-range cells were distributed throughout the superficial dorsal horn. These results suggest that neurones of different shapes and positions may subserve the same function and, conversely, that neurones of the same shape and position may subserve different functions.
Stimulation of high threshold A delta and C fibre peripheral afferents inhibits dorsal horn cells on the other side of the spinal cord. The substantia gelatinosa (SG) is an area full of interneurones known to have commissural connections across the spinal cord. The role of SG in this contralateral inhibitory pathway is investigated here. Forty-three SG cells were recorded in the lumbar dorsal horn of decerebrate spinal rats. Their ipsilateral excitatory receptive fields and responses to sciatic nerve stimulation were recorded. Repetitive electrical stimulation was then applied to the contralateral sciatic nerve. Eight (19%) units were excited by such stimulation. A brief tetanus was followed by an increase of ongoing activity lasting 30 s to 10 min. These cells did not, however, have excitatory contralateral fields. A small separate group of 4 cells (9%) were mildly inhibited by heating or pinching the contralateral limb. The significance of contralateral excitation of some SG cells is discussed in the light of the predominantly inhibitory contralateral effect on dorsal horn cells in laminae 4 and 5. It is suggested that some SG cells may be inhibitory interneurones in their effect on deeper cells.
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Four groups of normal human subjects were tested for their ability to reduce frontal muscle tension levels during presentation of veridical auditory biofeedback or auditory pseudofeedback. A double-blind methodology was used. Three groups of subjects assigned to the pseudofeedback conditions received a feedback signal that was not contingent on EMG activity but that followed one of three different patterns. One group received a truly random signal, the second received a signal that gradually increased in frequency (apparent failure), and the third received a signal that gradually decreased in frequency (apparent success). Dependent measures included both physiologic (frontal and neck EMG) and subjective reactions to the relaxation task. The different patterns of pseudofeedback did produce reliably different subjective responses, suggesting that the manipulations succeeded in producing unequal nonspecific effects that were unrelated to the feedback contingency specifically. However, these differential subjective effects were not strongly reflected in the physiologic responses since the differences in EMG levels among the four groups did not differ significantly at any stage of training. An analysis of the integrity of the double-blind procedure showed that although experimenters were effectively kept blind to group assignment, subjects' responding suggested a response bias as well as the possibility that the double-blind was breached. The utility of the double-blind methodology in biofeedback experiments is discussed and suggestions for future research are offered.
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