Search PubMed⌕ Search

Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 19 recordsLinked to original sources
PubMed1995

Long-term sensory hyperinnervation following neonatal skin wounds.

Skin innervation during wound healing was investigated using immunocytochemical staining with the panneuronal marker antiprotein gene product (PGP) 9.5, which labels the entire innervation of the skin throughout development and in the adult. Full-thickness skin wounds in the hairy skin of the foot in neonatal rats result in pronounced hyperinnervation of the tissue that persists long after the wound has healed (at least 12 weeks). Quantification of this hyperinnervation by image analysis indicates that skin innervation density in the wounded area can increase up to 300%. The effect is greatest when wounds are performed at postnatal day (P) 0 or 7, declining when performed at P14 and P21 to resemble the weaker and transient effect in the adult. Staining with selective markers for different neuronal populations innervating skin (monoclonal anti-RT97 staining the myelinated axons of large light sensory ganglion cells; anticalcitonin gene-related peptide staining unmyelinated C axons, thinly myelinated A delta axons, and a subpopulation of large A fibres) reveal that both A- and C-fibre sensory axons contribute to this response. Destruction of the majority of the C-fibre population with neonatal capsaicin pretreatment, which leaves large A fibres intact, significantly reduces the hyperinnervation response at 14 days, confirming a major contribution from both A and C fibres. Sympathetic axons, stained with anti-tyrosine hydroxylase, do not sprout into the wounded area. Furthermore, pretreatment of neonates with 6-hydroxydopamine, which destroys the sympathetic innervation, does not significantly reduce the overall sprouting response, as identified by anti-PGP9.5 staining. Behavioural sensory testing revealed a 50% drop in the mechanical threshold in the wounded area after 3 weeks. These remarkably long-term and specific effects on sensory terminal axons following neonatal skin wounding indicate the plasticity of cutaneous innervation density following alterations in the target tissue at a critical stage of development.

Aging↗
PubMed1995

Patient decision-making in relation to extensive restorative dental treatment. Part II: Evaluation of a patient decision-making model.

A theoretical model was proposed and tested to evaluate some of the factors involved in patients' decisions to undergo extensive restorative dental treatment. This model incorporates aspects of the environment within which the decision occurred (the patient/provider relationship, social influence and the role of cues in initiating treatment) and internal values held by the individual (perceptions of value of and barriers to treatment). Value of treatment was measured using aesthetics, function, health motivation and self-esteem. Barriers to treatment included fears and anxieties about treatment, the costs of treatment, the time involved in obtaining treatment and access to care. Data were collected by mailed questionnaire from 188 patients at a North American state university dental school who had received over $1,500 of restorative dental treatment during 1990/91. Data were analysed using path analysis multiple regression. The most important determinant in the decision to undergo treatment was patient/provider relationship. As expected, barriers exerted an inverse effect upon the outcome and had twice the influence compared with the patients' perceived value of treatment. Cues and social influence were not shown to play a significant role in initiating restorative dental treatment.

Adult↗
PubMed1995

Patient decision-making in relation to extensive restorative dental treatment. Part I: Characteristics of patients.

This paper presents descriptive and demographic data gathered in response to a mailed questionnaire of 188 patients at the University of Michigan School of Dentistry who had incurred costs of at least $1500 on restorative dental treatment between January 1990 and december 1991. The development and testing of the behavioural model used is described in part II. Descriptive information included primary reason for treatment, cues to treatment, previous attendance, aspects of the patient/practitioner relationship, treatment costs, satisfaction with appearance and insurance coverage.

Adult↗
PubMed1995

Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold.

The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e., > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.

Brain↗
PubMed1994

Nerve growth factor levels in developing rat skin: upregulation following skin wounding.

Levels of nerve growth factor (NGF) in rat hindpaw skin, measured with a sensitive two-site enzyme-linked immunosorbent assay, show two peaks during normal development. The first (57 +/- 5 pg mg-1) occurs at embryonic days (E) 18-20 and coincides with the arrival of axon terminals into the hindpaw skin. The second, larger peak (132 +/- 10 pg mg-1), occurs later, around postnatal day (P) 21 and may be involved in maintenance of neuronal phenotype. Levels outside the two peaks stay relatively constant throughout development (30 pg mg-1). Skin wounding at birth produces a marked increase in NGF levels (149 +/- 25 pg mg-1) which declines after 4 days. This large increase is not observed if wounding is performed at older ages and may underlie the sensory hyperinnervation that accompanies neonatal wounds.

Aging↗
PubMed1994

Dorsal root ganglion cell death and surviving cell numbers in relation to the development of sensory innervation in the rat hindlimb.

This study correlates the numbers of dying, surviving and proliferating L4 primary afferent neurons with the development of peripheral hindlimb sensory innervation in the rat. Cell death occurs from embryonic day 15 (E15) to just after birth and peaks at E17-E19. Despite this, surviving cell numbers rise steadily to birth indicating that cell death is more than balanced by cell proliferation over this period. GAP-43 immunostaining indicates that the peripheral sensory axons are only in central parts of the hindlimb by E15 and do not finish arriving at their distal peripheral targets until birth so prenatal cell death in the L4 ganglion is not well correlated with the development of the peripheral innervation by these primary sensory axons. Prenatal cell death does, however, correlate well with the innervation of the cord by central sensory axons. In contrast to the steady rise of surviving cell numbers from E15 to birth, cell numbers go down 16% in the period from birth to postnatal day 5. This loss is correlated with the development of the peripheral innervation. We conclude that the bulk of cell death in the rat L4 dorsal root ganglion, which is prenatal, is controlled by local or central factors whereas peripheral target factors may exert their influence postnatally to determine the final numbers of mammalian sensory neurons. The data also suggest that there may be two phases of cell death, an early phase involving large light cells and a late phase involving small dark cells.

Aging↗
PubMed1994

Developmental changes in the laminar termination of A fibre cutaneous sensory afferents in the rat spinal cord dorsal horn.

In order to establish the specificity of growth and termination of dorsal root afferents within the developing spinal cord, the central dorsal horn terminals of myelinated sensory afferents were labelled at various stages in the rat from embryonic day (E)18 through to postnatal day (P) 35 using horseradish peroxidase conjugated to choleragenoid (B-HRP). The preferential labelling of A fibre afferents with this tracer was found to be as clear in the neonate as has been reported for the adult. The results show that while the somatotopic arrangement of A fibre afferent terminals in the dorsal horn is established early in development, the laminar projections are not. Following peripheral nerve or local skin injections of B-HRP, A fibre terminals were found to project throughout laminae I to V, including lamina II (substantia gelatinosa). This widespread termination was observed consistently until the end of the third postnatal week. After P22 the terminal field becomes restricted to the normal laminae III to V.

Animals↗
PubMed1994

Inositol 1,4,5-trisphosphate receptor function in neonatal cardiomyocytes.

We have previously reported that the metabolism of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) is altered when rat neonatal ventricular cardiomyocytes are isolated and cultured. In the current study we show that the mass content of Ins(1,4,5)P3 is lower in the isolated cells than in the intact tissue. However, the properties of the Ins(1,4,5)P3 receptors were not different in the two preparations and the isolated cells remained insensitive to Ins(1,4,5)P3 in terms of 45Ca2+ release. Thus, despite the altered pattern of metabolism of Ins(1,4,5)P3 in isolated neonatal cells, the properties of the receptors were similar to those reported in other myocardial preparations.

Animals↗
PubMed1994

Of sound mind.

Explore the source record for details and available documents.

Humans↗
PubMed1994

Neonatal sciatic nerve section results in a rearrangement of the central terminals of saphenous and axotomized sciatic nerve afferents in the dorsal horn of the spinal cord of the adult rat.

Previous studies have shown that following neonatal peripheral nerve injury, adjacent intact myelinated and unmyelinated primary afferents sprout into the central denervated terminal area. The present study investigates this in more detail and goes further, to study the fate of the central terminals of the surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B-HRP), to label the A fibres, or wheatgerm agglutinin (WGA-HRP), to label C fibres were employed to investigate the central consequences of sciatic nerve section and ligation on the day of birth, in adult rats. Bulk labelling of the axotomized sciatic or intact saphenous nerve with either tracer and comparison with contralateral controls revealed alterations to the terminal field. The intact saphenous nerve terminal field expanded caudally from mid L4 to the L4-L5 boundary when labelled with WGA-HRP and to the sacral cord when labelled with B-HRP. Labelling the axotomized sciatic nerve with either tracer revealed little change in the overall somatotopic organization of central terminals, although labelling was less intense compared to control nerves and more variable with WGA-HRP. Invasion of the substantia gelatinosa (SG) by axotomized A fibres was observed in segments L3-5, into the area occupied by axotomized C fibres. This area was also invaded by intact saphenous A fibres in the L4-5 segments. These results demonstrate that following neonatal nerve section: (i) axotomized primary afferents are able to retain a 'normal' somatotopic map in the rostrocaudal plane; (ii) both A and C fibres from adjacent intact nerves sprout into the denervated territory, but A fibres sprout further caudally; (iii) axotomized A fibres and invading intact A fibres both sprout dorsally into denervated SG. As a result, there is considerable overlap between nerve territories in denervated spinal cord, suggesting that competition for laminar termination sites exists between A and C fibres and also between axotomized and intact primary afferents.

Animals↗