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Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 91 records · Page 5Linked to original sources

Morphology and somatotopic organization of the central terminals of hindlimb hair follicle afferents in the rat lumbar spinal cord.

The morphology of the central collateral arborizations of 24 A-beta hair follicle afferents (HFAs) innervating different regions of the skin of the hindlimb were studied by the intra-axonal injection of horseradish peroxidase (HRP) in adult rats. A total of 236 collaterals were recovered. These fell into three classes--complex, simple, and blind-ending--based on numbers of boutons and terminal branch patterns. The morphology of the HFA central arbors innervating the lateral and medial leg and dorsum of the foot was flame-shaped. Afferents with receptive fields on the glabrous-hairy skin border consistently had extra terminal branches running ventromedially into laminae IV/V. Differences in the width of terminal arbors were found. HFA terminals innervating the lateral leg formed narrower sheets than those innervating the dorsum of the foot and toes. The somatotopic organization of the collaterals and terminal arborizations of individual afferents were analyzed both by considering all the collaterals along an axon's rostrocaudal extent and by only examining arbors with boutons (the complex and simple arbors). Thirty-seven percent of blind-ending and 18% of simple collaterals were found to overlap in the rostrocaudal direction with the complex arborizations of afferents whose receptive fields were in a different cutaneous nerve territory. There was no overlap between complex arborizations of afferents from different nerve territories. However, the complex arbors of afferents with receptive fields within a particular nerve territory showed considerable terminal overlap even if they had nonadjacent peripheral receptive fields. The topographical organization of the central terminals of HFAs, forms a coarse somatotopic map of overlapping terminals whereby a particular region of dorsal horn has a maximal, but not exclusive, input from a particular area of skin.

Action Potentials

Cardiac transplantation in the seventh decade of life.

Twenty-five patients older than 60 years of age underwent cardiac transplantation using an immunosuppression protocol with cyclosporin and azathioprine, but without routine use of oral steroids. There were 24 men and 1 woman (age range 60 to 69 years, mean 63). The etiology of heart disease was coronary artery disease in 21 and idiopathic dilated cardiomyopathy in 4. Six patients had previous coronary artery bypass operations, 1 had undergone repair of an abdominal aneurysm and 1 had pulmonary embolism. Sixteen patients were in New York Heart Association class IV and 9 in class III. Donor mean age was 30 (14 to 46) years. Hospital stay after transplantation was 10 to 90 days (median 11). Four died within 30 days and none from 5 to 59 months (mean 22). The 1-year actuarial survival was 84%. The incidence of rejection was 2.16 episodes per patient. Only 1 patient (4%) had serious infection. Six patients received antihypertensive treatment, 3 had reversible impairment of renal function, 2 had gout and 1 had drop foot. No patient had convulsions, transient ischemic attack or cerebrovascular accident. None had significant psychological problems. The 21 patients currently alive are in New York Heart Association class I. Quality of life, assessed by the Nottingham Health Profile, showed marked improvement. It is concluded that the initial results of cardiac transplantation in the seventh decade of life are encouraging.

Actuarial Analysis

Marital adjustment and behaviour problems in children.

Previous research has suggested links between marital unhappiness and behaviour problems in children. A survey was carried out in a community based Child Psychiatric clinic in Ireland to investigate these links. Methods used involved self report questionnaires administered to mothers of forty-eight children attending the clinic. A control group was selected for comparison. Tests of correlation indicate significant associations between marital adjustment and behaviour problems for both clinic and control populations. Some possible mechanisms are suggested.

Adolescent

A study of emotion and behaviour in children attending a normal school in an urban area.

Anxiety, depression, self-esteem, behavioural deviance and prosocial behaviour were studied in children attending a normal school in a disadvantaged urban area, using self-rated and teacher-rated questionnaires. The prevalence of depression was rated as 5%. 15% described frequent suicidal thoughts. 40% scored as behaviourally deviant. Significant correlations were found between the variables studied. The rates of depression and behavioural deviance were higher than in comparable British populations.

Child

Differences in the chemical expression of rat primary afferent neurons which innervate skin, muscle or joint.

The fluorescent dye Fast Blue was injected in anaesthetized rats into either skin, muscle or knee joint of the hindlimb. Following retrograde transport of the dye to lumbar dorsal root ganglia, the cell bodies of primary afferent neurons innervating these different target tissues were identified in ganglion sections by fluorescence microscopy. The sections were processed to demonstrate activity of the enzyme thiamine monophosphatase, or immunoreactivity to calcitonin gene-related peptide, substance P, or somatostatin, in Fast Blue labelled neurons. In all cases immunoreactivity to the antineurofilament antibody RT97 was used to classify dorsal root ganglion cells as being either small dark (RT97 negative, unmyelinated axons) or large light (RT97 positive, myelinated axons). The proportion of small dark cells labelled from each target decreased in the order: skin, muscle, joint. Thiamine monophosphatase and somatostatin were present only in small dark cells, while calcitonin gene-related peptide and substance P were found in both small dark and large light cells. In large light cells of all three targets, more contained calcitonin gene-related peptide than substance P. Among small dark cells, thiamine monophosphatase and somatostatin were found predominantly in skin afferents, while calcitonin gene-related peptide and substance P were more common in muscle and joint afferents. The chemical expression of primary afferents is therefore characteristic of the peripheral target they innervate. This could reflect either a maintained influence of the target on the afferents, or the factors which operate only during development.

Animals

Primary cardiac tumours--is there a place for cardiac transplantation?

Between 1979 and 1985, seven patients (five children and two adults) were treated for primary cardiac tumours other than benign atrial myxomas. There were five malignant neoplasms (two non-classifiable sarcomas, one haemangiosarcoma, one histiocytoma and one neurofibrosarcoma) and two benign tumours (fibromas). Echocardiography, cardiac catheterisation, computed tomography and magnetic resonance imaging provided diagnostic confirmation. The two patients with fibroma are alive and well 4 and 5 years after radical resection of the tumours from the interventricular septum. The patient with a neurofibrosarcoma underwent orthotopic cardiac transplantation and is well 5.5 years postoperatively with no evidence of residual disease or recurrence. One patient died awaiting a donor heart for transplantation. Another patient who was a candidate for heart and lung transplantation was found to have an unresectable tumour at the time of operation. One patient with sarcoma who underwent a successful emergency partial resection for relief of cardiac tamponade died 18 months later from widespread metastases. The seventh patient was inoperable due to multiple secondaries. It is concluded that radical resection of large, benign, cardiac tumours can give good results and that early cardiac transplantation probably offers the only hope for patients with malignant tumours of the heart.

Adolescent

Rheumatoid factors in cystic fibrosis: associations with disease manifestations and recurrent bacterial infections.

Serum IgM and IgA rheumatoid factor (RF) levels were measured by ELISA in 71 adolescent and adult patients with cystic fibrosis (CF) and 69 control subjects. IgM RF values from 15 (21%) CF patients greater than 2 s.d. of control subjects (P less than 0.001). Elevated IgM RF values were significantly associated with worse spirometric measurements of pulmonary function (P less than 0.01) and with more frequent exacerbations of respiratory tract infection (P less than 0.001). A characteristic episodic arthropathy occurred in 27% of IgM RF positive patients, compared with 4% of IgM RF negative patients (P = 0.015). IgA RF values from 26 (37%) CF patients were elevated (P less than 0.001). Pulmonary function was significantly worse in patients with elevated IgA RF values (P less than 0.001). However, IgA RF was not associated with exacerbations of respiratory tract infection or episodic arthropathy. Both IgM and IgA RF values correlated significantly with their corresponding Ig levels, suggesting that RF synthesis was the result of polyclonal B cell activation. It is concluded that serum IgM RF values in CF are associated with worse lung disease and recurring bacterial antigenic stimulation. IgM RF may contribute to the development of arthropathy in some patients. Induction of IgA RF synthesis and its pathogenic potential may differ from IgM RF.

Adolescent

The effect of neonatal peripheral nerve section on the somadendritic growth of sensory projection cells in the rat spinal cord.

Sciatic nerve section and ligation on the day of birth results in marked growth retardation of the rat dorsal horn. This transneuronal effect was examined in spinal cord cells that project to the brain by retrograde labelling with HRP from contralateral dorso- and ventrolateral tracts in the thoracic white matter. HRP-impregnated gel pellets were implanted in the tracts for 48-72 h to allow intense somadendritic staining of the projection cells. The results show that cells in rats whose sciatic nerve has been sectioned at birth have a mean somal area that is 40% smaller than controls. Primary dendrites are reduced from a mean of 4.1 per cell to 3.1 per cell and secondary branching is reduced by 75%. The results suggest that there was no actual cell death, only growth retardation. An intact primary afferent input apparently has a strong transneuronal trophic influence on spinal cord sensory cells projecting to the brain.

Animals

The development of activity evoked by fine diameter cutaneous fibres in the spinal cord of the newborn rat.

The cutaneous afferent volley on the dorsal root was recorded in normal rat pups and in pups whose fine diameter afferents had been destroyed with capsaicin at birth. From postnatal day 2 (P2) it was possible to identify a long latency wave in the afferent volley that was reduced or absent in capsaicin treated pups and therefore attributable to A delta and C fibers. Despite this, no difference between the evoked activity of dorsal horn cells to electrical skin stimulation in normal and capsaicin treated rat pups could be detected at P2 or P5. Only at P9 was a clear long latency burst of spikes evoked in dorsal horn cells that was absent in capsaicin treated rats. The results support the idea that the postsynaptic activity evoked by small diameter A and C fibres in the rat dorsal horn in the first postnatal week is very immature.

Action Potentials

Postnatal development of the cutaneous flexor reflex: comparative study of preterm infants and newborn rat pups.

Cutaneous flexor reflex thresholds have been used as a measure of somatosensory function: the authors measured threshold in preterm infants and newborn rat pups. Preterm infants of less than 30 weeks postconceptional age (PCA) had very low thresholds of less than 1.0 g, but by 37.5+ weeks PCA thresholds were equivalent to those in normal term babies, although these are still well below adult levels. Newborn rat pups also have very low flexor reflex thresholds, which do not approach adult levels until four postnatal weeks. Repeated stimulation of the foot in preterm babies resulted in sensitization of the flexion reflex up to about 32 weeks PCA. After that age repeated stimulation resulted in habituation, as is observed in the adult. Sensitization also occurred in newborn rat pups, which changed at four postnatal weeks to habituation. The results demonstrate the sensitivity of spinal reflexes to cutaneous inputs in the neonate and it is argued that this results from lack of inhibitory control in the immature spinal cord.

Animals

Differences in the bioactivity of recombinant human TNF, LT, and T-cell-derived LT-3 on transformed cells in vitro and the Meth A tumor growing in BALB/c mice.

Cytolytic human T cells and the continuous human T cell line YM 1.2 can secrete a lymphotoxin (LT) form, termed LT-3, when stimulated in vitro. LT-3 is immunologically related to, but functionally distinct from, both alpha LT and tumor necrosis factor (TNF). Purified, native LT-3 and recombinant human LT and TNF were tested for their ability to destroy a panel of primary and continuous cell lines in vitro and cause necrosis of 8- to 9-day cutaneous Meth A tumors growing in BALB/c mice. LT-3 is more effective than either LT or TNF in inducing destruction of continuous cell lines in vitro. LT-3 induces destruction of cell lines that are resistant to both TNF and LT, and much less LT-3 is required to destroy cells that are LT and/or TNF sensitive. In contrast, none of these mediators had any measurable negative effects when tested on primary human fibroblasts. Additional studies revealed that LT-3 is also active in vivo and can cause necrosis of cutaneous Meth A tumors when administered intraperitoneally or intratumorally on BALB/c mice. LT-3 induces more rapid, consistent, and complete tumor necrosis than equivalent doses of either LT or TNF.

Animals