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Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 37 records · Page 2Linked to original sources

Reduced ryanodine receptor content in isolated neonatal cardiomyocytes compared with the intact tissue.

The effects of isolation and culture of rat neonatal ventricular myocytes on the properties of the ryanodine receptor were investigated. [3H]-Ryanodine bound to a single class of sites in membranes prepared from intact neonatal ventricle, with an affinity of 16.3 +/- 2.8 nm (mean +/- S.E.; n = 3) and a capacity of 546 +/- 64 fmol/mg protein (mean +/- S.E.; n = 3). In contrast, no detectable displaceable binding of [3H]-ryanodine was observed when similar experiments were performed using membranes prepared from isolated neonatal cardiomyocytes. The apparent absence of [3H]-ryanodine binding in the neonatal cardiomyocytes suggested either reduced ryanodine receptor protein or the conversion of the receptors to a low affinity state. To distinguish between these possibilities, the content of ryanodine receptor protein was measured using SDS-PAGE followed by western blotting. Membranes prepared from neonatal ventricle contained substantial amounts of ryanodine receptor, as demonstrated by a dense band on western blots. However the corresponding band in preparations of isolated cells, while having similar electrophoretic mobility, was barely detectable. It is concluded that the ryanodine receptor protein is strongly expressed in intact neonatal ventricle, but the level of expression is markedly reduced upon isolation of the cardiomyocytes. These findings demonstrate that ryanodine receptor expression is significantly down-regulated when rat neonatal ventricular myocytes are isolated and maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The implementation of a quality management system in a department of diagnostic radiology.

The quality management systems of the Departments of Diagnostic Radiology of St George's Hospital, London, and Bristol Royal Infirmary (BRI) have been certified with the British Standard 5750. These were the first clinical departments in the UK to be certified to this internationally recognized quality assurance (QA) standard. Quality is a much used term; in this context it is defined as 'fitness for purpose', and quality assurance is the mechanism by which quality is achieved. The paper describes the features of the quality system which have been implemented at St George's Hospital, and how a management concept for manufacturing industries has been adapted successfully to a National Health Service Department. The paper also demonstrates how the quality system has led to the setting and achieving of departmental objectives.

England

Fab fragments from the monoclonal antibody ML30 bind to treated human myeloid leukemia cells.

Traditionally, heat-shock proteins were believed to be located intracellularly; however, recent studies have demonstrated that under certain circumstances these proteins can be located at the cell surface. Murine ascites developed from the anti-mycobacterial hsp65 hybridoma ML30 have been shown to contain an antibody that binds to the surface of a range of stimulated myelomonocytic cell lines; however, as the purified ML30 monoclonal antibody produced in vitro did not bind to these cell lines, the results were not considered conclusive evidence of cell-surface expression of the hsp60 homologue of the mycobacterial hsp 65 on human cells. In an effort to clarify this situation, we have confirmed that the ascites derived from the ML30 hybridoma bound to the surface of human myeloid leukemia cell lines and myeloid blast cells purified from freshly diagnosed leukemic patients, but that the in vitro-derived ML30 antibody did not. In addition, we have isolated Fab fragments from the ascites derived from the ML30 hybridoma and demonstrated that these fragments bound to the surface of human myeloid leukemia cells after their treatment with the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) for various times up to four days. Evidence has been presented in the literature that the ML30 monoclonal antibody recognizes a molecule corresponding to the human hsp60 homologue of the mycobacterial hsp65; therefore our results from the binding of Fab fragment preparations from ascites imply that when human myeloid leukemic cells are treated with DON, they express a human hsp60 homologue on their surface.

Animals

Inositol-1,4,5-trisphosphate [ins(1,4,5)P3] and ins(1,4,5)P3 receptor concentrations in heart tissues.

1. The isolation and culture of neonatal cardiomyocytes causes changes in the metabolism of inositol(1,4,5) trisphosphate (Ins(1,4,5)P3) from primarily dephosphorylation in the intact tissue to a combination of phosphorylation and dephosphorylation in the cultured cells (Woodcock et al. 1992). 2. The content of Ins(1,4,5)P3 was found to be higher in intact heart tissue than in the isolated neonatal cells (10.9 +/- 1.3 and 0.5 +/- 0.1 pmol/mg tissue, mean +/- s.e.m., n = 4, P < 0.002, respectively). 3. Despite this difference, Ins(1,4,5)P3 receptors in intact tissue and in isolated cells were not different in terms of affinity (8.0 +/- 1.7 and 10.9 +/- 1.6 nmol/L, n = 3, respectively) or concentration (143.3 +/- 20.5 and 91.2 +/- 16.0 fmol/mg protein, n = 3, respectively). 4. Thus, while there appears to be a relationship between the tissue content of Ins(1,4,5)P3 and its metabolism, no relationship to the properties of Ins(1,4,5)P3 receptors could be demonstrated.

Animals

The fluroquinolones.

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Anti-Infective Agents

Making homework work at home: the parent's perspective.

This article views homework through the eyes of parents in a rural area whose children with disabilities spent a majority of their time in general education classrooms. The qualitative analysis of data from individual interviews, focus groups, and parent action research logs yielded five themes: (a) Parents felt ill-prepared to help their children with homework; (b) parents wanted more information about the classroom teachers' expectations of their child and of their roles as parents in helping with homework; (c) parents wanted their children to be given individualized homework assignments; (d) parents valued hands-on homework and projects in which the whole family could participate; and (e) parents wanted a two-way communication system that would allow them to become partners on their child's instructional team.

Communication

Erythrocyte nuclei resemble dying neurons in embryonic dorsal root ganglia.

Cell death or apoptosis is regarded as an important feature of mammalian neural development, but the evidence for this generalization depends on the assumption that cell death can be clearly recognized. The usual profile of a dying neuron is a deeply stained pyknotic homogeneous sphere. In this paper we present evidence that such profiles in embryonic rat T6 and L4 dorsal root ganglia are not dying neurons but rather nuclei of immature red blood cells. This observation, combined with recent work showing that the methods previously used for counting normal or dying neurons are biased, indicates that the classic work establishing the importance of apoptosis needs to be repeated.

Animals

Long term follow up of severely ill patients who underwent urgent cardiac transplantation.

OBJECTIVE: To assess long term survival (> 5 years) and quality of life in severely ill patients referred for urgent cardiac transplantation. SETTING: Tertiary referral centres: before transplantation at the National Heart Hospital (late 1984 to end 1986); after transplantation at Harefield Hospital. SUBJECTS: Eighteen patients (15 men; three women) who had required intensive support in hospital before cardiac transplantation and were alive at short term follow up. INTERVENTIONS: Intravenous infusions of cardiac drugs (mean 2.2 infusions), intravenous diuretics (17 patients), and many other drugs before transplantation. Intra-aortic balloon counterpulsation (four patients), temporary pacing (two), and resuscitation from cardiac arrest (three). Patients had specialised nursing care on a medical intensive care unit in almost every case. MAIN OUTCOME MEASURES: Long term survival in patients after urgent cardiac transplantation and perceived quality of life. RESULTS: Of 18 patients who were alive at short term follow up (mean (range) 19.4 (10-33) months), 14 were still alive in 1992 (69 (61-83) months). Ten still worked full time, and 11 reported no restrictions in their daily activities. Three of four patients who died in the intervening period survived > 5 years after transplantation. Overall, 17 of 18 patients survived at least 5 years. CONCLUSIONS: In severely ill patients who undergo urgent cardiac transplantation and survive in the short term, long term (5-7 year) survival and quality of life seem good.

Cardiomyopathy, Dilated

Methemoglobinemia due to skin application of benzocaine.

We report a 2-year-old child who presented with severe methemoglobinemia after topical application of Lanacane (with 3% benzocaine). The experience with our patient shows that intoxication can occur in children if the drug is applied to a large area of skin that has lost its integrity. We discuss the usefulness of the pulse oximeter in making the diagnosis and review the management of methemoglobinemia.

Administration, Topical

Ventral spinal cord inhibition of neurite outgrowth from embryonic rat dorsal root ganglia.

Organotypic culture of embryonic rat lumbar spinal cord and dorsal root ganglia has been used to demonstrate an inhibitory effect of ventral spinal cord on neurite growth from dorsal root ganglion explants. When dorsal root ganglion explants from 14-15 day old embryos were cultured alone or in close proximity to a dorsal cord explant, the pattern of dorsal root ganglion neurite outgrowth was typically radial. However, when E14-15 dorsal root ganglion explants were cocultured for 22-24 hours in proximity to a ventral spinal cord explant from the same embryo, few, if any, dorsal root ganglion neurites grew in the direction of the ventral cord explant. This inhibitory effect appeared to be developmentally regulated; it was diminished or absent in cocultures prepared from 18 day old embryos. In contrast, in cocultures of dorsal cord and ventral cord explants from E14-15 embryos, dorsal cord neurites grew abundantly toward the ventral cord explant suggesting that the inhibition is not likely to be due to a nonspecific neurotoxic effect and that the activity responsible selectively inhibits dorsal root ganglion neurite outgrowth. We conclude that a diffusible, primary afferent inhibitory factor(s) produced by embryonic ventral horn may be responsible for the inhibition. Our results are discussed with respect to the possible involvement of inhibition in the normal development of primary afferent innervation of the spinal cord.

Animals

Neonatal sciatic nerve section results in thiamine monophosphate but not substance P or calcitonin gene-related peptide depletion from the terminal field in the dorsal horn of the rat: the role of collateral sprouting.

The expression of substance P, calcitonin gene-related peptide (CGRP) and thiamine monophosphatase in the sciatic nerve terminal field of the lumbar dorsal horn of the rat was examined following neonatal sciatic nerve section and ligation. The total terminal field from L3 to L5 was mapped from semi-serial sections on the treated side and compared to equivalent maps on the contralateral intact side. To obtain a detailed time course of events, data were obtained 4, 7, 10, 15-20 and 40-60 days after sciatic nerve section. At 4-7 days thiamine monophosphate was depleted from the cut nerve terminals resulting in a gap in dorsal horn thiamine monophosphate stain similar to that seen after adult nerve section. In contrast, substance P and CGRP-containing terminals showed only a transient fall in expression in the first week following nerve section and then staining was no different from that seen on the control side. The depletion of peptides normally observed after adult nerve section did not occur. This phenomenon was only observed if the sciatic nerve was cut at birth. Nerve section at 10 days of age resulted in the same pattern of peptide depletion as is observed in the adult. A week after neonatal sciatic nerve section, thiamine monophosphate-containing nerve terminals from nearby intact nerves begin to sprout into the sciatic nerve territory in the dorsal horn. This, together with some recovery of thiamine monophosphate from the remaining sciatic terminals themselves, results in a slow filling in of the gap in the thiamine monophosphate stain. Resection of the cut sciatic nerve, together with adjacent intact nerves, re-establishes the depletion. Substance P and CGRP terminals from nearby intact nerves also sprout into the deafferented sciatic field and this can be demonstrated by the larger than normal area of depletion following section of these nerves when adult. Furthermore, resection of the neonatally cut sciatic nerve when adult also causes some depletion of substance P and CGRP within the sciatic field, indicating a degree of recovery or up-regulation of peptides in surviving cut afferents. However, even after resection of the cut sciatic nerve and nearby intact nerves, substance P and CGRP staining remained in the terminal region. We conclude that while central collateral sprouting does take place in both substance P and CGRP-containing afferents following peripheral nerve section, it cannot account for the lack of depletion of peptides observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging

Fractures in the under-3-year-old age cohort.

One hundred twenty-four urban children under 3 years of age admitted for fractures were retrospectively reviewed to determine the frequency of accidental and nonaccidental causes in this population. The fractures were categorized according to their mechanisms: motor-vehicle passenger or pedestrian accident, other accidents, or child abuse. There were no differences in the frequency of fractures by race, date of birth, or season in which the injury occurred. Skull fractures were most frequent (62%), followed by femur fractures (11%). There was a 26% increase in fractures between 1987 and 1989, especially in the non-motor vehicle cohort. Caretaker ignorance and/or carelessness was a common cause of fractures in the infant and toddler age group. Injuries were still occurring in spite of infant care seat use. The American public must be educated in preventive medicine and safety to decrease the senseless morbidity of our greatest resource.

Accidents

Community education on stroke.

A programme of community education on stroke in Micronesia is based on the use of brightly illustrated posters with a limited content of written material in the native languages. This approach has been favourably received by the people.

Audiovisual Aids

A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.

OBJECTIVE: To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia. DESIGN: Randomised study of two treatment groups with a minimum follow up of nine months. SETTING: Royal Berkshire Hospital, Reading. SUBJECTS: 51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy. TREATMENT: Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons. MAIN OUTCOME MEASURES: Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection. RESULTS: Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year. CONCLUSION: For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection.

Adult

The pattern and timing of cutaneous hair follicle innervation in the rat pup and human fetus.

The postnatal development of hair follicle innervation was studied in the rat hindlimb using a silver stain which detects large and medium calibre cutaneous nerve fibres. The pattern and timing of innervation in relation to postnatal changes in follicle growth were studied providing new data on nerve-target interactions in the developing peripheral nervous system. Sensory axons begin to leave the dermal plexus and grow towards follicles at P (postnatal day) 3 but do not start to innervate them until P7 or achieve an adult appearance until P19. The first terminals are circumferential, followed some days later by the appearance of palisade endings. The number of axons innervating a hair follicle increases steadily with age until P19 and there is no evidence of exuberant innervation of follicles during development. Hair follicle density in the rat is maintained during development due to waves of small, vellus follicle growth later in postnatal life as the skin grows. The percentage of follicles innervated however, decreases from the second postnatal week onwards presumably because late developing vellus hairs do not become innervated. Comparative analysis in human fetal abdominal skin using the same silver stain reveals a similar sequence and pattern of innervation to the rat over the period of 22 to 35 weeks EGA (estimated gestational age). Human skin does not, however, undergo the late waves of follicle growth seen in the rat. Follicular density decreases and the percentage of innervated follicles increases in the third trimester of fetal life.

Animals