Air-terminal stress and the older traveller.
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Aged↗
Biomedical subjects
A Blight
Publications and source records attributed to A Blight.
Experimental spinal cord injury: spatiotemporal characterization of elemental concentrations and water contents in axons and neuroglia.
To examine the role of axonal ion deregulation in acute spinal cord injury (SCI), white matter strips from guinea pig spinal cord were incubated in vitro and were subjected to graded focal compression injury. At several postinjury times, spinal segments were removed from incubation and rapidly frozen. X-ray microanalysis was used to measure percent water and dry weight elemental concentrations (mmol/kg) of Na, P, Cl, K, Ca, and Mg in selected morphological compartments of myelinated axons and neuroglia from spinal cord cryosections. As an index of axon function, compound action potentials (CAP) were measured before compression and at several times thereafter. Axons and mitochondria in epicenter of severely compressed spinal segments exhibited early (5 min) increases in mean Na and decreases in K and Mg concentrations. These elemental changes were correlated to a significant reduction in CAP amplitude. At later postcompression times (15 and 60 min), elemental changes progressed and were accompanied by alterations in compartmental water content and increases in mean Ca. Swollen axons were evident at all postinjury times and were characterized by marked element and water deregulation. Neuroglia and myelin in severely injured epicenter also exhibited significant disruptions. In shoulder areas (adjacent to epicenter) of severely injured spinal strips, axons and mitochondria exhibited modest increases in mean Na in conjunction with decreases in K, Mg, and water content. Following moderate compression injury to spinal strips, epicenter axons exhibited early (10 min postinjury) element and water deregulation that eventually recovered to near control values (60 min postinjury). Na(+) channel blockade by tetrodotoxin (TTX, 1 microM) perfusion initiated 5 min after severe crush diminished both K loss and the accumulation of Na, Cl, and Ca in epicenter axons and neuroglia, whereas in shoulder regions TTX perfusion completely prevented subcellular elemental deregulation. TTX perfusion also reduced Na entry in swollen axons but did not affect K loss or Ca gain. Thus graded compression injury of spinal cord produced subcellular elemental deregulation in axons and neuroglia that correlated with the onset of impaired electrophysiological function and neuropathological alterations. This suggests that the mechanism of acute SCI-induced structural and functional deficits are mediated by disruption of subcellular ion distribution. The ability of TTX to reduce elemental deregulation in compression-injured axons and neuroglia implicates a significant pathophysiological role for Na(+) influx in SCI and suggests Na(+) channel blockade as a pharmacotherapeutic strategy.
Animals↗
Myelin galactolipids are essential for proper node of Ranvier formation in the CNS.
The vertebrate myelin sheath is greatly enriched in the galactolipids galactocerebroside (GalC) and sulfatide. Mice with a disruption in the gene that encodes the biosynthetic enzyme UDP-galactose:ceramide galactosyl transferase (CGT) are incapable of synthesizing these lipids yet form myelin sheaths that exhibit major and minor dense lines with spacing comparable to controls. These CGT mutant mice exhibit a severe tremor that is accompanied by hindlimb paralysis. Furthermore, electrophysiological studies reveal nerve conduction deficits in the spinal cord of these mutants. Here, using electron microscopic techniques, we demonstrate ultrastructural myelin abnormalities in the CNS that are consistent with the electrophysiological deficits. These abnormalities include altered nodal lengths, an abundance of heminodes, an absence of transverse bands, and the presence of reversed lateral loops. In contrast to the CNS, no ultrastructural abnormalities and only modest electrophysiological deficits were observed in the peripheral nervous system. Taken together, the data presented here indicate that GalC and sulfatide are essential in proper CNS node and paranode formation and that these lipids are important in ensuring proper axo-oligodendrocyte interactions.
Action Potentials↗
Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability.
The vertebrate nervous system is characterized by ensheathment of axons with myelin, a multilamellar membrane greatly enriched in the galactolipid galactocerebroside (GalC) and its sulfated derivative sulfatide. We have generated mice lacking the enzyme UDP-galactose:ceramide galactosyltransferase (CGT), which is required for GalC synthesis. CGT-deficient mice do not synthesize GalC or sulfatide but surprisingly form myelin containing glucocerebroside, a lipid not previously identified in myelin. Microscopic and morphometric analyses revealed myelin of normal ultrastructural appearance, except for slightly thinner sheaths in the ventral region of the spinal cord. Nevertheless, these mice exhibit severe generalized tremoring and mild ataxia, and electrophysiological analysis showed conduction deficits consistent with reduced insulative capacity of the myelin sheath. Moreover, with age, CGT-deficient mice develop progressive hindlimb paralysis and extensive vacuolation of the ventral region of the spinal cord. These results indicate that GalC and sulfatide play important roles in myelin function and stability.
Animals↗
Incorrect diagnosis of thyroid disease by junior doctors.
Thyroid function tests (TFTs) are commonly performed on elderly patients admitted to hospital. Several diseases and commonly used drugs may alter thyroid function test results. We assessed the knowledge of such interactions among 50 junior doctors in our departments: 60% were unaware that (in our laboratory) the normal range for TFTs is the same in those above 65 years as in those below; 72% correctly noted the effect of an acute illness, while only 48% correctly noted the effect of a chronic illness on test results; 72% were well aware of common drug effects such as those of the oral contraceptive pill, but only 22% and 42% knew of the potentially more important interactions in the elderly with the salicylates and phenytoin respectively. Thyroid screening in elderly people is important. The knowledge of interactions between drugs, disease states and the normal range of biochemical assays used in routine thyroid screening needs to be improved if thyroid function tests are to be interpreted appropriately.
Clinical Competence↗
Birthmark due to cutaneous mosaicism for keratin 10 mutation.
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Child, Preschool↗
In vitro production of parathyroid hormone-related protein by cholesteatoma and normal skin.
Severe inflammation and infection of the middle ear occasionally results in clinical evidence of bone resorption but with the addition of the cholesteatoma epithelium it becomes inevitable. This study examined production by the cholesteatoma epithelium of a bone resorbing factor, namely parathyroid hormone-related protein (PTH-rP), which would not be expected in inflammatory states alone. PTH-rP was detected in the conditioned medium of primary and secondary cell cultures derived from 12 cholesteatoma biopsies. The levels of PTH-rP were significantly greater than in control cultures of cells derived from normal scalp tissue. Production by the cholesteatoma epithelium may explain the increased incidence of bone resorption in this disease, particularly in cases where inflammation is minimal.
3T3 Cells↗
An in vitro growth study on cholesteatoma and normal skin.
The ability of cholesteatoma to grow rapidly within the ear is well recognized. This study aimed to quantify the in vitro growth of cholesteatoma derived cells. Following removal of cholesteatoma explant cultures were established. Cellular outgrowths were subcultured and a colony forming assay performed. Cells were repeatedly passaged every 14 days until senescence was observed. In comparison with cells derived from normal scalp skin, cholesteatoma derived cells demonstrated a lower colony forming efficiency in both primary and secondary subcultures, achieved fewer passages and cell generations in serial culture, and achieved a lower total population expansion. No evidence was found to suggest an intrinsic loss of growth control. It is proposed that the majority of cholesteatoma is composed of cells with a limited capacity for growth. Explant studies suggested that these may be the progeny of more highly proliferative cells situated at the neck of the cholesteatoma sac.
3T3 Cells↗
Implications for would healing of patient age and time elapsed since burn injury.
To determine the relationship between growth potential in culture and the age of the patient, skin biopsies were obtained from over 60 patients of varying ages. The relationship between the length of time elapsed since burn injury and growth potential was also examined, using biopsies obtained from patients with burns during their treatment. Keratinocytes were extracted from biopsies and assessed for colony-forming ability by standard methods. Repeated subculture of cells was undertaken to determine the reproductive capacity of cells in vitro. Age had no effect on the colony-forming ability of keratinocytes in primary culture; however age did affect the total number of generations achieved by these cells. The growth potential of keratinocytes from patients with severe burns showed considerable variation according to the amount of time which had elapsed since the injury. This was most apparent around one week post-burn. These results need to be investigated further to understand their clinical implications. The study provides an insight into the influence of age and physiological response on the wound healing process in burn injuries.
Adolescent↗
Epidermal mosaicism and Blaschko's lines.
To test the hypothesis that epidermal rather than dermal mosaicism determines Blaschko's lines in hypomelanosis of Ito (HI), we studied the distribution of chromosomal mosaicism in four patients. In two, mosaicism had not been detected in lymphocytes or dermal fibroblasts, but was clearly shown in epidermal keratinocytes; furthermore, the abnormal cell line was confirmed to the hypopigmented epidermis and the normal epidermis contained only normal cells. Negative findings in the other two patients might be because of mosaicism which was undetected either because it was submicroscopic or because it was present in melanocytes, which have not yet been studied. These preliminary results support the ideas that (1) Blaschko's lines represent single clones of epidermal cells; (2) in patients with HI and severe neurological involvement mosaicism, if detectable, is best shown in keratinocytes; and (3) the cytogenetic defect in epidermal cells may be directly responsible for the failure of pigmentation in HI.
Adolescent↗
Immunochemical characterisation of parathyroid hormone-related protein from tumour and non-tumour cells.
The molecular forms of parathyroid hormone-related protein (PTHRP) in conditioned media from the BEN human lung cancer cell line, rat parathyroid cells (PT-r) and human keratinocytes were studied by gel-filtration chromatography with assay of PTHRP by immunoassays and bioassay. Immunoreactivity (1-86 and 1-34) and bioactivity (1-34) in conditioned media eluted as a coincident major peak (approx. molecular mass 19-22 kDa) and there was evidence of amino-terminal species in the molecular mass range 10-16 kDa in BEN and keratinocyte media. Western blotting of PTHRP affinity purified by monoclonal antibodies directed at regions 1-34 or 37-67, identified a major species in all cell cytosols and media with an apparent molecular mass of 24-25 kDa, consistently slightly larger than recombinant PTHRP(1-141) (mobility of 21 kDa) which may represent an intact or native form of PTHRP. Additional amino-terminal species were identified in medium from keratinocytes (16 and 7 kDa), BEN cells (18 and 14 kDa) and PT-R cells (17 kDa), suggesting that processing occurs at the C-terminus and within the mid-region to form a range of amino-terminal fragments.
Animals↗
Epidermal keratinocyte self-renewal is dependent upon dermal integrity.
The epidermis is a major site of self-renewal in which there is constant replacement by cell division in the basal layers of cells lost by desquamation in the superficial layers. Such a tissue is therefore likely to contain stem cells and in this study we have examined the role of the dermis in the maintenance of epidermal self-renewal. We have developed a mouse model to address the question of whether the maintenance of epidermal self-renewal is dependent, as in the hemopoietic system, upon a heterologous cell type. Intact epidermis separated from dermis at the dermo-epidermal junction or epidermis derived from disaggregated epidermal cells, can reconstitute a stratified squamous epithelium when grafted onto the lumbo-dermal fascia of the mouse or onto an experimentally induced granulation tissue bed. However, we have shown that, after grafting, the clonogenic capacity of the keratinocytes declines sharply and the colonies that are produced are incapable of self-renewal in vitro. Although initially hyperplastic, these epidermal grafts assume an atrophic appearance after 40-70 d and this may be related to the loss of self-renewal observed in vitro. With both experimental murine grafts and clinical grafts the failure of keratinocytes to self-renew can be alleviated, partially, by the presence of the dermis in full-thickness or split-thickness grafts, which implies that the dermis has a functional role in epidermal stem cell maintenance. The relevance of these observations to the clinical experience with cultured autologous keratinocyte sheets as wound dressings to patients is discussed.
Animals↗
Production of parathyroid-hormone-related protein by cholesteatoma cells in culture.
Specimens of cholesteatoma were removed at surgery from five patients who had evidence of bone resorption. Parathyroid-hormone-related protein (PTHrP) was detected, by radioimmunoassay, in conditioned media from keratinocyte cultures derived from all five samples. Concentrations of PTHrP in conditioned media from secondary cultures were higher for the cholesteatoma cells than for normal keratinocytes from controls matched for age and sex. Thus, production of PTHrP by cholesteatoma may be a contributory factor in the bone destruction commonly associated with this disorder.
Adolescent↗
Changes in urate metabolism after castration of patients suffering from carcinoma of the prostate.
13 patients with carcinoma of the prostate were investigated on a low purine diet before and after surgical castration, performed to slow progression of their disease. A control group of herniorrhaphy patients was similarly studied. The 2 groups were very similar pre-operatively except for urea which was higher pre-operatively in patients than controls (p0.004). Testosterone levels fell significantly in patients soon after surgery (W0.002). There was a significant fall in serum uric acid in the early post-operative phase in both patients (W0.004) and controls (W0.01) but the fall only remained significant one month after surgery in castrated patients (W0.007). Urinary uric acid levels in patients fell significantly soon after surgery (W0.04). This is a small study but results suggest that endogenous male hormones are at least partially responsible for serum uric acid levels since castration, with reduction in circulating testosterone, resulted in a fall in these levels.
Creatinine↗
The treatment of donor sites with cultured epithelial grafts.
In a significant number of elderly patients, the healing of split skin donor sites can be delayed. The cultured allogenic epithelial graft (CAG) has been reported to heal leg ulcers. The mechanism of action may be to improve the healing environment and thus stimulate the host skin cells. A clinical trial was undertaken to compare the healing rate of the donor sites of elderly patients using CAGs and two commercially available dressings. Compared to Jelonet, CAGs (p = 0.008) and OpSite (p = 0.013) significantly reduced the number of patients with delayed healing. There was no significant difference between CAGs and the occlusive dressing, OpSite.
Aged↗
Treatment of full skin thickness burn injury using cultured epithelial grafts.
This report presents the experience gained from 26 patients treated with autogenic cultured epithelial grafts (auto-CEG). All auto-CEG were applied to wounds clinically defined as full skin thickness injury. In total 89 separate sites were grafted. The overall estimate of 'take' ranged from 0 to 98 per cent with a mean value of 15 per cent. The highest level of 'take' (43 per cent) was observed when auto-CEG were applied to wounds which had been previously covered with allogenic split-thickness skin grafts. An increased incidence of wound colonization with pathogenic species of bacteria corresponded with a decreased graft 'take'. Ps. aeruginosa and Staph. aureus were found to be present on 32.6 per cent and 60.5 per cent of wound swabs respectively, where 10 per cent or less 'take' of auto-CEG was seen, indicating that bacterial infection is in part responsible for graft failure. However, in 20.9 per cent of such instances, no growth of bacteria was detected, perhaps suggesting that certain wound beds may not present the correct physical environment necessary to support proliferating epithelial cells isolated from their underlying dermal component.
Adolescent↗
Adverse effect of lignocaine (lidocaine) on skin destined for keratinocyte culture.
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Cells, Cultured↗