Biomedical subjects
Publications and source records attributed to S David.
Ultrasonography has been shown to be valuable in diagnosis of appendicitis in children. For the management of cases where clinical and ultrasonography findings lead to different results, we evaluated standard therapeutical concepts which have been proved to be reliable in our clinic.
OBJECTIVE: There is a known relationship between blood glucose control and development or progression of complications in diabetes mellitus. The aim of our study was to assess the quality of hospital care in patients with insulin-dependent diabetes. PATIENTS AND METHODS: A prospective study was conducted over a 6-month period (April 95-September 95) to perform a clinical audit comparing results obtained with care standards. The study group included 257 consecutive patients (age range 15-39 years) who consulted the hospital outpatient clinic of were hospitalized for insulin-dependent diabetes mellitus RESULTS: Results differed depending on the care standards used for comparison. There were 45 patients (17%) who consulted 4 times or more; 43% of the patients were not hospitalized and 32% did not had a fundus examination during the preceding year. There was a 51% deviation from the standard number of capillary blood glucose measurements and 72% of the patients stated they adapted their insulin dose. Mean glycosylated hemoglobin level (HPLC method) was 9.78 +/- 2.37% (standard = 7%). CONCLUSION: This assessment of hospital care demonstrated a deviation of medical surveillance from standard care. More frequent consultations would help improve patient information. It is important to recall that an annual hospitalization and rigorous application of clinical surveillance with annual fundus examination are essential. Information provided by physicians, nurses and dietitians should be an integral part of hospital care. Likewise, it is undoubtedly useful to provide psychological counselling for diabetic patients. A reassessment should evaluate the impact of such recommendations in order to determine the impact, in terms of reduced mortality, of improved hospital care.
Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in plasma of hepatic origin. We now provide evidence for a novel membrane-bound form of ceruloplasmin expressed by astrocytes in the mammalian central nervous system. Using a monoclonal antibody (1A1), we show that the cell surface antigen recognized by this antibody is ceruloplasmin and that it is directly anchored to the cell surface via a glycosylphosphatidylinositol (GPI) anchor. Our peptide mapping and other immunochemical studies indicate that, except for the GPI anchor, the membrane-bound and secreted plasma forms are similar. We also show that the membrane-bound form of ceruloplasmin has oxidase activity. These studies therefore suggest that the GPI-anchored form of ceruloplasmin may play a role similar to the secreted form in oxidizing ferrous iron. The GPI-anchored form of ceruloplasmin expressed by astrocytes is likely to be the major form of this molecule in the central nervous system because serum ceruloplasmin does not cross the blood-brain barrier. Lack of this form of ceruloplasmin in the central nervous system could lead to the generation of highly toxic free radicals, which can cause neuronal degeneration as seen in aceruloplasminemia and other neurodegenerative diseases such as Parkinson's and Alzheimer's disease.
Axon growth-promoting and -inhibitory molecules are likely to work in concert to promote and guide axons in vivo. In adult mammals, inhibitory molecules associated with myelin in the white matter of the central nervous system (CNS) play an important role in the failure of long-distance axon regeneration. The presence of neurite growth-inhibitory molecules in the adult rat gray matter has not been extensively studied. In this article we describe work on the characterization of neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter using various biochemical and cell culture approaches. We show using a neuronal cell line (NG108-15 cells) that neurite growth-inhibitory activity is present in membrane preparations of the cortical gray matter. Purified gray matter membranes also induce growth cone collapse of cultured embryonic rat dorsal root ganglion neurons. The inhibitory activity in the membrane preparations is extractable with 3-[(3-cholamidoprophyl)-dimethylammonio]-1-propane-sulfonate, but does not appear to be depleted by various lectins. Western blots and enzyme treatments showed that the inhibitory effect of the gray-matter preparations is not likely to be mediated by myelin-associated inhibitors or chondroitin sulfate proteoglycans. However, tenascin was detected in these samples and may contribute to some of the inhibitory activity. Selective separation of the inhibitory molecules can be achieved by ion-exchange chromatography, which also suggests the presence of multiple inhibitors in cortical gray matter membranes.
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Leptomeningeal cells migrate into the lesion cavity after stab wounds to the adult mammalian central nervous system (CNS) and interact with astrocytes that form a new glia limitans. However, it is not known if leptomeningeal cells alter the ability of astrocytes near the lesion to support axon growth. In this study, we have used an in vitro approach to assess leptomeningeal cell-astrocyte interactions in a model that resembles the interactions of these cells in vivo. We cultured rat cortical astrocytes on top of monolayers of leptomeningeal cells or astrocytes. Differences in the morphology, neurite growth promoting properties, and expression of various extracellular matrix molecules and beta 1-integrin were assessed. Astrocytes acquired a long slender morphology when plated on leptomeningeal cells. Functionally, astrocytes cultured on top of leptomeningeal monolayers supported less neurite growth. Similar results were also obtained when astrocyte monolayers were treated with leptomeningeal cell-conditioned medium. Quantitative immunofluorescence labeling showed a reduction in cell surface bound laminin on astrocytes plated on leptomeningeal monolayers. Qualitative assessment of the immunofluorescence labeling showed an increase in matrix-like deposits of tenascin-C and chondroitin sulfate proteoglycan under similar culture conditions. This study provides the first direct evidence that leptomeningeal cells reduce the neurite growth promoting properties of astrocytes. These results suggest that interactions with leptomeningeal cells may 1) induce the formation of the slender astrocyte processes that form parallel to the lesion wall after penetrating injuries to the CNS; and 2) contribute along with other factors to alter astrocytes near the site of injury to a state that is less permissive for axon growth and regeneration.
We have examined the regeneration of corticospinal tract fibers and expression of various extracellular matrix (ECM) molecules and intermediate filaments [vimentin and glial fibrillary acidic protein (GFAP)] after dorsal hemisection of the spinal cord of adult GFAP-null and wild-type littermate control mice. The expression of these molecules was also examined in the uninjured spinal cord. There was no increase in axon sprouting or long distance regeneration in GFAP-/- mice compared to the wild type. In the uninjured spinal cord (i) GFAP was expressed in the wild type but not the mutant mice, while vimentin was expressed in astrocytes in the white matter of both types of mice; (ii) laminin and fibronectin immunoreactivity was localized to blood vessels and meninges; (iii) tenascin and chondroitin sulfate proteoglycan (CSPG) labeling was detected in astrocytes and the nodes of Ranvier in the white matter; and (iv) in addition, CSPG labeling which was generally less intense in the gray matter of mutant mice. Ten days after hemisection there was a large increase in vimentin+ cells at the lesion site in both groups of mice. These include astrocytes as well as meningeal cells that migrate into the wound. The center of these lesions was filled by laminin+/fibronectin+ cells. Discrete strands of tenascin-like immunoreactivity were seen in the core of the lesion and lining its walls. Marked increases in CSPG labeling was observed in the CNS parenchyma on either side of the lesion. These results indicate that the absence of GFAP in reactive astrocytes does not alter axonal sprouting or regeneration. In addition, except for CSPG, the expression of various ECM molecules appears unaltered in GFAP-/- mice.
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The orientation of elderly patients, temporarily disabled, to acute care beds is inappropriate because of its adverse effects on functional status and its costs. The creation of short-stay units (SSU) in nursing homes provides an alternative to acute care hospitalization. The aim of this retrospective study, involving the first 64 patients oriented to the SSU from the emergency center, was to evaluate this new health care network. The analysis was focused on the rate of appropriate orientation (site of living at four month; subsequent medical events), as well as the functional quality of this health care network. Information were collected from medical records of the 64 patients oriented to SSU and 64 sex- and age-matched patients admitted during the same period, and the opinion of the network's partners. The mean age of patients and controls was 82 years. Four months after admission to the SSU, the orientation was considered appropriate in 58% of the cases (living at home without subsequent hospitalization), doubtful in 8%, and inappropriate in 33%; 27% of patients and 13% of controls were living definitely in nursing homes (p < 0.1). No medical or social characteristics was correlated to inappropriate orientations. In conclusion, the creation of SSU may be considered as an improvement in the care of elderly patients. The main problem of this orientation was the high percentage of patients living permanently in a nursing home four months later. Accurate assessment's tools capable to predict the subsequent decrease of the functional status should be used in the daily practice in order to improve the orientation of elderly patients.
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Spontaneous spinal epidural hematoma is an uncommon clinical entity. Patients with this disease may present with devastating neurological deficits that can mimic other diseases. Emergency physicians should be familiar with this condition to assure appropriate therapy in a timely manner. A typical case of spontaneous spinal epidural hematoma is presented with review of appropriate differential diagnosis and management.
The CD34 antigen is present at all differentiation stages of hematopoietic cells, from immature progenitor cells to committed precursor cells. In vivo, transplantation of CD34+ cells is sufficient to allow hematopoietic recovery after myeloablative chemotherapy, but a neutropenic period of 9-12 days still exists, even when hematopoietic growth factors are given posttransplantation. After ex vivo expansion cultures in the presence of cytokines, CD34+ cells can generate mature precursor cells in a stroma-free liquid culture system. This could lead to a shortening of the aplasia duration, but the persistence of primitive progenitor cells in the expanded CD34+ compartment remains to be demonstrated. In this study, CD34+ cells were isolated from eight peripheral blood (PB) and eight cord blood (CB) samples using either Isolex 50 (n = 6), Ceprate LC CD34 kit (n = 6), or Microcellector T-25 Stem Cell kit (n = 4). We have evaluated the functional potential of CD34+ cells after 7 days of ex vivo expansion culture in the presence of 500 UI/ml of interleukin-1 (IL-1), 10 ng/ml of IL-3, and 10 ng/ml of stem cell factor (SCF). The expansions of nucleated cells, granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive committed precursors, IL-1 + IL-3 + SCF + erythropoietin (EPO)-responsive multilineage progenitors, and 5-fluorouracil (5-FU)-resistant quiescent progenitor were 8-fold, 59-fold, 4.4-fold, and 2.2-fold, respectively. There was no significant difference in the amplification/expansion parameters between cultures initiated with CD34+ cells from PBSC or CB. Our data confirm that cytokine-mediated ex vivo expansion of blood CD34+ cells can produce large numbers of committed precursors and does not significantly affect the compartment containing more immature progenitors. Cytokine-mediated expansion could be of great interest in autologous transplantation to decrease the duration of marrow aplasia.
BACKGROUND: Proximal tubular epithelial cells express a surface C3-convertase activity which induces C fixation and insertion of the C5b-9 membrane attack complex (MAC) into the cell plasma membrane. The physiopathological consequences of this phenomenon are unknown. METHODS: The effect of C fixation on the production of inflammatory mediators by human proximal tubular epithelial cells in culture was explored. RESULTS: Proximal tubular epithelial cells incubated with a sublytic amount of normal human serum as a source of C, but not with heat-inactivated human serum, showed a time-dependent calcium influx and a concomitant release of 14C-arachidonic acid (14C-AA). Eicosanoid synthesis following the arachidonic acid mobilization was studied as prostaglandin E2 release. Mg2+/EGTA, which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl bromide a phospholipase A2-inhibitor, inhibited mobilization of 14C-AA. These results suggest the activation of an extracellular Ca(2+)-dependent, phospholipase A2. Complement fixation was associated with the synthesis of proinflammatory cytokines such as IL-6 and TNF-alpha. Experiments with C6-deficient sera indicated that the release of 14C-AA and the production of cytokines were dependent on the insertion of the terminal components of complement in the plasma membrane. Indeed, the reconstitution of normal haemolytic activity of C6-deficient sera with purified C6 restored also the release of 14C-AA and the production of cytokines. CONCLUSIONS: In vitro complement activation on the proximal tubular cell surface triggers the generation of proinflammatory mediators, which may potentially contribute to the pathogenesis of tubulointerstitial injury.
An epidemiologic study was carried out in order to evaluate the effects of prevention programs at the workplace aimed at reducing back, neck, and shoulder morbidity among active workers. The intervention group included 275 workers in three occupational subgroups: hospital workers, warehouse workers, and office workers. The control group included 250 workers as comparable as possible to the intervention group. Comparisons were made, according to one-year changes in morbidity scores, for low back, upper back, neck, and shoulder disorders separately. An overall measure was also used. The one-year change in the overall measure was significantly different between the intervention group and the control group, indicating a positive effect of the prevention programs. Positive effects were stronger for some sites of pain and some occupational groups.
Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-cellulose, 1.8 m2 for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-alpha1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs acetate cellulose). In the presence of fresh plasma, as source of complement, the differences between acetate cellulose vs polysulfone and benzyl-cellulose were even more evident, suggesting the role of complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of leukopenia was at 15 and 30 min with acetate-cellulose (79%) and benzyl-cellulose (50%) (p<0.05 acetate- vs benzyl-cellulose) and at 15 min with polysulfone (24%) (p<0.01 vs acetate- and benzyl-cellulose). Plasma C3a des Arg levels arose to 2037 +/- 120 ng/ml, 1216 + 434 ng/ml and 46 +/- 55 ng/ml with acetate-, benzyl-cellulose and polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of TNF-alpha was detected with any of three membranes. Clearance values of urea, creatinine and uric acid were superimposable for all the three membranes. However, benzyl cellulose had a significantly higher clearance for phosphorus (normalized for surface area) (p<0.01 vs acetate-cellulose, 0.001 vs polysulfone). These results implicate that synthetic modification of the cellulose polymer as for the benzyl-cellulose significantly reduces the in vitro adherence, delays the in vivo activation of "classic" biocompatibility parameters and notably improves the removal of inorganic phosphorus.
We have previously shown that myelin-associated glycoprotein (MAG) inhibits neurite growth from a neuronal cell line. In this study we show that 60% of axonal growth cones of postnatal day 1 hippocampal neurons collapsed when they encountered polystyrene beads coated with recombinant MAG (rMAG). Such collapse was not observed with denatured rMAG. Neurite growth from rat embryonic hippocampal and neonatal cerebellar neurons was also inhibited about 80% on tissue culture substrates coated with rMAG. To investigate further the inhibitory activity of MAG in myelin, we purified myelin from MAG-deficient mice and separated octylglucoside extracts of myelin by diethylaminoethyl (DEAE) ion-exchange chromatography. Although there was no significant difference in neurite growth on myelin purified from MAG-/- and MAG+/+ mice, differences were observed in the fractionated material. The major inhibitory peak that is associated with MAG in normal mice was significantly reduced in MAG-deficient mice. These results suggest that although MAG contributes significantly to axon growth inhibition associated with myelin, its lack in MAG-deficient mice is masked by other non-MAG inhibitors. Axon regeneration in these mice was also examined after thoracic lesions of the corticospinal tracts. A very small number of anterogradely labeled axons extended up to 13.2 mm past the lesion in MAG-/- mice. Although there is some enhancement of axon generation, the poor growth after spinal cord injury in MAG-/- mice may be due to the presence of other non-MAG inhibitors. The in vitro studies, however, provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse.
A lesion interface, consisting of a glia limitans lined by a laminin-rich basal lamina and leptomeningeal cells, forms within 2-3 weeks after penetrating wounds to the adult mammalian central nervous system (CNS). This interface prevents the growth of axons across the lesion. We have examined the effects of topically applied steroids on the formation of such an interface after stab wounds to the adult rat cerebral cortex. Immediately after lesioning, the surface of cortex in the region of the wound was treated with a topical application of either 0.1% halcinonide or 0.05% betamethasone dipropionate or their respective placebos. Cryostat sections through the lesioned area were obtained 3 weeks later and assessed by immunofluorescence. Steroid treatment attenuated all components of the lesion. The continuous anti-laminin labeling along the lesion in untreated rats became patchy after steroid treatment. The number of leptomeningeal cells that infiltrated into the wound was reduced in the laminin-negative regions in steroid-treated rats. In addition, astrocytic processes in the laminin-negative regions after steroid treatment were loosely arranged, compared with the tightly packed parallel processes forming the glia limitans in laminin-positive regions in controls. The mechanism of steroid-mediated attenuation of the lesion interface was examined in vitro. Betamethasone but not halcinonide reduced laminin secretion slightly in leptomeningeal cell cultures, but both steroids reduced cell proliferation. These results suggest that steroids modulate the formation of the lesion interface after CNS injury, at least in part by decreasing leptomeningeal cell proliferation. Such modulation of the lesion interface by steroids or other agents may permit the growth of axons across the lesion site and thus could enhance the overall degree of axon regeneration if other factors such as neurotrophic support and neutralization of axon growth inhibitory molecules are optimized.
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