Biomedical subjects
R Roger
Publications and source records attributed to R Roger.
Immunotoxicological investigation using pharmaceutical drugs. In vitro evaluation of immune effects using rodent or human immune cells.
In order to evaluate the relevance of in vitro methods for immunotoxicity assessment, the effects of pharmaceutical drugs on lymphoproliferative and cytotoxic functions of mouse splenocytes and human peripheral blood mononuclear cells (hPBMC) were studied. A comparison of sensitivity of immune cells from different origins to an in vitro exposure to different xenobiotics was performed using non-immunosuppressive (cimetidine and furosemide) and immunosuppressive (azathioprine (AZA), cyclosporine A (CSA), and dexamethasone (DEX)) drugs. For CSA, sensitivity of both rat and mouse splenocytes following in vitro exposure was compared to the one of hPBMC. Immune function tests included lymphoproliferative response to mitogenic lectins (concanavalin A (Con A) and phytohemagglutinin (PHA-P)) or to allogeneic cells (mixed leukocyte response (MLR)) and cytotoxicity assays (cytotoxic-T lymphocyte (CTL) and natural killer (NK) cell-mediated cytolysis). Additionally, to evaluate how well in vitro assays represent the in vivo situation, a comparison of the effect of cyclosporine A on the same immune function tests following in vivo or in vitro exposure was performed. The data obtained show numerous similarities in the effects observed following in vitro exposure of rodent or human cells to the drugs and a very similar sensitivity of rat and mouse cells to CSA in vitro. Discrepancies between human and rodent cells such as lymphoproliferative response to PHA-P following exposure to DEX or sensitivity of CTL-mediated cytolysis to CSA do exist. In vitro assays were very representative of the in vivo situation, both in the rat and in the mouse, following CSA exposure, except for NK cell activity in the rat. These data show the usefulness of in vitro systems for immunotoxicity assessment. They allow direct comparison of rodent and human systems, and could be representative, for drugs altering specifically the immune system like CSA does, of the in vivo situation.
Immunotoxicological investigation using pharmaceutical drugs: in vivo evaluation of immune effects.
Traditional methods for toxicological assessment have indicated that the immune system is a frequent target of toxic insult following subchronic or chronic exposure to xenobiotics. However, most of the xenobiotics evaluated in standardized protocols were environmental chemicals and correlation with available clinical data was not possible. The purpose of this work was to evaluate the potential immunosuppressive effects of pharmaceutical drugs using a standardized protocol developed for immunotoxicological assessment. Two groups of pharmaceutical drugs were utilized: (a) drugs without known immunosuppressive effect linked to their utilization in human therapy (cimetidine, furosemide, indomethacin, amoxicillin, and procainamide) and (b) immunosuppressive drugs (azathioprine, cyclosporine A, and dexamethasone). Ex vivo tests using B6C3F1 mice were performed after a 28-day repeat dose regimen and assessed: (a) immunopathology, (b) cell-mediated immunity, (c) humoral immunity, and (d) nonspecific immunity. Host resistance to Listeria monocytogenes was also assessed following exposure to immunosuppressive drugs. The results showed that (a) immunopathology and immune function assays were necessary to detect all immunotoxicants and (b) the effects observed with nonimmunotoxic drugs were sometimes statistically significant but the biological significance of these effects is unlikely.
Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (interleukin beta, interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans.
Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamo-pituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cytokines induced by ionizing radiation remain to be determined.
Quality of care and utilization management: contemporary tools and strategies.
An effective Quality-Utilization Management Program requires a contemporary and clinically relevant information system. Involvement of the medical staff and support of hospital personnel are critical to implement such a program. Equally important is the commitment of government and community representatives to address hospital quality and utilization issues in the context of the full range of community services. Outlining the background leading to the inception of a Quality-Utilization Management Program in a multi-hospital system, the authors also present the rationale for selecting a concurrent and retrospective review system.
Multiple intracranial hydatid cysts.
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Outcome in children with severe head injuries.
We present a series of 56 children who suffered severe head injuries, with a Glasgow Coma Score (GCS) of less than 8. The cases were classified according to the type of morphologic lesion on computed tomography (CT) scan. Intracranial pressure (ICP) was monitored in all children in this series. A protocol that included artificial ventilation and other measures of treatment for intracranial hypertension was applied. Results were analyzed according to age, type of lesion, and ICP. The usefulness of the ICP recording and of obtaining a correct classification of lesions using the CT scan is emphasized.
Intraventricular hemorrhage in severe head injury.
A series of 30 patients suffering posttraumatic intraventricular hemorrhage (IVH) after closed head injury is reviewed. Clotted blood and a mixture of blood and cerebrospinal fluid could be distinguished by computerized tomography (CT). Posttraumatic IVH was associated with diffuse brain lesions in most cases; intracerebral lesions with contusion, and subdural hematomas coexisted with posttraumatic IVH in eight and four instances, respectively. In two more cases, no CT abnormality other than IVH was noted. All patients in this series were in deep coma at the time of CT examination, and only seven survived. The early clinical findings, the site of ventricular hematoma, and the final outcome are analyzed.
Stereotactic biopsy of brain lesions visualized with computed tomography.
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Hydrocephalus in cerebral cysticercosis. Pathogenic and therapeutic considerations.
The cases of 11 patients with hydrocephalus secondary to cerebral cysticercosis are analyzed. Most of the patients had suffered from epilepsy before they developed hydrocephalic symptoms, and computerized tomography showed that infestation of the parenchyma coexisted with ventricular or cisternal colonization. In four cases, the parasitic vesicles compromised cerebrospinal fluid (CSF) flow in the ventricular system, resulting in internal hydrocephalus. Communicating hydrocephalus, caused by the presence of Cysticercus larvae in the basal cisterns (Cysticercus racemosus), or by the occurrence of a chronic basal meningitis, or both, developed in seven more patients. Changes in CSF pressure were related to the number and location of the cysts and to the leptomeningeal inflammatory reactions evoked by them. The majority of patients presented with a chronic and relatively normotensive hydrocephalus. All patients except one had identifiable ventricular or cisternal Cysticercus larvae; these patients were treated with open removal of the cysts, and did well. However, most of them had impairment of CSF flow through the basal cisterns and required permanent CSF shunting. Communicating hydrocephalus due to leptomeningeal scarring was also successfully managed with extracranial shunting. Epilepsy was controlled with anticonvulsant therapy. Although good lasting results may be obtained with aggressive treatment of neurocysticercosis, patients are liable to relapse because surgery is only palliative in most instances.
[Childhood epileptic crises in front of the television screen (author's transl)].
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Chronic adult hydrocephalus due to uncommon causes.
The authors report on four unusual cases of chronic adult hydrocephalus extracted from a large personal series of patients with hydrocephalic dementia. A syndrome resembling that of normal pressure hydrocephalus was due to the following aetiologies in these patients: Paget's disease of the skull, unruptured cerebral arteriovenous malformation, colloid cyst of the third ventricle, and cerebromeningeal cysticercosis. All these patients exhibited disturbances in cerebrospinal fluid dynamics at the time of study, and were considerably improved by CSF shunting. The value of the continuous CSF pressure monitoring and the constant infusion test in selecting patients with chronic hydrocephalus for shunt therapy is emphasized.
Intracoronary myocardial perfusion imaging: patterns in patients with coronary artery disease.
Myocardial imaging following the intracoronary injection of radiolabeled particles is used to identify transmural scars in patients being evaluated for coronary atherosclerosis. Selective imaging of the microcirculation derived from each major coronary vessel is accomplished using a dual radionuclide technique. This report illustrates the various normal and abnormal imaging patterns encountered in patients with coronary artery disease. The regional myocardial nomenclature proposed by the American Heart Association Council on Cardiovascular Surgery is used. Correlation of the nuclear study with the contrast arteriogram and ventriculogram is essential for identifying both transmural scars and regions of collateral circulation. The procedure is safe and can be performed during routine coronary angiography.
Vetebral hemangiomas: spinal angiography and preoperative embolization.
Seven cases of symptomatic spinal hemangiomas are discussed. Special emphasis is given to a patient in whom pre-operative embolization was necessary. A marked reduction in the blood supply was achieved, with the result that the subsequent laminectomy was carried out without great difficulty.
Intracardiac foreign body simulating double-chamber right ventricle.
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The chemistry of amidrazones.
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Late complications of percutaneous renal biopsy.
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Immune parameters are affected differently after cyclosporine A exposure in Fischer 344 rats and B6C3F1 mice: implications for immunotoxicology.
Knowledge of interspecies differences, commonly evaluated in other disciplines such as carcinogenesis, is a prerequisite for an appropriate assessment of immunotoxicological risks. The purpose of this study was to assess interspecies differences following exposure of Fischer 344 rats and B6C3F1 mice to cyclosporine A. These animals were exposed daily to cyclosporine A by oral gavage at 0, 5, 10, 25 mg/kg/day for 14 consecutive days. The results showed that splenocytes lymphoproliferation in response to concanavalin A or phytohemagglutinin, and IgM antibody-forming cells to sheep red blood cells, were affected in both species. Cytotoxic T-lymphocyte activity and mixed lymphocyte response were significantly inhibited in the rat following cyclosporine A exposure while they remained unaffected in the mouse. In contrast, natural killer cell activity was significantly depressed in the B6C3F1 mouse but not in the Fischer 344 rat. The discrepancies between the two species in cytotoxic T-lymphocyte activity and mixed lymphocyte response assays could partially be explained by the constantly higher blood level of cyclosporine A in the rat than in the mouse. When these tests were performed using rat and mouse splenocytes exposed to cyclosporin A in vitro (10(-9) to 10(-5) M) it was possible to correlate in vivo and in vitro data for concanavalin A- and phytohemagglutinin-induced lymphoproliferation and for cytotoxic T-lymphocyte activity but not for mixed lymphocyte response. Natural killer activity was 10-fold more sensitive in mice than in rats in vitro but these results did not clarify the in vivo difference. In conclusion, these results emphasize that the utilization of more than one species should be considered when assessing immunotoxicity.