Examples of the use of cell cultures in skin irritancy assessment.
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Biomedical subjects
Publications and source records attributed to A Rougier.
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An abundant literature provides informations upon the prognosis of supratentorial low grade (grade II) astrocytomas, but the series are quite heterogeneous in terms of clinical material, neuropathological evaluation and statistical methods of analysis. So, outcome, prognostic factors and therapeutical indications are poorly defined. A retrospective study of 141 adults patients suffering ordinary low grade astrocytoma diagnosed in our unit between 1978 and 1988 was conducted. A follow up of 5 years or more, since neuropathological diagnosis, was mandatory for inclusion. Endpoint of statistical analysis was duration of survival. Results were expressed after uni and multivariates analysis. Clinical and morphological features of our series were comparable to those previously reported in the literature. Median survival time was 52 months. Considering age at diagnosis, survival curve analysis showed highly significant differences (p < 0.0001) and established three prognostic classes of age (before 50, between 50 and 60, and after 60 years of age). Comparisons of survival curves showed significant statistical differences (p < 0.0001) according to pretreatment functional status. Analysis of a clinical condition using a functional scale is more powerful, from a statistical point of view, than an individual analysis of each constituting parameters. In this series a good correlation was found between functional status and age at diagnosis. Neurological deficit was more correlated to age than to tumor location. Multivariate analysis, using the Cox model, defined some parameters acting independently on duration of survival: fronto-parietal location (p < 0.0001), pretherapeutical functional status (p < 0.001), age at diagnosis (p = 0.001), deepseated or multicentric tumor, mass effect (p < 0.01), frontal location (p < 0.02), total surgical removal (p < 0.05). Non significant parameters were: radiotherapy, time before diagnosis, age of onset, sex, contrast enhancement on CT scan. Our results are in agreement with previously reported data confirmed literature data concerning prognostic factors characteristics of the host (age), characteristics of the tumor (location) and expressing the influence of the tumor on the host (functional status). Our series documented prognostic clinical forms of these tumors (function of age, of performance status, and of tumor location). Our results confirm the relative inefficacy of therapeutic weapons, considering the population as a whole, on duration of survival. Based on our results and on recently published data, a decision tree analysis was proposed for management of grade II astrocytomas.(ABSTRACT TRUNCATED AT 400 WORDS)
Seven observations, having in common an accumulation of polyglucosan bodies in the nervous system, are reported. In 2 cases of adult polyglucosan body disease, characteristic polyglucosan bodies were found on the peripheral nerve biopsies, and also on the cerebral biopsy in one of these patients who was demented. The 5 other cases presented medically intractable temporal lobe epilepsy. Recovery was obtained by a temporal lobectomy in which a massive accumulation of polyglucosan bodies was discovered. These personal observations are discussed with regard to other conditions characterized by accumulation of polyglucosan bodies in the nervous system. The non specificity of these formations is emphasized.
Results of 20 anterior callosotomies with regard to quality of life and social outcome were analysed according to seizure control. Data arise from a retrospective study with the medico-social teams. Drop attacks with tonic or atonic seizures decreased in 11 cases. Nevertheless only 8 cases (40%) have experienced a reduction of more than 70% in seizure frequency. Neurocognitive status slightly worsened in 3 cases. Age at intervention and type of epileptic syndrome were not predictors of seizure outcome. A subjective improvement in quality of life was reported in 10 cases. A significant improvement in social adjustment was obtained in 7 cases (35%). There was a close correlation between life comfort improvement and reduction in drop attack frequency. Not only seizure control has to be better but also surgery must be performed sooner to obtain a gain in social independence. Finally, successful outcome should be considered as limited. Nevertheless results may be considered taking into account the high severity of the condition and the low morbidity of anterior callosotomy.
Conditions were established for the in vivo determination of free long-chain bases (phytosphingosine, sphingosine and sphinganine) in human stratum corneum layers by reversed-phase HPLC analysis of adhesive-tape strippings. Long-chain bases were first extracted from individual strippings with pure methanol in an ultrasound bath, then o-phthalaldehyde derivatives were separated on a C18 column with a gradient from methanol-water (80:20, v/v) to pure methanol. By performing a second series of strippings for protein determination it was possible to express the amounts of free long-chain bases per milligram of protein for each individual stratum corneum layer. Co-elution of endogenous phytosphingosine, sphingosine and spinganine was demonstrated in separate experiments by addition of standards to typical strips. From a study of three human volunteers, average concentrations of free long-chain bases in the stratum corneum were found to be 2.8, 1.2 and 0.5 nmol/mg of protein for phytosphingosine, sphingosine and sphinganine, respectively.
In a large series of 116 cortical resections for treatment of medically intractable epilepsy, 10 glial hamartomas and 11 neuronoglial malformative lesions were found. Glial hamartomas were astrocytic in 3 cases, oligodendrocytic in 6 and mixed oligoastrocytic in 1. Neuronoglial lesions corresponded to "focal cortical dysplasia" in 6 patients and to "microdysgenesis" in 5 others. This study focuses on the various neuropathological presentations of these malformative epileptogenic lesions, and on correlations with neuro-imaging data.
The metabolism of xenobiotics by the epidermis can be studied in vitro by using keratinocyte cultures. We present a simple and rapid method for determining the activity of cytochrome P450-dependent enzymes (ethoxycoumarin-O-deethylase, ECOD, and ethoxyresorufin-O-deethylase, EROD) in intact cultured human keratinocytes. Using this method, we studied the effect of a well-known cytochrome P450 inhibitor (proadifen) and of two inducers (phenobarbital and 3-methylcholanthrene). As reported in vivo some imidazole compounds (miconazole and econazole) induced ECOD activity at low concentrations and inhibit it at high concentrations. In contrast, two other imidazoles (clotrimazole and sulconazole) only had an inducing effect on ECOD activity. Imidazole itself had no apparent effect on ECOD activity. In conclusion, this model appears to be useful for studying the biotransforming activity of human skin. It allows a rapid evaluation of the inducing/inhibitory effects of xenobiotics.
Histopathologic findings in 110 cortical resections performed for medically intractable epilepsy are reported. The abnormalities observed in our series fell into seven categories: vascular lesions, tumors, non-vascular malformative lesions, focal accumulation of polyglucosan bodies, non infectious inflammatory lesions, hippocampal sclerosis, and mild non-specific lesions. There was no microscopic abnormality in 14 cases. Several patients presented a double pathology, most often an hippocampal sclerosis as one part of the dual pathology.
Individual differences exist between patients, and, for topical therapy, differences in skin due to race may be a consideration. Pharmacological response depends upon the percutaneous absorption and the inherent activity of the chemical once absorbed into the biological system. Our objective was to determine the in vivo percutaneous absorption of three test chemicals in human subjects with Asian (A), black (B) and Caucasian (C) ethnic skin. Following a 30 min topical application on the upper outer arm of 1 mumol/cm2 14C-labeled chemical, percutaneous absorption was determined by both urinary excretion and the stripping technique. Amounts absorbed were: for benzoic acid 1.43 +/- 0.27% (SD) (A), 1.07 +/- 0.18% (B), 1.2 +/- 0.19% (C); for caffeine 1.06 +/- 0.17% (A), 1.01 +/- 0.19% (B) and 0.96 +/- 0.12% (C); for acetylsalicylic acid 1.8 +/- 0.31% (A), 1.59 +/- 0.31% (B) and 2.12 +/- 0.36% (C). No statistical difference (P > 0.05) was found in percutaneous absorption of benzoic acid, caffeine or acetylsalicylic acid between Asian, black and Caucasian subjects.
Massive occurrence of polyglucosan bodies (PB) was found in the surgically removed temporal lobe of a 34 year-old woman presenting with complex partial seizures. The term of PB was proposed in order to group Lafora bodies (LB), corpora amylacea (CA) and Bielschowsky bodies (BB) on the basis of their biochemical similitude. A rigorous histochemical differentiation between these anomalies appears to be impossible at present. LB, BB and CA are mainly made up of glucose polymers i.e. polyglocusans. The pathway(s) leading from glycogen accumulation to PB formation is still unknown. PB are a hallmark of two diseases: Lafora disease and adult polyglucosan body disease. PB have occasionally been reported in rare cases of a variety of other neurological diseases. In all cases they were located within the neurons. This site characterizes Lafora bodies. BB are intraneuronal inclusions but restricted to neurons of the external pallidum. CA occur predominantly in the astroglia during the course of ageing. The significance of these structures depends on their regional distribution. The resemblance does not imply a common etiology for all conditions in which such bodies occur; it is probably due to the sharing of the final path in their causative pathway. Our case does not correspond to any of the classical diseases in which PB have been found. In our opinion, the patient exhibited a localized form of glycogen storage disease.
A patient with a mass lesion of Müllerian origin associated with a spinal dysraphism is reported. The mass lesion was a genuine uterine formation, and a hemorrhage arose from a functional endometrium. A spinal dysraphism was associated, including a low-lying conus medullaris, a subcutaneous lipoma, and a sinus between the cul-de-sac and the lipoma. This ectopic and mature tissue may be differentiated from teratoma and endometriosis.
Massive occurrence of polyglucosan bodies (PBs) was found within the surgically removed temporal lobe of a 34 year old woman with complex partial seizures. This peculiar feature is very unusual in neuropathological examinations of epileptogenic foci. This patient could not be included in any of the classic diseases in which PBs are found. She exhibited a localised form of glycogen storage disease.
Results of 100 cortical resections for 76 temporal, 23 frontal and one parietal lobe epilepsies were studied in terms of seizure relief and overall benefit. A non-homogenous Markov chain model was used to take into account both the intravariability of post-surgical outcome and the differences in duration of follow-up in a group of patients consecutively operated. The seizure free (SF) state was defined as no seizure in the previous five months at first follow up visit and none in the preceding 12 months at subsequent annual visits. For the whole of the population the SF probability was 82%, 66%, 61%, and 62% at six months, one year, two and five years respectively. A better outcome was found for temporal lobe epilepsy (SF probability: 68% at the fifth postoperative year) than for frontal lobe epilepsy (SF probability: 42% at the fifth postoperative year) with a statistically significant difference. Pre- and postoperative interictal signs and symptoms were classified according to their clinical significance: (a) mild handicap--symptoms recognisable but no interference with usual life, and (b) moderate or severe handicap--interference with some or all daily activities. The interictal state was considered more impaired after surgery than before in two situations: (a) either symptoms, absent before surgery, appeared in the postoperative period involving a moderate or severe handicap, or (b) symptoms present before surgery and answerable for a mild or moderate handicap that increased to involve a moderate or severe handicap respectively in the postoperative period. Surgery was considered a major benefit when two conditions were fulfilled-namely, a SF state and no deterioration of the interictal stage when compared with the preoperative period. The probability of obtaining such a benefit was 58%, 51%, 48% and 56% at six months, one year, two and five years respectively. The results suggest that surgery is an effective treatment for more than 50% of long lasting medically intractable epilepsies.
Ocular irritation includes a wide variety of mechanisms some of which can be explored by in vitro methods. For example, the effects on epithelial cells that constitute the outer layers of both the conjunctiva and the cornea may result in direct cytotoxicity or impairment of cellular functions -such as impermeability-, phenomena that can be explored in vitro. Irritancy may also involve inflammation of the conjunctival connective tissue and of the corneal stroma with its vascular and cellular features; effects on the stroma can lead to the opacification of the cornea; this last phenomenon may be the consequence of mechanisms such as modification of the structure of proteins or changes in stroma hydration which in particular is closely related to corneal endothelium metabolic activity. Recovery after eye injury depends partly on the extent of ocular damage and on the residual mitotic activity of the remaining cells. We have studied 41 surfactants, lotions and shampoos in 6 to 8 in vitro methods each one exploring one or two endpoints that could be linked to the ocular irritancy phenomena described above. In vivo ocular irritancy data for these materials from previous studies were compared to in vitro results. The results obtained show that -among the techniques that were investigated and for the categories of substances that were studied- the Het-CAM test and more particularly the endpoint that is related to vascular effects gives the best assessment of acute ocular irritancy (Spearman's rho coefficients between in vivo and in vitro data greater than 0.90); however, cell culture methods, especially one based on short contact time between cells and products and on evaluation of early toxic effects, also proved interesting (Spearman's rho coefficients between in vivo and in vitro data greater than 0.85). Moreover, the isolated cornea opacity and permeability test gave complementary information more related to recovery from surfactant-induced damage. These encouraging results lead us to consider in vitro ocular safety assessment with optimism for the categories of products investigated.
The currently available surgical procedures for the treatment of epilepsy, from fundamental data to therapeutic results, including various means of investigation are reported. The work is based on a review of the literature and on the cases studied by the two teams from the Universities of Montreal and Bordeaux who share the same concept of epilepsy surgery. The patient groups of the two teams include 316 S.E.E.G., 214 cortectomies, 39 callosotomies and 2 multiple sub-pial transsections. In the first part, the authors attempt to demonstrate that the epileptic focus corresponds to the region where the seizures arise, that this focus is not directly comparable to the region where inter-ictal spikes are recorded and sometimes becomes autonomous from the causal lesion. The epileptic phenomenon has a definite harmful effect on cerebral functions and a probable self-aggravating potential. The second chapter summarizes the clinical data on which the indications and contraindications are based. These obviously depend on whether the intervention is intended to be curative or palliative. Various non-invasive and invasive investigations are then reviewed, according to their relative importance and the experience of each team. The main points developed are: the electroclinical correlations during seizures, the symptomatological data for differentiating between temporal and frontal lobe seizures, the contribution of M.R.I. in demonstrating the epileptogenic and epileptic lesions, the electrophysiological information suggesting that S.E.E.G. remains the most informative mean of investigation. The various methods of investigation of assessing electrical, functional (cerebral blood flow, metabolism) and morphological aspects of epilepsy, supply non-redondant findings about the localisation of the epileptic focus. The chapter on surgical techniques mainly discusses the various modes of implantation of subdural and intracerebral electrodes and reports the same rate of morbidity in both cases. Orthogonal teleradiography is still perfectly suited to the implantation of intracerebral electrodes. S.E.E.G. is still the most anatomically precise technique. However, in certain conditions, extraoperative E.Co.G. is more adequate. New surgical modalities have recently appeared such as the multiple subpial transsections which allow treatment of epileptic foci unapproachable by cortectomy and such as modified techniques of hemispherectomy, which by decreasing morbidity, renew interest in them. In the chapter on surgical results, the authors emphasize the methodological problems of evaluation that partly account for their wide variability. The results obtained with the various surgical modalities are reviewed. The outcome in cortectomies is discussed at length in terms of the data from the literature as well as the results reported by both teams.(ABSTRACT TRUNCATED AT 400 WORDS)
Three cases of pleomorphic xanthoastrocytomas (P.X.A.), a low grade leptomeningeal glioma are reported. Prominent histological features used for diagnosis were a cellular pleomorphism of G.F.A.P. positive cells, with intracytoplasmic lipidic vacuols. A reticulinic network and mononuclear cells infiltrates have been observed. A weak mitotic activity and lack of necrosis and of endothelial cells proliferation were significant additional features necessary for diagnosis. Our cases were observed during the surgical management of young patients with resistant epilepsy. Neuroradiological examinations showed a tumor superficially located within the temporal or the parietal lobe. This tumor could be calcified and/or cystic. Operative aspects showed a firm and non-encapsulated leptomeningeal tumor with possible various colors. Our patients were seizures-free after surgery even during the follow-up. From the currently reported cases clinical follow-up ranging for 1.5 to 3 years is not sufficient to predict a favorable carcinologic prognosis. P.X.A. is an uncommon tumor and less than 50 cases are reported throughout the literature. This tumor affecting young subjects mainly during the second decade is revealed in the majority of cases (3/4) by epileptic seizures, less frequently by a deficit or by an intracranial hypertension. The great majority of clinical events are observed before 20 years. The functional prognosis is rather good after surgery with a disappearance of epileptic fits in about 50% of the cases. Throughout the literature the prognosis of this tumor seems to be comparable to low-grade astrocytomas. Optimal management of P.X.A. seems to be primary surgical resection with later surgery for residual or recurrent tumor. The role of radiotherapy in the management of P.X.A. is at this time uncertain.
It is well known that spontaneous desquamation and corneocyte size can reflect respectively stratum corneum cohesiveness and epidermal cell proliferation. The influence of skin pigmentation on these parameters has been investigated on the upper-outer arm of black, white and oriental volunteers, using the detergent scrub method. We found no difference between race in corneocyte surface area, a mean size of 900 microns 2 agreeing closely with that generally encountered in Whites on the upper-outer arm. By contrast, spontaneous desquamation is increased in black vis-à-vis white and oriental skin (factor 2.5, p less than 0.001). Taking into account the importance of the intercellular cement for the cohesion between corneocytes, racial differences in epidermal lipid composition should be investigated.