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Biomedical subjects

P Loiseau

Publications and source records attributed to P Loiseau.

At least 163 records · Page 9Linked to original sources

Effects of josamycin on carbamazepine kinetics.

The steady state pharmacokinetics of oral carbamazepine in epileptic patients (n = 8) was compared before and after one week of treatment with josamycin (2 g/day). There was a small but statistically significant decrease in oral clearance of total (17%) and unbound (21.5%) drug. In spite of an unchanged AUC of 10,11-epoxide carbamazepine the ratio of metabolite to parent drug AUC was significantly decreased (20.2%). The plasma protein binding of carbamazepine and its 10,11-epoxide metabolite did not vary. The results demonstrate impairment by josamycin of the apparent clearance of carbamazepine. Care should be taken in patient receiving both carbamazepine and josamycin.

Adult↗

Symptomatology and prognosis in adolescent epilepsies (a study of 1033 cases).

A follow-up study was carried out on a group of 1033 epilepsy patients seen consecutively between 1955 and 1979. They were all aged between 11 and 19 years at the time of first seizure. Nine hundred and twelve patients were followed up for periods of 5-30 years. The aims of the study were (1) to test the practical applicability of the International Classification of Epilepsy and Epileptic Syndromes, and (2) to examine its prognostic value. The International Classification fitted this group of epileptic patients rather well. The prognosis of adolescent epilepsy varies with the particular syndrome, the probability of being in remission after 10 years ranging from 30 to 67%.

Adolescent↗

New antifilarial agents. 1. Epoxy sulfonamides and ethynesulfonamides.

Two series of 2-substituted 1,2-epoxyethanesulfonamides 2 and ethynesulfonamides 5 were synthesized and evaluated for their antifilarial activity. The trans epoxides 2T were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. The cis isomers 2c were obtained from ethynesulfonamides 5 by semihydrogenation followed by KOCl epoxidation. 2-Substituted ethynesulfonamides 5 were synthesized from appropriate trans-ethenesulfonamides by a bromination/dehydrobromination sequence. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinema dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the epoxides 2T and acetylenic derivatives 5 bearing a 2-aryl substituent were active in vitro. Among these compounds, four epoxides 2T and one acetylenic derivative 5 showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chemical stability of the epoxy sulfonamides 2T. Despite this limitation, the activities observed in this reliable animal model suggest further development and testing of both series 2T and 5 as macrofilaricides.

Animals↗

Long-term treatment of epilepsy: open multicenter trial with progabide in epileptic patients.

A long-term open multicenter trial was carried out in 15 European centers with therapy-resistant epileptics to evaluate the efficacy and safety of progabide, a new antiepileptic GABA receptor agonist; 187 patients, suffering from partial epilepsy (57%), primary generalized epilepsy (20%), secondary generalized epilepsy (21%), and unclassified generalized epilepsy (2%), participated in the study. All patients had a total seizure frequency higher than one per month in spite of standard antiepileptic medication; 46% had a mean partial seizure frequency from daily to weekly. Progabide was administered at a mean daily dose of 30.5 mg/kg/day as an add-on to the standard antiepileptic drugs up to one year in 115 patients; 37 patients (19.8%) dropped out because of reasons which were not drug-related (bad compliance, lost to follow-up); in 12 patients (6.5%) progabide was withdrawn for side effects and in 20 (10.7%) for lack of efficacy. 71.3% of patients treated for one year (62% considering the 'cumulative' number of patients) experienced more than a 50% reduction in seizure frequency. This reduction was equally present in patients with partial epilepsy (63.9%) and with generalized epilepsy (62.2% of patients with primary and 57.1% with secondary generalized epilepsy). No signs of tolerance phenomena to the antiepileptic effect of progabide were observed. No side effects were reported in 56.7% of the patients. Clinical side effects were mild and transient, leading to progabide discontinuation in 6.5% of the patients only; an increase in SGPT was observed in 5.7% of the patients, these increases were transient and without any clinical symptom.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Discontinuation of treatment in epileptic seizures in adolescence].

A retrospective survey on the frequency of seizure-recurrence after drug withdrawal in all forms of adolescent seizures has been undertaken to detect possible prognostic criteria. Patients were selected according to 3 criteria: first seizure between 11 and 19 years of age; out-patients seen by one of us between 1955 and 1979 within the year of onset of epilepsy; all patients followed for at least 5 years after the first seizure. Two-hundred and seventy two patients entered the study. One-hundred and four patients (49 per cent) relapsed, most of them (83 per cent) within the first year after drug withdrawal. In univariate analysis, partial seizures, a normal initial EEG, an isolated seizure, a short length of illness, a long seizure-free period, one seizure only during the first year were significantly linked to a low relapse rate. The probability of being seizure-free after drug withdrawal was about 73 per cent in partial epilepsy, 20 per cent in idiopathic generalized epilepsy, and 36 per cent in undetermined generalized epilepsy. In patients having had a single seizure a dramatic difference was noted according to the seizure type: 12 per cent of relapses after a partial seizure, 69 per cent after a generalized seizure. Neither the age of onset of epilepsy nor the presence of an etiological factor were significant variables in predicting the outcome. When all factors were analysed simultaneously with Cox's hazard function, the type of seizure and the initial EEG appeared to be the only two independent factors significant for a risk of relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Incidence of epileptic seizures in Gironde].

This survey was based on a questionnaire filled by all the neurologists and electroencephalographists of the area and completed with the files of hospitalized patients. Its aim was to ascertain all the residents of the Gironde department who experienced a first epileptic seizure during the period March 1st, 1984-February 28th, 1985. A high global annual incidence rate was found, close to 85 per 100,000 inhabitants. The age and sex-specific incidence rate was very high for elderly persons particularly for males. These figures do not represent the incidence rate of chronic epilepsy, which should be given by follow-up of this group of patients.

Age Factors↗

In vitro proliferation of human lymphocytes measured by an enzyme immunoassay using an anti-5-bromo-2-deoxyuridine monoclonal antibody.

A previously described, non radioactive method for the measure of in vitro mouse lymphocyte proliferation was applied to human lymphocyte proliferation assays. It involved incorporation into DNA, during cell multiplication, of 5-bromo-2-deoxyuridine (BUdR), a thymidine analogue. BUdR-DNA was then assayed by a sandwich enzyme immunoassay (BUdR-EIA) using an anti-BUdR monoclonal antibody (McAb 76-7). BUdR-DNA from crude cell extracts was first immobilized on microtitration plates coated with McAb 76-7. In a second step BUdR-DNA was reacted again with McAb 76-7 conjugated to horse radish peroxydase. The quantity of peroxydase in microtitration wells was then measured by the coloration of o-phenylenediamine (492 nm). Titration curves obtained with dilutions of crude extracts were compared to the curve obtained with a purified BUdR-DNA reference solution. Results were expressed as equivalent ng BUdR-DNA/ml. BUdR-EIA was compared to 3H-thymidine incorporating assay for the measure of lymphocyte proliferation induced by PHA mitogen, candidine and tuberculine antigens and mixed lymphocyte culture. Excellent correlation between both assays was observed for each experiments (r = 0.953 to 0.999). Overall correlation coefficient for the 5 experiments was 0.785, indicating greater variation of BUdR than 3H-thymidine incorporation, according to the mitogen or antigen used and the culture conditions. This could be due to that fact that BUdR-EIA measured only BUdR incorporated into DNA, while 3H-thymidine incorporation assay measured 3H-thymidine both incorporated into DNA, and stocked into the cell before DNA incorporation. BUdR-EIA would thus reflect cell proliferation more exactly than 3H-thymidine incorporation assay. The sensitivities of both techniques were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

[A technic for human basophil degranulation].

We had studied the human basophil degranulation test (HBDT) in 26 cases of allergic patients with drugs (penicillin, erythromycin, josamycin) one month after their anaphylactic reaction. This test was negative in 7 cases on 8 for penicillin, positive in 8 cases on 10 for erythromycin and in 6 cases on 8 for josamycin. The failure of this test with penicillin can be explained by a sensitization to a metabolic penicillin product or to the complex hapten-carrier.

Basophils↗

[Value of cellular immunity tests (lymphocyte transformation test and leukocyte migration test) in the detection of sensitivity to drugs].

We studied degranulation of human basophils (HBDT), lymphoblast transformation and leucocyte migration in 8 cases of patients who were sensitive to penicillin (type 1 hypersensitization of the Gell and Coombes classification). The HBDT was negative in 7 of the cases, whilst the lymphoblast transformation and leucocyte migration tests were positive in 6 cases and negative in 2. These latter tests are more efficient than HBDT in the detection of human sensitization to penicillin.

Cell Migration Inhibition↗

T cell rearranging gene gamma: diversity and mRNA expression in fresh cells from T cell acute lymphoblastic leukemia.

Rearrangement and in most cases expression of the T cell rearranging genes gamma (TRG gamma) and T cell antigen receptor beta chain (TCR beta) genes were studied in 19 cases of T cell acute malignancies where the surface phenotype is representative of the different stages of thymic maturation. TCR alpha gene transcription was also studied. TRG gamma and TCR beta genes were found to be rearranged in all but one case. The TRG gamma rearrangement pattern seen in most cases is compatible with biallelic rearrangement by loop excision involving the J gamma 2 regions. The sizes of all but two rearranged bands were identical to those of the rearranged bands seen in polyclonal T lymphocytes also studied in this work. One identical-sized band was found in 11 of the 18 rearranged cases. The expression of TRG gamma mRNA (transcripts of 1.6 kilobases [kb]) was highly variable from case to case and did not correlate with the stage of differentiation of the malignant cells, the expression of the molecules CD4 and CD8, the expression and size of the transcripts of the TCR beta genes, and the transcription of TCR alpha genes. In one CD3 + case, strong expression of the TRG gamma transcripts coexisted with the exclusive presence of TCR beta mRNA of 1.0 kb. The cells from this case did not react with anti-Ti antibody and exhibited no natural killer activity. These findings are suggestive of a malignancy that may express the recently isolated CD3-TRG gamma complex.

Acute Disease↗

[Subacute encephalopathy. Idiosyncratic reaction to carbamazepine?].

A 81 year-old female, weighing 56 kgs, had taken carbamazepine (10.2 mg/kg/day) for simple partial motor seizures of recent onset during 15 days. EEG recording showed slow waves on the left hemisphere. CT was normal. The seizures were controlled for a few days and then reappeared beginning as simple partial seizures and progressing to impairment of consciousness. The patient became confused. On admission she was severely confused. Neurological examination was otherwise normal. Plasma sodium level was 134 meq/l and CBZ plasma level was 4.3 micrograms/ml. EEG showed high voltage bilateral delta waves and a left focus. The drug was withdrawn with relief of clinical symptoms and to a lesser extent, of EEG abnormalities. Phenytoin encephalopathy is a well known pathological entity but to our knowledge there has been no report of carbamazepine encephalopathy with neither excessive plasma level of the drug nor water intoxication. An idiosyncratic reaction is considered likely.

Aged↗

Phenotypic and genotypic heterogeneity in large granular lymphocyte expansion.

The cellular heterogeneity of large granular lymphocyte expansions has been illustrated by the phenotypic and genotypic findings in five patients. In one patient whose circulating cells were CD2+, CD3-, CD5-, CD7+, CD8-, CD11+, Leu7+, CD16+, and displayed strong natural killer activity, no rearrangement of the T cell receptor beta-chain gene and T cell rearranging gene gamma was detected. The four other patients presented with neutropenia without overt lymphocytosis. In these patients the circulating lymphocytes expressed a predominant T cell phenotype CD2+, CD3+, CD5+, CD7+, CD8+, Leu7+. In three of them the presence of a T cell clone was demonstrated on the basis of a unique pattern of rearrangement of the T cell receptor beta-chain genes.

Aged↗

Correlation between an HLA-DQ alpha length polymorphism of messenger RNA and serologically defined specificities (DQw1, DRw53, DR3+5).

mRNAs for the two chains of the HLA-DQ molecule were analyzed, in particular the DQ alpha mRNA whose polymorphism had previously been suggested (Schenning et al. 1984). Northern blot transfers of the mRNA of 12 LCLs and of B lymphocytes from a healthy donor were carried out. We report that a length polymorphism of DQ alpha mRNA exists, and we show that it can be correlated with serologically defined specificities (DQw1, DRw53, DR3+5). This correlation could be explained by a linkage disequilibrium, as these specificities are considered to be different from those carried by the DQ molecule (except for the DQw1 specificity).

DNA Restriction Enzymes↗

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗