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Biomedical subjects

C Sebban

Publications and source records attributed to C Sebban.

At least 19 recordsLinked to original sources
PubMed1992

[Aging of heart function in animals].

Most of the laboratory animals studied for cardiovascular ageing are rodents. Anatomical studies have demonstrated an increase in heart weight and volume, hypovascularization of the myocardium and, more recently, hypertrophy of myocytes. Studies on the mechanical properties of rat papillary muscle have shown that ageing is associated with reduction of myocardial distensibility, whereas the habitual parameters of contractility (Tmax and Vmax) are unchanged in terms of baseline values. On the other hand, mechanical responses to stimulation of beta-adrenoceptors are reduced. The essential change in myocardial contraction in ageing rats is its chronology: ageing is attended by a longer duration of both contraction and relaxation. Biochemical studies of old rats' myocardium have yielded a fundamental information: in this species ageing is accompanied by a change in synthesized myosin subtype. This change is identical to that observed in experimental systolic overload; it is also adaptative, as it enables oxygen consumption to be reduced during a constant work, and it explains the modifications observed in the chronology of a contraction. Studies on the "pump" function of old rats' myocardium have confirmed the appearance with age of another adaptative change: isolated hearts of old animals have a greater output in a rigid circuit while the hearts of adult rats have their output in a more compliant circuit. Altogether, experimental studies on cardiac ageing lead to the conclusion that the changes observed are similar to those due to systolic overload, the origin of which is a loss of arterial compliance. These changes are adaptative in that they reduce oxygen consumption by a myocardium with systolic overload, but the resulting changes in contraction chronology are such that the aged heart cannot deviate from a mean rate without notably widening the differential blood pressure. Thus, experimental studies of myocardial ageing have presented ageing as a contradiction between ideal adaptation to a chronic stress and reduced possibilities of adaptation to acute aggressions.

Aging↗
PubMed1992

Maintenance with low-dose cytarabine for acute myeloid leukemia in complete remission.

Thirty-four patients with acute myeloid leukemia (AML) in complete remission (CR), 30 of them aged over 60, received maintenance therapy scheduling four courses of low-dose cytarabine (LDA) 20 mg/m2/day in two subcutaneous injections for 3 weeks every 6 weeks. Each course was stopped when hematologic toxicity occurred, and doses of LDA were subsequently reduced by 50% for the following courses. During the first course of LDA, 15 patients needed blood and four patients platelet transfusions. Overall, 28 patients received four courses of LDA: 11 did not require any dose reduction, while 14 required one dose reduction and three needed two successive dose reductions. Two patients were hospitalized during maintenance. Median disease-free survival (DFS) is 308 days, with 16% of patients surviving at 5 years. Seven patients relapsed during the 168 days of maintenance, while ten of the 27 patients remaining at risk on day 169 relapsed during the 168 days following maintenance. We conclude that in AML in CR, the maximal dose of LDA tolerated by ambulatory patients is 10 mg/m2/day for 3 weeks. LDA seemed to delay relapse; however, precise assessment of the efficacy of this approach would require a randomized trial.

Acute Disease↗
PubMed1992

Continuous-infusion daunorubicin and carboplatin for high-risk acute myeloid leukemia in the elderly.

Since continuous infusion of daunorubicin and of carboplatin have shown efficacy and reduced toxicity in early phase studies in acute myeloid leukemia (AML), 34 elderly patients with high-risk AML were treated with continuous infusion daunorubicin, 30 mg/m2 per day, from day 1 to day 4, and carboplatin, 200 mg/m2 per day from day 3 to day 7. Seven patients had therapy-related AML and/or AML following a myelodysplastic syndrome at diagnosis, 15 were in first and two in second relapse, and 10 were resistant to previous anthracycline and cytarabine therapy. Nine patients or 26%, with a 95% confidence interval (CI) ranging from 18-67%, achieved complete remission, including one patient at diagnosis (14%, CI: 0-58%), seven with relapsed AML (41%, CI: 18-67%), and one with resistant AML (10%, CI: 0-45%). Median durations of neutropenia below 0.5 x 10(9)/l and of thrombocytopenia below 20 x 10(9)/l were 24 and 20 days respectively. Severe toxicity included infections in 20 patients (59%), bleeding in two (6%), cardiac anomalies in two (6%), and vomiting in one (3%). Overall four patients (12%) died from chemotherapy related toxicity and 21 (62%) had resistant disease. Median overall survival was 4 months and median disease-free survival 8 months. We conclude that this regimen had efficacy with reduced toxicity in relapsed patients. Higher dosages for the same drugs could be tolerated by better risk patients for precise evaluation of cross reactivity with cytarabine-based regimens.

Acute Disease↗
PubMed1991

[The significance of quantified EEG in Alzheimer's disease. Changes induced by piracetam].

One study was performed in 12 patients with presenile Alzheimer's disease (group I), the other one in 16 patients with mild senile dementia of Alzheimer type (group II). In each study, patients were divided into two randomized parallel groups, one receiving placebo, the other piracetam (9 g daily in group I piracetam and 2.4 g daily in group II piracetam) during three months, piracetam induced a decrease in EEG power on the 2-6 Hz range (group I piracetam), 3-5 Hz and 7 Hz (group II piracetam) and an increase of EEG power in the 9-11 Hz range (group I piracetam) and in the 10 Hz and 13 Hz frequencies (group II piracetam). There was also a significant improvement in the Trail Making Test part A in group II piracetam. Correlations between decreased EEG low frequency components and improvement in some psychometric tests were found significant in the two groups. It seems that the main effect of piracetam was to induce increased alertness. The same results were found in both studies; the good reproducibility suggests that EEG spectral analysis is a reliable tool in the assessment of psychotropic drug effects.

Aged↗
PubMed1990

Successful treatment of adult acute lymphoblastic leukemia after relapse with prednisone, intermediate-dose cytarabine, mitoxantrone, and etoposide (PAME) chemotherapy.

Thirty-nine patients with relapsed acute lymphoblastic leukemia (ALL) and four with primarily refractory ALL were treated with a regimen that included cytarabine 1 gm/m2 (2-hour infusion) twice daily days 1 to 5, mitoxantrone 12mg/m2 daily days 1 to 5, prednisone 0.5 mg/kg daily days 1 to 5, and etoposide 200 mg/m2/day daily days 6 to 8. Of the 43 patients, 30 achieved a complete remission (CR), 28 out of the 39 relapsed patients and two among the four with refractory disease. Five patients died in aplasia. Eight patients were nonresponders. Nonhematologic side effects consisted predominantly of nausea, vomiting, and mucositis. One patient had transient cerebellar dysfunction. Recovery of blood counts occurred at a median of 24 days. The median time to CR was 38 days. As this regimen is highly effective in relapsed or refractory ALL, its use during earlier stage of the disease is warranted.

Adolescent↗
PubMed1990

A review of the EEG effects of the combination of almitrine and raubasine in animals and humans.

During recent years many studies on the electroencephalogram (EEG) changes induced by almitrine-raubasine (Duxil) have been performed in elderly patients and in animals. This article gives an overview of three questions raised by their results. Is there a simple addition of the raubasine and almitrine effects when they are coadministered? Are the EEG effects of this treatment dependent on the patient's disease? To what extent could EEG studies provide some knowledge about the mechanism of action of almitrine-raubasine therapy? In adult (8 months) and aged (22 months) rats the EEG changes induced by the coadministration of almitrine and raubasine were significantly different from the addition of individual almitrine and raubasine EEG effects. In adult rats the coadministration induced slighter EEG changes than those predicted by the addition of almitrine and raubasine effects. In aged rats, the coadministration induced a decrease in delta-theta power not predictable from the effects of almitrine or raubasine. These results could be taken as an indication that some biological targets are common for the two drugs and that the coadministration results in pharmacological effects more complicated than a simple addition of raubasine and almitrine properties. After 3 weeks of treatment in aged healthy subjects, the coadministration induced an increase in the alpha and beta power with a slight decrease of delta and beta-1 powers. In patients with cognitive decline of probable degenerative origin, 3 months of therapy with almitrine-raubasine was mainly associated with a decreased delta and theta power and a slight increase in high frequency components of the alpha band.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Almitrine-raubasine and cognitive impairment in the elderly: results of a 6-month controlled multicenter study.

Two-hundred four patients between 70 and 85 years of age were included in a double-blind randomized controlled multicenter study (almitrine-raubasine/placebo). Inclusion criteria were a complaint of cognitive disorders and an objective cognitive impairment evaluated by Folstein et al. "Mini-Mental State" (MMS) and by Sandoz Clinical Assessment for Geriatrics (SCAG). Patients were treated for 6 months and evaluations were performed at the beginning of the trial (T0), then 3 (T3) and 6 (T6) months later. Evaluations included a visual analogic self-rating scale and the following psychometric tests: Trail Making A (TMA), Shopping List Task, Word Fluency, Crossing Out Letters, Logical Memory, Digit Span, and Visual Retention. Anxiety and Depression Scales were also used to assess the effects of almitrine-raubasine on affective status. Statistical analysis involving the whole sample did not show any significant difference between the almitrine-raubasine and placebo groups concerning changes in assessment criteria from T0 to T6. However, these results may have been due to the wide heterogeneity of baseline performances in psychometric tests. To prevent this possible bias, further statistical analysis was performed for each psychometric test after patients had been divided into three classes according to baseline score levels. Considering scores on TMA and Digit Span for patients with scores in the intermediate class on TMA, almitrine-raubasine induced a significantly higher improvement in performance from T0 to T6 than that induced by placebo. On the other hand, no side effects were noted with almitrine-raubasine when compared with placebo. These data suggest that almitrine-raubasine enhances concentrated attention in patients with mild to moderate impairment of this function.

Aged↗
PubMed1990

[Duxil and cognitive deficiency in the elderly. Results of a 6-month controlled multicenter study].

Two hundred and four patients, 70-85 years old, were included in a double-blind (Duxil/placebo), controlled, multicentric study. The inclusion criteria were a subjective complaint of a cognitive deficiency and a cognitive deficit objectively determined using the Folstein mini-mental state test and the Sandoz geriatric clinical evaluation score. The patients, treated for 6 months, were examined at the onset of the study (T0), then 3 (T3) and 6 months (T6) later. The assessment criteria included: a visual self-evaluation test measuring cognitive function and the following psychometric tests: trail making A (TMA), memorization of a shopping list, verbal fluidity, letter identification, repetition of a story, immediate recall of numbers and immediate visual memory. Anxiety and depression evaluations were also used to assess the effects of Duxil on the affective state. Statistical analysis of the observations made on the entire population did not reveal a significant difference between the treated group and the control placebo group, in terms of assessment criteria, between T0 and T6. However, this lack of a difference could be explained, in part, by the very wide variation in the initial psychometric performance scores of the subjects. In an attempt to control this possible bias, another statistical analysis was made for each psychometric test, after the patients had been divided into 3 classes based on their initial performance scores. The results of this second analysis showed that Duxil was able to improve memory performances in TMA and number retention better than the placebo. However, this effect was limited to the group of patients whose initial scores were in the intermediate class for TMA. These findings suggest that Duxil improves the concentrating ability of patients with light to moderate deficits in this function.

Aged↗
PubMed1989

[Treatment of acute myeloblastic leukemia in aged patients].

Approximately 55 per cent of patients with acute myelogenous leukaemia (AML) are over 60 years of age, which raises therapeutic problems since the intensive chemotherapy generally used in younger patients is very toxic in the elderly. The three main therapeutic alternatives offered to the physician in elderly patients are: (1) initial therapeutic abstention followed by palliative chemotherapy habitually using hydroxyurea when control of hyperleukocytosis is required; (2) intensive chemotherapy with anthracyclines and cytosine arabinoside (araC) based regimens, which induces complete remission in 45 to 50 per cent of the cases at the price of an initial toxic death rate of approximately 30 per cent, with 5 to 15 per cent of the patients possibly being cured, and (3) low-dose araC inducing complete remission, generally of shorter duration, in 25 to 30 per cent of the patients with about 10 per cent toxic deaths. In the absence of randomized trial comparing these approaches, there are no objective criteria enabling precise therapeutic indications to be defined. Poor initial general condition and a past history of myelodysplastic syndrome are widely accepted factors of poor prognosis whatever the therapeutic strategy used.

Aged↗
PubMed1989

l-fenfluramine and haloperidol in rats: a qEEG comparison.

EEG effects of l-fenfluramine (l-F) (2.5, 5 and 10 mg/kg) and haloperidol (0.1, 0.25 and 0.5 mg/kg) were studied in 20 adult rats. The EEG signals of two prefrontal (A = +4, L = 2.5) and two sensorimotor (A = -4, L = 4) transcortical electrodes were analyzed in each rat during three 60-min periods, 1, 3 and 5 h after the intraperitoneal (IP) administration of the drugs. In the prefrontal cortex haloperidol induced a decreased power for the 1-3 Hz components and an increase in power for frequencies higher than 8 Hz, with a maximum around 13 Hz. These effects were already observed after 0.1 mg/kg. In this cortical area l-F administration was essentially associated with a decrease of power maximum for 3-8 Hz, an increased power for the 10-19 Hz band being present only after 10 mg/kg. In the sensorimotor cortex haloperidol appeared less potent than in the prefrontal site; a significant power increase for the frequencies higher than 8 Hz was only observed with 0.5 mg/kg. On the contrary, l-F appeared more effective in this area, its action being characterized by a decreased power from 2-8 Hz and a power increase already significant with 2.5 mg/kg for the frequencies higher than 10 Hz, with a maximum lying around 15 Hz. These results suggest that haloperidol induced cortical sedation (increased power) on the two recording sites. l-F also induced a net cortical sedation in sensorimotor cortex but up to 5 mg/kg acted in the opposite direction on the prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow↗
PubMed1989

Comparative effects of almitrine and raubasine, singly and in combination, on electroencephalographic activity in young and old rats.

A new method for quantification of electroencephalographic (EEG) signals was used to study the effects of almitrine and raubasine, alone and in combination, in two groups of six unanesthetized rats, aged 8 months (young) and 22 months (old). Coadministration of almitrine (7.5 mg/kg-1 i.p.) and raubasine (2.5 mg/kg-1 i.p.) induced an increased EEG power from 7 to 30 Hz; the frequencies concerned were identical in young and old rats, but the degree of their power variations was more marked in old rats. Almitrine induced a 20 to 50% increase in EEG power in young rats on nearly all spectral components. The effects of almitrine were only seen in the low-frequency range in old rats. Raubasine increased the EEG power in the 10 to 20 Hz frequency range; these effects were significantly greater in old rats. In both age groups, the effects on EEG power observed with coadministration of almitrine and raubasine were significantly different from those expected if raubasine and almitrine add their individual effects. These results show that a) almitrine and raubasine modify cortical electrical activity in a different manner as a function of age; b) the modification of the EEG activity induced by the coadministration is suggestive of an interaction between the cortical effects of each drug; and c) the modification of EEG power induced by the coadministration is qualitatively identical in young and old rats but quantitatively more marked in old rats.

Aging↗
PubMed1989

[Quantified EEG and psychometric effects of 3 doses of dexfenfluramine in the young adult].

In an acute, double-blind placebo-controlled study, three groups of nine healthy subjects were included. Each group received, in randomized and weekly intervals, a single oral dose of dexfenfluramine (15 mg, 30 mg or 60 mg) or placebo. Psychometric and EEG studies were carried out before as well as 1, 2, 3, 4, 5 and 6 h after drug administration. Changes from predrug to postdrug conditions for each time were determined by the ratio of absolute spectral power and compared to the evolution of power spectra under placebo conditions. Statistical evaluation was done with ANOVA. Dexfenfluramine induced a dose-dependent decrease of power spectra for theta and alpha 1 bands and an increase for the beta band. Topographic brain mapping of these significant changes displayed a central and posterior decrease for theta and alpha 1 bands, and a temporal localization for the beta-power. Maps of relative power-enhanced changes were seen in absolute power and provided false displays. Psychometric evaluation of dexfenfluramine effects only showed trends to extraversion and increased mood scores but no statistical significance was found. Arousal and performance tests were unchanged. These results suggest that qEEG variations are more sensitive to serotonergic drug effects than psychometric investigations. It appears that spontaneous EEG power spectra variations with time must be accounted for by drug evaluation. Absolute power variations are more reliable than relative power. Methodological implications are discussed.

Adult↗
PubMed1988

Treatment of acute myeloid leukemia in elderly patients. A retrospective study.

In an attempt to rationalize the use of therapy in acute myeloblastic leukemia (AML) in elderly patients, 69 cases of primary AML in patients older than 60 years of age were reviewed retrospectively. Therapy was empirical and 12 patients received supportive care (SC) only, 35 received aggressive chemotherapy (AC), and 22 received low-dose cytosine arabinoside (LD-araC). Patients receiving SC only often had a poor Karnofski index and their median survival was 17 days. Aggressive chemotherapy yielded complete remissions (CR) in 48% of the patients, whereas 23% of the patients had resistant disease (RD) and 29% had other failures (OF). Low-dose araC, which was administered to patients significantly older than those receiving AC, yielded 23% CR, 68% RD, and 9% OF, with important hematologic toxicity in most patients. Median survival was 211 days in patients receiving AC and 235 days in patients treated with LD-araC. Survival beyond 2 years from diagnosis was noted in the AC group only. A low Karnofski index was the strongest factor in poor prognosis, while age was not a prognostic factor. The initial characteristics of the patients did not allow us to define groups of patients who should be treated by either AC or LD-araC. We concluded that the decision to treat patients actively should rely more on the patient's general condition and socio-economical criteria than on age.

Aged↗
PubMed1988

Effects of apomorphine in quantified electroencephalography in the frontal cortex: changes with dose and time.

The purpose of this study was to investigate the role of four doses of apomorphine (0.01, 0.05, 0.25, 1 mg/kg s.c.) on the cortical activity by a quantified electroencephalography (EEG) method recently developed in our laboratory. The EEG-effects of apomorphine were changed significantly according to the dose and the time. When initial effects were considered an opposition in the apomorphine-induced variations between low (0.01 mg/kg) and higher doses were observed. In the time course with 0.01, 0.25 and 1 mg/kg SC, EEG variations changed the direction in 6-17 Hz and diminished in the other spectral components. Qualitatively, this tardive change with 0.01 mg/kg may show a feed-back response of the dopaminergic system to the initial low dose-induced depressant effects of apomorphine. On the other hand higher doses-induced tardive EEG pattern may show a possible changed balance in the stimulated D1 and D2 receptors.

Animals↗