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Biomedical subjects

P Danjou

Publications and source records attributed to P Danjou.

At least 19 recordsLinked to original sources
PubMed2001

Effects of the selective activation of 5-HT3 receptors on sleep: a polysomnographic study in healthy volunteers.

The respective role of various classes of central serotonin (5-HT) receptors in the regulation of sleep-wakefulness cycles has been the subject of many studies. Notably, it has been reported that 5-HT1A/B receptors are involved in the regulation of rapid eye movement sleep (REMS) and that 5-HT2A/C receptors participate in the control of slow wave sleep (SWS), but the role of 5-HT3 receptors is less well characterised. In this study we investigated the effects of SR 57227A, a potent and selective 5-HT3 agonist, on the sleep EEG of normal young male volunteers. SR 57227A (2.5, 5, 10, 20, 40 mg o.d. and 20 mg b.i.d.) or placebo were administered during 7 consecutive days in seven groups of ten subjects using a parallel group design. Sleep EEG recordings were performed on days 6 and 7 after an habituation session. SR 57227A produced a dose-dependent shift of REMS toward the end of the night without changing REMS and SWS duration nor altering sleep continuity. It suggests a role for the 5-HT3 receptor in the human sleep-wakefulness cycle and particularly in REMS regulation.

Adolescent↗
PubMed1999

Zaleplon pharmacokinetics and absolute bioavailability.

The pharmacokinetics and absolute oral bioavailability of zaleplon were assessed to evaluate the extent of presystemic metabolism of this new nonbenzodiazepine hypnotic agent. A partially randomized, single-dose, four-period crossover study was conducted in 23 healthy subjects. Subjects received 1 and 2.5 mg intravenous (i.v.) infusions of zaleplon during the first and second periods, respectively, and then were randomly assigned to receive a 5 mg oral dose or 5 mg i.v. infusion of zaleplon in a crossover design during the final two periods. Zaleplon pharmacokinetics were determined in 20 subjects (ten men and ten women) after the two 5 mg treatments. The oral and i.v. doses of zaleplon administered in this study were safe and well-tolerated. Following i.v. administration, zaleplon had a moderate to high systemic clearance (mean +/- S.D., 0.94 +/- 0.20 L/h/kg), rapid elimination (half-life, t1/2 = 1.05 +/- 0.13 h), and a steady-state volume of distribution of 1.27 +/- 0.25 L/kg, indicating substantial distribution into extravascular tissues. Zaleplon was rapidly absorbed after oral administration, and the mean apparent elimination t1/2 was similar to that obtained after i.v. infusion. The absolute bioavailability was 30.6 +/- 10.2%.

Acetamides↗
PubMed1999

A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2 h before awakening.

AIMS: To compare the duration of the residual hypnotic and sedative effects of zaleplon with those of zolpidem and placebo following nocturnal administration at various times before morning awakening. METHODS: Zaleplon 10 mg, zolpidem 10 mg, or placebo was administered double-blind to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study. Subjects were gently awakened and given medication at predetermined times 5, 4, 3, or 2 h before morning awakening, which occurred 8 h after bedtime. When the subjects awoke in the morning, a battery of subjective and objective assessments of residual effects of hypnotics was administered. RESULTS: No residual effects were demonstrated after zaleplon 10 mg, when administered as little as 2 h before waking, on either subjective or objective assessments, whereas zolpidem 10 mg showed significant residual effects on DSST and memory (immediate and delayed free recall) after administration up to 5 h before waking and choice reaction time, critical flicker fusion threshold and Sternberg memory scanning after administration up to 4 h before waking. Residual effects of zolpidem were apparent in all objective and subjective measurements when the drug was administered later in the night. CONCLUSIONS: The present results demonstrate that zaleplon at the dose of 10 mg is free of residual hypnotic or sedative effects when administered nocturnally as little as 2 h before waking in normal subjects. In contrast, residual effects of zolpidem are still apparent on objective assessments up to 5 h after nocturnal administration, longer than has been reported from studies involving daytime administration.

Acetamides↗
PubMed1998

Absolute bioavailability and electroencephalographic effects of conventional and extended-release formulations of venlafaxine in healthy subjects.

Venlafaxine is currently marketed for treatment of depressive disorders as a conventional tablet formulation with a twice or three times daily dosage regimen. The absolute bioavailability of the conventional (CF) and extended-release (XR) formulations and their effects on electroencephalograms (EEG) and on a visual analog scale (VAS) for nausea were assessed in a randomized, double-blind, four-way crossover, placebo-controlled study of 16 healthy young men who were given either a single oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or an intravenous dose of 10 mg of venlafaxine, or a placebo at 1-week intervals. The absolute bioavailability of venlafaxine was between 40% and 45% and was similar for both the CF and XR formulations. Venlafaxine produced central effects of a desipramine-like antidepressant. Regardless of formulation tested, the main EEG changes were an increase in fast beta (20-30 Hz) energy, which was more pronounced over the frontotemporal regions and extended within the full beta range (16-40 Hz). Maximum effect was reached at 6 hours for the CF and reached a plateau from 10 to 24 hours for the XR formulation. A dose-proportional increase in central activity, expressed as area under the effect curve (AUE) of the beta band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared with the CF tablet, the XR formulation also produced a much less intense maximum effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR formulation has the same absolute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present findings suggest that a once-daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.

Adult↗
PubMed1997

Sensitivity and specificity to amphetamine of a French version of the 49-item form of the addiction research center inventory.

The main metrological characteristics of a French version of the 49-item addiction research center inventory (ARCI) were evaluated using data collected in three controlled studies in healthy subjects. An analysis of variance showed no study effect, so the three studies were pooled. The test-retest reliability coefficients after placebo evaluated by a Spearman rank correlation test were 0.64 (P < 0.0001) for subscale A, 0.49 (P < 0.0001) for subscale BG, 0.55 (P < 0.0001) for MBG, 0.58 (P < 0.0001) for PCAG and 0.27 for LSD (not significant). Using the same test, the test-retest reliability coefficients after amphetamine were 0.73 (P < 0.0001) for subscale A, 0.61 (P < 0.0001) for subscale BG, 0.71 (P < 0.0001) for MBG, 0.46 (P < 0.0001) for PCAG and 0.66 for LSD (P < 0.0001). In order to assess the predictive validity of the translated questionnaire, areas under curves were calculated from the ROC diagrams for the three scores, amphetamine (A), benzedrine group (BG) and morphine benzedrine group (MBG). Two criteria validity were used: the desire to take amphetamine another time and the discrimination of the allocated treatment (amphetamine or placebo). The calculated areas under curves indicated a good capacity of prediction of the three ARCI subscales (A, BG, MBG) for both criteria.

Adolescent↗
PubMed1997

Distribution of gelsolin in human testis.

Gelsolin, an actin-binding and severing protein present in many mammalian cells, was characterized in human testis. Although abundant in testicular extracts, gelsolin was not detected in purified spermatogenic cells by immunoblot analysis. Immunofluorescence studies of testis sections showed that gelsolin has two main localizations: peritubular cells and the seminiferous epithelium. In peritubular cells, gelsolin was present together with alpha-SM actin, in agreement with the myoid cell characteristics of these cells. In a large proportion of the tubules, gelsolin was found mainly, together with actin, in the apical part of the seminiferous epithelium. This localization of gelsolin also was observed in seminiferous tubules with a partial or complete absence of germinal cells, which evokes a presence of gelsolin at the apex of Sertoli cells. However, in normal testis, a complex pattern of gelsolin labeling was also present, mostly in the apical third of the epithelium, around cells or groups of cells, mainly spermatids, and, less frequently, in various other localizations from the apical to the basal part of the seminiferous epithelium. Taken together, these observations suggest that gelsolin may play different functions in the seminiferous epithelium: (1) regulation of the dynamic alterations of the actin cytoskeleton in the apical cytoplasm of Sertoli cells, and (2) modification of actin filaments assemblies in specific structures at germ cell-Sertoli cell contacts. Thereby, the actin-modulating properties of gelsolin are probably involved in reorganization of the seminiferous epithelium related to germ cell differentiation.

Animals↗
PubMed1997

Efficacy of venlafaxine in depressive illness in general practice.

A double-blind, placebo-controlled study of 229 patients with a Research Diagnostic Criteria diagnosis of major, minor or intermittent depression was used to compare the clinical profiles of venlafaxine and imipramine in general practice. Venlafaxine produced a significant improvement compared to placebo in symptoms of depression and anxiety as rated by the total MADRS and percentage of responders, the CGI improvement, the CGI severity of illness, the BSA psychic anxiety item and the HSCL. On a number of these measures, venlafaxine was also significantly more effective than imipramine. Venlafaxine was significantly superior to both imipramine and placebo for the SARS total score and the items 'social/leisure' and 'extended family.' A similar proportion of patients discontinued treatment in each group, but fewer patients on venlafaxine discontinued treatment because of an unsatisfactory response.

Adult↗
PubMed1996

Plasma and skin suction-blister-fluid pharmacokinetics and time course of the effects of oral mizolastine.

OBJECTIVE: To investigate plasma and skin suction-blister-fluid pharmacokinetics of oral mizolastine in order to determine whether the drug concentration in the fluid of suction-induced skin blisters could better predict the antihistamine activity than the plasma concentration. SETTING: Department of Internal Medicine, Université Paris 6. SUBJECTS: Ten healthy male volunteers. METHODS: The volunteers (mean age 26.8 years, mean weight 75.8 kg) received a single 10-mg oral dose of mizolastine at 1000 hours. The pharmacokinetic study included 11 plasma and 9 blister fluid samples and blister epidermal-roof specimens. Mizolastine was assayed by high-performance liquid chromatography (HPLC). Each volunteer also received nine intradermal injections of 5 micrograms histamine. Antihistamine activity was assessed as the post-treatment percentages of changes in the histamine-induced relative wheal and flare areas versus baseline. RESULTS: Mizolastine mean Cmax (SD) and median tmax were, respectively, 380 ng.ml-1 and 0.8 h in plasma, and 21.8 ng.ml-1 and 10 h in blister fluid. Mizolastine could not be quantified in the epidermis. The maximal histamine-induced relative flare inhibition was 72.5% and was attained at the median time of 3 h post-dosing and therefore was delayed by 2.2 h with respect to the plasma tmax. Mean relative wheal inhibition, although lower, showed the same time profile. A direct relationship could not be found between drug concentrations in blister fluid and antihistamine activity. Simulated concentrations in the peripheral compartment better explain the maximum inhibition effect on flare, observed 3 h post-dosing, with a flatter hysteresis loop obtained when plotting relative flare inhibition versus plasma or blister-fluid drug concentrations. CONCLUSION: The mizolastine concentrations in the skin suction-blister fluid were not predictive of the antihistamine activity.

Administration, Oral↗
PubMed1996

[Eight cases of pyelo-ureteral junction syndrome treated by laparoscopic surgery].

From may 1994 to may 1995, eight consecutive patients with symptomatic congenital ureteropelvic junction syndrome (UPJS) were treated by pyeloplasty as described by Anderson, Hynes and Küss by laparoscopic surgery. Three patients had a lower pole artery crossing the anterior surface of the junction and two had a giant renal pelvis. The mean operating time was 120 minutes (min: 90 min; max: 147 min) and the mean hospital stay in the absence of complications (one case) was 3.5 days (min: 1.5 day; max: 8 days). This one complication was due to a postoperative fistula resulting from a technical error requiring an additional fortnight in hospital. All the patients are evaluable at three months. All are asymptomatic and the radiological results showed frank improvement in seven out of eight cases, while the dynamic appearance was improved in the other case. UPJS can be treated by laparoscopic surgery according to proven surgical principles, provided it is performed in a perfectly equipped operating room, by a surgeon and operating team experienced in this type of surgery.

Adolescent↗
PubMed1995

Beta-adrenoceptor agonists do not stimulate daytime melatonin secretion in healthy subjects. A double blind placebo controlled study.

Noradrenergic stimulation of pineal beta-adrenoceptors results in melatonin secretion. To investigate beta-adrenoceptor mediated plasma melatonin responses in humans, ritodrine, salbutamol (beta 2-adrenoceptor agonists) and dobutamine (beta 1-adrenoceptor agonist) were infused from 0900 to 1200 h to 8 healthy subjects (four men and four women) in a double blind, crossover, placebo controlled study. Ritodrine and salbutamol significantly increased plasma cyclic AMP and decreased serum potassium concentrations indicating the presence of beta 2-adrenoceptor stimulation. Dobutamine substantially increased systolic blood pressure corresponding to its beta 1-adrenoceptor agonist propriety. However, neither beta 2- nor beta 1-adrenoceptor stimulation modified plasma melatonin concentration. These results show that beta-adrenoceptor agonists do not increase daytime plasma melatonin concentration.

Adrenergic beta-Agonists↗
PubMed1995

Safety and tolerance profile of venlafaxine.

Venlafaxine has been shown in clinical trials to be safe and well tolerated in patients with major depression. Data were pooled from 19 studies in which 2181 patients were given venlafaxine, 451 were given placebo and 591 were given a reference antidepressant (imipramine, trazodone, clomipramine, maprotiline, dothiepin or amineptine). Long-term safety was evaluated in 422 patients who were given venlafaxine for at least 1 year; as well, a total of 229 elderly patients have been treated with venlafaxine, including 66 who were given it for at least 1 year. The adverse events that occurred during short-term treatment in > or = 10% of patients were nausea, headache, insomnia, somnolence, dry mouth, dizziness, constipation, asthenia, sweating and nervousness. In comparator-controlled trials, the frequency of anticholinergic events with the reference agents was approximately twice that with venlafaxine. The safety profile and patient acceptability of venlafaxine are comparable to those of third-generation antidepressants, and possibly better than those of first-generation agents.

Antidepressive Agents, Second-Generation↗
PubMed1995

Renal angiomyolipoma: growth followed up with CT and/or US.

PURPOSE: To follow up the growth of renal angiomyolipomas (AMLs). MATERIALS AND METHODS: Patients with known AML (n = 55) were divided into three groups on the basis of initial clinical and computed tomographic (CT) findings: group 1, isolated AML (n = 43); group 2, multiple AMLs without tuberous sclerosis (TS) (n = 6); group 3, multiple AMLs with TS (n = 6). Follow-up ultrasonography (US) and CT were performed in 55 and 31 patients, respectively. Growth of the AMLs (n = 59) was evaluated on the basis of area on initial and follow-up images. RESULTS: Mean percentage growth was 17%, 128%, and 47%, and mean growth rate per year was 5%, 22%, and 18% in groups 1, 2, and 3, respectively. New renal lesions were noted in three patients in groups 1 and 2, but no new lesions were detected in group 3, because of the large number of AMLs. New extrarenal lesions were observed in four, two, and three patients in groups 1, 2, and 3, respectively. No correlation was found between percentage of fatty tissue and growth rate. CONCLUSION: Multiple AMLs show more growth than solitary AMLs.

Adipose Tissue↗
PubMed1995

[Congenital pyeloureteral junction syndrome in adults treated with laparoscopic surgery].

OBJECTIVES: To perform pyeloplasty as described by Andrson, Hynes and Küss by laparoscopic surgery for the treatment of ureteropelvic junction syndrome (UPJS): METHODS: In patients with an indication for treatment for UPJS, we proposed laparoscopic pyeloplasty via a trans-abdominoretroperitoneal incision. The ureteroplevic junctions were exposed after detachment of the colon and were resected. Three Vicryl 4/0 running sutures were performed : two for the ureteropelvic anastomosis and one for the pelvic racket handle. The lower pole vessels were transposed posteriorly to the urinary tract and all anastomoses were protected by a previously inserted stent. Operating times and postoperative hospital stays, and volume of blood loss were recorded. At three months, five patients are evaluable clinically and radiologically by comparison of pre- and postoperative urographies. RESULTS: From May 1994 to May 1995, seven consecutive patients (mean age : 33.4 years, range : 17-65 years) presented with symptomatic congenital UPJS. Three patients had a lower pole artery crossing the anterior surface of the junction, and two had a giant renal pelvis. The mean operating time was 120 minutes (max : 147 min; min. : 90 min). The blood loss was always less than 50 ml. The mean hospital stay in the absence of complications (1 case) was three days (max. : 4 days, min. : 1.5 days). This one complication was due to a postoperative fistula resulting from a technical error requiring an additional fortnight in hospital. The five evaluable patients are asymptomatic. Radiological results showed frank improvement in four out of five cases, while the dynamic appearance was improved in the other case. CONCLUSIONS: UPJS can be treated by laparoscopic surgery according to proven surgical principles, provided it is performed in a perfectly equipped operating room, by a surgeon and operating team experienced in this type of surgery. Laparoscopic pyeloplasty therefore constitutes an alternative to open surgery and endopyelotomy, as the patients benefit from the advantages of laparoscopic surgery without impairing the efficacy of treatment of UPJS.

Abnormalities, Multiple↗
PubMed1994

Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.

The possible effects on memory, psychomotor performance and mood of eliprodil, a new non-competitive NMDA receptor antagonist acting through the polyamine modulatory site, was assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a placebo and midazolam 15 mg, a positive control, were administered as a single oral dose at 1 week wash-out intervals. Objective tests evaluated both memory (Sternberg memory scanning and paired words for short-term memory, delayed free recall of pictures for long-term memory) and psychomotor functions and arousal (critical flicker fusion threshold, choice reaction time, body sway). Mood was assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was performed using an ANOVA with pairwise comparisons using Tukey's method. A single dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled performance and did not produce either subjective sedation or excitation or psychotomimetic effects in comparison with placebo. In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory). The potent sedative activity of midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and had disappeared 8 h post-dose.

Adult↗
PubMed1993

Pharmacokinetics and pharmacodynamics of zolpidem following repeated doses in hemodialyzed uraemic patients.

Zolpidem, an imidazopyridine derivative, is a chemically novel, non-benzodiazepine hypnotic agent. Many uraemic patients complain of sleep disorders and ask for hypnotic medication which is well tolerated both clinically and biologically in such patients. We studied the pharmacokinetics and pharmacodynamics of zolpidem in 12 end-stage renal patients regularly treated by hemodialysis three times a week. Zolpidem (10 mg) was given orally for 14 or 21 days. Pharmacokinetic and pharmacodynamic evaluations were repeated at the end of the study on day 14 or day 21. Cmax, Tmax, t1/2 and the area under the curve were not modified in hemodialyzed patients. After daytime dosing, zolpidem induced the same level of sleepiness after the first and last dose and was well tolerated as a hypnotic agent after the night-time dosing. From these results, it can be said that zolpidem may be administered safely to patients with severe renal impairment without any modification of the dosage regimen.

Adult↗
PubMed1993

[A priori benign Leydig cell testicular tumor: enucleation or radical orchidectomy?].

The histological sections of 5 patients treated for clinically benign Leydig cell testicular tumour (LCTT) were reviewed according to histological criteria presumptive of malignancy. The absence of any sign of severity was only verified in a single case, as none of the other tumours could be considered to be strictly benign. In the light of these findings, great caution is required in conservative indications, especially as these tumours, when they are malignant, are particularly serious due to the inevitable diagnostic delay and their absence of radio- or chemo-sensitivity.

Adult↗
PubMed1993

[Acute necrotic pancreatitis secondary to asparaginase. Role of drug combinations--early diagnosis and treatment. Apropos of 2 cases].

Acute necrotic pancreatitis was diagnosed in two patients treated with asparaginase for, in the first case a highly malignant lymphoma and in the second an acute lymphoblastic leukemia. The diagnosis on clinical findings and amylase assay results was confirmed by LDH and/or C reactive protein values and abdominal CT scans. Both patients recovered after drainage of peripancreatic fluid collections, in the first patient by surgical followed by cutaneous drainage and in the second by cutaneous drainage of a pancreatic pseudocyst. In addition to the frequent pancreatic reaction observed during asparaginase treatment, signs of pancreatic necrosis requiring urgent treatment have to be identified. The necrotic nature of the pancreatitis was confirmed by clinical examination, assay to biologic markers and abdominal CT scans, eliminating other causes of the pancreatitis.

Acute Disease↗