Assessment of the phytotoxicity of seaport sediments in the framework of a quarry-deposit scenario: germination tests of sediments aged artificially by column leaching.

The aim of the Sustainable Management of Sediments Dredged in Seaports (SEDIGEST) project is to assess the risks of treated port sediments for terrestrial ecosystems when deposited in quarries. We simulated the "ageing" of these sediments up to the "moment" when plants can germinate. Sediments were leached by water percolating through a laboratory column. Sediments 1 and 2, taken from the port of Toulon (France), were dried and aired. Sediment 3, taken from the port of Guilvinec (France), was stabilised with lime. Phytotoxicity was evaluated on the three artificially aged sediments using germination and early development tests (48 h to 7 days) by Phytotoxkit F(TM) bioassays. The three dilutions tested were performed with the reference "ISO substrate" and with Lolium perenne sp. (rye grass), Sinapis alba (white mustard), and Lepidium sativum (watercress). The tests performed with sediments 1 and 2 showed (1) a decrease of their toxicity to the germination of the species selected following leaching and (2) that L. perenne was the most sensitive species. The tests performed with sediment 3 showed that it was improper for colonisation even after leaching simulating 16 months of ageing. These germination tests on aged sediments identified the effects of leaching and made it possible to appreciate the capacity of the sediments to allow colonisation by plants.

An architecture for online comparison and validation of processing methods and computerized guidelines in intensive care units.

Clinical decision support systems are a combination of software techniques to help the clinicians in their medical decision making process via functionalities ranging from basic signal analysis to therapeutic planning and computerized guidelines. The algorithms providing all these functionalities must be very carefully validated on real patient data and must be confronted to everyday clinical practice. One of the main problems when developing these techniques is the difficulty to obtain high-quality complete patient records, comprising data coming both from the biomedical equipment (high-frequency signals), and from numerous other sources (therapeutics, imagery, clinical actions, etc.). In this paper, we present an infrastructure for developing and testing such software algorithms. It is based on a bedside workstation where testing different algorithms simultaneously on real-time data is possible in the ward. It is completed by a collaborative portal enabling different teams to test their software algorithms on the same patient records, making comparisons and cross-validations more easily.

Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens.

This 3-month double-blind, randomized, parallel-group study compared the efficacy and tolerability of two regimens of the lipido-sterolic extract of Serenoa repens (Permixon) (two 160-mg capsules once daily [OD] and one 160-mg capsule twice daily [BID]) in 100 outpatients with symptomatic benign prostatic hyperplasia (BPH). Both regimens significantly (P < .0001) reduced the International Prostate Symptom Score (I-PSS) mean total score from baseline; improvements achieved statistical significance after the first month and were maintained for the duration of the study. Significant (P < .05) and rapid improvements from baseline to the end of month 1 also occurred in I-PSS quality-of-life (QoL) scores, maximum and mean urinary flow rates, and residual urine volume; this benefit was further increased at month 3 for I-PSS total score and QoL and residual volume, and was maintained for maximum and mean flow rates. A highly significant decrease (P < .001) in residual urine was observed in both groups. No significant differences were noted between regimens. Clinical adverse events occurred at a similar incidence in both groups (BID, 24%; OD, 22%) and were deemed unrelated or unlikely to be related to Permixon.

Multiple-dose pharmacokinetics of moxisylyte after oral administration to healthy volunteers.

The pharmacokinetics of moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylmoxisylyte (DAM) and the conjugate of desmethylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.

Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum.

The effect of the alpha-adrenergic blocker moxisylyte was examined on smooth muscle cells isolated from human corpus cavernosum, and compared with that of other adrenergic agents and papaverine. Isolated smooth muscle cells were shown to contract (reduction of the mean cell length) under noradrenaline and carbachol stimulations in a time-dependent and concentration-dependent manner (maximum at 30 seconds, EC50 [noradrenaline] = 5 nM., EC50 [carbachol] = 1 nM.). The contractile effect of noradrenaline was dose-dependently inhibited by moxisylyte (IC50 = 0.5 +/- 0.2 microM.) and by prazosin (IC50 = 0.9 +/- 0.2 microM.). The dose-response curves were parallel and no statistically significant difference could be shown between the IC50 values. The alpha 2-adrenergic antagonist tolazoline also inhibited noradrenaline-induced contraction, whereas the alpha-adrenergic agonist methoxamine did not change the mean cell length. As expected, isoproterenol caused relaxation of noradrenaline-precontracted cells by interaction with a beta 2-adrenergic receptor. Papaverine was also found to inhibit the contraction induced by noradrenaline in a dose-dependent manner (IC50 = 2 +/- 0.3 nM.). Tritiated-dihydroergocryptine (3H-DHE) specific binding was competitively inhibited by moxisylyte and prazosin with the same IC50 value of 0.01 microM. Methoxamine and tolazoline also inhibited this binding with lower affinity (IC50 = 0.1 +/- 0.02 microM.), while isoproterenol did not change specific binding. Scatchard plots from saturation experiments with 3H-DHE and with 3H-N-methyl scopolamine revealed the presence of 15 times more adrenergic than muscarinic binding sites (650,000 and 45,000 sites per cell, respectively). Together, these data support evidence for the presence of postsynaptic alpha 1-adrenergic receptors on smooth muscle cells from human corpus cavernosum. These receptors are coupled with the contraction of the cell and are blocked by the alpha 1-adrenergic antagonists moxisylyte or prazosin. They also show that the phosphodiesterase inhibitor papaverine and the beta-adrenergic agonist isoproterenol induced relaxation. This model constitutes a new approach to study the potential targets of the adrenergic agents in the erectile tissue.

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and intracavernous administration.

The concentration-time profiles of metabolites of moxisylyte, an alpha-adrenergic receptor blocking agent, in the plasma of 12 healthy volunteers were investigated after intravenous (iv) and intracavernous (ic) administrations. The study was conducted in open, randomized, Latin Squares. Plasma levels of moxisylyte and its biotransformation products were assayed by a specific high-performance liquid chromatography method with fluorescence detection. Three metabolites, unconjugated desacetylmoxisylyte (DAM), conjugated DAM, and conjugated monodesmethylated DAM (MDAM), were found in plasma. After iv administration, unconjugated DAM appeared in plasma in < 5 min; the formation of this metabolite is slightly lower after ic administration (half-life, 6.08 +/- 2.33 min). Maximum plasma levels (57.2 +/- 29.4 ng/mL) and area under the curve of concentration versus time (43.3 +/- 11.4 micrograms.h/L) were significantly lower after ic administration than after iv administration (352.8 +/- 287.6 ng/mL and 152.6 +/- 0.247 micrograms.h/L, respectively). For conjugated DAM, the time to reach the maximum concentration is significantly increased after ic administration (0.9 h instead of 0.46 h) and the maximum concentration is significantly decreased (163.5 ng/mL instead of 203.4 ng/mL). The other pharmacokinetic parameters show no change between the two routes of administration. The pharmacokinetic parameters computed for MDAM are in the same range after iv and ic administrations, and there are no significant statistical differences.

Dose-related effect of moxisylyte on maximal urethral closing pressure in patients with spinal cord injuries.

The effects of single intravenous doses of 0.25, 0.50, and 0.75 mg/kg moxisylyte on maximum urethral closure pressure were evaluated in a placebo-controlled double-blind experiment in 20 patients with spinal cord injuries. Pharmacodynamic testing was performed until 30 minutes, and blood pressure was assessed until 60 minutes. Our findings showed a dose-dependent decrease in maximum urethral closure pressure. At each individual time point, the three doses differed significantly from placebo. Ten minutes after dose administration the maximum effect (48% decrease) was obtained with 0.75 mg/kg. A significant difference in favor of the highest dose was shown from 15 to 20 minutes after administration. According to these findings and because 0.75 mg/kg was as well tolerated as the two other doses, such a drop in pressure indicates that the alpha-blocking agent moxisylyte may be an effective means of decreasing urethral resistance, with obvious implications for the management of urinary obstruction.

Efficiency and side effects of intracavernous injections of moxisylyte in impotent patients: a dose-finding study versus placebo.

We assessed the efficiency and tolerance of the alpha-blocking agent moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30 mg.) of moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequate for intercourse. Placebo induced such erection in only 25% of the cases and in 55% there was no response. Tolerance was good and no priapism occurred. Only 4 patients (5%) reported mild pain during injection but erections were never painful, 1 presented with moderate and transient hypotension at the 20 mg. dose and a painless prolonged erection was observed in 1 case after the lowest dose. Drugs such as moxisylyte should be given before less well tolerated drugs.

Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent?

In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.8, 1.2 ml and the volume usually injected of 2 ml, with a 7-day interval between 2 injections. The reduction in the volume from 2 to 0.4 ml did not thwart the quality of erection obtained by the intracorporeal administration of 20 mg moxisylyte. Indeed, for each erectile parameter (rigidity, abdominopenile angle, length and circumference of the penis), no statistically significant difference arose between the 4 tests. All patients achieved full rigidity. Neither priapism nor prolonged erection occurred. These results suggest that discreet and easily handled small-sized injection pens, containing little solution, could be conceived for autoinjection therapy.

Quantitative topographic distribution of epithelial and mesenchymal components in benign prostatic hypertrophy.

Excised tissue of benign prostatic hyperplasia from 15 men 60-89 years old was investigated by immunohistochemistry and specific histological staining. For each adenoma, 10 tissue sections (2-5 specimens per lobe according to its volume) were analyzed by computer-assisted image analysis (SAMBA 2002). There was evidence for a high ratio of stroma to glands: the mean proportions of glandular, muscular and fibrous areas were respectively 30.4, 14.9 and 54.7%. Each adenoma presented a homogeneous structure, but the proportions of the three tissue components differed significantly among adenomas (p < 0.001). These findings incite us to consider biopsy as a possible investigation of the morphology of benign prostatic hyperplasia, and thus we could choose an adequate therapy according to histologic composition.

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and oral administration.

The concentration-time profiles of metabolites of moxisylyte, an alpha-blocking agent, in the plasma and urine of 12 healthy volunteers were investigated after intravenous (iv) and oral (two formulations) administration. The study was conducted with an open, randomized Latin squares design. Plasma and urine levels of moxisylyte and its biotransformation products were assayed by a specific HPLC method with fluorescence detection. Plasma levels declined in a monophasic or biphasic pattern depending on the subject. Two metabolites, conjugated desacetylmoxisylyte (DAM) and conjugated monodesmethylated DAM (MDAM), were found in plasma and urine. Unconjugated DAM was found in plasma only after iv administration. The apparent elimination half-lives of unconjugated DAM, conjugated DAM, and MDAM were 0.86, 1.7, and 3 h, respectively. The total amounts of metabolites (expressed as the equivalent of DAM) excreted in the urine were 75% after i.v. administration and 68 and 69% after oral administration of the two formulations. Oral absorption appeared to be complete for the two treatments. There was no statistical difference between the two oral formulations studied.

Moxisylyte plasma kinetics in humans after intracavernous administration.

Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of moxisylyte has been defined. Unchanged moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylmoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study]. / Polyvidone iodée (bétadine) et prévention de l'infection postopératoire. Etude multicentrique.

A multicentre study of a new preparation of povidone iodine (5% betadine) was carried out on 150 patients undergoing cataract surgery. Pre-operatively the eye was prepared by daubing the peri-ocular skin and a two-minute instillation into the conjunctival fornices. No other antiseptic was applied. Tolerance to the product was evaluated in all the patients: clinical evaluation postoperatively and during a 60-day follow-up period confirmed that the preparation was harmless to the eye. Microbiological investigations (comprising conjunctival swabbing, bacterial culture and count of the bacterial species isolated, before and after application of the product) performed on 60 patients showed a significant fall in the number of colonies after treatment.

[Delayed-action theophylline versus placebo on the ventilatory function of stable asthmatic patients. Study in relation to circadian rhythm]. / Essai d'une théophylline longue action contre placebo sur la fonction ventilatoire de l'asthmatique stable. Etude en fonction du rythme nycthéméral.

The aim of this study was to measure the results of a long-acting theophylline (Planphylline) on the flow rates of stable asthmatic patients while taking into account the spontaneous circadian variations of the ventilatory function. 27 patients were involved in this randomized, double-blind, cross-over trial; they received 10 mg/kg/day in two doses at 8.30 a.m. and 8.30 p.m or the placebo. The product was administered over two 4-day periods separated by a 3-day wash-out period. The theophylline concentration and bronchial flows (FEV1; MMEFR 25-75) were measured at 8 a.m., 10.30 a.m., noon, and 3 p.m. on days 1 and 4 of each period; 11 patients measured their hourly PEFR from 8 a.m to 10 p.m those same days. The results can be analysed for 19 patients, including the 11 who measured their PEFR. The first day of treatment (D1), the theophylline concentration rose regularly without going above 10 micrograms/ml. On the fourth day of treatment (D4), the mean maximum concentration was above 10 micrograms/ml and the 8 a.m rate was superior to 8 micrograms/ml for 14 patients out of 19. The bronchodilating effect of Planphylline is significant for all bronchial flow rates (FEV1 less than 0.01; MMEFR 25-75 less than 0.05; PEFR less than 0.01, n = 11). On D1, the FEV1 becomes normal. On D4, the MMEFR 25-75 is still only partially improved, in spite of the theophylline concentration obtained. Because of the spontaneous diurnal improvement of bronchial rates, only the 8 a.m, 10.30 a.m. and 3 p.m. FEV1 obtained with Planphylline are statistically different from those obtained with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)