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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.

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.

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.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.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.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.

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.

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.

To perform pyeloplasty as described by Andrson, Hynes and Küss by laparoscopic surgery for the treatment of ureteropelvic junction syndrome (UPJS):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.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.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.

To follow up the growth of renal angiomyolipomas (AMLs).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.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.Multiple AMLs show more growth than solitary AMLs.

Among the methods developed in assessing abuse liability, the behavioural and subjective effects of drugs can be recorded using the Addiction Research Center Inventory (ARCI) in drug-experienced subjects and normal volunteers. Sixteen healthy volunteers with no history of drug abuse participated in the study. The subjective, behavioural and physiological effects of prednisone (30 and 60 mg) were compared with those of dextroamphetamine (15 mg) and placebo in a randomized double-blind Latin square design. The self-questionnaires (ARCI, Profile of Mood States, Visual Analogue Scales and Sleep Questionnaire) were completed before, 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of the two studied doses of prednisone did not resemble those induced by dextroamphetamine (15 mg). These results indicate that oral single doses of prednisone do not possess amphetamine-like subjective effects in a healthy population. The well established psychostimulant effect of amphetamine have been replicated on almost all subjective assessments.

Pharmacological studies revealed that SR 25776 possesses marked stimulant activity characteristic of a partial inverse agonist of benzodiazepine receptor. The effects of SR 25776 500 mg alone and in combination with triazolam 0.25 mg on psychomotor performance and memory were assessed in 8 healthy consenting male volunteers in a double-blind placebo controlled trial. Treatment effects were monitored before and two and half hours following oral medication. The present study suggest that at the studied dose SR 25776 may incompletely antagonize the sedative and amnesic effects of a benzodiazepine agonist without producing marked effects of its own.

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.

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.

We report a case of keratinizing desquamative squamous metaplasia (KDSM) of the kidney pelvis. The etiopathogenic and diagnostic aspects of this rare pathology are discussed. Absence of relationship between KDSM and the carcinoma of Upper Urinary Tract, allows to suggest a conservative management.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.

From a retrospective series of 75 patients, we try to determine the place of this treatment with respect to bladder urothelial cancer. Of our 75 patients the breakdown of tumours according to their stage is the following: PTA: 16 (21.3%) PT1: 12 (16%) PT2: 21 (28%) PT3 A: 15 (20%) PT3 B: 7 (9.3%) PT4: 4 (5.4%) 47 patients benefited from a complete check up of tumoural spread which is negative in any case. In 28 cases, an uretero-vesical reimplantation was necessary for carcinologic reasons. None of the patients benefited from chemotherapy and/or radiotherapy in pre or post-operative period. Mortality was 4% (3 cases) and morbidity 8% (6 cases)- Sixty two Patients were followed-up at 5 years. The results are expressed according to different carcinologic parameters. The overall rate of recurrence is 61.2% (38/62). The actuarial survival corrected at 5 years, all stages and grades included, is 53.2% (32/62). There was no recurrence in 18 patients (29%) and 29 patients preserved their bladder. The advantages of partial cystectomy are obvious: Its mortality and morbidity are weak. It also preserves the sexual function and mainly avoids resorting to urinary derivations. As a principle these indications apply to a small percentage of invasive tumours T2-T3 A located in the mobile part of the bladder that is unifocal and of small size (4 cms).

The personality characteristics of 62 subjects to be screened for eligibility in psychopharmacology studies have been assessed. The psychological screening comprised the Cattell anxiety scale (CAS), the Eysenck Personality inventory (EPI) and the Minnesota Multiphasic Personality Inventory (MMPI) in its complete version (550 items). The comparison of the results to a population matched for age and status showed that the anxiety level was not different, extraversion factor was higher (p less than 0.001) and various personality traits were different. The most striking differences were observed on the factors: Psychopathic deviation, Mania, Schizophrenia greater than controls and social introversion lower than controls. These differences may evoke several biases, such as a recruitment bias or a specific personality pattern of young healthy subjects. In order to discuss these hypothesis, further comparisons with other centers are required to conclude.

The effect on psychomotor and mnesic performances of acute oral dose (600 mg) of 2 Ginkgo biloba extracts were evaluated in twelve healthy female in a dummy placebo-controlled double blind study. Tests were performed comprising: objective measures of vigilance [critical flicker frequency (CFF), choice reaction time (CRT)], memory tasks (pictures and Sternberg scanning tests) and self-rating evaluation (visual analogue scales). Tests session took place before and 1 hour post-dosing. No statistically significant changes from placebo were observed on CFF, CRT or subjective rating of drug effects. No differences between treatment were evidenced on Sternberg scanning test and pictures recognition. Comparing to baseline, free recall score, while decreasing under placebo and Ginkgo, remained the same under Tanakan. As the differences between treatment are localized on one test, it appears important to examine the reproductility in healthy subjects. In order to verify the clinical relevance of these results, they need to be replicated in older healthy volunteers with age-associated memory impairment.

Forty cases of funnel chests were observed in a majority of 15-20 years old male youngsters. Twenty-six had respiratory or cardiac symptoms. A surgical correction was done for 22 patients; 12 had symptoms. Eighteen patients had no surgery and were advised to undertake physical therapy: 6 had symptoms. With a 1 to 25 years follow-up 12 operated patients were checked up: 10 were satisfied with the correction. None had any symptom. This subjective results were superior to the morphologic and functional criteria. As for non operated patients, 12 were contacted: 7 had followed our advice and felt a functional amelioration in 6 cases and a morphological amelioration in 4 cases. Five patients had no therapy: 4 considered themselves in a stable situation an 1 thought it was worse. Funnel chest symptoms are the expression of anxiety in a majority of cases. The subjective as well as the formal matters are to be considered to appreciate the results of treatment. Physical exercises are an important part of the therapy, either with or without surgery.

1. In a four period, double-blind, placebo-controlled study, apomorphine (0.009 mg kg-1 subcutaneous route) and yohimbine (0.30 mg kg-1 i.v. route) were administered to 10 male healthy volunteers. Penile circumference was monitored using plethysmography and subjective sexual arousal was self-assessed. Data were collected before, during and after a stimulation session during which 50 erotic slides were projected to the subjects. 2. Apomorphine induced an erection starting from the fourth minute post-injection, and potentiated the visually-induced response. Self assessment showed increased tumescence and rigidity without modifications of sexual arousal. 3. Yohimbine did not modify penile diameter without stimulation and did not affect the physiological response to erotic stimuli. 'Sexual excitement' was decreased by yohimbine during the post-stimulation phase. One subject experienced severe anxiety while he was infused with yohimbine. 4. These results are discussed with reference to animal data and to recent studies carried out in impotent patients.

The effects on psychomotor and mnesic performance of acute oral doses of maprotiline (25, 50 and 75 mg) were evaluated in twelve healthy men in a placebo-controlled double blind study. A battery of tests was performed comprising: objective measures (critical flicker frequency, choice reaction time, memory tasks) and self rating evaluation (visual analogue scales). Tests session took place 15 hours after each treatment. Plasma concentrations of maprotiline were determined. Compared with placebo, maprotiline induced psychomotor impairment on both objective and subjective assessment in a dose related manner. No significant difference between maprotiline and placebo on memory test could be evidenced.

A method of assessment of the erection in man, using numeric penile plethysmography, is presented. The data concerning the sensor, the electronic circuit, and the computer interfacing with an IBM PC are described. As a validation of this method, apomorphine (0.009 mg/kg) was tested in a double-blind, placebo-controlled study, carried out in healthy volunteers. Apomorphine induced an erection starting, as a mean, at the fourth minute postinjection. The treatment increased the penis volume without any other stimulation (p = 0.0008) and potentiated the physiologic response induced by visual erotic stimulation (p = 0.0012). The limits of plethysmography are discussed in reference to rigidimetry.