[Extrapyramidal adverse effects of veralipride (Agreal), a drug used to treat hot flushes: a propos of 17 cases]. / Troubles extrapyramidaux sous véralipride (Agréal), traitement symptomatique des bouffées de chaleur: à propos de 17 cas.

PURPOSE: Extrapyramidal disorders associated with veralipride therapy are rarely reported and often due to a drug misuse. METHODS: We evaluated cases of extrapyramidal disorders associated with veralipride. Cases were extracted from the regional pharmacovigilance centre of Amiens database. From January 1, 1995 to September 30, 2004, cases were selected on the basis of the occurrence of extrapyramidal disorders under veralipride therapy. RESULTS: Seventeen cases of veralipride-induced extrapyramidal disorders were found. They consist of 16 menopausal women and one old man with LH-RH antagonist-induced hot flushes. Mean age was 61 years (48-73). Adverse effects were acute dyskinesia (n=2) or parkinsonian syndrome, which occurred after several months or years of treatment (n=15). Parkinsonism was associated with other extrapyramidal symptoms in 8 cases: tardive dyskinesia (n=6), postural tremor (n=3), myoclonia (n=1), and trunk dystonia (n=1). In all cases, outcome was favorable after drug discontinuation. In most cases the tablet-free interval was not respected: this may lead to prolonged striatal D2 receptors blockade. It must be added that the diagnosis was often delayed and patients were considered as suffering from idiopathic Parkinson's disease. CONCLUSIONS: Prescribers should be aware that veralipride is a neuroleptic and could induce potentially severe extrapyramidal disorders. Increase veralipride prescription is expected due to the recent restriction of hormonal replacement therapy for menopause. The physicians should also use veralipride according to the Summary of the Product Characteristics.

Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.

PURPOSE: A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. PATIENTS AND METHODS: Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. RESULTS: A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. CONCLUSION: Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.

[Prognostic value of flow cytometry in squamous cell bronchogenic cancer. A retrospective study of 61 cases]. / Valeur pronostique de la cytométrie en flux dans les cancers bronchiques épidermoïdes. Etude rétrospective à propos de 61 cas.

To assess the prognostic value of flow cytometric analysis, 61 cases of operated squamous cell lung carcinoma were studied in terms of desoxyribonucleic acid (DNA) nuclear content and percentage of cells in DNA synthesis phase (% S). These parameters were determined on a fresh surgical sample. The S % was obtained in 25 cases. DNA index (DI) and % S were compared with survival and usual clinicopathologic characteristics for the prediction of survival. DNA content classified as DNA-diploid and DNA-aneuploid is not a prognostic factor for survival. DI higher than 2 seems to be predictive but needs confirmation. The % S and multiploidy are not predictive factors for survival.

[Prognostic evaluation of small cell lung carcinoma by flow cytometry. A retrospective study from bronchial brushing samples]. / Evaluation pronostique du carcinome bronchique à petites cellules par cytométrie en flux. Etude rétrospective à partir de prélèvements par brossage bronchique.

The authors determined the desoxyribonucleic acid (DNA) content of 45 small-cell lung cancers, by flow-cytometry (FC), from bronchial brushings to asses the prognostic meaning of the DNA index, the percentage of cells in DNA synthesis phase (% S) and the ploidy. Moreover, the value of this tumorous cells brushing was assessed for Flow-cytometric analysis. Bronchial brushing offers some advantages opposite to biopsies, but the low quantity of collected cells reduces the number of tumors analysable by FC. The output is low (39%) for determination of DNA index, and moreover low (22%) for determination of % S. In regard to the flow-cytometry analysis, the DNA content does not show any significant difference of survival where as the % S is related to survival, but it seems to be paradoxical in this study. Indeed, patients with small-cell lung cancer associated to high cells' percentage in DNA synthesis phase have the longest survival.

[Localized dilatation of the bronchi. A misunderstood etiology of coronaro-bronchial fistula]. / Dilatation des bronches localisée. Etiologie méconnue de fistule coronaro-bronchique.

The authors report the case of a coronary to bronchial artery anastomosis secondary to focal bronchiectasis. The diagnosis was made after finding large retroatrial vessels on coronary arteriography. A pulmonary steal syndrome, frequently reported in this condition in the literature, was not present in that particular case. The diagnosis of a coronary to bronchial artery anastomosis should alert the physician to possible underlying cardiac disease (Tetralogy of Fallot, supravalvular aortic stenosis, severe coronary artery disease). A bronchopulmonary etiology (chronic obstructive airways disease, multiple bullae, bronchiectasis) is less commonly found as the presentation is often atypical.

[Short-axis thallium 201 tomography. Changes in the isotope fixation on the circumference of the left ventricle]. / Tomographie au thallium 201 en coupes petit axe. Etude de la variation de fixation de l'isotope sur la circonférence du ventricule gauche.

Several authors have studied variations in myocardial thickness on short-axis sections cut through healthy postmortem hearts. The circumferential profiles showed a series of minima and maxima, with a minimum at the septum, a maximum at the anterior interventricular junction and another at the anterolateral papillary muscle, a minimum at the inferior wall followed by a maximum at the posterior papillary muscle, then at the posterior interventricular junction, after which came a septal minimum again. When examined by short-axis thallium 201 tomography, the left ventricle does not look like a ring of even density. The purpose of this study was to try and explain the changes in density observed by variations in thickness and to devise a quantification method that would take anatomical features into account. 23 patients with normal coronary angiography underwent thallium 201 scanning after exercise. Circumferential profiles were drawn from short-axis sections with the angle on the abscissa and the number of sections on the ordinate. 29 other patients with a more than 75 p. 100 stenosis of coronary vessels (anterior interventricular artery 15, right coronary artery 10, circumflex artery 8, diagonal artery 4) had the same examination. The circumferential profiles of normal subjects closely resembled those of anatomical sections, with a minimum at the upper and anterior septal wall (the limit between the two areas being undefinable), a maximum at the anterolateral papillary muscle and adjacent myocardium, a minimum at the inferior wall and a maximum at the posterior papillary muscle and adjacent septum. These curves enabled us to determine the relative perfusion values of one area compared with another, which will serve as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography in radiotherapy of prostatic carcinoma.

Hundred forty-four correlations are reported between radiological simulation and CT-scan in cases of prostate adenocarcinoma without metastases treated from 1980 to 1986 exclusively by transcutaneous radiotherapy using the box technique with 25 MV photons. Forty-eight percent of the cases were intracapsular forms. On the basis of correlation criteria defined, the prostatic boost volume was shifted in the sagittal plan in 18% of the cases. Suspect seminal vesicles were found in 60% of the cases. Our treatment plans were considered "correct" in 65% of the cases, "acceptable" in 26% of the cases and "unsatisfactory" in 29% of the cases. The corrections applied to the treatment plan do not vary according to grade but according to stage and concern mainly the posterior limit of the boost volume and to a lesser extent the superior and anterior limits. The boost volume should be determined specifically for each case. CT-scans thus seem indispensable in establishing treatment plans in prostate cancer.

[Cancer of the prostate: results of radiotherapy. Multicenter study]. / Cancer de la prostate: résultats de la radiothérapie. Etude intercentres.

From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90%, respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated.

Comparative flow DNA analysis of different cell suspensions in breast carcinoma.

This study compared three methods of dissociation of breast lesions for DNA flow cytometry. Eleven benign lesions and 66 cancers were dissociated using mechanical, Ficoll, or enzymatic methods. DNA flow analysis showed that the DNA index did not vary from one method of dissociation to another. All benign lesions were diploid and 67% of all cancers were aneuploid. Enzymatic dissociation gave a lower percentage of aneuploid cells with a diminution of the proportion of cells in the G2 + M phase (13.2% enzymatic against 17.6% Fi-coll); on the other hand, it provided cell populations of greater viability than the other methods (32.6% enzymatic, 17.2% Fi-coll; P less than 0.01). The mechanical and Ficoll suspensions did not differ significantly when they were analyzed on the basis of their DNA content and their cellular viability. When compared with mechanical preparation, Ficoll suspension showed a lower recovery of tumor cells, but this inconvenience was compensated for by a more homogeneous aspect where the contribution of aggregates and debris was clearly lessened. Therefore, this study led us to choose Ficoll suspension for subsequent flow analysis of breast tumors.