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N Mottet

Publications and source records attributed to N Mottet.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neurohormonal stimulation of histamine release from neuroendocrine cells of the human adenomatous prostate.

BACKGROUND: Neuroendocrine cells (NE) constitute a population of highly specialized cells in prostatic glands; histamine has never been described in these cells. This article shows the presence and the regulation of release of histamine in NE. METHODS: In 21 prostatic adenomas, NE were identified by specific antisera against neuroendocrine markers (chromogranin-A, synaptophysin), histamine, and histidine decarboxylase (HDC); a rate HDC-cDNA probe was used to detect this enzyme by in situ hybridization. RESULTS: Immunoreactive cells for chromogranin-A, histamine, and HDC were found among luminal epithelial glandular cells. Similar cells were also labeled with the HDC-cDNA probe. Glandular cells, isolated from prostatic adenomas, were shown to contain histamine (7-40 pmol/mg cellular protein). L(-) norepinephrine causes a time-dependent (t1/2 = 22 min) histamine release; the alpha 1-receptor antagonists WB-4101 and YM-617 specifically inhibited this release, in agreement with a mediation by alpha 1-adrenoreceptor subtype. CONCLUSIONS: There is some evidence for the presence in prostatic adenomas of histamine-forming cells of neuroendocrine type; histamine release from these cells is under the control of alpha 1-adrenoreceptor subtype.

Adrenergic alpha-Agonists↗
PubMed1998

Artificial urinary sphincter AMS 800 for urinary incontinence after radical prostatectomy: the French experience.

Post-radical prostatectomy urinary incontinence (PRP-UI) has a major negative impact on the patient's quality of life with the incidence accounting for over 30% on a patient questionnaire basis. In 1995 the French Urological Association started a prospective survey to investigate the efficacy and safety of the AMS 800 artificial urinary sphincter (AUS) in PRP-UI, and preliminary results are presented for the 103 men enrolled in the study in whom bulbar urethral cuff placement was used exclusively. Surgical revision was necessary in 22 patients (21%). Infection and erosion accounted for 12 non-mechanical revisions leading to complete removal of 6 AUS and to eventual replacement of 6 devices with new ones. Mechanical malfunction accounted for revision in l0 patients (9.7%). Fifty-nine patients (61.45%) reported no leakage for the 96 working devices. Twenty-seven patients (28%) wore no pads, 3 patients used 1 pad and 4 patients used 2 pads/day, and all these patients reported improvement, with only 3 patients (3%) having had more than 2 pads/day. Currently, no non-prosthetic procedure reliably affords such good objective results. Insertion of the AMS 800 AUS no doubt represents an attractive treatment modality available for male urinary incontinence following radical prostatectomy.

France↗
PubMed1998

[Can the prostatic capsule be preserved during cystectomy for bladder tumors: a study of urethral and prostatic involvement in the cystectomy specimens].

OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective histological study was based on 260 specimens: radical cystectomies performed in 7 operative sites. The prostate and urethra were analysed in 3 planes (upper, middle and lower thirds). The apex was studied separately. Urethral invasion was identified by continuity of the tumour or by the presence of vesical CIS. RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to contiguous invasion (43/80). CIS is the second pathological association (44 urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency of urethral and prostatic involvement does not justify preservation of the prostate during cystectomy. A serial prospective study should define the precise criteria able to minimize the risk of conservative surgery.

Adenocarcinoma↗
PubMed1998

[Treatment of stress urinary incontinence in women: rehabilitation or surgery?].

Considerable progress has been made in the treatment of female urinary incontinence over the last 20 years, affecting both surgical treatment, by the introduction, apart from reference techniques, of so-called "minimal" techniques, which allow an extension of the indications to elderly patients, and medical treatment, but also due to the introduction of increasingly better defined retraining techniques. A better understanding of the pathophysiology of incontinence and the growth of urodynamic techniques allow a better analysis of the mechanisms responsible for incontinence, which is often multifactorial. The prevalence of female urinary incontinence also gives this disease a considerable economic significance. Surgery is therefore no longer currently the only treatment that can be proposed to the patient. The respective indications for retraining and surgery need to be discussed, bearing in mind that, schematically, the 2-year results of surgery achieve 80 to 85% of cure with a more marked erosion over time when the initial repair was less solid, and retraining cures approximately 30% of women and improves another 30%.

Aged↗
PubMed1997

[Neuroendocrine tumor of the bladder apropos of a case. Review of the literature].

Neuroendocrine bladder tumours are exceptional, and the positive diagnosis is only established when they are already large and advanced. We report an original case in view of its small dimensions. We discuss the differential diagnosis (mainly bladder metastases from lung cancer) and pathological specificities, particularly the value of epithelial immunolabelling allowing exclusion of lymphoma. Because of the similarities with bronchial neuroendocrine tumours, the potential value of serum NSE assay should be emphasized. Combined surgery-cisplatin-based adjuvant chemotherapy is recommended.

Aged↗
PubMed1997

[Concomitant radiochemotherapy in invasive bladder tumors].

The treatment of muscle-invasive bladder tumors currently consists of radical cystectomy with lymph node dissection. A combined radio-chemotherapy treatment could allow to preserve a functional bladder without greater risk of relapse. We present a review of 38 available publications found in the international literature concerning this combination treatment. Only 9 publications with appropriate analysis were considered, including 552 evaluable patients, 44% of whom were suitable for radical cystectomy. Cisplatin is the most often used drug. The protocols are variable and generally well tolerated. The median follow-up time is 36 months. The immediate complete response rates vary between 48 and 92% and the overall survival rate is between 42 and 82%. The survival with bladder preservation is between 38 and 75%, while the disease-free survival with bladder preservation is between 33 and 53%. 11% of the initially complete responders had a superficial recurrence and 30% had distant metastases. There is no proven advantage of neoadjuvant polychemotherapy, there is no consensus for the therapeutical protocol, the follow-up protocol remains to be defined, and the function of the preserved bladder has to be studied. Only a prospective randomized trial could precise the role of this experimental technique compared to surgery despite the major evident difficulties (ethical and practical) to conduct such a trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Assessing the impact of urinary incontinence in a female population.

Urinary incontinence (UI) is a symptom. Patients seeking medical attention do so because of this symptom. As individuals' views of bothersomeness vary significantly, the objective degree of symptom severity is less important than the patient's overall outlook. Assessing well-being can be done by symptom evaluation, and general or condition-specific health-related quality of life questionnaire (HRQOL). Several studies using HRQOL questionnaires documented the negative effects of UI on the patient's well-being, especially on daily activities and psychological distress. Generalised HRQOL instruments can be used but they may lack sensitivity to the characteristics of incontinence and its impact. Recently condition-specific UI questionnaires have been developed for a better assessment of specific issues and a greater sensitivity to changes after treatments. They reveal a substantial impact on everyday life, but a poor correlation was observed between the objective and subjective measurements. More useful short-form versions have recently been developed that meet many of the needs of therapists.

Female↗
PubMed1997

Transrectal ultrasonography in prostatic cancer: interexaminer variability of interpretation.

OBJECTIVE: To compare the variability of transrectal ultrasonographic (TRUS) interpretation for the decision of performing biopsies and the lesions to biopsy. METHODS: We extracted at random from our videotape database 16 records of patients who had undergone biopsies, added 2 normal glands and duplicated 2 of these 18 records. Based on the records, 5 well-trained physicians had to describe the images on the tape, and to decide whether or not to biopsy the prostate. A kappa test was computed between each couple of readers, and for the whole group. The kappa test denotes the agreement between examiners. A value of kappa < 0.20 is considered poor to slight agreement, 0.2-0.40 is considered fair agreement. RESULTS: The agreement between the 5 readers was poor for the biopsy decision (kappa < 0.2) and the difficulty to read the records (kappa = 0.05). The results with the global kappa were similar with a highest value < 0.3. Most of the abnormalities were described in the peripheral zone. The global kappa for the seminal vesicles interpretation is poor, but better for the capsular penetration. CONCLUSION: TRUS has a poor informative value between different practitioners. This poor agreement between different practitioners must lead to more objective ultrasonographic methods.

Biopsy, Needle↗
PubMed1997

[5 alpha-reductase and prostate].

The human prostate is a complex organ composed of four glandular zones that differ in their histology and biology. In addition to this anatomical organization, the prostate is mainly composed of epithelial and mesenchymal tissues. Two pathologies affect the growth of the prostate: cancer and benign prostatic hyperplasia. Anatomical and pathological studies have shown that stromal enlargement is the first step in the process of BPH and that both transition and periurethral regions are the exclusive sites of origin. Because the first step of androgen action is the reduction of testosterone into dihydrotestosterone by the 5 alpha-reductase, it have been postulated that modification of this enzymatic activity may play an important role in BPH development. However DHT production alone cannot explain the hyperplastic development of the gland. Thus it has also been postulated that androgen-growth factor interaction may be an important feature of this growth: these growth factors include the IGF axis. An interaction between androgen pathway and sympathethic system, via alpha-adrenoreceptor may also be suspected.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet.

The concentration-time profiles of metabolites of moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylmoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.

Adult↗
PubMed1996

Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture.

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Because insulin-like growth factors (IGFs) with their binding proteins (IGFBPs) are involved in the control of cellular proliferation, differentiation, and metabolism, we compared their secretion by prostatic epithelial and stromal cells in primary culture from the four different zones of normal prostate and from hyperplastic tissue to assess their contributions to the hyperplastic development. IGF-I could not be detected in the conditioned medium from either epithelial or stromal cells from normal and BPH tissues. IGF-II concentrations were the same in the conditioned medium from the epithelial cells of the different zones of the normal prostate and that of BPH cells. IGF-II concentrations secreted in stromal cell culture medium, however, were higher in the periurethral zone than in the peripheral and central zones. Moreover, in the periurethral zone, stromal cells secreted higher concentrations of IGF-II than did epithelial cells. Also, BPH stromal cells secreted more IGF-II than did BPH epithelial cells. IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells. In contrast, IGFBP-5 was only produced by stromal cells of the periurethral zone of the normal prostate and BPH tissue. IGFBP-3 was predominantly secreted by normal stromal cells of the transitional zone. We observed that BPH stromal cells presented the same pattern of IGF-II and IGFBP production as normal stromal cells of the periurethral zone. These data support the hypothesis that the periurethral zone is the main region of the prostate implicated in the development of BPH. They also suggest that the variability in both IGF-II secretion and the secreted forms of IGFBPs, depending on anatomical location within the organ, may be important for the autocrine regulation of normal and hyperplastic prostate growth.

Cells, Cultured↗
PubMed1996

[Hot flashes and hormonal treatment of prostate cancer].

Androgen suppression in the context of the treatment of prostatic cancer is responsible for hot flashes in 75% of patients, which alter the quality of life to varying degrees depending on the patient. They constitute a source of major discomfort in 30 to 40% of patients. The pathophysiology of this effect is now known and involves: sex steroids, central opiates and intrahypothalamic catecholamines. The incidence of hot flashes appears to vary according to the type of hormonal treatment administered. The various treatments available are not equally effective. Non-hormonal treatments are of little value. Hormonal treatments: oestrogens and steroidal antiandrogens are the most effective. Progestogens also appear to be just as effective or even more effective than these other agents, with negligible adverse effects at the doses used in this indication.

Androgen Antagonists↗
PubMed1996

Effect of finasteride (Proscar) on the proliferation of cultured epithelial and stromal cells from normal and hyperplastic human prostates.

Finasteride is a potent 5 alpha-reductase inhibitor which has proven useful in the clinical management of benign prostatic hyperplasia. To determine a potential mode of action for finasteride in prostatic cell proliferation, we have studied the incorporation of [3H]-thymidine into the DNA of cultured epithelial and stromal cells from normal and hyperplastic human prostates. The effects of short treatment with 10(-9) M and 10(-6) M finasteride (48 hrs.) on the incorporation of labelled thymidine were studied. A significant effect of finasteride on prostatic cell proliferation was observed at 10(-6) M for both epithelium and stroma from normal prostate: the rate of thymidine incorporation decreased to 80 +/- 3% (p < 0.001) and 55 +/- 10% (p < 0.01), respectively, compared to the control cells. As observed for normal prostates, this rate of thymidine incorporation was less for hyperplastic epithelium (70 +/- 4%, p < 0.001) than that observed for the hyperplastic stroma (74 +/- 4%, p < 0.01). These data clearly demonstrate that the reduction of the prostate volume observed in BPH treatment by finasteride is partly due to an inhibition of cell proliferation. However, the absence of complete inhibition of cell proliferation at 10(-6) M, a concentration known to strongly inhibit the 5 alpha-reductase activity, supports the hypothesis that factors other than DHT are necessary to induce prostatic cell proliferation.

Adult↗
PubMed1995

Comparison between exact and parametric distributions of multiple inter-raters agreement coefficient.

The Global Kappa statistic can be used for measuring the degree of agreement between more than two raters. In this paper, we give simple computation formulas in the case of dichotomic and no missing responses in order to describe the exact distribution of Kappa for various sets defined by the number of raters, of different examinations and of positive responses. By programming those computations with the SAS software package, we were able to compare the exact and parametric distributions of Kappa. Although the correlation between parameters is high, a linear regression analysis shows that a strong imbalance between positive and negative responses can lead to misinterpretation of the results when using the parametric method.

Humans↗
PubMed1995

Percentage area density of epithelial and mesenchymal components in benign prostatic hyperplasia: comparison of results between single biopsy, multiple biopsies and multiple tissue specimens.

OBJECTIVE: To determine whether histological analysis of six multiple random biopsies of the gland or analysis of only one biopsy provides a good estimate of the different components of the hyperplastic gland compared with the results obtained from tissue specimens (reference values). MATERIALS AND METHODS: The various components of prostate tissue obtained from 30 men undergoing suprapubic adenomectomy were investigated. The histological analysis was performed on multiple tissue specimens reflecting adenoma (reference values) and on one and six biopsies performed at random on the enucleated material of the hyperplastic gland. Immunohisto chemistry using anti-actin as a label of smooth muscle and specific histological staining coupled with computer-assisted quantitative morphometric analysis was used to ascertain the histological composition of the prostate. RESULTS: The mean ( +/- SD) area densities obtained from tissue specimens were 34.1 +/- 5%, 32.4 +/- 6.9%, 17.6 +/- 4.5% and 15.9 +/- 5.5% of smooth muscular and fibrous tissue, and epithelium and glandular lumen, respectively. The mean ratio of stromal to epithelial hyperplasia averaged 4.05 +/- 1.73. Both one and six biopsies gave a good estimate of fibrous tissue and glandular epithelium, but the percentage of smooth muscles was overestimated and the percentage of glandular lumen was underestimated. There was a significant relation between the prostate area densities of glandular epithelium (r = -0.41, P < 0.05), the percentage area density of prostate smooth muscle (r = 0.43, P < 0.05), and the weight of enucleated adenoma. No correlation was found with prostate-specific antigen (PSA). CONCLUSION: It seems feasible to propose medical treatment of benign prostatic hyperplasia (BPH) based on the histological composition of the prostate gland. One biopsy, reflecting in good proportions the nature of the adenoma, would be used to provide insight into the pathogenesis and therapy of BPH.

Aged↗
PubMed1995

[Cancer of the prostate. 2. Physiology and cellular development].

Prostatic cancer is the second most frequent cancer in men in industrialised countries. The histological analysis of its initial development demonstrates the existence of precancerous lesions, PIN. The initial presence of several different cell populations accounts for the development of contingents of hormone-sensitive and hormone-resistant cells. The presence of numerous neuroendocrine cells appears to be a factor of poor prognosis. Hormones are intimately involved in the development of prostatic cancer and are an integral part of its treatment. Progress in molecular biology has furthered out knowledge of this disease. In particular, growth factors such as EGF and FGF are particularly involved and are starting to have a clinical application. The oncogene and anti-oncogene system is currently being explored (particularly p53 abd BCL 2). They are the basis for carcinogenesis and analysis of these factors will allow a better approach to the mechanisms of tumour induction and development.

Androgens↗
PubMed1995

5 alpha-reductase activity in cultured epithelial and stromal cells from normal and hyperplastic human prostates--effect of finasteride (Proscar), a 5 alpha-reductase inhibitor.

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Dysregulation of testosterone conversion to dihydrotestosterone (DHT) by 5 alpha-reductase has been described as a key step in the development of BPH. We investigated the 5 alpha-reductase activity in primary cultures of epithelial and stromal cells from the four different regions (periurethral, transition, central and peripheral zones) of normal and hyperplastic human prostates. No significant difference in DHT production was observed among the four epithelial zones and the hyperplastic epithelial cells, or among the four normal zones and the hyperplastic stromal cells. To investigate whether the two known 5 alpha-reductase isoenzymes were expressed in prostate, we performed specific enzymatic amplification after reverse transcription which showed the presence of 274 and 383 base-pair fragments, respectively, specific for 5 alpha-reductase type 1 and 5 alpha-reductase type 2, demonstrating the expression of mRNA for both isoenzymes in BPH tissue. To pharmacologically characterize the isoenzyme present in the two cell components of hyperplastic prostate, we used finasteride, a well known inhibitor specific to 5 alpha-reductase type 2, which only slightly inhibits 5 alpha-reductase type 1. In BPH, IC50 was estimated at 62 nM and 45 nM, for stromal and epithelial cells respectively, suggesting predominately 5 alpha-reductase type 2 activity. Our results provide further evidence that 5 alpha-reductase type 2 activity is mainly responsible for DHT production by human prostatic cells.

Base Sequence↗