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Biomedical subjects

Pierre Costa

Publications and source records attributed to Pierre Costa.

At least 19 recordsLinked to original sources
PubMed2006

Differentiated rabbit prostatic stromal cells in primary culture display functional alpha1A-adrenoceptors.

AIMS: BPH is characterized by uncontrolled proliferation and increased contractility of prostatic smooth muscle cells. The activation of alpha1-adrenoceptors (alpha1-AR) seems involved in the latter event, but the lack of in vitro models expressing these receptors has hampered a more specific characterization of their role. In order to do so, we attempted to develop a new model of rabbit cultured prostatic stromal cells (PSC) in a non-proliferative and differentiated state. METHODS: The expression of cytoskeletal and stromal markers was confirmed by immunohistochemistry on primary cultured PSC. Alpha1-AR subtype expression was assessed by RT-PCR, while receptor coupling to the ERK1/ERK2 and calcium pathways was studied by Western Blot and Fura-2 calcium imaging, respectively. RESULTS: Cells grown under non-proliferative conditions displayed a differentiated phenotype, with expression of contractile cytoskeletal and stromal proteins. Furthermore, the alpha1A-AR was shown to activate ERK1/ERK2 as well as calcium signaling. CONCLUSION: These results emphasize the interest of this model for the characterization of PSC adrenergic regulation, in particular through the little-known alpha1A-AR.

Animals↗
PubMed2006

Activating mutations of Gsalpha in kidney cancer.

PURPOSE: Heterotrimeric G proteins are signal transduction proteins coupled to hormone receptors that activate intracellular second messenger systems, mainly cyclic adenosine monophosphate mediated protein kinase. Recent studies indicate that G proteins may have a major role in oncogenesis as well as in tumor invasiveness and cell proliferation. The involvement of G proteins was formerly thought to be limited to hormonal signal transduction. Activating Gsalpha mutations have been reported in tumors arising only from highly specialized endocrine tissue, such as pituitary adenomas, toxic thyroid adenomas and differentiated thyroid carcinomas, but never in other nonendocrine tumors. We hypothesized that a constitutive activation of this pathway, that is activated Gsalpha and inhibited Gialpha, could be implicated in kidney cancers. We searched for alterations on the Gsalpha gene GNAS and the Gialpha gene in renal cell carcinoma. MATERIALS AND METHODS: Using nested polymerase chain reaction, enzyme digestions, laser microdissection and direct sequencing we looked for activating mutations on GNAS codons 201 and 227, and inhibiting mutations on the Gialpha gene in 30 consecutive patients with clear cell renal cell carcinoma between January 2003 and January 2004. RESULTS: Somatic (tumor specific) activating mutations of Gsalpha were present in a significant proportion of human clear cell renal cell carcinomas. Activating mutations were identified in 5 of the 30 patient DNA preparations (16.6%) with a substitution of arginine 201 by cysteine in 3 and histidine in 2. CONCLUSIONS: These findings suggest the implication of this pathway in human oncogenesis. It may provide a potential therapeutic approach to these frequent and aggressive tumors.

Adult↗
PubMed2006

Transobturator tape sling for female stress incontinence with polypropylene tape and outside-in procedure: prospective study with 1 year of minimal follow-up and review of transobturator tape sling.

OBJECTIVES: To assess the efficacy and safety of a minimally invasive surgical procedure using a polypropylene transobturator tape to treat female stress urinary incontinence during a minimal follow-up of 1 year and to present a review of this technique. METHODS: A total of 206 women with stress urinary incontinence who underwent the transobturator tape procedure in a French multicenter prospective open tracker study, with a minimal follow-up of 1 year (range 12 to 33 months), were assessed. A nonelastic, polypropylene tape was placed under the mid-urethra. The surgical placement technique used a vaginal and transobturator percutaneous approach. Postoperative assessments included clinical examination, cough-stress test (full bladder), uroflowmetry, and postvoid residual urine volume performed after 1, 6, 12, 18, and 24 months. RESULTS: The mean follow-up was 16 months (range 12 to 33). Of the 206 patients, 79.1% were completely cured, 13% improved, and 7% failed. No vascular, nervous system, or digestive perioperative complications were observed; however, 2.4% of the patients had postoperative urinary retention. CONCLUSIONS: The results of the present study have confirmed the optimal results in stress incontinence previously reported in short-term studies. These results suggest that the transobturator tape procedure is a valuable alternative to the transvaginal tape procedure, with a low rate of complications.

Adult↗
PubMed2006

[Management of urinary tract infections in women. Epidemiologic survey of 7916 women in general practice].

OBJECTIVE: To evaluate the management of urinary tract infections in women by general practitioners and compare it with official French guidelines. METHODS: This survey enrolled 1587 general practitioners in France and 7916 adult women. Exclusion criteria for patients included: pregnancy, diabetes, neurogenic bladder, or urinary catheters. During the visit at which the diagnosis was made, physicians completed a questionnaire that included diagnostic and management details, in particular, prescription of further examinations. RESULTS: According to the French guidelines, 37% of women had an upper or complicated urinary tract infection, although one third of the complicated infections were so defined only by the patient's age (>65 years). Additional testing was prescribed for 36% of the women with acute uncomplicated cystitis. CONCLUSION: This study shows that the management of urinary tract infections in women does not comply with current guidelines, especially in cases of acute uncomplicated cystitis. The use of age alone as a complicating factor should be reconsidered.

Adolescent↗
PubMed2006

Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts.

OBJECTIVE: To investigate the effect of Pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts; this extract is used for treating urinary disorders associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU) incorporation assays, and cytotoxicity by luminescent quantification of adenylate kinase activity. RESULTS: Cultured cells were labelled by an anti-vimentin antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed that proliferation of cultured human stromal cells, stimulated by fetal calf serum, by basic fibroblast growth factor and by epidermal growth factor, was dose-dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL, no acute cytotoxicity of the extract was detected after 24 h of culture. Similarly, the extract dose-dependently inhibited the proliferation of Madin-Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose of extract, no acute toxicity was evident on this cell line. CONCLUSION: PA extract inhibits the proliferation of cultured human prostatic myofibroblasts and fibroblasts. We propose that cultured human prostatic cells offer a reliable model for preclinical screening of therapeutic agents, and to study the mechanisms underlying the inhibition of proliferation.

Cell Proliferation↗
PubMed2006

Predictors of tadalafil efficacy in men with erectile dysfunction: the SURE study comparing two dosing regimens.

INTRODUCTION: The efficacy of phosphodiesterase-5 inhibitors in the treatment of erectile dysfunction may depend on patient characteristics. AIM: To determine whether patient characteristics influence the efficacy of two tadalafil dosage regimens and to identify prognostic factors predictive of tadalafil efficacy. METHODS: This was a multicenter, open-label study in which men with erectile dysfunction were randomized to tadalafil 20 mg either on demand or three times per week for a period of 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for another 5-6 weeks. MAIN OUTCOME MEASURES: Score of the Erectile Function (EF) domain of the International Index of Erectile Function Questionnaire (IIEF) and percentage of positive responses to questions 3 and 5 of the Sexual Encounter Profile (SEP) diary. RESULTS: A total of 4,262 patients were randomized. A normal EF domain score (> or =26) at the end of on-demand and three-times-per-week treatment was reported by 60.2% and 62.3% of patients, respectively. The percentage of patients who achieved a normal EF domain score and the percentages reporting positive responses to SEP3 and SEP5 depended on the severity of erectile dysfunction and the presence of certain comorbidities, irrespective of the tadalafil dosage regimen. On regression analysis, the two best predictors of tadalafil efficacy were the baseline score of the IIEF-EF domain and the baseline percentage of "Yes" responses to SEP2. CONCLUSIONS: On-demand and three-times-per-week dosage regimens of tadalafil 20 mg were equally efficacious in men with erectile dysfunction. Among the possible prognostic factors tested in this study, baseline disease severity scores were the strongest predictors of efficacy endpoint scores.

Adult↗
PubMed2005

An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries.

OBJECTIVE: To examine the preference for 2 dosing regimens (on demand or 3 times/week) for tadalafil, a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction (ED). DESIGN AND METHODS: SURE is a 14 European country, multicenter, crossover, and open-label study. Men with ED (N=4262) were randomized to tadalafil 20mg treatment on demand (maximum one dose per day and before sexual activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for 5-6 weeks. The patient's response to a treatment preference question (TPQ) was used to determine the preferred treatment regimen. RESULTS: The mean age of the randomized patients was 55 years and 85.2% reported a history of ED for one year or greater. Overall, the responses of 3861 men to the TPQ assessment showed that 57.8% preferred the on-demand regimen and 42.2% preferred the 3 times/week dosing. Both regimens were efficacious and well tolerated. CONCLUSIONS: In this study, while 57.8% of men preferred the on-demand regimen of tadalafil 20mg, a substantial number (42.2%) preferred the 3 times/week treatment. The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil.

Carbolines↗
PubMed2005

[Erectile dysfunction: a sentinel symptom?].

Erectile dysfunction (ED) is a frequent disorder affecting the man's sexual and relational quality of life. French epidemiological studies estimate that the prevalence of ED is between 11% and 44% and prevalence surveys show a correlation between ED and age: the relative risk of erectile dysfunction increases by a factor of 2 to 4 between the ages of 40 and 70 years. Few patients consult their doctor and only a small proportion of them receive treatment and few doctors take the initiative to discuss the question of their patients' sex life. Doctors should now have a good understanding of erectile dysfunction and must be aware of the importance of detecting or at least investigating any erectile dysfunction, which can be the first symptom of an underlying disease such as cardiovascular disease, diabetes, depression, benign prostatic hyperplasia, prostate cancer, androgen deficiency or a drug-induced effect. Demonstration of erectile disorders therefore represents an excellent opportunity to conduct a general work-up, as more than one-third of patients with ED ignore their underlying health problem and management of ED is therefore an integral part of preventive medicine.

Erectile Dysfunction↗
PubMed2004

Prevention of prostate cancer by androgens: experimental paradox or clinical reality.

Androgen replacement therapy in the aging male with partial androgen deficiency improved quality of life. However, such treatment is prohibited for men with a preexisting prostate cancer. The possibility of an increased risk of prostate cancer for healthy men has also been suggested on theoretical basis but recent experimental data showed that androgens may act in prevention of prostate cancer. In this review, we try to evaluate benefits and risks associated to a hormonal replacement therapy in regard to recent data. Several studies analyzing the role of testosterone for prostatic epithelial cells evidenced that testosterone acts in prostatic cell differentiation but does not have a direct role for induction of cell proliferation. Moreover, clinical studies have shown that low free testosterone levels in serum is associated with aggressive prostate cancer, like that has been observed in men with prostate cancer under prostate cancer chemoprevention by finasteride. These data suggest that an androgen pathway disruption in prostate is responsible of cell deregulations that may be associated not only with apoptosis of differentiated prostatic cells but also with potential cell transformation. The effects of androgens withdrawal for prostate cancer therapy induced in a short time the tumor arrest growth. However with time, cells adapt to low levels of androgens leading to the evolution of an androgen-independent tumor, which is more aggressive and most often fatal. The molecular mechanisms of this evolution begin to merge. A hypothesis is that such mechanisms could be initiated in elderly men with an androgen deficiency. The question is raised of whether hormonal replacement therapy could prevent prostate cancer. An encouraging recent study performed on rats demonstrated a protective effect of DHEA for prostate cancer. However, the putative role of the normalization of DHEA or other androgen levels in prevention of prostate cancer should be evaluated in clinical trials.

Adult↗
PubMed2004

Trans-obturator-tape procedure--"inside out or outside in": current concepts and evidence base.

PURPOSE OF REVIEW: Surgical treatment of female stress urinary incontinence has become very popular as a consequence of the good results given by the minimally invasive tension-free vaginal tape. This has attracted great attention from industry, resulting in a proliferation of new slings and different implantation techniques. This review focuses on published literature on the two trans-obturator procedures, outside in or inside out, recently described. RECENT FINDINGS: Tension-free vaginal tape was originally reported as a very safe procedure. However, analyses performed in Scandinavia and Austria and several clinical case reports have emphasized the risk of serious complications, related to the penetration of the retropubic space. Two new surgical approaches have been introduced maintaining the position under the mid-urethra of the tension-free vaginal tape but reducing or even eliminating complications related to the penetration of the retropubic space by placing the tape between the two obturator foramens, from outside to inside or from inside to outside. SUMMARY: Efficacy reported results are very close to those reported in most of the observational series of tension-free vaginal tape. Both trans-obturator procedures have been reported with very few complications. Anatomical dissections have shown that these two procedures can be very safe, but that the tip of the tunneller could injure the bladder, the urethra or the obturator pedicle. Surgeons have to respect the key points of the procedures. No evidence-based conclusion can yet be drawn on these two procedures. Long-term follow-up trials and tracker studies including very large cohorts of patients are needed.

Female↗
PubMed2004

[Benign prostatic hyperplasia (BPH): prevalence in general practice and practical approach of French general practitioners. Results of a study based on 17,953 patients].

OBJECTIVES: To determine the elements taken into account by French general practitioners to establish the initial diagnosis of benign prostatic hyperplasia (BPH) and to estimate the prevalence of BPH. MATERIAL AND METHODS: 1,698 doctors answered a questionnaire on their medical practice, and kept a register for two consecutive weeks comprising all men between the ages of 55 and 70 years seen in their practice. Men with no known BPH completed the IPSS (International Prostate Symptoms Score) questionnaire. The doctors described the management of the first three patients with an IPSS score > 8. RESULTS: The prevalence of BPH in the population of 33,077 men between the ages of 55 and 70 years consulting their general practitioner was 57.5%: 40.8% of patients had known BPH at the time of the visit and 29.9% of patients without known BPH reported voiding disorders (IPSS > or = 8). For the diagnosis of BPH, clinical interview was not systematically followed by digital rectal examination and urinalysis was rarely performed. Laboratory tests and ultrasound were the complementary investigations most frequently performed. CONCLUSION: BPH is a frequent disease whose prevalence is underestimated. This diagnosis should be considered more frequently when patients over the age of 55 consult their general practitioner.

Aged↗
PubMed2004

[Solitary fibrous tumours of the kidney].

Solitary fibrous tumours (SFT) are mesenchymal tumours that usually arise from the pleura. Renal SFT are exceptional (9 cases reported in the literature). The authors report a new case discovered during assessment of HT and treated by radical right nephrectomy. The histological appearance is characteristic: a tumour with a fibrous centre, composed of a monomorphic proliferation of spindle cells, with positive CD 34, CD 99, and bcl 2 labelling. The prognosis after complete resection is generally favourable.

Aged↗
PubMed2003

Prostatic tissual distribution of alfuzosin in patients with benign prostatic hyperplasia following repeated oral administration.

OBJECTIVES: The blood and prostatic concentrations of alfuzosin were determined in patients with benign prostatic hyperplasia (BPH). METHODS: 12 patients scheduled for BPH surgery were treated with alfuzosin 5 mg twice daily prior to surgery in an open trial. Seven doses were given over a 4-day period. Blood samples were drawn before the first and the last intake (day 3). On day 4 (surgery day), a blood and prostate tissue sample were taken simultaneously 12 hours after the last drug intake. RESULTS: Mean trough blood levels were 6.0+/-4.6 ng/ml and 5.8+/-3.7 ng/ml on day 3 and day 4, respectively, indicating a stable alfuzosin concentration. The mean prostate concentration on day 4 was 12.3+/-5.6 ng/g. Alfuzosin prostate and blood concentrations at 12 hours post dosing on day 4 were significantly correlated (r=0.804, p=0.0016); the prostate-blood ratio was 2.4+/-0.7. CONCLUSIONS: Oral administration of alfuzosin leads to a high diffusion of the drug into the prostate of BPH patients.

Administration, Oral↗
PubMed2003

Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.

BACKGROUND: Erectile dysfunction (ED) is common in men with renal failure, but is not always alleviated following kidney transplant. The objective of the present study was to assess the feasibility in renal transplant patients of sildenafil citrate treatment, an agent with proven efficacy in the management of ED. METHODS: This was a phase IV, open, multicentre, 3 month, dose-escalation study. All patients meeting the inclusion criteria were prescribed a dose of 50 mg sildenafil at the first visit. Thereafter the dose could be increased to 100 mg or reduced to 25 mg based on efficacy or tolerability. The primary efficacy parameter assessed the ability of patients to achieve erections sufficient for intercourse and to maintain erections after penetration. Secondary endpoints assessed patient satisfaction with sildenafil and the effect of sildenafil on their quality of life. Patients were carefully monitored throughout the study for adverse events, interactions with immunosuppressive therapy and effect on graft function. RESULTS: The study included 50 patients in the intent-to-treat population. Sildenafil significantly improved patient's erection ability and the frequency of their erection maintenance. Analysis of the secondary efficacy parameters revealed that 66% of patients believed treatment had improved their erections. Patients reported improvements in their sexual life and partner relationships and a high level of satisfaction with treatment. There were no interactions between sildenafil and the immunosuppressive drugs and there was no significant adverse effect of sildenafil on graft function. CONCLUSIONS: Sildenafil is an effective and well-tolerated agent for the treatment of ED in renal transplant recipients.

Dose-Response Relationship, Drug↗
PubMed2003

[Erectile dysfunction: knowledge, wishes and attitudes. Results of a French study of 5.099 men aged 17 to 70].

OBJECTIVE: Although erectile dysfunction is today considered as a frequent disease, few patients actually seek for medical advice and take medication. The purpose of the study was therefore to analyse use and behaviour of men with erectile dysfunction. MATERIAL AND METHODS: The study, performed between the 12th April and the 21st May 2002, involved 10,000 men 18 to 70 years old and consisted in self-administered questionnaires including 55 items (5099 questionnaires were eligible for analyse). RESULTS: Despite a high prevalence of erectile dysfunction (25%), increased with age (44% in the men aged 45 and over), the study showed that only 22.2% of men with erectile dysfunction take medical advice with 36.9% of them take medication. Men generally think erectile dysfunction is not very common in comparison to other diseases, and correlate it with stress and tiredness. However, men with erectile dysfunction (particularly those over 45) mention diseases as hypertension, prostatic and cardiovascular diseases. 94% of men would take medical advice if their problems should repeat. However, obstacles to consultation still remain for men presenting with erectile dysfunction and especially the difficulty to talk about sexuality with their physician (for 63% of men). CONCLUSION: This study confirms the high prevalence of erectile dysfunction and that few men concerned actually seek for professional assistance and take medication. Moreover, it demonstrates the major contribution of the physician in opening the dialogue on sexual problems because men are frequently embarassed or afraid to discuss this sensitive topic.

Adolescent↗