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N Thiounn

Publications and source records attributed to N Thiounn.

At least 37 records · Page 2Linked to original sources

Interleukin-18: biological properties and clinical implications.

IL-18, originally identified as interferon-gamma inducing factor (IGIF), is related to the IL-1 family in terms of its structure, processing, receptor, signal transduction pathway and pro-inflammatory properties. IL-18 is also functionally related to IL-12, as it induces the production of Th1 cytokines and participates in cell-mediated immune cytotoxicity. This review summarizes the recent advances in the understanding of IL-18 structure, processing, receptor expression and immunoregulatory functions, and focuses on the role of IL-18 modulation in tumours, infections, and autoimmune and inflammatory diseases.

Animals↗

[Brachytherapy in the curative treatment of localized prostatic cancer].

The treatment of clinically localized prostate cancer is based on total prostatectomy, radiotherapy or surveillance. The adverse effects of these treatments have led to an increasing interest in alternatives with decreased morbidity. Brachytherapy consists of placing radioactive sources in the prostatic tissue. High doses can therefore be delivered to the cancer while avoiding excessive irradiation of the bladder and rectum. Brachytherapy generally uses permanent implants (Iodine 125 or Palladium 103). The so-called Seattle technique requires planning before implantation, while, in the "ProCeed" technique, the position of the grains is determined at the time of treatment, with the help of a computer programme which determines the dosimetry. Brachytherapy is a reliable and reproducible technique with minimal morbidity, providing 10-year results comparable to those of total prostatectomy.

Brachytherapy↗

[In vitro study of the modulation of human ureteral tonus by nitric oxide and zaprinast, a phosphodiesterase inhibitor].

AIM OF THE STUDY: To assess the role of nitric oxide (NO) and its second messenger, cGMP, on the mechanisms underlying human ureteral smooth muscle relaxation. METHODS: Proximal segments of ureter were dissected from nephrectomy, then cut into rings and suspended in organ chambers. Isometric tone was recorded at baseline and after preincubation with KCl (120 mumol). The Increasing concentration (10-8-10-4 M) of NO donors, Sodium nitroprusside, (SNP) and molsidomine (SIN-1) and a type V phosphodiesterase inhibitor, Zaprinast were added to the organ chambers and a dose response curve was constructed from each experiment. RESULTS: Dose-dependent relaxation was seen with all compounds. This was, however, more pronounced with SNP as compared with SIN-1. Zaprinast alone had marginal relaxant effect but markedly potentiated the relaxing effect of the NO donor SNP (p < 0.05). Inhibition of NO synthesis by the arginine analogue L-NA increased electrical-induced contraction (98 +/- 4% vs 122 +/- 3%, p < 0.001). CONCLUSION: Activation of the soluble guanylate cyclase by NO donors markedly relaxed significantly human ureteral smooth muscle but inhibition of phosphodiesterase did not affect the in vitro relaxation. Our results suggest that cGMP is an important second messenger in the transduction signalling pathway leading to relaxation of human ureteral smooth muscle. By contrast, basal activity of phosphodiesterase seems to be marginal under physiological condition.

3',5'-Cyclic-GMP Phosphodiesterases↗

Modulation of interleukin-18 expression in human colon carcinoma: consequences for tumor immune surveillance.

The production in colon cancer of interferon-gamma (IFN-gamma), a type-1 T-helper (TH1) cytokine, is considered as a marker of good prognosis. We asked whether interleukin-18 (IL-18), which strongly induces IFN-gamma and regulates Fas ligand (Fas-L)-dependent cytotoxicity, may play a role in colon homeostasis, and if its expression was modulated in colon adenocarcinomas. We analyzed 14 specimens of colon adenocarcinomas, 6 of normal colon mucosa of the series, and 6 colon-tumor cell lines. The expression of IL-18, of ICE protease, involved in the processing of this cytokine, and of the downstream effectors of IL-18, IFN-gamma and Fas-L was analyzed by RT-PCR. We further performed IL-18 immunostaining of normal and tumor specimens. The results were correlated with tumor dissemination and clinical outcome. We report the synthesis of IL-18 in human normal colon, mainly by epithelial cells of the mucosa. Out of the 6 tumor cell lines, 4 expressed IL-18 transcripts, but neither ICE mRNA nor secreted forms of IL-18 were detected. We observed decreased or abolished synthesis of IL-18 in colon adenocarcinomas, as compared with normal mucosa. Thus, half of the colon-cancer tissues (7/14 cases) expressed neither IFN-gamma nor Fas-L. This feature was correlated with the existence of distant metastases (Fischer's exact test, p = 0.02) and an unfavorable outcome. These findings suggest that production of IL-18 in human colon may play a role in homeostasis and in tumor immune surveillance, by enhancing IFN-gamma production and Fas-L-dependent cytotoxicity of immune cells.

Caspase 1↗

[Intracytoplasmic sperm injection (ICSI) in the management of azoospermia].

OBJECTIVES: The objective of this study was to analyse all attempts of ICSI performed in our centre between 1995 and 1997 with surgically harvested sperm for the treatment of secretory and excretory azoospermia. MATERIAL AND METHODS: 71 infertile couples, in which the man suffered from secretory (n = 8) or excretory azoospermia (n = 63), were managed with 94 attempts of ICSI. RESULTS: ICSI was able to be performed 85 times with 82 embryo transfers resulting in 29 clinical pregnancies. The clinical pregnancy rate per ICSI attempt was comparable with sperm obtained on the day of ICSI or previously harvested and frozen (30.5% and 31.4% respectively). The clinical pregnancy rate per ICSI attempt was 33.3% for testicular sperm (n = 18), and 30.3% for epididymal sperm (n = 76). Twenty-seven clinical pregnancies (32.1%) were obtained for men with excretory azoospermia (47.2% for vas deferens agenesis and 20.8% for acquired urinary tract obstruction, p = 0.01), and 2 (20%) for men with secretory azoospermia. CONCLUSION: ICSI can achieve pregnancy in infertile couples in whom no other solution can be considered. Cryopreservation allows surgical harvesting to be dissociated from ICSI without decreasing the pregnancy rate, justifying freezing of sperm during any surgical procedure on the seminal tract. The better results obtained in congenital excretory azoospermia compared to acquired obstructions, usually post-infectious, suggest a harmful effect of infection on the quality of sperm.

Adult↗

High incidence of brain metastases in patients treated with an M-VAC regimen for advanced bladder cancer.

OBJECTIVE: We report on central nervous system metastases from urothelial bladder carcinoma in patients treated with M-VAC chemotherapy. METHODS: 50 patients with advanced transitional cell carcinoma of the bladder were treated with the M-VAC regimen at the Hôpital Cochin (Paris, France) between December 1989 and February 1995. Brain relapses were diagnosed by CT scanning. RESULTS: We observed a surprising increase in the number of central nervous system relapses (8/50) in patients treated consecutively at the same institution. The mean time to metastatic recurrence in the brain from the initiation of first chemotherapy was 21 months (range 7-38). Six patients had single and 2 patients had multiple central nervous system metastases. Treatment consisted of radiotherapy alone (n = 5) or both surgery and radiotherapy (n = 3). Median survival time from the appearance of cerebral metastases was 3 months (range 1-10). CONCLUSION: The prolonged duration of remissions which are achieved following M-VAC chemotherapy may explain the greater likelihood of the detection of cerebral involvement.

Aged↗

Corporeal plication for surgical correction of penile curvature. Experience with 60 patients.

OBJECTIVE: To evaluate the efficacy of tunica albuginea plication without excision in patients with congenital and acquired penile curvature. METHODS: Results were retrospectively analyzed in 60 consecutive patients treated from 1982 to 1996. Mean age was 42.8 years (range 16-77). 25 patients had congenital curvature and 35 patients had acquired curvature (29 Peyronie's disease, 5 postoperative and 1 posttrauma). All patients had penile curvature with angulation over 30 degrees and major intercourse difficulties. RESULTS: Postoperatively, 52 patients (87%) had satisfactory cosmetic results and 49 (82%) had satisfactory functional results. All patients (100%) with congenital or postoperative curvature had satisfactory cosmetic results and satisfactory functional results. Patients with Peyronie's disease had a lower success rate with 81% satisfactory cosmetic results and 62% satisfactory functional results. CONCLUSION: Tunica albuginea plication is a more simple procedure than tunica albuginea resection (Nesbit procedure) with a comparable success rate and minimal morbidity.

Adolescent↗

p53 status does not predict initial clinical response to bacillus Calmette-Guerin intravesical therapy in T1 bladder tumors.

PURPOSE: In superficial urothelial tumors of the bladder, p53 status is currently the most informative pretreatment parameter to define a population at higher risk for invasive carcinoma. Also, in T1 tumors, occurrence of muscular invasion is often related to an early relapse following BCG therapy. With the knowledge of biological parameters able to identify the group of initial BCG therapy non-responders, it would be possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the predictive value of the p53 tumor status on the early BCG therapy response. MATERIALS AND METHODS: The population included a selected group of 43 patients presenting T1 bladder tumors with no carcinoma in situ (Tis), treated by transurethral resection (TUR) followed by intravesical BCG therapy. Clinical outcome was analyzed in relation to usual clinical and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using DO7 monoclonal antibody. For 16 specimens, p53 gene was investigated using a Single Strand Conformation Polymorphism (SSCP) analysis and sequence determination. RESULTS: p53 anomalies were strongly correlated to smoking behavior (p = 0.003) and tumoral grade (p = 0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followup revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of DO7 immunostaining in detection of p53 anomalies. CONCLUSIONS: In T1 bladder tumors, pretreatment p53 determination was not useful to define a group of early BCG non-responders. Thus, p53 status and immunological response induced by BCG endovesical therapy are two independent events.

Adult↗

Endoscopic ureteroneocystostomy: palliative urinary diversion in advanced prostatic cancer.

Distal ureteral obstruction is a common complication in advanced prostatic cancer, secondary to direct compression at the ureterovesical junction and/or invasion of the ureteral orifice and/or of the intramural ureter by the tumor. The ureteral orifice may not be readily visible to the trigone-infiltrating tumor, but remains superficial as it is pushed upward by the tumoral tissue. The indications for palliative diversion in patients with pelvic malignant disease and renal failure from ureteral obstruction remain controversial. We present the results of our endoscopic ureteroneocystostomy technique by which the trigone is resected to restore continuity of the ureteral orifice and to place a double pigtail ureteral stent. Of the 31 operations performed for obstructive prostate cancer, continuity was restored in 76% of cases. Length of hospital stay was gradually reduced to a few days. Median survival after surgery was 8 months (0.25 to 27.5 months). Palliative diversion may be considered a reasonable option for many patients, even in the case of an apparently unpassable obstruction of the pelvic ureter, thereby prolonging survival and improving quality of life.

Aged↗

[Chemotherapy of metastatic cancer of the bladder. Apropos of 50 patients treated with M-VAC].

The most effective chemotherapy of metastatic bladder cancer in M-VAC (methotrexate, vinblastine, cisplatin), as it was shown M-VAC by phase III trials. The complete remission rate is 15-20%. The toxicity is severe, and M-VAC cannot be delivered to fragile patients. Survival is improved. This increase in survival results in an increased incidence in brain metastases. The Cochin Hospital experience with 50 patients treated with M-VAC for a metastatic bladder cancer is presented.

Antineoplastic Combined Chemotherapy Protocols↗

Image based renal stone tracking to improve efficacy in extracorporeal lithotripsy.

PURPOSE: We describe a method to reduce the number of shocks necessary to fragment renal stones during extracorporeal shock wave lithotripsy by automatically taking into account stone movements. MATERIALS AND METHODS: Echotrack computer software was developed and implemented on a lithotriptor. One software module uses image processing to detect instantaneous stone location based on ultrasound images generated by the lithotriptor. A second module uses the detected location to control the shock wave generator position, and automatically adjusts it to improve coincidence between the focal volume and stone. The reliability of the tracking algorithm was clinically tested in 65 patients with renal stones. These in vivo tests were qualitative and the goal was to assess software ability to track stones during actual treatments. A quantitative evaluation of the reduction in shocks necessary for fragmentation was performed in vitro. Artificial stones were moved according to computer generated trajectories. Each trajectory was applied once with and once without automatic adjustment of the generator position. RESULTS: The in vivo tests demonstrated software ability to track stones as far as they were visible in the images. During in vitro tests automatic adjustments of the generator position reduced the number of shocks necessary to fragment stones completely by a factor of 1.64. CONCLUSIONS: Image based renal stone tracking software that automatically adjusts the shock wave generator position according to the displacement of renal stones is useful during extracorporeal shock wave lithotripsy. Treatment time was significantly shorter with this software.

Humans↗

[Castleman's disease and chromophobe carcinoma of the kidney. An incidental association?].

We report a case of Castleman's disease in a 65-year-old female, revealed by a renal tumor associated with inter-aortico-cava adenopathies and renal chromophobe cell carcinoma. This observation points to the difficulties in differentiating local Castleman's disease, which may be cured by surgical excision, from multicentric disease associated with a dysimmune syndrome of uncertain prognosis. The association of multicentric Castleman's disease with a carcinoma has rarely been described. It could be the emergence of a neoplasia in a context of dysimmunity or Castleman's disease might be related to the production of interleukin 6 by a renal carcinoma.

Adenocarcinoma↗

Color Doppler-guided prostate biopsies in 591 patients with an elevated serum PSA level: impact on Gleason score for nonpalpable lesions.

OBJECTIVES: To compare results of color Doppler-guided ultrasonography (CDUS) versus those of systematic biopsies in 591 patients with an elevated serum PSA level and to correlate them with digital rectal examination (DRE) findings. METHODS: Biopsies were directed into hypervascularized (CDUS+) or hypovascularized (CDUS-) hypoechoic peripheral zone nodules (443 cases). When transrectal ultrasound (TRUS) was normal (148 cases), biopsies were directed into hypervascular area. Six additional posterior biopsies were also performed in every patient, together with four anterior biopsies in 117 patients with normal DRE and prostate weight above 40 g. RESULTS: Biopsies were positive in 339 patients (57%). Positive biopsy rate (PBR) of directed biopsies was 84% in hypervascular abnormalities (264 of 316) and 17% in hypovascular nodules (23 of 134) (P < 0.001). PBR of combined biopsies was 84% in CDUS+ patients (266 of 316) and 26% in CDUS- patients (73 of 275) (P < 0.001). Comparison of TRUS and CDUS showed a sensitivity of 0.9 and 0.78, respectively, and a specificity of 0.46 and 0.8, respectively. Of the 131 patients with a PSA level between 4 and 10 ng/mL and a normal DRE, PBR was 59% (22 of 37) when CDUS was positive and 11% (10 of 94) when it was negative, regardless of TRUS abnormalities (P < 0.001). Nonpalpable cancers with a negative CDUS showed a significantly (P < 0.001) lower Gleason score (5.5 +/- 0.9) than that of CDUS+ cancer (6.5 +/- 1.1). Eleven cancers were diagnosed by only anterior positive biopsies. All of them had a negative CDUS and a PSA level above 10 ng/mL. CONCLUSIONS: CDUS does not modify prostate biopsy policy except in patients with negative CDUS, normal DRE, and PSA level between 4 and 10 ng/mL, where deferment of biopsy can be advocated. Anterior biopsies are only useful in patients with a PSA level above 10 ng/mL and a negative CDUS.

Aged↗

Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases.

OBJECTIVES: Detection of circulating tumor cells may improve the preoperative local staging of prostate cancers. The aim of this study was to perform enhanced reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific antigen (PSA) mRNA to define the predictive value of PSA-positive circulating cells in a large series of patients. METHODS: The study included 46 patients with Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and 51 (including 9 women) with nonprostatic disease. PSA-positive cells from peripheral blood samples were detected by Southern blot analysis of the RT-PCR products. Original oligonucleotide primers were defined to exclusively detect the three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in 8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA-positive circulating cells was significantly increased in patients with prostate cancer versus patients with BPH (P = 0.03). Among clinically localized prostate cancers with a Gleason score less than 8, a correlation was observed between PSA-positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%. CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging, this study demonstrated the absence of tissue and tumor specificity of PSA-positive circulating cells, accounting for the weak positive predictive value of this technique.

Aged↗

IL-6 is a survival prognostic factor in renal cell carcinoma.

It has been reported that a high plasmatic concentration of interleukin-6 (IL-6) is correlated to a lack of response to immunotherapy in several malignancies, suggesting that IL-6 was either a marker of tumour aggressiveness or had only a predictive value of response to immunotherapy. To discriminate between these two possibilities, a retrospective study was performed in a series of 19 patients with metastatic renal cell carcinoma who did not respond to IL-2/IFNalpha/5-FU treatment. Serum levels of IL-6, C-reactive Protein (CRP), soluble IL-2-receptor (sIL-2R), M-CSF and neopterin were assayed before treatment. IL-6 showed a significant correlation with patients median survival time (P < 0.016), suggesting that serum concentration of IL-6 before treatment is a marker of tumour aggressiveness rather than a predictive parameter for an immunological response.

Adult↗