Dosimetry of human exposure to furan and 2-methylfuran by monitoring urinary biomarkers.

Furan and 2-methylfuran (2-MF) can form during food processing and accumulate in foods at various concentrations depending on processing technology and beverage/meal preparation methods applied prior to consumption. Here, we report a controlled dosimetry study with 20 volunteers (10 male, 10 female) to monitor dietary furan/2-MF exposure. The volunteers followed an eleven-day furan/2-MF-restricted diet in which they consumed freshly prepared coffee brew containing known amounts of furan and 2-MF on two separate occasions (250 mL and 500 mL on days 4 and 8, respectively). Urine was collected over the whole study period and analyzed for key metabolites derived from the primary oxidative furan metabolite cis-2-butene-1,4-dial (BDA) (i.e., Lys-BDA, AcLys-BDA and cyclic GSH-BDA) and the primary 2-MF metabolite acetylacrolein (AcA, 4-oxo-pent-2-enal) (i.e., Lys-AcA and AcLys-AcA). A previously established stable isotope dilution analysis (SIDA) method was utilized. Excretion kinetics revealed two peaks (at 0-2 and 24-36 h) for AcLys-BDA, Lys-BDA, AcLysAcA and LysAcA, whereas GSH-BDA showed a single peak. Notably, women on average excreted the metabolite GSH-BDA slightly faster than men, indicating gender differences. Overall, the study provided further insights into the spectrum of possible biomarkers of furan and 2-methyfuran metabolites occurring in the urine of volunteers after coffee consumption.

Fertility and sexual function following orchiectomy and 2 cycles of chemotherapy for stage I high risk nonseminomatous germ cell cancer.

PURPOSE: We investigate fertility and sexual function in patients following orchiectomy and adjuvant cisplatin based chemotherapy for high risk, stage I nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: Between 1985 and 1994, 59 patients with stage I nonseminomatous germ cell tumor and poor prognostic factors were treated with 2 cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin after orchiectomy. At least 32 months following treatment all patients were contacted and asked to complete a questionnaire regarding fertility and sexual activity, and to volunteer for a semen and hormonal analysis. RESULTS: Of the 59 patients 49 (83%) completed the questionnaire. Before chemotherapy 18 (37%) patients had fathered children, 6 (12%) were involuntarily childless and none had a major sexual dysfunction. After treatment 11 (22%) patients fathered children, and 5 (10%) were involuntarily childless, with 4 involuntarily childless before chemotherapy. There were no significant alterations in sexual function. Semen analysis in 27 patients was normal in 23, and revealed mild oligospermia in 2 and azoospermia in 2. In 18 patients with hormone analysis median values for luteinizing hormone and free testosterone were normal but median value for follicle-stimulating hormone was slightly increased. CONCLUSIONS: Two cycles of cisplatin based adjuvant chemotherapy do not seem to affect adversely fertility or sexual activity.

Five meters of H(2)O: the pressure at the urinary bladder neck during human ejaculation.

BACKGROUND: There are no data in the literature on pressure changes in the prostatic urethra during ejaculation. In healthy men, it has always been postulated that there must be a pressure gradient in order to prevent retrograde ejaculation, but scientific proof for that is pending. METHODS: In five healthy male volunteers, the pressure profile in the prostatic urethra was registered during ejaculation, using a 10 French balloon catheter with 16 pressure channels. The channels were arranged in pairs at 5-mm intervals, beginning just below the balloon at the bladder neck and extending down to the external urethral sphincter. RESULTS: In the proximal part of the prostatic urethra, a pressure of up to 500 cm of H(2)O was measured in all subjects. Contrary to that, pressures did not exceed 400 cm of H(2)O distally to the verumontanum. CONCLUSIONS: A novel method to register the pressure profile in the lower urinary tract during ejaculation (ejaculomanometry) is presented. This study adds to the knowledge of the normal physiology of reproductive function and may be useful in the evaluation of male sexual and reproductive disorders.

Long-term results following adjuvant chemotherapy in patients with clinical stage I testicular nonseminomatous malignant germ cell tumors with high risk factors.

PURPOSE: We determine the efficacy and safety of 2 cycles of adjuvant chemotherapy after orchiectomy in patients with high risk clinical stage I nonseminomatous germ cell tumor of the testis as an alternative to retroperitoneal lymphadenectomy or watchful waiting. MATERIALS AND METHODS: A total of 60 consecutive patients with clinical stage I nonseminomatous germ cell tumor of the testis and 1 or more risk factors were entered into this prospective study. Criteria for high risk were embryonal cell carcinoma, tumor invasion of blood or lymph vessels, or tumor stage pT2 or greater. Chemotherapy consisted of 2 cycles of cisplatin, vinblastine and bleomycin or bleomycin, etoposide and cisplatin. RESULTS: Of the 60 patients 1 refused chemotherapy and 1 was lost to followup 1.5 years after treatment. The remaining 58 patients have been followed for a median of 93 months (range 32 to 146). World Health Organization grade 4 toxicity was observed in 9 of the 116 chemotherapy cycles, and consisted mainly of transient neutropenia and thrombocytopenia. No significant long-term sequelae were detected. There was 1 relapse after 22 months in a patient with adult teratoma in the ipsilateral region of the iliac vessels who remained disease-free 85 months after surgical excision of the lesion. Another patient had a seminoma in the contralateral testicle with interaortocaval lymph node metastases 7.5 years after adjuvant chemotherapy. The remaining 56 men are without relapse or contralateral tumor to date. CONCLUSIONS: We recommend adjuvant chemotherapy as an efficient therapeutic alternative to retroperitoneal lymphadenectomy for high risk nonseminomatous germ cell tumor of the testis.

Endopyelotomy for primary ureteropelvic junction obstruction: risk factors determine the success rate.

PURPOSE: We prospectively assessed the feasibility, complications, and short-term and long-term results of endopyelotomy for primary ureteropelvic junction obstruction. MATERIALS AND METHODS: In 80 consecutive patients primary ureteropelvic junction obstruction was diagnosed by excretory urogram or nephrostomogram, retrograde pyelography, diuresis renography and the Whitaker test in ambiguous cases. In all patients antegrade endopyelotomy was performed with a cold knife and an indwelling stent was left for 6 weeks. At 6 and 24 months postoperatively results were assessed clinically by an excretory urogram and/or diuretic renography and later by questionnaire and ultrasound. RESULTS: The primary success rate was 89% (71 of 80 patients) after the first endopyelotomy and increased to 91% (73 of 80 patients) after 2 patients had a second endopyelotomy. After median followup of 26 months (range 1.5 to 72) 6 of the 73 initially successfully treated patients had relapse. Two were successfully re-treated by a second endopyelotomy, resulting in an overall success rate of 81% (65 of 80 patients) after 1 procedure and 86% (69 of 80 patients) after a second endopyelotomy in 4 patients. Mean preoperative pyelocaliceal volume decreased from 64 +/- 33 to 41 +/- 20 ml. (p = 0.0003) 6 months after endopyelotomy and did not change during the following 18 months. The probability of successful endopyelotomy was better in patients with a preoperative pyelocaliceal volume less than 50 ml. (87%) and worse in patients with a volume greater than 50 ml. (76%). A crossing vessel to the lower pole of the kidney causing persistent functional obstruction of the ureteropelvic junction was found in 6 of the 10 patients re-treated by open pyeloplasty (9) or nephrectomy (1). Preoperative mean renal function as determined by diuretic renography was significantly lower in patients with failed endopyelotomy than in successfully treated patients. Successfully treated patients showed no change in renal function 6 and 24 months postoperatively. CONCLUSIONS: Endopyelotomy in primary ureteropelvic junction obstruction is a safe, minimally invasive procedure with a high primary success rate and a low relapse rate. Open pyeloplasty could be avoided in 86% of our patients. Endopyelotomy is less invasive, has less functional and esthetic sequelae than open pyeloplasty and does not compromise open surgery if that becomes necessary. We recommend endopyelotomy as first line treatment for patients with primary ureteropelvic junction obstruction.

[Bloodless prostate treatment using high-intensity focused ultrasound (HIFU)]. / Unblutige Prostatabehandlung mit hochintensivem fokussiertem Ultraschall (HIFU).

High intensity focused ultrasound (HIFU) is a technique whereby energy with resultant heat and tissue destruction can be delivered to a discreet distant site without injury to intervening tissue. 27 patients with bladder outlet obstruction and 5 men with loco-regional prostate cancer were treated by this method. At 3 months' follow-up a highly significant improvement of objective and subjective parameters could be demonstrated. No significant complications of this minimally invasive technique have been encountered. Moreover, our preliminary experience suggests that transrectal HIFU may control localized prostate cancer with minimal morbidity and that retreatment is possible at any time without toxicity to surrounding structures.