In vitro effects of tibolone and its metabolites on human vascular coronary cells.

OBJECTIVES: Tibolone is a tissue selective compound with estrogenic, androgenic and progestogenic properties in classical bioassays. It is used for alleviation of menopausal symptoms and for osteoporosis prophylaxis in postmenopausal women. Only few data are available regarding the effects of tibolone on the cardiovascular system. We investigated therefore the in vitro effects of tibolone and its metabolites on the vasculature under special controlled conditions, using human female coronary endothelial and smooth muscle cells. METHODS: The effect on the production of the following markers in endothelial cells from human female coronary arteries was evaluated: nitric oxide synthase, prostacyclin, endothelin, plasminogen-activator-inhibitor-1 (PAI-1), E-Selectin, Intercellular adhesion molecule (ICAM-1), monocyte attracting protein-1 (MCP-1) and the precursor of matrix metalloproteinase-1 (pro-MMP-1). Tibolone, its metabolites, estradiol (E2), E2/norethisterone (NET) and E2/medroxyprogesterone acetate (MPA) were tested at 0.1 microM and 1 microM. The markers were determined by enzyme immunoassays in the cell supernatant. Cell proliferation of smooth muscle cells from female coronary artery was measured by an adenosine triphosphate-assay. RESULTS: Tibolone, its 3-hydroxy metabolites, E2/NET, E2/MPA and estradiol alone had significant effects on the synthesis of all markers tested. The magnitude of the tibolone effects, however, was mostly smaller than that of E2/NET and E2/MPA. Concerning smooth muscle cells tibolone and its 3-hydroxy metabolites also elicited an inhibition of the proliferation compared to control values. The strongest effect here was found for E2/NET and E2 alone, whereas E2/MPA had no effect. CONCLUSION: The results of this in vitro study conducted with cells of the most important vascular bed with respect to the problem of cardiovascular risk suggest that tibolone can positively influence the vasculature. However, these tibolone effects may depend on intact vascular cells and may vary due to the different atherosclerotic stages of the vessels. Thus, experimental studies are useful to explore mechanisms, but clearly cannot replace clinical studies.

Prospective randomized trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis.

OBJECTIVES: Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a well-established option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin. METHODS: Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response. RESULTS: The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressin-treated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups. CONCLUSION: Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the well-established desmopressin therapy and the alternative laser acupuncture.

Prostate cancer screening in the Tyrol, Austria: experience and results.

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Cryptorchidism, open processus vaginalis, and associated hernia: laparoscopic approach to the internal inguinal ring.

OBJECTIVES: A nonpalpable testis was the first indication for laparoscopy in urology. This primarily diagnostic procedure has evolved to complete laparoscopic orchidopexy. An associated inguinal hernia due to an open processus vaginalis is reported in 26% of cryptorchidism cases. Simultaneous laparoscopic orchidopexy and herniorrhaphy are therefore the next logical step. METHODS: Between 1992 and 1998, 61 children underwent laparoscopy for pathology of the internal inguinal ring. In 48 boys the operation was performed for a nonpalpable testis and in 13 boys laparoscopic transection of the processus vaginalis was performed because of clinical hydrocele. RESULTS: In 25 of the 48 cases an intra-abdominal location was found with 18 existing and 7 vanishing testicles. Laparoscopic orchidopexy was performed either as a two-stage Fowler-Stephens technique (n = 6) or as a direct one-stage repair (n = 12). In 6 boys with cryptorchidism a direct inguinal hernia was associated, which received simultaneous laparoscopic herniorrhaphy. In 23 cases of cryptorchidism with an inguinal location of the testis, 3 vanishing testicles were found. In 20 cases with normal testicular vessels, an inguinal exploration followed. In 4 of the hydrocele cases additional herniorrhaphy had to be performed. In all cases the operation could be performed as planned without complications. After orchidopexy all testicles were in the normal position and well perfused as revealed by flow Doppler sonography. All hydroceles disappeared within several days. There was no inguinal hernia recurrence. CONCLUSIONS: Laparoscopic dissection of the internal inguinal ring allows perfect delineation of the anatomic structures and their relationship. Transection of the processus vaginalis can be performed without disturbance of the inguinal canal. Hernias can be closed with essentially the same technique as used in open surgery. Morbidity was minimal in all patients.

Prostate cancer screening in Tyrol, Austria: experience and results.

BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antigen (PSA) and percent free PSA as the initial test. METHODS: The twelve projects studied included: (1) a mass screening study using PSA as the initial test in 21,079 volunteers; (2) an investigation of the usefulness of normal and age-referenced PSA cut-offs in 1,618 men; (3) a PSA-based screening study of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital rectal examination findings; (5) determination of percent free PSA in one retrospective and two prospective studies to determine the appropriate cutpoints for percent free PSA; (6) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers; (7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1, 543 men undergoing transurethral resection of the prostate; (8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program; (9) a study evaluating the probability of having prostate cancer given the patient's age, total PSA and digital rectal examination findings; (10) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens; (11) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level, and (12) a study whether age has an impact on the extension of prostate cancer. RESULTS: (1) of the 21,079 volunteers, 1,618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy. Ninety-five were found to be organ-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. (3) Of the 2,272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transition zone only. (5) In the retrospective study, receiver-operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated PSA levels <10.0 ng/ml were further evaluated and 37 prostate carcinomas were detected. By using a % free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/ml and a % free PSA <18% were further evaluated and 27 (22.5%) were found to have prostate carcinomas. (6) Receiver-operating characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm3 as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. (7) In the prescreening era the incidence of T1a grade 1 and 2 carcinomas was 3.1% and the incidence of T1a grade 3 and T1b carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. (8) The rate of organ-confined tumors increased from 28.7% in 1993 to 65.7% in 1997. (9) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rath