Cardiovascular effects of sildenafil citrate (Viagra): a naturalistic cross-over study.

In a cross-over study we investigated the effects of sildenafil (single doses of 25- or 50mg) on cardiovascular autonomic nervous system (ANS) function assessed by serial recordings of blood pressure, conventional 12-lead electrocardiograms and standardized, time-and frequency domain indices of heart rate variability (HRV) in 21 men with erectile dysfunction. More than half of these patients had multiple comorbidities. Sildenafil induced significant mean reductions from baseline in resting blood pressure, accompanied by a reflex increase in heart rate. There were no significant changes after administration of sildenafil in any other of the ANS function indices. These preliminary findings suggest that sildenafil does not significantly affect cardiac ANS function in patients with erectile dysfunction.

Comparison of the malignant phenotype and genotype of the human androgen-independent cell line DU 145 and a subline derived from metastasis after orthotopic implantation in nude mice.

To investigate the potential genetic changes underlying the progression of human hormone-resistant prostate cancer, we related chromosomal alterations of the DU 145 cell line and a subline isolated form a metastasis in an orthotopic model to tumorigenicity, metastasis and chemoresistance. In 15 mice 1 x 10(5) DU 145 cells were injected into the dorsal prostate. From a resulting paraaortic lymphnode metastasis, we isolated a subline (DU 145 MN1), which was injected into 15 nude mice. The sulforhodamine B (SRB) assay was used to analyze cell doubling time and the IC(50) of cisplatin and 5-fluorouracil for both cell lines. Cytogenetic characterization was performed with conventional karyotype analysis and fluorescence in situ hybridization (FISH). After orthotopic implantation of DU 145 cells tumorigenicity was 100% whereas only 2 mice revealed lymphnode metastases. In contrast, the take rate after implantation of DU 145 MN1 was 100%, with lymphnode metastases in 7 mice. The SRB assay revealed a 8-fold increased IC(50) for cisplatin and a 2.5-fold increase for 5-FU in DU 145 MN1 as compared to DU 145 cells. There was gain of a chromosome 8 and only two copies of chromosome 17 in the DU 145 MN1 cells as compared to the parental cell line. The emergence of an i(9)(q10) in addition to two normal chromosome 9 homologues in the DU 145 MN1 cell line was confirmed by FISH using a chromosome 9-specific painting probe. In summary, clonal evolution of the chromosomal changes following repeated orthotopic implantation, may assist in locating the genes involved in the progression and chemoresistance of human hormone-resistant prostate cancer.

Influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC3 in an orthotopic model.

OBJECTIVE: It has been demonstrated that quinoline-3-carboxamide, linomide, inhibited angiogenesis and reduced the volume of tumors grown from human hormone-resistant prostate cancer cell lines after subcutaneous implantation in mice. However, subcutaneous xenograft models may not mimic human conditions due to the absence of prostatic stromal cells at the ectopic site. Therefore, we investigated the influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC-3 in an orthotopic model. METHODS: In 30 athymic nude mice, 5x10(5) PC-3 cells were injected into the dorsal prostate after surgical exposure. After 7 days, group 1 (n = 15 mice) received linomide 100 mg/kg/day in the drinking water (per os). The other 15 mice (group 2) served as controls. All mice were sacrificed after 38 days followed by macroscopical and histological evaluation of local tumor growth and metastasis. Microvessel density was determined by immunohistochemical staining for von Willebrand factor as well as silver staining followed by morphometric analysis in an area of highest vessel density. RESULTS: In the control group, local tumorigenicity and locoregional lymph node metastasis was 100%. The mean weight of the local tumor was 894 mg (395- 1,261 mg). The mean transversal diameter of the lymph node metastases was 4.0 mm (1.5-5. 4 mm). In the treatment group, local tumor growth and lymph node metastasis was 100% with a mean local tumor weight of 869 mg (232-1, 131 mg) and a mean lymph node metastasis diameter of 4.6 mm (1.3-5.9 mm). Microvessel density of the local tumor in the control and treatment group did not differ significantly. CONCLUSION: Contrary to the results reported in subcutaneous animal models, linomide per os has no effect on net tumor growth and metastasis after orthotopic implantation of the human hormone-resistant prostate cancer cell line PC-3 in nude mice.

Influence of pertussis toxine on local progression and metastasis after orthotopic implantation of the human prostate cancer cell line PC3 in nude mice.

Tumor cell migration is a fundamental process of metastasis. Pertussis toxine inhibits lysophosphatidic acid related cell migration by ADP-ribosylation of G proteins. We examined the influence of pertussis toxine (PTX) on progression and metastasis of the human hormone-insensitive prostate cancer cell line PC-3 after orthotopic implantation in nude mice. In 30 athymic male nude mice (NMRI) 5x10(5) PC-3 cells were injected into the dorsal prostate. After 7 d 15 mice received a total of six intraperitoneal injections of 5 micro g PTX/100 g body weight at an interval of 4 d. The other 15 mice received phosphate buffered saline and served as control. All mice were killed at 37 d followed by macroscopical and histological evaluation of local tumor growth and metastasis. In the control group tumorigenicity was 100% (15 out of 15). Mean weight of the tumor bearing unit of prostate and seminal vesicles was 541 mg (243-763 mg). The rate of positive lymphnodes was 100% with a mean transversal diameter of 3.9 mm (1.2-5.4 mm). In the PTX group local take rate was 100% with a mean weight of 251 mg (88-478 mg) (P two sided <0.0001). The rate of positive lymphnodes was 60% (9 out of 15) (P=0.017) with a mean transversal diameter of 2.3 mm (1.0-4.5 mm). PTX following orthotopic implantation of the human hormone-insensitive PC-3 cell line significantly reduces local tumor growth as well as metastasis to locoregional lymphnodes.

Orthotopic implantation of human prostate cancer cell lines: a clinically relevant animal model for metastatic prostate cancer.

BACKGROUND: To study the metastatic behavior of human prostate cancer cell lines, orthotopic injection in nude mice was performed. METHODS: Local tumor growth, metastasis formation, prostate-specific antigen, and androgen receptor expression were examined. RESULTS: Hormone-independent cell lines (PC-3, PC-3-125-IL, and TSU-Pr1) were highly tumorigenic and had a higher rate of lymph node metastasis after orthotopic than after subcutaneous implantation. PC-3 cell lines also consistently metastasized to the lungs. The androgen-sensitive LNCaP cell line showed local growth in 7 of 10, and lymph node metastasis in 4 animals. Significant serum PSA levels and strong receptor expression in primary and metastatic tumor tissues were observed. CONCLUSIONS: These results demonstrates that orthotopic implantation of human prostate cancer cell lines, including LNCaP, reproducibly leads to metastasis formation in nude mice.

[Therapy of hormone refractory prostate carcinoma with mitoxantrone. A clinical phase II study]. / Die Therapie des hormonrefraktären Prostatakarzinoms mit Mitoxantron. Eine klinische Phase-II-Studie.

So far, no curative treatment is available for hormone-refractory prostate carcinoma. Therapy is thus focused on alleviating symptomatic tumor progression with the aim of improving quality of life. Therefore, anthracyclin-derived mitoxantrone was administered to 25 patients with hormone-refractory prostate carcinoma and symptomatic progressive disease. After a median treatment of 13 weeks, a median of 4 cycles and a follow-up of 14 months, 48% of the patients (12/25) reported improvement in tumor-related pain; in 60% (15/25) there was improvement of the self-assessment symptom score and 32% of the patients (8/25) gained weight. Additionally, partial tumor response with regression of lymph-node metastases occurred in 3/25 patients (12%). In 10/25 patients the serum level of prostate-specific antigen (PSA) decreased as well as the alkaline phosphatase (AP) in 7/25 patients. Side effects subsequent to chemotherapy were leucopenia WHO grade III in 25% of the patients and thrombocytopenia WHO grade III in 3/25 and grade V (treatment-related death) in 1/25 patients. Non-hematological toxicity occurred in 2 patients (cardiotoxicity n = 1, nephrotoxicity n = 1, WHO grade II each).

[Autotransplantation of the kidney. Indications and results]. / Die Autotransplantation der Niere. Indikationen und Ergebnisse.

Renal autotransplantation is an established but rarely used therapy in cases of renal vessel lesions, tumours of the kidney and ureter, long-distance ureter lesions, complex nephrolithiasis and retroperitoneal fibrosis. The indications and results of renal autotransplantation are discussed using three case reports and compared to the literature. In cases of central intrarenal tumours and aneurysms of the kidney, autotransplantation is indispensible in order to save the organ. For long-distance ureter lesions as well as for retroperitoneal fibrosis, autotransplantation of the kidney gives excellent results. In difficult clinical situations ileum segment interposition is an alternative treatment.

[Nuclear medicine pain therapy in osseous metastases of prostate cancer]. / Die nuklearmedizinische Schmerztherapie beim ossär metastasierten Prostatakarzinom.

In patients with advanced prostate cancer, adequate palliation of pain from skeletal metastases is of primary importance. Radionuclide therapy offers an effective treatment with few side effects or risks after the primary therapeutic modalities, i.e. androgen deprivation, chemotherapy, and percutaneous radiation therapy, are exhausted. This review discusses the potential and limitations of radionuclide therapy and provides recommendations for patient selection and practical implementation of radionuclide therapy.

E-cadherin: a marker for differentiation and invasiveness in prostatic carcinoma.

Considerable controversy exists concerning the value of histomorphological data in the assessment of the malignant potential of prostatic carcinomas. We investigated the expression pattern of E-cadherin in human prostate at the translational level. E-cadherin is a specific epithelial cell-cell adhesion molecule which has previously been found to be expressed in well-differentiated non-invasive carcinoma cell lines but is lost in many poorly differentiated invasive cell lines. The E-cadherin expression pattern in the prostate samples was correlated with histopathological findings in the same specimens. We found strong E-cadherin expression in normal prostate and benign prostatic hyperplasia. A decrease in or loss of E-cadherin was seen in 13 of 14 locally advanced and in 8 of 9 poorly differentiated prostatic carcinomas. We conclude that downregulation of E-cadherin expression plays a role in prostate carcinogenesis and invasiveness.

The forgotten double J stent. Case report of a multifractured ureter stent.

An 81-year-old male patient was admitted to hospital because of macrohematuria. The clinical examination revealed a multifractured double J stent which had been placed 17 months before in another clinic because of hydronephrosis. In the reported case, a combined endoscopic and open surgical management was necessary to remove all fragments from the renal pelvis, the ureter and the bladder. Occlusion, encrustration and migration are among the most frequent risks of ureter stenting. The breakage of the stent, however, is a rare but severe complication. Therefore, patients should generally be controlled by sonography every 2 months and when malfunction of the stent is suspected, a cystogram should follow. In general, a stent exchange should be performed after 12 months.

[Computed tomographic follow-up of cranio-cerebral injuries in children]. / Computertomographische Verlaufskontrollen nach Schädel-Hirn-Trauma im Kindesalter.

38 children with moderate and severe head injuries had CT follow-ups. On initial scans combined lesions dominated over diffuse (diffuse swelling, subarachnoid haemorrhage) and focal lesions (focal swelling, contusions). Contusion showed up until the 6th day after the accident. Two cases of focal lesions could be demonstrated only after intravenous contrast. Up to 40% of the children developed hypodense extracerebral accumulations. Long-term CT follow-ups showed ventricular (84%) and sulcal enlargement (63%) as well as hypodense parenchymal lesions (50%). Combined and diffuse lesions showed a correlation of initial scans and long-term follow-up which could not be demonstrated in case of focal lesions.