Drug combinations in the therapy of low response to phosphodiesterase 5 inhibitors in patients with erectile dysfunction.

Combinatorial drugs utilising a clinically-proven single agent approach in erectile dysfunction (ED) have led to the search for additional compounds to improve therapy and the safety profile. Selective inhibitors of Phosphodiesterase type 5, such as Sildenafil, demonstrate a defined failure rate in ED. The therapeutic concept to increase blood influx and or to decrease blood efflux in patients with ED under therapy encountered severe drawbacks.

Efficacy of once-a-day terazosin in benign prostatic hyperplasia: a randomized, double-blind placebo-controlled clinical trial.

This randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and safety of once-a-day terazosin (10 mg/day) in ambulatory patients (n = 57) with benign prostatic hyperplasia (BPH). After a 4-week placebo lead-in and a 24-week treatment period with terazosin (both single-blind), 30 patients who responded to terazosin were randomly assigned to either the terazosin or placebo treatment group for 12 weeks. During the single-blind treatment period, the peak urine flow rate increased 54% from a baseline average of 7.

Effects of terazosin in the treatment of benign prostatic hyperplasia. A pilot study.

Several reports in the literature suggest that alpha-receptor blockade may have therapeutic value in treating the symptoms of patients with benign prostatic hyperplasia (BPH). Terazosin (Heitrin, Hytrin) is a long acting, highly selective alpha 1-adrenergic blocking agent structurally similar to prazosin. The present study, which also can be regarded as a pilot study, was undertaken as part of a multicenter study to evaluate the safety and efficacy of terazosin in the treatment of patients with BPH.

Clinical experience: symptomatic management of BPH with terazosin.

Several reports in the literature have suggested that alpha-receptor blockade may have therapeutic value in treating the symptoms of patients with benign prostatic hypertrophy (BPH). Terazosin is an alpha-1 adrenergic blocking agent currently marketed as an antihypertensive. A multicenter study to evaluate the safety and efficacy of terazosin in the treatment of patients with BPH was initiated.

[Drug therapy of metastasizing prostate carcinoma with special reference to the bioavailability of fosfestrol after oral administration].

Prostata cancer is one of the most dangerous tumours occurring in the older man. No general accepted therapy has existed up to now. In this study we were engaged on the pharmacokinetics of fosfestrol (Honvan) after oral administration.

Quantification of alpha-fetoprotein and beta-HCG in testis tumor patients.

Patients with testis tumor were investigated for serum and tissue levels of alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). The tissue immune peroxidase-antiperoxidase staining for the tumor marker was quantitated by computer-assisted immunohistophotometry and immuno-gamma ray histospectrometry. The results supported the general view that mostly polynuclear giant cells produce beta-HCG in 66% of nonseminoma cancer.

[Lectin binding in immunohistologically AFP/HCG positive and negative testicular carcinoma].

The morphologic display of testicular cancer is a heterogenous cellular pattern. A biological heterogeneity is also true for the expression of tumor markers. The biosynthesis of tumor marker proteins alpha-fetoprotein (AFP), ferritin, Schwangerschaftsprotein (SP 1) glycoprotein, tissue polypeptide antigen and of hormones (beta-human chorionic gonadotropin (HCG) = significantly present in nonseminoma germ cell tumors--does, however, define only a small number of cancer cells.

[Plasma concentrations of fosfestrol as well as diethylstilbestrol on their conjugates following intravenous administration on prostatic carcinoma patients].

After the identification of E-diethylstilbestrol (DES)-glucuronide-sulphate-bis-conjugate in the plasma of patients suffering from metastatic prostatic cancer for the first time we have registered the plasma concentration-time curves of fosfestrol (Honvan) and its monophosphate as well as E-DES and its 3 conjugates over 8 h with a further 10 patients. Maximum concentrations fluctuate between 1 and 32 micrograms/ml plasma. Therefore the greatest amount of E-DES formed by hydrolysis and its conjugates are hidden in deeper compartments, probably in the lung.

[Direct determination of diethylstilbestrol and its monoconjugates in plasma].

Direct Determination of Diethylstilbestrol and its Monoconjugates in Plasma After "homogeneous ion pair extraction" with CH3OH from plasma of patients suffering from metastatic prostate cancer and subsequent partitioning on a C18-phase diethylstilbestrol (E-DES) and its monoconjugates (glucuronide, sulfate) as well as its glucuronide-sulfate conjugate may be detected quantitatively by HPLC/UV (236 nm) or HPLC/ED (+1.0 V). Working electrode is a special home-made carbon paste electrode.

Some aspects of clearance of mitoguazone in cancer patients and experimental cancer models.

Mitoguazone (methylglyoxal-bis(guanyl-hydrazone), MGBG) was studied by its first-pass mechanism in both cancer patients and experimental cancer models. It appears from the study that 90% of MGBG is cleared from the plasma within minutes. 24-h recovery in the urine, however, did not exceed 16% so that 84% of the drug seems to be bound to subcellular compartments.

Chemotherapy and trace element levels in blood and tissue of rats implanted with prostate tumor cells.

Male Copenhagen rats with transplanted prostatic adeno-carcinoma were treated with different polyamine synthesis inhibitors, such as methylglyoxal-bis-guanylhydrazone (MGBG), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) combined with 9-β-D-arabin-ofuranosyl-adenine (ARA-A), α-difluoromethyl-ornithine (DFMO), and some of their combinations. Levels of the essential trace elements-copper, zinc, magnesium, iron, selenium, and manganese -have been determined in blood, tumor, kidney, and liver of these animals and are discussed in terms of efficiency of the treatment. MGBG had the strongest effect on trace element levels in tissues of treated animals.

[Therapy with inhibitors of polyamine biosynthesis in refractory prostatic carcinoma. An experimental and clinical study].

Transplantable prostate adenocarcinoma were treated with polyamine biosynthetic inhibitors. alpha-difluoromethylornithine (alpha-DFMO), an inhibitor of ornithine decarboxylase and by s-methylglyoxal-bisguanylhydrazone (MGBG), an inhibitor of s-adenosylmethionine decarboxylase. The therapeutic regimen of 0.

[Polyamines, polyamine antimetabolites and urogenital tumors. State of research and clinical results].

The polyamine metabolism is pathologically changed in tumor tissues, and especially putrescine and spermidine demonstrate abnormally high values in kidney, bladder, and prostate cancer. The inductive processes which activate the biosynthetic polyamine enzymes in cancer are completely unknown. Of therapeutic interest is the fact that increased enzyme activities through irreversible inhibitors become significantly reduced, which consequently slows the tumor growth.

[Plasma levels of fosfestrol and its monophosphate, of diethylstilbestrol and its monoglucuronide following intravenous administration in patients with metastatic prostatic carcinoma].

A homogeneous ion pair extraction technique enables the nearly quantitative isolation of fosfestrol (1) (Honvan) and up till now of three of its metabolites from the plasma of patients suffering from metastatic prostata cancer. The detection occurs by HPLC with UV-detector. The range of detection is in the lower microgram range.

Some effects of inhibitors of polyamine synthesis on experimental prostatic cancer.

Difluoromethylornithine (DFMO) and methylglyoxal-bis(guanyl-hydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested in two experimental prostatic cancer models. DFMO resulted in a reduction in tumor size in both the rapidly growing R-3327 rat prostatic adenocarcinoma (30.5 +/- 15 versus 61 +/- 9.

Na-tartrate in the treatment of chronic nonbacterial prostatitis.

In an open investigation 20 patients with a history of chronic abacterial prostatitis (24 month duration) and of multiple therapies were treated by 0.07-0.15/kg Na-tartrate.

Experimental chemotherapy in a transplantable renal adenocarcinoma. I: Effects of some inhibitors of polyamine synthesis.

Difluoromethylornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested for antitumor activity in the BALB/C mouse renal adenocarcinoma model, wherein ODC and AMDC activity are elevated compared to the normal kidney. Additionally, an indirect effector of AMDC synthesis, arabinofuranosyladenine and an inhibitor of AMDC synthesis, cycloleucin (CL), were tested in this model. Simultaneous administration of both DFMO and MGBG affected the growth of renal adenocarcinoma less than did administration of DFMO or MGBG alone.

Antigrowth effect of some inhibitors of polyamine synthesis on transplantable prostate cancer.

Inhibitors of polyamine synthesis were tested for therapeutic effectiveness on transplantable prostate cancer. Inhibition of either ornithine decarboxylase or S-adenosyl-L-methionine decarboxylase (AMDC) by alpha-difluormethylornithine (DFMO) or methylglyoxal-bis[guanylhydrazone] (MGBG), respectively, was associated with significant antitumor effect. The combination of DFMO with MGBG was not only more effective but no more toxic than MGBG alone.

[Thyroid hormones in metastasizing prostate cancer treated with polyestradiol phosphate].

Patients with prostate cancer demonstrate a significant change in thyroid hormones when treated with estrogens after orchiectomy. Low-dose estrogen treatment for more than six months stimulates the synthesis of thyroxine-binding globulin. As a consequence, serum level of thyroxine is also increased.

The effect of high level CaCi2 injection on parathyroid hormone dependent cAMP in stone formation patients.

Patients with a history of idiopathic calcium oxalate stones but without current stone formation do not react to stimulation of parathyroid extract as expected after high dose calcium pretreatment. With Ca2+ pretreatment, these patients show higher serum and also renally generated levels of cAMP after rapid injection of extreme parathyroid extract-concentrations. Healthy controls show a modest increase of serum levels cAMP after similar stimulation with parathyroid extracts.

Effect of high level bovine parathyroid extracts on serum PTH, cAMP and urinary cAMP, Na+, and uric acid in stone-forming patients.

Patients with a history of idiopathic calcium oxalate stones, but without current stone formation, show distinctly higher levels of serum cAMP (cyclic adenosine 3',5'-monophosphate) after rapid injection of an extreme concentration of parathyroid extract (PTE). Extreme parathyroid hormone (PTH) levels, as induced by rapid injection of biologically active bovine PTEs, significantly affect the renal generation of cAMP and the elimination of electrolytes in a healthy control group. The stimulated increase of urinary cAMP, sodium, potassium, calcium and phosphate are observed to return to normal levels 120 min after extreme PTE injections for both groups studied.

[Therapy of prostate carcinoma with polyamine synthesis inhibitors. I. Physiological and pathophysiological principles].

The therapeutic concept of irreversible inhibition of both ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) by alpha-difluoromethylornithine (DFMO) and methylglyoxal bis-guanylhydrazone (MGBG) is based on pathologic activities of these enzymes in tumor tissue. The polyamines putrescine, spermidine and spermine are measured in highest concentration in the prostate of both men and animals, with a significant increase of spermine in benign hyperplasia of the prostate. Patients with metastatic cancer of the prostate have elevated putrescine levels in the 24-hour urine.

Plasma lipid bound sialic acid in patients with prostate and bladder cancer.

Plasma lipid bound sialic acid (LSA) was measured in patients with prostate and bladder cancer to determine the usefulness of this biochemical marker in teh staging of malignant disease and in monitoring the efficacy of therapy. Patients with advanced stages of prostate cancer with bone metastases exhibited LSA levels significantly higher than normal subjects. Patients with bladder cancer showed elevations in LSA both in early noninvasive and in advanced stages of the disease.