Reliability of the International Prostate Symptom Score in the Assessment of Patients With Lower Urinary Tract Symptoms and/or Benign Prostatic Hyperplasia

Purpose

The reliability of the International Prostate Symptom Score (I-PSS) was tested in patients with lower urinary tract symptoms and/or benign prostatic hyperplasia.

Materials and Methods

A total of 71 consecutive men with benign prostatic hyperplasia and/or lower urinary tract symptoms was asked to complete the I-PSS at baseline and 8 weeks later. At the second visit the physician also completed the I-PSS according to the complaints of the patient. Variability between both scores was evaluated by calculation of duplo errors and results were compared to the clinical data.

Results

A considerable variability existed between the I-PSS results obtained at baseline and 8 weeks. The duplo error was 4.3. In a regression analysis of I-PSS, including all clinical parameters, only free flow had some predictive value for I-PSS outcomes.

Conclusions

It is important to consider the variability of the I-PSS score when making decisions concerning treatment.     

Urodynamic and Clinical Effects of Terazosin Therapy in Patients with Symptomatic Benign Prostatic Hyperplasia

Purpose

We evaluated the urodynamic and clinical effects of terazosin in patients with symptomatic benign prostatic hyperplasia (BPH).

Materials and Methods

A total of 45 patients who participated in a multicenter trial was evaluated with urodynamic pressure-flow studies before and after 26 weeks of treatment.

Results

Maximum flow rate and symptom score improved significantly in 22 patients with and 11 without bladder outlet obstruction who completed 26 weeks of treatment. In patients with bladder outlet obstruction the condition was significantly reduced and in patients without obstruction, significant urodynamic changes could not be detected.

Conclusions

Terazosin treatment results in symptomatic relief and improved urinary flow in patients with and without bladder outlet obstruction, and in significant improvement in patients with urodynamically proved obstruction.     

Tumorigenic potential of carbaryl in the heterozygous p53 knockout mouse model.

The heterozygous p53 knockout mouse model was used to assess whether vascular tumors noted in a 2-year carcinogenicity study in CD-1 mice with carbaryl were induced through a genotoxic mechanism. This knockout mouse model was selected for carbaryl because of the high sensitivity of this model to genotoxic events and its low spontaneous incidence of tumors until 9-12 months of age. Carbaryl was administered continuously via the diet to groups of 20 male heterozygous p53 knockout mice at concentrations of 0, 10, 30, 100, 300, 1000 and 4000 ppm for 180 days. Histopathological examinations revealed no evidence of carbaryl-induced neoplasms of any type. In particular, no neoplastic or preneoplastic changes were noted in the vascular tissue of any of the organs examined. Only neoplasms, recognized as those that occur spontaneously in untreated mice of this strain, were sporadically observed in a few animals from the intermediate dose groups with no evidence of a dose- or treatment-related effect. Therefore, under the conditions of this study, the no-observed-effect level (NOEL) of carbaryl for neoplastic changes in male mice was 4000 ppm (around 716 mg/kg body weight/day). We conclude: (1) carbaryl does not appear to be a genotoxic carcinogen at least in male mice; (2) if the vascular tumors observed in the CD-1 mice are treatment-related, they could have been induced by a non-genotoxic mechanism; (3) the response in transgenic animals may provide useful complementary results to better assess carbaryl's potential genotoxic hazard to humans.     

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT.