Prostatic tissue pressure measurement as a possible diagnostic procedure in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome.

Forty-two patients with chronic nonbacterial prostatitis (CNP) and twelve men without any urological complaints or history underwent intraprostatic tissue pressure measurement with a Stryker intracompartmental pressure monitor device. The pressures were measured under spinal anesthesia in connection with various surgical procedures. Tissue pressure was monitored at 10, 60 and 120 s after an injection of 1 ml saline. Significantly (P < 0.001) higher intraprostatic pressure values were registered at all the three time points in the patients with CNP compared to the controls. Our study shows that patients with CNP have elevated intraprostatic tissue pressures, probably reflecting increased tissue resistance and a poor tissue microcirculation status. It seems that this method can be used as a diagnostic tool to differentiate between various causes of chronic pelvic pain in the male. The aim is to develop further this method so that it is also suitable for outpatient use.

Non-specific, rapidly generated cytotoxicity in lymphocytes induced by BCG in vitro: no evidence of enhancing effect from preceding interaction between BCG and transitional cell line cells.

PURPOSE: To study short-term events in the mechanism of action of BCG with an emphasis on the interaction between BCG and T24 cell line cells. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMNC) or/and several tumor cell lines were incubated with BCG (Oncotice) using various clinical and subclinical BCG concentrations. RESULTS: 3 h BCG incubation of PBMNC at 10(7) - 5*10(5) CFU/ml., followed by a 4 h cytotoxicity test, resulted in a significant augmentation of cytotoxicity of PBMNC against T24 cells, and the augmentation was almost significant at 10(5) CFU/ml. Overnight BCG incubation of PBMNC further augmented that cytotoxicity at all concentrations down to 10(4) CFU/ml. The minimum overall time (incubation with BCG + cytotoxicity test), where stimulation of PBMNC could be detected, was only 4 h. The BCG enhanced cytotoxicity of PBMNC could be demonstrated against all the tested cell line cells in a 4 h cytotoxicity test by using a preceding overnight BCG incubation of PBMNC, and against the majority of the cell lines by using a preceding 3 h BCG incubation of PBMNC. No convincing evidence was obtained to support the hypothesis that BCG should be first processed by T24 cells to make these cells more susceptible to cell mediated lysis by PBMNC. CONCLUSIONS: Clinical and subclinical concentrations of BCG are directly stimulatory to PBMNC, which become, in a minimum time of a few hours, more capable of killing tumor cells, without a need for preceding interaction between BCG and tumor cells.

Increased intraprostatic pressure in patients with chronic prostatitis.

The purpose of this prospective study was to develop a method for measuring intraprostatic pressure. Intraprostatic, extraprostatic and perineal subcutaneous pressures were measured in 43 patients. Twenty-four patients had chronic nonbacterial prostatitis (CNP) and prostatic hyperplasia (group A), 10 patients had benign prostatic hyperplasia (BPH) (group B) and 9 patients served as controls (group C). The pressure measurements were performed with a Stryker pressure monitor under transrectal ultrasonographic control at three different points: perineal subcutaneous tissue, paraprostatic tissue and the apex of the prostate beneath the capsule. Significantly higher intraprostatic pressure values (P < 0.001) were recorded in the patients with CNP compared with the BPH patients or the controls. We conclude that this novel method of measuring intraprostatic pressure, which has not been reported earlier, could be a new tool in the diagnosis of CNP and in the evaluation of the therapeutic effects of the different treatment modalities used in CNP.

Current concepts in the role of intravesical instillations in the therapy and prophylaxis of superficial transitional-cell cancer of the bladder. The Finnbladder Research Group.

A survey on superficial, local urinary bladder cancer, its prognostic factors, and instillation treatments is presented on the basis of experience with approximately 1,000 patients over a period of 20 years, experimental investigations, and the literature. Personal opinions and practical recommendations are presented in 11 conclusive theses.

Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. Finnbladder Group.

PURPOSE: We attempted to prove if alternating chemoprophylactic and immunoprophylactic instillations improved efficacy and decreased toxicity in patients with recurrent superficial bladder cancer. MATERIALS AND METHODS: A total of 188 patients with rapidly recurring stage Ta or T1 cancer was randomly treated with mitomycin C (group 1) or alternating mitomycin C and Pasteur strain bacillus Calmette-Guerin (BCG) instillations (group 2) for 2 years. Mean followup was 34 months. RESULTS: Median times to initial recurrence were 12 months in group 1 and 7 months in group 2 (p = 0.976), and treatment failed in 21.5% and 18.9%, respectively. Recurrence rates during the instillation period were 1.01 in group 1 and 0.86 in group 2 (p = 0.376). There was no difference in the disease-free interval between the 2 groups (p = 0.976). Instillations were discontinued because of adverse effects in 6 cases (6%) in both groups. CONCLUSIONS: Efficacy of alternating mitomycin C and BCG was equal to mitomycin C monotherapy, and both methods were effective in prophylaxis of recurrent papillary bladder cancer. Less toxicity occurred in the alternating treatment group compared to earlier BCG monotherapy results.

Cyclosporine in severe interstitial cystitis.

PURPOSE: Cyclosporine is a widely used immunosuppressive drug in organ transplantation and recently it has been used in several autoimmune disorders with good results. Because interstitial cystitis may have an autoimmune etiology, we wished to determine whether cyclosporine has any effect on symptoms in patients with severe interstitial cystitis. MATERIALS AND METHODS: A total of 11 patients, who fulfilled the criteria for interstitial cystitis according to an international accrual form, received cyclosporine for 3 to 6 months at an initial dose of 2.5 to 5 mg./kg. daily and a maintenance dose of 1.5 to 3 mg./kg. daily. Blood pressure, serum creatinine and cyclosporine concentrations were monitored regularly. The patients completed frequency-volume charts at 2-week intervals. RESULTS: The frequency-volume charts showed favorable effects. Micturition frequency decreased (p<0.01), and mean and maximum voided volumes increased significantly (p<0.001 and p<0.01, respectively). Bladder pain decreased or disappeared in 10 patients, allowing for storage of large urine volumes. Serum creatinine did not change with the dosages used. Mild hypertension occurred in 2 patients and resolved after the cyclosporine dose was lowered. After cessation of treatment symptoms recurred in the majority of patients. CONCLUSIONS: The findings revive the concept of interstitial cystitis as an autoimmune disease.

Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the bladder. The Finnbladder Group.

PURPOSE: Our aim was to prove if alternating chemotherapeutic and immunotherapeutic instillations improved efficacy and reduced toxicity in patients with carcinoma in situ of the bladder. MATERIALS AND METHODS: Of 68 carcinoma in situ patients randomly treated with instillations 40 received mitomycin C and 28 received mitomycin C and Pasteur bacillus Calmette-Guerin (BCG) in alternating courses. Mean followup was 33 months. RESULTS: The complete response rates with mitomycin C and mitomycin C/BCG were 45% and 71% at 3 months, 59% and 82% at 12 months, and 47% and 74% at 24 months, respectively (p = 0.041). The disease-free interval showed the superiority of alternating therapy (p = 0.043). Recurrence rates during the instillation period were 1.834 with mitomycin C and 0.922 with mitomycin C/BCG (p = 0.013). No remarkable side effects developed in the alternating group. CONCLUSIONS: Therapy of carcinoma in situ with alternating mitomycin C and BCG is more effective than mitomycin C alone. Compared to BCG monotherapy only few side effects occur.

In vivo behavior of 111In-labeled monoclonal anti-prostatic acid phosphatase antibody after intraprostatic and intravenous injections.

The 111In-labeled monoclonal anti-prostatic acid phosphatase (PAP) monoclonal antibody F(ab')2 fragment was used for the radioimmunodetection of prostate cancer in two different patient groups: 15 patients with surgically verified T1-2 prostate cancer were imaged prior to staging lymphadenectomy and total prostatectomy using lymphatic administration (intraprostatic (ipr) injection), and 15 patients with verified metastatic prostatic cancer were imaged after intravenous (i.v.) injection. The patients were studied on several occasions (at 0-180 hours) after injecting a 1 mg MoAb fragment labeled with 75-150 MBq111In (DTPA-chelation). The extirpated tissues were counted for radioactivity, and studied immunohistochemically (IHC) and histologically. The anti-PAP MoAb was labeled with high efficiency (87-99%) and it demonstrated good immunoreactivity (90-95%) and a high affinity to the target antigen. In the excised prostates, cut into 12-18 smaller pieces, there was a clear correlation between the PAP content (as detected by IHC) and absolute radioactivity (% ID of 111In anti-PAP/g prostate). However, there was no correlation between radioactivity and the amount of cancer tissue (% of histological slices) inside the removed prostate tissue. In the pharmacokinetic studies, maximum activity in the serum was obtained within 3-5 hours after ipr injection; after that the kinetic behavior was similar to that after i.v. injection. After i.v. injection, two components could be distinguished the pharmacokinetic curves; the half-lives for mean distribution and elimination were 0.62 and 35.6 hours, respectively. The mean distribution half-life as well as the AUC from the pharmacokinetic curves correlated significantly with serum PAP (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus Calmette-Guérin sensitises fresh transitional carcinoma cells and T24 cell line to non-MHC-restricted cytotoxicity in vitro.

The activity of lymphokine (interleukin-2) activated killer (LAK) cells from 9 patients with transitional cell carcinoma (TCC) was tested against autologous, freshly purified transitional carcinoma cells. Cytotoxicity was relatively low. Bacillus Calmette-Guérin (BCG) substantially augmented both LAK activity and the cytolytic activity of non-stimulated peripheral blood mononuclear cells (PBMC) against autologous TCC when tested with 6 additional TCC patients. A similar enhancing effect of BCG was noted with leucocytes obtained from normal donors when tested against an allogenic T24 cell line. Both natural killer (NK) cells and T cells appeared to be responsible for the increased cytolytic activity caused by BCG. No cytolytic activity was noted against normal transitional epithelial cells. Sensitisation of TCC cells to the immune system may explain the clinical effects of BCG.

A bioresorbable urethral stent. An experimental study.

The aim of the present study was to examine the suitability of biodegradable polymers as materials for a urethral stent. A new urethral stent made of biodegradable self-reinforced poly-L-lactide (SR-PLLA) was implanted in 16 male rabbits after urethrotomy. Seven stents of stainless steel served as controls. The dimensions of the two types of stents were identical: length 15 mm, diameter 8.2 mm. The mechanical construction was a helical spiral. The SR-PLLA spiral was sustained with three microspirals, and the whole device was coated with DL-lactide to achieve an active initial tissue reaction and better tissue penetration. The SR-PLLA stent showed more favourable implantation properties than the steel one. Within 6 months all PLLA stents had implanted, and the tissue reaction around the stent material was minimal. The helical spiral of stainless steel induced a remarkable inflammatory reaction due to poor implantation properties. We suggest that biodegradable SR-PLLA is a promising material for a urethral stent to prevent re-stenosis of urethral strictures.

Cardiovascular reflexes in the neurological evaluation of impotence.

Testing of the autonomic cardiovascular reflexes (single breath beat-to-beat variation and orthostatic blood pressure change) was performed in 542 patients with erectile dysfunction who were grouped according to aetiological factors and their response to visual sexual stimulation and the papaverine test. Age-related normal values for autonomic tests were determined in the group of 124 patients with psychogenic impotence. Abnormal cardiovascular reflexes were associated with ageing and organic impotence, indicating autonomic dysfunction as a major contribution to impotence. Single breath beat-to-beat variation, as a simple non-invasive test, is useful in the clinical evaluation of impotence, especially in patients with diabetes and a history of alcohol abuse.

Zinc compounds in urethral catheters. A possible source of toxicity?

The cytotoxicity of latex urinary catheters has been earlier documented. During the manufacturing process tens of chemicals are added to the natural rubber base. Several of the accelerators and other chemicals used have carcinogenic and acute toxic effects. Some of the accelerators are zinc compounds. In the present study, the cytotoxicity and zinc concentration of 68 latex catheter extracts were analysed. The siliconized latex catheters were the most toxic, and a correlation was seen between the IC50 values and the zinc concentration. The good manufacturing practice (GMP) has to some extent resolved the cytotoxicity problem of latex urinary catheters. There is, however, still a need to reformulate the manufacturing process and to find new catheter materials to meet the new EN standards concerning the biological safety of urinary catheters.

Duplex Doppler scanning with high-dose prostaglandin E1 stimulation in the diagnosis of arteriogenic impotence.

The aim of this study was to find out the normal range of penile duplex Doppler parameters with pharmacostimulation of 40 micrograms prostaglandin E1 and to assess the repeatability and clinical value of the method. Maximal systolic velocity increase (SVImax) is presented as a new flow parameter. 10 potent and 82 impotent patients were investigated. Peak systolic velocity values were significantly higher when recorded at proximal than at distal penis. Repeatability of SVImax was fairly good (coefficient of variation = 0.18). SVImax ranged from 32 to 100 cm/s in 10 control subjects. The distribution of SVImax values in patients grouped according to the number of arteriosclerotic risk factors indicates that this parameter may be useful in the diagnosis of arteriogenic impotence.

Cytostatic effect of different strains of Bacillus Calmette-Guérin on human bladder cancer cells in vitro alone and in combination with mitomycin C and interferon-alpha.

The cytostatic activity of five Bacillus Calmette-Guérin (BCG) strains (Pasteur, Evans, Tice, RIVM and Connaught) on human transitional cell cancer T24 cells was examined. A striking effect was noted even in 2-day cultures, and the effect was more pronounced when the cells were incubated for 5 days with different BCG strains alone. The concentrations needed were about the same as those used in clinical practice (10(9) colony-forming units of Pasteur strain in 100 ml buffered saline solution). Combination with mitomycin C or interferon-alpha-2b potentiated the cytostatic effect. A slight difference in cytostatic activity between different BCG strains was found.

Oncogenes in human testicular cancer: DNA and RNA studies.

Oncogene dosage and expression were studied in 16 testicular neoplasms, 14 of germ cell and two of non-germ cell origin. In comparison with normal DNA, tumour DNA of a total of eight patients (seven with germ cell neoplasm and one with testicular lymphoma) showed increased dosages of KRAS2, PDGFA, EGFR, MET and PDGFB. The most frequent (occurring in six tumours) and prominent (up to 3-4-fold) increases were detected in the dosages of KRAS2 (on chromosome 12p) and PDGFA (chromosome 7p), relative to a reference locus from chromosome 2. Importantly, there was a similar increase in 12p dosage in general in these tumours, suggesting the presence of the characteristic isochromosome 12p marker. On the contrary, possible 7p polysomy (assessed by molecular methods) did not explain the PDGFA (or EGFR) changes in all cases. NRAS, MYCN, CSFIR, MYB, MYC, ABL, HRASI, TP53, and ERBB2 did not reveal any consistent alterations in tumour DNA. In RNA dot blot assays the expression of KRAS2, PDGFA, EGFR, or MYC was generally not increased in the tumour samples when compared to that in normal testicular tissue of the same patients although there was interindividual variation in mRNA levels. It thus appears that while oncogene dosage changes occur in a proportion of testis cancers, they are often part of changes in large chromosomal regions or whole arms and are seldom accompanied by altered expression.

Urethral blood circulation during cardiopulmonary bypass.

The haemodynamic changes induced by extracorporeal circulation (ECC) are thought to be important in the induction of urethral strictures in open heart surgery when indwelling latex catheters are used. In the present study, 6 piglets were cannulated and connected to extracorporeal perfusion apparatus. Pump flows correlated with human ECC values with non-haemic prime were used. The mucosal and submucosal blood circulation in the urethra reduced by 66% during ECC (P less than 0.05). The brain and hepatic arterial flows increased. A significant reduction was seen in renal blood circulation. The changes in the urethral blood circulation during ECC correlated with previous findings. The reduced wash out levels of chemicals leaching from the indwelling latex catheters as a result of reduced local blood circulation are the main trigger for the induction of urethral strictures during ECC and in other shock-like circulatory disturbances in the human body.

Orchiectomy versus oestrogen in the treatment of advanced prostatic cancer.

The primary clinical efficacy of orchiectomy and the combination therapy of intramuscular polyoestradiol phosphate 80 mg monthly and oral ethinyl oestradiol 0.15 mg daily was evaluated by progression and cancer mortality rates in a series of 277 prostatic cancer patients representing part of the Finnprostate study. After a follow-up of 5 years there was a significant difference between the groups in terms of progression rate and prostatic cancer deaths. The oestrogen combination was more effective in delaying progression of the disease. The overall mortality rate was similar in both groups. About one-third of the patients were alive after 5 years.

Comparison of two different cell culture methods in evaluation of biocompatibility of latex urinary catheters.

International biocompatibility standards for urinary catheters have not yet been set. The used in vivo animal tests earlier have been shown to be insensitive and expensive. The present study compared the sensitivity and other properties of two in vitro cell culture methods, the reference method of the British Standards Institution (BSI) and the thymidine incorporation method (DNA synthesis inhibition test. The cell culture toxicities of thirty-seven latex catheters were measured and 84.8% of the catheters tested passed the BSI reference test while 94.6% passed the thymidine incorporation test. The overall batch-to-batch correlation was poor (p greater than 0.05), but within brands the correlation was better. This is obviously to be explained by the differences the characteristics of the tests and/or the chemical composition of the catheters. The thymidine incorporation test is easier to perform, requires less manpower, and is therefore less liable to subjective interpretations than the BSI test. The biocompatibility toxicity limits for latex urinary catheters need to be tightened. Our experience in this study indicates that the thymidine incorporation test or tests similar to it, which can be highly automated can be recommended for biocompatibility screening in large series, and BSI reference test can be used additionally in unclear cases.