A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer.

We have studied the forms of prostate-specific antigen (PSA) in serum of patients with prostatic cancer and benign prostatic hyperplasia. Fractionation of serum by gel filtration and assay of the fractions for PSA showed that a considerable part of the PSA immunoreactivity in serum consisted of complexes that were larger than PSA. The complexes were assayed by time-resolved immunofluorometric assays based on an antibody against PSA on the solid phase and europium-labeled antibodies against various protease inhibitors as indicator antibodies. In addition to its monomeric form, PSA was found to occur in complex with alpha 1-antichymotrypsin. The proportion of the alpha 1-antichymotrypsin complex was a major form of PSA and it increased with increasing PSA concentrations, being over 85% at PSA levels exceeding 1000 micrograms/liter. A complex with alpha 1-protease inhibitor was also observed in serum of patients with prostatic cancer and very high levels of PSA. Complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor were detected, but their concentrations were low and similar in sera of cancer patients, normal men, and normal women, suggesting that they were not prostate derived. Commercial immunoradiometric assays for PSA were found to measure free PSA and its complexes with alpha 1-antichymotrypsin but not the complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor. The proportion of the PSA-alpha 1-antichymotrypsin complex was higher in patients with prostatic cancer than in those with benign hyperplasia. Therefore, assay of the complex had a higher sensitivity for cancer than assay of total PSA immunoreactivity.

Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue.

Six patients with advanced prostatic cancer were treated with a potent GnRH agonist analog (buserelin, Hoechst; 600 micrograms, intranasally, three times a day) for 6 months. The first 2-6 days of treatment were associated with a 50% elevation (P less than 0.01) in serum testosterone (T) and a simultaneous elevation of 20% (P less than 0.01) in serum prostate-specific acid phosphatase (PAP). Serum T fell to the castrate range (less than 1 nmol/liter) in all patients in 2-3 weeks, and PAP decreased concomitantly in five of the six patients. Serum LH progressively decreased by about 80% during the treatment, whereas a secondary rise of FSH levels occurred after the first month of treatment. The patients were orchiectomized after 6 months of treatment. No differences were found between the pre- and postsurgical levels of serum T or in comparison with those of six patients orchiectomized as the first therapeutic measure. Testicular endogenous T concentrations, LH and FSH receptors, and in vitro T production were measured in three testis samples and compared with those values in testis tissue obtained from five control patients. The endogenous levels and in vitro production of T were depressed by over 95% in testes from agonist-treated patients. The small residual T production responded to hCG stimulation as in control patients. Interestingly, no change was found in testicular LH receptor content, but FSH receptors decreased by 80%. The elevation in serum PAP at the beginning of the agonist treatment and the small residual testicular T production after 6 months may not be clinically important. However, they indicate the necessity of comparative long term studies between orchiectomy and GnRH agonists in the treatment of patients with prostatic cancer.

Serum bioactive and immunoreactive follicle-stimulating hormone in prostatic cancer patients during gonadotropin-releasing hormone agonist treatment and after orchidectomy.

Serum bioactive and immunoreactive FSH levels were measured in five prostatic cancer patients during treatment for 6 months with the GnRH agonist analog buserelin (Hoechst; 600 micrograms, intranasally, 3 times per day) and for up to 12 weeks after subsequent orchidectomy. FSH bioactivity was measured using a sensitive specific in vitro granulosa cells aromatase bioassay. Before buserelin treatment, mean serum FSH bioactivity and immunoreactivity were 19.7 +/- 4.1 (+/- SE) IU/L (n = 5) and 13.7 +/- 3.8 IU/L, respectively, with a bioactivity to immunoactivity (B/I) ratio of 1.7 +/- 0.2. After the initiation of treatment with the GnRH agonist, FSH bio- and immunoactivities both transiently increased for 1-3 days. The increase in bioactivity was greater and prolonged, and the B/I ratio increased nearly 7-fold in 2 weeks. Serum FSH immunoreactivity declined to below the pretreatment level in 5 days and remained low for the rest of the treatment period. In contrast, serum FSH bioactivity did not decrease significantly below the pretreatment level during the 6-month treatment period, although the B/I ratio returned slowly toward the pretreatment value. After orchidectomy, both FSH activities increased dramatically, and the B/I ratio rose transiently from 1.5 to 7 in 2 weeks. Interestingly, serum FSH bioactivity and immunoreactivity decreased significantly (P less than 0.05) 1 day after orchidectomy in the buserelin-treated patients. In contrast, serum FSH immunoreactivity increased during the same period (P less than 0.05) in patients treated only by orchidectomy (FSH bioactivity was not measured). In conclusion, serum FSH bioactivity increases acutely more than FSH immunoreactivity after initiation of GnRH agonist treatment or orchidectomy. In the former case, serum FSH bioactivity subsequently returned to the pretreatment range. A clear decline during long term agonist treatment occurred only in serum FSH immunoreactivity, in contrast to the concomitant decline in serum LH bio- and immunoreactivities reported previously. The persistence of bioactive FSH may explain the inconsistent effects of GnRH agonist treatment on the suppression of spermatogenesis. The acute decrease in serum FSH after orchidectomy in the buserelin-treated men suggests that the testes may produce a factor that stimulates pituitary FSH secretion.

Testosterone regulates apoptosis in adult human seminiferous tubules in vitro.

In the present study an in vitro model was developed and characterized for evaluation of the role of apoptosis in adult human testes. The samples came from adult men undergoing orchidectomy for prostate or testicular cancer. Segments of seminiferous tubules were isolated and incubated under serum-free conditions in the absence or presence of testosterone. Apoptosis was assessed by low mol wt DNA fragmentation (185-bp multiples) by use of 3'-end-labeled DNA, in situ end labeling, and morphological detection under light and electron microscopy. During the 4-h incubation, a 15-fold increase was seen in apoptotic DNA fragmentation. The extent of low mol wt DNA showed a time-dependent increase and reached a 20-fold intensity in 24 h of incubation compared to the level at 0 h. Apoptosis was significantly suppressed by testosterone concentrations of 10(-7) and 10(-6) mol/L during the first 4 h of incubation. Apoptotic cells were identified mainly as spermatocytes and occasionally as spermatids. We conclude that apoptosis is induced in human seminiferous tubules under serum-free conditions in vitro. That this apoptosis is suppressed by testosterone indicates that testosterone in the human male is a critical germ cell survival factor. The model created in the present study provides a valuable tool for further investigation of hormonal and gene regulation of human germ cell death and survival.

Insulin-like growth factor I is not a useful marker of prostate cancer in men with elevated levels of prostate-specific antigen.

High serum levels of insulin-like growth factor I (IGF-I) and low levels of IGF-binding protein-3 (IGFBP-3) have been shown to correlate with increased prostate cancer risk. To evaluate this, IGF-I, IGFBP-3, and prostate-specific antigen (PSA) were measured in serum from 665 consecutive men (179 with prostate cancer), aged 55-67 yr, with elevated serum prostate-specific antigen (PSA; > or = 4 microg/L) in a screening trial. Men in the highest quartile of IGF-I levels had an odds ratio (OR) for prostate cancer of 0.50 [95% confidence interval (CI) 0.26-0.97] when adjusting for serum IGFBP-3. IGFBP-3 itself was not significantly associated with prostate cancer risk (OR, 1.24; 95% CI, 0.68-2.24). Prostate volume was larger in men without than in those with prostate cancer (P < 0.001), and after adjustment for prostate volume, the negative association between serum IGF-I and prostate cancer risk was no longer significant (OR, 0.57; 95% CI, 0.28-1.16). In screen-positive men with elevated serum PSA, serum IGF-I is not a useful diagnostic test for prostate cancer, but it may be associated with benign prostatic hyperplasia and enlargement.

Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. I. Circulating hormone levels.

Eight patients with advanced prostatic carcinoma (ages 59 to 78 years) were treated with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst; 600 micrograms intranasally, 3 times daily) and orchiectomized after 6 months of treatment. Endocrine responses were followed by serum hormone measurements during agonist treatment and for 3 months after orchiectomy. Six other patients (65 to 86 years) with advanced prostatic cancer had been orchiectomized as the first therapeutic measure and their blood samples were used as controls. In the GnRH agonist-treated patients, serum immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased after initial stimulation by 70 to 80%, within 1 to 3 weeks (P less than 0.01). FSH partly recovered (P less than 0.05) after the first month of treatment. Serum prolactin (PRL) displayed a slight tendency to decline during buserelin treatment (P less than 0.05). Serum total and free testosterone (T) of the buserelin-treated patients decreased to the castrate range within 3 to 4 weeks after an initial 5-day increase (P less than 0.01). Serum progesterone and 17-hydroxyprogesterone (17-OHP-4) decreased to the castrate range (by 50 to 70%) in 1 week. Only minor changes were observed in sex hormone binding globulin (SHBG). Significant, acute elevations of LH, FSH, T, and 17-OHP-4 were observed only on day 1 after an injection of buserelin (500 microgram i.m.) and not when assessed between day 7 and month 6 of treatment. After 6 months of buserelin treatment, orchiectomy did not affect the serum steroids measured. After orchiectomy, immediate increases in serum LH, and somewhat later in FSH, were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. II. Endocrinology and histology of the testis.

Endogenous testosterone (T), LH and FSH receptors, and in vitro production of cyclic adenosine-3':5'-monophosphate (cAMP), T and some of its steroid precursors were measured in testicular tissue obtained at orchiectomy from seven prostatic cancer patients treated for 6 months with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst, 600 micrograms 3 times a day intranasally). In addition, histologic and morphometric studies were carried out on the testicular tissue. Testicular tissue from age-matched prostatic cancer patients (n = 14), whose first therapy was orchiectomy, served as controls. The peptide treatment decreased intratesticular T by 95% (P less than 0.01) and FSH receptors by 57% (P less than 0.01), but had no effect on LH receptors. The in vitro production of T decreased by 94% (P less than 0.01), but that of cAMP was unaffected. Besides T, the in vitro production of testicular 17-hydroxyprogesterone (17-OHP-4), androstenedione and 5 alpha-dihydrotestosterone (5 alpha-DHT) dropped by 71 to 90% (P less than 0.01 to 0.05) during buserelin treatment, but those of pregnenolone, progesterone and dehydroepiandrosterone (DHEA) were not affected. Histologic studies revealed considerable variation in the seminiferous epithelium of the control group, but spermatogenesis was highly suppressed in nearly all of the buserelin-treated group. The number of Sertoli cells was unaffected, but tubular diameters were reduced (P less than 0.05) by buserelin treatment. Leydig cells appeared dedifferentiated in this group, although their number per testis was not altered. These data indicate that gonadotropin suppression by GnRH agonist most likely affects testicular steroidogenesis by inhibiting 3 beta-hydroxysteroid dehydrogenase and a step(s) prior to pregnenolone formation. The treatment does not impair testicular LH binding or cAMP production, but clearly suppresses FSH receptors. Spermatogenesis in general is suppressed but with considerable variation.

Response of circulating gonadotropin levels to GnRH agonist treatment in prostatic cancer.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) responses to 6-month treatments with a gonadotropin-releasing hormone (GnRH) agonist (buserelin) and subsequent orchiectomy were studied in patients with advanced prostate cancer. For treatments, either an intranasal (600 micrograms, 3/day, n = 8) or subcutaneous depot preparation (6.6 mg every other month, n = 5) were used. A third group of patients received intranasal buserelin (400 micrograms, 3/day, n = 12) for 35 months. LH and FSH were measured using radioimmunoassay (RIA) and a sensitive (0.04 IU/L) immunofluorometric assay (IFMA). In addition, selected samples were analyzed for bioactive (bio) LH. The RIA-LH levels decreased 70% with intranasal treatment. In contrast, when monitored by IFMA, the reduction was greater than 90%: 0.2 to 0.3 IU/L with intranasal and 0.044 to 0.052 IU/L with depot treatment (P less than 0.01). Gonadotropin suppression was stable up to 35 months. Bio-LH and IFMA-LH levels decreased in parallel during treatment, with no apparent changes in the bio/immuno ratio. FSH levels were suppressed temporarily during the treatments. After castration and cessation of buserelin treatment, serum LH and FSH increased rapidly in the intranasal treatment group but only marginally during 3 months in the depot group. Serum T reached the castrate range when IFMA-LH decreased below 0.5 IU/L. A further decrease in LH (less than 0.1 IU/L) still suppressed the intratesticular T concentration measured after orchiectomy. In conclusion, IFMA offers an improved method to monitor the antigonadotropic effect of GnRH agonist treatment. The results emphasize the necessity of profound LH suppression to achieve maximal inhibition of testicular androgen production.

Comparison of long-term indwelling catheters and bed-pads in the treatment of urinary incontinence in elderly patients.

Bed-pads and long-term indwelling catheters were compared in the treatment of urinary incontinence in two groups of eight elderly bedridden women. The same silicone catheter could be left in situ on average for 2 months. A detailed description of the changes of urinary bacterial flora in patients of both experimental groups is given. At the end of the 6 months' study all of the patients in both groups had significant bacteriuria (greater than or equal to 10(8) CFU/1), Proteus species being the most common pathogen in catheterised patients. The development of multiple resistance was observed in both groups, but it was more pronounced in the catheterised group. The indwelling catheter was more economical (P less than 0.001), but carried a higher risk of infection.

Histological and functional changes of the testis tissue during GnRH agonist treatment of prostatic cancer.

The purpose of this study was to examine long-term effects of GnRH agonists on human testicular histology and endocrine function. Patients with advanced prostate cancer (n = 7) were treated with the potent GnRH agonist analogue buserelin (Bu, Hoechst), 600 micrograms X 3/day intranasally. After 6 months, the patients were orchiectomized, and the testis tissue was used for histological studies and measurements of endocrine function in vitro. Fourteen other patients with matching ages and extent of the disease were castrated as the first form of therapy, and their testis tissue was used as controls (C). Severe atrophy of seminiferous tubules was seen in light microscopy in the testes of the Bu treated patients. Many tubules showed only Sertoli cells, and the seminiferous epithelium was frequently absent. In contrast, no clear changes were seen in the number of Leydig cells. Testicular content of testosterone (T) decreased greater than 95% by Bu treatment: C = 1.5 +/- 0.2 nmol/g wet wt (x +/- SE); Bu = 0.070 +/- 0.019 nmol/g. Likewise, a drop of 80% occurred in testicular high affinity receptors for FSH: C = 0.37 +/- 0.019 pmol/g; Bu = 0.067 +/- 0.009 pmol/g. In contrast, the number of LH receptors was unaffected by the treatment, C = 0.18 +/- 0.033; Bu = 0.18 +/- 0.032 pmol/g. When testis slices were incubated in the presence of maximally stimulating concentration of hCG (100 ng/ml), both groups of tissue responded similarly with a 50% increase in T production, albeit the absolute production rate was reduced by 95% in the Bu group. When several steroid precursors of T were analyzed in the incubation media, it appeared that decreased androgen synthesis was most clearly due to decreased 3 beta-hydroxysteroid dehydrogenase activity. It is concluded that long-term treatment with GnRH agonists in prostatic cancer patients brings about dramatic damage of seminiferous tubular function and reduces testicular androgen producing capacity, but has no effect on testicular capability of responding immediately to LH stimulation.

Patient specific doses used to analyse the optimum dose delivery in barium enema examinations.

The exposure and geometrical data for 89 barium enema examination patients were recorded manually in five hospitals in Finland. From the recorded data, organ and primary exit doses as well as effective individual doses were calculated for each patient using the ODS-60 program, which is capable of adjusting the calculation phantom according to a patient's size and sex. The mean (and standard deviation, SD) and median effective individual doses for the patients were 9.3 (5.7) and 6.8 mSv, respectively. Conversion functions from dose-area product to relevant organ doses and to effective individual dose were presented as a function of patient sex and weight. Mean primary exit dose values were calculated for each exposure. These were used to compare a theoretically justified exposure control (EC) function with the function of the automatic exposure (rate) control, AEC (AERC), at different hospitals. According to the analysis of primary exit doses, the implementation of the EC was far from optimum. With EC function proposed in this study the SD of effective individual doses to patients could be lowered considerably.

Tissue-air ratios for cobalt 60 therapy units.

Tissue-air ratio (TAR) is the widely used dosimetric parameter for treatment planning in radiation therapy. Comparison of the measured TAR values of 19 60Co therapy units of eight different types was made with the widely used tabulated data of Gupta & Cunningham (1966). The experimental data, and the analysis of the variation in the TAR values caused by individual, unit by unit features, show that discrepancies may be up to +/- 4%.

Computing patient doses of X-ray examinations using a patient size- and sex-adjustable phantom.

Both the use of traditional fluoroscopy and the increasing use of modern digital techniques in radiology and interventional radiology demand the development of versatile computer programs for patient dose determinations. Long computing times restrict the use of Monte Carlo (MC) methods in dose monitoring applications where the radiological views change frequently. In the Organ Doses Calculation Software application (ODS-60), the phantom model is similar in principle to the Alderson-Rando (A-R) phantom, but its sex, size and shape is modified according to a particular patient. Organ and effective doses are computed online (in a few seconds) using a method similar to the traditional dose planning systems used in radiotherapy. In this paper, the new ODS-60 software is presented in detail and its capabilities are demonstrated. Software performance was determined by comparing the results with those from independent methods. In the case of a reference man-sized male, the effective dose was about 7% larger than the effective dose given in another publication. In the case of a reference woman-sized female, the disagreement with the other method was greater (33%). Anatomical differences between the phantom models (ODS-60 and MC) were found to be the main reasons for these findings. This paper shows the advantage of using a patient size- and sex-adaptable phantom for patient dose determinations; the conversion coefficient from entrance surface dose-to-effective dose ratio between male (170 cm, 85 kg) and a female (160 cm, 43 kg) varies in the range 1.5-2.

Calculation of the estimated collective effective dose equivalent (SE) due to x-ray diagnostic examinations--estimate of the SE in Finland.

The collective effective dose equivalent caused by diagnostic x-ray examinations in Finland has been estimated. The influence of how the remaining organs are selected, as specified by the International Commission on Radiological Protection (ICRP), on the effective dose equivalent, HE, has been studied. The doses to 23 different organs, including the six primary organs and 17 relevant remaining organs, were calculated. The HE was assessed by first choosing the five most exposed remaining organs according to the ICRP, and subsequently the 12 remaining organs. Depending on the type of examination, the difference in the respective effective dose equivalents was typically 20-40%. The estimated dose equivalent per capita is 0.7 mSv.

Efficacy of orchiectomy versus high dose polyoestradiol phosphate (160 mg) in relieving infravesical obstruction in patients with prostatic cancer.

Post voiding residual urine volume (78 patients) and maximum urinary flow rate (59 patients) were measured in prostatic cancer patients treated by orchiectomy or oestrogen (polyoestradiol phosphate 160 mg i.m. monthly) to compare the effects of these endocrine treatments on bladder outlet obstruction caused by prostatic carcinoma. The relieving effect of orchiectomy seemed to be more apparent than that of high dose oestrogen during the first six months of therapy.

Prostatic cancer protruding into the bladder imaged by transurethral and transrectal ultrasound.

A case is described in which the nature of the tumour mass found in the bladder could be evaluated by combining transurethral and transrectal ultrasound.

The calibration of dosimetry instruments used in interventional radiology.

No general agreement about the definition of the patient dose exists. As regards the radiation health risk, the doses to specific organs, Hi, are the ultimate measures for a patient dose. Values of the calibration measured, Hi, are provided only by calculational means. Out of the whole process of patient dose determination, the instruments to measure X ray spectra, FSD, field dimensions and Ka can be calibrated, X ray quality is derived from the total filtration and kV value. The actual dynamic and X ray quality ranges shall be considered when air kerma and DAP meters are calibrated. A DAP meter measurement averages the uniform radiation field specific for the X ray tube assembly used and for the beam shaping technique performed. Therefore, a DAP meter calibrated on site is preferable for patient dosimetry in interventional radiology.

Pretreatment hormone levels in prostatic cancer.

Pretreatment plasma concentrations of total testosterone, prolactin, and total estradiol-17 beta (E2) were measured in 123 prostatic cancer patients who were categorized into groups according to the UICC classification. Patients with intracapsular tumour without metastases had significantly higher (p less than 0.05) pretreatment total estradiol levels than those with more advanced disease. The patients were treated either by orchiectomy or estrogens. The mean follow-up time was 48 months. Higher pretreatment estradiol and testosterone levels were associated with better survival. Prolactin assays seemed to be of no value in this respect.

Orchiectomy, estrogen therapy and radiotherapy in locally advanced (T3-4 M0) prostatic cancer.

In this randomized trial 151 patients with locally advanced prostatic carcinoma (T3-4 M0) were treated with orchiectomy, estrogens or radiotherapy. In comparison of these therapy modalities attention was paid to the progression free survival and to the complications associated with these therapies. There was no significant difference in the progression free survival during the four-year follow-up period. The frequency of cardiovascular complications was highest in the estrogen group, where 13 of 50 patients had 19 complications. In the radiotherapy group 19 of 45 patients had bowel or bladder complications.