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Biomedical subjects

S Rannikko

Publications and source records attributed to S Rannikko.

At least 19 recordsLinked to original sources

European randomized study of prostate cancer screening: first-year results of the Finnish trial.

Approximately 20000 men 55-67 years of age from two areas in Finland were identified from the Population Registry and randomized either to the screening arm (1/3) or the control arm (2/3) of a prostate cancer screening trial. In the first round, the participation rate in the screening arm was 69%. Of the 5053 screened participants, 428 (8.5%) had a serum prostate-specific antigen (PSA) concentration of 4.0 ng/ml or higher, and diagnostic examinations were performed on 399 of them. A total of 106 cancers were detected among them corresponding to a positive predictive value of 27%, which is comparable with mammography screening for breast cancer. The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml(-1) or higher was 2.1%. Approximately nine out of ten screen-detected prostate cancers were localized (85% clinical stage T1-T2) and well or moderately differentiated (42% World Health Organization (WHO) grade I and 50% grade II), which suggests a higher proportion of curable cancers compared with cases detected by other means.

Aged

The role of parenteral polyestradiol phosphate in the treatment of advanced prostatic cancer on the threshold of the new millennium.

Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.

Androgen Antagonists

Magnetic resonance imaging of clinically localized prostatic cancer.

PURPOSE: We assess the accuracy of endorectal coil magnetic resonance imaging (MRI) for detecting tumor localization, capsular penetration and seminal vesicle invasion in clinically organ confined prostate cancer. We also evaluate intra-observer and interobserver agreement in interpreting MRI studies. MATERIALS AND METHODS: MRI studies of 51 consecutive patients a mean of 61 years old with biopsy proved prostate cancer were retrospectively read twice by 2 radiologists in random order. Both radiologists marked tumor localization, capsular penetration and seminal vesicle invasion on standard tumor maps. These findings were compared with the histopathological results of radical prostatectomy specimens. RESULTS: The overall accuracy of detecting cancer localization was 61%. The detection rate for cancer foci less than 5 mm. was only 5% but for lesions greater than 10 mm. it was 89%. There was 91 and 80% accuracy for detecting capsular penetration and seminal vesicle invasion, respectively. Sensitivity and specificity were 60 and 63, 13 and 97, and 59 and 84% for localization, capsular penetration and seminal vesicle invasion, respectively. Intra-observer and interobserver agreement ranged from fair to good (kappa coefficient 0.240 to 0.647). CONCLUSIONS: Endorectal MRI seems to be better than previously reported for detecting seminal vesicle invasion and tumor foci in the anterior half of the prostate. Sensitivity in detecting minor capsular penetration of the tumor was low, which can probably be improved by methodological development. MRI may be useful for locating cancer foci in patients with high prostate specific antigen values but repeatedly negative biopsy findings.

Aged

Characterization and immunological determination of the complex between prostate-specific antigen and alpha2-macroglobulin.

Prostate-specific antigen (PSA) rapidly forms a complex with alpha2-macroglobulin (A2M) in vitro; however, PSA complexed with A2M (PSA-A2M) is not detected by conventional immunoassays for PSA because it is encapsulated by the A2M. In this study, we show that denaturation of PSA-A2M at high pH renders PSA immunoreactive. Part of the complexed PSA is released in free form and part remains bound to denatured A2M. These forms can be measured by a conventional immunoassay for PSA. This finding enabled us to design a dissociation assay for the detection of PSA-A2M, which was based on the removal of immunoreactive PSA in serum by immunoadsorption, denaturation of PSA-A2M at high pH, and measurement of the released PSA immunoreactivity by a conventional PSA immunoassay. This PSA-A2M assay was calibrated with PSA-A2M formed in vitro. The detection limit of the assay was 0.14 microg/L. Inter- and intraassay coefficients variation were 4-9% and 8-14%, respectively. When purified PSA was incubated with A2M, the loss of PSA immunoreactivity was highly correlated with the PSA-A2M formed, as measured by the dissociation assay for PSA-A2M (r = 0.99; P <0.0001). The concentration of PSA-A2M in serum correlated with that of total PSA both in prostate cancer (PCa) and benign prostatic hyperplasia (BPH); however, the ratio of PSA-A2M in relation to total PSA was significantly higher in BPH than in PCa (P <0.0003). ROC curve analysis suggested that measurement of the ratio of PSA-A2M to total PSA in serum improves the diagnostic accuracy for PCa compared with assays for total PSA only.

Aged

Radioiodinated estramustine phosphate and estramustine binding protein antibody accumulate in the prostate of a mouse.

BACKGROUND: The purpose of this study was to determine the distribution of radioiodinated estramustine (RI-EMP) and a radioiodinated antibody against estramustine binding protein (RI-EMBP-AB) in mice. METHODS: RI-EMP and RI-EMBP-AB were injected in male mice intravenously, and the activities of tissue samples were measured 1-31 hr from the injection. Pure iodine-125 (RI) was used as a control. RESULTS: RI-EMP accumulated in the prostate, which contained 2.6% of injected activity (ID) per gram tissue at 7 hr. The liver had an activity of 21.4% ID/g at 1 hr, which decreased as RI-EMP was secreted in bile. The lung contained 2.3% ID/g at 7 hr, and it retained the activity longer than the prostate. RI-EMBP-AB accumulated in the prostate: The activity was 2.9% ID/g at 7 hr. The gallbladder contained 6.5% ID/g at 7 hr. CONCLUSIONS: Due to its cytotoxic and radiosensitizing properties, RI-EMP can possibly be used for treating prostate cancer and other tumors.

Animals

Metabolic basis of hypotriglyceridemic effects of insulin in normal men.

The mechanism by which acute insulin administration alters VLDL apolipoprotein (apo) B subclass metabolism and thus plasma triglyceride concentration was evaluated in 7 normolipidemic healthy men on two occasions, during a saline infusion and during an 8.5-hour euglycemic hyperinsulinemic clamp (serum insulin, 490 +/- 30 pmol/L). During the insulin infusion, plasma triglycerides decreased by 22% (P < .05), and serum free fatty acid decreased by 85% (P < .05). The plasma concentration of VLDL1 apo B fell 32% during the insulin infusion, while that of VLDL2 apo B remained constant. A bolus injection of [3-(2)H]leucine was given on both occasions to trace apo B kinetics in the VLDL1 and VLDL2 subclasses (Svedberg flotation rate, 60-400 and 20-60, respectively), and the kinetic basis for the change in VLDL levels caused by insulin was examined using a non-steady-state multicompartmental model. The mean rate of VLDL1 apo B synthesis decreased significantly by 35% (P < .05) after 0.5 hour of the insulin infusion (523 +/- 87 mg/d) compared with the saline infusion (808 +/- 91 mg/d). This parameter was allowed to vary with time to explain the fall in VLDL1 concentration. After 8.5 hours of hyperinsulinemia, the rate of VLDL1 apo B synthesis was 51% lower (321 +/- 105 mg/d) than during the saline infusion (651 +/- 81 mg/d, P < .05). VLDL2 apo B production was similar during the saline (269 +/- 35 mg/d) and insulin (265 +/- 37 mg/d) infusions. No significant changes were observed in the fractional catabolic rates of either VLDL1 or VLDL2 apo B. We conclude that acute hyperinsulinemia lowers plasma triglyceride and VLDL levels principally by suppressing VLDL1 apo B production but has no effect on VLDL2 apo B production. These findings indicate that the rates of VLDL1 and VLDL2 apo B production in the liver are independently regulated.

Adult

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.

Adult

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.

Anthropometry

Renal function remains after unilateral total and contralateral partial nephrectomy: an experimental study in pigs using 99mTc-DTPA.

Twelve nephrectomies (NEs) were performed in 12 pigs (11-17 kg). Total NE was performed on the left side and partial NE on the right side (lower third of the kidney), thus two-thirds of the total kidney volume was removed. Renal function was studied with 99mTc-diethylenetriaminepentaacetic acid (DTPA) renography and serum urea and creatinine levels preoperatively, and 1 and 2 weeks postoperatively. The pigs were imaged in each session for 30 min by collecting 10-s frames from a posteroanterior (PA) view of an anaesthesized animal. The injected activity was 37 MBq. Serial blood samples were taken from the subclavian vein at 0, 1, 2, 3, 5, 15, 25, 40, 60 and 120 min (six animals) after 99mTc-DTPA injection. The DTPA disappearance rate (DDR) was determined from these samples and in other cases (six animals) a blood sample at 20 min was used. The DDR was also determined from the dynamic gamma imaging data: Regions of interest (ROI) were upper body, spleen, heart and kidneys. The ROI analysis correlated well with the blood sampling data (r = 0.97, P < 0.0001). The reference values for pig DDRs were 0.99 +/- 0.08%/min. These values were 0.71 +/- 0.08%/min at 1 week postoperatively and 0.63 +/- 0.08%/min at 2 weeks. DTPA clearance rates were preoperatively 0.53 +/- 0.06 ml/s; at 1 week postoperatively 0.41 +/- 0.06 ml/s; and at 2 weeks 0.35 +/- 0.06 ml/s. There were no significant differences pre- and postoperatively in creatinine and urea concentrations. The DTPA clearance (ml/s) and disappearance rates (%/min) when determined per kidney area (cm2) increased significantly (P < 0.001 at both 1 and 2 weeks); in 11 of 12 animals the function of the resected right kidney was higher than the split function of the whole right kidney preoperatively. Unilateral nephrectomy initiates a functional adaptation or a growth response in the contralateral kidney to compensate for the loss of a renal mass. These data also indicate that two-thirds of the kidney volume in young pigs can be removed without danger.

Adaptation, Physiological

Detection of prostatic cells in peripheral blood: correlation with serum concentrations of prostate-specific antigen.

We have studied the expression of prostate-specific antigen (PSA) mRNA by reverse transcriptase-polymerase chain reaction in peripheral blood of 25 patients with cancer of the prostate (CAP), four with benign prostatic hyperplasia (BPH), two with renal stones, three with other types of cancer, and six healthy male and three female controls. Expression of mRNA specific for a certain tissue in peripheral blood is thought to indicate the presence of circulating cancer cells and metastatic spread of a tumor originating from this tissue. We detected PSA mRNA in 9 of 18 CAP patients with metastatic disease but in none of 7 patients without metastases. Negative results in patients with metastatic disease were associated with successful endocrine therapy and low concentrations of serum PSA, and the correlation between serum concentrations of PSA and the presence of PSA mRNA in peripheral blood was statistically significant. PSA mRNA was not found in patients with BPH, other types of cancer, or in healthy controls. Thus the occurrence of PSA mRNA in peripheral blood is associated with metastatic CAP.

Aged

Residual stones after percutaneous nephrolithotomy; sensitivities of different imaging methods in renal stone detection.

Kidneys of 35 renal stone patients treated with percutaneous nephrolithotomy (PNL) were examined at 12-36 months (mean 23 months) after the procedure by plain radiography (PR), conventional linear tomography (LT), computed tomography (CT), and ultrasonography (US) to find out the long-term stone-free rate as well as the accuracy of these imaging methods to detect residual or recurrent renal stones. The present series included 36 kidneys with a 56% postoperative stone-free status examined by plain radiography and a 58% one examined by linear tomography at 12-36 months. CT showed 47% and US 72% of the kidneys to be stone-free, respectively. The sensitivity of CT was superior to plain radiography (P < 0.05), linear tomography (P < 0.05) or US (P < 0.001) in the detection of residual or recurrent stones after percutaneous nephrolithotomy analyzed statistically by McNemar's test. In the same group of 35 patients, which consisted of the above 36 postoperative kidneys together with 19 contralateral kidneys, a total of 55 kidneys were evaluated by the above methods, revealing 56 stones in 31 kidneys. Of these stones 95% were detected by CT, 70% by plain radiography, 68% by linear tomography, and 32% by renal US. Of the 55 kidneys, 14 contained 20 stone fragments smaller than 3 mm, and 26 kidneys carried 43 concrements smaller than 6 mm. The sensitivities of the four imaging methods in the detection of these small fragments were as follows: plain radiography 60% and 60%, linear tomography 55% and 58%, CT 95% and 93%, and US 15% and 26%.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies

Partial nephrectomy with a combined CO2 and Nd:YAG laser: experimental study in pigs.

Twenty-eight partial nephrectomies were performed on nine pigs with a simultaneous, coaxial CO2-Nd:YAG laser at power settings of 20 W and 40 W, or with a steel scalpel. A vascular pedicle clamp was used without renal cooling. The time for hemostasis was 4.5 +/- 3.2 min (mean +/- SD) with the laser and 6.4 +/- 2.5 min with the steel scalpel (P = 0.064). There was no difference in the total operation time (10.4 +/- 3.5 min with the laser vs. 11.0 +/- 3.2 min with the steel scalpel, P = 0.470). The mean blood loss with the laser was 17.5 +/- 6.7 g and 22.1 +/- 15.2 g with the steel scalpel (P = 0.299). The number of ligatures needed for complete hemostasis was 2.9 +/- 2.1 with the laser and 5.0 +/- 2.3 with the steel scalpel (P = 0.011). The average thermal damage was 0.23 +/- 0.10 mm. It is concluded that the simultaneous CO2-Nd:YAG laser method can be used in partial nephrectomy and it offers better hemostasis than the conventional technique. Further studies with different power levels are needed.

Aluminum

The role of radical surgery in the treatment of prostatic cancer.

At present, prostatic cancer is the most common malignancy in men in many Western countries and its incidence is continuously increasing. Radical prostatectomy has been used for over 80 years, but there is still controversy about its role in the treatment of localized prostatic cancer. Because of insufficient knowledge of the natural history of prostatic cancer and a lack of accurate prognostic factors there are possibilities for both over- and undertreatment. Better staging methods are also required to discriminate between intra- and extracapsular tumours, which is essential for curative treatment. On the basis of the facts mentioned above and because of the poor sensitivity and specificity of transrectal palpation, ultrasound examination and prostate-specific antigen, which are used in screening, diagnosing and staging of prostatic cancer, screening is not yet recommended for the detection of early prostatic cancer.

Humans

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)

Acid Phosphatase

Contact fibre Nd:YAG laser for partial nephrectomy: experimental study in pigs.

Thirty-two partial nephrectomies were performed without renal cooling on 13 pigs with a contact fibre Nd:YAG laser (10 W) or a steel scalpel with or without a vascular pedicle clamp. Nine pigs had a 2-week follow-up with an abdominal ultrasound 1 week postoperatively. The time for haemostasis was 6.9 +/- 5.2 min (mean +/- SD) with the laser and 9.1 +/- 5.8 min with the steel scalpel when the clamp was used (P = 0.028). There was no significant difference in the total operating time (13.2 +/- 4.5 min with the laser vs 12.6 +/- 4.6 min with the steel scalpel, P = 0.203). Intraoperative blood loss was similar in the two groups when the clamp was used. Clamping the renal pedicle decreased the blood loss by 61% in the laser group and 31% in the steel scalpel group. The number of ligatures used was significantly lower in the laser group (3.7 +/- 2.6) compared with the steel scalpel group (6.6 +/- 3.4) (P = 0.013). Five urinomas developed on the laser side and four on the steel scalpel side. These results indicate that the contact fibre Nd:YAG laser method can be used in partial nephrectomy, but it offers no definitive advantage over the conventional technique.

Aluminum

Parenchyma-conserving surgery for renal cell carcinoma.

Between 1969 and 1992, 32 patients underwent conservative surgery (partial nephrectomy or enucleation) for renal cell carcinoma (RCC). Elective parenchyma-conserving surgery (n = 10) was done in patients with small, peripheral kidney tumors and a normal contralateral kidney. Cancer in a solitary kidney, bilateral tumors, dysfunctional contralateral kidney or chronic renal failure were imperative indications (n = 22) for conservative surgery. In the elective group the tumors were 15-100 mm (mean 37 mm) in diameter, in the imperative group 5 to 200 mm (mean 41 mm). The follow-up was 0.2-192 months (mean 48.7 months). Nine of 22 (41%) patients in the imperative group have died of RCC. There were no renal cancer related deaths in the elective group. The 5-year cause-specific survival rates for the elective and imperative groups were 100% and 46%, respectively. Two patients in the elective group have died of unrelated causes. Local recurrences developed in three of 22 patients in the imperative group after a mean of 5.4 years; two of them had von Hippel-Lindau disease with bilateral RCC. Conservative surgery seems to be a feasible option in small peripheral kidney tumors.

Carcinoma, Renal Cell

Morphological effects of photodynamic therapy on rabbit bladder using Photofrin II and Photosan intravesically and intravenously.

Photodynamic therapy (PDT) has proved effective against superficial papillary bladder tumours and focal and diffuse carcinoma in situ. Effective topical administration of the sensitiser would be a welcome improvement. The morphological effects of PDT on the normal bladder were examined in 13 rabbits when 2 photosensitisers (Photofrin II and Photosan III) were applied intravesically (5 mg/kg for 1 h) and compared with intravenous administration (3 or 5 mg/kg). Four animals served as controls without a sensitiser. Intravesical red light (630 nm) from an argon dye laser was used to activate the photosensitiser, using light doses of 12 or 24 J/cm2. The animals were sacrificed either 1 or 5 to 7 days after the laser treatment. Intravenous dosage induced bladder wall oedema/haemorrhage and total necrosis of the epithelium. There was no difference between the effects of the 2 sensitisers. Intravesical application induced superficial epithelial necrosis. The control animals treated with laser light alone showed slight superficial injury to the cell layer.

Administration, Intravesical