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Biomedical subjects

O Lukkarinen

Publications and source records attributed to O Lukkarinen.

At least 55 records · Page 3Linked to original sources
PubMed1995

Mutated human androgen receptor gene detected in a prostatic cancer patient is also activated by estradiol.

Androgens are necessary for the development of prostatic cancer. The mechanisms by which the originally androgen-dependent prostatic cancer cells are relieved of the requirement to use androgen for their growth are largely unknown. The human prostatic cancer cell line LNCaP has been shown to contain a point mutation in the human androgen receptor gene (hAR), suggesting that changes in the hAR may contribute to the abnormal hormone response of prostatic cells. To search for point mutations in the hAR, we used single strand conformation polymorphism analysis and a polymerase chain reaction direct sequencing method to screen 23 prostatic cancer specimens from untreated patients, 6 prostatic cancer specimens from treated patients, and 11 benign prostatic hyperplasia specimens. One mutation was identified in DNA isolated from prostatic cancer tissue, and the mutation was also detected in the leukocyte DNA of the patient and his offspring. The mutation changed codon 726 in exon E from arginine to leucine and was a germ line mutation. The mutation we found in exon E of the hAR gene does not alter the ligand binding specificity of the AR, but the mutated receptor was activated by estradiol to a significantly greater extent than the wild-type receptor. The AR gene mutation described in this study might be one explanation for the altered biological activity of prostatic cancer.

Aged↗
PubMed1994

Comparison of a long-acting LHRH agonist and polyoestradiol phosphate in the treatment of advanced prostatic carcinoma. An open prospective, randomized multicentre study.

In a prospective, randomized open study, a long-acting LHRH agonist (Zoladex) was compared with polyoestradiol phosphate (Estradurin), both widely used in Finland for palliative treatment of prostatic carcinoma, as regards efficacy and side effects. Of the 236 enrolled patients, 129 were randomized to receive LHRH agonist and 107 to oestrogen treatment. The median follow-up was 25 months. Reduction of prostatic volume was quicker and more effective in the LHRH than in the oestrogen group, and serum testosterone concentrations fell to castration level after 1 month and 1 year, respectively. In locally advanced (M0) and histologically well or moderately differentiated tumours, LHRH agonist therapy was considerably more effective than oestrogen as regards time to progression of the carcinoma, but in metastatic (M1) and histologically poorly differentiated tumours both methods gave similar results. Cardiovascular complications showed equal incidence in both groups. LHRH agonist therapy thus seemed to be more effective than polyoestradiol phosphate against locally advanced prostatic cancer in the doses used.

Aged↗
PubMed1993

Radioimmunodetection of prostate cancer by 111In-labeled monoclonal antibody against prostatic acid phosphatase.

Purified human prostate acid phosphatase (PAP) was used to generate a specific monoclonal antibody (FC 3001) for detection of PAP expressed by some prostatic carcinomas. DTPA derivatives of MoAb-F(ab')2-fragments were labeled with indium-111 chloride. This labeled antibody was tested in 15 prostate cancer patients who underwent staging pelvic lymphadenectomy; 9 of them received labeled antibody alone whereas 6 received simultaneous injections of labeled and unlabeled antibody with two dose levels (40 or 80 mg). Biodistribution data obtained by direct blood measurements and imaging procedures indicated that simultaneous injection of unlabeled antibody reduced both the blood elimination rate and the accumulation in the liver. Accumulation of the radionuclide in pelvic lymph node metastases was observed in some patients but in a couple of patients accumulation was noted also in normal lymph nodes. The method cannot in its present design replace staging pelvic lymphadenectomy and further studies are needed for elaboration of clinically useful radioimmunodetection methods.

Acid Phosphatase↗
PubMed1993

Efficacy and safety of bladder neck incision in patients with benign prostatic hyperplasia.

A prospective series of 104 patients underwent bladder neck incision (44 unilateral and 60 bilateral) for urinary obstruction caused by a small benign prostate enlargement. The preoperative mean peak flow value improved significantly from 11.4 ml/s to 16.2 ml/s. There were no significant differences in peak flow values between the unilateral and bilateral incision groups. Subjective results seemed to be similar but transurethral resection of the prostate was needed more often after unilateral incision than after bilateral incision. Postoperative complications were recorded only in the bilateral incision group. Altogether 62% of the patients reported changes in erection or ejaculation ability. Bladder neck incision seems to be an effective means of treating urinary obstruction but adverse effects on sexual function are common, which should be kept in mind when offering this treatment to sexually active men. It can be regarded as the treatment of choice for older men with infravesical obstruction caused by a small prostate enlargement.

Erectile Dysfunction↗
PubMed1993

Prognostic factors of advanced prostatic carcinoma.

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.

Acid Phosphatase↗
PubMed1991

Effect of LH-RH analogue in patients with benign prostatic hyperplasia.

Twelve prostatic hyperplasia patients with total urine retention and, consequently, a permanent catheter, were treated for six months with luteinizing hormone-releasing hormone (LH-RH) analogue having long-term effect. Seven of the 12 patients no longer needed a permanent catheter after the six-month treatment period. Transurethral resection of the prostate was performed for 3 patients. The remaining 2 patients continued to have a catheter. The mean prostatic volume, which was 83 g at the start of the study, fell by 51 percent, to 41 g. Treatment with LH-RH proved to be safe even for patients in poor physical condition, and it also seemed to improve symptoms of prostatic hyperplasia.

Aged↗
PubMed1991

Lack of association between prostate-specific acid phosphatase RFLP genotypes and prostatic cancer or benign prostatic hyperplasia.

We have previously reported the identification and basic characterization of two biallelic TaqI RFLPs, A and B, of the 3' end of the human ACPP locus in an unselected Finnish population (Winqvist et al., 1989). In the present investigation, a similar allelic distribution was observed in patients with prostatic cancer or benign hyperplasia. In addition, it was found that the DNA sequences generating RFLP-B are located further downstream from the RFLP-A sequences.

Acid Phosphatase↗
PubMed1991

Efficacy and safety of clean intermittent catheterization in adults.

A prospective study was carried out on the efficacy and safety of clean intermittent catheterization (CIC). The series included 41 adults (15 females, 26 males), the mean follow-up time being 40 months. Most patients were suffering from neurogenic bladder disorders. All of them used a self-lubricating hydrophilic catheter. Thirty-one patients (76%) continued to undergo CIC, but 9 discontinued. Thirty patients (73%) experienced bacteriuria during the procedure. Three males had epididymitis. Contrary to many earlier reports, urinary tract infections seem to increase after CIC, raising the question of whether prophylactic antibiotic therapy should be used more often in these cases. There were no urethral complications suggesting that the self-lubricating hydrophilic catheters may be less traumatic than those used previously.

Adult↗
PubMed1991

Intravesical epirubicin with and without verapamil for the prophylaxis of superficial bladder tumours.

Seventy-five patients with recurrent bladder carcinoma were randomized after electroresection to receive either epirubicin (E) or epirubicin + verapamil (E + V) instillation of the bladder at regular intervals for 2 years. Samples of the bladder wall, tumour tissue and peripheral blood were taken from 20 patients. The average follow-up period was 21 months. Fifty per cent of the patients in the E group and 37% in the E + V group developed recurrent tumours. Recurrence rates (RR) were 6.3 and 4.7, respectively. Before the instillation therapy the RR was 16.0. There was a highly significant reduction of RR during the instillation therapies; in group E p less than 0.005 and in group E + V p less than 0.001. The difference between the treatment groups was not statistically significant. Verapamil increased epirubicin concentrations in both the bladder wall and the tumour tissue, but did not affect concentrations in the peripheral blood. Side effects were few and did not lead to discontinuation of treatment.

Administration, Intravesical↗
PubMed1991

Effect of prolonged experimental distension on the function and ultrastructure of the canine urinary bladder.

Urinary bladder distension was induced for 10 hours in dogs and micturition tests were made before over-stretching, immediately afterwards and 5 days later. Compliance and residual urine had increased and maximum pressure during voiding had decreased immediately after retention, but returned to normal after 5 days. Biopses for light microscopic and electronmicroscopic investigation taken from the anterior wall of the bladder on the fifth day showed submucosal haemorrhages and some necrosis. The consistent finding on electron microscopy was Schwann cell oedema, which was seen within the cytoplasm and between the cytoplasmic processes of the Schwann cells. Axonal degeneration was also a common finding. These anatomical changes, although found at the moment of functional recovery, may be linked to impaired conductivity of the nerves in the bladder wall, at least partly, causing its impaired function. Recovery of function occurs quite rapidly in healthy bladders.

Animals↗
PubMed1990

Expression of the gene coding for human prostate-specific antigen and related hGK-1 in benign and malignant tumors of the human prostate.

Human glandular kallikrein-1 gene (hGK-1) is closely related to the gene of human prostate-specific antigen (PSA) and both genes are expressed in the human prostate. We have studied PSA and hGK-1 mRNAs in human prostatic tissue samples from patients with benign prostatic hyperplasia (BPH) or adenocarcinoma (CA), using Northern and slot-blot analysis in order to gain insight into the expression of these highly similar genes. Multiple mRNAs were found to originate from both genes. The major mRNA species of 1.6 kb accounted for 57% to 76% of the total coding capacity for PSA in different tissue specimens, but a variant mRNA species of 1.9 kb was also abundant. Most of the BPH samples contained marked amounts of an aberrant 0.9 kb mRNA, and long PSA mRNAs of 6.1 kb, 4.5 kb and 3.1 kb were found in elevated amounts in some of the CA samples. The amount of PSA mRNAs that would produce aberrant PSA proteins if translated into protein varied from 18% to 38% in these tissue samples. The major mRNA species originating from hGK-1 was of 1.6 kb, but other less abundant mRNA species could also be observed. The amount of PSA and hGK-1 mRNAs was determined from slot blots hybridized with specific oligonucleotide probes. No significant differences could be found in the PSA gene expression between BPH and CA samples. The total amount of the PSA mRNAs in all the different BPH specimens was fairly similar, but there was a 3-fold difference between the highest and lowest PSA mRNA levels in the CA samples. The hGK-1 mRNA levels in the BPH specimens studied demonstrated greater variance than the PSA mRNA levels in the same samples. The correlation between PSA gene and hGK-1 expression in the BPH samples was good, suggesting that there are similarities in the regulation of these genes. However, the lack of correlation between the amounts of PSA and hGK-1 mRNAs in the CA samples except in sample C1 indicates that there are also differences in the gene regulation. The observed 3.7- to 6.5-fold excess of PSA mRNAs as compared with the amount of hGK-1 mRNAs present in the same tissue specimen also indicated differences in the cis- or trans-acting regulatory elements of these genes.

Antigens, Neoplasm↗
PubMed1989

Urodynamics in radical retropubic prostatectomy.

Urodynamic examinations were performed on 19 patients undergoing radical retropubic prostatectomy for localized prostatic carcinoma. Altogether 16 urodynamic parameters were analyzed preoperatively and 6 months afterwards. There was a significant decrease in bladder wall compliance and an increase in intravesical and abdominal pressure at maximum flow rate postoperatively. These findings may reflect a partial bladder decentralization caused by surgery. The amount of residual urine was reduced postoperatively. Two patients (10.5%) were totally incontinent, and in both the postoperative urethral closure pressures were low.

Carcinoma↗
PubMed1988

Ethanolamine oleate as a sclerosant for testicular hydroceles and epididymal cysts.

Forty patients with testicular hydroceles and 16 patients with epididymal cysts were treated by tapping and injection of ethanolamine oleate; 97.5% of the hydroceles and 31% of the epididymal cysts were completely cured, 50% of the latter partly cured and 19% failed. About half of the patients experienced pain after treatment. Two patients developed infection. Ultrasonography showed no change in the testicular tissue during the follow-up period. Sclerotherapy with ethanolamine oleate is a rapid and cost-effective modality which can be recommended as primary treatment for hydroceles and for unilocular epididymal cysts, especially in elderly males.

Adult↗
PubMed1988

Sequentially alternating hormone chemotherapy with high-dose medroxy-progesterone acetate and low-dose epirubicin for the treatment of hormone-resistant metastatic prostatic cancer.

Thirty patients with hormone-resistant metastatic progressive prostatic carcinoma were treated with sequentially alternating hormone chemotherapy. They were given 1,000 mg medroxyprogesterone acetate (MPA) orally for 26 days followed by intravenous doses of 25 mg/m2 epirubicin weekly for 4 weeks. The median duration of the treatment was 29 weeks (range 8-84). In 2 patients a more than 50% reduction in the size of measurable lymph node metastases was observed and in 2 others skeletal metastases decreased. Serum acid phosphatase normalized in 6 patients. Twenty-five patients achieved a subjective response (median duration 24 weeks; range 4-76 weeks). Median survival from the start of treatment (30 +/- 16 weeks) was unrelated to the achievement of subjective response. Normalization of serum acid phosphatase and a more than 50% reduction in serum alkaline phosphatase correlated with the achievement of a subjective response. Toxicity was generally mild, but in 1 case therapy was discontinued because of suspected cardiotoxicity. Sequentially alternating high-dose MPA low-dose epirubicin hormone chemotherapy has a marginal objective effect but a good subjective effect on progressing hormone-resistant prostatic cancer.

Actuarial Analysis↗
PubMed1988

Treatment of advanced prostatic carcinoma with a slow release depot LHRH analogue (Zoladex depot).

We treated 38 patients with newly diagnosed advanced prostatic cancer with monthly injections of a long acting depot preparation of a luteinizing hormone-releasing hormone superagonist (Zoladex depot). After 6 months' treatment 10% of the patients had complete objective regression, 77% had partial objective regression, 3% stable disease and 10% had objective progression. The LHRH analogue does not have the metabolic side effects of oestrogens. Depot luteinizing hormone-releasing hormone analogue may well become a preferred alternative for patients with advanced prostatic cancer.

Aged↗
PubMed1988

Radioimaging of lymph node involvement in prostatic carcinoma.

We have previously shown that Tc-99m- or In-111-labelled derivatives of monoclonal antibodies against prostatic acid phosphatase can be used to reveal bone metastases of prostatic carcinoma. In this study, seven patients who were candidates for radical prostatectomy and two patients with bone metastases, were investigated to evaluate the applicability of this technique for preoperative staging of the patients. One milligram of monoclonal antibodies was injected bilaterally into the periprostatic space, and the patients were subjected to measurements by gamma camera. In one patient metastases were detected in the left para-aortic, iliac and obturator lymph nodes by this technique. The lesions incorporating radioactivity were confirmed to be metastases of prostatic cancer following staging pelvic lymphadenectomy. In the other four patients, radioimaging did not show any lymph node metastases, and this negative finding was confirmed at the operation. These early data indicate the possibility of preoperative staging of prostatic cancer by means of radiolabelled derivates of monoclonal antibodies, raised against prostatic acid phosphatase and injected into the periprostatic area.

Antibodies, Monoclonal↗