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Biomedical subjects

O Alfthan

Publications and source records attributed to O Alfthan.

At least 19 recordsLinked to original sources

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.

BCG Vaccine

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.

Antigens, Neoplasm

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.

Animals

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.

Actins

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.

Administration, Oral

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.

Animals

Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette-Guérin) in superficial bladder cancer.

Both intravesical mitomycin C (MMC) and bacillus Calmette-Guérin (BCG; Pasteur strain F) were effective in the present prospective randomized multicenter study consisting of 91 patients with frequently recurrent superficial (Ta-T1) bladder cancer. The result was in favour of BCG, as shown by the measurements with complete response (CR), disease-free interval and recurrence rate. CR of 58% with MMC and 40% with BCG were reached in 22 instillation series on carcinoma in situ of 18 patients. Due to side effects, MMC instillations were discontinued in 8.6%, and BCG instillations in 19.6%, respectively. After the 2-year follow-up also 1 case of pulmonary tuberculosis occurred in the BCG group.

Administration, Intravesical

Hormone-resistant metastatic prostate cancer. Comparisons between estramustine phosphate and low-dose epirubicin treatments.

We compared the effect and toxicity of estramustine phosphate and weekly low-dose epirubicin in a prospective randomized trial in 41 patients with metastatic prostate cancer refractory to hormonal manipulation. No significant difference between treatment modalities was seen. Palliation was reached in over 60% of patients. The median survival was 15 months in both groups. Toxicity was mild. Further, we investigated the effect of epirubicin after the failure of preceding estramustine phosphate therapy in additional 20 patients. Pain relief was achieved in 50% of these patients. The median survival was 10 months. Toxicity was acceptable.

Aged

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.

Aged

Comparison of primary orchiectomy and polyoestradiol phosphate in the treatment of advanced prostatic cancer. Finnprostate Group.

The primary clinical efficacy of orchiectomy and polyoestradiol phosphate (PEP) 160 mg/month i.m. was evaluated by progression and cancer mortality rates in a Finnish multicentre study comprising 200 prostatic cancer patients. After the minimum follow-up time of 2 years there was a significant difference between the groups--orchiectomy delayed progression of the disease more effectively. The follow-up time is rather short for prostatic cancer, but on the basis of this preliminary study the dose of PEP seems to be insufficient in the treatment of advanced prostatic cancer.

Aged

The effect of parenteral estrogen versus orchiectomy on blood coagulation and fibrinolysis in prostatic cancer patients.

The effects of parenterally given polyestradiol phosphate (80 or 160 mg i.m. monthly) and bilateral subcapsular orchiectomy on blood coagulation and fibrinolytic parameters were compared in 11 patients with prostatic carcinoma. Estrogen therapy lowered antithrombin III, plasminogen and plasminogen activator inhibitor activities, whereas these parameters remained unchanged in orchiectomized patients. There were no significant changes in platelet count, fibrinogen, factor VII, protein C and alpha 2-antiplasmin in either group. Estrogen had unfavorable effects on hemostatic laboratory parameters in the direction of a hypercoagulable state. However, no thromboembolic complications were encountered.

Aged

Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients.

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.

Aged

Evaluation of principles in intravesical chemo- and immunotherapy for superficial bladder cancer.

There is still much controversy about the diagnostics and therapy of carcinoma in situ (TIS/CIS) of the bladder. Reliance on cytological possibilities in the primary diagnosis and grading varies in separate centres. Hence, the small series published hitherto are often incomparable due to different start points and end points of trials. We regard cytology as the key examination in TIS. Complete response (CR) and progressive disease (PD) are end points which can be defined by histology/cytology and the timer factor. Our philosophy concerning the evaluation of therapy-principles in superficial bladder cancer is mainly based on our own experience. The efficacy of MMC and of BCG was equally modest in the Finnbladder I study: the CRs 38% and 40%; the PDs 8% and 20%, respectively. The interim of the ongoing Finnbladder II study are more promising after 6 months follow-up: the CR with MMC 67% and with alternating therapy with MMC and BCG 80%; there were no progressions so far. The primary grade of TIS has been a significant prognostic factor for instillation therapy in our earlier series of 62 pts since 1976. There were no progressions of grade I but 19% of grade II and 13% of grade III. A wide consensus of concepts dominates as to the superficial bladder cancer (Ta-T1). The recurrence rate (RR) and the recurrence index (RI/m) as the end points of prophylactic trials are capable of indicating the recurrence-preventive efficacy of different instillations, allow the use of a patient as his own control, and are suitable for statistical evaluation (table I).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical