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Biomedical subjects

E Salminen

Publications and source records attributed to E Salminen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hormonal effects of MPV-2213ad, a new selective aromatase inhibitor, in healthy male subjects. A phase I study.

AIMS: A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration. METHODS: MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad. RESULTS: Serum oestradiol levels were suppressed by 58-65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort. CONCLUSIONS: MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.

Adult↗
PubMed1998

Biological day-to-day variation and daytime changes of testosterone, follitropin, lutropin and oestradiol-17beta in healthy men.

Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17beta concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CV(G)) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17beta concentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17beta occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone +/- 32.0 %, serum follitropin +/- 24.1 % and serum oestradiol-17beta +/- 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.

Adult↗
PubMed1997

CD106 (VCAM-1) in testicular immunoregulation.

The expression of CD18, CD49d/CD29, CD44, CD54 and CD106 was studied in the testis of normal mice at various ages, in the cryptorchid testis, in the testis of estrogen-treated mice and in the testis of non-obese diabetic (NOD) mice, using immunocytochemistry to see which of these lymphocyte and endothelial adhesion proteins may be involved in lymphocyte regulation in the testis. CD18-, CD49d/CD29-, CD44- and CD54-expressing cells were not found in the normal > 10-week-old BALB/c mouse testis. Leydig cells expressed CD106 strongly at this age. In contrast to the > 10-week-old testis, only very few interstitial cells of the 2-week-old normal mice expressed CD106. The expression of CD106 increased gradually with age so that at 6 weeks of age the expression of CD106 was moderate in the interstitial tissue. In the experimentally abdominal testis, CD106 was expressed in the interstitial tissue as strongly as in the contralateral scrotal testis. CD44- and CD18-expressing cells were occasionally present in the interstitial tissue of the abdominal testis, but not in the contralateral scrotal testis. CD54 was present in the epithelium of the ductuli efferentes. In the testis of the estrogen-treated mice, CD106 was expressed in the interstitial tissue as strongly as in the normal mice. Occasional CD44- and CD18-expressing cells were found in the testicular capsule. In the testis of adult NOD mice, CD106 was present in the interstitial tissue, but none of the other studied proteins. Immunoblotting of CD106 from the adult testis under reducing conditions demonstrated a single broad band with a M(r) of 51-65 kDa. This is a novel isoform of CD106. In a modified Stamper-Woodruff assay, lymphocytes bound to the testicular interstitial tissue. In co-incubations of native Leydig cells and lymphocytes, anti-CD106 antibodies prevented formation of Leydig cell-lymphocyte rosettes more than isotype-matched irrelevant control antibodies, suggesting that Leydig cell lymphocyte binding occurs through CD106-CD49d interactions. In lymphocyte cultures in the presence of anti-CD3, anti-CD28, the M(r) > 5 K fraction of testis extract (containing CD106 as shown by immunoblotting) and anti-CD106 or control antibody, anti-CD106 did not consistently affect T cell 3H-TdR incorporation. The present results suggest that CD106 expressed by the Leydig cells may act as an adhesion-promoting molecule or a co-stimulatory factor for T cells migrating to the testis.

Animals↗
PubMed1997

Paclitaxel changes sympathetic control of blood pressure.

Paclitaxel has become part of standard therapy in the treatment of ovarian and breast cancer. Concern has been raised about the effects of paclitaxel on cardiovascular function. Therefore, this study of the effects of paclitaxel on autonomic cardiovascular control was initiated. Eighteen women treated for ovarian or breast cancer were examined with autonomic cardiovascular function tests, once before the treatment and once after the second course of paclitaxel. Heart rate and blood pressure variability and changes in heart rate and blood pressure responses to the tests were measured. Baroreflex sensitivity was calculated from the Valsalva manoeuvre non-invasively. Paclitaxel did not change heart rate variability at rest compared with the pretreatment level. However, medium frequency variability of blood pressure was smaller after treatment with paclitaxel. Paclitaxel treatment did not impair the heart rate and blood pressure responses to the autonomic function tests. The results do imply that paclitaxel alters sympathetic control of blood pressure. Nevertheless, paclitaxel does not appear to precipitate autonomic cardiac neuropathy.

Adult↗
PubMed1997

Detection of residual tumours in postchemotherapy testicular cancer by FDG-PET.

The aim of this study was to investigate whether 2-(F-18)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) could reliably detect testicular cancer in patients following chemotherapy. Twenty FDG-PET studies were performed on 15 patients with metastatic seminoma or non-seminoma. Tracer uptake in the PET study was measured by calculating the standardised uptake value (SUV) for the tracer. Nine lesions out of 20 were judged to be positive based on high FDG uptake. Three proved to represent inflammatory changes in non-cancerous tissue. Eleven PET studies were negative. In one of these, viable tumour was found at retroperitoneal lymphadenectomy. The median SUV values of metastatic tumours and benign residual tumours were 2.7 (range 1.6-9.5, n = 10) and 1.7 (range 0.7-5.5, n = 15), respectively. The large overlap of SUVs between these groups was due to the relatively high FDG uptake in inflammatory tissue (median 4.2, range 2.0-5.5, n = 4). The results indicate that FDG imaging of metastatic testicular cancer after chemotherapy has limited value because of a potentially high accumulation of FDG in inflammatory tissues.

Adult↗
PubMed1997

Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection.

During the fermentation of lactulose, short-chain fatty acids are formed with consequent lowering of the colon pH and modification of the microflora. Lactulose promotes the growth of lactic acid bacteria and bifidobacteria and, more specifically, Lactobacillus acidophilus in the colon. Lactulose and lactulose-containing products fermented with lactic acid bacteria lower colonic pH balancing intestinal microecology and normalizing intestinal transit. In animal studies, lactulose promotes a mainly Gram-positive faecal microflora, but large doses of lactulose may be associated with transient diarrhoea. Our studies indicate that lactulose with lactic acid bacteria effectively relieves constipation in human volunteers. Lactulose with lactic acid bacteria in a fermented diary product can balance and prevent radiotherapy-associated diarrhoea and intestinal side effects. Normalizing the intestinal flora and stabilizing mucosal integrity with lactulose has beneficial effects in intestinal disorders. Lactulose and lactic acid bacteria offer a promising ingredient combination for future functional and special dietary foods in treating intestinal disturbances.

Aged↗
PubMed1997

Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery.

The value of daily monitoring of the blood CD34+ cell concentration as a guide to the optimal timing of stem cell harvests was studied in 60 patients who underwent 66 stem cell mobilizations and 189 leukaphereses. There was a highly significant correlation between the blood CD34+ count and the CD34+ cell content in the apheresis product of the same day (r = 0.904, p < 0.01). Thus, the target yield of 4 x 10(6) CD34+ cells/kg can be harvested in one or two leukaphereses when the blood CD34+ cell count exceeds 50 x 10(6)/L. However, an insufficient harvest is to be expected when the blood CD34+ cell count is below 20 x 10(6)/L. The data from 35 autologous blood cell transplantations with a minimum CD34+ cell yield of 1.5 x 10(6)/kg showed that the recovery of blood neutrophil counts to 1.0 x 10(9)/L occurred in all patients within 9-14 days, but the time to recovery of the platelet counts to 20 x 10(9)/L may exceed 14 days, especially if the CD34+ cell content is below 4 x 10(6)/kg. Daily monitoring of blood CD34+ cell counts is a rapid and reliable means to guide the timing of stem cell collections. The count predicts well the CD34+ cell content of the harvests, the number of leukaphereses needed, and the speed of hematopoietic recovery.

Adult↗
PubMed1997

Transport of carbon-11-methionine is enhanced by insulin.

UNLABELLED: The anabolic effects of insulin are not restricted to carbohydrate and lipid metabolism but also include protein metabolism. However, the effects of insulin on protein metabolism have been difficult to demonstrate in vivo. Amino acid transport is partly regulated by insulin according to the experimental data. PET provides a way to measure fractional uptake rates of amino acids. The purpose of this study was to measure the effect of insulin on amino acid transport from the plasma to the human parotid glands. METHODS: We compared the uptake of L-[methyl-11C]methionine ([11C]methionine) into the parotid glands and cerebellum in seven healthy volunteers during the fasting state and euglycemic insulin clamp technique (1 mU/kg per minute). RESULTS: The fractional uptake rate of [11C]methionine was increased by 31% for the right parotid gland (p = 0.003) and by 29% for the left parotid gland (p = 0.009) during insulin clamp, while the increase was 19% for the cerebellum (p = 0.01). The concentration of amino acids typical for the hormone-sensitive transport system A was 11% lower during insulin infusion than in the fasting state. CONCLUSION: The uptake of methionine into brain tissue does not seem to be under major control by insulin, while the transport of methionine in the parotid glands is stimulated by insulin. PET provides a sophisticated method to study the transport system of amino acids in vivo.

Adult↗
PubMed1996

Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful strains and future challenges.

Probiotic bacteria are used to treat disturbed intestinal microflora and increased gut permeability which are characteristic to many intestinal disorders. Examples include children with acute rotavirus diarrhoea, subjects with food allergy, subjects with colonic disorders and patients undergoing pelvic radiotherapy and sometimes changes associated with colon cancer development. In all such disease states altered intestinal microflora, impaired gut barrier and different types of intestinal inflammation are present. Successful probiotic bacteria are able to survive gastric conditions and colonize the intestine, at least temporarily, by adhering to the intestinal epithelium. Such probiotic microorganisms appear to be promising candidates for the treatment of clinical conditions with abnormal gut microflora and altered gut mucosal barrier functions. They are also promising ingredients to future functional foods and clinical foods for specific disease states provided that basic requirements for strains and clinical studies are carefully followed.

Animals↗
PubMed1996

Multivariate analysis of prognostic factors in 106 patients with malignant glioma.

The aim of this study was to evaluate the outcome and prognostic factors influencing survival in 106 patients with supratentorial malignant gliomas treated with radiotherapy. The study group included 84 patients treated by surgery and post-operative radiotherapy and 22 patients treated by postbiopsy irradiation. Radiotherapy was delivered to the tumour area with a 2 cm margin, the aimed curative dose was 60 Gy in 6-7 weeks. The 60-month overall survival (Kaplan-Meier) was 20%. Following a univariate analysis, younger age (P < 0.001), longer duration of symptoms (P = 0.009), good performance status after radiotherapy (P < 0.001), other than grade 4 histology (P < 0.001) and higher radiation dose (P < 0.001) were associated with better overall survival rates. Multivariate analysis found that age, symptom duration, histology, extent of symptoms and radiation dose were independent prognostic factors influencing survival. In conclusion, conventional radiotherapy of supratentorial malignant gliomas results in survival that is comparable to results from clinical experiments with different fractionation schedules and radiation with chemotherapy or radiosensitisers. To improve the results, new approaches are needed, especially for patients with the poorest prognosis after standard treatment.

Adolescent↗
PubMed1995

Risk of second cancers among lung cancer patients.

The risk of a second cancer among lung cancer patients was investigated using Finnish Cancer Registry data from 1953 to 1989. Among the 36,528 patients with a primary cancer of the lung, 504 new cancers were diagnosed six months or more after the diagnosis of lung cancer, yielding a standardized incidence ratio significantly lower than expected (SIR = 0.81). A significant excess of cancers of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed Among lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk of a second cancer among lung cancer patients increased with the length of follow-up, and there was some indication of an excess risk of oesophageal cancer and leukaemia among lung cancer patients subject to radiotherapy.

Age Factors↗
PubMed1994

Subsequent primary cancers following bladder cancer.

The incidence of a subsequent primary cancer was investigated among 10,014 patients with cancer of the urinary bladder diagnosed in 1953-1989 in Finland. During the follow-up period of 1953-1989, 652 new metachronous cancers were diagnosed. The number equals the expected number based on the national incidence figures. There were 195 second cancers of the lung. The standardised incidence ratio (SIR) for lung cancer was 1.3 among males [95% confidence interval (CI) 1.1-1.4] and 2.6 among females (95% CI 1.4-4.5). An increased SIR for larynx cancer in males (SIR = 1.7, 95% CI 0.91-2.8) and for kidney cancer in females (SIR = 3.6, 95% CI 1.8-6.2) was observed. The risk of a second cancer was greater among patients less than 60 years of age at the time of first diagnosis than among older patients. No consistent differences were observed in the risk of new cancer between bladder cancer patients treated with or without radiotherapy.

Adult↗
PubMed1994

Bladder cancer and the risk of smoking-related cancers during followup.

The risk of smoking-related secondary cancers developing in bladder cancer patients was studied. The study population consisted of 10,014 bladder cancer patients reported to the Finnish Cancer Registry between 1953 and 1989. The risk of contracting a new primary cancer was estimated as a standardized incidence ratio, defined as the ratio of the observed and expected numbers of cases. Of 660 secondary cancers (6.6%) observed (standardized incidence ratio 0.96) 44% were considered to be smoking-related. Lung cancer was the most common secondary cancer (30% overall), and it occurred significantly more often than expected (standardized incidence ratio 1.31, 95% confidence interval 1.13 to 1.50). Also, larynx cancer among men (standardized incidence ratio 1.67, 95% confidence interval 0.95 to 2.79) and kidney cancer among women (standardized incidence ratio 3.55, 95% confidence interval 1.84 to 6.20) were found more often than expected. These excess risks were observed up to 20 years after diagnosis of bladder cancer. Therefore, bladder cancer patients experience an excess risk of smoking-related new tumors, which must be acknowledged during the initial evaluation and regular followup of such patients.

Adult↗