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Biomedical subjects

P Finne

Publications and source records attributed to P Finne.

At least 19 recordsLinked to original sources
PubMed2001

Preoperative serum concentration of hCGbeta as a prognostic factor in ovarian cancer.

In spite of a gradual improvement, survival in epithelial ovarian cancer is disappointingly low. New therapeutic regimens are emerging, and it would be important to be able to predict the prognosis and to stratify patients for clinical trials before therapy. We have evaluated the prognostic value of the pretreatment serum concentrations of 3 tumor markers. The free beta subunit of human chorionic gonadotropin (hCGbeta), CA125 and tumor-associated trypsin inhibitor (TATI) were measured in pretreatment serum samples from 146 patients treated for ovarian cancer between 1990-1995. The patients were followed up until 1998. Elevated concentrations of hCGbeta, CA125 and TATI were observed in 29%, 79% and 33%, respectively. When tested as single variables in Cox's proportional hazards model, stage, grade, size of residual tumor and hCGbeta (all p < 0.001) and CA125 (p = 0.004) correlated with prognosis. However, when fitted as multiple variables together with stage, grade and age in the same model, hCGbeta (RR = 3.42) stage (RR = 2.77) and grade (RR = 3.80) were the only significant variables. When serum hCGbeta was normal, 5-year survival was 80%, but it was only 22% when hCGbeta was elevated. In patients with stage III or IV and minimal residual disease, 5-year survival was 75% if hCGbeta was normal compared with 0% if hCGbeta was elevated. hCGbeta in serum is a strong independent prognostic factor in epithelial ovarian cancer, and its prognostic value is similar to that of grade and stage. The availability of this marker before surgery could facilitate selection of treatment modalities.

Adult↗
PubMed2001

Relative levels of SCCA2 and SCCA1 mRNA in primary tumors predicts recurrent disease in squamous cell cancer of the head and neck.

Squamous cell carcinoma antigen (SCCA) is widely used as a serum marker in cancers of the uterine cervix, the head and neck, lung and esophagus. Two isoforms of SCCA, deriving from 2 highly homologous serine proteinase inhibitor genes, are co-expressed in normal and malignant squamous epithelium, but it is mainly the acidic isoform SCCA2 that is present in the circulation of cancer patients. We studied the relative levels of SCCA2 and SCCA1 mRNA in frozen sections of squamous cell carcinomas of the head and neck (SCCHN) in relation to disease recurrence, using a new reverse transcription-polymerase chain reaction-based technique for accurate quantitation of relative mRNA levels. Primary tumors from 30 SCCHN patients, recurrent tumors from 11 patients and normal epithelium from 16 controls were examined. In patients responding to initial therapy (n = 26), an elevated SCCA2/SCCA1 mRNA ratio in the primary tumor predicted recurrence independent of clinical stage (p = 0.011). The relative risk of developing a recurrence was 7.2 (CI 1.2-13.3) in patients with elevated vs. normal SCCA2/SCCA1 mRNA ratios. We demonstrate that subtle differences in expression levels of the SCCA genes are reflected in the course of the SCCHN disease and may provide a target for molecular grading of SCCHN tumors. If this finding can be confirmed in a larger study the SCCA2/SCCA1 mRNA ratio in primary tumors could be useful for individual selection of treatment strategy for patients with head and neck cancer.

Adult↗
PubMed2001

The ratio of trypsin-2-alpha(1)-antitrypsin to trypsinogen-1 discriminates biliary and alcohol-induced acute pancreatitis.

BACKGROUND: Rapid determination of the etiology of acute pancreatitis (AP) enables institution of appropriate treatment. We evaluated the ability of trypsinogen-1, trypsinogen-2, trypsin-1-alpha(1)-antitrypsin (AAT), and trypsin-2-AAT in serum to identify the etiology of AP. METHODS: The study consisted of 67 consecutive patients with AP admitted to Helsinki University Central Hospital. Forty-two had alcohol-induced AP, 16 had biliary AP, and 9 had unexplained etiology. Serum samples were drawn within 12 h after admission. Trypsinogen-1, trypsinogen-2, trypsin-1-AAT, and trypsin-2-AAT were determined by time-resolved immunofluorometric assays. Logistic regression was used to estimate the ability of the serum analytes to discriminate between alcohol-induced and biliary AP. The validity of the tests was evaluated by ROC curve analysis. RESULTS: Patients with alcohol-induced AP had higher median values of trypsin-1-AAT (P = 0.065), trypsinogen-2 (P = 0.034), and trypsin-2-AAT (P <0.001) than those with biliary AP, who had higher values of amylase (P = 0.002), lipase (P = 0.012), and alanine aminotransferase (P = 0.036). The ratios of trypsin-2-AAT to trypsinogen-1, lipase, or amylase efficiently discriminated between biliary and alcohol-induced AP (areas under ROC curves, 0.92-0.96). CONCLUSIONS: Trypsinogen-2 and trypsin-2-AAT are markedly increased in AP of all etiologies, whereas trypsinogen-1 is increased preferentially in biliary AP. The trypsin-2-AAT/trypsinogen-1 ratio is a promising new marker for discrimination between biliary and alcohol-induced AP.

Acute Disease↗
PubMed2001

Predicting the severity of acute pancreatitis by rapid measurement of trypsinogen-2 in urine.

BACKGROUND: Early identification of patients at risk of developing a severe attack of acute pancreatitis (AP) is of great importance because rapid therapeutic interventions improve outcome. At a cutoff of 50 microg/L, trypsinogen-2 measured by a rapid urinary dipstick is a sensitive and specific diagnostic test in AP. The trypsinogen-2 concentration correlates with the severity of the disease, and a test with a higher cutoff might therefore be useful for prediction of disease severity. METHODS: We increased the detection limit of the urinary trypsinogen-2 test strip (Actim Pancreatitis) from 50 microg/L to 2000 microg/L and evaluated the prognostic value of this test. The results were compared with those obtained with serum C-reactive protein and the acute physiology and chronic health evaluation II (APACHE II) score. The study population consisted of 150 consecutive patients with AP (42 with severe disease). RESULTS: The sensitivity of the rapid urinary test strip (detection limit, 2000 microg/L) for prediction of severe AP, both on admission and at 24 h, was 62%; specificities were 87% and 85%, respectively, positive predictive values were 65% and 62%, and negative predictive values were 85% and 85%. C-Reactive protein had a sensitivity of only 38% on admission, but at 24 h, it was 83%; specificities were 90% and 70%, respectively, whereas positive predictive values were 59% and 52%, and NPVs were 79% and 91%, respectively. On admission the positive-likelihood ratio for the urinary trypsinogen-2 test strip was 4.8, and at 24 h it was 4.2; for C-reactive protein, the values were 3.7 and 2.7, respectively. CONCLUSIONS: The urinary trypsinogen-2 dipstick is a simple and rapid method for prediction of severe acute pancreatitis.

Acute Disease↗
PubMed2000

Predicting the outcome of prostate biopsy in screen-positive men by a multilayer perceptron network.

OBJECTIVES: To assess whether an artificial neural network (multilayer perceptron, MLP) and logistic regression (LR) could eliminate more false-positive prostate-specific antigen (PSA) results than the proportion of free PSA in a prostate cancer screening. METHODS: MLP and LR models were constructed on the basis of data on total PSA, the proportion of free PSA, digital rectal examination (DRE), and prostate volume from 656 consecutive men (aged 55 to 67 years) with total serum PSA concentrations of 4 to 10 ng/mL in the randomized population-based prostate cancer screening study in Finland. The MLP and LR models were validated using the "leave-one-out" method. RESULTS: Of the 656 men, 23% had prostate cancer and 77% had either normal prostatic histology or a benign disease. At a 95% sensitivity level, 19% of the false-positive PSA results could be eliminated by using the proportion of free PSA versus 24% with the LR model and 33% with the MLP model (P < 0.001). At 80% to 99% sensitivity levels, the accuracy of the MLP and LR models was significantly higher than that of the proportion of free PSA. At 89% to 99% sensitivities, the accuracy of the MLP was higher than that of LR (P </= 0.001). CONCLUSIONS: At clinically relevant sensitivity levels, the MLP and LR models based on total PSA, the proportion of free PSA, DRE, and prostate volume could reduce the number of unnecessary biopsies significantly better than the proportion of free PSA alone in men with total PSA levels in the range 4 to 10 ng/mL.

Aged↗
PubMed2000

Determination of prostate-specific antigen complexed to alpha(2)-macroglobulin in serum increases the specificity of free to total PSA for prostate cancer.

OBJECTIVES: To determine whether prostate-specific antigen (PSA) complexed to alpha(2)-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and total PSA (tPSA) for the diagnosis of prostate cancer (PCa). METHODS: In a series of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA, tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific immunoassays. The assay for PSA-A2M was based on the immunoadsorption of immunoreactive PSA in serum and the measurement of the PSA immunoreactivity released by denaturation of PSA-A2M at pH 11.4. RESULTS: The median proportion of PSA-A2M [ %PSA-A2M=PSA-A2M/(tPSA+PSA-A2M)] and that of fPSA ( %fPSA=fPSA/tPSA) were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively). The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH (P <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for PCa, 57% of patients with "falsely" elevated PSA concentrations (4 to 10 ng/mL) caused by BPH could be correctly identified without missing patients with PCa compared with 18% of the patients with BPH but not PCa using %fPSA alone. CONCLUSIONS: Measurement of the sum of %PSA-A2M and %fPSA in serum significantly improves the cancer specificity of the PSA test compared with the use of tPSA and %fPSA.

Aged↗
PubMed2000

Induction of endometrial plasminogen activator-inhibitor 1: a possible mechanism contributing to the effect of intrauterine levonorgestrel in the treatment of menorrhagia.

OBJECTIVE: To elucidate molecular mechanisms accounting for excessive menstrual blood loss, and to present the therapeutic effect of an intrauterine levonorgestrel system (LNG-IUS) in menorrhagia. DESIGN: A multicenter study comparing hysterectomy with the LNG-IUS in treating menorrhagia. SETTING: A university hospital. PATIENT(S): Women with (n = 27) and without (n = 14) menorrhagia, and women with uterine fibroids but undetermined menstrual blood loss (n = 35). INTERVENTION(S): An LNG-IUS was inserted into the uterine cavity in 11 women with menorrhagia and six women experiencing normal menstrual blood loss. MAIN OUTCOME MEASURE(S): Expression of the messenger ribonucleic acid (mRNA) of tissue-type plasminogen activator (t-PA) and that of a specific PA inhibitor type 1 (PAI-1) in endometrial tissue samples, as evaluated with the use of Northern blot analysis. RESULT(S): t-PA mRNA was expressed in the endometrium throughout the menstrual cycle, with no statistically significant difference between a proliferative (n = 30) and a secretory endometrium (n = 40), or between women experiencing normal menstrual blood loss (n = 14) and those with menorrhagia (n = 27). The levels of t-PA mRNA in menstrual phase samples (n = 6) were significantly higher than those in proliferative or secretory endometrium. PAI-1 mRNA was detected in the endometrium during menstruation only. Both t-PA mRNA and PAI-1 mRNA were expressed in all endometrial samples (n = 17) obtained 6 months after an LNG-IUS was inserted, regardless of the menstrual cycle phase. The relative levels of both types of mRNA were significantly higher in LNG endometrium than in proliferative or secretory endometrium, but levels did not differ from those in menstrual-phase endometrium. CONCLUSION(S): The mean (+/-SD) levels of t-PA mRNA and PAI-1 mRNA in the endometrium of women with and without menorrhagia did not differ, suggesting that the PA system is not the major determinant of menstrual blood loss. However, continuous induction of PAI-1 may contribute to the therapeutic effect of LNG-IUS in treating menorrhagia.

Adult↗
PubMed2000

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.

Aged↗
PubMed2000

Use of the complex between prostate specific antigen and alpha 1-protease inhibitor for screening prostate cancer.

PURPOSE: We assess whether the complex between prostate specific antigen (PSA) and alpha1-protease inhibitor in serum can be used to reduce further the number of false-positive PSA screen results independent of total and free PSA. MATERIALS AND METHODS: Sera from 304 consecutive screen positive subjects, including 78 with and 226 without prostate cancer, and serum PSA of 4 to 10 microg./l. or higher in the Finnish, randomized, population based prostate cancer screening trial were analyzed for PSA-alpha-protease inhibitor, and total and free PSA. Main outcome measures were specificity, sensitivity and area under receiver operating characteristics curve for proportions of free PSA and PSA-alpha 1-protease inhibitor, and for a combination of these among screen positive cases. RESULTS: The proportion of serum PSA-alpha 1-protease inhibitor of total PSA was lower in cancer cases than in controls (0.9% versus 1.6%, p <0.001). Logistic regression analysis of total PSA, free PSA and PSA-alpha 1-protease inhibitor showed that PSA-alpha 1-protease inhibitor in serum was an independent variable for discrimination between subjects with and without prostate cancer (p = 0.006) in the PSA range of 4 to 10 microg./l. The proportion of PSA-alpha 1-protease inhibitor alone improved specificity less than the proportion of free PSA but when these were combined by logistic regression they performed better than the proportion of free PSA alone at sensitivities of 85% to 95% (p <0.001). CONCLUSIONS: Serum PSA-alpha 1-protease inhibitor improves the specificity of total and free PSA in a screening population with total PSA 4 to 10 microg./l.

Aged↗
PubMed2000

Characterization and determination of the complex between prostate-specific antigen and alpha 1-protease inhibitor in benign and malignant prostatic diseases.

Prostate-specific antigen (PSA) is a tissue-specific serine protease which forms complexes with protease inhibitors such as alpha 1-antichymotrypsin and alpha 2-macroglobulin. We have studied the interaction between PSA and alpha 1-protease inhibitor (API) in vitro and found that 15% of the added PSA binds to API while the majority of API is cleaved between Met358 and Ser359 when PSA is incubated with a 5-fold excess of API at 37 degrees C for 7 days. The complex between PSA and API (PSA-API) formed in vitro displays the same chromatographic behavior, molecular size and immunoreactivity as endogenous PSA-API occurring in serum, indicating that they are identical. PSA-API can be detected in serum by a time-resolved immunofluorometric assay (IFMA), in which a monoclonal antibody to PSA is used as a catcher and a polyclonal antibody to API labeled with a Eu-chelate is used as a tracer. Purified PSA-API formed in vitro is used as a calibrator. PSA-API in serum represents 1.0-7.9% (median 2.4%) of total PSA (tPSA) in prostate cancer (PCa, n = 82) and 1.3-12.2% (median 3.6%, p < 0.01) in patients with benign prostatic hyperplasia (BPH, n = 66). The IFMA for PSA-API in serum is hampered by a variable background, which is caused by non-specific adsorption of the huge excess of API in serum to the solid phase. The background can be determined by an assay using the same tracer as in the IFMA for PSA-API but PSA-unrelated antibody on the solid phase. The background signal is subtracted from the PSA-API signal. The clinical utility of PSA-API in serum has been evaluated in PSA-positive subjects from the Finnish PCa screening trial. After subtraction of the background, the proportion of PSA-API in relation to tPSA is lower in PCa than in controls, 0.9% vs. 1.6%, respectively (p < 0.001). Logistic regression analysis showed that the concentration of PSA-API was independent of the proportion of free PSA as a diagnostic variable among subjects with a tPSA of 4-10 micrograms/l (p = 0.009). The probability of PCa calculated by logistic regression using the concentration of PSA-API and the proportion of free PSA in serum significantly improved cancer specificity at high sensitivity levels (85-95%) as compared to the proportion of free PSA alone.

Humans↗
PubMed1999

Concentration of free hCGbeta subunit in serum as a prognostic marker for squamous-cell carcinoma of the oral cavity and oropharynx.

This study was conducted to evaluate the clinical usefulness of serum hCGbeta in the diagnosis and prognosis of patients (n = 59) with cancers of the oral cavity and oropharynx. As a reference marker we used squamous-cell carcinoma antigen (SCCAg). A blood sample was obtained from all patients before primary surgery. Serum hCGbeta was determined by a time-resolved immunofluorometric assay (IFMA) and SCCAg by a solid phase immunoenzymometric assay. Elevated preoperative hCGbeta levels were observed in 8 (14%) and elevated SCCAg in 12 (20%) out of 59 patients. Patients with preoperatively elevated hCGbeta had a shorter recurrence-free survival when compared with those with normal hCGbeta levels (log-rank Chi-squared = 6.83, p =.009), and the risk-ratio for recurrence during follow-up for those was 3.6 (95% CI = 1.29-9.94). In a Cox multivariate model hCGbeta (p = 0.039) and stage (p = 0.044) were independent prognostic factors. SCCAg showed no correlation with recurrence-free survival. We conclude that determination of hCGbeta in serum is a potential marker in the prognostic evaluation of patients with SCC of the oral cavity and oropharynx.

Adult↗
PubMed1999

Prostate-specific antigen.

Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of PSA is increased in prostatic disease. Thus PSA is a sensitive serum marker for prostate cancer but its specificity is limited by a high frequency of falsely elevated values in men with benign prostatic hyperplasia (BPH). Approximately two-thirds of all elevated values (>4 microg/l) in men over 50 years of age are due to BPH. In serum, most of the PSA immunoreactivity consists of a complex between PSA and alpha1-antichymotrypsin (PSA-ACT) whereas approximately 5-40% are free. The proportion of PSA-ACT is larger and the free fraction is smaller in prostate cancer than in benign prostatic hyperplasia (BPH). Determination of the proportion of free PSA has become widely used to improve the cancer specificity of PSA especially in men with PSA values in the 'grey zone' (4-10 microg/l). PSA also occurs in complexes with other protease inhibitors and determination of these and other markers may further improve the diagnostic accuracy for prostate cancer. Interpretation of the results for many different markers is complicated, but this can be simplified by using statistical methods. The diagnostic accuracy can be further improved by using logistic regression or neural networks to estimate the combined impact of marker results and other findings like digital rectal examination (DRE), transrectal ultrasound (TRUS) and heredity.

Humans↗
PubMed1999

Measurement of the complex between prostate-specific antigen and alpha1-protease inhibitor in serum.

BACKGROUND: Prostate-specific antigen (PSA) occurs in serum both free and in complex with protease inhibitors. The complex with alpha1-antichymotrypsin (ACT) is the major form in serum, and the proportion of PSA-ACT is higher in prostate cancer (PCa) than in benign prostatic hyperplasia (BPH). PSA also forms a complex with alpha1-protease inhibitor (API) in vitro, and the PSA-ACT complex has been detected in serum from patients with prostate cancer. The aim of the present study was to develop a quantitative method for the determination of PSA-API and to determine the serum concentrations in patients with PCa and BPH. METHODS: The assay for PSA-API utilizes a monoclonal antibody to PSA as capture and a polyclonal antibody to API labeled with a Eu-chelate as a tracer. For calibrators, PSA-API formed in vitro was used. Serum samples were obtained before treatment from 82 patients with PCa, from 66 patients with BPH, and from 22 healthy females. RESULTS: The concentrations of PSA-API are proportional to the concentrations of total PSA. PSA-API comprises 1.0-7.9% (median, 2.4%) of total immunoreactive PSA in PCa and 1.3-12.2% (median, 3.6%) in BPH patients with serum PSA concentrations >4 microgram/L. In patients with 4-20 microgram/L total PSA, the proportion of PSA-API serum is significantly higher in BPH (median, 4.1%) than in PCa (median, 3. 2%; P = 0.02). CONCLUSIONS: The proportion of PSA-API in serum is lower in patients with PCa than in those with BPH. These results suggest that PSA-API is a potential adjunct to total and free PSA in the diagnosis of prostate cancer.

Electrophoresis, Polyacrylamide Gel↗
PubMed1998

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↗