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U H Stenman

Publications and source records attributed to U H Stenman.

At least 19 recordsLinked to original sources
PubMed2006

Past chlamydial infection is not associated with primary fallopian tube carcinoma.

We conducted a retrospective seroepidemiological study to evaluate the relationship between past chlamydial infection and primary fallopian tube carcinoma (PFTC). Postoperative serum samples were drawn from 79 consecutive patients treated for PFTC in 1985-2000. For each case two controls were selected. Serum samples were analysed for IgG antibodies to different C. trachomatis serotype pools and to C. pneumoniae. Seropositivity in general or serum antibody levels to different C. trachomatis serovars or C. pneumoniae did not differ between PFTC patients and controls. The lack of association between anti-chlamydial antibodies and PFTC suggests that past chlamydial infection does not play a role in the etiopathogenesis of PFTC. However, because chlamydial infection is common at young age and PFTC develops decades later, we cannot definitively exclude the possibility that C.trachomatis contributes to the development of PFTC.

Adult↗
PubMed2005

Preoperative serum hCGbeta as a prognostic marker in primary fallopian tube carcinoma.

OBJECTIVES: It was the aim of this study to evaluate the prognostic value of the pretreatment serum concentrations of the beta-subunit of human chorionic gonadotropin (hCGbeta), CA 125 and tumour-associated trypsin inhibitor (TATI) in primary fallopian tube carcinoma (PFTC). METHODS: The pretreatment serum concentrations of hCGbeta, CA 125 and TATI were analyzed in serum samples from 60 women with a mean age of 61 years, treated for PFTC between 1985 and 2000. Of the 91 patients treated during this period, 31 were excluded because no serum sample was available. The patients were followed-up for recurrence and survival until February 14, 2003. The prognostic value of the serum markers were compared with those of stage, grade and histological type. RESULTS: The median survival time was 27 months and the overall 5-year survival rate 33%. Stage and size of the residual tumour (<1 vs. > or =1 cm) predicted both overall and disease-free survival (p < 0.050). Histology (serous vs. others) (p = 0.023) also influenced overall survival. Overall 5-year survival was 38% when serum hCGbeta was below 3.5 pmol/l, while it was 18% when the level was higher (p = 0.052). The corresponding disease-free 5-year survival was 38 and 20%, respectively (p = 0.014). Patients with CA 125 values above 1,017 kU/l had an overall 5-year survival of 39% as compared with 14% for those with lower values (p = 0.009), while the disease-free survival was 37 and 23%, respectively (p = 0.096). Serum TATI was not a prognostic marker. Serum concentrations of hCGbeta and CA 125 correlated significantly with stage (p = 0.049 and p = 0.050, respectively). In multivariate Cox proportional hazards regression analysis, only hCGbeta, stage and histology emerged as independent prognostic factors. CONCLUSIONS: Clearly elevated serum concentrations of hCGbeta and CA 125 predict survival in fallopian tube carcinoma, but in multivariate analyses, only hCGbeta is a prognostic factor independent of stage and histology.

Adult↗
PubMed2005

Innovations in serum and urine markers in prostate cancer current European research in the P-Mark project.

An overview is given of serum and urine prostate cancer markers that are currently under investigation and subsequently the P-Mark project is introduced. There are many markers showing promise to overcome the limitations of prostate specific antigen (PSA). Eventually, these markers should be able to increase the specificity in diagnosis, differentiate between harmless and aggressive disease and identify progression towards androgen independence at an early stage. In the P-Mark project, several recently developed, promising markers will be evaluated using clinically well-defined biorepositories. Following successful evaluation, these markers will be validated on a sample set derived from two large, European, prostate cancer studies and used for the identification of special risk groups in the general population. In addition, novel markers will be identified in the same biorepositories by different mass spectrometry techniques.

Biomarkers, Tumor↗
PubMed2005

Determination of 17alpha-hydroxyprogesterone in serum by liquid chromatography-tandem mass spectrometry and immunoassay.

17Alpha-hydroxyprogesterone (17OHP) is the most important serum marker for congenital adrenal hyperplasia (CAH). 17OHP is usually measured by immunoassay but its detection by mass spectrometry (MS) is a potentially superior method. An LC-MS (liquid chromatography-mass spectrometry) method was developed which utilizes 0.5 ml serum spiked with 6-alpha-methylprednisolone (6-MP) or deuterated 17OHP (d8-IS) as the internal standard. The samples were extracted with ether/ethylacetate, and the extract was evaporated to dryness and analysed by LC-MS/MS operating in the positive mode after separation on a reversed-phase C18 column. The calibration curves for analysis of serum 17OHP exhibited consistent linearity and reproducibility in the range of 5-250 nmol/l. Interassay CVs were 8.5 and 9.2% at mean concentrations of 7.9 and 23 nmol/l, respectively. The detection limit was 1 nmol/l (signal-to-noise ratio=3). The mean recovery of 17OHP added to serum ranged from 76 to 89% and that of internal standards from 75 to 82%. The regression equation for the LC-MS/MS (x) and in-house radioimmunoassay (RIA) (y) methods was: y=0.87x+0.26 (r=0.97; n=100) and for a commercial RIA it was: y=1.32x+0.02 (r=0.97; n=26).

17-alpha-Hydroxyprogesterone↗
PubMed2005

Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues.

Animals↗
PubMed2004

Quantification of prostate specific antigen mRNA levels in circulation after prostatic surgery and endocrine treatment by quantitative reverse transcription-polymerase chain reaction.

Various methods to detect prostatic cells in circulation have given conflicting results. This is probably because qualitative rather than quantitative methods have been used to detect mRNA from prostatic cells. A quantitative method has been developed based on reverse transcription-polymerase chain reaction (RT-PCR) for detection of prostate specific antigen (PSA) mRNA in peripheral blood. A competitive internal mRNA standard was used for quantification of absolute amounts of PSA mRNA. The detection limit of the assay was 7 copies of mRNA, and the highest level of circulating PSA mRNA in 88 control subjects was 25 copies per milliliter of blood. This method was used to study the influence of prostatic surgery and endocrine treatment on prostatic cells in the circulation of 56 patients undergoing biopsy, radical prostatectomy, transurethral resection of the prostate (TURP), orchiectomy, or androgen blockade. Blood samples were drawn before, during and up to 26 weeks after these procedures had been carried out. The highest level of PSA mRNA in controls was 25 copies per milliliter of blood. After RP, TURP or orchiectomy, PSA mRNA levels increased above this level in 27%, 29%, and 25% of the samples, respectively. After prostate biopsy, two out of 15 patients became positive. PSA mRNA levels that were elevated by surgery became undetectable within 1-3 days. No significant correlation was found between PCR positivity and the clinical characteristics of the patients. It is concluded that the level of PSA mRNA in peripheral blood increases after prostatic surgery, indicating temporary dissemination of prostatic cells. However, preoperative levels do not correlate with serum PSA, stage or grade.

Cell Line↗
PubMed2003

Sequential changes in pancreatic markers in acute pancreatitis.

BACKGROUND: Trypsinogen activation within acinar cells plays a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize temporal changes of trypsinogen-1, trypsinogen-2, complexes of trypsin-1-alpha1-antitrypsin (T1-AAT) and trypsin-2-alpha1-antitrypsin (T2-AAT), trypsinogen activation peptide (TAP) and pancreatic secretory trypsin inhibitor (PSTI) in patients with AP. METHODS: The study comprised 64 consecutive patients with AP (19 with severe disease) and 32 controls. The concentrations of trypsinogen-1 and -2, PSTI, T1-AAT and T2-AAT were determined by time-resolved immunofluorometric assays (IFMA), and TAP was measured using a competitive enzyme immunoassay from serum and urine. RESULTS: The concentrations of trypsinogen-1 and -2 in serum reflected similar patterns, but excretion of trypsinogen-1 into urine was markedly lower than that of trypsinogen-2, the concentration of which correlated strongly with disease severity. The concentrations of T1-AAT were no higher in severe AP than in mild AP, while T2-AAT concentrations were significantly higher in severe than in mild disease. PSTI increased over the course of several days, showing strong correlation with disease severity. The concentrations of plasma and urinary TAP decreased rapidly to undetectable levels. During the early phase of AP, TAP correlated with the disease severity in plasma and urine but there was no difference between controls and patients with mild AP. CONCLUSION: More pronounced changes in trypsinogen-2 and its complex with AAT than in those of trypsinogen-1 were demonstrated, suggesting that trypsinogen-2 might play a more important role in the pathogenesis of AP than earlier believed. Urinary PSTI showed features warranting further investigations as a marker of disease severity.

Acute Disease↗
PubMed2003

Quality assessment for prostate-specific antigen (PSA) in relation to ERSPC: report of the PSA committee.

OBJECTIVE: To assess the application of a quality control scheme for total prostate-specific antigen (PSA) as used for participants of the European Randomized Study for Screening of Prostate Cancer (ERSPC) during 1996-2002. METHODS: From 1996, the first complete year being 1997, an external scheme was organized by the Dutch Quality Assessment Foundation especially for the ERSPC. This scheme consists of one control round every 2 months with two different human serum samples and is only meant to compare the recovery of methods. From 1998 an internal scheme was also applied by adding two distinct samples to every round. RESULTS: Initially there was a wide variation (coefficient of variation of +/- 15% at threshold PSA of 4.0 ng/mL) among all ERSPC participants who were all using the Tandem assay (Hybritech Inc, USA). After introducing the internal scheme the performance of some intra-ERSPC group comparisons for PSA and the introduction of the completely automated Beckman-Access analyser in 2001 there was state-of-the-art precision for PSA of +/- 5% in the 2002 surveys. CONCLUSIONS: The ERSPC group measurements of PSA have considerably improved since 1996 because of the application of a quality-assessment scheme and with the introduction of complete automation of the PSA assay. Both findings are in line with earlier developments in clinical chemistry.

Humans↗
PubMed2003

Determination of urinary free cortisol by liquid chromatography-tandem mass spectrometry.

Measurement of urinary free cortisol is clinically important in the diagnosis of Cushing's syndrome. While liquid chromatography (LC) with UV detection provides much better specificity than immunologic methods, certain drugs cause interference. Detection by mass spectrometry (MS) is a potentially superior method. Our analysis utilizes 1 mL urine spiked with 6-alpha-methylprednisolone as internal standard. The samples were extracted with dichlormethane and the extract was washed, evaporated to dryness and analyzed by LC-MS/MS operating in the negative mode after separation on a reversed-phase C18 column. The calibration curves for analysis of urinary cortisol exhibited consistent linearity and reproducibility in the range of 10-400 nmol/L. Inter-assay CVs were 4.0-7.6%, at mean concentrations of 21-153 nmol/L. The detection limit was 1 nmol/L (signal-to-noise ratio=3). The mean recovery of cortisol added to urine ranged from 67% to 87% and that of the internal standard from 71% to 76%. The regression equation for the LC-MS/MS (x) and HPLC (y) methods was: y=1.095x+8.0 (r=0.996; n=111). Drugs known to interfere with UV detection did not cause problems here. The sensitivity and specificity of the MS/MS method for urinary free cortisol offer advantages over HPLC with UV detection by eliminating drug interference. The higher equipment costs in comparison with HPLC methods using UV detection are balanced by higher throughput, thanks to shorter chromatographic run times.

Chromatography, Liquid↗
PubMed2002

Elevated levels of trypsinogen-2 and trypsin-2-alpha1-antitrypsin in sera of infants and children after cardiac surgery.

Acute pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass but amylase is not a reliable marker in infants. We evaluated whether the serum concentrations of trypsinogen-2 and trypsin-2-alpha1-antitrypsin (AAT) can be used to study disturbances in pancreatic function in children and infants undergoing cardiac surgery. The study comprised 21 infants < 1 year and 25 children aged 1-16 years undergoing cardiopulmonary bypass at the Children's Hospital, Helsinki University Central Hospital. Consecutive serum samples were taken before surgery, at 12 h, 1, 2 and 3 days after surgery, and before discharge from the hospital. A moderate increase in trypsinogen-2 and trypsin-2-AAT in serum was found in more than two-thirds of the patients. On day 3, there was a 4.3-fold mean increase (CI 95% 2.8-6.5) in trypsinogen-2 and a 2.4-fold mean increase (CI 95% 1.8-3.1) in trypsin-2-AAT. In 4 patients trypsinogen-2 was elevated by more than 20-fold. One patient had clinical pancreatitis, but there were no clinical signs of pancreatitis in the other three patients. The changes in trypsinogen-2 and trypsin-2-AAT were similar in infants and children. The moderate increase in the serum concentrations of trypsinogen-2 and trypsin-2-AAT after cardiac surgery in the absence of signs of pancreatitis may be due to a subclinical pancreatic disturbance, but it could also be caused by an inflammatory response and expression of extrapancreatic trypsin. Contrary to amylase, trypsinogen-2 is expressed in the pancreas of infants.

Acute Disease↗
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

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation.

Proteolysis mediated by matrix metalloproteinases (MMPs) and serine proteinases is associated with cancer invasion and metastasis. Activation of latent proMMPs, and especially the proforms of the type IV collagen degrading gelatinases A and B (proMMP-2 and proMMP-9), is thought to be a critical step in this process. We have recently found that human tumour-associated trypsin-2 is a potent activator of proMMP-9 and it also activates proMMP-2 in vitro. Trypsinogen, MMP-2, and MMP-9 are expressed in ovarian cancer. To elucidate the function of trypsin in vivo, we studied whether high concentrations of trypsinogen-1, trypsinogen-2, their alpha(1)-proteinase inhibitor (API) complexes, and tumour-associated trypsin inhibitor (TATI) are associated with proMMP-2 and proMMP-9 activation in ovarian tumour cyst fluids. Zymography and immunofluorometric analysis of 61 cyst fluids showed a significant association between high trypsin concentrations and the activation of MMP-9 (P = 0.003-0.05). In contrast, the trypsin concentrations were inversely associated with the activation of MMP-2 (P = 0.01-0.02). Immunohistochemical analysis of ovarian tumour tissue demonstrated expression of trypsinogen-2 and TATI in the secretory epithelium. MMP-2 was detected both in stromal and epithelial cells whereas MMP-9 was detected in neutrophils and macrophage-like cells in stromal and epithelial areas. These results suggest that trypsin may play a role in the regulation of the MMP-dependent proteolysis associated with invasion and metastasis of ovarian cancer.

Adolescent↗
PubMed2001

Plasma prolactin and prostate cancer risk: A prospective study.

Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49-1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, IGF-I and IGF-binding protein-3. Elevated circulating levels of prolactin were not related to an increase in prostate cancer risk, indicating that high circulating prolactin is not associated with development of prostate cancer.

Adult↗