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26 result(s) for "Alfthan, Henrik"
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Serum erythropoietin level is increased during stimulation for IVF but not in OHSS
Background Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS). Methods 24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo. Results During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2–13.4 IU/L and 12.5; 10.3–13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4–19.2 IU/L vs. 10.2; 8.8–12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1. Conclusions Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo’s involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.
Rapid Fecal Calprotectin Test and Symptom Index in Monitoring the Disease Activity in Colonic Inflammatory Bowel Disease
Background Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD). Aims For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn’s disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity. Methods The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week. Results The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone. Conclusion The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission.
Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women
PurposePentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF).MethodsThis two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC).ResultsThe circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15–20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level.ConclusionThe elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.
Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients
Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer. We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time. A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival. Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.
Negative Interference in Cardiac Troponin I Immunoassays from a Frequently Occurring Serum and Plasma Component
Background: Cardiac troponin I (cTnI) is a sensitive marker of cardiac injury, but cTnI assays, like other immunoassays, are susceptible to interferences. We evaluated the presence of interfering substances by measuring the recovery of cTnI added to samples from volunteers and from patients with acute coronary syndromes (ACS). Methods: We added a ternary complex of human cardiac troponin (30–500 μg/L) or cTnI from serum to samples from healthy volunteers and ACS patients. We measured cTnI with a two-site sandwich time-resolved immunofluorometric assay using two antibodies against epitopes in the central stable part of cTnI. We also analyzed 108 heparin-plasma samples from 16 ACS patients with this assay, with an assay based on four antibodies, and with two commercial cTnI assays, AxSYM and ACS:180. Results: In samples from both healthy persons and ACS patients, recoveries for our assay were 1–167% (range). Recoveries were increased by addition of an antibody with an epitope in the N-terminal region of cTnI to the solid phase and an antibody with an epitope in the C-terminal region as a second detection antibody. In 2 of 16 patients with ACS, normal cTnI concentrations found when measured with the original assay demonstrated clinically abnormal (up to 10-fold higher) results with the additional N- and C-terminal antibodies in the early phase of infarction. Both commercial cTnI assays also demonstrated clinically misleading, falsely low cTnI concentrations. Conclusions: Some yet unidentified, variable component, present in the blood from healthy volunteers and ACS patients, interferes with the binding of antibodies against epitopes in the central part of cTnI used in two commercial assays. Our approach to supplement the mid-fragment cTnI antibodies with antibodies in the N- and C-terminal parts of the molecule in an experimental assay represents a step in resolving this interferent.
Increased Human Chorionic Gonadotropin Due to Hypogonadism after Treatment of a Testicular Seminoma
The pituitary is a source of hCG, and low serum concentrations can be detected with sensitive assays in most healthy men and women (2,3). hCG concentrations increase with age, and with our assay values up to 10 IU/L can be observed in postmenopausal women (2). Testicular cancer and its treatment, particularly cytotoxic chemotherapy, may cause gonadal suppression leading to hypogonadism, which is mostly transient (4) and may lead to increased serum concentrations of LH and FSH, which normalize with testosterone replacement therapy (1), Increased hCG immunoreactivity after treatment of testicular cancer has been described previously but was ascribed to crossreaction of LH in the hCG assay rather than to hCG itself (1 ).
Exercise and gastrointestinal symptoms: running-induced changes in intestinal permeability and markers of gastrointestinal function in asymptomatic and symptomatic runners
Purpose Athletes frequently experience gastrointestinal (GI) symptoms during training and competition. Although the prevalence of exercise-induced GI symptoms is high, the mechanisms leading to GI distress during exercise are not fully understood. The aim of this study was to identify running-induced changes in intestinal permeability and markers of GI function and investigate their association with gastrointestinal symptoms. Methods We recruited 17 active runners who we allocated as either asymptomatic or symptomatic based on their history of experiencing GI symptoms during running. The participants took part in a running test where they were asked to run for 90 min at 80% of their best 10 km race speed. Intestinal permeability was measured at baseline and after the running test. Levels of serum intestinal fatty acid-binding protein (I-FABP), zonulin, bacterial lipopolysaccharide (LPS), and fecal calprotectin were also measured at baseline and after the running test. Results Running induced a significant increase in intestinal permeability and serum I-FABP concentration but there were no differences between asymptomatic and symptomatic runners. Serum LPS activity did not change from baseline following the running test but the symptomatic group exhibited higher LPS activity at baseline compared to the asymptomatic runners. Conclusions Running for 90 min at a challenging pace causes small intestinal damage and increases intestinal permeability. However, these alterations in GI function do not appear to correlate with the development of GI symptoms during running.
Comparative Analysis of Commercial Immunoassays for the Determination of Total, Intact, and Nonintact Luteinizing Hormone in Urine
Background In our recent publications, we reported the identification of three different molecular forms of total luteinizing hormone (LH) in urine, the intact LH, the free beta‐subunit (LHβ), and its core fragment of LHβ (LHβcf), the latter two establishing the nonintact portion of LH. Following the discontinuation of the Delfia immunofluorometric assay (IFMA) (Wallac, PerkinElmer Finland, Finland), a leading method for detecting urinary LH for 30 years, this study seeks to assess the efficacy of three alternative commercial immunoassays in identifying various forms of U‐LH. Methods Diluted urine samples underwent gel filtration to separate them into fractions, each containing different forms of LH. These were then assayed using Delfia IFMA, Architect LH (Abbott, USA), Elecsys LH Cobas (Roche, Switzerland), and Immulite 2000 LH (Siemens, Germany) immunoassays. Results Both Delfia and Immulite assays detected total U‐LH, that is, all three forms of U‐LH, including intact LH, LHβ, and LHβcf. Cobas detected only intact LH and LHβ, whereas Architect detected solely the intact LH. Conclusions Immulite assay can be an alternative tool to detect all forms of urinary LH, a feature likely to be instrumental in developing noninvasive, practical, and scalable solutions for evaluating total U‐LH changes during minipuberty in neonates, during the onset of central puberty in peripubertal children, puberty‐associated disorders in adolescents, and the fertility window in women, with a special focus on postpeak changes. In our study, we evaluated alternative assays to replace a discontinued method for detecting all forms of urinary LH, including its degradation products. By analyzing LH in gel‐filtrated urine samples, we assessed the comprehensive detection capabilities of various diagnostic tests. Our novel findings revealed diverse fields of utility for different assays, offering a nuanced understanding of their specific clinical applications as choosing the correct assay with an informed decision would facilitate enhanced clinical practice in investigating minipuberty in neonates, the onset of central puberty in peripubertal children, puberty‐associated disorders in adolescents, and the fertility window in women, with a particular emphasis on postpeak changes.
Elimination of Complement Interference in Immunoassay of Hyperglycosylated Human Chorionic Gonadotropin
Hyperglycosylated human chorionic gonadotropin (hCG-h)1 is the major form of hCG occurring in early pregnancy and trophoblastic disease, whereas the glycans are smaller in hCG produced later in pregnancy (1, 2 ). hCG-h can be measured by immunoassays based on monoclonal antibody B152, which reacts with a type 2 core O-glycan attached to Ser132 and surrounding peptide structures but not with hCG lacking this glycan or having a type 1 core O-glycan in this position (3 ). The sandwich immunoassay for hCG-h was performed via a 2-step incubation protocol in 96- well plates, essentially as previously described, but we used monoclonal antibody B152 (3 ) as the capture antibody, and as the tracer, we used a Eu chelate-labeled in-house monoclonal antibody (1B2) to the β subunit of hCG (hCGβ). hCG-h produced by cultured JEG-3 choriocarcinoma cells was used as the calibrator.
Second-Trimester Placental and Thyroid Hormones Are Associated With Cognitive Development From Ages 1 to 3 Years
Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free α- [hCGα] and β-subunits [hCGβ]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCGα was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCGα, hCGβ, and hCG-h in relation to TH regulation and child brain function.