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.

Persistently elevated serum concentrations of human chorionic gonadotropin (hCG).

OBJECTIVES: We describe a woman with constantly elevated hCG levels in serum. Since assay interference, pregnancy or cancer did not explain the elevated levels, we measured the concentrations of hCG, its ß subunit (hCGß) and its core fragment (hCGßcf) in serum and urine using specific assays, to understand the nature of the elevated hCG levels. METHODS: We used 3 assays for total hCG (these assays also recognize hCGß and to various degrees hCGßcf), 3 for intact hCG heterodimer, 3 for free hCGß and one for hCGßcf. RESULTS: With an hCG assay detecting total hCG the serum concentrations were in the range of 150-260 IU/L for the whole study period of almost 5 years, except for a peak of 1,200 IU/L, coinciding with a spontaneous abortion. Quantitation of different forms of hCG with specific immunoassays showed that the immunoreactivity in serum consisted of hCGß. Urine contained hCGß and hCGßcf. CONCLUSIONS: The laboratory findings are in keeping with familial hCG syndrome. However, so far the condition remains to be determined in any family members. Elevated hCG levels without any explanation are problematic as they cause suspicion of cancer or ectopic pregnancy and may lead to harmful therapy. Specific assays, as used here, will aid in diagnosis of such cases.

Concentration of fecal calprotectin in 11,255 children aged 0-18 years.

OBJECTIVES: Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. SUBJECTS AND METHODS: To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. RESULTS: There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants < 1 year of age (95th percentile 648 mg/kg; n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. CONCLUSIONS: Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.

Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women.

PURPOSE: Pentraxin 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). METHODS: This 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). RESULTS: The 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. CONCLUSION: The 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.

Is home monitoring of inflammatory bowel disease feasible? A randomized controlled study.

Objectives: The aim of this prospective study was to evaluate the home monitoring with a rapid fecal calprotectin test combined with a symptom questionnaire in patients with colonic IBD in real-life setting. Methods: We randomized 180 patients with colonic IBD in a study or a control group. The home monitoring patients performed the fecal calprotectin test and filled in a symptom questionnaire every second month and in cases with increasing symptoms. The control patients filled in the symptom questionnaire at baseline and at 6 and 12 months as well as for the appointment at the outpatient clinic. The study duration was 12 months. Results: The patient adherence to the self-monitoring program was low. Patients with a higher disease burden were more adherent than patients with better health-related quality of life, but otherwise, there were no significant factors predicting the adherence. The home monitoring patients had fewer contacts with the outpatient clinic, but otherwise, the disease course between the home monitoring and the control group were similar. Conclusions: The self-monitoring of IBD activity with a combination of a rapid fecal calprotectin home test and a symptom questionnaire provides an option for individualized care for IBD patients. However, adherence to the self-monitoring program remains a challenge.

Premature ovarian insufficiency and early depletion of the ovarian reserve in the monogenic Mulibrey nanism disorder.

STUDY QUESTION: What is the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gene? SUMMARY ANSWER: The number of ovarian follicles is highly reduced already in infant and young MUL girls and the majority of them will have early depletion of follicles resulting in clinical and biochemical signs of POI. WHAT IS KNOWN ALREADY: Both female and male patients with MUL show failure of sexual maturation, signs of hypogonadism and infertility. STUDY DESIGN, SIZE, DURATION: We studied the gonadal function, pubertal development and ovarian reserve in 33 MUL patients aged 5.1-47.3 years (median age 22.3) at the end of observation. The patients were followed between 2004 and 2014 and 19 pubertal or postpubertal patients were enrolled in a cross-sectional study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The period of postnatal activation of the hypothalamic-pituitary-gonadal axis (minipuberty), pubertal development and menstrual history were assessed longitudinally. The cross-sectional study included gynecological examination, analysis of reproductive hormones and ultrasonography with evaluation of ovarian volume and antral follicle count. MAIN RESULTS AND THE ROLE OF CHANCE: Infant girls experienced a transient minipuberty with a high FSH surge. In childhood, gonadotropins were normal or slightly elevated but began to rise to hypergonadotropic levels in prepuberty. Anti-Müllerian hormone (AMH) levels remained undetectable or low throughout childhood. The onset of puberty occurred spontaneously and the median age at menarche was 12.5 years. Of the patients, 54% never attained regular menses and 10 years from menarche, only 8% of the women menstruated regularly. In the cross-sectional study, none of the patients had normal ovarian morphology under ultrasonography. Ovaries were hypoplastic and 82% had no or fewer than two visible antral follicles. AMH levels were undetectable in the vast majority (89%). LIMITATIONS, REASONS FOR CAUTION: The Finnish MUL patients genotypically form a homogenous group and therefore it is possible, that different TRIM37 mutations lead to different hypogonadal phenotypes. However, to date there is no known genotype-phenotype correlation in MUL. WIDER IMPLICATIONS OF THE FINDINGS: In MUL, AMH is a useful marker of ovarian function. MUL should be added to the list of syndromes associated with POI and correspondingly, TRIM37 should be added to the list of genes associated with POI. To our knowledge, TRIM37 is the first known gene coding for a peroxisomal membrane protein associated with female gonadal failure and infertility. Elucidating the role of syndromic genes in reproduction may aid in a greater understanding of ovarian biology. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Finnish Foundation for Pediatric Research, Finska Läkaresällskapet, the Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Fecal Calprotectin Test Performed at Home: A Prospective Study of Pediatric Patients With Inflammatory Bowel Disease.

OBJECTIVES: Measuring fecal calprotectin (FC) in a laboratory is time-consuming and that is why home tests have been developed. We studied the use of an FC home test in pediatric patients with inflammatory bowel disease (PIBD) in real-life settings. METHODS: The patients were asked to perform the IBDoc FC home test monthly for 6 months and to report their clinical disease activity at testing. Clinical decision-making, however, was guided by routine FC enzyme-linked immunosorbent assay (ELISA) for patients with raised IBDoc values. Spare frozen samples were analyzed using ELISA and IBDoc in the laboratory. The participants completed a questionnaire about FC testing at the start and end of the study. RESULTS: Of the 52 patients, 35 (67%) ages 5 to 18 years completed the study, and 197 home tests were performed. Of these, 15% failed, mainly because of technical reasons. Just under half of the patients (47%) considered home testing comparable or superior to routine testing. In contrast, the parents were unsatisfied (61%), mostly because the IBDoc results were significantly different from ELISA and they found the phone application difficult to handle but whenever the IBDoc was performed by a laboratory professional it was comparable with ELISA, suggesting that practical issues hampered home testing. Despite their reservations, more than 80% of parents felt that home testing would improve disease management. CONCLUSIONS: PIBD patients and their families were interested in FC home monitoring and willing to adopt testing as a part of their disease management, but this approach requires thorough guidance.

Saliva and serum biomarkers in periodontitis and coronary artery disease.

AIM: Matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS). MATERIALS AND METHODS: The population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non-periodontitis, and ACS versus non-ACS patients were compared. RESULTS: Saliva MMP-8, MMP-9 and MPO provided significant area-under-curve (AUC) values for periodontitis, 0.69 (<0.001), 0.66 (<0.001) and 0.68 (<0.001), respectively. Serum MMP-8, MMP-9 and MPO levels distinguished ACS from non-ACS patients with AUCs of 0.73 (<0.001), 0.58 (0.03) and 0.68 (<0.001), respectively. Periodontitis confounded the use of serum MMP-9 in diagnostics of ACS. Cardiac status complicated the use of saliva TIMP-1 in periodontal diagnostics. Saliva biomarkers could not be used in ACS diagnosis, and serum biomarkers were not useful in diagnosis of periodontitis. CONCLUSIONS: MMP-8, MMP-9, TIMP-1and MPO are valuable biomarkers for both ACS and periodontitis, but the selection of sample material is crucial; serum is suitable for ACS and saliva for periodontal diagnostic aid.

Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors.

OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs). METHODS: The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared. RESULTS: HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT. CONCLUSIONS: HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.

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.

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.

Rapid faecal tests for detecting disease activity in colonic inflammatory bowel disease.

BACKGROUND: Increasing numbers of patients with inflammatory bowel disease (IBD) have raised the need for a rapid noninvasive means to monitor disease activity. We validated two rapid tests for faecal calprotectin and one for faecal lactoferrin and compared them to the most common clinical and endoscopic scores, enzyme-linked immunosorbent assay (ELISA) calprotectin test and systemic inflammation markers. MATERIALS AND METHODS: The clinical and endoscopic disease activity of 72 patients with colonic IBD, who underwent ileocolonoscopy, was determined. The patients provided stool samples to measure calprotectin and lactoferrin, and blood samples to measure systemic inflammation markers. RESULTS: Rapid calprotectin tests correlated significantly with clinical and endoscopic indices and standard ELISA calprotectin in ulcerative colitis, but not in Crohn's disease. CalDetect correlated more closely with ELISA calprotectin than CerTest FC in concentrations exceeding 200 µg/g. CalDetect was also more sensitive in indicating histological remission or mild disease than was CerTest FC at cut-off of 200 µg/g. CerTest Lactoferrin was comparable to CalDetect in their correlation with clinical, endoscopic and histological scores. CONCLUSIONS: These rapid tests are suitable for identifying patients with inactive or mildly active disease, but as semiquantitative or qualitative tests, they cannot totally replace ELISA calprotectin in decision-making related to therapy.

The risk of adverse pregnancy outcome among pregnancies with extremely low maternal PAPP-A.

OBJECTIVE: The aim of the study was to analyze the risk of adverse pregnancy outcome in three subgroups with extremely low maternal pregnancy-associated plasma protein-A (PAPP-A), that is, <0.3 multiples of median (MoM) at the first trimester screening. METHOD: A cohort of 961 pregnancies with PAPP-A levels < 0.3 MoM at the first trimester combined screening was followed up during the study period of January 2009 to December 2012. The incidences of adverse outcomes was determined in three subgroups with PAPP-A levels < 0.1 MoM, 0.1 to 0.2 MoM, and 0.2 to 0.3 MoM, respectively. RESULTS: The risks of aneuploidy and spontaneous abortion increased with decreasing PAPP-A levels (p < 0.001), but no difference was detected in the rate of structural anomalies among the three groups. Rates of preterm delivery (p < 0.001) and birth weight < 2 standard deviation below the mean (p < 0.001) increased with decreasing PAPP-A levels. The rates of preeclampsia, stillbirth, and cesarean delivery were not significantly different across the three subgroups. CONCLUSION: The risks of aneuploidy, spontaneous abortion, preterm delivery, and small for gestational age newborn increased with decreasing PAPP-A. © 2016 John Wiley & Sons, Ltd.

The clinical utility of serum anti-Müllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors--A comparative study with inhibin B.

Ovarian adult-type granulosa cell tumors (AGCTs) require prolonged follow-up, but evidence regarding the optimal follow-up marker is lacking. The objective of our study was to validate the clinical usefulness of serum anti-Müllerian hormone (AMH) and the current marker inhibin B as single and combined markers of AGCTs. We conducted a longitudinal, partially prospective cohort study of 123 premenopausal and postmenopausal AGCT patients with a median follow-up time of 10.5 years (range 0.3-50.0 years). Serum AMH and inhibin B levels were measured from 560 pretreatment and follow-up serum samples by using immunoenzymometric assays. We found that serum AMH and inhibin B levels were significantly elevated in patients with primary or recurrent AGCTs. The levels of both markers positively correlated to tumor size (p < 0.05). AMH and inhibin B performed similarly in receiving operator characteristic analyses; area under the curve (AUC) values were 0.92 [95% confidence interval (CI) 0.88-0.95] for AMH, and 0.94 (95% CI 0.90-0.96) for inhibin B. AMH was highly sensitive (92%) and specific (81%) in detecting a macroscopic AGCT. However, in AUC comparison analyses, the combination of the markers was superior to inhibin B alone. In conclusion, serum AMH is a sensitive and specific marker of AGCT, and either AMH or inhibin B can be monitored during follow-up. However, combining AMH and inhibin B in AGCT patient follow-up improves the detection of recurrent disease.

Hyperglycosylated human chorionic gonadotropin in serum of testicular cancer patients.

BACKGROUND: 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. METHODS: We determined the serum concentrations of hCG-h, hCG, and the free ß subunit of hCG (hCGß) 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 hCGß with known prognostic factors and progression-free survival time. RESULTS: 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 hCGß concentration predicted shorter progression-free survival. CONCLUSIONS: 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.

Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn's disease detected by wireless capsule endoscopy.

OBJECTIVE: Data on fecal calprotectin and S100A12 in predicting wireless capsule endoscopy (WCE) findings in suspicion of Crohn's disease (CD) are scarce. Our aim was to study the role of calprotectin and S100A12 in predicting inflammatory lesions of small bowel in patients undergoing WCE. MATERIAL AND METHODS: 84 patients undergoing WCE (77 for suspicion of CD and 7 CD patients for evaluation of disease extent) were prospectively recruited. WCE findings were scored. Patients provided a stool sample for measurements of biomarkers. Patients underwent an esophagogastroduodenoscopy and ileocolonoscopy before WCE. RESULTS: WCE was abnormal in 35 (42%) of 84 patients: 14 patients with CD, 8 with NSAID enteropathies, 8 with angioectasias, 4 with polyps or tumors, and 1 with ischemic stricture. Median calprotectin concentration in the study population was 22 µg/g (range 2-342) and S100A12 concentration 0.048 µg/g (range 0.003-1.215). Fecal calprotectin was significantly higher in CD patients (median 91, range 2-312) compared with those with normal WCE or other abnormalities (p = 0.008), whereas fecal S100A12 (0.087 µg/g, range 0.008-0.896) did not differ between the groups (p = 0.166). In detecting inflammatory small bowel lesions, sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin (cutoff 50 µg/g) were 59%, 71%, 42%, and 83%, and for S100A12 (cutoff 0.06 µg/g) these were 59%, 66%, 38%, and 82%. CONCLUSIONS: In predicting small bowel inflammatory changes, fecal biomarkers calprotectin and S100A12 have moderate specificity, but low sensitivity. Neither fecal calprotectin nor S100A12 can be used for screening or excluding small bowel CD.

Effect of bowel cleansing for colonoscopy on fecal calprotectin levels in pediatric patients.

The recent development of easily applicable fecal surrogate markers of intestinal inflammation, such as fecal calprotectin (FC), has provided a new means for objectively assessing disease activity in patients with chronic inflammatory bowel disease. Because the use of these markers is about to emerge, it is important to be aware of the possible limitations of measurements. We assessed levels of FC during bowel cleansing. In patients with high FC levels at baseline, the values measured during bowel cleansing varied considerably, remaining high or even returning to normal. Thus, stool sampling for FC assessment is not recommended during bowel preparation for colonoscopy.

Erythropoietin is detectable in the ascitic fluid in patients with ovarian tumors.

BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is a glycoprotein that stimulates proliferation and migration of human endothelial cells and promotes angiogenesis, which are crucial phenomena in cancer biology. The objective of this study was to investigate whether Epo is detectable in the ascitic fluid of patients with ovarian tumors. PATIENTS AND METHODS: We investigated the presence of Epo in the ascitic fluid of 100 women undergoing laparotomy for an ovarian tumor. Epo concentration was quantitated with an immunochemiluminometric assay. RESULTS: Ten women had a benign tumor, 13 women had a borderline tumor, and 77 women had ovarian cancer. Epo was detected in all ascitic fluid samples, in similar amounts as in corresponding serum samples. Ascitic fluid Epo concentration did not differ between the 3 study groups (P = 0.081), but in multiple comparisons, ascitic fluid Epo was higher in the women with cancer than in the women with a benign tumor (P = 0.006). Ascitic fluid Epo concentration correlated positively with serum Epo (P < 0.0001) and the volume of ascites (P < 0.0001). In regression analyses, serum Epo, volume of ascites, blood hemoglobin, plasma CA125, tumor stage, tumor grade, and the presence of residual tumor after surgery had no significant independent effect on ascitic fluid Epo. CONCLUSION: Considerable amounts of Epo are present in the ascitic fluid of women with ovarian tumors. The origin of Epo in the ascitic fluid of women with ovarian tumors as well as the clinical relevance of our finding remain to be clarified.

Identification of the LH surge by measuring intact and total immunoreactivity in urine for prediction of ovulation time.

OBJECTIVES: In our earlier study, we separated three different molecular forms of urinary LH-ir (U-LH-ir) by gel filtration and identified them by immunoassay in urine from regularly menstruating women on periovulatory days. U-LH-ir is composed of intact luteinizing hormone (LH), its free beta-subunit (LHß), and the core fragment of LHß (LHßcf), the latter two establishing the non-intact portion of LH-ir. The aim was to determine whether timing of ovulation can be improved by detecting different molecular forms of U-LH-ir in women of reproductive age. METHODS: We determined intact and total U-LH-ir in 14 regularly menstruating women on consecutive periovulatory days during the menstrual cycle. Non-intact LH-ir was calculated as the arithmetic difference between total and intact LH-ir. In addition, LH-ir was determined in both serum and urine from four of the women throughout the menstrual cycle. RESULTS: During the LH surge, U-LH-ir consisted mainly of intact LH and presented with an abrupt increase. Intact U-LH-ir dropped rapidly within 1 day after the surge, reaching baseline levels at the end of the luteal phase. In contrast, LHßcf in urine increased further 1 day after the surge. After this, most of the U-LH-ir consisted of LHßcf and it remained strongly elevated (over fivefold compared to intact LH) for the first 3 days after the LH surge, moderately elevated (over threefold) thereafter until day + 5, and mildly elevated until day + 7. CONCLUSIONS: Total and non-intact LH-ir are potential add-on characteristics which can be utilized in ovulation predictor kits to measure LH-ir in urine beyond the LH surge during a broader time frame, thereby paving the way for more precise prediction of the timing of ovulation than that obtained with currently available products.

Intact luteinizing hormone (LH), LHß, and LHß core fragment in urine of menstruating women.

OBJECTIVES: We examined different molecular forms of luteinizing hormone (LH) in urine samples taken during periovulatory days with the aim of revealing different forms of LH immunoreactivity (LH-ir) in normally menstruating women. METHODS: Serum and first-morning-voided urine serum samples were obtained from six healthy, 22 to 38 years old, regularly menstruating women during their periovulatory days based on their previous menstrual cycles. The day of the LH surge was determined on the basis of serum LH concentrations and confirmed by an at least two-fold increase in urinary concentrations of intact LH on consecutive days. Different molecular forms of LH-ir were identified by gel filtration of first-morning-voided urine samples obtained from regularly menstruating women on periovulatory days. RESULTS: Different forms of LH immunoreactivity (LH-ir) were distinguished as intact LH, its free beta-subunit (LHß), and the core fragment of LHß (LHßcf) according to their molecular sizes. The latter two are also called non-intact LH. Intact LH was the dominating form on the day before and on the day of LH surge while LHßcf was the major form of LH immunoreactivity after the LH surge for the following 5-7 days. LHß was detected on the day of the LH surge as well as on the following day. CONCLUSIONS: These results indicate that LH is degraded in the kidneys and excreted as LHß, and mainly as LHßcf for 7 days following the LH peak.