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Biomedical subjects

Johan Schiettecatte

Publications and source records attributed to Johan Schiettecatte.

15 recordsLinked to original sources

Spuriously elevated serum estradiol concentrations measured by an automated immunoassay rarely cause unnecessary cancellation of in vitro fertilization cycles.

OBJECTIVE: To report a case of a patient in whom serum E2, as measured by an automated E2 assay, remained elevated at levels corresponding to the periovulatory phase (>380 pg/mL), despite 3 weeks of treatment by a GnRH agonist (GnRH-a). DESIGN: Case report. SETTING: Tertiary-care academic center. PATIENT(S): A 39-year-old patient accepted for IVF treatment. In view of controlled ovarian hyperstimulation, down-regulation by a GnRH-a was monitored by serum E2 measurement. INTERVENTION(S): Obvious causes for high serum E2 levels (pregnancy, E2-producing ovarian cysts, and noncompliance of the patient) were excluded. The IVF cycle was canceled. MAIN OUTCOME MEASURE(S): Serum samples were analyzed retrospectively by radioimmunoassay (RIA), and ether extraction of the samples was performed before measurement by the automated E2 assay. RESULT(S): Radioimmunoassay revealed adequately suppressed serum E2 levels under GnRH-a treatment (<15 pg/mL). Ether extraction revealed an interfering component that was soluble in the aqueous phase. CONCLUSION(S): If a patient on a long controlled ovarian hyperstimulation IVF protocol still has high serum E2 levels after 2 to 3 weeks of down-regulation, and obvious reasons for this (pregnancy, E2 producing ovarian cysts, noncompliance of the patient) are excluded, E2 immunoassay interference should be excluded to avoid unnecessary cancellation of the IVF cycle.

Adult↗

Elevated serum levels of S-100beta protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock.

OBJECTIVE: We investigated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. DESIGN: Prospective study. SETTING: University hospital. PATIENTS AND MEASUREMENTS: In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100beta and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. MAIN RESULTS: S-100beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p = .001), and the highest values were found in patients who died early, within 4 days of inclusion (p = .005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100beta (p = .004). S-100beta levels of >or=4 microg/L were associated with severe brain ischemia or hemorrhage, and values of <2 microg/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100beta levels were associated with higher intensive care unit mortality (p = .04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. CONCLUSIONS: S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.

Adolescent↗

Rheumatoid factor interference in the determination of carbohydrate antigen 19-9 (CA 19-9).

BACKGROUND: Investigation of a 61-year-old Caucasian male suffering from fatigue and weight loss led to the finding of a carbohydrate antigen 19-9 (CA 19-9) concentration of 80 kU/L using an ADVIA Centaur analyser. Determination of CA 19-9 on Vidas, AxSYM and Architect i2000 systems gave normal results. His rheumatoid factor concentration was very high (900 kIU/L) and assay interference was suspected. METHODS: Besides using several laboratory procedures to show the cause of the interference, we tried to estimate the frequency of the suspected interference. Therefore, two studies were performed. The first was carried out in a multicentre setting using four different CA 19-9 methods on 51 randomly selected samples with high rheumatoid factor concentrations and ten samples containing no or very low rheumatoid factor. In the second study we used heterophilic blocking tubes for 68 routinely analysed samples with CA 19-9 concentrations ranging between 37 and 250 kU/L using an ADVIA Centaur analyser. RESULTS: In the multicentre study we found eight discrepant CA 19-9 results, but only one was clearly due to interference. We showed that the interference detected, just as in the index case, was caused by rheumatoid factor. The other discrepancies could not be explained, but are probably related to method-dependent differences. In the 68 routinely analysed samples, no interference could be shown using the heterophilic blocking tubes. CONCLUSIONS: Although interferences in the CA 19-9 assay are not frequent, the ADVIA Centaur system appears to be more sensitive to rheumatoid factor interference. The lack of standardisation remains an important issue for this assay. The determination of CA 19-9 during the follow-up of patients should be performed using a single method. If, however, there is any clinical doubt about a result, CA 19-9 should be determined using another method to exclude possible interferences.

Artifacts↗

Thyroid function after assisted reproductive technology in women free of thyroid disease.

OBJECTIVE: To evaluate thyroid function in women undergoing a first assisted reproductive technology (ART) procedure and to compare women with ongoing pregnancy or miscarriage. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENT(S): Seventy-seven women free of thyroid disease. INTERVENTION(S): Serum TSH and FT4 were determined before and 2, 4, and 6 weeks after ET. All women received the same ART protocol. MAIN OUTCOME MEASURE(S): Thyroid function. RESULT(S): Forty-five women had ongoing pregnancies, and 32 suffered a miscarriage after 6.7 weeks (range 5-11). Mean age and number of ET were similar in both groups. Compared with baseline values, TSH and FT4 increased significantly 2 weeks after ET (ongoing pregnancies group: TSH 2.5 +/- 1.3 vs. 1.6 +/- 0.8 mU/L and FT4 13.8 +/- 1.4 vs. 12.4 +/- 1.8 ng/L; miscarriage group: TSH 2.1 +/- 1.0 vs. 1.5 +/- 0.7 mU/L and FT4 14.2 +/- 2.0 vs. 12.4 +/- 1.9 ng/L). Pregnancy outcome did not affect thyroid function and its evolution over time. CONCLUSION(S): In women free of thyroid diseases, thyroid function changed significantly after ART, but these changes were not different between women with ongoing pregnancy and miscarriage.

Abortion, Spontaneous↗

Serum hormones for predicting pregnancy outcome after assisted reproductive technology.

Serum human chorionic gonadotrophin (HCG) in the second and third week after embryo transfer has been used for prediction of pregnancy outcome after assisted reproduction. There are few data on the clinical utility of HCG, progesterone and oestradiol, measured by contemporary immunoassay, in the fourth week after embryo transfer and later. Moreover, large inter-method differences have been described between automated immunoassays, making method-specific cut-off values mandatory. The main aim of this study was to determine assay-specific optimal cut-off values for serum HCG, progesterone and oestradiol for prediction of clinical pregnancy outcome in singleton pregnancies after assisted reproductive techniques, at days 11, 18 and 25 and at week 6 after embryo transfer. A retrospective study was performed on frozen serum samples of 67 singleton pregnancies after assisted reproduction techniques. HCG, oestradiol and progesterone were determined with the automated (random access) VIDAS immunoanalyser. Receiver operating characteristic curve analysis was performed to determine optimal cut-off values. Predictive values were calculated based on the prevalence of non-viable pregnancy after assisted reproduction. It was concluded that measurement of HCG by VIDAS at days 18 and 25, and at week 6 after embryo transfer yields high positive (70.5-100%) and negative (87.2-94.4%) predictive values for clinical pregnancy outcome.

Chorionic Gonadotropin↗

Evaluation of a new automated electrochemiluminescent sex hormone-binding globulin (SHBG) immunoassay.

Serum sex hormone-binding globulin (SHBG) regulates the cellular bioavailability of SHBG-bound steroid hormones. Since variations in SHBG levels may affect the concentration of free, i.e., biologically active testosterone in serum, SHBG levels are commonly measured as a supplement to total testosterone determination. The recently developed electrochemiluminescence Elecsys SHBG immunoassay was evaluated analytically on a Modular E170 (Roche Diagnostics, Mannheim, Germany) immunoanalyzer. Major differences in SHBG concentrations have been described among the commercially available methods; we therefore compared the new method with an established SHBG immunoradiometric assay (IRMA) in 99 routine serum samples. To provide reference values to clinicians, SHBG concentration was measured by Elecsys in 304 serum samples from healthy volunteers and several relevant clinical subgroups. The within-run and total imprecision coefficients of variation were </=2.9% and </=3.3%, respectively. Functional sensitivity was at least 0.74 nmol/L. Recoveries after dilution of high-concentration samples in low-titer human serum or in assay diluent were within the range of 85-110%. The Elecsys SHBG assay correlated well (r=0.98) with the SHBG immunoradiometric assay, but values were higher for the Elecsys assay (Passing Bablok regression analysis: slope 1.14, intercept +2.5). In healthy subjects and clinical subgroups, we confirmed the differences in SHBG values reported in the literature. The Elecsys SHBG immunoassay provides precision and reliability in combination with reduced turnaround time.

Contraceptives, Oral, Hormonal↗

Impact of ovarian hyperstimulation on thyroid function in women with and without thyroid autoimmunity.

Pregnancy is accompanied by changes in thyroid function, but limited data are available on these changes in the very first weeks of pregnancy. Yet, T(4) plays a major role in implantation and early fetal development. We sought to determine thyroid function during this period and during the first trimester, in pregnancies achieved by assisted reproductive technology. Furthermore, the thyroid hormone profile was compared between euthyroid women with (TAI+) and without (TAI-) thyroid autoimmunity. We prospectively analyzed data from 35 women who received ovarian hyperstimulation (OH) and presented clinical pregnancies. The mean age of the women was 32 +/- 5 yr. Thyroid function tests [serum TSH and free T(4) (FT(4))] and thyroid antibody status were determined before OH (baseline values) and every 20 d after ovulation induction during the first trimester of pregnancy. Serum TSH and FT(4) increased significantly at d 20, compared with baseline values (3.3 +/- 2.4 vs. 1.8 +/- 0.9 mU/liter; P < 0.0001 and 13.2 +/- 1.7 vs. 12.4 +/- 1.9 ng/liter; P = 0.005). During the first trimester of pregnancy, there was a significant change over time for TSH and FT(4) (P < 0.001 and P = 0.005, respectively). Nine women (27%) were TAI+. The TSH curve among these TAI+ women was significantly higher compared with TAI- women (P = 0.010). The opposite was observed for the FT(4) curve (P = 0.020). In conclusion, the present study showed a significant increase of serum TSH and FT(4) levels after OH in the very first period of pregnancy compared with pre-OH levels and a significant impact of TAI on the thyroid hormone profile during the first trimester. This provides evidence for an altered thyroid function in euthyroid TAI+ patients.

Adult↗

Multicentre performance evaluation of the E170 module for modular analytics.

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 microg/l, total prostate-specific antigen (PSA) 0.03 microg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel 'hands-on-time' could be reduced.

Calibration↗

Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes.

OBJECTIVE: Macroprolactinemia, which can be detected by a polyethylene glycol (PEG) precipitation test, is a clinically and biologically heterogeneous condition. In this study, we analyzed whether the clinical presentation, the hormonal findings and the in vitro lactogenic activity differed between macroprolactinemic patients with and without circulating prolactin (PRL)-IgG complexes. DESIGN: Clinical data were reviewed and additional hormonal studies were performed in 50 hyperprolactinemic patients with macroprolactinemia. METHODS: Macroprolactinemia was identified by a PRL recovery after PEG precipitation of <50%, as measured by an automated commercial immunoassay system and circulating PRL-IgG complexes by an abnormal PRL binding to anti-IgG agarose. RESULTS: PRL-IgG complexes were found in 46 patients. The origin of hyperprolactinemia in these 46 patients was idiopathic in 33 patients, while a pituitary lesion or stalk magnetic resonance imaging or computed tomography scan was detected in 13 patients found compression. Galactorrhea was found in 11 of these 46 patients, while this condition was present in three of the four patients without circulating PRL-IgG complexes. The median free PRL concentration was significantly lower in patients with PRL-IgG complexes than in the group without complexes (243 vs 969 mIU/l; P<0.005), whereas median total PRL immunoreactivity and median PRL bioactivity in the Nb2 assay were not significantly different. In patients with circulating PRL-IgG complexes, Nb2 bioassay results correlated significantly with total PRL immunoreactivity (r=0.64; P<0.0001), but not with free PRL results (r=0.24; P<0.17). CONCLUSIONS: These results indicate that PRL-IgG complexes (i) account for most cases of macroprolactinemia--as identified by PEG precipitation--in hyperprolactinemic patients presenting with a variety of diagnoses, (ii) are not associated with a specific clinical presentation, (iii) can be found in patients with diverse pituitary pathologies, and (iv) possess an in vitro lactogenic activity in the Nb2 bioassay in relation to their immunoreactivity.

Adolescent↗

Circulating anti-prolactin auto-antibodies must be considered in the differential diagnosis of hyperprolactinaemia in adolescents.

UNLABELLED: In four adolescents (two girls and two boys), who were investigated for galactorrhoea or short stature, we found moderately elevated serum prolactin (PRL) levels, but without a decreased gonadotropin and sex hormone production. Serum PRL levels were not responding to the intravenous injection of thyrotropin releasing hormone. Magnetic resonance imaging of the hypothalamic-pituitary region revealed no abnormality. Initial diagnoses were idiopathic and drug-induced hyperprolactinaemia. The presence of anti-prolactin auto-antibodies was suspected because of low recovery of PRL after precipitation with polyethylene glycol and confirmed by immunoprecipitation with anti-human IgG-agarose. CONCLUSION: anti-prolactin auto-antibodies causing high prolactin values in some immunoassays can cause hyperprolactinaemia in adolescents without other signs of hormonal disturbances or auto-immune disease.

Adolescent↗

S-100 protein as early predictor of regaining consciousness after out of hospital cardiac arrest.

BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest (CA) have a high mortality rate. Prognostic evaluation based on clinical observations is uncertain and would benefit from the use of biochemical markers of hypoxic brain damage. The purpose of the study was to validate the use of the serum astroglial protein S-100 levels at admission with regard to regaining consciousness after out of hospital CA. METHODS: Fifty-eight patients resuscitated from out-of-hospital CA were followed up until they regained consciousness or until their death or permanent vegetative state occurred. Serum samples for measurement of S-100, using an immunoradiometric assay, were obtained at admission. RESULTS: At admission, the mean value+/-standard error of the mean of serum S-100 protein was significantly higher in patients who did not regain consciousness compared with patients who regained consciousness, respectively 4.66+/-0.61 microg/l and 0.84+/-0.21 microg/l. A serum S-100 value of >0.7 microg/l at admission was found to be a predictor that consciousness would not be regained, with a specificity of 85%, a sensitivity of 66.6%, a positive predictive value of 84%, a negative predictive value of 78% and an accuracy of 77.6%. CONCLUSIONS: Serum S-100 protein at admission gives reliable and independent information concerning the short term neurological outcome after resuscitation; and could be a good marker of brain cell damage.

Aged↗

Thyroid dysfunction and autoimmunity in infertile women.

A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.

Adult↗

Clinical validation of a fully automated 17beta-estradiol and progesterone assay (VIDAS) for use in monitoring assisted reproduction treatment.

Measurement of serum estradiol (E2) and progesterone (PRG) allows monitoring of follicular growth and prediction of the day of ovulation in natural cycles. In combination with vaginal ultrasonography, serum E2 and PRG are used for the monitoring of ovarian superovulation for assisted reproduction. We carried out a clinical evaluation of the VIDAS E2 and PRG assays on a fully automated random access analyzer (miniVIDAS, bioMérieux) by retrospective analysis of frozen serum samples obtained from 16 natural cycles monitored for frozen embryo transfer (FRET) and in superovulation cycles. The superovulation cycles consisted of 28 long gonadotropin-releasing hormone (GnRH) agonist protocol cycles and 15 GnRH antagonist protocol cycles. In FRET cycles we found a good correlation between serum E2 and the diameter of the dominant follicle measured by ovarian ultrasonography. Serum E2 values measured throughout the cycles and follicular phase PRG values were representative of normo-ovulatory cycles. In GnRH agonist long protocols, we found serum E2 and PRG values compatible with castration levels induced by pituitary desensitization. During gonadotropin treatment a close, highly significant correlation was observed between serum E2 and ultrasonographic follicle measurements with both GnRH analogue protocols. Serum PRG measured for 5 days prior to human chorionic gonadotropin (hCG) administration in the agonist cycles was compatible with the absence of premature luteinization. In conclusion, VIDAS E2 and PRG assays are precise and sensitivetoolsforevaluating natural cycles (based on the results in FRET cycles) and for monitoring ovarian superovulation.

Automation↗