Marker Levels (marker + level)

Distribution by Scientific Domains


Selected Abstracts


Effect of Fracture on Bone Turnover Markers: A Longitudinal Study Comparing Marker Levels Before and After Injury in 113 Elderly Women,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007
Kaisa K Ivaska PhD
Abstract In this longitudinal, prospective, and population-based study (n = 1044), seven BTMs were assessed before and after trauma in 113 elderly women (85 with fractures). Markers were not altered in the immediate postfracture period but were clearly elevated during fracture repair. Recent fracture should thus be taken into account when markers are used in clinical practice. Introduction: Fracture may influence the levels of bone turnover markers (BTM) and have implications for their use in clinical practice. In this longitudinal, prospective, and population-based study, we assessed prefracture levels of BTMs and compared them with postfracture levels of the same individuals immediately after fracture and during fracture repair. This is the first study in which the effect of fracture on bone markers has been evaluated with prefracture samples available. Materials and Methods: Serum and urine were collected at the emergency unit from 85 women (77.9 ± 1.8 yr) who sustained a fracture after low-energy trauma and 28 controls (77.8 ± 2.0 yr) with similar trauma but no fracture. All were participants of the Malmö OPRA study (n = 1044), and pretrauma samples were collected 1.05 ± 0.85 yr before. Bone turnover was assessed by seven different BTMs reflecting different stages of bone metabolism {C-terminal cross-linked telopeptides of type I collagen [S-CTX], S-TRACP5b, N-terminal propeptides of type I collagen [S-PINP], serum osteocalcin (S-OC[1,49] and S-TotalOC), urinary deoxypyridinoline [U-DPD], and urinary osteocalcin [U-OC]}. Results: BTMs sampled within a few hours after fracture were not altered from preinjury levels. Both bone formation and bone resorption markers were, however, significantly increased 4 mo after fracture. The elevation was most pronounced after hip fracture. Bone turnover remained elevated up to 12 mo after fracture. Conclusions: We believe this study extends our knowledge on the skeletal postfracture metabolic processes. In addition, it may provide a basis for future means to monitor pharmacological intervention promoting fracture healing. [source]


Correlation of ultrasound findings and biochemical markers in the second trimester of pregnancy in fetuses with trisomy 21

PRENATAL DIAGNOSIS, Issue 3 2002
Vivienne L. Souter
Abstract Objective The aim of the present study was to assess possible correlations between ultrasound findings and maternal serum biochemical (,triple test') markers among fetuses with trisomy 21 in the second trimester of pregnancy. Methods The study was a retrospective cohort study of 72 pregnancies affected by trisomy 21 who had a second trimester ultrasound and biochemical screen performed at a single center between 1990 and 1999. The biochemical screen consisted of alpha-fetoprotein (AFP), total beta human chorionic gonadotrophin (hCG) and estriol (uE3). Marker levels were expressed in multiples of the median (MoM). The ultrasound findings assessed were major structural anomalies, short humerus length, short femur length, increased nuchal fold thickness (NF), hyperechoic bowel, echogenic intracardiac focus (EIF), ventriculomegaly, choroid plexus cysts and renal pyelectasis. Results Second trimester maternal serum biochemical markers and ultrasound findings appeared to be largely independent of each other. However, some significant correlations were observed. Estriol was significantly lower when a fetal cystic hygroma was detected on ultrasound compared to those with no cystic hygroma (0.40 vs 0.70 MoM, p<0.05). The median hCG level was significantly lower in those pregnancies with a normal second trimester fetal ultrasound compared to those with positive ultrasound findings (2.07 vs 2.87 MoM, p<0.05). Median hCG levels were also significantly higher in those cases with NF,5,mm as compared to those with NF<5,mm (2.99 vs 2.49 MoM, p<0.05). This difference persisted after exclusion of the five cases with cystic hygromas (2.99 vs 2.49 MoM, p<0.05). A significant positive correlation was observed between log10 hCG and log10 NF MoM (Spearman's ,=0.252, p<0.05). NF was significantly greater among fetuses with an identifiable cardiac defect compared with those without a detectable cardiac defect (median of 7.0,mm vs 3.8,mm, p<0.01). This difference persisted when expressed as multiples of the median (2.8 vs 1.3 MoM, p<0.01). Conclusion Second trimester ultrasound and biochemical markers are largely independent in fetuses with trisomy 21, however significant correlations between the two were observed in the present series. These may be important in screening protocols that combine second trimester ultrasound and biochemical markers. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Pretreatment Levels of Bone Turnover and the Antifracture Efficacy of Alendronate: The Fracture Intervention Trial

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006
Douglas C Bauer MD
Abstract The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. Introduction: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. Materials and Methods: We randomized women 55,80 years of age with femoral neck BMD T scores , ,1.6 to alendronate (ALN), 5,10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score , ,2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > ,2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. Results and Conclusions: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover. [source]


Prenatal screening for Down syndrome: the problem of recurrent false-positives

PRENATAL DIAGNOSIS, Issue 5 2004
Nicholas J. Wald
Abstract Objectives It has been reported that, in prenatal screening programmes for Down syndrome, women who have false-positive results in one pregnancy have an increased risk of a false-positive result in a subsequent pregnancy. We examined the effect of this in the screening programme conducted from the Wolfson Institute of Preventive Medicine with a view to determining the magnitude of the effect, and to describe a method of avoiding the problem. Methods Six thousand four hundred and forty-eight women were identified who had had two singleton pregnancies without Down syndrome in the screening programme based at the Wolfson Institute of Preventive Medicine, in which both pregnancies were screened using a Quadruple test (maternal age with alphafetoprotein (AFP), unconjugated oestriol (uE3), total or free ,-human chorionic gonadotrophin (hCG) and either free ,-hCG or inhibin-A as the fourth serum marker). Results Among women who had a false-positive result in their initial pregnancy, the false-positive rate in the subsequent pregnancy was high: 20% (46/229), about three times higher than both the overall observed false-positive rate (6.6%), and the expected false-positive rate, in subsequent pregnancies that were false,positive in their initial pregnancy (7.5%) (p < 0.001). This arises because serum marker levels in one pregnancy are associated with the levels in a subsequent pregnancy. Using the slope (the regression coefficient b) of each marker level in a subsequent pregnancy regressed on the value in the first pregnancy, it is possible to adjust all marker values in a subsequent pregnancy to allow for the higher-than-expected false-positive rate. This can be done by dividing the observed MoM value for each marker by the ,expected' MoM, which is the MoM value in a previous pregnancy raised to the power b. Conclusions If a woman has had a false-positive result in one pregnancy, she is much more likely to have a false-positive screening result in a subsequent pregnancy than women in general. The problem can be avoided by adjusting the serum markers in all women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down syndrome. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Estimating driver risk using alcohol biomarkers, interlock blood alcohol concentration tests and psychometric assessments: initial descriptives

ADDICTION, Issue 2 2010
Paul Marques
ABSTRACT Aim To identify alcohol biomarker and psychometric measures that relate to drivers' blood alcohol concentration (BAC) patterns from ignition interlock devices (IIDs). Design, setting, participants, measurements In Alberta, Canada, 534 drivers, convicted of driving under the influence of alcohol (DUI), installed IIDs and agreed to participate in a research study. IID BAC tests are an established proxy for predicting future DUI convictions. Three risk groups were defined by rates of failed BAC tests. Program entry and follow-up blood samples (n = 302, 171) were used to measure phosphatidyl ethanol (PETH), carbohydrate deficient transferrin (%CDT), gamma glutamyltransferase (GGT) and other biomarkers. Program entry urine (n = 130) was analyzed for ethyl glucuronide (ETG) and ethyl sulphate (ETS). Entry hair samples were tested for fatty acid ethyl esters (FAEE) (n = 92) and ETG (n = 146). Psychometric measures included the DSM-4 Diagnostic Interview Schedule Alcohol Module, Alcohol Use Disorders Identification Test (AUDIT), the time-line follow-back (TLFB), the Drinker Inventory of Consequences (DRINC) and the Temptation and Restraint Inventory (TRI). Findings Except for FAEE, all alcohol biomarkers were related significantly to the interlock BAC test profiles; higher marker levels predicted higher rates of interlock BAC test failures. PETH, the strongest with an overall analysis of variance F ratio of 35.5, had significant correlations with all nine of the other alcohol biomarkers and with 16 of 19 psychometric variables. Urine ETG and ETS were correlated strongly with the IID BAC tests. Conclusions The findings suggest that several alcohol biomarkers and assessments could play an important role in the prediction and control of driver alcohol risk when re-licensing. [source]


Quantitative microbial faecal source tracking with sampling guided by hydrological catchment dynamics

ENVIRONMENTAL MICROBIOLOGY, Issue 10 2008
G. H. Reischer
Summary The impairment of water quality by faecal pollution is a global public health concern. Microbial source tracking methods help to identify faecal sources but the few recent quantitative microbial source tracking applications disregarded catchment hydrology and pollution dynamics. This quantitative microbial source tracking study, conducted in a large karstic spring catchment potentially influenced by humans and ruminant animals, was based on a tiered sampling approach: a 31-month water quality monitoring (Monitoring) covering seasonal hydrological dynamics and an investigation of flood events (Events) as periods of the strongest pollution. The detection of a ruminant-specific and a human-specific faecal Bacteroidetes marker by quantitative real-time PCR was complemented by standard microbiological and on-line hydrological parameters. Both quantitative microbial source tracking markers were detected in spring water during Monitoring and Events, with preponderance of the ruminant-specific marker. Applying multiparametric analysis of all data allowed linking the ruminant-specific marker to general faecal pollution indicators, especially during Events. Up to 80% of the variation of faecal indicator levels during Events could be explained by ruminant-specific marker levels proving the dominance of ruminant faecal sources in the catchment. Furthermore, soil was ruled out as a source of quantitative microbial source tracking markers. This study demonstrates the applicability of quantitative microbial source tracking methods and highlights the prerequisite of considering hydrological catchment dynamics in source tracking study design. [source]


Telangiectatic adenoma: An entity associated with increased body mass index and inflammation,

HEPATOLOGY, Issue 1 2007
Valérie Paradis
What were previously called telangiectatic focal nodular hyperplasias are in fact true adenomas with telangiectatic features (TAs) without overt characterized genetic abnormalities. The aim of our study was to review a surgical series of TAs in order to describe clinical, biological, and radiological findings of these lesions and to evaluate their outcomes. From January 1996 to November 2005, 284 patients with benign hepatocellular nodules underwent surgical resection at Beaujon Hospital. Among them, 32 TAs from 27 patients were diagnosed. Ninety-two percent of the patients were women. Mean age was 38 years (range 17,63). Mean body mass index was 28 (range 18,49), with 16 patients being overweight. Symptoms revealed lesions in 10 patients. In 13 patients, TA was associated with another benign liver lesion. Mean size of the TAs was 5 cm (range 1,17 cm). Histological analysis showed cellular atypias in 6 cases (19%), steatosis in 17 cases (53%), vascular changes in 19 cases (59%), and significant inflammatory infiltrate in 29 cases (91%). In 1 case, the TA had foci of well-differentiated hepatocellular carcinoma. In 18 of the 26 cases (69%), adjacent liver showed significant steatosis. Serum biomarkers of inflammation were increased in 90% of patients (19 of 22). After surgical resection, inflammatory marker levels returned to normal values in all patients tested. Conclusion: This study has shown that TAs occur in a characteristic background of overweight patients and are often associated with a biological inflammatory syndrome. Moreover, a TA may progress to malignancy. (HEPATOLOGY 2007;46:140,146.) [source]


Preoperative staging and evaluation of resectability in pancreatic ductal adenocarcinoma

HPB, Issue 1 2004
R Andersson
Background Cancer of the pancreas is a common disease, but the large majority of patients have tumours that are irresectable at the time of diagnosis. Moreover, patients whose tumours are clearly beyond surgical cure are best treated non-operatively, if possible, by relief of biliary obstruction and percutaneous biopsy to confirm the diagnosis and then consideration of oncological treatment, notably chemotherapy. These facts underline the importance of a standard protocol for the preoperative determination of operability (is it worth operating?) and resectability (is there a chance that the tumour can be removed?). Recent years have seen the advent of many new techniques, both radiological and endoscopic, for the diagnosis and staging of pancreatic cancer. It would be impracticable in time and cost to submit every patient to every test. This review will evaluate the available techniques and offer a possible algorithm for use in routine clinical practice. Discussion In deciding whether to operate with a view to resecting a pancreatic cancer, the surgeon must take into account factors related to the patient, the tumour and the institution and team entrusted with the patient's care. Patient-related factors include age, general health, pain and the presence or absence of malnutrition and an acute phase inflammatory response. Tumour-related factors include tumour size and evidence of spread, whether to adjacent organs (notably major blood vessels) or further afield. Hospital-related factors chiefly concern the volume of pancreatic cancer treated and thus the experience of the whole team. Determination of resectability is heavily dependent upon detailed imaging. Nowadays conventional ultrasonography can be supplemented by endoscopic, laparoscopic and intra-operative techniques. Computed tomography (CT) remains the single most useful staging modality, but MRI continues to improve. PET scanning may demonstrate unsuspected metastases and likewise laparoscopy. Diagnostic cholangiography can be performed more easily by MR techniques than by endoscopy, but ERCP is still valuable for preoperative biliary decompression in appropriate patients. The role of angiography has declined. Percutaneous biopsy and peritoneal cytology are not usually required in patients with an apparently resectable tumour. The prognostic value of tumour marker levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy or chemoradiation may have a role in down-staging an irresectable tumour sufficiently to render it resectable. Selective use of diagnostic laparoscopy staging is potentially helpful in determination of resectability. Laparotomy remains the definitive method for determining the resectability of pancreatic cancer, with or without portal vein resection, and should be undertaken in suitable patients without clear-cut evidence of irresectability. [source]


Pretreatment Levels of Bone Turnover and the Antifracture Efficacy of Alendronate: The Fracture Intervention Trial

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006
Douglas C Bauer MD
Abstract The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. Introduction: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. Materials and Methods: We randomized women 55,80 years of age with femoral neck BMD T scores , ,1.6 to alendronate (ALN), 5,10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score , ,2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > ,2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. Results and Conclusions: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover. [source]


Long-Term Variability of Markers of Bone Turnover in Postmenopausal Women and Implications for Their Clinical Use: The OFELY Study,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003
Patrick Garnero
Abstract Bone marker variability has raised concern for its use in individual patients. Serum osteocalcin (formation) and CTX (resorption) were measured every year for 4 years in 268 postmenopausal women. Seventy percent to 80% of women classified as having high bone turnover at baseline were similarly classified by the same methods 4 years later. Introduction: High bone marker levels are a risk factor for osteoporosis in postmenopausal women, but variability of measurements has raised doubts about their clinical use in an individual patient. Methods: We studied 268 untreated postmenopausal women (50,81 years of age) belonging to a population-based prospective cohort. We collected fasting morning blood samples every year for 4 years to measure serum intact osteocalcin (OC) and serum C-terminal cross-linked telopeptide of type I collagen (CTX) as bone formation and resorption markers, respectively. Results: Serum OC and CTX remained stable during follow-up (+1.2%/year, p = 0.003 and ,0.13%/year, p = 0.70 for OC and S-CTX, respectively). At baseline, women were classified as having low (tertile 1), intermediate (tertile 2), or high (tertile 3) bone turnover. Agreement of classification between baseline and 4-year measurements was moderate (, [95% CI]: 0.51 [0.43,0.59] and 0.52 [0.44,0.60] for OC and S-CTX, respectively). Less than 10% of women in tertile 1 or 3 of either marker at baseline were found in the opposite tertile 4 years later. When the two markers were combined, only 2% of women at high turnover at baseline,defined as OC and/or S-CTX in tertile 3,were classified at low turnover 4 years later. Among women classified at high bone turnover at baseline (tertile 3), 70,80 % were also found at high turnover 4 years later. Among women in tertile 2, only 51% and 43% for OC and CTX, respectively, remained in the same tertile at the second measurement. Conclusions: Serum levels of bone formation and resorption markers are stable over 4 years in postmenopausal women, on average. The majority of women classified as having high bone turnover were similarly classified by the same methods 4 years later. However, 20,30 % of these women at risk for fracture would be incorrectly classified, suggesting that further investigation would be required to reduce the number of patients who would be treated unnecessarily if the decision was made on bone marker measurement. For women with intermediate levels, classification may be improved by a second measurement or by combining two markers. [source]


Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005
Christophe Céleste
Abstract Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis was performed weekly on both joints for 13 weeks. The initial results from the first 3 weeks of the experimental period established baseline untreated control marker levels for each joint, each being its own control. On weeks 3, 5, and 7, a sterile suspension of 12mg of TA was injected into the treated joint and an equivalent volume of sterile saline solution (0.9%) was injected into the control joint. SF was immunoassayed for biomarkers of aggrecan turnover (CS 846 & KS), types I and II collagen cleavage (C1,2C) and type II collagen synthesis (CPII). In treated joints, there was a significant increase in CS 846, KS, C1,2C and CPII epitope concentrations following IA TA injections when compared to baseline levels. There was also a significant increase in C1,2C and CPII epitope concentrations in the contralateral control joints following IA TA injections in the treated joint. Significant differences were observed between treated and control joints for all markers except CPII. These findings indicate that TA alters articular cartilage and collagen metabolism in treated and, interestingly, also in control joints, suggesting a systemic effect of the drug. Though intuitively the observed findings would favor the hypothesis that long-term IA TA treatment changes joint metabolism and this may have detrimental effects; further studies would be necessary to confirm this. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]


The influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy

PRENATAL DIAGNOSIS, Issue 10 2005
Kevin Spencer
Abstract Objective To evaluate the influence of maternal insulin dependent diabetes mellitus (IDDM) on maternal serum free ,-hCG, PAPP-A and fetal nuchal translucency (NT), thickness at 11 to 13+6 weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Methods Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two first-trimester screening centres. In total the control group included 33 301 pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16 305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and maternal serum biochemistry results and 127 with NT only. The median maternal weight corrected free ,-hCG and PAPP-A, expressed as multiple of the median (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. Results There were no significant differences between the IDDM and non-IDDM groups in median maternal weight corrected free ,-hCG (IDDM 0.87 MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to 1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002 mm). Conclusions In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT. However, more data are required before the possible reduction in maternal serum free ,-hCG and the reduction of PAPP-A suggested by the published world series can be considered sufficiently important to take into account in the calculation of risks for chromosomal defects. Copyright © 2005 John Wiley & Sons, Ltd. [source]


First and second-trimester biochemical markers of chromosomal anomalies and their relationship to maternal haemoglobin levels

PRENATAL DIAGNOSIS, Issue 8 2005
N. J. Cowans
Abstract Objective To evaluate a previous hypothesis that maternal serum biochemical markers used in the assessment of Down syndrome risk are related to maternal haemoglobin concentrations. Methods A series of 1306 second-trimester prenatal screening records were retrieved including information on marker levels (AFP and f,hCG MoMs), Down's risk, a priori age risk, maternal weight and maternal height. Each individual record was merged with data from haematological investigations on samples collected on the same day. A similar series of 1688 first-trimester screening records were also retrieved including the maker levels for PAPP-A, and f,hCG MoMs were merged with data from haematological investigations carried out on the same day. The two groups were categorised according to their haemoglobin levels; anaemic (less than 11.0 g/dL in first trimester and 10.5 g/dL in the second trimester), high haemoglobin (greater than 14.0 g/dL and 13.2 g/dL) or normal (between these ranges). An analysis was made of marker levels in the various groups before and after correction for ethnicity and of the screen-positive rate in the various groups. Using a formula based on maternal height and weight, variation of marker levels with plasma volume was assessed. Results In the first trimester, 12.6% of the pregnant population was anaemic and 1.6% had elevated haemoglobin levels. In the second trimester this was 12.7 and 3.9%. These figures varied considerably with ethnic origin, with Asian and Afro-Caribbean women being more anaemic than Caucasian women. Haemoglobin levels declined by 7% between the 11- and 21-week period. Maternal plasma volume (as calculated by a widely used maternal height and weight relationship) was not correlated with weight-corrected biochemical marker MoMs in either trimester. A weak but significant correlation of maternal plasma volume and haemoglobin concentration was observed. There was no significant correlation between biochemical marker MoMs and haemoglobin concentration. Although the proportion of pregnancies designated screen positive decreased as haemoglobin levels increased, this was paralleled by a decrease in the maternal age apriori risk. Conclusions There is no relationship between maternal haemoglobin levels and the levels of Down syndrome markers in either the first or second trimester. Biochemical marker levels do not need to be corrected for haemoglobin concentrations when used in screening for Down syndrome. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Prenatal screening for Down syndrome: the problem of recurrent false-positives

PRENATAL DIAGNOSIS, Issue 5 2004
Nicholas J. Wald
Abstract Objectives It has been reported that, in prenatal screening programmes for Down syndrome, women who have false-positive results in one pregnancy have an increased risk of a false-positive result in a subsequent pregnancy. We examined the effect of this in the screening programme conducted from the Wolfson Institute of Preventive Medicine with a view to determining the magnitude of the effect, and to describe a method of avoiding the problem. Methods Six thousand four hundred and forty-eight women were identified who had had two singleton pregnancies without Down syndrome in the screening programme based at the Wolfson Institute of Preventive Medicine, in which both pregnancies were screened using a Quadruple test (maternal age with alphafetoprotein (AFP), unconjugated oestriol (uE3), total or free ,-human chorionic gonadotrophin (hCG) and either free ,-hCG or inhibin-A as the fourth serum marker). Results Among women who had a false-positive result in their initial pregnancy, the false-positive rate in the subsequent pregnancy was high: 20% (46/229), about three times higher than both the overall observed false-positive rate (6.6%), and the expected false-positive rate, in subsequent pregnancies that were false,positive in their initial pregnancy (7.5%) (p < 0.001). This arises because serum marker levels in one pregnancy are associated with the levels in a subsequent pregnancy. Using the slope (the regression coefficient b) of each marker level in a subsequent pregnancy regressed on the value in the first pregnancy, it is possible to adjust all marker values in a subsequent pregnancy to allow for the higher-than-expected false-positive rate. This can be done by dividing the observed MoM value for each marker by the ,expected' MoM, which is the MoM value in a previous pregnancy raised to the power b. Conclusions If a woman has had a false-positive result in one pregnancy, she is much more likely to have a false-positive screening result in a subsequent pregnancy than women in general. The problem can be avoided by adjusting the serum markers in all women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down syndrome. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Maternal serum,integrated screening for trisomy 18 using both first- and second-trimester markers

PRENATAL DIAGNOSIS, Issue 3 2003
Glenn E. Palomaki
Abstract Objectives To estimate the prenatal screening performance of an integrated serum test for detecting trisomy 18, which combines measurements of first- and second-trimester markers with maternal age to assign patient-specific risks. Methods Published and new observations of maternal serum marker levels in trisomy 18 and unaffected pregnancies are used to derive population parameters. These parameters are then combined in a multivariate Gaussian model to assign patient-specific risks for trisomy 18. Results The best combination of serum markers includes pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin in the second trimester. At a second-trimester risk cutoff of 1 : 100, these 4 markers, in combination with maternal age, detect 90% of trisomy 18 pregnancies at a false-positive rate of 0.1%. The odds of a trisomy 18 pregnancy among screen-positive women are 1 : 4. Without the first-trimester marker, detection is reduced to 67% at about the same false-positive rate. Conclusion The algorithm described here is highly efficient for detecting trisomy 18 and should be considered by programs that offer serum-integrated screening for Down syndrome. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Sputum carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis

RESPIROLOGY, Issue 1 2004
Ioannis Kalomenidis
Objective: The aim of the present study was to examine the impact of sputum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin fragment 19 (CYFRA 21-1) levels in lung cancer diagnosis and to compare the diagnostic usefulness of sputum assays with that of serum assays. Methodology: Forty-seven patients with lung cancer and 62 with benign lung disease were studied. Tumour marker levels in sputum (sp.) and serum (ser) were measured by immunoradiometric assays. Results: Sputum and serum tumour marker levels were significantly higher in lung cancer than in benign disease. When the specificity was 95%, the sensitivity was 57%, 43%, 36%, 30%, 28% and 19%, for spCEA, serCYFRA 21-1, spCYFRA 21-1, serCEA, serNSE, and spNSE, respectively. Bayesian analysis showed that the best predictive values correspond to spCEA and serCYFRA 21-1. The maximum overall gain was obtained in pretest probability of 0.35 for both spCEA and serCYFRA 21-1, with predictive values of 84% and 80% for spCEA and serCYFRA 21-1, respectively. Conclusion: Sputum tumour marker levels were no more useful than the serum levels in lung cancer diagnosis. SpCEA offered the best predictive values but these were still not sufficiently satisfactory for spCEA to be proposed for routine use. [source]


The significance of tumour markers as an indication for mediastinoscopy in non-small cell lung cancer

RESPIROLOGY, Issue 2 2003
Soichiro ANDO
Objective: The purpose of this study was to verify the significance of tumour markers as indicators for mediastinoscopy in non-small cell lung cancer. Methodology: In the past 4 years, 205 patients with non-small cell lung carcinoma (NSCLC) underwent surgical resection at Chiba Cancer Center, Chiba, Japan. The correlation between the serum levels of eight tumour markers (CEA, AFP, CA19-9, SCC, NSE, CA125, CYFRA, ProGRP) and the presence of N2 disease was analysed. Univariate and multivariate analyses were performed to determine the relationship between both marker levels and clinical findings and N2 disease. Results: In multivariate analysis, positive CEA was significantly associated with the diagnosis of N2 disease. We also demonstrated that when CA125, CYFRA and ProGRP were positive, they were individually significantly associated with N2 disease. However, CEA was superior to the other markers and equivalent to a combination of various tumour markers. Conclusion: It was concluded that evaluation of CEA in addition to CT is of use in the diagnosis of N2 disease in NSCLC patients and should be used as an indication for mediastinoscopy. [source]


Basal serum testosterone as an indicator of response to clomiphene treatment in human epididymis, seminal vesicles and prostate

ANDROLOGIA, Issue 5 2002
Dr. G. F. GonzalesArticle first published online: 13 AUG 200
Summary. The present study was designed to determine the response of human epididymis, seminal vesicles and prostate function after a 5-day course of clomiphene citrate in men attending an infertility service. In 45 men, the secretions of the epididymis, seminal vesicles and prostate were assessed by measurements of seminal ,-glucosidase, fructose and acid phosphatase, respectively. Subjects were classified as normal or abnormal: abnormal men were defined as those who either had history of a sexually transmitted disease (STD), leukocytosper-mia, hypoandrogenism, or a low response of Leydig cells to clomiphene stimulation; and normal subjects were those who did not have these conditions. Mean serum testosterone luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly increased after the short course with clomiphene citrate. After clomiphene citrate stimulation, the men in the normal group showed significantly increased marker levels of the seminal vesicles (P <0.02) and prostate (P <0.05), but not of the epididymis (P: NS). Men classified as abnormal showed no response according to the markers of the seminal vesicles and epididymis. Men with history of STD and abnormal basal values of acid phosphatase did not respond to the treatment. Men with history of STD but normal basal values of seminal acid phosphatase increased significantly in their levels of seminal acid phosphatase after clomiphene stimulation (P <0.02). Multivariate analysis showed that the basal serum testosterone level was the only variable in predicting the probability of response to the clomiphene in terms of true-corrected seminal fructose, seminal acid phosphatase and seminal ,-glucosidase levels. In fact, a high response of the seminal vesicles was observed in men with the highest basal serum testosterone levels (0.45 *** 0.17; coefficient of regression *** standard error; P <0.018). However, a high response in terms of seminal acid phosphatase (P <0.004) or ,-glucosidase (P <0.037) was observed in men with low basal serum testosterone levels. In conclusion, in the normal men, true-corrected fructose and acid phosphatase but not ,-glucosidase in semen increased after duplicate androgen stimulation. An absence of response was observed in cases with history of STD/leukocytospermia or hypoandrogenism. [source]


Positron emission tomography for urological tumours

BJU INTERNATIONAL, Issue 2 2003
S.F. Hain
SUMMARY For urological tumours, positron emission tomography (PET) is currently most useful in testicular cancer. In patients with residual masses or raised marker levels after treatment, PET is both sensitive and specific for detecting recurrent disease, at suspected and unsuspected sites. Although fewer studies are available it also appears to be useful for staging at diagnosis, although this requires further investigation. Prostate cancer imaging has been more variable, with studies showing that PET cannot reliably differentiate between tumour and hypertrophy. It is not as good as a bone scan for defining bone metastases. In renal cancer, PET can be used to define the primary tumour, providing better staging of local recurrence than computed tomography (CT), and to define metastatic disease. There are few studies in bladder cancer, and despite excretion of the tracer via the bladder in early studies, it has better results than CT or magnetic resonance imaging for local staging; again it can detect metastases. Overall, the place of PET in urological tumours is developing, with the strongest areas undoubtedly being testicular and renal cancer. Tracers other than fluorodeoxyglucose are being examined and are providing further information. [source]


Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases,

CANCER, Issue 5 2008
Julie King MPH
Abstract BACKGROUND. There are limited effective treatment options available and a poor 5-year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 (90Y) radioactive microspheres for patients with unresectable NETLMs. METHODS. Radioactive 90Y resin microspheres (selective internal radiation [SIR-Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7-day systemic infusion of 5-fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies. RESULTS. Thirty-four patients (22 men) with a mean age 61 years (range, 32-79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (±standard error) follow-up was 35.2 ± 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after 90Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 ± 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after 90Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months. CONCLUSIONS. In this open study of 34 patients, the results demonstrated that radioembolization with 90Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs. Cancer 2008. © 2008 American Cancer Society. [source]