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Biochemical Screening (biochemical + screening)
Selected AbstractsEvaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasiaCONGENITAL ANOMALIES, Issue 1 2005Julie Travitz ABSTRACT Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an ,active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs. [source] Molecular neonatal screening for homocystinuria in the Qatari population,HUMAN MUTATION, Issue 6 2009Johannes Zschocke Abstract We report the results of molecular neonatal screening for homocystinuria (cystathionine beta-synthase deficiency) in neonates of Qatari origin, developed in conjunction with a novel biochemical screening approach. DNA was extracted from dried blood spots (DBS); the prevalent Qatari CBS gene mutation p.R336C (c.1006C>T) and a second mutation were tested with specific TaqMan assays. Over a period of 2 years we screened 12,603 neonates and identified six affected neonates homozygous for p.R336C. There were 225 heterozygous carriers for p.R336C. One additional child with homocystinuria detected through biochemical screening was homozygous for a mutation not previously identified in Qatar. Homocystinuria in the Qatari population has an incidence of 1:1,800, the highest in the world and even higher than previously estimated. Allele frequency of the mutation p.R336C is approximately 1%, displaying a significant deviation from Hardy Weinberg equilibrium. In conclusion, first-line molecular neonatal screening is technically feasible and may be developed as an option for presymptomatic identification of genetic disorders caused by specific mutations or a limited number of prevalent mutations. However, sensitivity for the diagnosis of disorders caused by various mutations is limited even in a homogeneous population such as Qatar. Hum Mutat 30:1,2, 2009. © 2009 Wiley-Liss, Inc. [source] Spectrum of idiopathic photodermatoses in a Mediterranean countryINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2003Alexander J. Stratigos md Background ,Idiopathic photodermatoses are considered to be common disorders in the population of northern latitude countries, presumably because of the dominance of more "sun-sensitive" individuals with a light-skinned complexion. The incidence of these disorders in the Mediterranean or tropical countries is often under-appreciated because of the higher degree of perennial presence of sunlight and the prevalence of darker skin-type individuals who are seemingly more resistant to the development of sun sensitivity. Methods ,We performed a retrospective, chart-based review of all patients who were diagnosed with idiopathic photodermatoses at a photodermatology referral center in Athens, Greece, during a period of 10 years. Our aim was to assess the pattern of idiopathic photosensitivity disorders in a Mediterranean country and to determine their epidemiological, clinical, and photobiological profile. Results ,A total of 310 patients were referred to our center with symptoms of photosensitivity. One hundred and forty-six patients (47.0%) were diagnosed with an idiopathic photosensitivity disorder by means of history, clinical examination, biochemical screening, histology, and phototesting. The most prevalent disorder was polymorphous light eruption, which was diagnosed in 95 patients (65.0%) of our cohort. Chronic actinic dermatitis occurred in 15 patients (10.2%), solar urticaria in 26 patients (17.8%), actinic prurigo in three patients (2.0%), hydroa vacciniforme in one patient (0.6%) and juvenile spring eruption in six patients (4.1%). Conclusions ,Compared with the results of other studies, the prevalence of idiopathic photodermatoses appears to have a similar trend to that of higher latitude countries. Distinct features in our series include the higher incidence of idiopathic photosensitivity in patients with a fair-skinned complexion (skin types II,III) and the frequent appearance of photo-induced eruptions during sunny weather breaks in the winter period. [source] Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2003a Jantová Previous studies on the anticancer activity of protoberberine alkaloids against a variety of cancer cell lines were extended to human tumour HeLa and murine leukemia L1210 cell lines. An attempt was also made to investigate the relationship between the cytotoxic activity of berberine and its molecular mechanism of action. Cytotoxicity was measured in-vitro using a primary biochemical screening according to Oyama and Eagle, and the growth inhibition assay. The in-vitro cytotoxic techniques were complemented by cell cycle analysis and determination of apoptotic DNA fragmentation in L1210 cells. Berberine acted cytotoxically on both tumour cell lines. The sensitivity of leukemia L1210 cells to the berberine was higher than that of HeLa cells. The IC100 was below 100 ,g mL,1 for HeLa cells and approached a 10 , mL,1 limit for the leukemia L1210 cells. For both cell lines the IC50 was found to be less than 4 ,g mL,1, a limit put forward by the National Cancer Institute (NCI) for classification of the compound as a potential anticancer drug. In L1210 cells treated with 10,50 , mL,1 berberine, G0/G1 cell cycle arrest was observed. Futhermore, a concentration-dependent decrease of cells in S phase and increase in G2/M phase was detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25,100 ,g mL,1 berberine-treated cells by monitoring the apoptotic DNA fragmentation (DNA ladder) using agarose gel electrophoresis. [source] Maternal serum biochemistry at 11,13+6 weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screeningPRENATAL DIAGNOSIS, Issue 11 2005Simona Cicero Abstract Background Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free ,-hCG and pregnancy associated plasma protein-A (PAPP-A) at 11,13+6 weeks of gestation is associated with a detection rate of 90%, for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21 the nasal bone is not visible at the 11,13+6 week scan and that the frequency of absence of nasal bone differs in different ethnic groups. In addition, there is a relationship between absent nasal bone and nuchal translucency thickness. In a preliminary study we showed that while PAPP-A levels were lower and free ,-hCG levels were higher in trisomy 21 fetuses with an absent nasal bone, this difference was not statistically different. In fetuses with trisomy 13 and trisomy 18, there is also a high (57 and 67%) incidence of an absent nasal bone. The aim of this present study was to extend our examination of whether the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone in cases with trisomy 21 and to ascertain if any differences exist in cases with trisomies 13 and 18. Methods This study data comprised 100 trisomy 21 singleton pregnancies at 11,13+6 weeks of gestation from our previous study and an additional 42 cases analysed as part of routine OSCAR screening. A total of 34 cases with trisomy 18 and 12 cases with trisomy 13 were also available. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free ,-hCG and PAPP-A were measured using the Kryptor rapid random access immunoassay analyser (Brahms Diagnostica AG, Berlin). The distribution of maternal serum free ,-hCG and PAPP-A in chromosomally abnormal fetuses with absent and present nasal bone was examined. Results The nasal bone was absent in 29 and present in 13 of the new trisomy 21 cases and in 98 (69%) and 44 respectively in the combined series. For the trisomy 18 cases, the nasal bone was absent in 19 (55.9%) cases and in 3 (25%) of cases of trisomy 13. There were no significant differences in median maternal age, median gestational age, NT delta, free ,-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone, and similarly for those with trisomies 13 or 18. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 96% of cases with trisomy 21. For a false-positive rate of 0.5%, the detection rate was 88%. Conclusions There is no relationship between an absent fetal nasal bone and the levels of maternal serum PAPP-A or free ,-hCG in cases with trisomies 13, 18 or 21. An integrated sonographic and biochemical test at 11,13+6 weeks can potentially identify about 88% of trisomy 21 fetuses for a false-positive rate of 0.5%. Copyright © 2005 John Wiley & Sons, Ltd. [source] Lack of correlation between elevated maternal serum hCG during second-trimester biochemical screening and fetal congenital anomalyPRENATAL DIAGNOSIS, Issue 3 2005Claudio Celentano Abstract Objective Isolated elevations in midtrimester maternal serum human chorionic gonadotrophin concentrations (MShCG) have been reported to be associated with a substantially increased likelihood of fetal congenital malformations. The reported malformations included a wide range of organ systems, originating at different embryologic developmental stages. The purpose of our study was to determine the significance of an isolated elevated MShCG (>2.5 MoM) in midtrimester for the detection of fetal structural anomalies in a large population. Methods Among 10 144 women who underwent a biochemical triple screen at 15 to 18 weeks' gestation, 463 patients, who had an elevated MShCG, but normal ,-fetoprotein (AFP) and unconjugated estriol (uE3) levels, were identified. Patients with an integrated calculated Down syndrome risk above 1:250 were excluded. Only nonsmokers, at ages <35 years, without a history of prior fetal anomalies were included. The control group consisted of 463 patients with normal serum analyte concentrations and Down syndrome risks below 1:250, who were matched for maternal age and date of biochemical screen. All patients underwent a detailed genetic sonogram in which an anatomic survey and multiple ,soft markers' for aneuploidy were looked for. Newborns were examined by a senior pediatrician trained in dysmorphology. Results MShCG levels were 3.18 ± 0.72 versus 0.99 ± 0.43 MoM (p < 0.0001) in study and control groups respectively. Sonography revealed 8 versus 6 cases of major congenital anomalies among the 463 patients of their respective groups, and 39 versus 36 sonographic ,soft markers' for aneuploidy. Fetal karyotyping and neonatal examination for dysmorphology revealed 6 chromosomal anomalies (4 Down syndrome; 2 Turner syndrome) among the 8 major malformations in the study group, but none in the controls (p < 0.0001). Three of the 39 fetuses with ,soft markers' and elevated MShCG were found to have trisomy 21. Conclusion Isolated elevation of MShCG does not confer an increased risk of fetal congenital anomalies other than chromosomal abnormalities. However, elevated MShCG levels in combination with sonographic ,soft markers' for aneuploidy were associated with a high incidence of chromosomal anomalies, despite a normal biochemical triple screen risk estimate. Copyright © 2005 John Wiley & Sons, Ltd. [source] Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency, absent fetal nasal bone, free ,-hCG and PAPP-A at 11 to 14 weeksPRENATAL DIAGNOSIS, Issue 4 2003Simona Cicero Abstract Background Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free ,-hCG and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 14 weeks of gestation is associated with a detection rate of 90% for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21, the nasal bone is not visible at the 11th- to 14th-week scan (Cicero et al., 2001). The aim of this study was to examine whether fetal NT thickness and the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone, and to estimate the performance of a screening test that integrates the two sonographic and the two biochemical markers. Methods This was a retrospective case-control study comprising 100 trisomy 21 and 400 chromosomally normal singleton pregnancies at 11 to 14 weeks of gestation. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free ,-hCG and PAPP-A were measured using the Kryptor rapid random-access immunoassay analyser (Brahms Diagnostica GmbH, Berlin). The distribution of fetal NT, maternal serum free ,-hCG and PAPP-A in trisomy 21 fetuses with absent and present nasal bone was examined. Results The nasal bone was absent in 69 and present in 31 of the trisomy 21 fetuses. There were no significant differences in median maternal age, median gestational age, NT delta, free ,-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 97%. For a false-positive rate of 0.5%, the detection rate was 90.5%. Conclusions An integrated sonographic and biochemical test at 11 to 14 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 0.5%. Copyright © 2003 John Wiley & Sons, Ltd. [source] The effect of fast reporting by amnio-PCR on anxiety levels in women with positive biochemical screening for Down syndrome , a randomized controlled trialPRENATAL DIAGNOSIS, Issue 3 2002Wing Cheong Leung Abstract Objective To study the effect of fast reporting by polymerase chain reaction on amniotic fluid cells (amnio-PCR) on anxiety levels in women with positive biochemical screening for Down syndrome. Method Between May 2000 and April 2001, 60 screen-positive women were randomized before amniocentesis into either having (group A) or not having (group B) fast-reporting by amnio-PCR. Anxiety levels were measured by the Spielberger State-Trait Anxiety Inventory just prior to amniocentesis, three days (when PCR results were known to group A) and three weeks (when standard karyotype results were known to both groups) afterwards. Results Two women were excluded because in one woman amnio-PCR showed trisomy 21 and the other miscarried shortly after amniocentesis. The state-anxiety scores increased over the three-week period after being informed of the positive-screen result in both groups. The trait- and state-anxiety scores at all points did not differ between the two groups. Conclusions In contrast to the general belief, fast reporting by amnio-PCR did not alleviate anxiety in women who are screen-positive for Down syndrome. Copyright © 2002 John Wiley & Sons, Ltd. [source] Maternal serum levels of dimeric inhibin A in pregnancies affected by trisomy 21 in the first trimesterPRENATAL DIAGNOSIS, Issue 6 2001Kevin Spencer Abstract Dimeric inhibin A was measured in maternal serum samples from 45 pregnancies affected by trisomy 21 and 493 samples from unaffected pregnancies at 10,14 weeks of gestation. Inhibin A levels in affected pregnancies were compared with levels of free ,-hCG and PAPP-A in the same series. In the trisomy 21 group, the median multiple of the median (MoM) inhibin A was not significantly elevated (1.28 vs 1.00) with only 15.5% being above the 95th centile. In contrast, the median MoM free ,-hCG was significantly increased (2.05 vs 1.00) with 36% above the 95th centile and PAPP-A was significantly reduced (0.49 vs 1.00) with 42% below the 5th centile. Inhibin A levels in the trisomy 21 group were significantly correlated with gestational age such that median levels rose from 1.04 at 11 weeks to 1.30 at 12 weeks and 1.67 at 13 weeks. These findings suggest that first trimester biochemical screening for trisomy 21, which is currently optimised using maternal serum free ,-hCG and PAPP-A and fetal nuchal translucency, will not benefit from the inclusion of inhibin A. Copyright © 2001 John Wiley & Sons, Ltd. [source] The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's SyndromeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2001G.D. Michailidis Objective To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. Design Retrospective five-year review. Setting Maternity unit of a university hospital. Population An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were , 37 years old. A subgroup (n=4864) also had second trimester biochemical testing by alpha-fetoprotein and free ,-human chorionic gonadotrophin. Main outcome measures Prenatal and postnatal diagnosis of trisomy 21. Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. Conclusion First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester. [source] Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2005P. Hellman Background: Pancreatic tumours are common in patients with multiple endocrine neoplasia type 1 (MEN1), and close surveillance is needed to detect pancreatic lesions at an early stage. Conventional radiology is inefficient in verifying the small tumours indicated by biochemical screening. During the past decade, endoscopic ultrasonography (EUS) has evolved as a sensitive method for the detection of small pancreatic lesions. Methods: EUS was evaluated in 25 patients with MEN1, two of whom had symptoms due to hormonal secretion. Twenty-two patients had biochemical signs of pancreatic tumours, and in five patients lesions were located by either computed tomography (two) or transabdominal ultrasonography (three). Results: EUS visualized pancreatic tumours in the five patients in whom lesions were detected by the other methods and in a further nine patients. Eight of these 14 patients had surgery, and tumours were confirmed histopathologically. No lesion was detected in any of the 11 patients with no tumour detected by EUS. Conclusion: EUS is a more sensitive technique for the detection and localization of potentially malignant lesions in patients with MEN1 than computed tomography or transabdominal ultrasonography. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||