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1.
Vaccine ; 29(17): 3284-92, 2011 Apr 12.
Article in English | MEDLINE | ID: mdl-21349366

ABSTRACT

GMZ2 adjuvanted by aluminum hydroxide is a candidate malaria vaccine that has successfully passed phase 1 clinical testing in adult German and Gabonese volunteers and Gabonese children under five. Here we report a preclinical study screening a series of adjuvant vehicles and Toll-like receptor (TLR) agonists in CB6F1 mice to identify an improved formulation of GMZ2 suitable for further human clinical studies. GMZ2 formulated in an oil-in-water emulsion plus the synthetic TLR4 agonist GLA elicits the highest (a) vaccine-specific IgG2a and total IgG titers, (b) parasite-specific IFA titers, (c) levels of Type 1 cytokine responses (IFN-γ), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, GLA helps to elicit a vaccine-specific Type 1 antibody profile together with high levels of LLPC, both of which are thought to be essential for the development of long-term protective immunity against clinical malaria.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Antibodies, Protozoan/blood , Lipid A/administration & dosage , Malaria Vaccines/immunology , Th1 Cells/immunology , Toll-Like Receptor 4/agonists , Animals , Female , Immunoglobulin G/blood , Malaria Vaccines/administration & dosage , Mice , Mice, Inbred C57BL
2.
Malar J ; 9: 296, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20977761

ABSTRACT

BACKGROUND: In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological studies have indicated an association of cytophilic anti-parasite IgG with protection against malaria. It has been hypothesized that the initial antibody responses against parasite antigens upon first few Plasmodium falciparum infections is dominated by non-protective IgG2/IgG4 and IgM antibodies, which then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P. falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high molecular weight (≥ 70 kDa) or low molecular weight (< 70 kDa). The number of discernable low molecular weight parasite antigens detected by different IgG subclass antibodies from each plasma sample was recorded. Using Wilcoxons rank sum test these reactivities were compared amongst groups of individuals with different levels of exposure to P. falciparum infections. RESULTS: IgG4 and IgM antibodies in plasma samples from all groups detected very few parasite antigens. IgG2 antibodies from all groups detected a common pattern of high molecular weight parasite antigens. Cytophilic IgG subclasses in plasma samples from individuals with higher levels of exposure to P. falciparum infections distinctly detected higher numbers of low molecular weight parasite antigens. CONCLUSIONS: In the present study, there was no evidence for switching of antibody responses from non-cytophilic to cytophilic subclasses against blood-stage parasite antigens as a likely mechanism for induction of protective immunity against malaria.


Subject(s)
Antibodies, Protozoan/blood , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Adult , Antigens, Protozoan/analysis , Antigens, Protozoan/chemistry , Antigens, Protozoan/immunology , Blotting, Western , Child , Child, Preschool , Electrophoresis, Polyacrylamide Gel , Humans , Immunoglobulin G/blood , Infant , Infant, Newborn , Molecular Weight , Plasma/immunology , Plasmodium falciparum/chemistry
3.
Prenat Diagn ; 30(2): 110-4, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20013872

ABSTRACT

BACKGROUND: ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. MATERIALS AND METHODS: ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research Delfia ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. RESULTS: ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A + hCG beta + NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR. CONCLUSION: ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases.


Subject(s)
ADAM Proteins/blood , Down Syndrome/blood , Down Syndrome/diagnosis , Membrane Proteins/blood , ADAM12 Protein , Adult , Biomarkers , Case-Control Studies , False Positive Reactions , Female , Humans , Mass Screening , Pregnancy , Pregnancy Trimester, First , Prenatal Care
4.
Acta Derm Venereol ; 89(6): 607-11, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19997692

ABSTRACT

The aim of this study was to describe the epidemiology of chronic wounds in a large cohort of patients from a tertiary hospital out-patient clinic, and examine the significance of serum mannan-binding lectin for the occurrence and clinical presentation of such wounds. The study comprised 489 consecutive patients with chronic foot and leg ulcers. A clinical classification of wound- aetiology was performed, and mannan-binding lectin was measured in the sera of patients and healthy controls. The patients presented with 639 wounds altogether; diabetic foot ulcers (309), venous leg ulcers (188), arterial ulcers (109), and vasculitis (33). The mannan-binding lectin levels of patients with venous leg ulcer, alone or in combination with other types of wounds, differed significantly from the control group, and the frequency of values < 100 ng/ml was significantly higher. In diabetic and arterial ulcer patients the frequency of values >or= 3000 ng/ml was significantly higher than that of the control group. This suggests a role for the innate immunity in the pathology of venous leg ulcers, and indicates different roles for mannan-binding lectin in the development of ulcers with different aetiologies; it further suggests that mannan-binding lectin substitution should be tested in a controlled clinical trial.


Subject(s)
Leg Ulcer/blood , Mannose-Binding Lectin/blood , Vasculitis/blood , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chronic Disease , Cohort Studies , Female , Humans , Leg Ulcer/epidemiology , Male , Middle Aged , Vasculitis/epidemiology
7.
Prenat Diagn ; 28(4): 319-22, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18317998

ABSTRACT

BACKGROUND: First-trimester maternal serum screening for Down syndrome (DS) can be improved by the use of additional serum markers. We examined whether progesterone (P), synthesized by placenta, might be a first-trimester maternal serum marker for fetal DS. MATERIALS AND METHODS: P was quantified in first-trimester maternal serum from 42 DS, six trisomy 18 and two trisomy 13 pregnancies and 115 controls. Log-regression of P versus gestational age in days was used to convert P concentrations into multiples of the median (MoM). RESULTS: The P concentrations in controls increased with gestational age (p = 9.5 x 10(-7)). The log10MoM P distribution in DS pregnancies was not significantly different from that in controls. However, from day 58-67, the log10MoM P was elevated in DS pregnancies (n = 10) with a mean (SD) of 0.1040 (0.0956), compared to a mean (SD) of - 0.0109 (0.1661) in controls (n = 24) (p = 0.05). Five out of six trisomy 18 and both trisomy 13 pregnancies had a P MoM < 1. CONCLUSION: P is not a useful marker for DS in first trimester, except perhaps in a narrow gestational age window from day 58 to 67. P is a trisomy 18/13 marker.


Subject(s)
Aneuploidy , Mothers , Pregnancy Trimester, First/blood , Progesterone/blood , Adult , Biomarkers/blood , Case-Control Studies , Down Syndrome/blood , Down Syndrome/diagnosis , Female , Humans , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/genetics , Prenatal Diagnosis/methods
8.
Prenat Diagn ; 28(3): 247-53, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18302310

ABSTRACT

OBJECTIVE: To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-beta (beta-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. METHODS: A retrospective cohort study including 1,734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. RESULTS: There was a significant relation between low PAPP-A MoM, low beta-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. CONCLUSION: First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor.


Subject(s)
Chorionic Gonadotropin, beta Subunit, Human/blood , Down Syndrome/diagnosis , Nuchal Translucency Measurement , Pregnancy-Associated Plasma Protein-A/analysis , Adult , Cohort Studies , Female , Gestational Age , Humans , Infant, Low Birth Weight/blood , Infant, Newborn , Mass Screening , Obstetric Labor, Premature/blood , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First , Retrospective Studies
9.
J Crohns Colitis ; 2(2): 162-9, 2008 Jun.
Article in English | MEDLINE | ID: mdl-21172207

ABSTRACT

BACKGROUND AND AIMS: The etiology of the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to investigate the influence of genetic, serological, and environmental factors on phenotypic presentation of IBD at diagnosis in a population-based Danish inception cohort from 2003-2005. METHODS: Three-hundred-forty-seven (62%) of 562 cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients answered a questionnaire concerning environmental factors with possible influence on IBD. RESULTS: Fourteen percent of CD patients vs. 11% of controls were positive for common CARD15 mutation (ns), whereas more CD patients than healthy controls were homozygous for the OCTN-TC haplotype (p=0.03). ASCA was more common in CD (22%) than UC (14%) (p=0.045) and was related to age and localization of CD. p-ANCA was more frequent in UC (p=0.00001) but was related to pure colonic CD (p=0.0001). Sugar consumption was significantly higher in CD patients than in UC patients (p=0.0001) and more CD patients than UC patients had undergone appendectomy prior to IBD diagnosis (p=0.03). A possible relation between tonsillectomy and disease severity in CD, and a relation between use of oral contraception and disease localization of UC to rectum/left-sided colon were found. CONCLUSIONS: In this cohort of unselected IBD patients we found a very low frequency of mutations in IBD susceptibility genes and observed a greater impact of ASCA and ANCA than of genetic factors on disease phenotypes. In addition, several environmental factors seemed to influence disease occurrence and disease presentation in both UC and especially CD.

10.
Prenat Diagn ; 27(7): 611-5, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17465398

ABSTRACT

BACKGROUND: ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. MATERIALS AND METHODS: The concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log(10) MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (free beta-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. RESULTS: The ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log(10) MoM (SD) of 0.268 (0.2678) compared to a mean log(10) MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free beta-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%--by adding ADAM 12 to the double test (AFP + free beta-hCG) was 4%, similar to that of adding uE3 to the double test. CONCLUSION: ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additional or alternative marker to those currently used in the second-trimester.


Subject(s)
ADAM Proteins/blood , Down Syndrome/diagnosis , Membrane Proteins/blood , Pregnancy Trimester, Second/blood , ADAM12 Protein , Biomarkers/blood , Down Syndrome/blood , Female , Humans , Mass Screening , Pregnancy
11.
Prenat Diagn ; 26(10): 973-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16892462

ABSTRACT

BACKGROUND: A Disintegrin And Metalloprotease 12 (ADAM 12) is a glycoprotein synthesised by placenta and it has been shown to be a potential first-trimester maternal serum marker for Down syndrome (DS) in two small series. Here we analyse further, the potential of ADAM 12 as a marker for DS in a large collection of first-trimester serum samples. MATERIALS AND METHODS: The concentration of ADAM 12 was determined in 10-14-week pregnancy sera from 218 DS pregnancies and 389 gestational age-matched control pregnancies, which had been collected as part of routine prospective first-trimester screening programs (DS = 105) or as part of previous research studies (DS = 113). ADAM 12 was measured using a semi-automated time resolved immunofluorometric assay and median values for normal pregnancies were established by polynomial regression. These medians were then used to determine population distribution parameters for DS and normal pregnancy groups. Correlation with previously established PAPP-A and free beta-hCG multiple of the medians (MoMs) and delta nuchal translucency (NT) were determined and used to model the performance of first-trimester screening with ADAM 12 in combination with other first-trimester markers at various time periods across the first trimester. The benefits of a contingent testing model incorporating early measurement of PAPP-A and ADAM 12 were also explored. RESULTS: The maternal serum concentration of ADAM 12 was significantly reduced (p = 0.0049) with an overall median MoM of 0.79 in the DS cases and a log(10) MoM SD of 0.3734 in the DS cases and 0.3353 in the controls. There was a significant correlation of ADAM 12 MoM in DS cases with gestational age (r = 0.375) and the median MoM increased from 0.50 at 10-11 weeks to 1.38 at 13 weeks. ADAM 12 was correlated with maternal weight (r(controls) = 0.283), PAPP-A (r(controls) = 0.324, r(DS) = 0.251) but less so with free beta-hCG (r(controls) = 0.062, r(DS) = 0.049) and delta NT (r(controls) = 0.110, r(DS) = 0.151). ADAM 12 was significantly (p = 0.026) lower in smokers (0.87 vs 1.00) and elevated in Afro-Caribbean women compared to Caucasian women (1.34 vs 1.00). Population modelling using parameters from this and an earlier study showed that a combination of ADAM 12 and PAPP-A measured at 8-9 weeks and combined with NT and free beta-hCG measured at 12 weeks could achieve a detection rate of 97% at a 5% false-positive rate or 89% at a 1% false-positive rate. PAPP-A and ADAM 12 alone at 8-9 weeks could identify 91% of cases at a 5% false-positive rate. Using this as part of a contingent-screening model to select an intermediate risk group of women for NT and free beta-hCG at 11-12 weeks would enable the detection of 92% of cases with a 1% false-positive rate at a cost of providing NT and free beta-hCG for 6% of women with 94% of women having completed screening by the 10th week of pregnancy. CONCLUSION: ADAM 12 in early first trimester is a very efficient marker of DS. In combination with existing markers, it offers enhanced screening efficiency in a two-stage sequential first-trimester screening program or in a contingent-screening model, which may have benefits in health economies where universal access to high quality ultrasound is difficult. More data on early first-trimester cases with DS are required to establish more secure population parameters by which to assess further the validity of these models.


Subject(s)
ADAM Proteins/blood , Disintegrins/blood , Down Syndrome/diagnosis , Membrane Proteins/blood , Placenta/metabolism , ADAM12 Protein , Biomarkers/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Female , Gestational Age , Humans , Normal Distribution , Pregnancy , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/analysis
12.
Prenat Diagn ; 26(3): 218-20, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16450349

ABSTRACT

OBJECTIVES: To establish the distribution of serological and ultrasound first-trimester Down syndrome markers in twins and identify correlations of significance for risk calculation. METHODS: Nuchal translucency (NT), PAPP-A and betahCG data were extracted from 181 twin pregnancies (31 mono- and 150 dichorionic) with a normal outcome. All pregnancies were consecutively and prospectively included and examined in the Copenhagen First-Trimester Study. The variance of the sum and the difference of log MoM NT values in twin pairs was used to calculate the correlation. RESULTS: The serological markers did not correlate and were nearly twice the value seen in singleton pregnancies with a median PAPP-A MoM of 2.14 and a median free betahCG MoM of 2.06. Chorionicity was not found to influence the level of biochemical markers. In all twin pairs (r = 0.343, p < 0.001, F-test), as well as mono- (r = 0.404, p = 0.011, F-test) and dichorionic twins (r = 0.316, p < 0.001, F-test) there was a significant correlation between log MoM NT in each pair. CONCLUSION: As the NT values of fetuses in subsequent pregnancies from the same woman do not correlate, the correlation between NTs in twins reflects that the NT is influenced by placental and maternal factors specific for the particular pregnancy, for example, nutrient supply or vascularisation. The correlation may be useful to improve the precision of the prenatal risk assessment for Down syndrome in first-trimester twin pregnancies. The serological markers were elevated in the examined twins as previously described.


Subject(s)
Diseases in Twins/diagnostic imaging , Down Syndrome/diagnostic imaging , Nuchal Translucency Measurement , Prenatal Diagnosis/methods , Algorithms , Biomarkers/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Crown-Rump Length , Diseases in Twins/diagnosis , Down Syndrome/diagnosis , Female , Fetal Diseases/diagnosis , Humans , Linear Models , Pregnancy , Pregnancy-Associated Plasma Protein-A/analysis , Risk Assessment , Twins, Dizygotic , Twins, Monozygotic , Ultrasonography, Prenatal
14.
Am J Cardiol ; 96(3): 405-7, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-16054468

ABSTRACT

The 97T polymorphism of the KCNE5 gene, coding for an inhibitory beta-subunit, MiRP4, of the repolarizing cardiac potassium ion channel KCNQ1, was significantly more frequent in 96 controls than in 158 patients with atrial fibrillation (AF). KCNQ1 is involved in cardiac action potential, and increased function has been associated with AF. Because the KCNE5 gene is located on the X chromosome, the protection conferred by the 97T polymorphism may help explain the gender-related difference in the risk of AF.


Subject(s)
Atrial Fibrillation/genetics , Polymorphism, Genetic , Potassium Channels, Voltage-Gated/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chi-Square Distribution , Female , Genotype , Humans , Male , Middle Aged , Risk Assessment
15.
Prenat Diagn ; 25(6): 484-8, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15966040

ABSTRACT

OBJECTIVE: To assess whether existing weight correction formulas for PAPP-A and free-beta-hCG developed for weeks 11 to 14 can be applied to pregnancies in weeks 8 to 10. METHODS: Development of formulas based on limited data sets of 8- to 10-week pregnancies and comparison with existing formulas. Calculation of median MoMs adjusted with different formulas for weight correction. RESULTS: Weight correction formulas for the gestational age of 11 to 14 weeks were not appropriate in the 8- to 10-week gestational age interval for PAPP-A, whereas existing weight correction formulas could be applied to free-beta-hCG, independent of gestational age interval. CONCLUSION: If PAPP-A is used in different gestational age intervals, weight corrections should be developed for the interval.


Subject(s)
Body Weight , Chorionic Gonadotropin, beta Subunit, Human/blood , Down Syndrome/diagnosis , Gestational Age , Pregnancy-Associated Plasma Protein-A/analysis , Prenatal Diagnosis/methods , Female , Humans , Linear Models , Pregnancy , Pregnancy Trimester, First
16.
Prenat Diagn ; 23(7): 593-8, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12868091

ABSTRACT

OBJECTIVES: To estimate the screening performance of different combinations of first- and second-trimester markers, including a new marker, the proform of eosinophil major basic protein (proMBP). METHODS: The population comprised 195 singleton pregnancies with a normal outcome enrolled in the Copenhagen First Trimester Study, in which a serum sample was available from both the first and the second trimester. The performance of different marker combinations was estimated by receiver-operator-characteristics (ROC) analysis using a Monte Carlo simulation and distributions of log(10)MoM markers and their correlations, derived from our normal material and Down syndrome cases from the literature. RESULTS: Using a fixed screen-positive rate (SPR) of 5%, the first-trimester combined test [nuchal translucency (NT), PAPP-A and free beta-hCG] yielded a detection rate (DR) of 76%, and the integrated test (NT, PAPP-A, AFP, hCG, uE3 and inhibin A) yielded a DR of 86%. With a DR of 90%, the best combination was the first-trimester beta-hCG and NT with the second-trimester proMBP and AFP. ProMBP combined with the triple test increased the DR from 62 to 83%, whereas the addition of inhibin A only increased the DR to 69%. CONCLUSION: These results suggest that proMBP may be an important new marker in Down syndrome screening and, in particular, a good substitute for inhibin A.


Subject(s)
Down Syndrome/blood , Down Syndrome/diagnosis , Prenatal Diagnosis , Ribonucleases/blood , Adult , Biomarkers/blood , Blood Proteins , Down Syndrome/diagnostic imaging , Eosinophil Granule Proteins , Female , Humans , Monte Carlo Method , Neck/diagnostic imaging , Neck/embryology , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , ROC Curve , Ultrasonography
17.
Prenat Diagn ; 22(13): 1207-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12478634

ABSTRACT

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses.


Subject(s)
Biomarkers/blood , Down Syndrome/diagnosis , Pregnancy/blood , Sex Characteristics , Adult , Chorionic Gonadotropin, beta Subunit, Human/blood , Denmark/epidemiology , Down Syndrome/epidemiology , Female , Humans , Male , Mass Screening , Neck/diagnostic imaging , Neck/embryology , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/analysis , Prenatal Diagnosis , Ultrasonography , alpha-Fetoproteins/analysis
19.
Ugeskr Laeger ; 164(39): 4532-6, 2002 Sep 23.
Article in Danish | MEDLINE | ID: mdl-12380396

ABSTRACT

INTRODUCTION: The aim of the study was to describe maternal age-based screening for Down's syndrome (DS) in Denmark, 1980-1998, and to describe and discuss the possibilities for more effective screening procedures. MATERIAL AND METHODS: The prenatally diagnosed and delivered infants with DS as registered in the Danish Cytogenetic Registry, were compared with the expected number calculated from each year's maternal age distribution and the age-dependent DS incidence, taking into account the high probability of miscarriage in DS pregnancies. The expected performance of various screening procedures was calculated by Monte Carlo simulation. RESULTS: Because of an older maternal age in the pregnant population, the annual expected number of infants with DS rose from about 60 in 1980 to about 110 in 1998. Despite a high frequency (about 11%) of invasive diagnostic procedures, the annual number of DS births also increased in the same period, namely from about 45 to about 65. It is calculated that a change from age-based screening to screening based on a serological risk evaluation could--with the full participation of all pregnant women--have reduced the total number of DS births in this period by about 300. DISCUSSION: Revised guidelines from age-based screening to serological screening may potentially reduce the number of DS births cases in Denmark from about 65 per year to about 15.


Subject(s)
Down Syndrome/diagnosis , Prenatal Diagnosis , Adult , Denmark/epidemiology , Down Syndrome/epidemiology , Female , Humans , Incidence , Infant, Newborn , Mass Screening/methods , Mass Screening/trends , Maternal Age , Practice Guidelines as Topic , Pregnancy , Prenatal Diagnosis/methods , Prenatal Diagnosis/trends
20.
Ugeskr Laeger ; 164(20): 2617-23, 2002 May 13.
Article in Danish | MEDLINE | ID: mdl-12043405

ABSTRACT

INTRODUCTION: Our main aims were to establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes of haemorrhagic rashes accompanied by fever. MATERIALS AND METHODS: This prospective study comprised 264 infants and children hospitalised with fever and skin haemorrhages. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables discriminated meningococcal disease from other conditions on admission: skin haemorrhages of (1) characteristic appearance; (2) universal distribution and (3) a maximum diameter of > 2 mm; (4) poor general condition; and (5) nuchal rigidity. DISCUSSION: If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false-positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.


Subject(s)
Fever/diagnosis , Hemorrhage/diagnosis , Meningitis, Bacterial/diagnosis , Meningitis, Viral/diagnosis , Meningococcal Infections/diagnosis , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Viral/diagnosis , Skin/pathology , Child , Child, Preschool , Diagnosis, Differential , Fever/microbiology , Fever/virology , Hemorrhage/microbiology , Hemorrhage/pathology , Humans , Infant , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/pathology , Meningitis, Viral/microbiology , Meningitis, Viral/pathology , Meningococcal Infections/microbiology , Meningococcal Infections/pathology , Microbiological Techniques , Prospective Studies , Skin Diseases, Bacterial/microbiology , Skin Diseases, Bacterial/pathology , Skin Diseases, Viral/microbiology , Skin Diseases, Viral/pathology
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