ABSTRACT
BACKGROUND: Students with mathematical learning disabilities (MLD) struggle with number processing skills (e.g., enumeration and number comparison) and arithmetic fluency. Traditionally, MLD is identified based on arithmetic fluency. However, number processing skills are suggested to differentiate low achievement (LA) from MLD. AIMS: This study investigated the accuracy of number processing skills in identifying students with MLD and LA, based on arithmetic fluency, and whether the classification ability of number processing skills varied as a function of grade level. METHODS AND PROCEDURES: The participants were 18,405 students (girls = 9080) from Grades 3-9 (ages 9-15). Students' basic numerical skills were assessed with an online dyscalculia screener (Functional Numeracy Assessment -Dyscalculia Battery, FUNA-DB), which included number processing and arithmetic fluency as two factors. OUTCOMES AND RESULTS: Confirmatory factor analyses supported a two-factor structure of FUNA-DB. The two-factor structure was invariant across language groups, gender, and grade levels. Receiver operating characteristics curve analyses indicated that number processing skills are a fair classifier of MLD and LA status across grade levels. The classification accuracy of number processing skills was better when predicting MLD (cut-off < 5 %) compared to LA (cut-off < 25 %). CONCLUSIONS AND IMPLICATIONS: Results highlight the need to measure both number processing and arithmetic fluency when identifying students with MLD.
Subject(s)
Dyscalculia , Mathematics , Humans , Female , Male , Child , Dyscalculia/diagnosis , Dyscalculia/physiopathology , Adolescent , Mathematics/education , Learning Disabilities/diagnosis , Students , Mathematical Concepts , Factor Analysis, Statistical , Achievement , Problem SolvingABSTRACT
INTRODUCTION: The aim of this review is to describe how various AI-supported applications are used in head and neck cancer radiotherapy treatment planning, and the impact on dose management in regards to target volume and nearby organs at risk (OARs). METHODS: Literature searches were conducted in databases and publisher portals Pubmed, Science Direct, CINAHL, Ovid, and ProQuest to peer reviewed studies published between 2015 and 2021. RESULTS: Out of 464 potential ones, ten articles covering the topic were selected. The benefit of using deep learning-based methods to automatically segment OARs is that it makes the process more efficient producing clinically acceptable OAR doses. In some cases automated treatment planning systems can outperform traditional systems in dose prediction. CONCLUSIONS: Based on the selected articles, in general AI-based systems produced time savings. Also, AI-based solutions perform at the same level or better than traditional planning systems considering auto-segmentation, treatment planning and dose prediction. However, their clinical implementation into routine standard of care should be carefully validated IMPLICATIONS TO PRACTICE: AI has a primary benefit in reducing treatment planning time and improving plan quality allowing dose reduction to the OARs thereby enhancing patients' quality of life. It has a secondary benefit of reducing radiation therapists' time spent annotating thereby saving their time for e.g. patient encounters.
Subject(s)
Artificial Intelligence , Head and Neck Neoplasms , Humans , Quality of Life , Radiotherapy Planning, Computer-Assisted/methods , Head and Neck Neoplasms/radiotherapy , Organs at RiskABSTRACT
Background: Journalists who cover traumatic events are at risk of developing long-term impairment, such as post-traumatic stress disorder (PTSD). The exposure may also result in perceived positive outcomes, conceptualised as post-traumatic growth (PTG). Social support (SS) at work is one factor that might affect the outcome. Objective: To investigate the relationship between three subtypes of workplace SS (perceived support, received support, received recognition), and post-traumatic stress symptoms (PTSS) and between SS and PTG in journalists who have covered a large terror attack. Furthermore, to examine the relationship between ethical dilemmas (ED) experienced while covering the incident, PTSS and PTG. Method: The study was performed as a web-based survey sent out eight to nine months after the incident to Norwegian journalists (N = 375) who covered the terror attack in Norway in 2011. Results: Journalists who received more support also reported a higher level of PTSS (r = .168, p = .044). Recognition and perceived support showed no significant association with PTSS. Journalists who received more recognition also experienced more PTG (r = .542, p < .001). Neither perceived nor received support were significantly associated with PTG. More ED was positively associated with both PTSS (r = .469, p < .001) and PTG (r = .402, p < .001). Conclusions: Journalists with more PTSS may have participated more in organised support such as debriefing activities in the aftermath of the coverage. Some journalists may have experienced stress related to a fear of causing additional harm to first-hand victims (ED). Others may have experienced PTG related to reflections and discussions about their ED in the aftermath of a coverage. Media companies may promote PTG among their journalists by developing a culture for recognition of employees' contributions during demanding missions.
Antecedentes: los periodistas que cubren eventos traumáticos corren el riesgo de desarrollar una discapacidad a largo plazo, como el trastorno de estrés postraumático (TEPT). La exposición también puede dar lugar a resultados positivos percibidos, conceptualizados como crecimiento postraumático (CPT). El apoyo social (AS) en el trabajo es un factor que podría afectar el resultado. Objetivo: investigar la relación entre tres subtipos de AS en el lugar de trabajo (apoyo percibido, apoyo recibido, reconocimiento recibido) y síntomas de estrés postraumático (SEPT) y entre AS y CPT en periodistas que han cubierto un gran ataque terrorista. Adicionalmente, examinar la relación entre los dilemas éticos (DE) experimentados al cubrir el incidente, SEPT y CPT. Método: El estudio se realizó como una encuesta basada en la web, enviada ocho a nueve meses después del incidente a periodistas noruegos (n = 375) que cubrieron el ataque terrorista en Noruega en 2011. Resultados: los periodistas que recibieron más apoyo también informaron un nivel más alto de SEPT (r = .168, p = .044). El reconocimiento y apoyo percibido no mostraron asociación significativa con SEPT. Los periodistas que recibieron más reconocimiento también experimentaron más CPT (r = .542, p <.001). Ni el apoyo percibido ni recibido se asociaron significativamente con el CPT. Más DE se asoció positivamente con SEPT (r = .469, p <.001) y CPT (r = .402, p <.001). Conclusiones: Los periodistas con más SEPT pueden haber participado más en apoyo organizado, como actividades de reporte y discusión (debriefing) después de la cobertura. Algunos periodistas pueden haber experimentado estrés relacionado con el temor de causar daño adicional a las víctimas de primera mano (DE). Otros pueden haber experimentado CPT relacionado con reflexiones y discusiones sobre su DE en las repercusiones de una cobertura. Las compañías de medios podrían promover el CPT entre sus periodistas desarrollando una cultura de reconocimiento de las contribuciones de los empleados durante misiones exigentes.
ABSTRACT
PURPOSE: Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. MATERIALS AND METHODS: A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. RESULTS: Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. CONCLUSION: The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images.
Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Organs at Risk , Radiotherapy Dosage , Tomography, X-Ray ComputedABSTRACT
BACKGROUND AND AIMS: Aneurysmal bone cysts represent about 1% of primary bone tumors. The standard treatment is curettage, followed by local adjuvant treatments and bone grafting. The problem is the high recurrence rate. The purpose of this study was to evaluate retrospectively the use of bioactive glass as a filling material in the treatment of aneurysmatic bone cysts in children. MATERIAL AND METHODS: A total of 18 consecutive children (mean 11.3 years at surgery; 10 males; 11 lower, 6 upper limb, 1 pelvis; 15 with primary surgery) with histologically proven primary aneurysmal bone cysts operated with curettage and bioactive glass filling between 2008 and 2013 were evaluated after a mean follow-up of 2.0 years (range, 0.7-5.1 years). RESULTS: Two (11%) patients showed evidence of aneurysmal bone cyst recurrence and both have been re-operated for recurrence. Bone remodeling was noted in all patients with remaining growth and no growth plate disturbances were recorded. Two patients needed allogeneic blood transfusion. No intraoperative or postoperative complications were recorded. CONCLUSION: We conclude that bioactive glass is a suitable filling material for children with primary aneurysmal bone cyst. Bioactive glass did not affect bone growth and no side effects were reported.
Subject(s)
Biocompatible Materials/therapeutic use , Bone Cysts, Aneurysmal/diagnostic imaging , Bone Cysts, Aneurysmal/surgery , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Ceramics/therapeutic use , Adolescent , Bone Remodeling/physiology , Child , Child, Preschool , Cohort Studies , Databases, Factual , Female , Follow-Up Studies , Humans , Male , Preoperative Care , Radiography/methods , Retrospective Studies , Risk Assessment , Treatment OutcomeABSTRACT
AIM: To report a case of successful endovascular treatment of mycotic aneurysms of the inferior mesenteric artery and the aorta. CASE REPORT: Infrarenal aortitis in a 55-year-old multimorbid man resulted in formation of two mycotic aneurysms, one in the infrarenal aorta and the other in the inferior mesenteric artery. The patient was treated with a bifurcated aortic endograft. Antibiotic therapy was continued postoperatively for one year. Shrinkage of both aneurysms was obtained with no signs of infection or endoleaks at five year follow-up. CONCLUSION: Aortic endografting combined with long-term antibiotic treatment may be considered as a treatment option in similar cases.
Subject(s)
Aorta, Abdominal , Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Mesenteric Artery, Inferior , Aneurysm, Infected , Anti-Bacterial Agents/administration & dosage , Aorta, Abdominal/pathology , Aorta, Abdominal/surgery , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/physiopathology , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/methods , Humans , Male , Mesenteric Artery, Inferior/pathology , Mesenteric Artery, Inferior/surgery , Middle Aged , Perioperative Period , Stents , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
We conducted a retrospective study to assess the prevalence of adverse reactions to metal debris (ARMD) in patients operated on at our institution with metal-on-metal (MoM) total hip replacements with 36 mm heads using a Pinnacle acetabular shell. A total of 326 patients (150 males, 175 hips; 176 females, 203 hips) with a mean age of 62.7 years (28 to 85) and mean follow-up of 7.5 years (0.1 to 10.8) participating in our in-depth modern MoM follow-up programme were included in the study, which involved recording whole blood cobalt and chromium ion measurements, Oxford hip scores (OHS) and plain radiographs of the hip and targeted cross-sectional imaging. Elevated blood metal ion levels (> 5 parts per billion) were seen in 32 (16.1%) of the 199 patients who underwent unilateral replacement. At 23 months after the start of our modern MoM follow-up programme, 29 new cases of ARMD had been revealed. Hence, the nine-year survival of this cohort declined from 96% (95% CI 95 to 98) with the old surveillance routine to 86% (95% CI 82 to 90) following the new protocol. Although ARMD may not be as common in 36 mm MoM THRs as in those with larger heads, these results support the Medicines and Healthcare Products Regulatory Agency guidelines on regular reviews and further investigations, and emphasise the need for specific a follow-up programme for patients with MoM THRs.
Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Metal-on-Metal Joint Prostheses/adverse effects , Metals/adverse effects , Adult , Aged , Aged, 80 and over , Chromium/blood , Cobalt/blood , Female , Follow-Up Studies , Hip Joint/diagnostic imaging , Humans , Male , Middle Aged , Prevalence , Radiography , Reoperation , Retrospective StudiesABSTRACT
PURPOSE: To determine whether bones could be localized accurately by using MR images only in radiotherapy treatment planning. Furthermore, to measure absorbed dose in a material behind different parts of the bone, and to evaluate dose calculation error in a pseudo-CT image by assuming a single electron density for the bones. METHODS: A dedicated phantom was constructed using fresh deer bones and gelatine. The accuracy of the bone edge location and the bone diameter in MR images were evaluated by comparing those in the images with the actual measures. The absorbed dose behind the bones was measured by a matrix detector at 6 and 15 MV. Thedose calculation error in the bulk density pseudo-CT image was quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00, Elekta CMS Software). RESULTS: The examination of bone position revealed that the bones can be localized within a 1-mm-pixel-size in the MR images. The measured dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15 MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations illustrated that the bulk density pseudo-CT image used causes errors up to nearly 2% to the dose behind the middle part, but also, the edge of the femur. CONCLUSIONS: This research ascertains that the bone localization is not a restrictive issue for radiotherapy treatment planning by using MR imageonly. The work indicates also that the decrease in absorbed dose is not necessarily dependent on the diameter of the bone. Future research shouldinvestigate the generation of more complex pseudo-CT images and the dosecalculations by using these. Supported by Elekta.
ABSTRACT
We aimed to determine the minimum inhibitory concentrations (MICs) of Lactobacillus rhamnosus (n=75) strains, to study their antibiotic resistance genes with microarray, and to assess the microbiological cut-off values of tested antimicrobial agents. L. rhamnosus strains were tested with agar dilution, broth microdilution and Etest methods for ampicillin, clindamycin, erythromycin, gentamicin, streptomycin, and tetracycline using specific LSM medium. Most of the L. rhamnosus strains were found phenotypically susceptible to all six antibiotics tested. Four of the strains were phenotypically multiresistant, three strains to clindamycin, erythromycin and streptomycin and one strain to streptomycin and tetracycline. Some of the resistant (n=8) and susceptible (n=5) strains were further studied with a microarray method to reveal the antibiotic resistance genes behind the phenotypic resistances. From our experience, we recommend that microbiological cut-off values should be proposed according to the method used.
Subject(s)
Anti-Bacterial Agents/pharmacology , Lacticaseibacillus rhamnosus/drug effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Bacterial , Lacticaseibacillus rhamnosus/genetics , Lacticaseibacillus rhamnosus/metabolism , Microbial Sensitivity TestsABSTRACT
* The variability of branch-level hydraulic properties was assessed across 12 Scots pine populations covering a wide range of environmental conditions, including some of the southernmost populations of the species. The aims were to relate this variability to differences in climate, and to study the potential tradeoffs between traits. * Traits measured included wood density, radial growth, xylem anatomy, sapwood- and leaf-specific hydraulic conductivity (K(S) and K(L)), vulnerability to embolism, leaf-to-sapwood area ratio (A(L) : A(S)), needle carbon isotope discrimination (Delta13C) and nitrogen content, and specific leaf area. * Between-population variability was high for most of the hydraulic traits studied, but it was directly associated with climate dryness (defined as a combination of atmospheric moisture demand and availability) only for A(L) : A(S), K(L) and Delta13C. Shoot radial growth and A(L) : A(S) declined with stand development, which is consistent with a strategy to avoid exceedingly low water potentials as tree size increases. In addition, we did not find evidence at the intraspecific level of some associations between hydraulic traits that have been commonly reported across species. * The adjustment of Scots pine's hydraulic system to local climatic conditions occurred primarily through modifications of A(L) : A(S) and direct stomatal control, whereas intraspecific variation in vulnerability to embolism and leaf physiology appears to be limited.
Subject(s)
Adaptation, Physiological , Climate , Phenotype , Pinus sylvestris/physiology , Water/physiology , Adaptation, Physiological/genetics , Carbon Isotopes , Dehydration , Environment , Genetic Variation , Nitrogen/analysis , Pinus sylvestris/genetics , Plant Leaves/anatomy & histology , Plant Stomata , Principal Component Analysis , Wood/anatomy & histology , Xylem/anatomy & histologyABSTRACT
AIMS: To examine the lactic acid bacteria flora of weaning piglets, to define the distribution of different lactobacilli species in piglet faecal samples, and to determine the susceptibility phenotype to 11 antibiotic of different families. METHODS AND RESULTS: The faecal samples were taken from piglets with good herd status at 11 and 28 days after weaning. The Lactobacillus isolates (n = 129) from 78 animals housed in pairs in 39 pens were preliminarily identified by their morphology and biochemical characteristics. Partial 16S ribosomal DNA (16S rDNA) was used to identify the isolates to the species level, and RAPD (randomly amplified polymorphism DNA) profiles to differentiate Lactobacillus isolates to the strain level. Based on these studies, 67 strains were selected for antibiotic resistant tests. The most numerous Lactobacillus species found in the piglets was Lactobacillus reuteri (n = 43). Other lactobacilli were L. salivarius (n = 15), L. agilis (n = 4), L. johnsonii (n = 2), L. vaginalis (n = 1), L. mucosae (n = 1) and L. gallinarum (n = 1). All the strains were susceptible to chloramphenicol, ampicillin and gentamicin. Two L. salivarius isolates and two L. reuteri isolates were found to be multiresistant. CONCLUSIONS: This study indicates that the faecal Lactobacillus flora in piglets consists mainly of L. reuteri, L. salivarius and L. acidophilus group lactobacilli, and the distribution of lactobacilli is similar between individuals of the same age and with the same diet. Most of the Lactobacillus isolates tested were sensitive to the antibiotics used in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Valuable information on Lactobacillus species distribution and their antibiotic resistance profiles in piglets is obtained.
Subject(s)
Drug Resistance, Microbial/genetics , Feces/microbiology , Lactobacillus/isolation & purification , Probiotics/isolation & purification , Swine/microbiology , Animals , DNA Fingerprinting , Lactobacillus/genetics , Microbial Sensitivity Tests , Molecular Sequence Data , Random Amplified Polymorphic DNA Technique , Sequence Analysis , WeaningABSTRACT
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune disease with autosomal recessive inheritance. APECED is characterized by the breakdown of tolerance to several organ-specific selfantigens. The symptoms of APECED fall into three main categories: autoimmune polyendocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies. The gene defective in APECED, AIRE, has been cloned and numerous mutations in this gene have been found in patients with APECED. AIRE is predicted to encode a 545-amino-acid protein containing structural domains characteristic for transcription regulators. The protein has been shown to act as a transcriptional activator in vitro. The AIRE protein is mainly localized to the nucleus, where it can be detected as speckles resembling nuclear bodies. In humans, the expression of AIRE has been observed predominantly in immunologically relevant tissues, especially the thymus. Recently, we have shown in the mouse that Aire is also expressed in various tissues and cell types outside the immune system.
Subject(s)
Polyendocrinopathies, Autoimmune/etiology , Animals , Female , Gene Expression , Genes, Recessive , Humans , Male , Mice , Mutation , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/metabolism , Tissue Distribution , Transcription Factors/genetics , Transcription Factors/metabolism , AIRE ProteinABSTRACT
Industrial ecology (IE) promotes the development of industrial systems based on recycling of matter and cascading of energy through cooperation. In this paper, the local/regional industrial ecosystem approach is reflected in two examples from Finland. The local forest industry system is based on renewable resources, waste materials and energy utilisation between forestry companies, a saw-mill, a pulp mill, a paper mill and a forest industry power plant. Waste energy from electricity production is used for production of heat and process steam. Regional city energy supply systems in Finland are also to a large extent arranged around power plants that utilise waste energy. The potential of combining the forest industry system with the energy supply systems of cities is considered and the conditions for success in the Finnish case are discussed.
Subject(s)
Conservation of Natural Resources/economics , Ecology , Energy-Generating Resources , Forestry , Refuse Disposal/economics , Cities , Finland , Industry , Power PlantsABSTRACT
The Gab1-docking protein has been shown to regulate phosphatidylinositol 3-kinase PI3K activity and potentiate nerve growth factor (NGF)-induced survival in PC12 cells. Here, we investigated the potential of Gab1 to induce neurite outgrowth and DNA synthesis, two other important aspects of NGF-induced neuronal differentiation of PC12 cells and NGF-independent survival. We generated a recombinant adenovirus encoding hemagglutinin (HA)-epitope-tagged Gab1 and expressed this protein in PC12 cells. HA-Gab1 was constitutively tyrosine-phosphorylated in PC12 cells and induced the phosphorylation of Akt/protein kinase B and p44/42 mitogen-activated protein kinase. HA-Gab1-stimulated a 10-fold increase in neurite outgrowth in the absence of NGF and a 5-fold increase in NGF-induced neurite outgrowth. HA-Gab1 also stimulated DNA synthesis and caused NGF-independent survival in PC12 cells. Finally, we found that HA-Gab1-induced neuritogenesis was completely suppressed by pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) activity and 50% suppressed by inhibition of PI3K activity. In contrast, HA-Gab1-stimulated cell survival was efficiently suppressed only by inhibition of both PI3K and MEK activities. These results indicate that Gab1 is capable of mediating differentiation, DNA synthesis, and cell survival and uses both PI3K and MEK signaling pathways to achieve its effects.
Subject(s)
DNA/biosynthesis , Neurites/physiology , Phosphoproteins/physiology , Protein Serine-Threonine Kinases , Adenoviridae/genetics , Amino Acid Sequence , Animals , Apoptosis , Cell Survival , Molecular Sequence Data , Nerve Growth Factor/pharmacology , PC12 Cells , Phosphatidylinositol 3-Kinases/physiology , Phosphorylation , Proto-Oncogene Proteins/physiology , Proto-Oncogene Proteins c-akt , Rabbits , Rats , Ribosomal Protein S6 Kinases/metabolism , Tyrosine/metabolismABSTRACT
The Tie gene encodes an endothelial cell receptor tyrosine kinase necessary for normal vascular development. The Tie gene promoter targets expression of heterologous genes specifically to endothelial cells in transgenic mice. Here we have characterized the promoter sequences critical for endothelial cell-specific activity in cultured cells and transgenic mice. Progressive deletions and site-directed mutations of the promoter showed that the critical endothelial cell-specific elements are an octamer transcription factor binding site and several Ets binding sites located in two clusters within 300 bp upstream of the major transcription initiation site. Among members of the Ets transcription factor family tested, NERF-2 (a novel transcription factor related to the ets factor ELF-1), which is expressed in endothelial cells, and ETS2 showed the strongest transactivation of the Tie promoter; ETS1 gave lower levels of stimulation and the other Ets factors gave little or no transactivation. Furthermore, the Tie promoter directed the production of high amounts of human growth hormone into the circulation of transgenic mice. The secreted amounts correlated with transgene copy number, being relatively insensitive to the effects of the transgene integration site. These properties suggest that Tie promoter activity is controlled by endothelial cell Ets factors and that it has potential for use in vectors for endothelial cell-specific gene expression.
Subject(s)
Endothelium, Vascular/enzymology , Gene Expression Regulation, Enzymologic , Promoter Regions, Genetic , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Transcription Factors/genetics , Animals , Base Sequence , Cell Line , Endothelium, Vascular/embryology , Gene Expression Regulation, Developmental , Humans , Mice , Mice, Transgenic , Molecular Sequence Data , Proto-Oncogene Protein c-ets-1 , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-ets , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptors, TIE , Transcription Factors/metabolism , TransfectionABSTRACT
We have used high-specificity and precision immunofluorometric assays to measure the elimination half-times of human chorionic gonadotropin (hCG), hCG alpha, and hCG beta in serum over 21 days after delivery in six women with term pregnancies. Baseline concentrations and half-times were calculated with the use of a curve-fitting algorithm for multiexponential decay. In contrast to the two-component model, a three-component exponential function with baseline provided a fit for which predicted values could not be distinguished from the observed values by analysis of variance. Median half-times were 3.6, 18.0, and 53.0 h for hCG; 1.0, 23.4, and 194 h for hCG beta; and 0.6, 6.2, and 21.9 h for hCG alpha. The mean ratio of hCG alpha to hCG decreased rapidly from 36.9% to 3.3% on day 3; thereafter it increased to 64.3% 21 days after delivery because of a higher baseline concentration of hCG alpha. hCG beta had the slowest total elimination rate, and the ratio of hCB beta to hCG in serum increased from 0.8% before delivery to 26.7% after 21 days. If the metabolism of hCG and hCG beta is similar in patients with trophoblastic disease, the ratio of hCG beta to hCG must be evaluated with caution in samples taken several days after initiating therapy. We conclude that the disappearance of hCG beta from plasma is slower than previously recognized and that the ratios of hCG beta or hCG alpha to intact hCG vary as a function of postpartum time. Such information may be important in clinical studies of pregnancy disorders.
Subject(s)
Chorionic Gonadotropin, beta Subunit, Human/blood , Chorionic Gonadotropin/blood , Glycoprotein Hormones, alpha Subunit/blood , Postpartum Period/blood , Pregnancy/blood , Adult , Female , Fluorometry , Humans , Immunoassay , Middle Aged , Sensitivity and Specificity , Time FactorsABSTRACT
The pregnancy hormone human chorionic gonadotropin (hCG) is also present at low concentrations in plasma and urine of men and nonpregnant women. hCG immunoreactivity occurs in various molecular forms: Besides the intact hCG heterodimer, considerable amounts of proteolytically cleaved forms, free subunits, and fragments are found in plasma and urine. Especially in urine, proteolytic fragments constitute a major part of the hCG immunoreactivity. The different forms of hCG cross-react to various degrees in immunoassays and constitute a problem for standardization of specific hCG determinations. After injection of hCG (10,000 IU of Pregnyl; Organon), above-normal concentrations of hCG can be detected in serum and urine for 7-11 days. Most immunoassays for hCG also measure hCG beta. Quantitative hCG determinations are mainly performed on serum samples, and very few commercial hCG determinations have been validated for determination of urine samples. Considerable care must therefore be exercised when utilizing such assays to analyze urines for doping control.
Subject(s)
Chorionic Gonadotropin/blood , Chorionic Gonadotropin/urine , Doping in Sports , Immunoassay , Chorionic Gonadotropin/pharmacokinetics , Chorionic Gonadotropin, beta Subunit, Human/analysis , Female , Glycoprotein Hormones, alpha Subunit/analysis , Humans , Male , PregnancyABSTRACT
We studied the dynamics of serum human chorionic gonadotrophin (HCG) and its free alpha (HCG alpha) and beta (HCG beta) subunits in 49 early pregnancies achieved by in-vitro fertilization (IVF) and embryo transfer. Of the 49 early pregnancies, nine were normal singleton pregnancies, 11 were twin pregnancies, 11 were ectopic, eight ended in a clinical (spontaneous) abortion and 10 ended in a preclinical abortion. The HCG, HCG alpha and HCG beta concentrations in serum were measured on days 12, 19 and 26 after embryo transfer. Most ectopic pregnancies could be distinguished from singleton (and twin) pregnancies on the basis of low HCG concentrations by 12 days after embryo transfer, but clinical abortions could not be distinguished from singleton pregnancies. In general, the measurement of HCG alpha and HCG beta and the molar ratios of the various forms provided only marginal additional value to that obtained from HCG, but on days 19 and 26 after embryo transfer HCG alpha was the most sensitive indicator of a normal pregnancy after IVF and embryo transfer. We conclude that in ectopic pregnancies the concentrations of HCG, HCG alpha and HCG beta increase as expected but 1.5 days later than in normal pregnancies. This appears to be the result of a delay in implantation.
Subject(s)
Chorionic Gonadotropin/blood , Embryo Implantation , Fertilization in Vitro , Pregnancy, Ectopic/physiopathology , Abortion, Spontaneous/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Embryo Transfer , Female , Glycoprotein Hormones, alpha Subunit/blood , Humans , Pregnancy , Pregnancy, Ectopic/blood , Pregnancy, Multiple/blood , Time Factors , TwinsABSTRACT
OBJECTIVE: To investigate recovery times and need for laparoscopy in women with ectopic pregnancy who were treated for 5 days 2.5 mg/day of oral methotrexate or placebo. METHODS: Sixty women with ectopic pregnancy among patients of an outpatient clinic specializing in early pregnancy disorders were selected for medical treatment in a double-blind, placebo-controlled study. The diagnosis was made by transvaginal sonography and serum hCG determinations, either at admission or after repeated examinations. Women were recruited for the study if they had mild symptoms: the hCG increase was less than 50% within 2 days, the diameter of the ectopic pregnancy was less than 40 mm, there were no signs of intra-abdominal bleeding by transvaginal sonography, and there were no secondary reasons for laparoscopy. Either 2.5 mg of methotrexate or placebo was given orally for 5 days. Serum hCG was determined after 2 days, and hCG, red blood cell count, white blood cell count, platelet count, and serum glutamic-oxaloacetic transaminase were measured; transvaginal sonography was performed after 5 and 12 days. Expectant management was continued individually with check-ups at 1-3-week intervals. Laparoscopy was performed if the patient developed abdominal pain or intra-abdominal hemorrhage, as seen by transvaginal sonography. Statistical analysis was by paired or unpaired t test, Mann-Whitney U test, regression analysis, and repeated measures analysis of variance. RESULTS: Seventy-seven percent of the patients recovered without the need for laparoscopy in both groups, and there were no significant differences in recovery times or the need for laparoscopy between groups. CONCLUSION: Oral methotrexate, 2.5 mg for 5 days, does not appear to be more effective than placebo in the treatment of ectopic pregnancy in women eligible for expectant management.