ABSTRACT
BACKGROUND: Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC). METHODS: Publically available datasets were used for clinical analysis of TFPI and miRNAs expression by web analysis tools. miRNA mimics targeting TFPIα 3'untranslated region (UTR) were selected from target prediction programs and verified by luciferase reporter assay. In vitro effects of miRNAs overexpression in HCC cell lines on TFPI expression and cell proliferation and apoptosis were analysed. RESULTS: TFPI expression was significantly increased in HCC tumours compared to normal tissue. Low TFPI tumour expression was associated with better survival probability. Four candidate miRNAs were selected from the target prediction programs. miR-7-5p and miR-1236-3p were validated in HepG2 and Huh7 cells to reduce TFPI mRNA and protein levels following overexpression. Furthermore, miR-7-5p and miR-1236-3p reduced TFPIα-3'UTR-controlled luciferase activity. The two validated miRNAs inhibited proliferation of HepG2 cells, and had clinical significance in HCC. CONCLUSIONS: TFPI was increased in HCC tumours compared to normal tissue and high TFPI expression was associated with an unfavorable outcome in HCC patients. miR-7-5p and miR-1236-3p were identified as novel regulators of TFPI in vitro.
Subject(s)
Carcinoma, Hepatocellular , Lipoproteins , Liver Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Lipoproteins/genetics , Lipoproteins/metabolism , Prognosis , Female , Male , Middle Aged , Hep G2 Cells , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, NeoplasticSubject(s)
Alzheimer Disease/complications , Drug Development/methods , Psychomotor Agitation/drug therapy , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Benzodiazepines/administration & dosage , Benzodiazepines/adverse effects , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Consensus , Humans , Psychomotor Agitation/diagnosis , Psychomotor Agitation/etiology , Randomized Controlled Trials as TopicABSTRACT
In the field of Alzheimer's disease, there is an urgent need for novel analytical tools to identify disease-specific biomarkers and to evaluate therapeutics. Preclinical trials commonly employ amyloid beta (Aß) peptide signatures as a read-out. In this paper, we report a simplified and detailed protocol for robust immunoprecipitation of Aß in brain tissue prior to mass spectrometric detection exemplified by a study using transgenic mice. The established method employed murine monoclonal and rabbit polyclonal antibodies and was capable of yielding well-reproducible peaks of high intensity with low background signal intensities corresponding to various Aß forms.
ABSTRACT
AIM: To compare the frequency of misconceptions amongst dental students resulting from assessments in different subject areas using different types of multiple-choice questions (MCQs). We wanted to know whether misconceptions, or strongly held incorrect beliefs, differed by subject area or question type. METHODS: A total of 104 students completed two assessments that included 20 MCQs on endodontics and 20 MCQs on dental implants. On each examination, 10 questions were scenario-type questions requiring interpretation or analysis and 10 questions were factual-based, knowledge questions. Incorrect responses and confidence levels by student and subject were recorded for a comparison of average misconceptions by question type and for correlations between scenario and knowledge question types for misconceptions on both assessments. RESULTS: Students were overly confident on their incorrect responses and misconceptions for both assessments. On the endodontic examination, students held a statistically significant higher number of mean misconceptions on scenario questions than for knowledge questions, but the difference was not statistically significant for the dental implant examination. There was a moderately weak relationship between scenario and knowledge questions for misconceptions on the endodontic (r=.31) and dental implant (r=.20) assessments, suggesting students who have misconceptions on knowledge questions are somewhat more likely to have misconceptions on scenario questions. CONCLUSION: Students had a consistent rate of overconfidence (75%) in their incorrect responses regardless of question type or dental subject. Questions that prompted a higher per cent of incorrect responses were more likely to detect misconceptions, as students were highly confident in their mistakes, for both assessments.
Subject(s)
Education, Dental , Health Knowledge, Attitudes, Practice , Self Efficacy , Students, Dental/psychology , Cross-Sectional Studies , Female , Humans , Male , Self ReportABSTRACT
In high-income countries a large proportion of all deaths occur in hospitals. A common way to translate knowledge into clinical practice is developing guidelines for different levels of health care organisations. During 2012, national clinical guidelines for palliative care were published in Sweden. Later, guidance for palliative care was issued by the National Board of Health and Welfare. The aim of this study was two-fold: to investigate perceptions regarding these guidelines and identify obstacles and opportunities for implementation of them in acute care hospitals. Interviews were conducted with local politicians, chief medical officers and health professionals at acute care hospitals. The Consolidated Framework for Implementation Research was used in a directed content analysis approach. The results showed little knowledge of the two documents at all levels of the health care organisation. Palliative care was primarily described as end of life care and only few of the participants talked about the opportunity to integrate palliative care early in a disease trajectory. The environment and culture at hospitals, characterised by quick decisions and actions, were perceived as obstacles to implementation. Health professionals' expressed need for palliative care training is an opportunity for implementation of clinical guidelines. There is a need for further implementation of palliative care in hospitals. One option for further research is to evaluate implementation strategies tailored to acute care.
Subject(s)
Attitude of Health Personnel , Guidelines as Topic , Palliative Care , Government Employees/psychology , Guideline Adherence , Hospital Administration , Hospitals , Humans , Medical Staff, Hospital/psychology , Qualitative Research , Sweden , Terminal CareABSTRACT
Tsunamis caused by landslides may result in significant destruction of the surroundings with both societal and industrial impact. The 1958 Lituya Bay landslide and tsunami is a recent and well-documented terrestrial landslide generating a tsunami with a run-up of 524 m. Although recent computational techniques have shown good performance in the estimation of the run-up height, they fail to capture all the physical processes, in particular, the landslide-entry profile and interaction with the water. Smoothed particle hydrodynamics (SPH) is a versatile numerical technique for describing free-surface and multi-phase flows, particularly those that exhibit highly nonlinear deformation in landslide-generated tsunamis. In the current work, the novel multi-phase incompressible SPH method with shifting is applied to the Lituya Bay tsunami and landslide and is the first methodology able to reproduce realistically both the run-up and landslide-entry as documented in a benchmark experiment. The method is the first paper to develop a realistic implementation of the physics that in addition to the non-Newtonian rheology of the landslide includes turbulence in the water phase and soil saturation. Sensitivity to the experimental initial conditions is also considered. This work demonstrates the ability of the proposed method in modelling challenging environmental multi-phase, non-Newtonian and turbulent flows.
ABSTRACT
Here, we provide the dataset associated with our research article on the potential effects of ocean acidification on antimicrobial peptide (AMP) activity in the gills of Mytilus edulis, "Impact of ocean acidification on antimicrobial activity in gills of the blue mussel (Mytilus edulis)" [1]. Blue mussels were stimulated with lipopolysaccharides and samples were collected at different time points post injection. Protein extracts were prepared from the gills, digested using trypsin and a full in-depth proteome investigation was performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Protein identification and quantification was performed using the MaxQuant 1.5.1.2 software, "MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification" [2].
ABSTRACT
Here, we aimed to investigate potential effects of ocean acidification on antimicrobial peptide (AMP) activity in the gills of Mytilus edulis, as gills are directly facing seawater and the changing pH (predicted to be reduced from â¼8.1 to â¼7.7 by 2100). The AMP activity of gill and haemocyte extracts was compared at pH 6.0, 7.7 and 8.1, with a radial diffusion assay against Escherichia coli. The activity of the gill extracts was not affected by pH, while it was significantly reduced with increasing pH in the haemocyte extracts. Gill extracts were also tested against different species of Vibrio (V. parahaemolyticus, V. tubiashii, V. splendidus, V. alginolyticus) at pH 7.7 and 8.1. The metabolic activity of the bacteria decreased by â¼65-90%, depending on species of bacteria, but was, as in the radial diffusion assay, not affected by pH. The results indicated that AMPs from gills are efficient in a broad pH-range. However, when mussels were pre-exposed for pH 7.7 for four month the gill extracts presented significantly lower inhibit of bacterial growth. A full in-depth proteome investigation of gill extracts, using LC-Orbitrap MS/MS technique, showed that among previously described AMPs from haemocytes of Mytilus, myticin A was found up-regulated in response to lipopolysaccharide, 3 h post injection. Sporadic occurrence of other immune related peptides/proteins also pointed to a rapid response (0.5-3 h p.i.). Altogether, our results indicate that the gills of blue mussels constitute an important first line defence adapted to act at the pH of seawater. The antimicrobial activity of the gills is however modulated when mussels are under the pressure of ocean acidification, which may give future advantages for invading pathogens.
Subject(s)
Antimicrobial Cationic Peptides/genetics , Climate Change , Escherichia coli/physiology , Mytilus edulis/genetics , Seawater/chemistry , Vibrio/physiology , Animals , Antimicrobial Cationic Peptides/metabolism , Gills/metabolism , Gills/microbiology , Hemocytes/microbiology , Hydrogen-Ion Concentration , Mytilus edulis/metabolism , Mytilus edulis/microbiology , ProteomeABSTRACT
BACKGROUND: Despite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of this study were to assess whether treatment of pregnant women with schistosomiasis at 12-16 weeks gestation leads to improved maternal and newborn outcomes and to collect maternal and newborn safety data. METHODS: This phase 2, randomised, double-blind, placebo-controlled trial was done in 72 baranguays (villages) serviced by six municipal health centres in a schistosomiasis endemic region of northeastern Leyte, Philippines. Pregnant women (at 12-16 weeks gestation) who were otherwise healthy but infected with Schistosoma japonicum were enrolled and randomly assigned (1:1) to receive either over-encapsulated praziquantel (total dose 60 mg/kg given as two split doses) or placebo. Participants, investigators, midwives, and laboratory staff were all masked to treatment. The primary outcome was birthweight. Safety data were collected including immediate reactogenicity, post-dosing toxicology ascertained 24 h after study drug administration, and maternal and newborn serious adverse events. Analysis followed the intention-to-treat principle. Analyses were done using hierarchical generalised linear models to adjust for identified confounders and account for potential clustering of observations within villages and municipalities. This trial is registered with ClinicalTrials.gov, number NCT00486863. FINDINGS: Between Aug 13, 2007, and Dec 3, 2012, 370 pregnant women were enrolled and randomly assigned to each treatment group (184 to the placebo group, 186 to the praziquantel group). Most women had low-intensity infections (n=334, 90%). Treatment with praziquantel did not have a significant effect on birthweight (2·85 kg in both groups, ß=-0·002 [95% CI -0·088 to 0·083]; p=0·962). Treatment was well tolerated with reactogenicity rates similar to those seen in non-pregnant participants (severe reactions occurred in five patients in the praziquantel group and two in the placebo group, and included headache, fever, and malaise). There were no significant differences in key safety outcomes including abortion, fetal death in utero, and congenital anomalies. INTERPRETATION: Results from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO. FUNDING: National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).
Subject(s)
Anthelmintics/administration & dosage , Anthelmintics/adverse effects , Birth Weight/drug effects , Fetus/drug effects , Praziquantel/administration & dosage , Praziquantel/adverse effects , Schistosomiasis/drug therapy , Adult , Double-Blind Method , Female , Gestational Age , Humans , Infant, Newborn , Philippines , Pregnancy , Young AdultABSTRACT
BACKGROUND: The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target. METHODS: Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA. RESULTS: In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA. CONCLUSIONS: STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
Subject(s)
Carcinoma, Transitional Cell/metabolism , Cell Movement , Cell Proliferation , Stathmin/metabolism , Urinary Bladder Neoplasms/metabolism , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/secondary , Cell Line, Tumor , Female , Gene Silencing , Humans , Kaplan-Meier Estimate , Ki-67 Antigen/analysis , Male , Molecular Targeted Therapy , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Stathmin/genetics , Tissue Array Analysis , Tumor Suppressor Protein p53/analysis , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathologyABSTRACT
Adult-onset copper deficiency with neurological manifestations is a newly recognised syndrome. Long-term oral copper replacement therapy has been the mainstay of treatment in the literature. A case of relapsing hypocupraemic myelopathy responsive to increased doses of copper replacement is reported. Standard doses of copper may not be sufficient for all patients.
Subject(s)
Copper/deficiency , Copper/therapeutic use , Spinal Cord Diseases/drug therapy , Spinal Cord Diseases/etiology , Deficiency Diseases/complications , Female , Humans , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Severe hereditary hypercholesterolaemia is most frequently due to familial hypercholesterolaemia (FH), caused by mutations in the LDL receptor (LDLR) gene. However, a phenotype very similar to FH may also be caused by defects in other genes like the genes for apolipoprotein (apo) B-100 or autosomal recessive hypercholesterolaemia (ARH). SUBJECT: An 8-year-old male of Lebanese origin was diagnosed with severe hypercholesterolaemia and extensive cutaneous and tendon xanthomas. Plasma LDL cholesterol before treatment was 17 mmol L(-1), whilst parents and both siblings had normal levels. DIAGNOSIS: Degradation of (125)I-labelled LDL in blood lymphocytes was reduced, but not abolished. Sequencing analysis of the LDLR and apoB-100 genes were negative, whilst a splice acceptor mutation in intron 1 (IVS 1 -1G>C) was detected in the ARH gene. The patient was homozygous for the mutation, whilst the parents were heterozygous. These findings were in agreement with a diagnosis of ARH. TREATMENT AND CLINICAL COURSE: Monthly LDL apheresis and atorvastatin 120 mg daily reduced LDL cholesterol preapheresis level to 4.8 mmol L(-1). When ezetimibe was given 10 mg day(-1) in combination with rosuvastatin 80 mg day(-1), LDL cholesterol was further lowered to 1.6 mmol L(-1), which made apheresis unnecessary. Cutaneous and tendon xanthomas disappeared completely and the intima-media thickness of the common carotid arteries decreased. At age 23 he developed a small myocardial infarction. CONCLUSION: ARH should be considered in cases of severe hypercholesterolaemia with a pattern of recessive inheritance. Combination therapy with high-dose statin and ezetimibe seems to be the treatment of choice in ARH and may reduce or eliminate the need for LDL apheresis treatment.
Subject(s)
Anticholesteremic Agents/administration & dosage , Azetidines/administration & dosage , Fluorobenzenes/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hyperlipoproteinemia Type II/drug therapy , Pyrimidines/administration & dosage , Sulfonamides/administration & dosage , Adult , Child , Cholesterol, LDL/blood , Drug Combinations , Ezetimibe , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Male , Pedigree , Rosuvastatin Calcium , Xanthomatosis/drug therapyABSTRACT
Familial hypercholesterolemia (FH) is an autosomal codominant disease, caused by mutations in the LDL receptor gene. To characterize the distribution of genetic aberrations in Swedish FH-patients fulfilling the clinical criteria of FH, we have investigated 150 unrelated Swedish patients for mutations in the LDL receptor gene and for the most common mutation causing familial ligand defective apo B-100 (FDB). Of the patients, 77 were recruited from Huddinge University Hospital in Stockholm and 73 from Sahlgren's University Hospital in Göteborg. Screening was carried out using SSCP and Southern blotting techniques, combined with DNA sequence analysis. In total, mutations regarded as cause for disease were identified in 55 patients (37%), representing 32 different types of mutations. In the LDL receptor gene we detected four nonsense mutations, 13 missense mutations, seven splice junction mutations, and four major rearrangements. In addition, two small deletions were identified and one base exchange in the promoter region. The most common mutation (apo B3500) causing FDB was found in three patients. The most frequent mutation was FH-Helsinki, reflecting the admixture of Finnish immigrants. We further identified 15 point mutations which were not considered to affect the function of the gene, and thus were regarded as polymorphic changes. This multitude of mutations reflects a heterogeneous genetic background in our series of Swedish FH-patients and differs from the situation in the other Scandinavian countries. Future studies should aim at characterizing the importance of other genes for the development of the FH phenotype.
Subject(s)
Genetic Heterogeneity , Hyperlipoproteinemia Type II/genetics , Mutation , Receptors, LDL/genetics , Adult , Aged , Aged, 80 and over , Apolipoprotein B-100 , Apolipoproteins B/genetics , Female , Humans , Male , Middle Aged , SwedenSubject(s)
Alzheimer Disease/nursing , Alzheimer Disease/psychology , Life Change Events , Nursing Care/methods , Aged , HumansABSTRACT
Because micromolar concentrations of adenosine (Ado) have been documented recently in the interstitial fluid of carcinomas growing in animals, we examined the effects of low concentrations of Ado on the growth of cultured human carcinoma cells. Ado alone had little effect upon cell growth. In the presence of one of a number of Ado deaminase (ADA) inhibitors, Ado led to significant growth inhibition of all cell lines tested. Similar effects were found when ATP, ADP, or AMP was substituted for Ado. Surprisingly, the ADA inhibitor coformycin (CF) had a much greater potentiating effect than did 2'-deoxycoformycin (DCF), although DCF is a more potent ADA inhibitor. The growth inhibition of the Ado/CF combination was not abrogated by pyrimidines or caffeine, a nonspecific Ado receptor blocker. Toxicity was prevented by the addition of the Ado transport inhibitor dipyridamole or the Ado kinase inhibitor 5'-amino 5'-deoxyadenosine. S-Adenosylhomocysteine hydrolase is not involved because neither homocysteine thiolactone nor an S-adenosylhomocysteine hydrolase inhibitor (adenosine dialdehyde) potentiated toxicity of the Ado/CF combination. Unexpectedly, substitution of 2'-deoxyadenosine (the toxic moiety in congenital ADA deficiency) for Ado, did not lead to equivalent toxicity. The Ado/CF combination inhibited DNA synthesis and brought about morphological changes consistent with apoptosis. Together, these findings indicate that the Ado-mediated killing proceeds via an intracellular route that requires the action of Ado kinase. The enhanced cofactor activity of CF may be attributable to its being a more potent inhibitor of AMP deaminase than is DCF.
Subject(s)
Adenosine/physiology , Cell Survival/drug effects , Coformycin/toxicity , Pentostatin/toxicity , Adenine/analogs & derivatives , Adenine/pharmacology , Adenosine/analogs & derivatives , Adenosine/pharmacology , Adenosine Deaminase Inhibitors , Adenosine Kinase/antagonists & inhibitors , Apoptosis/drug effects , Breast Neoplasms , Carcinoma, Squamous Cell , Cell Division/drug effects , Deoxyadenosines/pharmacology , Dipyridamole/pharmacology , Enzyme Inhibitors/pharmacology , Female , Humans , Kinetics , Ovarian Neoplasms , Tumor Cells, CulturedSubject(s)
Composite Resins , Dental Polishing , Dental Restoration, Permanent , Aluminum Oxide/chemistry , Carbon Compounds, Inorganic/chemistry , Chemical Phenomena , Chemistry, Physical , Composite Resins/chemistry , Dental Polishing/instrumentation , Dental Polishing/methods , Dental Restoration, Permanent/instrumentation , Dental Restoration, Permanent/methods , Equipment Design , Glycerol/chemistry , Humans , Polyethylene Terephthalates/chemistry , Rubber/chemistry , Surface PropertiesABSTRACT
Errors in questionnaire surveys are usually of one of two sources: non-responses or incorrect answers. The aim was to investigate the validity of a questionnaire survey and to estimate the respective bias of these answers. Of 9,283 subjects selected to receive a questionnaire by post, 3,949 (43%) responded, and, of these, 3,400 correctly reported their Swedish social security number. Answers in the questionnaire survey were given as proportions of the claims registered at local insurance offices. In the group of respondents who had correctly reported their social security number, the answers were compared individually with the registrations in dental insurance claims. In Sweden, these claims are labeled with the patient's social security number and it is thereby possible to make such comparisons. It was shown that errors were caused by non-response and also by respondents giving incorrect answers. Incorrect answers accounted for approximately one-third of the total bias. The remaining bias was caused by a non-response error. It is concluded that questionnaire studies have a bias caused by both non-response and incorrect answers and that together these can be substantial. Scientific reports that include questionnaire surveys must describe the procedure carefully. If possible, other sources of information should be considered.
Subject(s)
Surveys and Questionnaires , Bias , Dental Health Surveys , Humans , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The International Normalized Ratio (INR) system was introduced a decade ago as a way of standardizing the results of prothrombin time testing for patients taking oral anticoagulants. A strong emphasis has been placed upon using thromboplastin reagents that are very sensitive to the effects of oral anticoagulants upon the prothrombin time [i.e. reagents with low International Sensitivity Index (ISI)]. In order to assess how well the INR system functions as currently used in clinical laboratories, we compared the INRs determined using thromboplastins of differing ISIs in samples collected during a large clinical trial of oral anticoagulation for atrial fibrillation (Stroke Prevention in Atrial Fibrillation III trial). Frozen plasma was subjected to prothrombin time testing using thromboplastins with ISIs ranging from 0.97 to 2.49. INRs were calculated using machine-specific ISIs and Westgard's rules were followed to maintain quality control. An unanticipated coagulometer failure allowed a determination of the effect of machine recalibration upon the INR of control plasmas. The correlation between each pair of INRs obtained from 1181 plasmas was high (> 0.9), but the differences between reagents were statistically different from zero (P<0.001 for pairwise comparisons). Plasmas had INRs within the therapeutic range (2.0-3.0) with one reagent but not with another in an average of 20% of instances. Among the 20% discordant pairings, 43% (8.5% of the total tested) showed a difference in INR of more than 0.2 INR units above or below the target range. Low ISI thromboplastins did not perform better in this pairwise comparison than other reagents or the locally determined INR. Recalibration of a coagulometer resulted in a significant change in the INRs obtained from control plasmas (P<0.0001), which confirms and extends the observations of other authors concerning the sensitivity of the INR to coagulometer-related variables. There was a clinically significant difference in the INRs obtained with different thromboplastins, and low ISI reagents did not perform better than others. Since the risk of thrombosis rises sharply below the lower limit of the currently recommended target ranges, consideration should be given to narrowing the recommended range, or advising clinicians to aim for its mid-point. These findings illustrate the difficulties in imposing standardization upon coagulation testing after a test is in widespread use.
Subject(s)
Atrial Fibrillation/blood , International Normalized Ratio , Prothrombin Time , Administration, Oral , Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Humans , Indicators and ReagentsABSTRACT
Coagulation system activation is most commonly assessed by measuring levels of one or more proteins in peripheral blood. Because faulty blood-drawing can cause activation of the coagulation system, artifactual elevations of such markers have been reported. We have therefore investigated the possibility of using randomly collected ('spot') urine samples as a non-invasive means of assessing the state of coagulation system activation. Using a commercially available enzyme-linked immunosorbent assay kit designed to measure plasma levels of fragment 1 + 2, we found immunoreactive fragment 2 in healthy control subjects, and significantly increased levels in diabetic and non-diabetic pregnant subjects, and patients with venous thromboembolism, prostate cancer, and diabetes. Measurements of excretion of immunoreactive fragment 2 are worth further study as an adjunct or alternative to plasma-based assays designed to detect or quantify coagulation system activation.
Subject(s)
Blood Coagulation , Peptide Fragments/urine , Prothrombin/urine , Adult , Diabetes Mellitus/blood , Diabetes Mellitus/urine , Female , Humans , Immunoassay/methods , Male , Pregnancy/blood , Pregnancy/urine , Prostatic Neoplasms/blood , Prostatic Neoplasms/urine , Venous Thrombosis/blood , Venous Thrombosis/urineABSTRACT
OBJECTIVES: This study sought, first, to explain and reconcile the provocation and inhibition theories of the effect of rising unemployment on the incidence of antisocial behavior. Second, it tested the hypothesis, implied by the provocation and inhibition theories, that the relationship between unemployment and foster home placements forms an inverted "U." METHODS: The hypothesis was tested with data from California for 137 months beginning in February 1984. RESULTS: Findings showed that the hypothesis was supported. CONCLUSIONS: Rising joblessness increases the incidence of foster home placements among families that lose jobs or income. Levels of joblessness that threaten workers who remain employed, however, inhibit antisocial behavior and reduce the incidence of foster home placements. This means that accounting for the social costs of unemployment is more complicated than assumed under the provocation theory.