D-dimer,other markers of haemostasis activation and soluble adhesion molecules in patients with different clinical probabilities of deep vein thrombosis

Two automated turbidimetric D-dimer assays (BC D-dimer Plus, Dade Behring, Marburg, Germany and Auto-Dimer, Biopool, Ume?, Sweden) were compared to two enzyme-linked immunosorbent assays (ELISAs) (Enzygnost D-dimer micro, Dade Behring and Asserachrome D-dimer, Diagnostica Stago, Asnières, France) and two rapid D-dimer assays (SimpliRed, Agen Biomedical, Brisbane, Australia and Minutex, Biopool) in out-patients with suspected deep vein thrombosis (DVT). In addition, the performance of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble adhesion molecules VCAM-1 and P-selectin for DVT diagnosis was assessed. One hundred and thirty-five consecutive out-patients with suspected DVT of the lower limb were included, and in 52 (39%), DVT was confirmed by compression ultrasound. All D-dimer assays investigated reliably excluded DVT in those patients without DVT irrespective of their pre-test clinical probability of DVT. One D-dimer ELISA (Dade Behring) gave the highest area under the receiver operating characteristic (ROC) curve compared to other assays, and therefore, this was the most accurate assay in differentiating patients with from patients without DVT. The diagnostic performance of one automated turbidimetric assay (Auto Dimer, Biopool) was similar to ELISA and its convenience close to rapid latex agglutination assays. Most patients with a high pre-test clinical probability of DVT had positive D-dimer regardless of the presence or absence of DVT, which decreased the specificity of the tests and made D-dimer determination less useful for this group of patients. Because the diagnostic accuracy [sensitivity, specificity, negative (NPV) and positive predictive value (PPV)] of F1+2, TAT, VCAM-1 and P-selectin was inferior to D-dimer assay, these assays could not substitute or supplement D-dimer testing in diagnosis of DVT. Levels of VCAM-1 and P-selectin were increased in patients with DVT and should therefore be investigated further to clarify their role in DVT.     

Clones,parents, persons and the law in Australia

Current understanding of cloning and artificial reproductive technology was reviewed. The results show that they are in contradiction with fundamental concepts upon which our society is built, such as person and parenthood. Analyses of some recent British and Australian laws show that attempts to protect the individual by regulating some biological technologies through carefully drafted legislation are bound to fail.     

Second trimester total human chorionic gonadotropin,alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy

OBJECTIVE: To assess the value of alpha-fetoprotein (AFP), total human chorionic gonadotropin (ThCG) and unconjugated estriol in predicting certain complications of pregnancy other than fetal aneuploidy. STUDY DESIGN: Among 2384 women that underwent biochemical screening between 15 and 22 weeks of gestation, pregnancy outcome was evaluated in 677 women under 35 years of age according to serum marker levels by using cut-off points discriminative for Down syndrome or neural tube defect (NTD). RESULTS: High alpha-fetoprotein levels (MoM>/=2.0) were found to be significantly more frequent (P<0.05) in cases of fetal growth restriction (odds ratio=2.7), miscarriage (odds ratio=4.4) and intrauterine fetal death (odds ratio=5.8). High chorionic gonadotropin levels (MoM>/=2.02) were associated with intrauterine growth restriction (odds ratio=2.1; P<0.05), miscarriage (odds ratio=4; P<0.01), preterm birth (odds ratio=2.5; P<0.05), and intrauterine fetal death (odds ratio=4.2; P<0.01). Among pregnancies with intrauterine growth restriction and threatening preterm delivery, low unconjugated estriol levels (MoM相似文献   

The potential value of the protein S-100B level as a criterion for hyperbaric oxygen treatment and prognostic marker in carbon monoxide poisoned patients

Carbon monoxide (CO) poisoning resulting in diffuse tissue hypoxia. Cerebral hypoxia is a major cause of morbidity and mortality after CO poisoning. There are some clinical criteria that could help a physician to make a decision concerning the application of hyperbaric oxygenation therapy. However, it would be convenient to discover an objective biochemical serum marker that could help in the grade evaluation of CO poisoning and indication of therapy in CO-poisoned patients. We present two case reports where the established criteria for the CO poisoning were not optimum for the decision regarding therapy. It seems that the S-100B protein could be used as a biochemical marker of CO induced brain injury. S-100B values could perhaps help us to select patients for hyperbaric oxygen therapy and to predict the short and long term outcome.     

Influence of subcutaneous administration of recombinant TNF-alpha on ligature-induced periodontitis in rats

Proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) was found in inflamed periodontal tissues and many studies pointed to its significant role in development of periodontal disease. In this study, the influence of subcutaneously administered recombinant human TNF-alpha (rhTNF-alpha) on inflammatory reaction and periodontal breakdown in rats was analyzed during experimental periodontitis, induced by placing silk ligatures around the maxillary right second molar tooth. The rats were divided into two groups with five animals in each; the first group was infused subcutaneously with rhTNF-alpha via osmotic pumps for 2 weeks and the second group was infused with phosphate-buffered saline (PBS) in the same manner. Inflammatory reaction and periodontal breakdown was evaluated morphometrically on hematoxylin and eosin stained sections. Serum ionized calcium and inorganic phosphates were monitored colorimetrically. Serum calcium and phosphate levels were similar in rats receiving rhTNF-alpha and PBS. Ligation resulted in accelerated periodontal breakdown, while subcutaneous rhTNF-alpha administration by itself had no significant effect. Combined effect of subcutaneous rhTNF-alpha administration and ligation resulted in a significantly greater inflammatory reaction and periodontal breakdown then either treatment alone. We concluded that the subcutaneous administration of rhTNF-alpha accelerates the progression of experimental periodontitis in rats.     

In vivo administration of recombinant TNF-alpha promotes bone resorption in mice

BACKGROUND: In vitro studies demonstrated that proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) modulates bone metabolism. OBJECTIVE: The aim of our study was to confirm the ability of TNF-alpha to induce osteoclastogenesis and bone resorption in an in vivo experiment, with the use of calvarial model in mice. MATERIALS AND METHODS: Twenty C57-Black mice were divided into four groups with five animals in each. The first group was infused subcutaneously on their back with recombinant mouse (rm) TNF-alpha via osmotic minipumps for 3 d, the second group was similarly infused with phosphate-buffered saline (PBS), the third group was infused with rmTNF-alpha to the region above the parietal bone and the fourth group with PBS in the same manner. Number of osteoclasts on parietal bone was determined morphometrically. Serum calcium and phosphates were monitored colorimetrically. RESULTS: Serum calcium level and number of osteoclasts on parietal bone were significantly greater after infusion of rmTNF-alpha above the parietal bone, whereas after subcutaneous delivery these parameters were similar to the control group. CONCLUSION: We are concluding that TNF-alpha has the ability to change the bone metabolism in a paracrine manner only.     

Sera from patients with rheumatic diseases recognize different epitope regions on the 52-kD Ro/SS-A protein.

Patients suffering from systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS) often contain autoantibodies directed to the Ro(SS-A) complex. In this study the antigenic determinants on two of the components of the Ro complex, i.e. the Ro60 and the Ro52 polypeptides, were investigated. Anti-Ro+ sera were selected by counter-immunoelectrophoresis. Depending on the detection method, 59-68% of the SLE patients produced anti-Ro but not anti-La antibody, while 72-81% of the SS patients produced both anti-Ro and anti-La antibody. Immunoprecipitation of recombinant Ro-proteins showed that 61 sera (87%) were reactive with both Ro proteins, seven sera with Ro60 only, one serum with Ro52 only, and one serum did not precipitate the proteins at all. The anti-Ro60 reactivity of human sera is strongly associated with the native form of Ro60, suggesting that conformational autoepitopes are an important feature of Ro60. In the case of Ro52, frequently the residues located between amino acids 216 and 292 were essential for reactivity with the antibodies. With 70% of the lupus sera tested this appeared to be the only region important for reactivity. The antibodies of SS patients generally recognized multiple B cell epitopes located between amino acids 55 and 292. The results of this study indicate that the antigenic determinants on Ro52 are different for autoantibodies produced by lupus patients compared with those of SS patients.     

Evaluation of automated sample preparation and quantitative PCR LCx assay for determination of human immunodeficiency virus type 1 RNA

Efforts have been made to achieve full automation of molecular assays for quantitative detection of human immunodeficiency virus type 1 (HIV-1). In the present study, the Abbott LCx HIV RNA Quantitative assay was evaluated in conjunction with automated HIV-1 RNA extraction on the MagNA Pure LC instrument and compared to the conventional LCx HIV RNA Quantitative assay, which uses a manual nucleic acid extraction protocol. Accuracy, linearity, and interassay and intra-assay variations were determined. The performance of the assay in a routine clinical laboratory was tested with a total of 105 clinical specimens. When the accuracy of the LCx HIV RNA Quantitative assay with the automated sample preparation protocol was tested, all results were found to be within +/- 0.5 log unit of the expected results. Determination of linearity resulted in a quasilinear curve over 3.5 log units. For determination of interassay variation, coefficients of variation were found to be between 21 and 66% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 10 and 69% for the LCx HIV RNA Quantitative assay with manual sample preparation. For determination of intra-assay variation, coefficients of variation were found to be between 7 and 25% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 7 and 19% for the LCx HIV RNA Quantitative assay with manual sample preparation. When clinical samples were tested by the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and the results were compared with those of the LCx HIV RNA Quantitative assay with manual sample preparation, 95% of all positive results were found to be within +/- 0.5 log unit. In conclusion, the assay with automated sample preparation proved to be suitable for use in the routine diagnostic laboratory and required significantly less hands-on time.     

Pleural mesothelioma and membranous nephropathy

Underlying malignancy has been thought to be responsible for 5-10% of the cases of membranous nephropathy in adults, with the risk being highest in patients over the age of 60 years. Solid tumors such as carcinomas of lung or colon, are most often involved. It is presumed that tumor antigens are deposited in the glomeruli; this is followed by antibody deposition and complement activation, leading to epithelial cell and basement membrane injury and proteinuria due to the associated increase in glomerular permeability. We describe a patient with a resistant nephrotic syndrome and massive proteinuria due to membranous nephropathy associated with pleural mesothelioma.     

Healthcare technology and technology assessment

New technology is one of the primary drivers for increased healthcare costs in the United States. Both physician and industry play important roles in the development, adoption, utilization and choice of new technologies. The Federal Drug Administration regulates new drugs and new medical devices, but healthcare technology assessment remains limited. Healthcare technology assessment originated in federal agencies; today it is decentralized with increasing private sector efforts. Innovation is left to free market forces, including direct to consumer marketing and consumer choice. But to be fair to the consumer, he/she must have free knowledge of all the risks and benefits of a new technology in order to make an informed choice. Physicians, institutions and industry need to work together by providing proven, safe, clinically effective and cost effective new technologies, which require valid pre-market clinical trials and post-market continued surveillance with national and international registries allowing full transparency of new products to the consumer—the patient. No grant support. An erratum to this article can be found at