Reactions to awareness of activated protein C resistance carriership: a descriptive study of 270 women.

Background. Around 25 million Caucasian women are carriers of the FV Leiden mutation that causes activated protein C (APC) resistance. This is a heritable condition with a lifelong increased risk of venous thromboembolism. We performed this study to investigate women's reactions to their awareness of being APC-resistant and the consequences of this awareness. Methods. All APC-resistant women (n = 270) included in a prior study on APC resistance and pregnancy (n = 2480) were invited by written questionnaire to describe their reactions to having APC resistance, how this had changed their lives, and how they experienced our information. Answers were obtained from 215 of the 270 women (80%). Results. More than 94% of the APC-resistant women were satisfied with knowing themselves to be APC-resistant and pleased that they had enrolled in the study. Of the women on combined oral contraceptives (COC), 84% changed their method of contraception, but 16% continued on COC. One-third of the women reported becoming more worried or afraid of getting pregnant again as a result of their awareness of being APC-resistant. The proportion of women who sought legal abortions during a 2-year period after receiving this information was similar in both subgroups: 4.4% (12/270) vs. 4.3% (94/2210), p = 0.9. Conclusions. We conclude that most APC-resistant women were pleased to learn of their APC resistance status, that there was not an increased incidence of legal abortions, but almost one-third reported being more worried or afraid of getting pregnant again

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Individual risk assessment of thrombosis in pregnancy.

Thromboembolic complications during pregnancy are major contributors to maternal death, but there is no reliable way to estimate the absolute risk of thrombosis before the occurrence of a thromboembolic complication. OBJECTIVE: To create a model for individual estimation of thrombosis risk during pregnancy and to determine the distribution of risk estimates in a series of gravidae. METHOD AND PATIENTS: Estimates of absolute risk of pregnancy-related thromboembolism were calculated by multiplying reported figures of thrombosis incidence by prevalence-adjusted odds ratios of the following variables: smoking, parity, preeclampsia, mode of delivery, age, overweight, activated protein C resistance (FV Leiden or FV:Q506), thrombosis heredity, and previous thrombosis. We present the risk distribution among a unselected prospectively gathered cohort of 2384 unselected gravidae who were interviewed and tested for activated protein C resistance in early pregnancy. RESULTS AND CONCLUSIONS: A model for individual estimation of the absolute risk of thrombosis is presented, which is provided to the readers as a free automatic Internet-based service (http://www.riskpreg.com). As compared with antepartum, more women at high risk can be identified in the postpartum period and we suggest that this might be of use in planning the prevention of thrombosis

Protein S binding in relation to the subunit composition of human C4b-binding protein

AbstractThe human regulatory complement component C4b-binding protein (C4BP) circulates in plasma either as a free protein or in a bimolecular complex with the vitamin K-dependent protein S. The major form of C4BP is composed of 7 identical, disulfide-linked 70 kDa subunits (α-chains), the arrangement of which gives the C4BP molecule a spider-like appearance. Recently, we identified a unique 45 kDa subunit (β-chain) in C4BP. We have now isolated a subpopulation of C4BP, which does notbind protein S. This C4BP species, which had a molecular weight slightly lower than that of the predominant form, was found to lack the β-chain. Another lower molecular weight form of C4BP was also purified. It contained the β-chain and was efficient in binding protein S. Its subunit composition was judged to comprise six α-chains and one β-chain. These results indicate C4BP in plasma to be heterogeneous at a molecular level vis-a-vis subunit composition and/or protein S binding ability and provide support for the concept that the β-chain of C4BP contains the single protein S binding site

Fibrillin Immunoreactive Fibers Constitute a Unique Network in the Human Dermis: Immunohistochemical Comparison of the Distributions of Fibrillin, Vitronectin, Amyloid P Component, and Orcein Stainable Structures in Normal Skin and Elastosis

Fibrillin, a 350-kD glycoprotein, was recently localized to elastin-associated 10nm microfibrils. Here, the distribution of fibrillin immunoreactivity was determined in normal skin in individuals of different ages and in lesions of solar elastosis or anetoderma. It was compared with the distribution of orcein-stainable fibers and with the immunoreactivities of vitronectin and amyloid P component. These glycoproteins are known to occur in conjunction with the orcein-stainable elastic fibers in adults, but not in the young. Fibrillin immunoreactivity was associated with orcein-stainable fibers in normal skin of both adults and the young. In addition, the fibrillin immunoreactive fiber network comprised fine fibers that were unstainable by orcein, anti-vitronectin, or anti- amyloid P component. Such fine fibers were especially abundant close to the dermal-epidermal junction zone. Immunoreactivities of anti-vitronectin and anti-amyloid P component were not always associated with fibrillin immunoreactivity but were consistently found to co-localize with orcein-stainable fibers in adults. This suggests vitronectin and amyloid P component to be associated with the amorphous elastin rather than with the microfibrils, although alternative interpretations are possible. In elastotic lesions, fibrillin immunoreactivity was generally fainter than that obtained using anti-vitronectin or anti-amyloid P component. In contrast, an extensive network of dermal fibers stained by anti-fibrillin, but not by anti-amyloid P component, anti-vitronectin, or orcein, was seen in an anetoderma lesion. In conclusion, fibrillin immunoreactivity is associated with a unique dermal network, which ultrastructurally is composed of microfibrils. These fibers are proposed to have an important structural and functional role in anchoring the dermal elastic fibers in the extracellular matrix and to the lamina densa

Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes

Introduction: Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. Methods: Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. Results: ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. Conclusions: During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS

The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. In ccRCC, microRNAs (miRs) differentially expressed in tumour tissue have been identified and have been proposed to predict prognosis. The purpose of this study was to evaluate candidate miR markers identified from analysis of The Cancer Genome Atlas (TCGA) datasets in a large RCC cohort and to elucidate whether a ratio of miRs provided additional prognostic information