Genetic evidence for fetal origin of transcobalamin II in human cord blood

Phenotypes of transcobalamin II (TC2) were determined in 95 maternal- cord serum pairs in order to identify the origin of TC2 in human cord blood. Unsaturated (apo) TC2 in serum was labeled with radioactive (57Co) cobalamin (CbI) and separated into isoproteins by polyacrylamide gel electrophoresis and autoradiography. Discordancy between the maternal and the cord serum type was observed in 45% of the pairs. The results demonstrated that, at the end of pregnancy, the fetus is capable of TC2 synthesis and that there is no detectable transplacental passage of maternal apo-TC2. Presence of maternal saturated (holo) TC2 in cord serum could be excluded in 9 informative discordant pairs by exchanging endogenously bound CbI with 57Co-CbI. Our finding that TC2 in human cord serum is of fetal rather than maternal origin suggests an essential role for fetal TC2 in CbI utilization and appears to contradict the hypothesis that transplacental passage of maternal TC2 may explain the normal fetal development in cases of congenital TC2 deficiency. The total immunoreactive TC2 content in 23 maternal serum samples collected at the end of pregnancy (812 +/- 175 pM CbI equivalent) was significantly higher than in the corresponding cord sera (605 +/- 148 pM; p less than 0.001) and did not significantly differ from the value in a control group of healthy male and female adults (841 +/- 192 pM). At the end of pregnancy, the apo-TC2 content in 12 maternal serum samples (760 +/- 347 pM) was significantly higher than in the corresponding cord sera (501 +/- 254 pM; p less than 0.05) and did not significantly differ from the value in the control group (747 +/- 137 pM).     

Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines

Purpose

To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media.

Areas covered

Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been reviewed.

Key Points

? Clinical features, risk factors and prevention of nephrogenic systemic fibrosis are reviewed ? Patients with GFR below 30 ml/min/1.73 m ² have increased risk of developing NSF ? Low stability gadolinium contrast media show the strongest association with NSF ? Following guidelines regarding gadolinium contrast agents minimises the risk of NSF ? Potential long-term harm from gadolinium accumulation in the body is discussed     

Contrast venography: reassessment of its role

To compare contrast venography with noninvasive methods, 353 patients clinically suspected of having deep venous thrombosis were examined with venography and independently with combined Doppler flow sounds and plethysmography. Noninvasive examinations had a sensitivity of 96% and a specificity of 90%. Positive noninvasive tests had a 94% predictive value, and negative noninvasive tests had a 93% predictive value. The overall accuracy of the noninvasive tests was 94% (331 of 353) compared with venography. Since venography itself may be subject to misinterpretation, noninvasive examinations should be the preferred initial method for diagnosing deep venous thrombosis. Venography should be reserved for situations that require additional diagnostic confirmation.     

Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m2 and abolished at 50 J/m2. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus- host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m2 of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m2) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m2. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m2 survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m2 survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m2) and 2 of 9 (100 J/m2). These data indicate that UV-B irradiation inhibits lymphocyte reactivity and can prevent GVHD. However, there is clear in vitro and in vivo evidence of stem cell damage, such that autologous marrow recovery was demonstrated in a proportion of recipients. In parent----F1 UV-irradiated transplants, sustained hematopoietic recovery was effected in the majority by donor stem cells.     

Practical methods for dealing with 'not applicable' item responses in the AMC Linear Disability Score project

Background  

Whenever questionnaires are used to collect data on constructs, such as functional status or health related quality of life, it is unlikely that all respondents will respond to all items. This paper examines ways of dealing with responses in a 'not applicable' category to items included in the AMC Linear Disability Score (ALDS) project item bank.