Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

One of two patients in whom early homograft rejection developed after renal transplantation had many antidonor antibodies before operation. By the measurement of gradients across intracorporeal and extracorporeal homografts in this patient, the new kidneys were shown to sequester host immunoglobulins, platelets, white cells and clotting factors. Moreover, the renal venous blood then contained fibrinolytic activity. This presensitized recipient, as well as a second patient who did not have detectable preformed humoral antibodies, gave evidence from clinical observation and from the various clotting tests of disseminated intravascular coagulation with fibrinolysis and a severe bleeding diathesis. Immunofluorescent and histologic studies revealed a laying down of fibrin in the homograft vessels that continued in some cases to cortical necrosis of the transplanted kidneys or, alternatively, receded at the time fibrinolysis occurred. The variety of rejection seen in these patients has been characterized as an immunologically induced coagulopathy. © 1970, Massachusetts Medical Society. All rights reserved

The Role of I Region Gene Products in Macrophage - T Lymphocyte Interaction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73965/1/j.1600-065X.1978.tb00400.x.pd

Chlamydiatrachomatis and placental inflammation in early preterm delivery

Chlamydiatrachomatis may infect the placenta and subsequently lead to preterm delivery. Our aim was to evaluate the relationship between the presence of Chlamydiatrachomatis and signs of placental inflammation in women who delivered at 32 weeks gestation or less. Setting: placental histology and clinical data were prospectively obtained from 304 women and newborns at the Erasmus MC-Sophia, Rotterdam, the Netherlands. C.trachomatis testing of placentas was done retrospectively using PCR. C.trachomatis was detected in 76 (25%) placentas. Histological evidence of placental inflammation was present in 123 (40%) placentas: in 41/76 (54%) placentas with C.trachomatis versus 82/228 (36%) placentas without C.trachomatis infection (OR 2.1, 95% CI 1.2–3.5). C.trachomatis infection correlated with the progression (P = 0.009) and intensity (P = 0.007) of materno-fetal placental inflammation. C.trachomatis DNA was frequently detected in the placenta of women with early preterm delivery, and was associated with histopathological signs of placental inflammation

Quantified light-induced fluorescence, review of a diagnostic tool in prevention of oral disease

Diagnostic methods for the use in preventive dentistry are being developed continuously. Few of these find their way into general practice. Although the general trend in medicine is to focus on disease prevention and early diagnostics, in dentistry this is still not the case. Nevertheless, in dental research some of these methods seem to be promising for near future use by the general dental professional. In this paper an overview is given of a method called quantitative light-induced fluorescence or (QLF) in which visible and harmless light excites the teeth in the patient's mouth to produce fluorescent images, which can be stored on disk and computer analyzed. White spots (early dental caries) are detected and quantified as well as bacterial metabolites on and in the teeth. An overview of research to validate the technique and modeling to further the understanding of the technique by Monte Carlo simulation is given and it is shown that the fluorescence phenomena can be described by the simulation model in a qualitative way. A model describing the visibility of red fluorescence from within the dental tissue is added, as this was still lacking in current literature. An overview is given of the clinical images made with the system and of the extensive research which has been done. The QLF™ technology has been shown to be of importance when used in clinical trials with respect to the testing of toothpastes and preventive treatments. It is expected that the QLF™ technology will soon find its way into the general dental practice

Differential Dynamic Properties of Scleroderma Fibroblasts in Response to Perturbation of Environmental Stimuli

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-β pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-β pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40 years). Intervention(s) Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH â¥15 pmol/L: 0.10â0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study

Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and may influence pregnancy outcome. This study was conducted to assess the effect of chlamydial infection during pregnancy on premature delivery and birthweight. Pregnant women attending a participating midwifery practice or antenatal clinic between February 2003 and January 2005 were eligible for the study. From 4,055 women self-administered questionnaires and urine samples, tested by PCR, were analysed for C. trachomatis infection. Pregnancy outcomes were obtained from midwives and hospital registries. Gestational ages and birthweights were analysed for 3,913 newborns. The C. trachomatis prevalence was 3.9%, but varied by age and socio-economic background. Chlamydial infection was, after adjustment for potential confounders, associated with preterm delivery before 32 weeks (OR 4.35 [95% CI 1.3, 15.2]) and 35 weeks gestation (OR 2.66 [95% CI 1.1, 6.5]), but not with low birthweight. Of all deliveries before 32 weeks and 35 weeks gestation 14.9% [95% CI 4.5, 39.5] and 7.4% [95% CI 2.5, 20.1] was attributable to C. trachomatis infection. Chlamydia trachomatis infection contributes significantly to early premature delivery and should be considered a public health problem, especially in young women and others at increased risk of C. trachomatis infection