Search

Background Umbilical cord blood (UCB) is an important source of hematopoietic stem and progenitor cells (HSC/HPC) for the reconstitution of the hematopoietic system after clinical transplantation. Cryopreservation of these cells is critical for UCB banking and transplantation as well as for research applications by providing readily available specimens. The objective of this study was to optimize cryopreservation conditions for CD34 + HSC/HPC from UCB. Methods Cryopreservation of CD34 + HSC/HPC from UCB after mononuclear cell (MNC) preparation was tested in a research-scale setup. Experimental variations were concentration of the cryoprotectant, the protein additive and cell concentration. In addition, protocols involving slow, serial addition and removal of DMSO were compared with standard protocols (fast addition and removal of DMSO) in order to avoid osmotic stress for the cryopreserved cells. Viability and recoveries of MNC, CD34 + cells and total colony-forming units (CFU) were calculated as read-outs. In addition, sterility testing of the collected UCB units before further processing was performed. Results The optimal conditions for cryopreservation of CD34 + HPC in MNC preparations were 10% DMSO and 2% human albumin at high cell concentrations (5×10 7 MNC/mL) with fast addition and removal of DMSO. After cryopreservation using a computer-controlled freezer, high viabilities (89%) and recoveries for CD34 + cells (89%) as well as for CFU (88%) were observed. Microbial contamination of the collected UCB samples was reduced to a rate of 6.4%. Discussion Optimized cryopreservation conditions were developed for UCB MNC in respect of the composition of the cryosolution. In addition, our results showed that fast addition of DMSO is essential for improved cryopreservation and post-thaw quality assessment results, whereas the speed of DMSO removal after thawing has little influence on the recoveries of CD34 + cells and CFU. [ABSTRACT FROM AUTHOR]

Background: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N-, HR+, HER2neu-, >35 years]. This study was performed to verify in normal clinical settings how many CTX cycles and how much CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and consecutive decision making in the clinical setting for AOK Bayern-insured patients. CTX regimen and cycles avoided were identified for each case and direct costs for CTX and CTX-related medication costs for concomitant medication calculated for each patient individually according to body weight and body surface as well as potential FN prophylaxis according to physicians' decision. All medication costs were taken from the pharmaceutical price list for Germany Rote Liste of 2012. EURO [ ] to US Dollar conversion rate as of June 12 2012: 1.00 = US$ 1.25. Results: In n=93 breast cancers n=35 CTX (37.6%; FEC n=25, FEC+DOC n=8 and TC n=2) were avoided according to uPA/PAI-1 test result. Consecutively 210 CTX cycles or 12.1 years of CTX application were saved improving patients' quality of life. uPA/PAI-1 testing saved direct medication costs for avoided CTX of US$ 221.816, CTX-related concomitant medication of US$ 34.353 and G-CSF prophylaxis of US$ 25.749, overall US$ 281.918. At process costs for a single uPA/PAI-1 test calculated at US$ 359, uPA/PAI-1 testing resulted in additional costs of US$ 33.387 for all breast cancer cases. Overall, testing of uPA/PAI-1 has been proven to be cost-effective regarding direct medication costs alone at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. Conclusions: Innovative and individual cancer diagnostics like biomarkers uPA/PAI-1 can decrease need of CTX and increase patients' quality of life and thereby reduce costs for health care systems. Since application of this test is inadequate at present time measures are suggested to fully implement such cost-effective diagnostics. [ABSTRACT FROM AUTHOR]

Objective: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N-, HR+, Her2neu-, >35 years]. For quality assurance of uPA/PAI-1 testing an analysis of test-therapy concordance was performed. Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and use of the result in consecutive decision making in Tumor Board decision and actual therapy in the clinical setting for AOK Bayern-insured patients. Concordance and discordance rates of uPA/PAI-1 testing in daily clinical setting were calculated and individual reasons for decision making analyzed. Results: Among n=93 uPA/PAI-1 tests evaluated n=42/93 (45.2%) were uPA+PAI-1 negative and n=51/93 (54.8%) uPA and/or PAI-1 positive. In the group of uPA+PAI-1 negative test result in n=35/42 (83.3%) CTX was avoided and and in n=7/42 (16.7%) CTX performed. In the group of uPA and/or PAI-1 positive test result in n=26/51 (51.0%) CTX was performed and in n=25/51 (49.0%) not. Concordance of uPA/PAI-1 test result vs. consecutive therapy was (35+26)/93=65.6% and discordance of uPA/PAI-1 test-therapy (7+25)/93 = 34.4%. However, discordance of uPA/PAI-1 test result vs. Tumor Board recommendation was only n=21/93 (22.6%). As reasons for discordance a variety of influencing and/or interference factors were indentified, affecting use of test and test results or even changing therapy decision, e.g. individual therapy decision by physician, parallel use of competitive biomarkers, study participation, missing CTX therapy option in advance (like advanced age), wrong target group, timing of uPA/PAI-1 test too early, test result in contradiction of physicians' expectations (expected negative result) and rejection of CTX recommended by patients despite uPA/PAI-1 test-proven benefit. Conclusions: Individual process optimization of uPA/PAI-1 test indication, performance and result assessment could improve quality of care, reduce costs and lead to an improved application of uPA/PAI-1 test results as well as more stringency and consistency of testtherapy decisions in daily clinical setting. [ABSTRACT FROM AUTHOR]

Background: Arterial hypertension is one of the most important causes of cardiovascular diseases, and the latter are responsible for almost half of the deaths in the industrialised nations. Hypertensive disorders of pregnancy constitute one of the most frequent causes of feto-maternal morbidity and mortality; on the other hand the occurrence of a hypertensive disorder of pregnancy represents a risk for the later development of hypertension and the cardiovascular risks resulting therefrom. The aim of this article is to demonstrate the association of hypertensive disorders of pregnancy with consecutive cardiovascular diseases. Materials and Methods: Specific selective literature research. Results: After the occurrence of a hypertensive disorder of pregnancy the relative risks for hypertension are 3.7 (2.70-5.05), for ischaemic heart disease 2.2 (1.86-2.52), for cerebral insult 1.8 (1.45-2.27) and for mortality resulting from cardiovascular causes 1.5 (1.05-2.14) and are thus significant. According to a recent study 56 % of internal specialists and 23 % of gynecologists do not know about the association of preeclampsia with ischemic heart disease, 48 % and 38 % respectively are not aware of the link with stroke and 79 % and 77 % respectively are not aware of the association with a reduced life expectancy after preeclampsia. The presence of hypertension is not known by many of the patients, merely 28-38 % receive an appropriate therapy. Conclusion: Adequate follow-up after hypertensive disorders of pregnancy and the early recognition of and therapy for hypertension represent the cornerstones in the prevention of late cardiovascular sequelae. General practitioners, specialist for internal medicine and gynaecologists have a special responsibility with regard to the reduction of later complications.

Introduction: Afterbirth tissues, which include the umbilical cord, placenta, amnion, and cord blood, are usually discarded. Recent progress in regenerative medicine suggests that we re-evaluate these tissues and assess their therapeutic potential., Methods: Firstly the unique properties of afterbirth tissues and their current use in regenerative medicine are summarised. Then we introduce the cooperation of our institutions and our experiences regarding the collection and utilisation of afterbirth tissues., Results: A literature survey suggests that besides the well-known transplantation of hematopoietic stem cells from cord blood, afterbirth tissues were also used as a source of stem cells, progenitor cells, differentiated cells, and blood vessels for tissue engineering purposes. According to our own experience, the two participating OB/GYN departments and the blood donation service were able to organise a sufficient supply of umbilical cords for research purposes. The yield correlated with incentives for the midwives. A total of more than 4,300 cords was collected for experiments designed to create small caliber vessel grafts. The contamination rate was low. Birth mode significantly affected umbilical vein function, whereas ischaemia for up to 40 h did not have any deleterious effects. Umbilical veins were cryopreserved with a moderate loss of function. Fresh umbilical veins were endothelium-denuded and reseeded with endothelial cells harvested from coronary artery disease patients to generate an autologous surface., Conclusions: Afterbirth tissues have unique properties which make them ideally suited for regenerative medicine. These tissues can be procured and utilised in research facilities even in the absence of an in-house birthing centre., (© Georg Thieme Verlag KG Stuttgart · New York.)

Umbilical cord blood (UCB) of a newborn contains stem cells with a remarkably high differentiation and regeneration potential. They are therefore useful for application in regenerative medicine. In this review current clinical applications are summarised and the necessity for the storage of UCB stem cells is derived and discussed. A Medline search for publications regarding clinical application of UCB stem cells was carried out and other data bases were reviewed. The transplantation of UCB stem cells, a special class of adult stem cells, has not only been established successfully in a variety of haematoblastoses but could also improve the prognosis in diseases which are related to degeneration and/or injuries of body cells and organs. The current focus in worldwide research is tissue engineering of bioartificial heart valves and vessels as well as applications of UCB stem cells in acute myocardial infarction, diabetes mellitus type 1 and neurodegenerative diseases. In urology the first results regarding the successful application of UCB stem cells in incontinence have been published. This definite progress in adult stem cell research as well as in clinical application requires a more rational handling of the resource UCB stem cells. Personal strategies as well as governmental concepts for storage of UCB stem cells for personal precautions, for donation to others or for research, respectively, have to be developed.

Objective: Private umbilical cord blood (UCB) banking after delivery has increased over the last decade. For adult/somatic stem cell research UCB is an essential source of stem cells and researchers question if the number of UCB samples for research might be reduced by private banking., Methods: A survey among seven private blood banks in Germany and analysis and comparison of the number of UCB samples donated for research within the STEMMAT project with private blood banking were performed from 03/2003 to 06/2005 at the Frauenklinik (OB/GYN), Technical University Munich, Germany., Results: Within 27.5 months 1,551 UCB samples were collected for research purposes; the effective recruitment rate was higher than expectations at an effective 66.2 %. Private UCB banking [n = 24] was distributed among three cord blood banks [n = 16, 6 and 4]. The rate of private blood banking was 0.99 % for all deliveries, thus reducing the effective rate for research purpose by only 1.5 %., Conclusion: Under the assumption of active and successful recruitment of scientific UCB samples, private blood banking does not significantly reduce this rate and therefore is a negligible rival in the competition for sufficient numbers of UCB samples for research.

Adult stem cells from umbilical cord and cord blood are an interesting alternative to embryonic stem cells because such research is commonly recognized as ethical undisputed and many aspects are still insufficiently investigated. In the context of the STEMMAT research project (STEM = Stem Cell and MAT = Material) different aspects of stem cells from umbilical cord and cord blood are investigated, to improve basic science understanding and potentially leading someday to a clinical application.

Preeclampsia is accompanied by high fetal and maternal morbidity and mortality and to a high degree responsible for preterm delivery. The pathophysiologic mechanisms underlying this disease remain poorly understood. Accordingly, only few causative or preventive therapeutical strategies are known. One such example for a preventive strategy is the use of aspirin (ASA) which directly affects the imbalance of vasodilative prostacycline and vasoconstrictive thromboxane. Recently, some studies are indicating a preventive effect of vitamin C and E substitution. In contrast, early antihypertensive therapy did not prevent later progression of the disease. Furthermore, sodium restriction, calcium and magnesium substitution, fish oil substitution, or steroid therapy are without any effect regarding the later development of preeclampsia. It is of utmost importance to further elucidate underlying pathophysiological mechanisms to improve therapeutical and preventive strategies.