Showing papers by "German Red Cross published in 2006"

Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.

Abstract: Mesenchymal stem cells (MSCs) represent a promising tool for new clinical concepts in supporting cellular therapy. Bone marrow (BM) was the first source reported to contain MSCs. However, for clinical use, BM may be detrimental due to the highly invasive donation procedure and the decline in MSC number and differentiation potential with increasing age. More recently, umbilical cord blood (UCB), attainable by a less invasive method, was introduced as an alternative source for MSCs. Another promising source is adipose tissue (AT). We compared MSCs derived from these sources regarding morphology, the success rate of isolating MSCs, colony frequency, expansion potential, multiple differentiation capacity, and immune phenotype. No significant differences concerning the morphology and immune phenotype of the MSCs derived from these sources were obvious. Differences could be observed concerning the success rate of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs could be cultured longest and showed the highest proliferation capacity, whereas BM-MSCs possessed the shortest culture period and the lowest proliferation capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation capacity, in contrast to BM- and AT-MSCs. Both UCB and AT are attractive alternatives to BM in isolating MSC: AT as it contains MSCs at the highest frequency and UCB as it seems to be expandable to higher numbers.

A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor α‐chain promoter

Abstract: Summary The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn-dependent transport across the placenta may influence antibody-mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1–VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7·5 and 92·0%, respectively). Real-time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1·66-fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0·003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG-binding capacities.

Protection from type 1 diabetes by vitamin D receptor haplotypes.

Abstract: Vitamin D has been involved in the modulation of calcium and bone metabolism as well as in the immune system, where it suppresses the proliferation of activated T cells. These effects are exerted via the vitamin D receptor (VDR). Polymorphisms within this gene have been exhaustively studied in diverse autoimmune diseases but with inconsistent results. We previously reported a positive association of polymorphisms within the VDR gene (Apa I, Taq I, Bsm I, and Fok I). In the present article we extended our previous reports to seven additional polymorphisms (rs757343, rs9729, rs2853559, rs1989969, rs3847987, rs2238135, and rs4516035) in a larger set of German simplex type 1 diabetes families. Additionally we correlated serum levels of 25(OH)D(3) and 1,25(OH)(2)D(3) with VDR genotypes and haplotypes. The haplotypes "CG" (Taq I-Apa I), "CGG" (Taq I-Apa I-Tru I), "CGC" (Taq I-Apa I-Fok I), "GCTG" (rs9729-Taq I-Apa I-Tru I), and "CGGC"(Taq I-Apa I, Tru I, Fok I) were less often transmitted, thus negatively associated with type 1 diabetes. Patients who carried the genotype "CC" of the rs3847987 polymorphism had higher median serum levels of 25(OH)D(3). Furthermore, the majority of patients with this genotype possessed normal serum levels of 25(OH)D(3). We conclude that variants of the VDR may confer a genetic protection from type 1 diabetes. Furthermore, normal serum levels of 25(OH)D(3) appear to correlate with a VDR genotype. This supports a role of vitamin D in the immune pathogenesis of type 1 diabetes.

Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer.

Abstract: . Purpose: To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer. Methods: Twenty-two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies. Results: In eight of 22 (36%; 95% confidence interval [CI] 17–59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65–97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies. Conclusions: Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.

Role of bladder neck mobility and urethral closure pressure in predicting outcome of tension-free vaginal tape (TVT) procedure.

Abstract: Objective To investigate how urethral mobility and urethral closure pressure affect the outcome of tension-free vaginal tape (TVT) insertion for stress incontinence. Methods A total of 191 consecutive women with genuine stress urinary incontinence with or without intrinsic sphincter deficiency were evaluated prospectively with multichannel urodynamics, 24-h voiding diaries, clinical stress tests and introital ultrasound measurements preoperatively and 6 months after surgery. Additional introital ultrasound examinations were performed immediately after the operation, at 12 months and annually thereafter. 177/191 patients had completed a 36-month follow-up at the time of writing. Urethral mobility was described as linear dorsocaudal movement (LDM), with hypermobility being defined as LDM > 15 mm on sonography. Intrinsic sphincter deficiency was defined by a maximum urethral closure pressure (MUCP) of <20 cmH2O. Results The overall cure rate at the 36-month follow-up was 89.5% (Kaplan-Meier estimator), with secondary cure (within 6 months of surgery) in 10.5% of these patients. The operation failed in 4.2% of the women and recurrence was seen in 6.3% of the cases. Bladder neck mobility was significantly reduced at the 6-month follow-up (P < 0.001). Compared with primary cure, therapeutic failure and secondary cure were associated with a significantly lower postoperative bladder neck mobility (P < 0.05). Postoperative hypermobility reduced the risk of therapeutic failure. In addition, women with therapeutic failure or secondary cure had a significantly lower MUCP than did those with primary cure (P < 0.01). Conclusion The effectiveness of the TVT sling appears to depend on adequate postoperative urethral mobility and urethral closure pressure. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Urethral hypermobility after anti-incontinence surgery - a prognostic indicator?

Abstract: The aim of this study was to define the concept of hypermobility of the bladder neck and determine its effects on the cure rate and postoperative complications in patients undergoing colposuspension. In a retrospective study, 310 patients who underwent primary colposuspen- sion for urodynamically proven genuine stress urinary incontinence were assessed by introital ultrasound before surgery and during follow-up for up to 48 months post- operatively. A total of 152 women completed 48 months of follow-up. Mobility of the bladder neck during straining was described as linear dorsocaudal movement (LDM) with LDM >15 mm being defined as hypermobility. The overall objective cure rate was 90.0% at 6-month follow-up vs 76.8% at 48-month follow-up (Kaplan-Meier estima- tors). Urge symptoms occurred in 12.6% (39/310) of the women and de novo urge incontinence in 2.3% (7/310). Bladder neck hypermobility was significantly reduced after anti-incontinence surgery, from 67.1% (208/310) before surgery to 5.5% (17/310) immediately after surgery (P<0.0001). Postoperative hypermobility was associated with a higher recurrence rate. In the hypermobility group, 52.9 and 34.0% of the patients were continent for up to 6 and 48 months, respectively, as opposed to 92.2 and 79.2% in the group without hypermobility (P<0.0001). Women with postoperative hypermobility had a 3.2-fold higher risk of recurrence within 48 months. Bladder neck hypermo- bility after surgery was also associated with postoperative voiding difficulty (P=0.0278). Patients in whom hypermo- bility of the bladder neck diagnosed before surgery persists after colposuspension have a higher risk of recurrence and are more likely to develop postoperative complications than those without this hypermobility.

High-dose-rate (HDR) or pulsed-dose-rate (PDR) perioperative interstitial intensity-modulated brachytherapy (IMBT) for local recurrences of previously irradiated breast or thoracic wall following breast cancer.

Abstract: In patients receiving salvage high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy for a local recurrence on the chest wall or in the previously treated breast, clinical outcome and benefit were investigated. All patients had previously been treated with full-dose adjuvant external-beam irradiation (EBRT). Disease-free interval after salvage treatment, local tumor control and side effects were analyzed retrospectively. Between 1996 and 2002, a total of 32 consecutive patients were treated. 13 patients initially treated with mastectomy and postoperative irradiation and 19 patients initially treated with breast-conserving surgery and postoperative irradiation developed a local recurrence. The mean dose of previous radiation therapy was 58 Gy (range, 42–64 Gy), applied by conventional fractionation. After implantation ± surgery of recurrent disease and CT-based 3-D planning, 15 patients were irradiated with HDR-IMBT (intensity-modulated brachytherapy) with a mean dose of 28 Gy (range, 10–30 Gy, 2 × 2.5 Gy/day at 6-h daily interfraction interval) and 17 patients received PDR-IMBT with a mean dose 30 Gy (range, 10–45 Gy, 5 × 1 Gy/day at 2-h pulse intervals). Four patients underwent additional EBRT using a dose of 24–40 Gy electrons. Treatment was performed only on working days. After a mean post-implant follow-up of 19 months (range, 1–83 months), no signs of local recurrence were observed in 20 of the 32 patients. In twelve patients, local recurrence occurred after a mean follow-up of 13 months (range, 1–78 months). 20 of the 32 patients experienced an additional systemic progress. In one patient, an EORTC/RTOG grade 3 side effect (ulceration of the skin) was described, which was followed by a local recurrence 12 months posttherapeutically. Perioperative interstitial HDR/PDR-IMBT of localized breast or thoracic wall recurrences following previous full-dose EBRT appears to be a meaningful salvage treatment with acceptable toxicity.

Proposal for a new scoring system in international interhospital air transport.

Abstract: Several advanced scoring systems have been established for the assessment of patients in clinical intensive care medicine.1 Currently, the widespread use of these systems allows an assessment of outcome, as well as assisting in the optimal choice of treatment settings, for example, time point to admission to the ICU.2 Furthermore, scoring systems can be an advantageous tool for purposes such as quality control and improvement of cost effectiveness.3 Some of these scores have been modified to provide a consistent scoring system in transport medicine, as for example, the rapid acute physiology scoring (RAPS). RAPS, a truncated version of the acute physiology and chronic health evaluation (APACHE II) score, has proved to be a reliable and predictive measurement of patient severity, and physiologic stability, in short distance helicopter transport systems.4,5 As a modified ICU score, RAPS however, is naturally limited, as it solely ranks illness severity, whereas other transport related aspects, such as, specific risk factors, and limitations for aeromedical transport, are not considered.6 RAPS therefore seems to be feasible for short helicopter transport between intensive care units, rather than for international transport. In contrast,patients undergoing long distance interhospital transfer by air ambulance or commercial airline are, if at all, scored by the NACA (National Committee of Aeronautics) score system, which was introduced about 35 years ago during the Vietnam war (Table 1), and last modified in 1976.7 The aim of this score system was a rapid triage of patients evacuated from battlefields, and not the ranking of patients transported between hospitals. Although also modified to accommodate patients suffering from internal diseases, the NACA score system poorly reflects the complex setting of modern interhospital transfer and travel medicine.

Blood transfusion in Europe: basic principles for initial and continuous training in transfusion medicine: an approach to an European harmonisation.

Abstract: Over the past few decades, transfusion medicine and haemotherapy have evolved into complex medical disciplines comprising a broad field of subspecialties such as immunohaematology, blood component production, haemapheresis and haemostaseology. Transfusion medicine is thus an important qualification at the interfaces of analytical laboratory medicine, pharmaceutical production and clinical disciplines such as internal medicine, anaesthesiology or surgery. Physicians specialising in transfusion medicine are valuable and competent partners for these related disciplines when it comes to safe, effective and tailored haemotherapy. Why has transfusion medicine become so complex? On the one hand, one can discern problems such as infectious diseases like the HIV disaster in the past century, resulting in guidelines, directives and laws such as the transfusion law in Germany. Thereby, we now enjoy the highest level of blood product safety ever regarding viral transmission thanks to the broad implementation of PCR testing. On the other hand, there are numerous positive reasons for the increasing complexity of transfusion medicine: Modern medical therapies like stem cell transplantation, cellular therapy, transplantation of solid organs, regenerative medicine and surgery cannot exist without a safe supply of blood products and high quality standard as well as special blood products and laboratory services provided by blood banks and transfusion medicine specialists. Good laboratory practice (GLP), good manufacturing practice (GMP), quality management systems and quality control on the pharmaceutical manufacturer's level are only few examples of the standards in today's blood banking. European directives in the field of blood products, stem cell preparations and tissue have led to higher uniform quality standards for biological preparations in a unified Europe, which is the desired outcome, but which also increases the complexity of this field. In contrast, directives 93/16/EEC and 2001/19/EC, the directives of the European Parliament and of the Council on the mutual recognition of professional qualifications of European doctors currently in force, as well as the impending directive 2005/36/EC, which has to be translated into national law until October 2007, do not include transfusion medicine, blood transfusion or immunohaematology at all. Other medical specialities, which like our field, are not common to all member states of the European Union, are listed in the above mentioned directives with the minimum length of training and minimal requirements for the qualifications. Examples include clinical biology, biological haematology, microbiology-bacteriology, biological chemistry, immunology, thoracic, paediatric or vascular surgery as well as physiotherapy, stomatology, neuro-psychiatry, dermato-venerology, occupational medicine, allergology, geriatrics, gastro-enterological surgery, community medicine, nuclear medicine, pharmacology, accident and emergency medicine or tropical medicine. Most of the above are medical specialities in some member states, but not in all. A concerted initiative inaugurated by the European Network of Transfusion Medicine Societies (EuroNet-TMS) and the European Blood Alliance (EBA) aims to compile the situation of the transfusion medicine speciality throughout Europe. A preliminary summary of the current situation in 15 European states was prepared in 2005 after a first set of questions, which was sent out by us via the EBA platform. The authors appreciate Clair Watts' compilation of the answers provided by the 15 European colleagues. A summary of these answers is depicted in Table 1. However, the initiative aims at a more complex analysis of the different requirements and constituent parts of the qualification in transfusion medicine in different countries. A long-term objective of this initiative might be to introduce the transfusion medicine specialisation into the above mentioned EC directives in order to facilitate mutual recognition of transfusion medicine qualifications throughout Europe.

Isolation of monocytes from whole blood-derived buffy coats by continuous counter-flow elutriation

Abstract: Monocytes (MOs) are the most commonly used precursors for the generation of dendritic cells (DCs) in vitro. Continuous counter-flow elutriation represents a promising tool to isolate MOs from white blood cell (WBC) products. Thirty whole blood–derived, AB0-identical buffy coats (BCs) were pooled using sterile technique (n = 5 experiments). For red blood cell (RBC) and polymorphonuclear cell (PMN) depletion, the BC pools were processed in a Cobe® Spectra device (Gambro BCT) using the bone marrow program. Subsequently, continuous counter-flow elutriation in an Elutra® device (Gambro BCT) was performed to enrich and purify MOs. BC pool volume averaged 1,260 ± 14 ml containing 7.7 ± 1.1 × 109 MOs. During 107 ± 7 min, Cobe Spectra operation, the BC pools were processed for several times, and approximately 9,749 ± 605 ml volume passed the device. Product volume and MO yield averaged 160 ± 16 ml, and 4.3 ± 1.3 × 109 cells, respectively. Elutra operation was performed within 59 ± 0 min and yielded 2.5 ± 0.9 × 109 MOs with a purity of 60 ± 12%. Compared with the Cobe Spectra product cell count, MO recovery by Elutra averaged 59 ± 10%. Elutriation of MOs from pooled BCs using Elutra exhibited comparatively low recovery and purity rates. This shortcoming may be due to the nature of the source material. Optimization of the elutriation procedure is necessary to improve MO enrichment from BCs. J. Clin. Apheresis 2006. © 2006 Wiley-Liss, Inc.

Neither an intronic CA repeat within the CD48 gene nor the HERV-K18 polymorphisms are associated with type 1 diabetes.

Abstract: Type 1 diabetes is an autoimmune heterogeneous disease that is determined by environmental and genetic factors A possible retroviral etiology has been inferred from the observation that human endogenous retrovirus (HERV)-K18 encoding a superantigen (SAg) has a polymorphism associated with this disease Type 1 diabetes families from Germany and Belgium were genotyped for the novel HERV-8914 (303 families) and for the known HERV-8594 (284 families) polymorphisms within the SAg-coding region on the HERV-K18 Case-control analysis was performed for the HERV-8914 polymorphism (506 patients) and for the HERV-8594 polymorphism (370 patients) and compared with 350 German controls Haplotypes were constructed Additionally, a microsatellite within the CD48 gene was analyzed in German type 1 diabetes families (n=125) as well as in patients (n=375) and in healthy controls (n=350) No association was found for HERV-K18 polymorphisms or the CA repeat within the CD48 gene with type 1 diabetes mellitus either in families or by comparing patients and controls In conclusion, we cannot confirm a role of HERV-K18 polymorphisms -HERV-8914 and HERV-8594- or of the CD48 CA repeat for type 1 diabetes susceptibility