Showing papers by "German Red Cross published in 2007"

Number development and developmental dyscalculia

Abstract: There is a growing consensus that the neuropsychological underpinnings of developmental dyscalculia (DD) are a genetically determined disorder of 'number sense', a term denoting the ability to represent and manipulate numerical magnitude nonverbally on an internal number line. However, this spatially-oriented number line develops during elementary school and requires additional cognitive components including working memory and number symbolization (language). Thus, there may be children with familial-genetic DD with deficits limited to number sense and others with DD and comorbidities such as language delay, dyslexia, or attention-deficit-hyperactivity disorder. This duality is supported by epidemiological data indicating that two-thirds of children with DD have comorbid conditions while one-third have pure DD. Clinically, they differ according to their profile of arithmetic difficulties. fMRI studies indicate that parietal areas (important for number functions), and frontal regions (dominant for executive working memory and attention functions), are under-activated in children with DD. A four-step developmental model that allows prediction of different pathways for DD is presented. The core-system representation of numerical magnitude (cardinality; step 1) provides the meaning of 'number', a precondition to acquiring linguistic (step 2), and Arabic (step 3) number symbols, while a growing working memory enables neuroplastic development of an expanding mental number line during school years (step 4). Therapeutic and educational interventions can be drawn from this model.

Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction.

Abstract: Aim The recently published REPAIR-AMI and ASTAMI trial showed differences in contractile recovery of left ventricular function after infusion of bone marrow-derived cells in acute myocardial infarction. Since the trials used different protocols for cell isolation and storage (REPAIR-AMI: Ficoll, storage in X-vivo 10 medium plus serum; ASTAMI: Lymphoprep, storage in NaCl plus plasma), we compared the functional activity of BMC isolated by the two different protocols. Methods and results The recovery of total cell number, colony-forming units (CFU), and the number of mesenchymal stem cells were significantly reduced to 77 ± 4%, 83 ± 16%, and 65 ± 15%, respectively, when using the ASTAMI protocol compared with the REPAIR protocol. The capacity of the isolated BMC to migrate in response to stromal cell-derived factor 1 (SDF-1) was profoundly reduced when using the ASTAMI cell isolation procedure (42 ± 8% and 78 ± 3% reduction in healthy and CAD-patient cells, respectively). Finally, infusion of BMC into a hindlimb ischaemia model demonstrated a significantly blunted blood-flow-recovery by BMC isolated with the ASTAMI protocol (54 ± 6% of the effect obtained by REPAIR cells). Comparison of the individual steps identified the use of NaCl and plasma for cell storage as major factors for functional impairment of the BMC. Conclusion Cell isolation protocols have a major impact on the functional activity of bone marrow-derived progenitor cells. The assessment of cell number and viability may not entirely reflect the functional capacity of cells in vivo . Additional functional testing appears to be mandatory to assure proper cell function before embarking on clinical cell therapy trials.

The pathogenesis of transfusion-related acute lung injury (TRALI).

Abstract: In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

In vitro differentiation of human mesenchymal stem cells to epithelial lineage

Abstract: Our study examined whether human bone marrow-derived MSCs are able to differentiate, in vitro, into functional epithelial-like cells. MSCs were isolated from the sternum of 8 patients with different hematological disorders. The surface phenotype of these cells was characterized.To induce epithelial differentiation, MSCs were cultured using Epidermal Growth Factor, Keratinocyte Growth Factor, Hepatocyte Growth Factor and Insulin-like growth Factor-II. Differentiated cells were further characterized both morphologically and functionally by their capacity to express markers with specificity for epithelial lineage. The expression of cytokeratin 19 was assessed by immunocytochemistry, and cytokeratin 18 was evaluated by quantitative RT-PCR (Taq-man). The data demonstrate that human MSCs isolated from human bone marrow can differentiate into epithelial-like cells and may thus serve as a cell source for tissue engineering and cell therapy of epithelial tissue.

Phenothiazinium derivatives for pathogen inactivation in blood products.

Abstract: Phenothiazine-based photosensitisers have been employed in photoantimicrobial research for nearly 80 years, both as lead and novel compounds. However, the main structural variations have mainly involved the auxochromic side chains and little has been reported concerning either peripheral substitution or structures with chromophores other than those of the phenothiazinium or annelated benzo[a]phenothiazinium type. In terms of application, the phenothiazinium series has featured commonly in cytology and cytopathology, as well as in haematological staining. The current work covers the evolution of improved photosensitisers based on the phenothiazine ring system, with particular reference to the field of pathogen inactivation, and the structural alteration of lead compounds such as methylene blue and Nile blue to yield improved photosensitisers for this important aspect of blood product safety.

Germline NF1 Mutational Spectra and Loss-of-Heterozygosity Analyses in Patients with Pheochromocytoma and Neurofibromatosis Type 1

Abstract: BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma. MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed. RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype. CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.

HBsAg non‐reactive HBV infection in blood donors: Transmission and pathogenicity

Abstract: Five blood donors with occult persistent and one donor with an early window phase HBV infection were identified. They were negative in regular HBsAg screening and had low levels of HBV DNA that were probably not detectable by current mini-pool nucleic acid amplification testing. In four donors several mutations were found located in the HBs antigen loop. In three donors the mutations were predominantly outside the "a" determinant; one donor had a wild type HBsAg sequence. Fifty-five recipients of donations from the persistently infected donors could be tested for previous or ongoing HBV infection and of them 53% (29/55) were anti-HBc positive. Based on the prevalence of anti-HBc in Germany (7%), it was assumed that four of those recipients had already been positive before transfusion. In 22 cases, it was assumed that they acquired infection by the donations, but the infection remained asymptomatic and was resolved. In three cases transmission was proven by the time course of the acute infection and sequence identity The resulting infection was fatal and associated with immunological disorders at the time of transmission: in one case sepsis and in the othertwo cases immunosuppression. In a further asymptomatic case of proven transmission from the early window phase donation passively administered anti-HBs could not prevent spread of wildtype HBV but antiviral treatment lead to resolution. Surprisingly the typical acute hepatitis B was not observed in a single one of the 26 cases of assumed or proven transmission.

Comparison of three bacterial detection methods under routine conditions.

Abstract: Background and Objectives Since 2004, bacterial screening of platelets has been required in the USA and is also done on a voluntary basis in many European countries. The German Red Cross blood donor services conducted a prospective multicentre study in order to investigate the prevalence of bacterially contaminated pool platelet concentrates and apheresis platelet concentrates. This substudy compares three different bacterial detection systems. Study Design and Methods Platelet concentrates were tested in parallel with BacT/ALERT, Scansystem‘ and Pall eBDS (n = 6307) in pool platelets. Apheresis platelets were tested in parallel with BacT/ALERT and Pall eBDS (n = 4730). All initially positive results were evaluated by a standardized procedure including evaluation by a microbiology reference laboratory. Results One in 6307 pool platelets were confirmed positive by BacT/ALERT, whereas Pall eBDS and Scansystem failed to detect these samples. Only three samples were initially reactive with Pall eBDS without proof of any bacteria strains. The rate of false-positive results was substantially higher for BacT/ALERT (0·25%, 28 in 11 037 tested samples) than for eBDS (0·03%, 3 in 11 037 tested samples) or Scansystem (0·0%, 0 in 6307 tested samples). Three of 4730 apheresis platelets were confirmed positive by BacT/ALERT. These were negative with Pall eBDS. Conclusion Sensitivity was best for BacT/ALERT, whereas specificity was enhanced for Pall eBDS and Scansystem. Scansystem required specially trained staff, whereas BacT/ALERT and Pall eBDS were easy, quick, user-friendly and objective methods.

Bovine colostrum as a biologic in clinical medicine: a review. Part I: biotechnological standards, pharmacodynamic and pharmacokinetic characteristics and principles of treatment.

Abstract: Mammals supply their newborn before birth, at birth or shortly after birth with antibodies, immunocytes and humoral constituents. This "borrowed immunity" is a form of passive immunization to protect the newborn against environmental pathogens until it establishes its own pathogen recognition and disposal systems. In cows, goats, horses and some other animal species, most immunoglobulins are obtained from the colostrum, the first milk after birth, via the gut but in humans the majority of immunoglobulins, and those of the IgG-class in particular, are acquired from the mother by placental transport in the weeks prior to parturition. It has long been known that the consumption of bovine colostrum by humans has therapeutic effects e.g. in gastrointestinal infections, but only since the second half of the last century has it been possible to prepare stable, standardized preparations of colostrum. These biologics are administered to patients in combination with standard therapies as so-called balanced supportive diets. Investigations with standardized colostrum preparations in animal models of human disease and estimates of bovine IgG activity in the human GI-tract, described in this review, have provided preclinical data supporting the use of bovine colostrum in human diseases. On the other hand, the number of bovine colostrum products with a sufficiently large and reliable database is limited and the precise nature of the therapeutic targets is still being evaluated.

Simultaneous blockade of VEGFR-1 and VEGFR-2 activation is necessary to efficiently inhibit experimental melanoma growth and metastasis formation.

Abstract: Metastasis continues to be the major cause of morbidity and mortality in malignant melanoma. In our study, we explored whether inhibition of VEGFR-1 or VEGFR-2 signaling conveys distinct suppressive effects on B16 melanoma subcutaneous growth and metastasis formation. The inhibition of VEGFR-1 or -2 alone had no significant influence on both melanoma growth and metastasis formation. In contrast, simultaneous blockade of VEGFR-1 and -2 signaling strongly suppressed progression in both B16 tumor models. There was no expression of VEGFR-1 or -2 detectable on the B16 cells used, excluding the melanoma cells as direct therapeutic targets. Analyzing the contribution of progenitor-like cells during melanoma metastasis formation, we observed an enhanced proliferation and mobilization of VEGFR-1+ myeloid and VEGFR-2+ endothelial cells with progenitor potential by the induction of melanoma lung metastasis, which was not influenced by interference with VEGFR signaling. These results indicate that the antimetastatic effects exerted by combined inhibition of VEGFR-1 and -2 signaling were mediated via targeting cell populations other than progenitors only. Sole inhibition of VEGFR-1 signaling led to a strong reduction of the CD45-positive inflammatory infiltrate in the tumor tissue. However, the formation of lung metastasis was not affected, indicating that inhibition of the inflammatory response was not sufficient to efficiently block B16 melanoma metastasis development. Taken together, our data suggest that in the utilized B16 tumor models the blockade of both the inflammatory and the VEGFR-2-dependent angiogenic response are necessary to effectively inhibit solid tumor growth and formation of lung metastasis by B16 melanoma cells.

Consensus statements, evidence-based medicine and guidelines in allergic diseases.

Abstract: The American College of Chest Physicians (1) defines aconsensus statement as a document that represents thecollective opinion of a convened expert panel. Theopinions expressed in the statement do not reflect aformal evidence review and were not developed inaccordance with the process outlined for evidence-basedclinical practice guidelines. Therefore, certain caveatsmay apply when developing such consensus statements(Table 1).The development of clinical guidelines should followthe strict process which has been established by severalorganizations: various systems have been used to gradethe quality of evidence (sometimes called levels ofevidence) (2, 3).Early guidelines were predominantly derived fromunsystematically compiled opinions of experts based onclinical trials and mechanistic approaches (opinion-based medicine) (4). Evidence-based medicine (EBM)has become an essential component in the preparationof guidelines. It is the ability to track down, criticallyJ. Bousquet

Blood Screening for Influenza

Abstract: Influenza viruses, including highly pathogenic avian influenza virus (H5N1), could threaten blood safety. We analyzed 10,272 blood donor samples with a minipool nucleic acid amplication technique. Analytical sensitivity of the method was 804 geq/mL and 444 geq/mL for generic influenza primers and influenza (H5N1) subtype–specific primers. This study demonstrates that such screening for influenza viruses is feasible.

Management of humeral head fractures with a trauma shoulder prosthesis: correlation between joint function and healing of the tuberosities.

Abstract: This prospective follow-up study investigated the correlation between healing of the tuberosities and the functional outcome after arthroplasty with a trauma shoulder prosthesis in elderly patients with non-reconstructible humeral head fractures. Surgery was performed on 65 patients (66 shoulders) with a mean age of 74.9 years. A total of 56 patients (57 cases) underwent clinical and radiological evaluation after a mean follow-up of 16 months (range : 4 to 62). Mean Constant Score was 50 and the age- and gender-corrected value was 73%. The Constant Score was significantly higher (62 points, p = 0.015) if the tuberosities healed. Mean ASES index was 68 and correlated significantly with the Constant Score (r = 0.77). Healing of the tuberosities appears to be crucial to achieve good function in patients treated with a humeral head prosthesis. For elderly patients, the main objectives are to recover the ability to perform activities of daily living, to become pain free, and to reach a high level of satisfaction. All these criteria were largely achieved by the procedure described in this paper.

Phenotype – genotype correlation in eight Polish patients with inherited Factor XIII deficiency: identification of three novel mutations

Abstract: Inherited factor XIII (FXIII) deficiency is known as one of the most rare blood coagulation disorder in humans. In the present study, phenotype and genotype of eight FXIII deficient Polish patients from five unrelated families were compared. The patients presented with a severe phenotype demonstrated by a high incidence of intracerebral haemorrhages (seven of eight patients), haemarthrosis (six patients) and bleeding due to trauma (five patients). Introduction of regular substitution with FXIII concentrate prevented spontaneous bleeding in seven patients. In all patients, mutations within the F13A gene have been identified revealing four missense mutations (Arg77Cys, Arg260Cys, Ala378Pro, Gly420Ser), one nonsense mutation (Arg661X), one splice site mutation (IVS5-1 G>A) and one small deletion (c.499-512del). One homozygous large deletion involving exon 15 was detected by failure of PCR product. The corresponding mutations resulted in severely reduced FXIII activity and FXIII A-subunit antigen concentration, while FXIII B-subunit antigen remained normal or mildly decreased. Structural analysis demonstrated that the novel Ala378Pro mutation may cause a disruption of the FXIII catalytic triad leading to a non-functional protein which presumably undergoes premature degradation. In conclusion, the severe phenotype with high incidence of intracranial bleeding and haemarthrosis was in accordance with laboratory findings on FXIII and with severe molecular defects of the F13A gene.

Funneling before and after anti-incontinence surgery—a prognostic indicator? Part 2: tension-free vaginal tape

Abstract: Does the presence of pre- and postoperative funneling of the proximal urethra affect the outcome of tension-free vaginal tape (TVT)? This prospective study of 191 women with proven primary genuine stress urinary incontinence treated by TVT insertion and assessed by pre- and postoperative introital ultrasound aims to answer that question. At 36-month follow-up, the cure rate was 89.5% (Kaplan–Meier estimator). At 6-month follow-up, 6.3% of the women had urge symptoms and 0.5% de novo urge incontinence. The cure rate in preoperative funneling was 77.5% as opposed to 96.6% in the group without funneling (P<0.0001). The funneling rate significantly decreased from 37.2% preoperatively to 17.3% immediately postoperatively (P<0.0001). The continence rate was 57.5% in persistent postoperative funneling vs 96.2% in the group without postoperative funneling (P<0.0001). The complication rate was not higher in the group with persistent postoperative funneling. The TVT procedure significantly reduces bladder neck funneling. Both preoperative and persistent postoperative funneling are associated with an increased probability of therapeutic failure or recurrence.

Multimodal Home Monitoring of Elderly People--First Results from the LASS Study

Abstract: Monitoring elderly or disabled people in smart home environments is a major area of research because it allows for controlling chronic diseases and promises cost reduction. Context recognition and in particular activity recognition is of key importance as it facilitates the interpretation of data from medical monitoring devices. In our study with five elderly or disabled people we used data from multi-sensor wearable devices to generate intra- and interindividual machine-learned classifier models to determine activity patterns. Furthermore we computed the relative relevance of each parameter measured, and assessed the acceptance of computerized questionnaires in computer- illiterate people. The mean classification accuracy was 91.4% for the intraindividual classifiers and 53.7% for the interindividual ones. The most relevant parameters for activity classifications were those derived from accelerometric data, the least relevant one was galvanic skin response. Both the sensor device and the computerized questionnaires were well-received by the study participants. Individually-trained machine-learned classifiers used on data from a wearable device are an adequate means to determine context in elderly or disabled people.

Systematic screening and treatment evaluation of hereditary neck paragangliomas

Abstract: Familial paragangliomas of the neck are often bilateral and more aggressive than spontaneous forms. Tumors appear earlier (2nd-4th decade) often with diffuse, multifocal involvement. Without treatment, these tumors can lead to significant morbidity. Three families with succinate dehydrogenase subunit D (SDHD) germline mutations underwent clinical and genetic evaluation. Patients were screened using ultrasound and evaluated further with conventional and functional imaging. Tumors with a diameter >1.5 cm were surgically removed. Multicentric and bilateral tumors were detected in 9/13 (69%) and 8/13 (62%) patients, respectively. Surgical morbidity occurred in 64% of patients. Local recurrence was 57%, although this was lower in tumors with a diameter <2 cm. We recommend an algorithm for a systematic approach to the diagnosis, monitoring, and treatment of familial head and neck paragangliomas. Operative treatment in advanced stages often leads to unwanted morbidity, such that earlier detection and treatment of smaller tumors seems to be of benefit.

Multimodal fusion imaging ensemble for targeted sentinel lymph node management: initial results of an innovative promising approach for anatomically difficult lymphatic drainage in different tumour entities.

Abstract: Purpose There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble.

Insights and diagnostics of immune and non‐immune TRALI

Abstract: Non-cardiogenic lung oedema as a result of blood transfusion was first described by Barnard in 1951 [1]. In 1983, Popovsky et al . recognized this pulmonary transfusion reaction as a distinct clinical entity and coined the term transfusion-related acute lung injury (TRALI) [2]. In recent years, TRALI has developed from a nearly unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities [3]. In 2004, a clinical definition of TRALI has been established based on temporal association with transfusion, acute respiratory distress, non-cardiogenic lung oedema and hypoxaemia (Table 1). TRALI is one of the pulmonary transfusion reactions including TRALI, transfusionassociated circulatory overload (TACO), transfusion-induced bronchial asthma, and transfusion-associated dyspnea (TAD) (Table 2). TAD is defined as acute dyspnea in temporal association with transfusion without any indication of TRALI, TACO or bronchial asthma (allergic dyspnea) [5].