A bone marrow transplant with an acquired anti-Le(a): a case study

A patient with aplastic anemia received an ABO incompatible bone marrow transplant (BMT) from an HLA identical sibling. Weekly HLA antibody screens were performed as part of the BMT protocol. At the time of transplant, a hemolytic anti-Le(a) was detected in the Le (a-b-) donor. The Le (a-b+) recipient had no red cell or LCT antibody. A hemolytic anti-Le(a) was detected in the recipient on day 8, but no LCT reactivity was noted at this time. On day 15, the LCT panel demonstrated reactivity with 9 of 50 panel cells without apparent HLA specificity. Graft vs. host disease (GVHD) was present on the skin at this time. The dose of cyclosporin A was increased, but by day 20 the GVHD worsened and the LCT titers increased to 8. This strong reactivity was noted only in the Le (a+) panel members (12/50) and was neutralized with commercial Lewis substance. On day 34 there was no evidence of GVHD, but the lymphocytotoxic anti-Lea continued to be present. The patient began experiencing renal and gastrointestinal difficulties by day 48, and expired on day 60. In renal transplants the kidneys retain their Lewis type and secrete Lewis substance in the urine. In our experience BMT patients retain their Lewis type regardless of the type of the donor. The Lewis system has been linked to renal allograft rejection, and Lewis antigens may function as transplantation antigens in BMT patients as well. In addition, lymphocytotoxic Lewis antibodies can mask other significant HLA antibodies and must be identified when screening patients in need of plateletpheresis products.     

Empirical evaluation of the transfusion medicine tutor

Previous research during the development of Antibody IDentification Assistant (AIDA) revealed that many medical technology students and other laboratory personnel have serious difficulties in determining the specificity of blood group alloantibodies, especially weak or multiple antibodies. Based on these previous results, AIDA was modified to provide a teaching environment for medical technology students. We report the results of a rigorous, objective evaluation of the resultant system, the Transfusion Medicine Tutor (TMT). The results show that the students who were taught by an instructor using TMT to provide the instructional environment went from 0 percent correct on a pretest case to 87 percent correct on posttests (n = 15). This increase compares with an improvement rate of 20 percent by a control group (n = 15) who used a passive version of the system with the tutoring functions turned off.     

Mnestische Störungen nach experimenteller Alkohol-Tranquilizer-Belastung

Zusammenfassung Im Rahmen einer pharmakopsychologischen Untersuchung über mögliche Wechselwirkungen zwischen Alkohol und Diaklium-Chlorazepat (Tranxilium) fielen bei 8 von 13 Probanden mnestische Störungen auf. Dieses Phänomen wurde unter formalen und inhaltlichen Kriterien beschrieben. Die Blutalkoholkonzentrationen lagen zwischen 0.87 und 1.32, die Serumkonzentrationen des wirksamen Metaboliten Noridazepam im therapeutischen Bereich zwischen 145 ng/ml und 345 ng/ml. Konstitutionelle, dispositionelle und situative Bedingungen werden dargestellt. Die rechtsmedizinische Bewertung derartiger mnestischer Störungen für die Beurteilung eines psychopathologischen Zustandsbildes mu\ zurückhaltend und kritisch vorgenommen werden.Herrn Prof. Dr. O. Grüner zum 60. Geburtstag gewidmet     

Progressive dyspnea and signs of right heart dysfunction

A 40‐year‐old woman was admitted due to dyspnea and fever. Transthoracic echocardiography revealed signs of right heart volume overload and vegetations on the tricuspid valve with insufficiency. Transesophageal echocardiography showed a sinus venosus defect (SVD) with significant left‐to‐right shunt. Computed tomography scanning was primarily performed to rule out pulmonary embolism; however, it showed interatrial communication. Due to the concomitant tricuspid insufficiency with additional volume overload, the diagnosis of SVD was more challenging. Usually, transthoracic echocardiography remains the initial diagnostic imaging modality; however, detection rates are very low. Therefore, further imaging is mandatory in unexplained substantial right heart dilatation.     

Aktueller Stand der kardiovaskulären MRT und CT

The recent technical advances in magnetic resonance imaging (MRI) and multislice computed tomography (MSCT) have led to a routine use of both methods in clinical cardiology. MRI is established for the diagnosis of complex congenital heart disease, aortic and pericardial disease as well as cardiac tumours. New indications include the diagnosis of myocardial infarction and inflammatory heart disease as well as myocardial perfusion measurements. CT is used for the diagnosis of coronary calcification for risk stratification. Moreover, stenoses of the coronary arteries and bypass grafts can be depicted using contrast enhanced multi-slice CT in selected patients. Training of cardiologists in the field of MRI has been defined by the Deutsche Arztetag in 2003 and demands 24 months of full-time training. At least 12 months must be spent in a department of radiology. Alternatively, the approach of the Landes?rztekammer Baden-Württemberg is presented.     

Partner choice and fidelity stabilize coevolution in a Cretaceous-age defensive symbiosis

Many insects rely on symbiotic microbes for survival, growth, or reproduction. Over evolutionary timescales, the association with intracellular symbionts is stabilized by partner fidelity through strictly vertical symbiont transmission, resulting in congruent host and symbiont phylogenies. However, little is known about how symbioses with extracellular symbionts, representing the majority of insect-associated microorganisms, evolve and remain stable despite opportunities for horizontal exchange and de novo acquisition of symbionts from the environment. Here we demonstrate that host control over symbiont transmission (partner choice) reinforces partner fidelity between solitary wasps and antibiotic-producing bacteria and thereby stabilizes this Cretaceous-age defensive mutualism. Phylogenetic analyses show that three genera of beewolf wasps (Philanthus, Trachypus, and Philanthinus) cultivate a distinct clade of Streptomyces bacteria for protection against pathogenic fungi. The symbionts were acquired from a soil-dwelling ancestor at least 68 million years ago, and vertical transmission via the brood cell and the cocoon surface resulted in host–symbiont codiversification. However, the external mode of transmission also provides opportunities for horizontal transfer, and beewolf species have indeed exchanged symbiont strains, possibly through predation or nest reuse. Experimental infection with nonnative bacteria reveals that—despite successful colonization of the antennal gland reservoirs—transmission to the cocoon is selectively blocked. Thus, partner choice can play an important role even in predominantly vertically transmitted symbioses by stabilizing the cooperative association over evolutionary timescales.Cooperation is ubiquitous in nature, yet it presents a conundrum to evolutionary biology because acts that are beneficial to the receiver but costly to the actor should not be favored by natural selection (1). In interspecific associations (i.e., symbioses), the two most important models to explain the maintenance of cooperation are partner fidelity and partner choice (2, 3). In partner-fidelity associations, host and symbiont interact repeatedly and reward cooperating individuals while punishing cheaters, thereby reinforcing mutually beneficial interactions (2, 4). In partner-choice associations, individuals may interact only once, but one member can select its partner in advance of any possible exploitation (2, 4). Partner choice appears to select for cooperative strains among environmentally acquired microbial symbionts, e.g., the bioluminescent Vibrio fischeri bacteria of squids (5), the nitrogen-fixing rhizobia of legumes (6), and mycorrhizal fungi of plants (7). By contrast, partner fidelity is generally assumed to be the major stabilizing force in the widespread and ecologically important vertically transmitted symbioses of insects (4).However, localization and transmission routes of mutualistic bacteria in insects are diverse, and the differences across symbiotic systems have important implications for the evolutionary trajectory of the associations. Symbionts with an obligate intracellular lifestyle are usually tightly integrated into the host’s metabolism (e.g., ref. 8) and development (9), and the mutual interdependence of both partners coincides with perfect vertical symbiont transmission. Over evolutionary timescales, the high degree of partner fidelity results in host–symbiont cocladogenesis, and, concordantly, phylogenies of hosts and their intracellular symbionts are often found to be congruent (10–13). Although such a pattern is also observed for some extracellular symbioses with especially tight host–symbiont integration (14, 15), the ability of many extracellularly transmitted symbionts to spend part of their life cycle outside of the host’s body is often reflected in more or less extensive horizontal transmission or de novo acquisition of symbionts from the environment (16, 17). In these cases, partner choice mechanisms are expected to ensure specificity in the establishment and maintenance of the association (18). The nature of such control mechanisms, however, remains poorly understood.Although many of the well-studied mutualistic associations in insects have a nutritional basis (19, 20), an increasing number of symbioses for the defense of the host against predators (21), parasitoids (22), or pathogens (23–25) have recently been discovered. Among defensive symbionts, Actinobacteria are particularly prevalent, probably due to their ubiquity in the soil and their ability to produce secondary metabolites with antibiotic properties (23). Antibiotic-producing actinobacterial symbionts have been discovered on the cuticle of leaf-cutting ants (26), in the fungal galleries of a bark beetle (27), and in the antennae and on cocoons of beewolf wasps (28). While in the former two cases the symbionts have been implicated in the defense of the hosts’ nutritional resources against competing fungi (26, 27), the beewolves’ bacteria protect the offspring in the cocoon against pathogenic microorganisms (28, 29).Beewolves are solitary wasps in the genera Philanthus, Trachypus, and Philanthinus (Hymenoptera, Crabronidae, Philanthini). They engage in a defensive alliance with the Actinobacterium ‘Candidatus Streptomyces philanthi’ (CaSP) (28, 30, 31), which is cultivated by female beewolves in specialized antennal gland reservoirs (32). The uniqueness and complexity of the glands suggest a long history of host adaptation towards cultivating its actinobacterial symbionts (32). From the antennae, the streptomycetes are secreted into the brood cell, taken up by the larva, and incorporated into its cocoon (33), where they provide protection against pathogenic fungi and bacteria (28) by producing at least nine different antimicrobial compounds (29). Weeks or months later, eclosing adult females acquire the bacteria from the cocoon surface (33), thus completing the vertical transmission of CaSP. However, this mode of transmission provides opportunities for the horizontal transfer of symbionts among beewolf species or the de novo uptake of bacteria from the environment. Despite these opportunities, a monophyletic clade of CaSP strains has previously been found in 31 species of beewolves, suggesting an ancient and highly coevolved relationship (30, 31, 34).Here we combine cophylogenetic analyses of beewolves and their vertically transmitted defensive symbionts with experimental manipulation of symbiont infection status and subsequent observations of transmission from female antennal gland reservoirs into the brood cell to (i) reconstruct the coevolutionary history of the symbiosis, (ii) estimate the age of the symbiosis, (iii) elucidate the ancestral lifestyle of the symbionts, and (iv) assess the importance of partner fidelity and partner choice for the long-term stability of the association.     

Clinical results after different operative treatment methods of radial head and neck fractures: A systematic review and meta-analysis of clinical outcome

Introduction

There is no consensus on optimal treatment strategy for Mason type II–IV fractures. Most recommendations are based upon experts’ opinion.

Methods

An OVID-based literature search were performed to identify studies on surgical treatment of radial head and neck fracture. Specific focus was placed on extracting data describing clinical efficacy and outcome by using the Mason classification and including elbow function scores.A total of 841 clinical studies were identified describing in total the clinical follow-up of 1264 patients.

Results

For type II radial head and neck fractures the significant best treatment option seems to be ORIF with an overall success rate of 98% by using screws or biodegradable (polylactide) pins.ORIF with a success rate of 92% shows the best results in the treatment of type III fractures and seem to be better than resection and implantation of a prosthesis. For this fracture type the ORIF with screws (96%), biodegradable (polylactide) pins (88%) and plates (83%) showed the best results.In the treatment of type IV fractures similar results could be found with a tendency of the best results after ORIF followed by resection and implantation of a prosthesis.If a prosthesis was implanted, the primary implantation seems to be associated with a better outcome after type III (87%) and IV (82%) fractures compared to the results after a secondary implantation.

Discussion

Recommendations for surgical treatment of radial head and neck fractures according to the Mason classification can now be given with the best available evidence.Level of evidence: IV     

The somatotrophic system in patients with dilated cardiomyopathy: relation of insulin-like growth factor-1 and its alterations during growth hormone therapy to cardiac function

OBJECTIVE: Treatment with human recombinant growth hormone has yielded conflicting results in patients with congestive heart failure. In addition, growth hormone resistance has been reported in severe heart failure. Therefore, the purpose of this study was to evaluate the somatotrophic axis and effects of growth hormone on haemodynamics in patients with heart failure due to dilated cardiomyopathy. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Fifty clinically-stable patients with moderate heart failure (mean left ventricular ejection fraction = 26 +/- 2%) due to dilated cardiomyopthy were examined. MEASUREMENTS: Patients were randomly assigned to treatment with placebo or 2 IU/d sc human recombinant growth hormone for a mean of 14 weeks. Cardiac size and function were evaluated by magnetic resonance imaging. Central haemodynamics were obtained by right heart catheterization. Measurements of plasma noradrenaline, serum insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were performed by standard assays at baseline and at the end of the treatment period. RESULTS: The severity of heart failure as determined by stroke volume, left ventricular end diastolic diameter and plasma noradrenaline concentrations correlated significantly to baseline serum insulin-like growth factor-1 levels (each P < 0.05). The growth hormone-induced increase of insulin-like growth factor-1 predicted the changes in ejection fraction (P < 0.05). A significant increase in ejection fraction of 7% was observed in patients whose insulin-like growth factor-1 increased by more than the median increase in comparison to the patients with an increase below the median (+ 4.0 +/- 2.3% vs. - 3.0 +/- 1.8%; P = 0.03). CONCLUSIONS: Serum levels of insulin-like growth factor-1, reflecting growth hormone secretion, are diminished in relation to the severity of heart failure in patients with dilated cardiomyopathy. Growth hormone induced increases of insulin-like growth factor-1 of more than 77 ng/l caused significant improvement of ejection fraction.