Adaptive short-term plasticity in the typical reading network.

The left temporo-parietal cortex (TPC) is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings, and appears hypoactive in dyslexia. Here, we tested the causal contribution of this area for reading in typical readers with transcranial magnetic stimulation (TMS) and explored the reading network's response with fMRI. By investigating the underlying neural correlates of stimulation-induced modulations of the reading network, we can help improve targeted interventions for individuals with dyslexia. 28 typical adult readers overtly read simple and complex words and pseudowords during fMRI after effective and sham TMS over the left TPC. To explore differences in functional activation and effective connectivity within the reading network, we performed univariate and multivariate analyses, as well as dynamic causal modeling. While TMS-induced effects on reading performance and brain activation showed large individual variability, multivariate analyses revealed a shift in activation in the left inferior frontal cortex for pseudoword reading after effective TMS. Furthermore, TMS increased effective connectivity from the left ventral occipito-temporal cortex to the left TPC. In the absence of effects on reading performance, the observed changes in task-related activity and the increase in functional coupling between the two core reading nodes suggest successful short-term compensatory reorganization in the reading network following TMS-induced disruption. This study is the first to explore neurophysiological changes induced by TMS to a core reading node in typical readers while performing an overt reading task. We provide evidence for remote stimulation effects and emphasize the relevance of functional interactions in the reading network.

[Treatment of proximal humeral fractures in Germany: Influence of the level of hospital care and the frequency of treatment]. / Behandlung proximaler Humerusfrakturen in Deutschland: Einfluss von Krankenhausversorgungsstufe und Behandlungsfrequenz.

BACKGROUND: Various treatment options exist for displaced proximal humeral fractures. The impact of the level of hospital care and frequency of treatment on current treatment regimens in Germany was analyzed. MATERIAL AND METHODS: A total of 576 hospitals were included. The survey covered questions on frequency, diagnostics, classification, therapy, complications, and clinical scenarios. RESULTS: In all, 48% of the hospitals returned the questionnaire: 73% treat more than 60% of the fractures surgically, mainly with angle-stable implants. The angle-stable plate is the treatment of choice for young patients, but older patients are treated using other treatment options. Problems and complications included malreduction, secondary displacement, screw perforation, avascular necrosis, and impingement. According to treatment indication, implant choice, and common complications, no significant differences between the level of hospital care and frequency of treatment were observed. CONCLUSION: Independent of the level of hospital care and frequency of treatment, there is a trend for head-preserving angular-stable surgery with a homogenous level of treatment in Germany.

A fast direct solver for surface-based whole-head modeling of transcranial magnetic stimulation.

Background: When modeling transcranial magnetic stimulation (TMS) in the brain, a fast and accurate electric field solver can support interactive neuronavigation tasks as well as comprehensive biophysical modeling. Objective: We formulate, test, and disseminate a direct (i.e., non-iterative) TMS solver that can accurately determine global TMS fields for any coil type everywhere in a high-resolution MRI-based surface model with ~200,000 or more arbitrarily selected observation points within approximately 5 sec, with the solution time itself of 3 sec. Method: The solver is based on the boundary element fast multipole method (BEM-FMM), which incorporates the latest mathematical advancement in the theory of fast multipole methods - an FMM-based LU decomposition. This decomposition is specific to the head model and needs to be computed only once per subject. Moreover, the solver offers unlimited spatial numerical resolution. Results: Despite the fast execution times, the present direct solution is numerically accurate for the default model resolution. In contrast, the widely used brain modeling software SimNIBS employs a first-order finite element method that necessitates additional mesh refinement, resulting in increased computational cost. However, excellent agreement between the two methods is observed for various practical test cases following mesh refinement, including a biophysical modeling task. Conclusion: The method can be readily applied to a wide range of TMS analyses involving multiple coil positions and orientations, including image-guided neuronavigation. It can even accommodate continuous variations in coil geometry, such as flexible H-type TMS coils. The FMM-LU direct solver is freely available to academic users.

A fast direct solver for surface-based whole-head modeling of transcranial magnetic stimulation.

When modeling transcranial magnetic stimulation (TMS) in the brain, a fast and accurate electric field solver can support interactive neuronavigation tasks as well as comprehensive biophysical modeling. We formulate, test, and disseminate a direct (i.e., non-iterative) TMS solver that can accurately determine global TMS fields for any coil type everywhere in a high-resolution MRI-based surface model with ~ 200,000 or more arbitrarily selected observation points within approximately 5 s, with the solution time itself of 3 s. The solver is based on the boundary element fast multipole method (BEM-FMM), which incorporates the latest mathematical advancement in the theory of fast multipole methods-an FMM-based LU decomposition. This decomposition is specific to the head model and needs to be computed only once per subject. Moreover, the solver offers unlimited spatial numerical resolution. Despite the fast execution times, the present direct solution is numerically accurate for the default model resolution. In contrast, the widely used brain modeling software SimNIBS employs a first-order finite element method that necessitates additional mesh refinement, resulting in increased computational cost. However, excellent agreement between the two methods is observed for various practical test cases following mesh refinement, including a biophysical modeling task. The method can be readily applied to a wide range of TMS analyses involving multiple coil positions and orientations, including image-guided neuronavigation. It can even accommodate continuous variations in coil geometry, such as flexible H-type TMS coils. The FMM-LU direct solver is freely available to academic users.

[30 years of osteosynthesis: developments in surgical fracture treatment over the last three decades]. / 30 Jahre Osteosynthese : Entwicklung der operativen Knochenbruchbehandlung in den letzten drei Dekaden.

The primary objective of surgical fracture management by means of osteosynthesis used to be achieving the maximum fracture stability possible; this maxim has given way over time to a more biological approach. Advances in the technical development of implants, including their material properties, have created the conditions for osteosynthetic procedures with minimal soft tissue disruption. The technical conditions of modern external fixator systems allow an unlimited number of assemblies matched to the requirements of each individual patient. Special changes in plate holes and interlocking nails have increased the angular and axial stability of the assembly and are particularly suitable for fractures with inferior bone quality, for example in the case of osteoporosis. Navigated osteosynthetic procedures permit reliable and low-risk implantation of implants in anatomically challenging regions. Out of the sometimes distressing experiences of early osteosynthetic procedures where postoperative radiographs showed delayed or absent bone healing, grew the realisation that good vascularity of the soft tissues and bones is a prerequisite for good healing and a timely and favourable outcome. This means that in each individual case an appropriate implant and stabilization method should be selected by the surgeon, who is not only familiar with anatomy but also with soft-tissue-conserving (minimally invasive) operative techniques.

[Rupture of the quadriceps tendon after lateral retinaculum release by arthroscopy]. / Quadrizepssehnenruptur nach arthroskopischem lateralem Retinakulumrelease.

Complications after arthroscopic surgery of the knee joint are infrequent. Quadriceps tendon ruptures after knee arthroscopy are rarities. Only two cases have been published in the medical literature. This article presents a case of a quadriceps tendon rupture that occurred in a 19-year-old patient 5 weeks after lateral release of the retinaculum by arthroscopy. The late occurrence differentiates this case from the other previously published cases.

Neonatal organ donation: Ethical insights and policy implications.

In the realm of clinical ethics as well as in health policy and organizational ethics, the onus of our work as ethicists is to optimize the medical care and experience of the patient to better target ethical dilemmas that develop in the course of care delivery. The role of ethics is critical in all aspects of medicine, but particularly so in the difficult and often challenging cases that arise in the care of pregnant women and newborns. One exemplary situation is that when a pregnant woman and her partner consider neonatal organ donation after receiving news of a terminal diagnosis and expected death of the newborn. While a newer, less practiced form of organ donation, this approach is gaining greater visibility as an option for parents facing this terminal outcome. The aim of our paper is to highlight some of the key ethical issues associated with neonatal organ donation and identify clinical and logistical aspects of implementing such an approach to facilitate organ donation.

[Therapy of articular cartilage lesions]. / Therapie von Gelenkknorpelschäden.

Lesions of adult articular cartilage do not heal or regenerate. They give rise to the development of osteoarthritis, and surgical treatment is necessary before the initiation of joint degeneration. Various treatment modalities ranging from microfracture to autologous mosaicplasty and autologous chondrocyte transplantation are available. Commonly they are distinguished by the presence or absence of cell transplantation. The treatment choice depends on size, depth, and location of the lesion; therefore exact classification is mandatory. The surgical procedure aims to reconstruct a physiological distribution of the biomechanical forces by surface restoration. Additional joint pathologies such as mechanical axis deviation, meniscal defects, and ligament insufficiencies threaten the surgical success and must be addressed simultaneously.

3-Dimensional ultrasound imaging for meniscal lesions.

PURPOSE: The aim of this prospective study was to evaluate preoperative three-dimensional ultrasound scans for the detection of meniscal lesions with a special focus on interobserver reliability. METHODS: Forty one patients with clinical signs of meniscal lesions were preoperatively examined by ultrasound using the 3-D technique (11.7 MHz linear transducer). The 3-D dataset was stored and examined by a second orthopaedic surgeon. The second ultrasound examiner was blinded to the results of the first. Any meniscal pathology was confirmed arthroscopically and documented. RESULTS: At arthroscopy eight lateral meniscal lesions and 57 medial meniscal lesions were detected at different locations. The sensitivity and specificity of the original ultrasound examination was acceptable whereas the results of the second ultrasound session were not as sensitive. CONCLUSION: Three-D-ultrasound with a high resolution transducer, in the hands of an experienced operator, provides acceptable results in the detection of meniscal lesions, however, analysis of the volume dataset from the 3-D ultrasound investigation indicates that it does not offer sufficient accuracy for clinical use.

[Arrosion of flexor tendons after palmar plate osteosynthesis of the distal radius: three case reports]. / Arrosion der Beugesehnen nach palmarer Plattenosteosynthese des distalen Radius: Drei Fallberichte.

Indication of palmar plate osteosynthesis of the distal radius has steadily broadened over recent years. The reason for this has been the introduction of angle stable implants. In addition, advantages were attributed to the palmar plate over the dorsal plate position on the distal radius through the covering of the M. pronator quadratus as a means of preventing the occurrence of arrosion of the tendon. Over a period of 12 months we treated 3 patients with varying degrees of flexor tendon rupture after palmar plate osteosynthesis, indicating that the incidence of flexor tendon arrosion occurring through palmar plate osteosynthesis is possibly greater than previously assumed.

[Bone tunnel fixation versus suture anchor: mid- and long-term results after distal biceps tendon rupture]. / Transossäre Refixation versus Fadenankerreinsertion, mittel- bis langfristige Ergebnisse nach distaler Bizepssehnenruptur.

AIM: The aim of this study was to assess the range of movement, isometric and isokinetic postoperative outcome, Morrey score and heterotropic ossifications after refixation of distal biceps tendon rupture with either suture anchor or bone tunnel fixation. METHODS: 48 patients were surgically treated between 1990 and 2005. Elbow function was investigated isometrically and isokinetically with the CYBEX-NORM. The presence and extent of heterotropic ossifications were assessed by A/P and lateral view X-rays. The Morrey score was used to evaluate the clinical outcome. RESULTS: 13 patients received distal biceps refixation with the bone tunnel method and 35 with suture anchors. The range of motion of the elbow was statistically not significantly different except for pronation, which was slightly but significantly reduced after bone tunnel refixation. Isometric and isokinetic results as well as Morrey scores were statistically not different between the two surgical techniques. Both groups showed excellent postoperative results. CONCLUSION: Bone tunnel and suture anchor techniques are both equal and sufficient methods for the refixation of distal biceps tendon ruptures with excellent clinical and functional postoperative results. The slight but significantly reduced pronation after bone tunnel refixation was clinically not relevant.

[Open augmented repair according to Silfverskjöld for Achilles tendon rupture: an alternative for athletes?]. / Die Umkipp-Plastik nach Silfverskjöld bei Achillessehnenruptur: Eine Alternative für Sportler?

AIM: The most recent meta-analysis of randomized trials recommended open repair for competitive athletes suffering from Achilles tendon rupture due to low re-rupture rates and recommended for all other patients percutaneous repair. The report did not include patients with open augmented repair. The aim of this study was to analyse our results with open augmented repair after Silfverskjöld and to discuss whether this method is an alternative form of treatment, especially for athletes. METHODS: This retrospective study included all patients who received open augmented repair in the Silfverskjöld technique between the years 1996 and 2002. A total of 104 patients were clinically evaluated, involving ultrasound as well, and were scored according to the Thermann scale. The average age was 43 years. The operation took place on average within 5.7 days. Twenty athletes were identified and were compared with non-athletes using the Thermann scale and the two randomsample t-tests. The follow-up period averaged 3.7 years. RESULTS: Overall, the results were rated as good, with an average of 88.1 points. The re-rupture rate was 1.9% (2 out of 104) with a deep infection incidence of 2.8% (3 out of 104). Athletes averaged 88.7 and non-athletes 88.0 points. No significant difference was recorded (t=0.98). Nineteen out of 20 (95%) athletes and 48 out of 84 (57%) non-athletes were able to return to their original level of sport activity. CONCLUSIONS: Open augmented repair after Silfverskjöld is found to be a real alternative to simple open reconstruction of Achilles tendon ruptures. Clinical outcome in both athletes and nonathletes was recorded as good to very good. Especially athletes were able to regain their original activity level with an overall low re-rupture and infection rate.

Bayesian decision threshold, detection limit and confidence limits in ionising-radiation measurement.

Based on Bayesian statistics and the Bayesian theory of measurement uncertainty, characteristic limits such as the decision threshold, detection limit and limits of a confidence interval can be calculated taking into account all sources of uncertainty. This approach consists of the complete evaluation of a measurement according to the ISO Guide to the Expression of Uncertainty in Measurement (GUM) and the successive determination of the characteristic limits by using the standard uncertainty obtained from the evaluation. This procedure is elaborated here for several particular models of evaluation. It is, however, so general that it allows for a large variety of applications to similar measurements. It is proposed for the revision of those parts of DIN 25482 and ISO 11929 that are still based on conventional statistics and, therefore, do not allow to take completely into account all the components of measurement uncertainty in the calculation of the characteristic limits.

Acute musculoskeletal infection: comparison of different methods for intraoperative bacterial identification.

PURPOSE OF THE STUDY: Various techniques are used for detection of pathogens in musculoskeletal infection. These methods differ with respect to reliability and ease of handling. A prospective study was performed to evaluate the efficacy of three intraoperative techniques. MATERIAL AND METHODS: In 20 cases (18 patients) with clinically confirmed acute musculoskeletal infections, intraoperative collected swab samples, tissue samples and fluid samples injected into standard blood culture vials were used for microbiological diagnosis. Identification of bacteria, time necessary for detection and ease of handling during surgery was evaluated. RESULTS: In 19 cases bacterial growth was demonstrated using either intraoperative swabs or blood culture technique (95% sensitivity), whereas 18 tissue biopsies were positive (90% sensitivity. 27 bacterial species were isolated. In 18 instances for the swab technique, 14 instances for the tissue biopsy and 4 operations for the blood culture vials, ease of handling was rated as excellent. DISCUSSION: The study demonstrated differences between the three tested methods with respect to ease of handling. With respect to the number of detected organisms and time for their detection there are no significant differences. These last findings are in contrast to of the results of other authors. The reason for this could be that during operative dissection an accurate and specific collection of specimens from the acute deep infected soft tissues and bones independent from the type of surgical procedure is possible. Therefore, even with the swab method a high amount of microorganisms can be recovered. Especially for intraarticular infections, fluid samples injected into standard blood vials is a practical method for the surgeon. In acute musculoskeletal infections other than joint infections, there is less benefit for the blood culture vials. CONCLUSION: Intraoperative swab technique yields valid results comparable to other techniques and is an accurate technique for detection of pathogens from acute musculoskeletal infections. Key words: implant, infections, bacteriological techniques, comparative study.

Primary stability of various forms of osteosynthesis in the treatment of fractures of the proximal tibia.

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase.

Change of processing and nucleocytoplasmic transport of mRNA in HSV-1-infected cells.

A monoclonal antibody (MAb) raised against the pore-complex lamina fraction from CV-1 cells was used to study alterations of gene expression in herpes simplex virus type 1 (HSV-1)-infected cells. This MAb, which recognized only one cellular polypeptide of 60,000 Da, selectively stained the nucleus in immunofluorescence microscopy, showing a punctuated pattern either at the nuclear surface or at the nuclear rim. By immunoelectron microscopy, the p60 antigen could be localized in the nuclear pore complex structure. Infection of CV-1 cells with HSV-1 resulted in a drastic change of the nuclear staining pattern. Four hours p.i., a clustering of the p60 antigen and, 12 h p.i., a formation of finger-like holes, penetrating the nucleus, occurred. Later in infection (22 h p.i.) the antigen was found to be almost absent. By RNA blot hybridization it was demonstrated that, after HSV-1 infection, the level of cellular mRNA (beta-tubulin) gradually decreased, while the level of HSV major DNA binding protein (DBP) mRNA increased, reaching maximal level 3-6 h p.i. Interestingly, the level of beta-tubulin gene transcripts changed differentially in the polysomal and in the nuclear fraction during the initial phase of infection, in contrast to the viral DBP transcripts, indicating that, after HSV infection, host cell transcripts accumulate in the nucleus. Evidence is presented indicating that this change is not due to altered nucleocytoplasmic mRNA transport but is due to an impaired splicing of host cell transcripts in HSV-infected cells. The MAb, directed against the nuclear pore p60 antigen, strongly inhibited the ATP-dependent efflux of both cellular and viral mRNA from isolated nuclei. The ATP-dependence of the efflux did not change during viral infection. However, the inhibitory potency of the MAb was found to be lost at the final stage of HSV infection, paralleling the loss of p60 antigen.

The karyotype of the glucocorticoid-sensitive, lymphoblastic human T-cell line CCRF-CEM shows a unique deleted and inverted chromosome 9.

Chromosome karyotypes were prepared from the highly glucocorticoid-sensitive clone C7 of the human acute lymphoblastic leukemia T-cell line CCRF-CEM. The modal number of chromosomes is 47, and one chromosome #9 has a pericentric inversion of the heterochromatin region (9qh) plus a deletion of the short arm. In most cells, there is an extra chromosome #20. All other chromosomes appear to be normal. Examination of the uncloned line CCRF-CEM (ATCC CCL 119), which was frozen away shortly after the line was originated and has undergone fewer passages than CEM C7, also revealed the same abnormality of chromosome #9. Each of 10 other clones isolated from CCRF-CEM in this laboratory also contained the abnormal chromosome #9.

Vaginal infection of mice with HSV type 2 variant ER-: a new animal model for human primary genital HSV type 2 infections.

Studying the pathogenesis of vaginal infections in mice with two variants of Herpes simplex virus type 2 (HSV-2) strain ER we observed that both variants ER+ and ER- caused severe vaginitis but only ER+ invaded the CNS leading to lethal neurological disease. In contrast, mice infected with ER- cleared the virus from the vagina and recovered from infection. ER+ and ER- expressed equal levels of thymidine kinase (TK) indicating a TK-independent difference in neurovirulence. Using the non-neurovirulent variant ER-, we were able to investigate humoral immune responses later after infection. Vaginal infection with ER- suppressed serum antibody formation after a secondary systemic HSV-1 infection. Fresh isolates of HSV-1 and HSV-2 caused uniformly a lethal neurological disease after vaginal inoculation of mice. However, some animals survived an intraperitoneal infection with these isolates. Infection with HSV-1 isolates stimulated a strong antibody production, whereas infection with HSV-2 isolates suppressed antibody formation, thus supporting earlier results from our group obtained with laboratory strains. Since suppression of antibody formation could be demonstrated with clinical HSV-2 isolates and likewise after vaginal infection with HSV-2 variant ER- we consider this phenomenon to be of relevance in human genital HSV-2 infections. Vaginal infection of mice with variant ER- represents a new model for primary genital HSV-2 infections; this model could be useful for histopathological, virological, immunological and drug testing studies.

Allogeneic cancellous bone graft and a Burch-Schneider ring for acetabular reconstruction in revision hip arthroplasty.

BACKGROUND: There is an ever-increasing number of failed hip arthroplasties associated with massive deficiency of acetabular bone stock consisting of a segmental or cavitary defect. This study was undertaken to evaluate the long-term results after use of morselized cryopreserved allogeneic bone graft and an antiprotrusio cage to treat such a deficiency. METHODS: From January 1, 1988, to January 1, 1994, forty-one patients (forty-one hips) with an acetabular defect classified as type IIl or IV according to the American Academy of Orthopaedic Surgeons system were operated on with use of a Burch-Schneider ring and morselized cryopreserved allogeneic cancellous bone graft. Thirty-eight patients (thirty-eight hips) were available for clinical and radiographic follow-up examinations at an average of 7.3 years (range, 4.2 to 9.4 years) after surgery. RESULTS: All measured clinical parameters had improved significantly by the time of the follow-up examination (p < 0.0001). Radiographs confirmed that none of the thirty-eight hips had any measurable migration or displacement of the acetabular component and that osseous consolidation occurred only within the grafted area in all patients. CONCLUSION: Acetabular reconstruction with use of morselized cryopreserved allogeneic cancellous bone graft and the Burch-Schneider ring can be highly successful in managing massive acetabular deficiencies in revision hip arthroplasty.

Receptor physiology: clinical implications.

As scientists and physicians have gained sophistication in understanding and treating illness, our view of disease has changed in scope. We appreciate more fully the diverse and wide-ranging effects of stress on the ability of the organism to maintain homeostasis. As our study of the failure of homeostasis has advanced from the organ to the intracellular level, we have gained insight into processes that, through conveyance of chemical messages, cross organ boundaries to tie together multiple systems involved in preserving metabolic balance. We have come to recognize that our pharmacologic interventions are seldom unique in the sense of providing the patient with an entirely new means of fighting an illness; we more often support a system that has been deranged by disease or injury, using agonists, inhibitors, buffers, substitutes, supplements, and mechanical devices in hopes that the body will adjust to its stresses over time. Multiple receptor systems have been studied in regard to their function in normal and abnormal states. Of primary impact on the critically ill patient are adrenergic, thyroid, and insulin receptors, which are of major importance in maintaining metabolic stability and are either the targets of many of our therapies or are inadvertently affected by them in adverse ways. Of doubtless importance, but currently with less clinical application in this setting, are steroid, cholinergic, and histamine receptors. The recent growth of data concerning the role of endogenous opioids in the response to stress will, it is hoped, add to our armamentarium in the future. Future research in signal transduction will continue to increase our understanding of the mechanisms through which our patients maintain homeostasis in the face of disease, as well as our role in helping to regain a balance that has been lost. With further study, we may develop pharmacologic agents that allow us to effect changes with greater tissue or subcellular specificity and hence more specific physiologic consequences. As in many other fields of medicine, continued description of normal states will aid in recognition of defects in the abnormal, or unregulated, state, by understanding derangements in control that can result in primary disease.