[Low-dose helical CT-dacryocystography in nasolacrimal duct obstruction-a prospective study]. / Low-Dose-Spiral-CT-Dakryozystographie bei Tränenwegsstenosen ­ eine prospektive Studie.

BACKGROUND: In addition to basic ophthalmologic diagnostic workup, different radiologic procedures can be performed for assessment of nasolacrimal duct obstruction. However, no gold standard imaging technique has yet been established. Using the results of the present study, the advantages of helical CT-dacryocystography (CT-DCG) are demonstrated, particularly when performed before endonasal endoscopic dacryocystorhinostomy. MATERIALS AND METHODS: In 21 patients with uni- or bilateral epiphora, 24 low-dose helical CT-DCGs were performed with non-ionic iodine-containing contrast medium and including three-dimensional reconstruction. For 8 patients, digital subtraction angiography (DSA)-DCG results were available for comparison with CT-DCG. RESULTS: Using low-dose helical CT-DCG, either the location of nasolacrimal duct pathology could be exactly identified (n = 19; stenosis presaccal n = 3, intrasaccal n = 11, postsaccal n = 5) or nasolacrimal system block could be definitively excluded as the cause of epiphora (n = 5). For imaging of the perilacrimal and periorbital bony structures, CT-DCG is significantly better than DSA-DCG. CONCLUSION: Low-dose helical CT-DCG with reconstruction of the coronal and sagittal planes represents an ideal imaging technique with low exposure for detection of nasolacrimal duct obstruction. By demonstrating all relevant anatomic landmarks for endoscopic dacryocystorhinostomy, helical CT-DCG enables head and neck surgeons to plan surgery optimally.

[The Pathogenesis of Pulmonary Emphysema - Laennec was right!] / Die Pathophysiologie des Lungenemphysems ­ Laënnec (1781­1826) hatte Recht!

Pulmonary emphysema is characterised by irreversible destruction and enlargement of alveolar structure distal to terminal bronchioles. Small conducting airways < 2 mm in diameter are the major site of chronic airway inflammation and obstruction in COPD patients. 80 - 90 % of the last generation of small conducting airways, the terminal bronchioles, are destroyed in patients with very severe COPD. Recent data showing, that small airways disease is also a pathological feature in patients with COPD GOLD stage 1 and 2. Although 40 % of terminal and 60 % of transitional bronchioles were destroyed, there was no sign for emphysema. Only a significant loss of terminal and respiratory bronchioles seems to be able to induce pulmonary emphysema and respiratory symptoms.

Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus.

Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a 15N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated 15N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.

[Treatment Strategies for Septic Arthritis of the Sternoclavicular Joint]. / Behandlungsstrategie der septischen Arthritiden des Sternoklavikulargelenks.

Septic arthritis of the sternoclavicular joint (SCJ) is a relatively rare disease. Due to serious complications including mediastinitis and generalised sepsis early diagnosis and rapid onset of treatment are mandatory. The disease often affects immunocompromised patients, diabetics, or patients with other infectious diseases. The therapeutic options range from administration of antibiotics to extended surgery including reconstructive procedures. Apart from rare situations where conservative treatment with antibiotics is sufficient, joint resection followed by plastic surgical procedures are required. We present a retrospective analysis with data from two hospitals. From January 2008 to December 2012 23 patients with radiographically confirmed septic arthritis of various aetiology were included. Fourteen (60.8 %) male, nine (39.2 %) female patients with an average age of 60.3 ± 14.2 years (range: 23-88 years) with septic arthritis of the SCJ were treated. Seven (30.4 %) patients suffered from Diabetes mellitus, nine (39.1 %) had underlying diseases with a compromised immune system. In 14 (60.8 %) out of 23 patients a bacterial focus was detected. Only six (26 %) patients suffered from confined septic arthritis of the SCG, in 17 (73,9 %) patients osteomyelitis of the adjacent sternum, and the clavicle was present. In addition, 15 (65.2 %) patients already suffered from mediastinitis at the time of diagnosis, eight (35 %) patients even from septicaemia. In conclusion, septic arthritis requires an active surgical treatment. Limited incision of the joint and debridement alone is only successful at early stages of the disease. The treatment concept has to include the local joint and bone resection as well as complications like mediastinitis. After successful treatment of the infection, the defect of the chest wall requires secondary reconstructive surgery using a pedicled pectoralis muscle flap.

[Effects of soccer-specific strains on the locomotor system]. / Auswirkungen fussballspezifischer Belastungen auf den Bewegungsapparat.

PROBLEMS: Soccer as a Stop-and-Go-sport goes along with a high level of physical strain on the locomotor system. Compared to similar kinds of sports, soccer is characterized by a high prevalence of overloads/injuries in the pelvic region. Since soccer frequently involves one-sided shot-training, modifications in the pelvic statics are possible. METHODS: In a pilot study including 15 football-players-FP (age 26.9 +/- 3.1 yrs; 4.4 +/- 0.4 training units/week+ 1 leaque game) the pelvic statics was measured using the 3-d-recording system CMS70 (Zebris, Germany) directly before and after a defined shot training. The positions of the right and the left posterior superior iliac spines - PSIS were compared. Additionally, the stiffness of selective muscles was analyzed. RESULTS: Before intervention the right PSIS was heightened in 8 FP. In 4 FP the pelvic statics was balanced and in 3 FP the right PSIS was abased. After the shot training, the pelvic statics was balanced in 4 FP. In contrast, 10 FP showed a higher right PSIS and 1 FP had a lower right PSIS. However, modifications of the pelvic statics were detected in all directions. DISCUSSION: Our study demonstrates modification of the pelvic statics by asymmetric soccer-specific strains, but the reactions were individually different. It is possible, that changes in the pelvic statics may lead to changed function or overstrain of advertising muscles.

Interference of DOACs in different DRVVT assays for diagnosis of lupus anticoagulants.

OBJECTIVE: Determination of lupus anticoagulants (LA) is an important, but still challenging test in the diagnosis of antiphospholipid syndrome (APS). This is especially the case in patients using one of the direct oral anticoagulants (DOACs). The aim of our study was to examine the influence of these drugs on DRVVT assays from two companies (in each case: screening test, confirming test and calculated ratio) and on aPTT and lupus-sensitive aPTT. METHODS: We used plasma samples from healthy volunteers spiked with the DOACs dabigatran, rivaroxaban and apixaban (0, 10, 30, 50, 100 ng/mL) for testing. Furthermore, samples from patients receiving a DOAC were investigated. The plasma concentrations of the DOACs were determined using ultra-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Depending on type and concentration, all the DOACs resulted in pathological values in the DRVVT screening assays. In samples spiked with apixaban, no influence on the DRVVT normalized ratio of the two assays was observed, but 7 to 15% of samples from patients receiving apixaban displayed pathological values. In contrast, up to 71% of dabigatran-spiked samples showed normalized ratio values above the cut-off, whereas there was no influence in the patients' samples. In both spiked and patient samples containing rivaroxaban, the DRVVT assays were influenced. CONCLUSION: LA diagnostics should, under DOAC therapy, be limited to situations in which time-critical evaluation is warranted. It is crucial to take into account the finding that even samples containing DOAC concentrations below the limit of detection of the drugs may lead to false-positive DRVVT measurements.

Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.

The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B2 and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.

Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL.

Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab. Blinatumomab responders (n=22) had an average of 4.82% Tregs (confidence interval (CI): 1.79-8.34%) in the peripheral blood, whereas non-responders (n=20) demonstrated 10.25% Tregs (CI: 3.36-65.9%). All other tested markers showed either no prediction value or an inferior prediction level including blast BM counts and the classical enzyme marker lactate dehydrogenase. With a cutoff of 8.525%, Treg enumeration can identify 100% of all blinatumomab responders and exclude 70% of the non-responders. The effect is facilitated by blinatumomab-activated Tregs, leading to interleukin-10 production, resulting in suppression of T-cell proliferation and reduced CD8-mediated lysis of ALL cells. Proliferation of patients' T cells can be restored by upfront removal of Tregs. Thus, enumeration of Treg identifies r/r ALL patients with a high response rate to blinatumomab. Therapeutic removal of Tregs may convert blinatumomab non-responders to responders.

Release of albumin from oligoester plastic matrices: effect of magnesium oxide and bivalent stearates.

Biodegradable implantable matrices containing bovine serum albumin were prepared from oligoesters by melting, and subsequently tested on in vitro albumin release. The linear poly (DL-lactic acid) and the branched terpolymer of DL-lactic acid, glycolic acid, and mannitol were synthesized. Products were of similar molecular weight and possessed different thermal and swelling characteristics. Oligoesters were loaded with 4% albumin and plasticized by 30% triacetin. Other additives added into the matrices as albumin stabilizers were divalent stearates and magnesium oxide. The influences of oligomer molecules constitution, divalent ion stearates or magnesium oxide addition, and triacetin concentration on the albumin release were quantified. SDS-PAGE revealed protein hydrolysis during the dissolution tests.

[Measurement of adhesive properties of polymers in vitro]. / Merení adhezivních vlastností polymeru in vitro.

Adhesive force of branched oligoesters under the in vitro conditions was studied by measuring the maximal force necessary to separate the tested sample from the base (F(max)) under different testing conditions. Branched oligoesters were synthesized from lactic and glycolic acids in the molar ratio 1:1, and from mannitol or dipentaery thritol as the branching components in concentrations of 3%, 5% or 8%. To decrease viscosity and thus to facilitate the workability and administration, triethyl citrate (TEC) in a concentration of 30% was employed. Polymeric systems for adhesive force measurements were prepared by melting oligoesters in a micro oven and by homogenization with TEC. Adhesive force was measured on a material testing device T1-FR050TH.A1K Zwick/Roell at the set rate of separation 10 mm/min or 100 mm/min, contact force 10 N or 20 N, and a period of contact of the sample with the base of 5 s or 10 s. The adhesive force of branched oligoesters was found to be significantly higher than the adhesive force of gelatine gels, methylcellulose, carmelose sodium salt or sodium carbomer salt. Dipentaerythritol-branched oligoesters exerted higher adhesive force than mannitol-branched oligoesters. The value of adhesive force was increased with growing concentration of the branching component in the oligoester. Of the experimental parameters tested, a statistically significant influence of the separation rate of the sample from the base on the magnitude of F(max) was observed. The influence of different periods of contacts was manifested only in some samples, and the influence of different contact forces on F(max) value was not demonstrated in any sample.

Influence of processing conditions on the release of sodium fluoride from oligomeric L-lactic acid matrices.

Matrices were prepared in the shape of rods with a diameter of 4 mm and a length of 10 mm. They were composed of oligomers of L-lactic acid (Mw 2550-11730 Daltons) and micronized sodium fluoride particles. Sodium fluoride concentration was kept in the range 5-60%. Matrices were prepared by melting the mixture of L-lactic acid oligomer and sodium fluoride. Two types of products according to the applied cooling rate were prepared and evaluated for release characteristics in vitro. Sink conditions of isotonic phosphate buffer solution pH = 7.4 at 37 degrees C were maintained throughout the experiment. The concentration of dissolved sodium fluoride was determined by ion-selective electrode. It was documented that the release rate of sodium fluoride is strongly dependent on the molecular weight of oligomer. The effects of sodium fluoride concentration and cooling rate of melted mixture were evaluated by ANOVA, separately for each oligomer. The effect of sodium fluoride concentration was significant at each oligomer studied, while the influence of cooling rate was significant with higher molecular weight oligomers. Moreover, this effect is ambiguous and dependent on the capability of oligomers to form crystalline phases and on the form and geometric arrangement of this phase.

Ultrasonography as a diagnostic aid for a district hospital in the tropics.

To improve diagnostic capabilities, an ultrasound unit was installed at a major hospital in Wad Medani, Sudan. During the implementation period (October 1986 to March 1987) of ultrasound service, 863 patients were examined cooperatively by Sudanese and German physicians. The service covered internal medicine (47.5%), obstetrics and gynecology (31.6%), surgery (12.5%), and pediatrics (8.4%). Pathologic findings were seen in 75% of the patients. In obstetrics, the rate of pathologic findings was 40%. Five hundred eighty-three pathologic findings were detected in organ systems that constituted the primary indication for ultrasonography (of a total of 1,009 indications). The clinical benefit of ultrasonography was evaluated in 289 randomly selected patients in a standardized questionnaire completed by the attending physicians. The final clinical diagnosis was established or substantially revised in 21.5% of the patients, based on the ultrasonographic report. The previously reported diagnosis was supported in 69.5% of the patients. Medical management was directly influenced in 26% of the patients. We conclude that the clinical benefit of ultrasonography at a district hospital in the tropics is substantial, providing cost-effective, immediate therapeutic benefits in 25% of the patients examined. The technique thereby contributes to better and more rational patient management in institutions with limited resources.

The effect of lidocaine on peripheral hemodynamics.

Lidocaine was given in increasing step-wise dose concentrations of 1, 2, 3, 4, and 5 mg/minute and the resulting serum concentrations correlated with the effect of this agent on the peripheral vasculature of seven patients. Lidocaine infusion causes an immediate sustained increase in mean calf venous capacitance but little effect on mean diastolic blood pressure. In high concentration levels this agent causes an increase in mean calf blood flow and systolic blood pressure. Its effect on calf vascular resistance is variable, but there is a tendency to reduce resistance, particularly at a high concentration level. The effect of lidocaine infusion rate on serum lidocaine levels was such that the greater the infusion rate, the higher the resultant serum lidocaine levels.

Evaluation of ultrasonographic staging systems for the assessment of Schistosoma mansoni induced hepatic involvement.

For the sonographic assessment and grading of hepatosplenic morbidity induced by Schistosoma mansoni infection, several quantitative and qualitative classification systems have been used. In an attempt to evaluate two staging systems, a study was performed as part of a schistosomiasis research and control programme in Richard Toll, Senegal. A total of 700 residents of the township N'diangué were parasitologically, clinically and sonographically examined in July 1993. Two ultrasound observers (M.D. and E.D.) applied the Cairo and the Managil classification (E.D. only) for the grading of periportal thickening of the liver. In spite of high prevalence and intensity of infection, severe hepatic morbidity was rare. According to the Cairo classification, there was a high percentage of subjects with grade I periportal thickening, with considerable inter-observer variability. In the Cairo classification, which is based on the diameter of peripheral portal vein branches, firm cut-offs are used, independent of body height. We show the relationship between body height and portal vein diameters and recommend the use of body height-dependent reference values to avoid falsely high percentages of periportal thickening, especially in children. To minimize inter-observer variability, a clarification of existing instructions for taking measurements for grading is suggested. These suggestions have been considered during the follow-up expert meeting on the Cairo classification in Niamey under the auspices of the World Health Organization in October 1996.

NMR follow-up studies of CNS-tumors in infancy and childhood.

Sixteen children with brain tumors, fifteen of which were located in the posterior cranial fossa, were followed-up postoperatively with NMR. Four recurrences of medulloblastoma and one recurrence of an ependymoma were found. Three children showed signs of known therapeutic sequelae such as hygroma, atrophy and dilatation of the subarachnoid space. Previously unreported, boundary layer lesions were found in 8 children. The etiology of these lesions and their differentiation from tumor recurrence are discussed.

[Anthracycline-induced cardiotoxicity: cardiac MRI after treatment for childhood cancer]. / Anthrazyklin-induzierte Kardiotoxizität: MRT des Herzens bei Kindern und Jugendlichen mit malignen Erkrankungen.

PURPOSE: Quantification of left and right ventricular function using MRI in young cancer patients treated with cardiotoxic anthracyclines. MATERIALS AND METHODS: Twenty-eight patients (mean age 16.4 years) underwent cardiac MRI at 1.5 T. The study protocol consisted of morphologic T2-weighted images with fat suppression and cine steady-state free precession sequences (SSFP) for functional analysis. Seven patients were examined at the end of chemotherapy, two of them also repeatedly during therapy, and 21 patients following an average period of three years after finishing chemotherapy (range one month--20 years) RESULTS: The end-systolic volume index increased and the ejection fraction of the left and right ventricle decreased during anthracycline therapy. Two of seven patients showed a myocardial edema at the end of the therapy. In 15 of all 28 patients, the left ventricular ejection fraction was reduced to less than 55 % (minimum 44 %). No clinical signs of cardiac insufficiency or cardiomyopathy were observed. CONCLUSION: MRI is able to detect acute as well as chronic subclinical cardiotoxic effects of anthracyclines. Impairment of the right ventricular function should be considered in the diagnosis of anthracycline-induced cardiomyopathy.

[MR tomography of thoracic and abdominal tumors in childhood and adolescence]. / MR-Tomographie thorakaler und abdominaler Tumoren im Kindes- und Jugendalter.

MRI was performed on 25 infants, children and adolescents with thoracic and abdominal tumours. The specific contribution of MRI to diagnosis, treatment planning and therapy monitoring is demonstrated. In some cases the T1 and T2 relaxation times were determined; this may clarify the different signal intensities of tumour and neighbouring organs and contribute to differentiation between Wilm's tumour and neuroblastoma.

[31-phosphorus spectroscopy of osteogenic sarcoma. Possibilities in therapy control in comparison with imaging methods]. / 31Phosphorspektroskopie bei osteogenem Sarkom. Möglichkeiten der Therapiekontrolle im Vergleich mit bildgebenden Verfahren.

31-phosphorus spectroscopy was used to control the results of chemotherapy in a patient with an osteogenic sarcoma. The findings were compared with conventional imaging methods (DSA, MRT and conventional radiography). The imaging methods do not provide reliable information regarding growth of tumour tissue during treatment, whereas the determination of phosphate concentration in the tumour provides direct information concerning tumour metabolism.

Antigenic and adjuvant activities of branched aliphatic oligoester (M-DL-LA) microspheres with incorporated bovine rotavirus.

Branched aliphatic oligoester microspheres (msp) with incorporated rotavirus were used to induce the production of systemic and mucosal antibodies in mice. The msp with a mean diameter of 7.4 microm were prepared by the w/o/w technique. The mice were immunized intraperitoneally or orally. High ELISA titres of systemic and local IgG and IgA antibodies were indicative of rotavirus incorporation and of the adjuvant activity of msp. Oral immunization with a split dose administered on three consecutive days, resulted in the production of systemic IgG and IgA antibodies, but failed to induce the production of mucosal antibodies even if the immunization dose was increased threefold. Specific antibodies were detectable in faeces of orally immunized mice only after another triple administration of the same dose in the fourth week of the experiment. Reactions of blood serum IgG with the structural viral proteins VP4, VP6, and VP7 were demonstrated by western blotting. Both systemic, and faecal IgA antibodies were specific for the VP6 protein and the dimeric form of the glycoprotein VP4.

[Use of synthetic biodegradable polymers in medicine]. / Vyuzití syntetických biodegradabilních polymeru v medicíne.

Synthetic biodegradable polymers, such as polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphoesters, polyphosphazenes, polyesteramides, polyalkylenoxalates, polyalkylcyanoacrylates, etc., are represented as materials which are being tested for use, or which have been already used in surgery, orthopaedics, and pharmacy. A particular attention is devoted to their use in the preparation of systems with prolonged release or with targeted biodistribution of active ingredients.