[Nanomedicine. Innovative applications in medicine]. / Nanomedizin. Innovative anwendungen in der medizin.

Nanomedicine is a new and upcoming area in medicine. In particular, superparamagnetic iron oxide nanoparticles (SPION) deserve attention as they can be used for diagnostics and therapy ("theranostics"). For diagnosis in vivo SPION are already used as contrast agents in magnetic resonance imaging; in vitro they are used for cell separation. For therapy, magnetic drug targeting is a particularly promising approach. It enables a goal-oriented local application of active substances. Very promising animal experiments have already been performed. Moreover, SPION can be heated by alternating magnetic fields, so combination with hyperthermia is also possible. However, many effects of nanotechnology on the human organism are not known. Hence, further investigations are indispensable to elucidate possible toxic effects. Implementation of this promising therapy into the clinical setting will be possible due to interdisciplinary cooperation and respective financial support.

Isolated late metastasis from testicular seminoma presenting as a parotid gland mass: case report and review of the literature.

Parotid metastases from non-head-and-neck cancers are rare and may represent a diagnostic and therapeutic challenge. A late metastasis to the parotid gland from a seminoma is an unusual manifestation of disease. A 45-year-old man with a history of testicular seminoma 5 years earlier presented with a rapidly progressing parotid mass. Ultrasonography and computed tomography showed a space-occupying lesion at the angle of the right jaw. The mass was infiltrating into the parotid gland and into the parapharyngeal space. A primary parotid neoplasm was suspected, and panendoscopy combined with open biopsy was performed. Histology examination confirmed a seminoma metastatic to the parotid gland, and comparison with the primary tumour showed identical histology. The patient received chemotherapy for recurrent seminoma in accordance with the pei (cisplatin, etoposide, ifosfamide) protocol. After 4 courses of chemotherapy, salvage radical parotidectomy with removal of all suspicious residual tumour tissue was performed. This case illustrates the difficulties that may be encountered in the differential diagnosis of parotid gland masses and underlines the necessity for a detailed clinical history and for strong interdisciplinary collaboration between oncologists and pathologists to correctly diagnose cases with such unusual presentations.

Prescribing and adjusting exercise training in chronic respiratory diseases - Expert-based practical recommendations.

BACKGROUND: International guidelines recommend endurance (ET) and strength training (ST) in patients with chronic respiratory diseases (CRDs), but only provide rough guidance on how to set the initial training load. This may unintentionally lead to practice variation and inadequate training load adjustments. This study aimed to develop practical recommendations on tailoring ET and ST based on practices from international experts from the field of exercise training in CRDs. METHODS: 35 experts were invited to address a 64-item online survey about how they prescribe and adjust exercise training. RESULTS: Cycling (97%) and walking (86%) were the most commonly implemented ET modalities. Continuous endurance training (CET, 83%) and interval endurance training (IET, 86%) were the frequently applied ET types. Criteria to prescribe IET instead of CET were: patients do not tolerate CET due to dyspnoea at the initial training session (79%), intense breathlessness during initial exercise assessment (76%), and/or profound exercise-induced oxygen desaturation (59%). For ST, most experts (68%) recommend 3 sets per exercise; 62% of experts set the intensity at a specific load that patients can tolerate for a range of 8 to 15 repetitions per set. Also, 56% of experts advise patients to approach local muscular exhaustion at the end of a single ST set. CONCLUSIONS: The experts´ practices were summarized to develop practical recommendations in the form of flowcharts on how experts apply and adjust CET, IET, and ST in patients with CRDs. These recommendations may guide health care professionals to optimize exercise training programs in patients with CRDs.

[Nanomedicine in otorhinolaryngology--future prospects]. / Nanomedizin in der HNO-Heilkunde--ein Ausblick.

BACKGROUND: Nanotechnology becomes more and more important in the world of today. Equally, it does generally in medicine and of course specifically in otorhinolaryngology. Essentially, there are the following fields: Diagnostics, new therapies and agents, drug delivery and medical implants. MATERIAL AND METHODS: An extensive literature research on nanomedicine in otorhinolaryngology was carried out in the standard online medical reference databases "PubMed/Medline" and "Web of Science". Furthermore, we are giving an overview of the work of the Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen. RESULTS: A lot of new and innovative studies on nanotechnology in diagnostics and therapy were recovered. Depending on the variety in otorhinolaryngology, there are numerous versatile approaches, according to the different areas. The main part is engaged in drug delivery. CONCLUSIONS: The efforts to exploit the potential of nanotechnology in otorhinolaryngology are multifaceted, innovative and seminal. The best perspective of success is attributed to nanoparticulate drug delivery systems.

Effect of portable noninvasive ventilation on thoracoabdominal volumes in recovery from intermittent exercise in patients with COPD.

We previously showed that use of portable noninvasive ventilation (pNIV) during recovery periods within intermittent exercise improved breathlessness and exercise tolerance in patients with COPD compared with pursed-lip breathing (PLB). However, in a minority of patients recovery from dynamic hyperinflation (DH) was better with PLB, based on inspiratory capacity. We further explored this using Optoelectronic Plethysmography to assess total and compartmental thoracoabdominal volumes. Fourteen patients with COPD (means ± SD) (FEV1: 55% ± 22% predicted) underwent, in a balanced order sequence, two intermittent exercise protocols on the cycle ergometer consisting of five repeated 2-min exercise bouts at 80% peak capacity, separated by 2-min recovery periods, with application of pNIV or PLB in the 5 min of recovery. Our findings identified seven patients showing recovery in DH with pNIV (DH responders) whereas seven showed similar or better recovery in DH with PLB. When pNIV was applied, DH responders compared with DH nonresponders exhibited greater tidal volume (by 0.8 ± 0.3 L, P = 0.015), inspiratory flow rate (by 0.6 ± 0.5 L/s, P = 0.049), prolonged expiratory time (by 0.6 ± 0.5 s, P = 0.006), and duty cycle (by 0.7 ± 0.6 s, P = 0.007). DH responders showed a reduction in end-expiratory thoracoabdominal DH (by 265 ± 633 mL) predominantly driven by reduction in the abdominal compartment (by 210 ± 494 mL); this effectively offset end-inspiratory rib-cage DH. Compared with DH nonresponders, DH responders had significantly greater body mass index (BMI) by 8.4 ± 3.2 kg/m2, P = 0.022 and tended toward less severe resting hyperinflation by 0.3 ± 0.3 L. Patients with COPD who mitigate end-expiratory rib-cage DH by expiratory abdominal muscle recruitment benefit from pNIV application.NEW & NOTEWORTHY Compared with the pursed-lip breathing technique, acute application of portable noninvasive ventilation during recovery from intermittent exercise improved end-expiratory thoracoabdominal dynamic hyperinflation (DH) in 50% of patients with COPD (DH responders). DH responders, compared with DH nonresponders, exhibited a reduction in end-expiratory thoracoabdominal DH predominantly driven by the abdominal compartment that effectively offset end-expiratory rib cage DH. The essential difference between DH responders and DH nonresponders was, therefore, in the behavior of the abdomen.

[Unilateral neck mass, dysphagia and dyspnea]. / Einseitiger Halstumor, Dysphagie und Dyspnoe.

Extraocular sebaceous carcinoma is a rare malignant tumor, arising from skin and salivary glands. An important differential diagnosis in the head and neck region is metastasizing squamous cell carcinoma. Using case histories, the clinical and histological findings as well as the therapeutic principles of this entity are described. Only a few cases of this malignancy in the ENT area are published in the literature.

[Unclear parapharyngeal mass]. / Unklare parapharyngeale Raumforderung.

A 20-year-old male patient presented with a left cervical solid indolent swelling. On mirror examination a prominence in the lateral wall of the oro- and hypopharynx and, in the throat, a solid indolent and easily movable swelling in regions II-III were seen. B-mode and Doppler ultrasound demonstrated a sharply defined, hypoechoic, inhomogeneous mass without perfusion, while on MRI a contrast-enhancing left pharyngeal homogenous mass causing carotid artery and jugular vein displacement was seen. No invasive growth was observed.

[Nanomedicine : Magnetic nanoparticles for drug delivery and hyperthermia - new chances for cancer therapy]. / Pharmakotherapie mittels Nanomedizin : Magnetische Nanopartikel für Drug Delivery und Hyperthermie - neue Chancen für die Krebsbehandlung.

The application of nanotechnology for the treatment, diagnosis, and monitoring of illnesses is summarized under the term nanomedicine. A particularly promising application is attributed to nanoparticular drug delivery systems. The goal of these new carrier systems is the selective enrichment of active substances in diseased tissue structures, an increase in bioavailability, the decrease of the active substance degradation and, above all, the reduction and/or avoidance of unwanted side effects. Apart from numerous nanosystems acting as carriers, the use of iron oxide nanoparticles has to be particularly emphasized. On the one hand, those particles are the carriers of the active substance and, on the other hand, can also be visualized with conventional imaging techniques (x-ray tomography, magnetic resonance imaging), called theranostic. In addition, they can be used for hyperthermia, another important supporting pillar of nanomedicine. Both procedures should lead to a personalized and goal-oriented therapy, which is of special medical and socioeconomic importance in view of the increasing number of cancer patients worldwide.

[Dislocation of voice prostheses. Interdisciplinary management of diagnostics and treatment]. / Dislokation von Stimmprothesen. Interdisziplinäres Vorgehen bei Diagnostik und Therapie.

Tracheoesophageal voice prostheses after total laryngectomy are infrequently the cause of severe complications. We report on a patient with threefold dislocation of a Provox prosthesis, each with suspected oesophageal loss. The patient came to our hospital with acute dyspnoea. An urgent bronchoscopy showed two prostheses in the right and one in the left main bronchus, which had caused inflammation with extensive occlusion of the bronchus. All three prostheses could be recovered.

[Recurrent and metastasizing atypical fibroxanthoma]. / Rezidivierendes und metastasierendes atypisches Fibroxanthom.

Atypical fibroxanthoma is a rare skin tumor that arises particularly on sun-exposed skin. Although it is considered to be a benign tumor, rarely, metastases arise. The accurate classification of aggressive processes of atypical fibroxanthoma is currently still the subject of discussion. The case of an 81-year-old patient with relapsing atypical fibroxanthoma of the right auricle is presented. With the second relapse, a single metastasis in the right parotid gland was detected. A complete tumor excision was performed, and the patient declined the recommended postoperative radiotherapy. The patient has not show any signs of relapse for 60 months now. Atypical fibroxanthoma and the appropriate therapy for it are described, and the newest discoveries regarding this disease are discussed on the basis of the current literature.

[Computer-assisted orbital floor reconstruction. Use of a CAD/CAM implant with intraoperative contact-free 3D endo- and exophthalmometry]. / Computerassistierte Enophthalmuskorrektur. Nutzung eines CAD/CAM-Implantats unter intraoperativer, berührungsfreier 3D-en- und exophthalmometrischer Kontrolle.

Pronounced enophthalmos can restrict patients both functionally and aesthetically. Typical symptoms are double vision on both eyes and obvious asymmetry, both of which were present in the 67-year-old male patient presented in this paper. The resulting data of computed tomography was used to fabricate a patient specific ceramic implant for reconstruction of the left orbital floor with an enophthalmos of 4mm. During the surgery the implant fitted anatomically correct, but exophthalmos occurred. The implant needed to be regraded and recontoured in the dorsal fraction, so that overcorrection could be reduced. With the assistance of optical 3D en- and exophthalmometry during surgery, the position of the cornea vertex was reproducible measured. At the end of surgery, exophthalmos was 1.5 mm. After 12 months, enophthalmos of only 1mm exists. This case displays the combination of a patient specific fabricated implant for reconstruction of the orbital floor with optical 3D-en-and exophthalmometry to correct enophthalmos with a high degree of accuracy. Therefore these two techniques in combination should be used when complex corrections of enophthalmos are needed.

Taenia saginata: a rare cause of bowel obstruction.

Taenia saginata infection is caused by the bovine tapeworm and can be the cause of emergency surgical conditions. We report one case of small bowel obstruction leading to necrosis and another case of large bowel obstruction and volvulus due to an impacted tapeworm. The diagnosis of these rare circumstances is usually made intraoperatively.

Non-invasive measurement of peripheral venous oxygen saturation using a new venous oximetry method: evaluation during bypass in heart surgery.

Monitoring of mixed venous oxygen saturation (SvO(2)) is currently performed using invasive fibre-optic catheters. This procedure is not without risk as complications may arise from catheterization. This paper describes an alternative, non-invasive method of monitoring peripheral venous oxygen saturation (SxvO(2)) which, although it cannot replace pulmonary artery catheters, can serve as an adjunct/early warning indicator of when there is an imbalance in oxygen supply and demand. The technique requires the generation of an artificial venous pulse at the finger, thereby causing modulation of the venous blood volume within the digit. The blood volume changes are monitored using an optical sensor. Just as pulse oximetry utilizes the natural arterial pulse to perform a spectrophotometric analysis of the peripheral blood in order to estimate the arterial blood oxygen saturation, the proposed venous oximetry technique uses the artificially generated venous pulse to estimate SxvO(2). A prototype device was tested in a pilot study with patients undergoing heart surgery. Data from this study support the notion that the method is capable of tracking haemodynamic changes and suggests the technique is worthy of further development and evaluation.

Medical applications of magnetic nanoparticles.

In recent years biomedical research indicated, that magnetic nanoparticles can be a promising tool for several applications in vitro and in vivo. In medicine many approaches were investigated for diagnosis and therapy and offered a great variety of applications. Magnetic cell separation, magnetic resonance imaging (MRI), magnetic targeted delivery of therapeutics or magnetically induced hyperthermia are approaches of particular clinical relevance. For medical use, especially for in vivo application it is of great importance that these particles do not have any toxic effects or incompatibility with biological organism. Investigations on applicable particles induced a variability of micro- and nanostructures with different materials, sizes, and specific surface chemistry.

Quantification of magnetic nanoparticles by magnetorelaxometry and comparison to histology after magnetic drug targeting.

Magnetic nanoparticles can be used in medicine in vivo as contrast agents and as a drug carrier system for chemotherapeutics. Thus local cancer therapy is performed with Magnetic Drug Targeting (MDT) and allows a specific delivery of therapeutic agents to desired targets, i.e., tumors, by using a chemotherapeutic substance bound to magnetic nanoparticles and focused with an external magnetic field to the tumor after intraarterial application. Important for this therapeutic principle is the distribution of the particles in the whole organism and especially in the tumor. Therefore we used magnetorelaxometry to quantify ferrofluids delivered after MDT. Tissue samples of some mm3 volume of a VX2 squamous cell carcinoma were measured by magnetic relaxation and the amount of iron was determined using the original ferrofluid suspension as a reference. From this the distribution of the magnetic particles within the slice of tumor was reconstructed. Histological cross-sections of the respective tumor offer the opportunity to map quantitatively the particle distribution and the vascularisation in the targeted tumor on a microscopic scale. Our data show that the integral method magnetorelaxometry and microscopic histological methods can complete each other efficiently.

[Magnetically based enhancement of nanoparticle uptake in tumor cells: combination of magnetically induced cell labeling and magnetic heating]. / Magnetisch basierte Steigerung der Nanopartikelaufnahme in Tumorzellen: Kombination von magnetisch induzierter Zellmarkierung und magnetischer Wärmebehandlung.

PURPOSE: Magnetic nanoparticles (MNP) are known to be versatile tools in diagnostic and interventional radiology. The goal of the present study was to assess whether MNP can be selectively accumulated on human adenocarcinoma cells in vitro using an external magnetic field (magnetically induced cell labeling) and whether these labeled tumor cells can then be destroyed after being exposed to an alternating magnetic field (magnetically induced heating). In this context, a long-term goal is to combine these two developing methods to achieve an additive effect in tumor therapy. MATERIALS AND METHODS: BT-474 cells were incubated until confluence. Magnetic nanoparticles (0.32 mg Fe/ml culture medium) were then added and the flask was exposed to an external magnetic field gradient (magnetically induced cell labeling, 56 or 83 mT magnets) for 24 hours in order to label the tumor cells with nanoparticles. Cells without both MNP and magnetic labeling as well as cells with MNP incubation but without magnetic labeling served as controls. After MNP incubation, the magnetically labeled cells (5 x 10 (7) cells/ml) were exposed to an alternating magnetic field for 5.45 minutes (frequency 400 kHz, amplitude 24.6 kA/m). The combination effect of both magnetic labeling and magnetic heating was assessed by determining the temperature increase. The amount of MNP accumulated within the cells was determined by measuring the iron content via atomic absorption spectrometry. For statistical analysis mean values and standard deviations of temperature increases and iron contents were calculated and the differences were analyzed using the Student's t-test. RESULTS: A significant temperature increase (p < 0.01) during magnetic heating of 41.76 +/- 4.60 K was detected after magnetic labeling of the cells (5 x 10 (7) cells/ml, 83 mT) incubated with MNP. In comparison, the cells incubated with MNP but without magnetic labeling revealed a temperature increase of 32.03 +/- 3.33 K, naked cells of only 2.69 +/- 0.34 K. CONCLUSION: The results demonstrated the magnetically based enhancement of cellular uptake of nanoparticles by tumor cells, resulting in the intensification of the generated temperature increase during magnetic heating. Consequently, magnetic nanoparticles are shown to be valuable tools for the combination of magnetically based therapy modalities.

Locoregional cancer treatment with magnetic drug targeting.

The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. One approach, developed in the past to address this problem, is the i.v. injection of magnetic particles [ferrofluids (FFs)] bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squamous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) that was concentrated with a magnetic field. Experimental VX-2 squamous cell carcinoma was implanted in the median portion of the hind limb of New Zealand White rabbits (n = 26). When the tumor had reached a volume of approximately 3500 mm3, FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumor. FF-MTX i.a. application with the external magnetic field resulted in a significant (P < 0.05), complete, and permanent remission of the squamous cell carcinoma compared with the control group (no treatment) and the i.v. FF-MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus, our data show that i.a. application of FF-MTX is successful in treating experimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without systemic toxicity. Furthermore, it may be possible to use these magnetic particles as a "carrier system" for a variety of anticancer agents, e.g., radionuclides, cancer-specific antibodies, and genes.

A blast without power - cell death induced by the tuberculosis-necrotizing toxin fails to elicit adequate immune responses.

In this study, we deploy a doxycycline-dependent suicide switch integrated in a tumor challenge model. With this experimental setup, we characterized the immunological consequences of cells dying by four distinct cell death stimuli in vivo. We observed that apoptotic cell death induced by expression of the truncated form of BH3 interacting-domain death agonist (tBid) and a constitutively active form of caspase 3 (revC3), respectively, showed higher immunogenicity than cell death induced by expression of the tuberculosis-necrotizing toxin (TNT). Our data indicate that the early release of ATP induces the silent clearance of dying cells, whereas the simultaneous presence of 'find me' signals and danger-associated molecular patterns (DAMPs) promotes inflammatory reactions and increased immunogenicity. This proposed model is supported by findings showing that the production and release of high concentrations of IL-27 by bone-marrow-derived macrophages (BMDM) is limited to BMDM exposed to those forms of death that simultaneously released ATP and the DAMPs heat-shock protein 90 (HSP90) and high-mobility group box-1 protein (HMGB1). These results demonstrate that the tissue microenvironment generated by dying cells may determine the subsequent immune response.

Management of spontaneous enophthalmos due to silent sinus syndrome: a case report.

Silent sinus syndrome (SSS) is a rare disease exhibiting unilateral enophthalmos and hypoglobus. A 26-year-old white female presented with right side enophthalmos and hypoglobus. There was no history of previous trauma or maxillary sinus diseases. A CT scan showed an opacified right maxillary antrum with decreased volume and downward bowing of the right orbital floor. From clinical and radiological findings the diagnosis SSS was made. Biopsies were collected from the maxillary sinus for the exclusion of malignancy. Two months later orbital floor reconstruction was carried out. Before antrostomy of the affected maxillary sinus, a relative enophthalmos of 4mm was determined. Five days after antrostomy the value reduced to 2.3mm. During the following 2 months the enophthalmos remained constant. At the end of the operation for orbital floor reconstruction it was 0.1mm. Five days after surgery the relative enophthalmos increased to 0.8mm. The value remained constant during the following 3 months. Initial antrostomy of the affected maxillary sinus may lead to a relevant, spontaneous reduction of enophthalmos. After a minimum period of 2 months a re-evaluation should be made, if a reconstruction of the orbital floor is still necessary for the correction of the globe position.