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We report on a 69-year-old man suffering from chronic progressive oligoarthritis (localized in metacarpal and knee joints), which clinically was interpreted as steroid-sensitive seronegative chronic arthritis. The patient died from sudden death at the emergency department after a 4-week history of increasing cough and dyspnea (meanwhile obtaining negative testing results for SARS-CoV-2). During the autopsy, we found massive pancarditis affecting all cardiac compartments, in particular exhibiting constrictive pericarditis, myocarditis, and multivalvular endocarditis. Microscopically, interstitial myocarditis could be observed. Performing extensive molecular analyses, we detected Tropheryma whipplei in the tissue specimens of the heart, but not in various duodenal tissue probes or in the synovial membrane. Taken together, in the present case the cause of death was acute cardiac failure due to multivalvular pancarditis due to T. whipplei. Besides from classical symptoms and morphological signs, Whipple's disease may present with various features. Regarding the differential diagnosis of a chronic multisystem disorder with aspects of hitherto unknown arthralgia, Whipple's disease should be considered.Wir berichten über einen 69-jährigen Patienten mit einer chronisch fortdauernden Oligoarthritis (Hand- und Kniegelenke), die klinisch als steroidsensible seronegative chronische Arthritis eingestuft wurde. Der Patient starb in der Notaufnahme am plötzlichen Herztod, nachdem er seit 4 Wochen unter Husten und Atemnot litt (SARS-CoV-2[„severe acute respiratory syndrome coronavirus 2“]-negativ getestet). Bei der Obduktion fand sich eine massive Pankarditis mit Pericarditis constrictiva, Myokarditis und multivalvulärer Endokarditis. Histologisch zeigte sich eine interstitielle Myokarditis. In einer ausführlichen molekularen Diagnostik konnte Tropheryma whipplei aus dem Herzgewebe gesichert werden, nicht aber aus der Synovialmembran und auch nicht aus diversen Duodenalbiopsien. Abschließend diagnostizierten wir als Todesursache eine akute kardiale Dekompensation bei einer durch Tropheryma whipplei ausgelösten multivalvulären Pankarditis als Todesursache. Dieser Fall untermauert das vielgestaltige klinische und morphologische Bild des Morbus Whipple. Bei einem unklaren chronifizierten Krankheitsprozess mit Hinweis auf eine Multisystemerkrankung unter Beteiligung des Gelenksystems sollte der Morbus Whipple in die Differenzialdiagnostik mit einbezogen werden.

Nebulizers used to treat prehospital emergency patients should provide a high output efficiency to achieve a fast onset of therapeutic drug effects while remaining unaffected by the presence of supplementary oxygen flow or the patient's breathing pattern. On the other hand, nebulizer performance is directly influenced by differences in device design, gas flow and patients' breathing patterns. Several studies from emergency departments were able to demonstrate an improvement in patient outcome when using a mesh nebulizer instead of a jet nebulizer. Data or bench studies regarding prehospital care are non-existent.The aim of the present in vitro study was to evaluate which type of aerosol generator would best address the requirements of a prehospital adult emergency patient suffering from respiratory distress.We evaluated the performance of a jet nebulizer (Cirrus™ 2, Intersurgical®) and two mesh nebulizers (Aerogen Solo® with USB controller, Aerogen Limited and M‑Neb® mobile, NEBU-TEC International med. Produkte Eike Kern GmbH) with the possibility of portable operation in an in vitro model of a spontaneously breathing adult emergency patient. One physiological and three pathological breathing patterns (distressed breathing pattern as well as stable and acute exacerbated chronic obstructive pulmonary disease) were simulated. Nebulizer output and salbutamol lung deposition were measured at different oxygen flow rates using a face mask as the delivery interface.The mesh nebulizers produced a significantly higher aerosol output when compared to the jet nebulizer. The M‑Neb® mobile was able to significantly exceed the output of the Aerogen Solo®. Oxygen flow had the largest influence on the output of the jet nebulizer but hardly affected the mesh nebulizers. After a nebulization time of 10 min the M‑Neb® mobile also achieved the highest total salbutamol lung deposition (P 0.001). Aerosol drug deposition was therefore mainly determined by the nebulizer's drug output per unit time. The deposition could not be improved using a spacer but was strongly influenced by the simulated emergency patients' breathing pattern.The use of mesh nebulizers might have the potential to improve the aerosol therapy of prehospital emergency patients. In general, mesh nebulizers seem to be superior to jet nebulizers regarding aerosol output per unit time and total lung deposition. The present data suggest that aerosol output and drug deposition to the collection filter in this simulated setting are closely connected and crucial for total salbutamol deposition, as the deposition could not be improved by adding a spacer. Aerosol drug deposition in simulated emergency patients' lungs is therefore mainly determined by the nebulizer's drug output per unit time. The level of oxygen flow used had the largest influence on the output of the jet nebulizer but hardly affected the output of the tested mesh nebulizers. Mesh nebulizers could therefore enable a demand-adapted oxygen therapy due to their consistent performance despite the presence of oxygen flow. A high respiratory rate was associated with a high drug deposition, which is clinically desirable in the treatment of patients in respiratory distress; however, drug underdosing must also be expected in the treatment of bradypneic patients. Further clinical studies must prove whether our findings also apply to the treatment of real prehospital emergency patients.HINTERGRUND: Medikamentenvernebler im Rettungsdienst sollten eine hohe Vernebelungsleistung haben, um schnell eine therapeutische Wirkstoffkonzentration des vernebelten Medikaments zu erreichen. Eine Umfrage im süddeutschen Rettungsdienst zeigte allerdings, dass fast ausschließlich die wenig effizienten Jet-Vernebler zum Einsatz kommen.Ziel der vorliegenden In-vitro-Studie war es herauszufinden, ob der Einsatz von Mesh-Verneblern die prähospitale Aerosoltherapie verbessern könnte.Die Vernebelungsleistung eines Jet-Verneblers (Cirrus™ 2, Fa. Intersurgical®) und 2 mobil einsatzbarer Mesh-Vernebler (Aerogen Solo®, Fa. Aerogen Limited, M‑Neb® mobile, NEBU-TEC International med. Produkte Eike Kern GmbH) wurde in einem In-vitro-Modell spontan atmender Notfallpatient*innen mit 4 unterschiedlichen Atemmustern bei verschiedenen Sauerstoffflussraten getestet.Die Mesh-Vernebler zeigten im Vergleich zum Jet-Vernebler eine signifikant höhere Verneblungsleistung und Salbutamol-Filterdeposition, wobei der M‑Neb® mobile die höchsten Werte für Leistung und Deposition erreichte. Der Sauerstofffluss hatte den größten Einfluss auf die Leistung des Jet-Verneblers, wirkte sich aber kaum auf die Mesh-Vernebler aus. Die Deposition wurde zudem stark vom Atemmuster beeinflusst.Der Einsatz von Mesh-Verneblern mit hoher Verneblungsleistung konnte in einem In-vitro-Modell die Aerosoltherapie von prähospitalen Notfallpatient*innen verbessern. Sie waren dem Jet-Vernebler in Bezug auf die Verneblungsleistung und die Lungendeposition überlegen und ermöglichten zudem eine bedarfsangepasste Sauerstofftherapie. Die höchste Medikamentendeposition wurde bei den tachypnoischen Patient*innen erreicht, welche in der praktischen Anwendung auch am meisten von einem erhöhten Medikamentenspiegel profitieren würden.

In German emergency rescue services, inhalation treatment is routinely carried out by qualified health personnel. Standard operating procedures (SOP) for nebulization are neither uniform throughout Germany nor available in all federal states. Standardized recommendations with respect to which nebulizer type should be used are missing. The aerosol output as well as the drug deposition rates of jet and mesh nebulizers, however, differ considerably. Mesh devices can achieve a threefold higher lung deposition. Their use in emergency departments has also been shown to be associated with a better patient outcome when compared to jet nebulizers.This survey was designed to evaluate the type of nebulizer used in the south German rescue services. Special attention was paid to the influence of existing SOP on the decision to perform nebulization during emergency treatment.A total of 4800 emergency paramedics working in Baden-Württemberg, Bavaria and Rhineland-Palatinate received a questionnaire with a total of 17 questions on the implementation of drug nebulization in the daily practice.Despite the existence of more efficient nebulizer types, the jet nebulizer was by far the most frequently used nebulizer in the south German rescue services. The deposition rates of both the jet and mesh nebulizers were considerably overestimated by most respondents; however, 77.5% of all respondents could not give any information about the deposition rates of the mesh nebulizer. Only two thirds of all respondents carried out nebulization treatment on the basis of SOP. The implementation of SOP, however, was pivotal to the application of nebulization during emergencies. If SOP were in place,76.9% of the responders used aerosol treatment compared to 23.1% when there were none. The perceived safety when using nebulization during emergencies was also significantly higher (p = 0.013) when SOP were implemented.The exclusive use of mesh nebulizers could standardize the treatment of emergency patients in the south German rescue services. The use of mesh devices might possibly improve patient outcomes, even if clinical studies are still lacking. Nebulizer treatment differs between the federal states. A comprehensive implementation of SOP for nebulization treatment might support this process and could increase the application frequency and the perceived safety of nebulization during emergencies. A better training of paramedic personnel could improve the knowledge of aerosols as a treatment option for emergency patients and help to classify the advantages and disadvantages of the different aerosol generators available.HINTERGRUND: In der Notfallmedizin ist die Durchführung der inhalativen Therapie auch durch Rettungsfachpersonal vorgesehen. Standard Operating Procedures (SOP) und Handlungsempfehlungen zum Einsatz sind nicht bundeseinheitlich und liegen im Falle der Vernebelung von Notfallmedikamenten nicht in allen Bundesländern und Rettungsdienstbereichen vor. Es existieren auch keine Empfehlungen, welcher Verneblertyp genutzt werden soll. Die Medikamentendepositionsraten von Jet- und Mesh-Verneblern unterscheiden sich aber erheblich; klinisch ist die Verwendung von Mesh-Systemen mit einem besseren Patienten-Outcome assoziiert.Die vorliegende Umfrage sollte die Praxis des Vernebelns von Notfallmedikamenten im süddeutschen Rettungsdienst evaluieren. Ein besonderes Augenmerk wurde auf den eingesetzten Verneblertyp sowie den Einfluss von SOP und Handlungsempfehlungen auf die Anwendung gelegt.Insgesamt 4800 in Baden-Württemberg, Bayern und Rheinland-Pfalz tätige Notfallsanitäter*innen und Rettungsassistent*innen erhielten insgesamt 17 Fragen zur Durchführung der Medikamentenvernebelung in ihrer alltäglichen Praxis.Der Jet-Vernebler ist mit Abstand der am häufigsten eingesetzte Verneblertyp. Die Depositionsraten sowohl des Jet- als auch des Mesh-Verneblers werden deutlich überschätzt. Nur 67,3 % aller Befragten vernebelten im Rahmen von SOP oder Handlungsempfehlungen. Das Vorhandensein dieser war allerdings maßgeblich für den Einsatz der Vernebelung ohne Beisein eines*er Notarzt*ärztin und die gefühlte Sicherheit beim Vernebeln.Der flächendeckende Einsatz von Mesh-Verneblern könnte die Therapie von Notfallpatient*innen homogenisieren und möglicherweise das Outcome verbessern. SOP und Handlungsempfehlungen zur Anwendung von Vernebelung in der Notfallsituation könnten die inhalative Therapie verbessern und homogenisieren.

The pathological hallmarks of Alzheimer's disease are aggregation and accumulation of amyloid-β and tau proteins. So far most interventional studies have focused on the removal of the toxic protein products, such as antibody-based immunotherapies targeted against amyloid-β and tau proteins; however, the development of gene therapies targeting gene products involved in the disease has opened up new therapeutic strategies to reduce the development of toxic protein aggregates by inhibiting the translation of pathological Alzheimer genes using antisense oligonucleotides (ASO). This has a timely influence on development of the disease. This article gives an overview of new advances in ASO-based treatment strategies for Alzheimer's disease.

Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines ( www.DGPPN.de ). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (Aβ 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other). Generally, CSF-NDD should be combined with blood-based routine diagnostics and should be part of routine CSF diagnostics, e. g. cell count and cell differentiation (if applicable), intrathecal antibody synthesis and blood-CSF barrier analysis. The CSF-NDD are most valuable for the improved differentiation between reversible dementia syndromes and irreversible neurodegenerative dementia, e. g. cognitive deficits due to late onset depression (pseudodementia due to depression) or AD. Combined with extended psychometric neuropsychological evaluation and neuroimaging methods, such as magnetic resonance imaging (MRI), dopamine transporter scanning (DaTscan) by single photon emission computed tomography (SPECT), 18F-fluorodeoxyglucose positron emission tomography (glucose-PET) and amyloid-PET, CSF-NDD also significantly improve the differential diagnostics within the heterogeneous group of primary neurodegenerative dementias. Meanwhile, several independent studies have indicated that the Aβ 1-42:Aβ 1-40 ratio is superior to the determination of Aβ 1-42 alone. Currently, several international research initiatives have been launched to further harmonize and optimize preanalytical procedures and CSF-NDD biomarker assays.

Snake bites are rare events in Germany and are not life-threatening with usually only mild clinical symptoms. The most widespread venomous snake is the common European adder (Vipera berus). Here we present the case of a 53-year-old woman who was bitten by a common adder. Although the patient was initially in stable condition she developed edematous swelling of the complete lower limb, subcutaneous bleeding, and rhabdomyolysis. The aim of this report is to raise awareness that even in a central European country like Germany snake bites with a life-threatening course can occur and need immediate attention and medical care.

The diagnosis of infections in patients with arthritis and/or in joint prostheses requires interdisciplinary cooperation and the application of up-to-date methods. The histological investigation of the synovial membrane allows the differentiation of acute, chronic and granulomatous synovialitis. Detection of conserved regions of the microbial genome by PCR, especially 16S rRNA for bacteria and 18S rRNA for fungi, is a broad approach for the classification of pathogens which cannot be cultured. Acute infectious arthritis and periprosthetic infections share the spectrum of pathogens with sepsis, therefore multiplex PCR-based methods for the detection of sepsis can be employed. Molecular diagnostics can detect minimal infections in periprosthetic tissues even after antibiotic therapy. The anamnesis (enteral or urogenital infection), clinical picture (oligoarthritis) and further parameters (e.g. HLA B27 status) are important for the diagnosis of reactive arthritis. In many cases of reactive arthritis, molecular methods allow the detection of bacterial DNA or RNA in synovial fluid or tissue samples. The low sensitivity of histopathological methods may be compensated by application of PCR techniques, especially in the differential diagnosis of granulomatous synovitis including mycobacterial infections. Molecular methods can be used to support the differential diagnosis of septic and reactive arthritis. MicroRNA techniques combined with PCR for detection of pathogens support the differential diagnosis of rheumatoid arthritis with severe inflammatory activity compared to infectious arthritis. Proteomic methods could expand the methodological spectrum for the diagnosis of infections.

The classification of meniscal lesions requires correlation with clinical data. For the standardization of histopathology reports a discrimination between normal, low-grade lesions and high-grade lesions is feasible. This classification can be further specified using other methods.Formalin-fixed, paraffin-embedded specimens of meniscal tissue from 68 patients were analyzed by matrix-assisted laser desorption ionization (MALDI) imaging.The classification of meniscal lesions and differentiation between low-grade and high-grade and acute versus non-acute degeneration is possible by determination of the differential expression of mass-to-charge ratios by statistical comparisons using the P-value from combined Wilcoxon and Kruskal-Wallis (PWKW) tests and a predefined average two-fold difference in intensity.The concept of a "meniscus report" is introduced for documentation of meniscus tissue specimens integrating histological, histochemical and proteomic data, thereby specifying the degree of degeneration and the assessment of acute or non-acute lesions. Mass spectrometry contributes to an objective histopathology report. An advisory opinion should always be based on close correlation of clinical and morphological evaluations.

When facing the well-known demographic development with an increasing number of people suffering from dementia, there is a need of programmes to support nursing relatives and care at home. Many support services have been established in the past few years but they are rarely used by the relatives and the patients. The purpose of the Lighthouse Project Ulm (ULTDEM Study) was to prove the effectiveness of a single advisory approach in order to provide support services after care level classification and to relieve the burden placed on relatives caring for family members suffering from dementia ("initial case management").The ULTDEM Study is a prospective, open, randomized, controlled, interventional study with different parallel outcome measures (burden of caring, quality of life and mood). After the randomization, the interventional group was given comprehensive, individual advice about available treatment possibilities for dementia patients. Control group participants received standard treatment. Inclusion criteria were application of a care level (0 or 1) as well as dementia diagnosis. All participants (patients/relatives) underwent an initial and a 6 month comprehensive assessment.Our results show that a single advisory approach does not lead to a significant difference in outcome measures in interventional and control groups. Those tendencies described have to be interpreted as clinically not relevant. Although utilization of support services increases, it remains similar in both study groups. A confirmatory interpretation has not been possible due to a lack of adjustment to the findings regarding multiple testing and an insufficient degree of recruitment. Possible causes will be discussed such as premature intervention during the course of the disease, a lack of intervention blinding, recruitment bias and lack of an influence on adherence with regard to the use of support services.The study demonstrates that there is a substantial information deficit for persons affected by dementia and their relatives. Innovative ways still have to be developed to ensure that this information actually reaches the target audience.

Frontotemporal lobar degeneration (FTLD) is an umbrella term for an aetiologically diverse group of neurodegenerative disorders with prominent lobar cortical atrophy. First this disease group was restricted to Pick's disease or Pick's complex. Several updates of the clinical classification systems were performed and discussed. Currently we summarize the following diseases under the FTLD spectrum: frontotemporal dementia (FTD) as a behavioural variant, primary non-fluent aphasia (PNFA) and semantic dementia as language variants, amyotrophic lateral sclerosis with FTD (ALS-FTD), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).From the pathophysiological aspect major progress was made. Neuropathologically FTLDs are now defined based on the molecular composition of these protein accumulations. A major distinction of tau-associated (FTLD-tau) and TDP43-associated (FTLD-TDP43) and to a lesser extend FUS-associated (FTLD-FUS) has been made. Additional risk genes were described. However from the therapeutic perspective even symptomatic therapy is under discussion. A major aim of our consortium is to develop parameters allowing an early diagnosis and follow-up, thus providing effective and objective parameters for therapeutic strategies.

The diagnostic investigation of CT-negative subarachnoid haemorrhage (SAH) is a particular challenge in clinical neurology. Cerebrospinal fluid (CSF) analysis via lumbar puncture is the method of choice. The diagnosis of SAH in CSF is based on a bloody or xanthochromic discoloration of the CSF as well as on findings in non-automated CSF cytology including the detection of erythrophages and siderophages. The automated determination of CSF ferritin concentrations or spectrophotometric detection of xanthochromia may contribute to the diagnosis but are only useful with regard to the overall clinical picture. Generally, the knowledge of the time flow of CSF changes associated with SAH is essential for a correct interpretation of CSF findings.

CURRENT RECOMMENDATIONS OF DACRYOCYSTORHINOSTOMYOBJECTIVE: With the implementation and the development of endoscopic systems, especially in functional endoscopic sinus surgery (FESS) in the last two decades, the gold standard considered external dacryocystorhinistomy (DCR) by Toti in patients with an obstruction of the lacrimal sac or the nasolacrimal duct has been replaced more and more by endonasal techniques. The endonasal approach, first performed in 1893 by Caldwell and publiciced by West 1911, has been modified since than, reached increasing acceptance and is nowadays often performed be ENT surgeons and ophthalmologists.This review article presents the possible reasons of an obstruction of the lacrimal sac or the nasolacrimal duct with consecutive epiphora or recurrent dacryocystitis, describes diagnostic procedures and indications of therapy, and tries to demonstrate the surgical change towards endoscopic endonasal techniques. We compare both operation techniques and discuss their advantages with the focus on the endonasal approach. The relevance of additional adjuvants described in literatur (laser, use of mitomycin or fluoruracil or silicon intubation) are presented and discussed, too.At the end we discuss the published results of both techniques (endonasal vs. external DCR) and compare their success rates. In spite of the tendency towards endonasal endoscopic techniques the results of this approach seem to be a little worse in comparison to the results after external DCR.

Meniscal degeneration (MD) is a structural change of fibrous cartilage that is common in orthopaedic diagnostics and relevant for health insurance matters. So far, there has been neither a standardised scoring system nor an immunohistochemical marker for MD.In this retrospective trial, the meniscal tissue of 60 patients was assessed immunohistochemically for NITEGE (G1 fragment of the proteoglycan aggrecan) expression. NITEGE expression was correlated with defined grades of MD: little (grade 0/1), medium (grade 2), or severe (grade 3).Detection of extracellular NITEGE deposits in grade 2 or 3 MD had a positive predictive value and specificity of 100%, whereas no deposits were found in grade 0/1 MD. Sensitivity in advanced MD was 55%. Detection of extracellular NITEGE correlated positively with the grade of degeneration, as did patient age and the grade of degeneration. The patient age of those with grade 0/1 MD was significantly lower than for grade 3 (p0.0001).The thoroughly defined degeneration score (grade 1 - grade 3 MD) is suitable to assess the severity of degeneration. Extracellular NITEGE deposits can be regarded as an immunohistochemical marker for advanced (grades 2 and 3) MD.

The diagnosis of infections in patients with arthritis and/or joint prostheses requires interdisciplinary cooperation and the use of up-to-date methods. Massive bacterial infection can be identified by bacterial culture, and minimal infection can be detected by molecular pathological methods. These processes include specific enrichment of bacterial and fungal DNA, amplification, and identification of the DNA by gel electrophoresis, sequencing techniques, and chip technologies.Anamnesis (enteral or urogenital infection), the clinical picture (oligoarthritis), and further parameters (e.g., HLA B27 status) are important for the diagnosis of reactive arthritis. In many cases of reactive arthritis, molecular methods allow detection of bacterial DNA or RNA in synovial fluid or tissue. Molecular pathological methods allow the fast and reliable differential diagnosis of granulomatous synovialitis without prior cultivation of bacteria or fungi. The development of new molecular pathological methods for detecting bacterial and fungal nucleic acids will increase diagnostic accuracy.

The durability of endoprosthetic implants of the large joints has increased over the last decades. North American studies have shown a 10-year durability of 94% for prosthetic hip implants, and European studies have shown 10-year durabilities of 88-95%. Pathologists differentiate three etiological disease patterns for the"pathology of endoprosthetics" that lead to reduction of implant durability: 1) periprosthetic particle disease (aseptic loosening), 2) infection, and 3) arthrofibrosis. Four types of neosynovitis/periprosthetic membrane have been determined in a consensus classification: particle-induced type (type I), with a mean prosthesis durability (MPD) of 12 years; infectious type (type II), MPD 2.5 years; combined type (type III), MPD 4.2 years; and indeterminate type (type IV), MPD 5.5 years. There are three histopathologic degrees of arthrofibrosis; grade 1 always needs clinical information for diagnosis, whereas grades 2 and 3 are distinct histopathologic entities.

This review will suggest an algorithm for standardised histopathological diagnosis of synovial biopsies and synovectomy specimens. In principal, changes of the synovial membrane can be inflammatory or non-inflammatory. To the latter group belong some benign tumors, such as tenosynovial giant cell tumor, lipoma or synovial chondromatosis. Rare non-inflammatory changes are the group of storage diseases. Inflammatory synovial diseases can be differentiated into crystal-induced arthropathy, such as gout and pseudogout, granulomatous diseases, such as tuberculosis, sarcoidosis and foreign body reactions and into the large group of non-granulomatous synovitis. This last group is by far the most common and often causes difficulties in assigning the histopathological findings to a definite diagnosis. Therefore, the synovitis score should be applied in these cases as a diagnostic means, leading to the diagnosis of low-grade synovitis (which is associated with degenerative and posttraumatic arthropathies) or high-grade synovitis (associated with rheumatic diseases), the sensitivity and specificity being 60.5% and 95.5%, respectively. In detritus synovitis the synovitis score is not applicable.

The aseptic prosthetic loosening of hip and knee prosthesis is the most important cause of implant insufficiency. Bone loss as a result of the biological effect of wear particles is the main cause of such loosening. Wear particles develop their biological activity along different cellular pathways, above all via macrophages, foreign body giant cells as well as fibroblasts of the periprosthetic membrane. These cells induce particle-dependent bone resorption by means of proinflammatory cytokines, such as IL-1beta, TNF-alpha, IL-6 and PGE2. These factors induce the activation of osteoclasts as well as the suppression of osteoblasts. Neutrophil granulocytes and lymphocytes do not play an important role in the process of aseptic loosening. The different wear particles, such as ultra-high molecular weight polyethylene, metal particles, ceramic particles and polymethylmethacrylate can be morphologically recognized very easily. From the clinical point of view, the differentiation between acute or chronic implant infection and particle induced prosthetic loosening is very important, with the histomorphological differential diagnosis between septic and aseptic loosening and their combination being the key clinicopathological factor.

Synovectomy specimens represent important material submitted from the orthopedist to the pathologist. However, no consistent histopathological grading system for chronic synovitis has been established so far.The three compartments of chronic synovitis (enlargement of lining cell layer, density of synovial stroma cells, leukocytic infiltrate) are graded semiquantitatively (from 0=absent to 3=strong), and the points for each compartment add up to the synovitis score: 0-1 = no synovitis, 2-4 = low-grade synovitis, 5-9 = high-grade synovitis. A total of 618 synovial specimens (resections n=559, biopsies n=59) from degenerative and inflammatory joint diseases were graded by two independent observers.Median synovitis scores when correlated to clinical diagnoses were: 1, control; 2, osteoarthritis and post-traumatic arthritis; 3, psoriatic arthritis; 5, reactive and rheumatoid arthritis. The differences between rheumatic and non-rheumatic diseases were significant (p0.001). The correlation between the two observers was high (p0.001).The proposed synovitis score enables stratification of chronic synovitis into low-grade (score 2-4) and high-grade (score4), which is correlated to the nature of the disease (low-grade to non-rheumatic, high-grade to rheumatic), and it therefore contributes to the diagnosis of rheumatic and non-rheumatic joint diseases.

During recent years, sensor chip-based systems have been developed which monitor functional changes of living cells. Key elements of such cellular assays are silicon or glass chips with integrated sensors for physico-chemical parameters, i.e. pH, pO2, electric impedance and temperature. Analysis of these primary parameters yields information about cell metabolism, cell growth and adhesion, and cell morphological changes. The operation principles of individual sensor types are described together with examples of experimental results.

Popliteal artery aneurysms (PAA) are a dangerous complication of general atherosclerosis or other diseases. PAAs with a diameter of less than 2 cm are observed despite the fact that small aneurysms may also result in peripheral embolism. The spectrum of complications in the course of the disease ranges from multiple embolism into the crural arteries or complete thrombosis of the popliteal artery associated with complete ischaemia. Rupture is rare even in large aneurysms. Interventional therapy using covered stents does not lead to results comparable with surgery and is not considered as standard therapy. Surgical technique in asymptomatic aneurysms includes resection/exclusion of the PAA with reversed vein PI-PIII vein bypass. In case of acute ischaemia the therapy has to be modified according to anatomic aspects and has to be combined in some cases with intraoperative lysis. Amputation rate may be as high as 40%. Large aneurysms (3 cm) should be treated by aneurysmorrhaphy or resection with graft interposition rather than simple bypass. In our study with short follow-up only 3 of 10 patients were asymptomatic. Survival rate, limb salvage and patency amounted to 100%.

Myospherulosis is a chronic-inflammatory lesion that is most commonly iatrogenic of origin and occurs in tissues exposed to petrolatum-based products. The disease does not exhibit characteristic symptoms and is therefore not diagnosed in some instances. In previous otorhinolaryngological studies, myospherulosis was mainly found in paranasal sinuses, while only four otitic cases have been reported.A 48-year-old female Egyptian patient suffered from bilateral chronic otitis media that had been treated in Egypt by tympanoplasty. The patient presented few months later at the university ENT department (Mainz) with deteriorated otorrhea and otalgia. Clinical, otoscopical, and radiological examination led to the diagnosis of cholesteatoma. During revision surgery of the right side, ointment-like material was found, which was embedded in granulation tissue. Middle ear biopsies were taken from both sides and routinely processed for standard histological examination and transmission electron microscopy.Histological examination of the right middle ear biopsy showed cystic tissue spaces lined by histiocytes and foreign-body giant cells in a fibrous stroma. In the tissue spaces, scattered debris and sac-like structures containing round spherules of aggregated erythrocytes were found. In addition, erosion of adjacent bone matrix was seen. Diagnosis of myospherulosis was made. By contrast, histological evaluation of the left middle ear biopsy revealed cholesterol granuloma.Myospherulosis of the middle ear has been hitherto diagnosed in a very few otitic cases, but might be overlooked as it mimicks other chronic proliferative and inflammatory lesions such as cholesteatoma in the present case. Thus myospherulosis should be considered in otitic cases with a suspicious history (exposure to petrolatum-based products). Furthermore, patients with myospherulosis have a significantly higher likelihood of developing postoperative complications. Since the lesion exhibits distinct histological findings, microscopy plays a central role for the diagnosis of this important disease.

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

An alternative assay for replacing animal experiments should serve the specific microphysiological needs of the cells and be endowed with multiparametric signal monitoring. These requirements are provided by a test system in which the key elements are biocompatible electronic sensor-chips. It is also connected to a medium perfusion set-up, which allows to control the supply of nutrients and test compounds, and the removal of culture medium. The chips are equipped with sensors that continuously monitor basic metabolic parameters and membrane-associated changes of living cells: pH-ISFETs for extracellular acidification, amperometric O2-sensors for oxygen consumption, and IDES for electrical impedance of the cell layer. Experiments with LS174T colon carcinoma cells in culture show the metabolic and electrical changes upon incubation with Zytochalasin B and chloroacetaldehyde. The signal patterns vary and indicate different mechanisms of action for these test compounds. With this test system it is possible to detect effects of unknown substances and mixtures, and to analyse the cellular probe for prolonged times.

Lupus nephritis is a common phenomenon in Systemic Lupus Erythematosus (SLE). We analyzed a renal biopsy of a 30-year-old woman with SLE. The clinical history showed a typical SLE with generalized symptoms without demonstrable lupus coagulant, positive for anti-nuclear antibodies and anti-ds-DNA antibodies but negative for rheumatoid factor, cryoglobulins and antiphospholipid antibodies. A paraproteinemia for IgA, IgG and IgM was not detectable. Using light, electron and immunoelectron microscopy electron-dense deposits were noted in subepithelial, subendothelial and mesangial position. Most remarkably, the electron-dense deposits and mesangial areas in the vicinity of deposits contained an electron-dense crystalline material. The crystalline structures were composed of IgG and kappa light chains, while they were negative for IgM, IgA and lambda light chains, as demonstrated by immunoelectron microscopy. As far as we know, this is the first case of lupus nephritis with crystalline structures. Since we could not detect cryoglobulinemia or paraproteinemia, other mechanisms possibly favor organization of macromolecular structures.

A 26-year-old female patient was admitted to the hospital because of fever of unknown origin and renal failure. Diagnosis of Fabry's disease, extracapillary proliferative (crescentic) glomerulonephritis and granulomatous interstitial nephritis was made by histological, immunohistochemical and electron microscopical diagnosis in a kidney biopsy and confirmed by further investigations. Years ago the brother of the patient had a kidney biopsy diagnosed as metabolic disease. The re-evaluation of this biopsy confirmed Fabry's disease while in this patient an association with tubulointerstitial nephritis occurred. To our knowledge this is the first family with two members having Fabry's disease combined with further kidney diseases.

The botryoid odontogenic cyst (BOC) is considered a rare multilocular variant of the lateral periodontal cyst. The origin of the BOC can be seen in aberrant odontogenic tissue. The BOC is found especially in the premolar region of the mandible, as well as in the frontal region of the maxilla of patients aged between 60 and 70 years. Most of the 11 published articles of BOC have shown high rates of recurrence. Histopathologically the BOC is marked by multilocular cysts lined by a thin, nonkeratinized epithelium. Clusters of glycogen-rich epithelial cells may be noted in nodular thickenings of the cyst lining. For the clinician, the differentiation of the BOC from the keratocyst and ameloblastoma is relevant. One case of a large BOC (65-year-old male, BOC regio 33-45, diameter 5 cm, radiographically and histologically multilocular) is presented with a review of the literature, including the therapeutic management, and the possible diagnostic criteria are discussed. The immunohistochemically determined expression of cytokeratin (CK) 13 implicates the histogenetic origin of the BOC from the squamous epithelium of the oral cavity and excludes the origin from the small salivary glands. The expression of CK 19 and the lack of expression of p53, as well as the higher proliferation rate of the basal epithelial cell layer by the BOC, may be useful for distinction between the keratocyst.

From May 1993 to September 1997 we treated 22 patients with complications after laparoscopic surgery. We report on 18 patients after laparoscopic cholecystectomy, three patients after diagnostic laparoscopy and one after TAPP. Two patients died (hepatic failure and without any possibility of definitive therapy) and the injuries of the other 20 patients were repaired.

Continuous ambulatory peritoneal dialysis (CAPD) has become an established procedure and is an equal alternative to haemodialysis (HD) in the management of terminal renal failure. Nevertheless CAPD still plays a minor role compared with HD (10% of all dialyses). CAPD offers advantages in quality of live but is still associated with a significant number of complications. The improvement of surgical technique and development of new peritoneal dialysis catheters (PDK) improved the results of peritoneal dialysis. 3 methods for implantation of PDK are used: the open surgical technique, the blind percutaneous procedure and the laparoscopic method. The latter technique is currently an accepted practice. 10 patients were treated by the laparoscopic method. Additionally to the PDK-tunnel of the abdominal wall we used 2 trocars (1 x 5 mm, 1 x 12 mm). Advantages of this technique are avoiding of perforating lesions, possibility for further operations and a safe implantation of the PDK. Peritoneal dialysis was started 7 days after operation with initially low dialysate volumes. The observed incidence of complications and removed catheters are comparable to the reports in the literature.

Decisions or statements about the health effects of "pollutants" are often based on not exactly known exposure conditions and/or doubtful cause-effect relationships. Even searches in international databases will not always give adequate answers or produce new problems for the specialist in environmental medicine because the information may be contradictory or leave a wide scope for interpretation, perhaps requiring detailed specialized knowledge (e.g. mutagenicity testing, immunotoxicological parameters etc.). In situations like these, inter-disciplinary working is the mandatory condition. Therefore electronic communication systems might be used to resolve problems, because they provide access to well-presented knowledge of competent colleagues. However, the fundamental concept of such mailbox system for environmental medicine requires active participation by all its users who should contribute to its files and not remain passive, i.e. only call for information.

The ultrasonically activated scalpel works by means of the longitudinally vibrating sharp blade. The most important advantages- compared with electrosurgery-are the lack of current flow through the patient and limited local heat generation. It can be used as an instrument for coagulation, dissection and preparation. There is no generation of smoke. It is easy to use. Disadvantages are the slow speed of cutting and the high costs. In the future it could be an alternative to preparation on with dissector, scissors, and electrosurgery.

In two camps in Ibbenbüren occupied by refugees from Balkan countries we found in 121 inhabitants, among them 56 children, high mercury concentrations in urine and blood. The median of the urinary concentrations was 12 micrograms/l (range: 0.15-770 micrograms/l) or 11.4 micrograms/g creatinin (range: 0.2-446 micrograms/g). 12 adults and 15 children had values above 50 micrograms/l. As source, a mercury-containing bleaching ointment, sold by foreign vendors, was identified. Mercury concentrations in several samples of this ointment ranged from 708 to 17,200 micrograms/g. Similar exposure to mercury may occur elsewhere. Hence, chronic mercury poisoning should by taken into differential diagnostic consideration.

Injuries of the subclavian artery are rare; still rarer are aneurysms of the subclavian artery due to blunt or penetrating trauma. Diagnosis can be performed by careful clinical investigation. To identify precisely the nature and site of the injury, angiography and CT are necessary. Rarely associated injuries, such as arteriovenous fistulas, can be recognized by means of these diagnostic tools. This will be of value for planning the surgical approach, which varies with the anatomical site of the injury and the kind of accompanying damage. Subclavian aneurysms should be treated surgically, because embolic or thrombotic complications may threaten the extremity and the brain.

The symptom "craniotabes" means rickets only in few cases. Determinations of calcium, alkaline phosphatase, phosphorus and if possible 25-OH-vitamin D are necessary for confirmation of the rickets-diagnosis. As denotation for the not rickets-caused forms of craniotabes the definition positioning caused craniotabes is suggested.

Of 28 newborns with prolonged jaundice and lowered or subnormal values of alpha-1-antitrypsin in the serum six patients were found to have a Pi-type MZ, three a Pi-type MS and one patient a Pi-type MP. One of the newborns had Pi-type SZ (double heterozygous), one infant was a homozygous carrier of the Pi-type S. It seems to the possible that one of the reasons for the not yet explained cases of prolonged jaundice of the newborns period can be found in the high frequency of homozygous or heterozygous genotype carriers of Pi-system.

A child aged 4 years was stung by more than 250 wasps. There was no anaphylactic shock. There rather were increasingly heavy ictero-hemorrhagic symptoms with simultaneous insufficient kidney function. On the second day of the disease disorders of the CNS started, as well as circulation insufficiency and disorder of the heart function. According to the signs there was no intravasal coagulation or hemolysis. Heavy doses of corticoids were successless, just as a peritoneal dialysis starting on the 3rd day of the disease. The child died 5 and 1/2 day after the wasps' attack. The pathophysiology and the possible therapeutic consequences of the case as well as rapid protective actions in such a case of insect attack are being discussed.

The syndrome of septo-optic dysplasia with congenital hypopituitarism consists of optic nerve hypoplasia, midline malformations of the prosencephalon and hypothalamic hypopituitarism. There is great variability of these features and clinical manifestation is age-dependent: Newborns present with hypoglycemic seizures, apnea, cyanosis, hypotonia, prolonged jaundice (and micropenis in boys) because of growth hormone and/or ACTH-deficiencies. Wandering eye movements and more or less visual disturbance become evident during infancy and growth retardation even later in some cases. Early recognition is facilitated by the pathognomonic fundoscopic findings, together with normal electroretinogram, absent visually evoked potentials and computer tomography. Early hormone substitution is essential to prevent hypoglycemic damage.

Of 104 patients treated in a psychiatric hospital because of mental disturbances caused by an infection, almost one-half had been referred directly to the psychiatric hospital on account of their psychically abnormal behaviour. The infectious disease causing these disturbances was diagnosed only after their admission. In most of the cases the psychic abnormalities did not seem to be due to a physical cause, so that the somatic examination was frequently delayed. Pneumonic infections were most frequently seen, but there were also numerous other infections from all other disciplines of medicine. Clouding of consciousness developed rapidly in 84% of the patients during the course of inpatient treatment with an incidence that was almost fivefold that of the initial stage. Visual hallucinations (37%) were the most frequent productive-psychotic phenomenon. 45% of the patients presented with a delirious pattern and 4% with a psychosis resembling schizophrenia. In 35% of the patients treatment with psychotropic drugs proved necessary, whereas with the remaining 65% therapy remained antibiotic or generally somatic only. 18% of the patients died.