The Matrilin-3 T298M mutation predisposes for post-traumatic osteoarthritis in a knock-in mouse model.

OBJECTIVE: The human matrilin-3 T303M (in mouse T298M) mutation has been proposed to predispose for osteoarthritis, but due to the lack of an appropriate animal model this hypothesis could not be tested. This study was carried out to identify pathogenic mechanisms in a transgenic mouse line by which the mutation might contribute to disease development. METHODS: A mouse line carrying the T298M point mutation in the Matn3 locus was generated and features of skeletal development in ageing animals were characterized by immunohistology, micro computed tomography, transmission electron microscopy and atomic force microscopy. The effect of transgenic matrilin-3 was also studied after surgically induced osteoarthritis. RESULTS: The matrilin-3 T298M mutation influences endochondral ossification and leads to larger cartilage collagen fibril diameters. This in turn leads to an increased compressive stiffness of the articular cartilage, which, upon challenge, aggravates osteoarthritis development. CONCLUSIONS: The mouse matrilin-3 T298M mutation causes a predisposition for post-traumatic osteoarthritis and the corresponding knock-in mouse line therefore represents a valid model for investigating the pathogenic mechanisms involved in osteoarthritis development.

Diagnosis and treatment of malignant eyelid tumors.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

[Diagnosis and treatment of malignant eyelid tumors]. / Diagnose und Therapie der malignen Lidtumoren.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

In Vitro Evaluation of Intra-Aneurysmal, Flow-Diverter-Induced Thrombus Formation: A Feasibility Study.

BACKGROUND AND PURPOSE: Intracranial aneurysm treatment by flow diverters aims at triggering intra-aneurysmal thrombosis. By combining in vitro blood experiments with particle imaging velocimetry measurements, we investigated the time-resolved thrombus formation triggered by flow diverters. MATERIALS AND METHODS: Two test setups were built, 1 for particle imaging velocimetry and 1 for blood experiments, both generating the same pulsatile flow and including a silicone aneurysm model. Tests without flow diverters and with 2 different flow-diverter sizes (diameter: 4.5 and 4.0 mm) were performed. In the blood experiments, the intra-aneurysmal flow was monitored by using Doppler sonography. The experiments were stopped at 3 different changes of the spatial extent of the signal. RESULTS: No thrombus was detected in the aneurysm model without the flow diverter. Otherwise, thrombi were observed in all aneurysm models with flow diverters. The thrombi grew from the proximal side of the aneurysm neck with fibrin threads connected to the flow diverter and extending across the aneurysm. The thrombus resulting from the 4.0-mm flow diverter grew along the aneurysm wall as a solid and organized thrombus, which correlates with the slower velocities near the wall detected by particle imaging velocimetry. The thrombus that evolved by using the 4.5-mm flow diverter showed no identifiable growing direction. The entire thrombus presumably resulted from stagnation of blood and correlates with the central vortex detected by particle imaging velocimetry. CONCLUSIONS: We showed the feasibility of in vitro investigation of time-resolved thrombus formation in the presence of flow diverters.

Urinary pharmacokinetics of cyanidin glycosides in healthy young men following consumption of elderberry juice.

We investigated the urinary pharmacokinetics of monomeric anthocyanins in seven healthy volunteers. The volunteers were administered a single oral dose of 3.57 g total anthocyanins contained in 150 ml of a concentrated elderberry juice under fasting conditions. Within 24 h the urinary excretion of unchanged cyanidin-3,5-diglucoside (cyanidin-3-sambubioside-5-glucoside and cyanidin-3,5-diglucoside were calculated as cyanidin-3,5-diglucoside equivalents), cyanidin-3-glucoside, cyanidin-3-sambubioside and total anthocyanins (i.e., the sum of all quantifiable anthocyanidin glycosides) was 0.16, 0.06, 0.05 and 0.06% of the administered doses, respectively. Maximum excretion rates were determined within 1.0 h after intake. The estimates (arithmetic mean +/- SD) of t1/2 were 1.25 +/- 0.25, 1.53 +/- 0.36, 1.38 +/- 0.20 and 1.35 +/- 0.18 h for cyanidin-3,5-diglucoside, cyanidin-3-glucoside, cyanidin-3-sambubioside and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and the decline of excretion rates appeared to be monophasic, suggesting a one-compartment pharmacokinetic model. The low urinary excretion of dietary anthocyanidin glycosides with values below 1% indicates that a large proportion of these plant pigments consumed are metabolized before entry into the circulation.

Extracellular deoxyribonuclease production by anaerobic bacteria.

The production of extracellular deoxyribonuclease was examined with anaerobic organisms isolated from clinical specimens. Nuclease activity was extraordinarily common. All strains of Fusobacterium, including eight species, as well as Bacteroides fragilis and B. melaninogenicus, displayed enzyme activity. Whereas the gram-positive bacteria were generally less productive, all strains of Clostridium perfringens, Peptostreptococcus intermedius, and P. anaerobius specifically produced deoxyribonuclease. The test is taxonomically valuable, particularly in the characterization of gram-positive cocci, since a deoxyribonuclease-producing coccus indicates P. intermedius or P. anaerobius. Additionally, possession of the enzyme may prove to be a useful correlate of the potential pathogenicity of anaerobes.

[Prevalence of varicella zoster virus in pregnant patients]. / Durchseuchung von Schwangeren mit dem Varicella-Zoster-Virus.

The prevalence of IgG antibodies to varicella-zoster (VZ) virus was estimated by indirect immunofluorescence test in a sero-epidemiological study in 295 healthy pregnant women at the age of 17 to 36 years. 93.2% were considered to be seropositive and consequently protected against varicella. No antibodies to VZ virus were detected in 6.8%. Owing to the lacking protective antibodies the occurrence of maternal varicella has to be taken into account.