Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice.

BACKGROUND: How microbial infections exacerbate immune complex glomerulonephritis remains speculative. Toll-like receptors (TLRs) may be involved in this phenomenon, because TLRs have potent immunostimulatory functions when exposed to selected pathogen-associated molecules. METHODS: We addressed this issue by characterizing the expression of TLR1-9 in MRLlpr/lpr mice that spontaneously develop immune complex glomerulonephritis as part of a systemic lupus-like autoimmune syndrome. RESULTS: Five-week-old healthy MRLlpr/lpr mice expressed TLR3 mRNA in kidneys at comparable levels as in the spleen, while all other TLRs were expressed at low levels in the kidney. In 20-week-old nephritic MRLlpr/lpr mice, renal mRNA levels had increased for TLR1-9. Renal TLR mRNA originated at least in part from glomeruli as evidenced by real-time RT-PCR from laser capture microdissected glomeruli. Immunostaining for TLR3, TLR7 and TLR9 revealed their expression by F4/80-positive infiltrating macrophages in 20-week-old nephritic MRLlpr/lpr mice. In addition, TLR3 localized to glomerular mesangial cells. Cultured mesangial cells expressed TLR1-4 and TLR6, while murine macrophages expressed TLR1-9. TNF-alpha and IFN-gamma induced TLR2, TLR3 and TLR6 mRNA in mesangial cells, while they down-regulated TLR1-9 mRNA in macrophages. Stimulation of both cell types with ligands for TLR1-4, TLR5, TLR7 and TLR9 induced IL-6 production consistent with their respective TLR expression patterns. TNF-alpha and IFN-gamma enhanced ligand-induced IL-6 production in both cell types irrespective of their modulatory effect on respective TLR mRNA levels. CONCLUSION: Thus, cell-type-specific expression and regulation of TLRs may be involved in infection-associated exacerbation of immune complex glomerulonephritis of MRLlpr/lpr mice.     

Neurofibromatose Typ 1 (NF1) im Kindes- und Jugendalter Merkmalsauspr?gung, Diagnostik- und Therapieoptionen

Hintergrund  

Die Neurofibromatose Typ 1 (NF1) ist eine häufige autosomal-dominant erbliche neuroektodermale Erkrankung. Die Diagnose wird nach den NIH-Konsensus-Kriterien von 1987 gestellt. Bei Kindern gestaltet sie sich schwierig, da sich einzelne Merkmale erst entwickeln.     

Extrakranielles Meningeom in der Glandula parotis

Zusammenfassung Extrakranielle Meningeome der Kopf-Hals-Region sind ?u?erst selten. Neben Meningeomen prim?r extrakraniellen Ursprungs sind in der Literatur sekund?r extrakranielle Meningeome beschrieben. In der Pathogenese sekund?r extrakranieller Meningeome werden Traumen, Strahlenfolgen und in seltenen F?llen auch eine Metastasierung diskutiert. Wir berichten über den Fall eines 53j?hrigen Patienten, bei dem ein Tumor aus der linken Glandula parotis exstirpiert wurde. In der Vorgeschichte erfolgten insgesamt sechs neurochirurgische Eingriffe wegen eines rezidivierenden intrakraniellen Meningeoms. Bei der histologischen Aufarbeitung des Operationspr?parates wurde die Diagnose eines atypischen meningotheliomat?sen Meningeoms gestellt. Der Patient ist bis zum jetzigen Zeitpunkt, 17 Monate nach der Operation, rezidivfrei.      

Effect of constrained posterior screw and rod systems for primary stability: Biomechanical in vitro comparison of various instrumentations in a single-level corpectomy model

Cervical corpectomy is a frequently used technique for a wide variety of spinal disorders. The most commonly used approach is anterior, either with or without plating. The results for single-level corpectomy are better than in multilevel procedures. Nevertheless, hardware- or graft-related complications are observed. In the past, constrained implant systems were developed and showed encouraging stability, especially for posterior screw and rod systems in the lumbar spine. In the cervical spine, few reports about the primary stability of constrained systems exist. Therefore, in the present study we evaluated the primary stability of posterior screw and rod systems, constrained and non-constrained, in comparison with anterior plating and circumferential instrumentations in a non-destructive set-up, by loading six human cadaver cervical spines with pure moments in a spine tester. Range of motion and neutral zone were measured for lateral bending, flexion/extension and axial rotation. The testing sequence consisted of: (1) stable testing; (2) testing after destabilization and cage insertion; (3a) additional non-constrained screw and rod system with lateral mass screws, (3b) with pedicle screws instead of lateral mass screws; (4a) constrained screw and rod system with lateral mass screws, (4b) with pedicle screws instead of lateral mass screws; (5) 360°set-up; (6) anterior plate. The stability of the anterior plate was comparable to that of the non-constrained system, except for lateral bending. The primary stability of the non-constrained system could be enhanced by the use of pedicle screws, in contrast to the constrained system, for which a higher primary stability was still found in axial rotation and flexion/extension. For the constrained system, the achievable higher stability could obviate the need to use pedicle screws in low instabilities. Another benefit could be fewer hardware-related complications, higher fusion rate, larger range of instabilities to be treated by one implant system, less restrictive postoperative treatment and possibly better clinical outcome. From a biomechanical standpoint, in regard to primary stability the constrained systems, therefore, seem to be beneficial. Whether this leads to differences in clinical outcome has to be evaluated in clinical trials.     

Prim?res Synovialsarkom der Lunge

Bei einem 54j?hrigen Mann mit r?ntgenologisch auffallendem Lungentumor lag im Biopsiematerial aus einer polyp?sen intrabronchialen L?sion das Bild einer spindelzelligen Neoplasie vor. Eine klare histogenetische Einordnung des Tumorprozesses war an dem submuk?s sichtbaren Tumorgewebe nicht m?glich. Nach Resektion des rechten Lungenoberlappens konnte unter Berücksichtigung der immunhistochemischen Zusatzuntersuchungen die Einordnung des Tumors als ein biphasisches Synovialsarkom erfolgen. Hierfür war der fokale immunhistochemische Nachweis des epithelialen Membranantigens (EMA) neben einem Vimentinnachweis wegweisend. Ein extrapulmonal gelegener Prim?rtumor konnte durch umfangreiche klinische Untersuchungen ausgeschlossen werden. Der vorliegende Fall verdeutlicht die Schwierigkeit zur korrekten Einordnung der Histogenese bzw. Differenzierungsrichtung beim Bild des seltenen prim?ren pulmonalen Synovialsarkoms. Insbesondere in einer kleinen Biopsieprobe mit dem Bild eines überwiegend spindelzelligen, submuk?s entwickelten Tumors der Lunge ist neben der Differentialdiagnose h?ufigerer Metastasen von Sarkomen auch ein prim?res Synovialsarkom der Lunge zu berücksichtigen.     

Peak inspiratory flow rates generated through the Novolizer and the Turbuhaler dry powder inhaler devices by children with stable asthma.

We compared the peak inspiratory flows (PIF) generated through a novel dry powder inhaler device, the Novolizer (PIF-N), and the Turbuhaler (PIF-T). Forty-six pediatric patients with stable bronchial asthma were randomized in an open-label, multicenter, crossover trial. No drug was administered during the inhalation maneuvers that were spaced by 10 min. There was neither a carryover nor a sequence effect. The patients were characterized by mean age of 8.5 years, mean FEV(1) of 1.79 L, and mean PIF without any device (baseline, PIF-B) of 185 L/min. Through the devices mean PIF-N of 94 L/min and mean PIF-T of 69 L/min were achieved, calculated from the maxima of three inhalations. This resulted in p < 0.0001 for the difference. The median PIFN/PIF-T ratio was estimated as 1.39. Each child achieved a higher PIF-N than PIF-T and was able to release the feedback mechanisms of the Novolizer indicating sufficient inhalation performance. We conclude that the PIF through the Novolizer is higher than the PIF through the Turbuhaler in stable asthmatic children. The flow rates achieved through the Novolizer allow for sufficient lung deposition even in children as young as 6 years.     

Outcome of Trochanteric Femoral Fracture Treatment with Gamma Nail Procedure is Independent of Bone Density

Trochanteric femoral fractures are frequently associated with severe osteoporosis in elderly patients. The failure of devices intended to repair trochanteric fractures, such as the gamma locking nail (GLN), might be related to reduced bone desity. Osteoporosis may also influence pain and walking ability because of low stability in the fracture area. In 74 patients (mean age 76 - 16.5 years), the stability and clinical outcome following treatment with GLN were prospectively evaluated and recorded after 9 (n = 43) and 24 months (n = 34). Vertebral bone mineral density (BMD) was measured via quantitative computed tomography (QCT) at time of operation. Mechanical failure of GLN was recorded by radiographs of the hip. Assessment of outcome included the Harris Hip Score. Regression analysis was done to show the influence of age and BMD on clinical outcome. 9 months after treatment, complete fracture healing without dislocation of the lag screw of the GLN was observed even in patients with low BMD (< 55 mg/cm³ trabecular BMD). Clinical outcome assessed by the Harris Hip Score was independent of BMD at both follow-ups. At the first follow-up, outcome depended on the patient's age, with younger patients (< 70 years) showing better results than elderly patients. The stability of fracture also seemed to influence the outcome. Our results indicate that stabilization of unstable osteoporotic fractures with GLN is associated with few complications and can be accomplished with identical clinical and radiologic results seen in patients with high BMD. The critical factor influencing outcome is patient's age, stability of fracture and not BMD.     

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung.

The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers. In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity x Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P=0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P=0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P=0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P=0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.