视网膜母细胞瘤眼球的病理取材方法

目的：探讨视网膜母细胞瘤病理标本的不同取材方法对脉络膜浸润检出率的影响，寻求理想的常规取材方法。方法：复查297只原发摘除的视网膜母细胞瘤眼球的病理切片，比较五平面取材法（151只眼）和单平面取材法（146只眼）对脉络膜浸润的检出率。结果：五平面取材法对脉络膜浸润的检出率（31％）明显高于单平面取材法（17％），且主要是对玻璃膜在肿瘤细胞影响下发生变化的检出率高。脉络浸润的各期都主要分布在五平面取材法的各平面上。结论：五平面取材法能提供判断视网膜母细胞瘤患者预后的较大量病理信息，在日常医疗工作中从人力、物力、财力上能够承受，可作为常规取材方法应用于临床。连续切片取材只作为在特殊情况下对五平面取材法的补充。单平面取材法有可能丢失一些重要的病理信息而应由五平面取材法代替。     

Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus

The effects of 5-week doxycycline treatment on the depletion of Wolbachia endobacteria from Onchocerca volvulus, on the interruption of embryogenesis and on microfilariae production, and with regard to macrofilaricidal activity were studied. In 2003, in an endemic area in Ghana, 22 onchocerciasis patients received 100 mg/day doxycycline for 5 weeks. Two years after the start of the study, 20 treated and ten untreated patients were nodulectomized and skin microfilariae were counted. The onchocercomas were examined by immunohistology for the presence of Wolbachia, embryogenesis, and vitality of adult filariae. The latter two parameters were further assessed by alternating logistic regression analysis, taking into account the dependency of worms and nodules in patients. Doxycycline resulted in depletion of Wolbachia and in complete interruption of embryogenesis in all worms that were assumed to have been present during treatment. In the treated patients, only 51% of the female worms were alive, compared to 84% in the untreated patients, indicating a moderate but distinct macrofilaricidal activity of doxycycline at this dose. It is concluded that, in areas with ongoing transmission, doxycycline cannot replace regular ivermectin mass treatment because new infections would require repeated rounds of doxycycline. However, doxycycline can be used for the treatment of individuals outside transmission areas, in foci where ivermectin resistance may occur, and in countries where onchocerciasis and loiasis are co-endemic.     

Biometrical analysis of the shoulder joint regarding glenoid implant dimensions for arthroplasty

Purpose

Reduced bone stock and difficult intraoperative orientation are challenges in glenoid replacement surgery. New implant designs and methods for fixation, such as locking screws, extra-long central pegs and/or central compression screws are targeting these issues. The objective of this study is the analysis of the glenoid dimension regarding maximum central peg diameter and peg length (PL), and maximum screw length (SL) for glenoid fixation.

Methods

Retrospective analysis of magnetic resonance imaging (n = 50) scans. Measurement of the maximum inferior glenoid diameter (GD), SL, maximum length of a 9.9, 10 and 11.4 mm central peg (PL) in the transverse plane; glenoid version (GV), humeral head diameter (HHD). Two independent measurements.

Results

Mean age: 49.0 ± 15.7 years (17–80) (n = 20 female, 49.6 ± 16.0; n = 30 male, 48.6 ± 15.7). Mean values of measurement were GD: 28.9 ± 3.7 mm (21–39); SL: 34.1 ± 4.9 mm (26–44); PL 9.9 mm: 19.4 ± 4.3 mm (9–30); PL 10 mm: 19.0 ± 4.4 mm (8–30); PL 11.4 mm: 16.5 ± 4.1 mm (7–26) with significant gender differences (p = 0.001; p = 0.022; p = 0.001); GV: ?0.6° ± 4.9° (?10 to 11); HHD: 50.0 mm ± 4.9 (41–61). There was good correlation between PL and SL (r = 0.32, p = 0.024) and for GD and PL (r = 0.61, p = 0.001; r = 0.57, p = 0.001; r = 0.96, p = 0.001). The ratio of HHD and GD was very constant with 0.6 ± 0.07.

Conclusions

These data indicate the high interindividual variability of glenoid morphology including significant gender-related differences. The good correlation between humeral head size and GD and maximum central PL can be helpful for cases with reduced bone stock in decision-making about implant size and bone grafting.     

PLAG1 immunohistochemistry is a sensitive marker for pleomorphic adenoma: a comparative study with PLAG1 genetic abnormalities

Aims

Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex‐PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex‐PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in‐situ hybridisation (FISH).

Methods and results

PLAG1 immunostaining was performed on 83 salivary gland tumours, including 23 PA, 15 CA ex‐PA and 45 other salivary gland tumours. In addition, PLAG1 FISH was performed in 44 cases for the presence of gene rearrangements/amplifications. The results showed high sensitivity of PLAG1 IHC in 96% of PA; however, discordant results between PLAG1 FISH abnormalities and IHC were noted in 15 of 44 cases (34%). Seven PA, four de‐novo myoepithelial carcinomas and one basal cell adenocarcinoma had negative FISH results, but were positive for IHC; while three salivary duct carcinomas (SDC) ex‐PA were positive for FISH but negative for IHC. PLAG1 IHC can differentiate CA ex‐PA from de‐novo SDC (P = 0.02), but not from de‐novo myoepithelial carcinoma. PLAG1 IHC is a sensitive marker for PA. This could be due to PLAG1 gene abnormalities beyond FISH resolution.

Conclusions

A negative PLAG1 IHC might be helpful in excluding a PA diagnosis. Interestingly, in the context of CA ex‐PA, FISH is more sensitive than IHC in detecting PLAG1 abnormalities.     

Cellular‐FLIP,Raji isoform (c‐FLIPR) modulates cell death induction upon T‐cell activation and infection

Dysregulation of apoptosis caused by an imbalance of pro‐ and anti‐apoptotic protein expression can lead to cancer, neurodegenerative, and autoimmune diseases. Cellular‐FLIP (c‐FLIP) proteins inhibit apoptosis directly at the death‐inducing signaling complex of death receptors, such as CD95, and have been linked to apoptosis regulation during immune responses. While the isoforms c‐FLIP_L and c‐FLIP_S are well characterized, the function of c‐FLIP_R remains poorly understood. Here, we demonstrate the induction of endogenous murine c‐FLIP_R in activated lymphocytes for the first time. To analyze c‐FLIP_R function in vivo, we generated transgenic mice expressing murine c‐FLIP_R specifically in hematopoietic cells. As expected, lymphocytes from c‐FLIP_R transgenic mice were protected against CD95‐induced apoptosis in vitro. In the steady state, transgenic mice had normal cell numbers and unaltered frequencies of B cells and T‐cell subsets in lymphoid organs. However, when challenged with Listeria monocytogenes, c‐FLIP_R transgenic mice showed less liver necrosis and better bacterial clearance compared with infected wild‐type mice. We conclude that c‐FLIP_R expression in hematopoietic cells supports an efficient immune response against bacterial infections.     

Empfehlungen zu Ernährung und Bewegung von Kleinkindern

Monatsschrift Kinderheilkunde -     

Isolated polyarteritis nodosa of the male reproductive system associated with a germ cell tumor of the testis: a case report

Polyarteritis nodosa (PAN) presents mostly as a systemic disease with poor prognosis, rarely in an isolated form with a usually favorable outcome. Both forms may affect the male reproductive system and both forms have been associated with malignancies. We describe for the first time the occurrence of isolated PAN in the reproductive system combined with a mixed germ cell tumor of the testis in a 21-year-old man presenting with symptoms of chronic epididymitis. Two years after surgery he is without evidence of recurrence of either the tumor or PAN.     

Involvement of Toll-like receptor 4 in the embryogenesis of the rodent filaria <Emphasis Type="Italic">Litomosoides sigmodontis</Emphasis>

To examine the role that lipopolysaccharide (LPS)-like molecules from the filarial intracellular endobacteria Wolbachia might play in the development of filarial infections, a natural infection in the LPS-nonresponsive C3H/HeJ mouse strain was compared to that of the LPS-responsive C3H/HeN mouse strain. C3H/HeN mice have been shown to be susceptible to the rodent filarial nematode Litomosoides sigmodontis, with the development of adult worms including females containing mature microfilariae (first stage larvae) in the uterine tubes. However, free microfilariae are not detected. In this study the worm burden and worm length were not significantly different between the C3H/HeN and C3H/HeJ mice. However, the fertility of worms from CeH/HeJ mice was found to be higher than those from C3H/HeN mice. Significantly, mature microfilariae were found at the site of infection only in C3H/HeJ mice. These results indicate a role for TLR4 signaling in the immune response that inhibits worm embryogenesis and prevents the release of microfilariae or directly kills released microfilariae.     

Transcriptional oscillation of lunatic fringe is essential for somitogenesis

A molecular oscillator that controls the expression of cyclic genes such as lunatic fringe (Lfng) in the presomitic mesoderm has been shown to be coupled with somite formation in vertebrate embryos. To address the functional significance of oscillating Lfng expression, we have generated transgenic mice expressing Lfng constitutively in the presomitic mesoderm in addition to the intrinsic cyclic Lfng activity. These transgenic lines displayed defects of somite patterning and vertebral organization that were very similar to those of Lfng null mutants. Furthermore, constitutive expression of exogenous Lfng did not compensate for the complete loss of cyclic endogenous Lfng activity. Noncyclic exogenous Lfng expression did not abolish cyclic expression of endogenous Lfng in the posterior presomitic mesoderm (psm) but affected its expression pattern in the anterior psm. Similarly, dynamic expression of Hes7 was not abolished but abnormal expression patterns were obtained. Our data are consistent with a model in which alternations of Lfng activity between ON and OFF states in the presomitic mesoderm prior to somite segmentation are critical for proper somite patterning, and suggest that Notch signaling might not be the only determinant of cyclic gene expression in the presomitic mesoderm of mouse embryos.