Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

Malignant peripheral nerve sheath tumour of the cervical vagus nerve in a neurofibromatosis type 1 patient.

One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear.     

Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

三维骨建模在全膝关节置换术中韧带平衡的作用

目的探讨以三维骨建模为基础、无需影像的计算机辅助系统在人工全膝关节置换术(totalknee arthroplasty,TKA)中韧带平衡的作用。方法2002年11月～2003年6月,采用后稳定型人工全膝关节,在Ceravision无需影像资料的三维骨建模系统导航监控下,辅助完成TKA21例。男5例,女16例,年龄64～79岁,平均72.4岁。其中2例既往行胫骨近端截骨术,1例行股骨远端截骨术。14例膝内翻,7例膝外翻。术前下肢全长X线正位片测量,内翻13°～外翻13°,平均2.36°;膝关节X线正位片测量,应力下内翻平均8.47°(内翻2°～内翻20°),应力下外翻平均3.63°(内翻7°～外翻12°)。结果术中导航系统测量,额面内翻12°～外翻10°,平均3.33°,与术前比较差异有统计学意义(P<0.05);额面应力下内翻平均6.47°(内翻0°～内翻24°),应力下外翻平均4.32°(内翻8°～外翻15°),与术前比较差异有统计学意义(P<0.05)。术毕导航系统测得膝内外翻平均0.175°(内翻2°～外翻3°),而术后下肢全长X线正位片测量平均0.3°(内翻3.5°～外翻1.5°),二者差异无统计学意义(P>0.05)。术后3个月关节活动度为105～130°,平均115°,膝关节额面松弛度0.2～0.5cm,平均0.27cm。人工膝关节胫、股骨假体取得满意的对位置入和韧带平衡,无关节失稳和髌骨脱位等并发症发生。结论以三维骨建模为基础、无需影像的Ceravision系统,具有三维立体定位、优化截骨,并通过旋转对位和韧带松解获得伸屈膝关节等距间隙与韧带平衡稳定的作用,近期临床疗效满意,可在TKA中常规使用。     

Is atrial fibrillation an inflammatory disorder?

I read with great interest the excellent review on the influenceof inflammation in the pathogenesis of atrial fibrillation (AF)by Boos