Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release.

5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process.     

Isolated neuropraxy of the musculocutaneous nerve

Authors describe a case of isolated posttraumatic neuropraxy of the musculocutaneous nerve. With the presentation of this very rare case attention is called, based on literary date, to the fact that the above injury can be mixed with the distal tendon rupture of the biceps.     

A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles.

Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient.     

躯干运动和负重时对足底支撑面侧向横移的姿势控制

目的:本研究假设自主运动命令和姿势控制信号间有冲突,因此设计在附加重物和不同自主任务的同时给予足底一个模拟受滑的干扰(横移)来观察姿势变化并分析其是否受冲突命令或者力学参数的影响.方法:受试者在执行各种不同的自主任务时,随机给予足底支撑面一个左侧或右侧的横移干扰.这些不同的自主任务包括不负重静止站立、静止站立单手负重5kg、负重5kg站立并躯干静止侧屈15°、负重5kg动态地提重物和放重物5项任务.测量和分析下列参数:中心压力的侧位移(COP)、躯干和股部在冠状面上的角位移和腹内压(IAP).结果:干扰离开质量(向右)、始反应超射的幅度、达到终平衡的时间和达到平衡前COP位移的次数都增加,这种情况可以看作是为了再获得平衡的姿势反应效率降低,因此,如果质量的重力效果能对抗干扰,则再获得平衡的反应效率甚至可以被增进.结论:提重和负重是危害姿势反应效率的因素,因为提重和负重改变了重力效果,加大了对躯干的干扰.在动态条件下躯干的运动不是被横移干扰增强就是被横移干扰抵消,并没有显著地影响改变最终平衡位置姿势校正的效应.因此附加任务的同时给一个支持面上的横移干扰,姿势控制的效应可以被抵消.这个减低的效应可以引起脊柱周围结构的负荷增加和增加受伤的危险性.但是,在恰当地放置负重的位置时,反而可以增进躯干控制和协助恢复姿势平衡.     

Malignant tumours after renal transplantation.

The incidence of malignant tumours in 570 patients with kidney transplants was examined. It was found to be 20-30 times higher than in the average (normal) population. In accordance with the literature, mainly skin cancers were observed, but at variance with these data, the number of lymphoreticular malignancies was small. On the basis of their study, the authors emphasize the oncogenetic effect of immunosuppression. By comparing the conventional (AZA+PRED) and Cyclosporine (CYA+PRED) treatments, they point out that this risk should be taken into consideration even in Cyclosporine therapy which has otherwise a much more favourable effect.     

Association between vertical development of the cervical spine and the face in subjects with varying vertical facial patterns.

The upper cervical spine and face were compared longitudinally from 6 to 15 years of age in 2 groups of children with low (n = 16) and high (n = 14) MP-SN angles. The purpose of the study was to assess morphological and incremental associations between the vertical development of the cervical spine and the face in subjects with varying vertical facial patterns. Morphological associations were not detected during the observation period. Long faces were found on children with short necks, and short, square faces on those with long necks. Vertical growth of the upper cervical spine and face were weakly correlated in the 6-to-12-year period but strongly correlated later during puberty. The vertical distance between gonion and the body of the second cervical vertebra was remarkable for its constancy during childhood and puberty, indicating that gonion and the second cervical vertebra body were anatomically interrelated. This anatomical relationship strongly suggests that a mutual relationship also exists between vertical growth of the upper cervical spine and the face, especially the lower face. In addition, the lower face had the ability for independent vertical growth that was not coordinated with vertical cervical growth. This was the case in the 6-to-12-year period, but not later.     

Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course of a cervicothoracic astrocytoma WHO grade II

CASE REPORT: The reported female patient underwent sub-total resection of an intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at the age of 18 months and received local irradiation. In 1989, a local recurrence was diagnosed and a partial resection was performed. Sixteen years later, a small recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve roots and the left cerebellar cortex was apparent on MRI. The patient was implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing papilloedema, which eventually lead to amaurosis. After an extended biopsy, the invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months later, the patient died after rapid progression of the caudal cranial nerve dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination of spinal astrocytomas even two decades after initial diagnosis and treatment are rare. Therapies and diagnostic follow-up strategies are discussed.