长期使用芬太尼透皮贴剂的疗效和安全性分析

 背景：芬太尼透皮贴剂与口服吗啡控释片的止痛效果相近,近年来已被广泛用于晚期癌痛止痛治疗,但与芬太尼相关的严重不良反应事件屡有报道,其长期使用的安全性受到某些质疑。 目的：探讨长期接受芬太尼透皮贴剂治疗对罹患晚期癌痛患者的临床疗效,并分析其安全性。 方法：纳入309例晚期癌痛患者,其中男143例,女166例,年龄26-72岁,前2周使用口服缓释吗啡止痛,第3周开始改用芬太尼透皮贴剂止痛,直至第12周。采用自身前后对照方法,比较两种药物的止痛效果、使用过程中的不良反应和毒性反应及患者的接受程度。 结果与结论：患者在使用口服缓释吗啡及芬太尼透皮贴剂期间疼痛均获得良好控制。使用口服吗啡缓释片治疗后,出现的不良反应依次为便秘、恶心、疲劳和食欲减退。在转换为芬太尼透皮贴后,便秘(χ²=5.22,P=0.02)、恶心(χ²=4.38,P=0.04)症状较口服吗啡缓释片治疗明显减轻,呕吐症状虽有所减轻但差异无显著性意义  (χ²=2.7,P=0.10);有2.3%患者出现皮肤反应,更换贴片区域后好转,皮肤反应在使用后2-10周时有所减轻,一些不常见的不良反应如头痛、腹泻、呼吸困难、出汗增多等症状在增加剂量后初期出现。与口服缓释吗啡相比,91%患者偏爱或强烈偏爱芬太尼透皮贴剂止痛治疗。说明芬太尼透皮贴剂可以稳定地控制疼痛,减轻口服药物的不良反应,具有良好的患者依从性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

On the occurrence of Schwann cells within the normal central nervous system

Summary The presence of Schwann cells and P.N.S. myelin are reported in subpial areas of apparently normal spinal cord from one control rabbit, two experimental rabbits and one experimental guinea pig. These P.N.S. elements exerted no adverse effects upon local C.N.S. components. The occurrence of ectopic Schwann cells in the normal C.N.S. has also been reported elsewhere in studies on normal human spinal cord tissue. The propensity for Schwann cells to reside in the normal C.N.S. of several species makes it necessary for experiments and hypotheses on the aetiology of Schwann cell invasion into the abnormal C.N.S. to take the present phenomenon into consideration.     

Electron microscopy of previously identified cells and processes within the central nervous system

Summary It is possible to partially transform the silver chromate precipitate present in Golgi stained structures into lead chromate. When this partial replacement is followed by a treatment in a solution containing thiosulphate ions, only lead chromate is left in the tissue. This results in a depleted impregnation of the originally Golgi stained structures without fading of their borderlines. The tissue is then embedded in Araldite. Prior to ultramicrotomy, nerve cells and other structures can be identified under incident light microscopy. When studied with the electron microscope, they may reveal a relatively preserved cytoplasm within which organelles can be recognized.     

Long-term treatment with zimelidine leads to a reduction in 5-hydroxytryptamine neurotransmission within the central nervous system of the mouse and rat

Male rats and mice received a 14 day peroral treatment with zimelidine, a novel antidepressant drug. Zimelidine produced a 70 and 60% reduction in the number of high affinity [3H]5-hydroxytryptamine (5-HT) and [3H]D-lysergic acid diethylamide (LSD) binding sites, respectively, and induced low affinity binding sites for [3H]5-HT and for [3H]D-LSD. The head twitch behaviour induced by 5-hydroxytryptophan and 5-methoxydimethyltryptamine was attenuated and reductions of prolactin and growth hormone were observed. These findings give further evidence that long-term treatment with zimelidine can produce a reduction of 5-HT neurotransmission in several brain regions.     

Selective central nervous system tropism of primary central nervous system lymphoma

Primary Central nervous system lymphoma (PCNSL) is most frequently a diffuse large B cell lymphoma (DLBCL), which is confined to the Central nervous system (CNS). We performed an experiment in which lymphoma cells from a PCNSL patient were implanted subcutaneously in an athymic mouse. The lymphoma cells were shown to home to the CNS with histologic evaluations of the brain showing multiple large B cells in blood vessels consistent with intravascular large B cell lymphoma (IVL). We did not find any evidence of lymphoma at the site of implantation or other locations. The findings are consistent with highly selective tropism of PCNSLforthe CNS and its vasculature.     

The ultrastructure of prosternal sensory hair afferents within the locust central nervous system

The sensory neurones innervating long prosternai hairs of Locusta migratorioides were backfilled with horseradish peroxidase through their dendrites. The neurones' central projections in and around the medial ventral tract were examined with electron microscopy. Most synapses occur on axon collaterals which ramify through the neuropile around the tract where both input and output synapses were observed. Serial sectioning methods were used to determine the relative distribution of inputs and outputs which often lie in close proximity to one another on the axon terminals. The prosternai hair terminals contain agranular synaptic vesicles approximately 37 nm in diameter. Surrounding unidentified neuropilar profiles contain vesicles which are either statistically indistinguishable in size, or are larger, 45 nm diameter agranular vesicles. Neurones which are pre- or postsynaptic to labelled terminals generally contain vesicles of the second type.Input synapses onto the central terminals of primary afferent neurones can be recognised as a widespread phenomenon in the nervous systems of both invertebrates and vertebrates which will allow a fine degree of control of sensory inflow into the central nervous system.     

Arboviruses and the central nervous system

Summary Arboviruses cause encephalitis by infecting neurons of the host. Virus infection per se may cause death or dysfunction of neurons. The severity of the virus effect is dependent on the virulence of the virus and the maturity of the infected neuron. Neurons do not directly interact with T cells since they do not express MHC class I or class II antigens in vivo. Other cells such as microglia and perivascular macrophages probably present viral antigen to activated T cells coming to the brain from lymphoid organs. Infection elicits a local immune response that is characterized by mononuclear cell infiltration and local production of cytokines and antiviral antibody. The cytokines are primarily characteristic of type 2 T cells providing B cell help and macrophage deactivation. Control of virus replication is effected by antibody which does not eliminate infected cells. Therefore, viral RNA persists in the CNS, requiring continuous intraparenchymal production of antiviral antibody.     

Localization of a glutathione-dependent dehydroascorbate reductase within the central nervous system of the rat

In this study, we describe for the first time the occurrence, within the central nervous system of the rat, of a dehydroascorbate reductase analogous to the one we recently described in the liver. Dehydroascorbate reductase plays a pivotal role in regenerating ascorbic acid from its oxidation product, dehydroascorbate. In a first set of experiments, we showed that a dehydroascorbate reductase activity is present in brain cytosol; immunoblotting analysis confirmed the presence of an immunoreactive cytosolic protein in selected brain areas. Immunotitration showed that approximately 65% of dehydroascorbate reductase activity of brain cytosol which was recovered in the ammonium sulphate fraction can be attributed to this enzyme. Using immunohistochemistry, we found that a variety of brain areas expresses the enzyme. Immunoreactivity was confined to the gray matter. Amongst the several brain regions, the cerebellum appears to be the most densely stained. The enzyme was also abundant in the hippocampus and the olfactory cortex. The lesion of norepinephrine terminals following systemic administration of DSP-4 markedly decreased immunoreactivity in the cerebellum. Apart from the possible co-localization of the enzyme with norepinephrine, the relative content of dehydroascorbate reductase in different brain regions might be crucial in conditioning regional sensitivity to free radical-induced brain damage. Given the scarcity of protective mechanisms demonstrated in the brain, the discovery of a new enzyme with antioxidant properties might represent a starting-point to increase our knowledge about the antioxidant mechanisms operating in several central nervous system disorders.     

异丙酚诱导大鼠中枢FOS核蛋白表达的研究

目的　通过检测异丙酚静脉全麻诱导大鼠中枢FOS核蛋白的表达 ,明确静脉全身麻醉的中枢作用位点。方法　 2 1只Wistar大鼠随机分成 3组 :对照组 (C组 )腹腔注入生理盐水 2ml,异丙酚组 (P组 )腹腔注入异丙酚 10 0mg kg ,异丙酚作用后断尾刺激组 (S组 )。 1h后应用FOS蛋白免疫组织化学法 (ABC法 ) ,检测FOS免疫反应 (FOS IR ,immunityreactionofFOS)阳性神经元在大脑的分布。结果　C组可见部分散在FOS IR阳性神经元分布 ,P组FOS IR阳性神经元数比C组明显增多 (P <0 .0 1) ,并呈核特异性分布 ,S组在杏仁基底外侧核、丘脑室旁核、外侧缰核及海马回嗅觉小岛等核团发现FOS IR阳性神经元较P组分布增多 (P <0 .0 1)。结论　异丙酚在大鼠中枢神经系统有与其静脉麻醉作用相关的神经核团。     

Widespread neuroendocrine malignancy within the central nervous system: a diagnostic conundrum.

A 75 year old female presented with a sellar tumour, and was subsequently found also to have a cauda equina tumour, a parietal dural tumour, a pontine tumour, an intradural spinal tumour, and several vertebral body tumours. Histological examination revealed a neuroendocrine tumour forming cell nests surrounded by reticulin. There was moderate nuclear pleomorphism, prominent mitoses, and focal necrosis. Immunohistochemistry showed diffuse positive staining with cytokeratins, chromogranin and 5-hydroxytryptamine, and focal positive staining with S100. This case is an unusual and ultimately insoluble, diagnostic problem; however, the differential diagnoses include pituitary carcinoma, malignant paraganglioma, and atypical carcinoid.     

Antibody synthesis within the central nervous system: comparisons of CSF IgG indices and electrophoresis

Various laboratories have reported differing success rates in their ability to detect intrathecal synthesis of antibody when comparing the index of [Formula: see text] with electrophoretic analysis. We selected 44 patients in the borderline area of minimal and/or equivocal abnormality by IgG index. Electrophoretic analysis (on polyacrylamide gels for oligoclonal gamma globulin pattern) of parallel specimens was performed at the same time. The number of samples giving a normal index but showing oligoclonal bands varied between 34% and 43% depending on the cut-off point. The views about normal barrier functions underlying such indices are discussed with particular reference to the pathophysiology of the blood-CSF barrier.     

Infections of the central nervous system

The brain can be infected by innumerable agents from prions to worms. Most diagnoses are made by microbiology following clinical and imaging investigations. Pathologists get involved with biopsies and autopsy scenarios; many are straightforward but some are difficult, and we must involve microbiology – including molecular diagnostics – appropriately. Optimum protocols of sampling need to be developed for meningo-encephalitis diagnostics. New scenarios of infectious encephalitis are still emerging, e.g. with changing treatment for HIV disease. The autoimmune encephalitides are emerging as a major differential diagnosis with infection.