Trabecular Shear Stresses Predict <Emphasis Type="Italic">In Vivo</Emphasis> Linear Microcrack Density but not Diffuse Damage in Human Vertebral Cancellous Bone

Linear microcracks and diffuse damage (staining over a broad region) are two types of microscopic damage known to occur in vivo in human vertebral trabecular bone. These damage types might be associated with vertebral failure. Using microcomputed tomography and finite element analysis for specimens of cancellous bone, we estimated the stresses in the trabeculae of human vertebral tissue for inferosuperior loading. Microdamage was quantified histologically. The density of in vivo linear microcracks was, but the diffuse damage area was not, related to the estimates of von Mises stress distribution in the tissue. In vivo linear microcrack density increased with increasing coefficient of variation of the trabecular von Mises stress and with increasing average trabecular von Mises stress generated per superoinferior apparent axial stress. Nonlinear increase in linear crack density, similar to the increase of the coefficient of variation of trabecular shear stresses, with decreasing bone stiffness and bone volume fraction suggests that damage may accumulate rather rapidly in diseases associated with low bone density due to the dramatic increase of shear stresses in the tissue. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8759Ls, 8759Fm, 8710+e     

Post-traumatic diffuse brain swelling: isolated or associated with cerebral axonal injury

Eighteen children with severe head injuries and diffuse brain swelling were studied. They were separated into two groups based on the computed tomography (CT) findings. Seven patients had small ventricles in the normal location and small or absent cisterns. Eleven had these signs plus small deep-seated intraparenchymal hemorrhagic foci and/or intraventricular hemorrhage. Patients in the first group were in relatively good neurological condition; their intracranial pressure was easily controlled and all had a favourable outcome. On contrast, children in the second group had a more severe clinical presentation, frequently had uncontrollable intracranial hypertension, and more than 50% died.     

Occurrence of diffuse amyloid deposits in the presubicular parvopyramidal layer in Alzheimer's disease

Summary Silver staining by a modified Bielschowsky's technique and immunostaining for -amyloid protein BAP have revealed the occurrence of diffuse amyloid deposits bilaterally in the presubiculum in each of fourteen Alzheimer's disease cases examined. Observations on serial blocks show these deposits to be localized in the parvopyramidal layer of the presubiculum proper and the transsubiculum. They are also observed in the cellular islands within the molecular layer of the subiculum but not in the parasubiculum. These amyloid deposits are not accompanied by neurofibrillary tangles, neuropil threads, or the aggregated microglial reaction which is characteristically associated with classic senile plaques. Convergence of input from limbic and cortical areas might play a significant role in the formation of these diffuse amyloid deposits.Supported by grants from the MRC of Canada, the Alzheimer's Society of B.C., the American Health Assistance Foundation and the McLean Foundation     

Characterization of a shared epitope in cortical Lewy body fibrils and Alzheimer paired helical filaments

The straight fibrils of the Lewy body contain an epitope related to phosphorylation of the KSPV motif common to the C termini of the 200- and 170-kDa neurofilament subunits and . To further characterize this phosphorylated neurofilament/ epitope in Lewy bodies and to analyze the constituents of isolated Lewy bodies we used a combined biochemical and immunochemical approach. In formalin-fixed paraffin-embedded tissue cortical Lewy bodies were labelled by monoclonal antibodies directed to phosphorylation-dependent KSPV epitopes in the sequences of neurofilament and phosphorylation-independent epitopes. Immunoblotting of solubilized Lewy body fibrils with the same antibodies which stained Lewy bodies in tissue sections revealed that the immunoreactive Lewy body proteins were phosphorylated neurofilament subunits. An antibody to the 68-kDa neurofilament subunit labelled Lewy bodies and Lewy body protein at 50–68 kDa. We conclude that the shared phosphorylated epitope in Lewy body fibrils and paired helical filaments is related to the common KSPV sequence in neurofilament and , and that all three neurofilament subunits are present in the Lewy body. This result indicates that although Lewy bodies and neurofibrillary tangles share epitopes they are comprised of distinct structural subunits.Supported by grants from the Parkinson Foundation of Canada and the Alzheimer Society of Canada to C.B. M.S.P. is a recipient of a Medical Research Council of Canada Studentship     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Neuron-specific enolase as an effective immunohistochemical marker for injured axons after fatal brain injury

Recently, it has been reported that a diagnosis of diffuse axonal injury in cases with a short survival period can be made with the use of immunolabelling for β-amyloid precursor protein (APP). We examined whether immunostaining for neuron-specific enolase (NSE) can also be a useful marker for the detection of axonal injury in its early stages. Sections of the corpus callosum from 19 cases of head injury and from 9 cases of no head injury were immunostained for NSE and stained by the standard Holmes’ silver method. For comparison, serial sections from several cases were immunostained for APP. Immunostaining for NSE as well as for APP, labelled injured axons in head injury cases with as early as 1.5 h survival where Holmes’ staining failed to detect any changes of axons. Since NSE and APP labelled only injured axons but not normal axons, the results were readily interpretable. These findings indicate that NSE should be an effective marker for the detection of axonal injury in its early stages. Received: 7 December 1998 / Received in revised form: 11 March 1999     

Deposition of β/A4 protein along neuronal plasma membranes in diffuse senile plaques

Summary The origin of the extracellular -amyloid protein (/A4) found in senile plaques and the cellular mechanisms responsible for its deposition in cerebral tissues are still an unresolved issue in Alzheimer's disease. In this study we analyzed in detail the distribution of various epitopes of /A4 in relation to local cellular elements in diffuse plaques of the hippocampal region. We also correlated our findings with the presence and distribution of non-/A4 epitopes of the amyloid precursor protein (APP) and with synaptophysin immunoreactivity in the cortical neuropil. Discontinuous /A4-immunoreactive deposits were found along dendrites, and around the soma of neurons included in the plaques. Furthermore, increased synaptophysin reactivity with slightly dilated synaptophysin-immunolabeled presynaptic terminals were found in diffuse plaques. APP epitopes could not be found in diffuse plaques. However, some of the APP antibodies, mainly those to the C-terminal portion of APP, and antibodies to /A4 recognized clusters of flat vesicular profiles (0.6–1.4 m in width and 2–3 m in length) in the neuropil of cortical areas where plaques had developed. Our findings are compatible with a neuronal origin of /A4 in diffuse plaques and with a primary release of /A4 at synaptic sites along the immunostained neurites. They also suggest that diffuse plaques might be preceded by minute lesions of the neuropil where /A4 is not yet released from the precursor molecule.     

磁共振成像诊断脑弥漫性轴索损伤

目的　探讨MRI诊断脑弥漫性轴索损伤 (DAI)的方法及价值。方法　回顾性分析 38例临床诊断脑弥漫性轴索损伤患者的MRI资料 ,对其病灶的分布特点、信号特征及不同序列对病灶的显示能力进行统计分析。结果　 38例DAI患者 ,共发现病灶 1338个 ,其中双侧大脑半球皮髓交界处病灶 4 6 9个 ,脑叶白质 4 6 0个 ,基底节区 2 0 2个 ,胼胝体 89个 ,小脑 70个 ,脑干 4 8个。DAI病灶在不同序列中的信号特征不同 ,所显示病灶T1WI为等、低信号 ,T2 WI及FLAIR为高信号 ,SE EPI弥散像为稍高信号或高信号 ,FLASH为显著低信号。病灶在不同序列的显示程度不同 ,FLASH序列能得到显示的病灶 ,SET1WI仅能显示 15 3% ,FSET2 WI能显示 38 9% ,FLAIR能显示 5 4 7% ,SE EPI能显示 6 3 6 %。DAI合并症的显示各序列有着大致相同的特异性 ,但敏感性略有差异。结论　MRI对DAI有非常高的诊断价值 ,不同序列对DAI病灶的显示能力不同 ,FLASH序列能显示常规序列所不能显示的出血灶 ,可作为MRI诊断DAI的首选序列。     

弥漫性肺部感染临床诊治分析

目的 探讨分析阿奇霉素治疗弥漫性肺部感染临床治疗效果.方法 选取2010年1月-2012年12月该院收治的80例肺部感染的患者为研究对象,随机将患者分为观察组和对照组,每组40例患者,其中观察组患者采用阿奇霉素静脉滴注进行治疗,对照组患者静脉滴注阿莫西林进行治疗,观察两组患者临床疗效、不良反应率以及住院时间的差异.结果 观察组患者的临床显效率为95％,对照组患者的临床显效率为72.5％,两组患者临床治疗效果差异有统计学意义（P＜0.05）,观察组患者的临床不良反应率为7.5％,对照组患者不良反应率为20％,两组患者临床不良反应率差异有统计学意义（P＜0.05）.结论 采用阿奇霉素静脉滴注治疗弥漫性肺部感染安全有效,可有效缩短临床用药时间,提高患者治疗效果,值得在临床上应用.