抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

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Modern Applied Statistics With S

http://sistemas.eel.usp.br/docentes/arquivos/2166002/1234Nb/Geetha-review2009.pdf

Ti based biomaterials, the ultimate choice for orthopaedic implants – A review

The American Society for Testing and Materials (ASTM) is an independent organization devoted to the development of standards.

American Society for Testing and Materials

Thirty patients with isolated patellofemoral complications after total knee arthroplasty were compared with 20 patients with well functioning total knee replacements without patellofemoral complications. The epicondylar axis and tibial tubercle were used as references on computed tomography scans to measure quantitatively rotational alignment of the femoral and tibial components. The group with patellofemoral complications had excessive combined (tibial plus femoral) internal component rotation. This excessive combined internal rotation was directly proportional to the severity of the patellofemoral complication. Small amounts of combined internal rotation (1°-4°) correlated with lateral tracking and patellar tilting. Moderate combined internal rotation (3°-8°) correlated with patellar subluxation. Large amounts of combined internal rotational (7°-17°) correlated with early patellar dislocation or late patellar prosthesis failure. The control group was in combined external rotation (10°-0°). The direct correlation of combined (femoral and tibial) internal component rotation to the severity of the patellofemoral complication suggests that internal component rotation may be the predominant cause of patellofemoral complications in patients with normal axial alignment. The epicondylar axis and tibial tubercle are reproducible landmarks which are visible on computed tomography scans and can be used intraoperatively. Using this computed tomography study can determine whether rotational malalignment is present and thus, whether revision of one or both components may be indicated.

Malrotation causing patellofemoral complications after total knee arthroplasty.

In situ degradation of metal-alloy implants is undesirable for two reasons: the degradation process may decrease the structural integrity of the implant, and the release of degradation products may elicit an adverse biological reaction in the host Degradation may result from electrochemical dissolution phenomena, wear, or a synergistic combination of the two Electrochemical processes may include generalized corrosion, uniformly affecting the entire surface of the implant, and localized corrosion, affecting either regions of the device that are shielded from the tissue fluids (crevice corrosion) or seemingly random sites on the surface (pitting corrosion) Electrochemical and mechanical processes (for example, stress corrosion cracking, corrosion fatigue, and fretting corrosion) may interact, causing premature structural failure and accelerated release of metal particles and ions

The clinical importance of degradation of metal implants is evidenced by particulate corrosion and wear products in tissue surrounding the implant, which may ultimately result in a cascade of events leading to periprosthetic bone loss Furthermore, many authors have reported increased concentrations of local and systemic trace metal in association with metal implants1,4,5,9-11,14,18,25,26,28,29,47,49-55,58,71,72,75-77,87,90,108-110 There also is a low but finite prevalence of corrosion-related fracture of the implant

This review focuses on electrochemical corrosion phenomena in alloys used for orthopaedic implants A summary of basic electrochemistry is followed by a discussion of retrieval studies of the response of the implant to the host environment and the response of local tissue to implant corrosion products The systemic implications of the release of metal particles also are presented Finally, future directions in biomaterials research and development …

/pdf/corrosion-of-metal-orthopaedic-implants-2h3sv09cdv.pdf

Corrosion of metal orthopaedic implants.

All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with endogenous proteins.

Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a metal device, metal sensitivity should be considered. Currently, there is no generally accepted test for the clinical determination of metal hypersensitivity to implanted devices.

The prevalence of dermal sensitivity in patients with a joint replacement device, particularly those with a failed implant, is substantially higher than that in the general population.

Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal.

It is currently unclear whether metal sensitivity is a contributing factor to implant failure.

Implant-related metal sensitivity has been well documented in case and group studies; however, overall it remains a relatively unpredictable and poorly understood phenomenon in the context of orthopaedic implant materials1-3. Dermal hypersensitivity to metal is common, affecting about 10% to 15% of the population1,2,4,5. Dermal contact with and ingestion of metals have been reported to cause immune reactions, which most typically manifest as hives, eczema, redness, and itching1,6,7. Historically, the ability of implant materials to demonstrate appropriate host and material responses has resulted in the elimination of candidate materials based on observation of adverse host responses. However, some adverse responses are difficult to characterize in preclinical and clinical settings because of their infrequent or subtle nature. In vivo metal hypersensitivity or hypersensitivity-like reactivity to metallic biomaterials is one such response. Although little is known …

/pdf/metal-sensitivity-in-patients-with-orthopaedic-implants-2vb9pvk2hl.pdf

Metal sensitivity in patients with orthopaedic implants.

A fundamental question in neuroscience concerns the relation between the spiking of individual neurons and the aggregate electrical activity of neuronal ensembles as seen in local field potentials (LFPs). Because LFPs reflect both spiking activity and subthreshold events, this question is not simply one of data aggregation. Recording from 20 neurosurgical patients, we directly examined the relation between LFPs and neuronal spiking. Examining 2030 neurons in widespread brain regions, we found that firing rates were positively correlated with broadband (2-150 Hz) shifts in the LFP power spectrum. In contrast, narrowband oscillations correlated both positively and negatively with firing rates at different recording sites. Broadband power shifts were a more reliable predictor of neuronal spiking than narrowband power shifts. These findings suggest that broadband LFP power provides valuable information concerning neuronal activity beyond that contained in narrowband oscillations.

https://www.jneurosci.org/content/jneuro/29/43/13613.full.pdf

Broadband Shifts in Local Field Potential Power Spectra Are Correlated with Single-Neuron Spiking in Humans

Background: The importance of particles generated by wear and corrosion of joint replacement prostheses has been understood primarily in the context of the local effects of particle-induced periprosthetic osteolysis and aseptic loosening. We studied dissemination of wear particles in patients with total hip and knee replacement to determine the prevalence of and the histopathological response to prosthetic wear debris in the liver, spleen, and abdominal para-aortic lymph nodes.

Methods: Postmortem specimens from twenty-nine patients and biopsy specimens from two living patients with a failed replacement were analyzed. Specimens of tissue obtained from the cadavera of fifteen patients who had not had a joint replacement served as controls. The concentration of particles and the associated tissue response were characterized with the use of light microscopy of stained histological sections. Metallic particles were identified by electron microprobe analysis. Polyethylene particles were studied with the use of oil-red-O stain and polarized light microscopy. The composition of polyethylene particles was confirmed in selected cases by Fourier transform infrared spectroscopy and hot-stage thermal analysis.

Twenty-one of the patients studied post mortem had had a primary total joint replacement. Eleven of them had had a hip prosthesis for a mean of sixty-nine months (range, forty-three to 171 months), and ten had had a knee replacement for a mean of eighty-four months (range, thirty-one to 179 months). The other eight patients studied post mortem had had a hip replacement in which one or more components had loosened and had been revised. The mean time between the initial arthroplasty and the time of death was 174 months (range, forty-seven to 292 months), and the mean time between the last revision procedure and the time of death was seventy-one months (range, one to 130 months).

Results: Metallic wear particles in the liver or spleen were more prevalent in patients who had had a failed hip arthroplasty (seven of eight) than in patients who had had a primary hip (two of eleven) or knee replacement (two of ten). The principal source of wear particles in the majority of these patients involved secondary nonbearing surfaces rather than wear between the two primary bearing surfaces as intended. In one living patient, dissemination of titanium alloy particles from a hip prosthesis with mechanical failure was associated with a visceral granulomatous reaction and hepatosplenomegaly, which required operative and medical treatment.

Metallic wear particles were detected in the para-aortic lymph nodes in 68 percent (nineteen) of the twenty-eight patients with an implant from whom lymph nodes were available for study. In 38 percent (eleven) of all twenty-nine patients with an implant who were studied post mortem, metallic particles had been further disseminated to the liver or spleen, where they were usually found within small aggregates of macrophages occurring as infiltrates without apparent pathological importance. Polyethylene particles elicited a similar response. They were identified in the para-aortic lymph nodes of 68 percent (nineteen) of the twenty-eight patients and the liver or spleen of 14 percent (four) of the twenty-nine patients. The majority of the disseminated wear particles were less than one micrometer in size. Currently available methods lack the sensitivity and specificity necessary to detect very low concentrations of submicrometer polyethylene particles and probably underestimated the prevalence of polyethylene wear debris in the liver and spleen.

Conclusions: In this study, systemic distribution of metallic and polyethylene wear particles was a common finding, both in patients with a previously failed implant and in those with a primary total joint prosthesis. The prevalence of particles in the liver or spleen was greater after reconstructions with mechanical failure. In the majority of patients, the concentration of wear particles in these organs was relatively low and without apparent pathological importance. However, in one rare case, granulomas formed in the liver, spleen, and abdominal lymph nodes in response to heavy accumulation of wear debris from a hip prosthesis with mechanical failure and compromised hepatic function.

Clinical Relevance: These findings underscore the necessity of minimizing the production of particulate debris by joint replacement devices and the need for the surgeon to consider expeditious revision in patients in whom large amounts of particulate debris may be generated. Serum and urine trace-metal analyses may provide early confirmation of failure and aid in the timing of a revision operation in a patient with a symptomatic or failed device.

Joshua J. Jacobs

Papers

Malrotation causing patellofemoral complications after total knee arthroplasty.

Corrosion of metal orthopaedic implants.

Metal sensitivity in patients with orthopaedic implants.

Broadband Shifts in Local Field Potential Power Spectra Are Correlated with Single-Neuron Spiking in Humans

Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement.