The detection and management of complications following the treatment of liver metastases

While once considered as incurable systemic disease, treatment options for liver metastases have increased over the last 30 years and safety has improved dramatically, such that for a selected group of patients the hope of cure can now be offered with radical treatment, and low morbidity interventions can be offered which prolong survival, even in patients with more widely disseminated disease. Advances have been made in selection and surgical technique for liver resection and several adjuncts to resection now exist in the form of portal vein embolization, thermal ablation and targeted drug or radiotherapy delivery options. A natural consequence of these developments has been the delivery of services within fewer specialist units, with the result that later complications of therapy may present to local hospitals, rather than directly to the specialist centres. This article will describe the current common liver-directed therapies and outline the presentation and management of their complications.     

Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules.

HLA-DR molecules are heterodimeric transmembrane glycoproteins that associate intracellularly with a polypeptide known as the invariant (I) chain. Shortly before expression of the HLA-DR alpha beta dimer on the cell surface, however, the I chain is removed from the intracellular alpha beta I complex by a mechanism thought to involve proteolysis. In this report, we show that treatment of purified alpha beta I with the cysteine proteinase cathepsin B results in the specific proteolysis of the HLA-DR-associated I chain in vitro. As a consequence of this, the I chain is removed and free alpha beta dimers are released from alpha beta I. Although alpha beta I fails to bind an immunogenic peptide, the released alpha beta dimers acquire the ability to bind the peptide after proteolysis of the I chain. These results suggest that the I chain inhibits immunogenic peptide binding to alpha beta I early during intracellular transport and demonstrate that proteolysis is likely to be the in vivo mechanism of I chain removal.     

Mechanisms of MHC class I-restricted antigen processing and cross-presentation

Summary: In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I‐restricted antigen processing. First, we consider the nature of the peptide‐loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I‐β₂ microglobulin (β₂m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide‐loading complex. Second, we discuss mechanisms of cross‐presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen‐presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8⁺ T cells. The focus of the discussion is mainly on the human MHC class I system.     

Interaction between voluntary and postural motor commands during perturbed lifting

STUDY DESIGN: An experimental study was conducted to evaluate the effect of an unexpected postural perturbation during a lifting task. OBJECTIVES: To investigate electromyographic responses in the erector spinae to a postural perturbation, simulating slipping, during an ongoing voluntary lifting movement. It was hypothesized that specific combinations of voluntary movement and postural perturbation present a situation in which injury caused by a rapid switch between conflicting motor commands can occur. SUMMARY OF BACKGROUND DATA: Studies of postural perturbations have mainly focused on behavior during static tasks such as quiet, upright standing. To date, there are no published studies of the effect of a perturbation during an ongoing voluntary lifting movement. METHODS: Subjects standing on a movable platform were exposed to random perturbations while lifting a 20-kg load. Muscle activity was recorded from flexor and extensor muscles of the trunk and hip. Trunk flexion angle in the sagittal plane was recorded with a video system. RESULTS: Perturbations forward were followed by an increased activity in erector spinae superimposed on the background activation present during the lift, indicating that both the voluntary and postural motor programs caused an activation of erector spinae. During backward perturbation, however, there was a sudden cessation of erector spinae activity followed by an extended period of rapid electromyographic amplitude fluctuations while the trunk was flexing, indicating an eccentric contraction of the erector spinae. CONCLUSIONS: This erratic behavior with large electromyographic amplitude fluctuations in the erector spinae after a backward slip during lifting may indicate a rapid switch between voluntary and postural motor programs that require conflicting functions of the back muscles. This may cause rapid force changes in load-carrying tissue, particularly in those surrounding the spine, thus increasing the risk of slip-and-fall-related back injuries.     

COPD患者急性加重期血清与痰中TNF-α、白细胞三烯B4水平的变化及意义

目的 探讨TNF-α、白细胞三烯B4（LTB4）在慢性阻塞性肺病急性加重期（AECOPD）血清与痰中的含量变化及临床意义.方法 分别检测28例AECOPD患者治疗前后血清与痰中TNF-α、LTB4的含量变化,并以26例健康体检者作对照.结果 AECOPD患者治疗前血清与痰中TNF-α水平分别为（30.12±9.32）ng/L、（9.86±2.56）ng/L,明显高于治疗后[（16.69±4.28）ng/L、（4.69±1.06）ng/L]（P均〈0.05）; AECOPD患者治疗前血清与痰中LTB4水平分别为（2.925±0.855）ng/L、（3.152±0.986）ng/L,明显高于治疗后[（2.206±0.653）ng/L、（2.355±0.701）ng/L]（P均〈0.05）.结论 动 态监测血清与痰中TNF-α、LTB4变化对于评价COPD急性加重期患者病情具有一定的临床意义.