The effects of training, immobilization and remobilization on musculoskeletal tissue

Compared with the knowledge on immobilization, the effects of remobilization on musculoskeletal tissues have not been well established. What is sure is that remobilization and rehabilitation of any component of the musculoskeletal tissues require much more time than the time needed to cause the immobilization atrophy. With intensive rehabilitation, the functional properties of skeletal muscles can be improved significantly even years after the injury and following immobilization, but no study has shown whether full recovery is possible and whether these rehabilitated muscles are able to respond normally to further training. Experimental studies have given evidence that slow-twitch muscle fibres have better capacity for recovery than fast-twitch fibres, most likely due to better circulation and higher protein turnover. Also evidence has been given that fibre regeneration is possible through satellite cell activation and myotube formation. Very little is known, however, about the effects of age, gender or the level of preimmobilization muscle performance on the restoration capacity. Also the fate of the marked structural changes (for example, connective tissue accumulation) induced by immobilization is unknown. Tendon and ligament tissues are likely to respond appropriately to remobilization, resulting in acceleration of collagen synthesis and fibril neoformation. However, there is a strong suspicion that remobilized tendons and ligaments will not achieve all the biochemical and biomechanical properties of their healthy counterparts. Specifically, the amount of weak type III collagen has been shown to be overrepresented in these tissues instead of mature, strong type I collagen. It is not known whether this is an important risk factor for ruptures during later activity. The effects of remobilization on muscle-tendon junction and proprioceptive organs are not known. It would not be surprising if the serious structural changes induced by immobilization were unrestorable. In the literature dealing with immobilization and remobilization, cartilage degeneration is always a major concern, because not only too strenuous training or immobilization, but also unskilful remobilization may activate this process leading finally to osteoarthrosis. Bone may be one of the best components of musculoskeletal tissues to respond to remobilization, probably because the immobilization atrophy of bone is largely quantitative (osteoporosis) only. The prerequisites for bony recovery are that the follow-up time is long enough (months) and that immobilization has not exceeded about 6 months, the time limit between active and inactive (irreversible) osteoporosis. Prevention of the atrophying effects of immobilization can be very successful if performed properly. According to present knowledge, there are many methods for the purpose, including preimmobilization training early, controlled mobilization; optimal positioning of the immobilized joint; muscular training during immobilization; early weightbearing; exercise with the nonimmobilized extremity; and electrical stimulation. Lots of education and information will be needed, however, before these methods are deeply rooted in the daily routines of the attending physicians, physical therapists, athletic trainers and other persons involved in the treatment of musculoskeletal problems.     

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.     

Lens opacity in patients with hypercholesterolemia and ischaemic heart disease

Lens opacity studies were performed using an electronic Lens Opacity Meter (Interzeag Opacity Lensmeter 701) in a population (n = 321) with ischaemic heart disease. These patients are participating in a trial targetting at the reduction of mortality and incidence of myocardial infarction using a cholesterol-lowering drug, simvastatin. A separate study to evaluate the reliability of the method showed good reproducibility. Repeated measurements after a short time-interval (2–10 days) gave statistically lower opacity values either due to a change in lens transparency or perhaps a change in pigment and cell dispersion in the acqueous caused by repeated mydriasis. Lens opacity values showed a highly significant positive correlation to age. Serum cholesterol, systolic blood pressure and smoking habits showed no significant correlations to the levels of lens opacity when adjustments for age were made.Abbreviations HMG-CoA hydroxy-methylglutarylcoenzyme A - 4S Scandinavian Simvastatin Survival Study - LOM lens opacity meter     

Fibronectin, laminin, and collagen types I, III, IV and V in the healing rat colon anastomosis.

The purpose of this work was to study normal anastomotic healing in the rat colon. The unprepared sigmoid colon was divided and a colo-colostomy performed using a one-layer inverting technique. Frozen sections were taken and studied immunohistologically with specific antibodies to fibronectin, laminin and collagen types I, III, IV and V. From day one onwards a strong fibronectin reaction was observed in the anastomosis, reaching maximum staining intensity on postoperative day five. Type III collagen and pericellular type V collagen were at first detected in the anastomosis on day two. From day three onwards all collagens studied and laminin were present in the repair tissue (laminin and type IV and V collagen in the regenerating capillary walls). Maximum immunofluorescence was observed on day seven and it remained on a high level throughout the study, except for fibronectin, which weakened gradually after the fifth postoperative day. The results indicate that healing of the colon anastomosis occurs by rapid accumulation of connective tissue components between the inverted leaves of the colonic wall, as also new capillaries consisting of the basement membrane components, type IV and V collagen as well as laminin, are formed.     

全膝关节置换翻修术的Meta分析

目的 通过对已报道的全膝关节置换翻修术文献进行总结分析,讨探膝关节置换翻修术前后的膝关节功能、翻修的主要原因、主要并发症及不同假体的术后疗效.方法 按照以下标准收集和分析有关全膝关节置换翻修术的文献:①1990年至2002年间发表,②报告患者数大于10例,③采用通用的膝关节评分标准.一名骨科专科医生独立收集数据,一名医学统计学专家独立采用Meta统计方法分析数据.结果 共有33 篇符合条件的文献被收集.患者共1356 例,其中男429例,女611例(部分文献性别分类数据缺失),平均年龄67岁(45～49岁),加权平均随访时间57个月( 6～108 个月),加权平均术前膝关节功能总评分为49 分(15～94分),术后为84分( 58～109分),全膝关节置换翻修术前后的总评分、功能评分、活动范围等有显著性提高,差异有统计学意义(总评分t=12.507,P<0.01, 功能评分t=4.704,P<0.01,活动范围:t=5.346,P< 0.01).全膝关节置换翻修术的原因主要是假体松动(55%),其它包括聚乙烯磨损(11%)、假体不稳(10%)、感染(7%).翻修术后的主要并发症仍然为假体松动(18%),其它包括假体不稳(16% )、感染(16% )、髌骨问题( 15% )及不明原因的膝关节疼痛(13%).髌骨问题包括髌骨脱位、半脱位、髌韧带撕裂、髌股关节疼痛等.结论 可以认为膝关节置换后翻修术是一种安全有效的手术.假体松动是膝关节置换翻新的主要原因和并发症.     

Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins

Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc-/- mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.     

Weighted expectation maximization reconstruction algorithms with application to gated megavoltage tomography

We propose and investigate weighted expectation maximization (EM) algorithms for image reconstruction in x-ray tomography. The development of the algorithms is motivated by the respiratory-gated megavoltage tomography problem, in which the acquired asymmetric cone-beam projections are limited in number and unevenly sampled over view angle. In these cases, images reconstructed by use of the conventional EM algorithm can contain ring- and streak-like artefacts that are attributable to a combination of data inconsistencies and truncation of the projection data. By use of computer-simulated and clinical gated fan-beam megavoltage projection data, we demonstrate that the proposed weighted EM algorithms effectively mitigate such image artefacts.     

Tenascin immunoreactivity in normal and pathological bone marrow.

AIMS: To determine the distribution of tenascin in normal and pathological bone marrow. METHODS: 48 different bone marrow lesions were studied immunohistochemically using a monoclonal antibody to tenascin. RESULTS: Tenascin immunoreactivity was found in lesions with increased fibrosis and high numbers of reticular fibres. The strongest immunoreactivity was found in myelofibrosis. Bone marrow from acute and chronic myeloid and lymphatic leukaemias showed weak or moderate immunoreactivity. In hyperplasias inconsistent reticular tenascin immunoreactivity was found; in normal bone marrow, only a few scattered positive fibres were occasionally seen. CONCLUSIONS: Tenascin was generally observed in conditions in which megakaryocytic hyperplasia was a feature. This is in line with the notion that tenascin synthesis in bone marrow fibroblasts is stimulated by TGF-beta which is synthesised by the megakaryocytic lineage. Tenascin also contains EGF-like repeats. It might therefore function as a growth promoter and in this way could also stimulate synthesis of other matrix components. On the other hand, tenascin could function as an adhesive molecule to some cells of the bone marrow. The presence of tenascin in many pathological states of the bone marrow suggests that it may have a role in their pathogenesis and that it also could be a potential marker of disease.