A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

再发骨质疏松性椎体压缩骨折保守治疗患者出院后生存质量

目的：对比初次和再发骨质疏松性椎体压缩骨折(osteoporotic vertebral compression fractures,OVCFs)患者保 守治疗的生存质量,了解再次骨折对此类患者生存质量各方面的影响。方法：回顾性观察治疗OVCFs后出现再骨折 的患者30名(再骨折组)和同时期行保守治疗OVCFs后未发生再骨折的基本条件相似的患者30例(对照组),比较两组出 院后3个月时SF-36简明健康健康状况调查表的调查结果。结果：再骨折组治疗后的8个维度均不同程度较对照组变差 (均P<0.01)。结论：再骨折组患者的生存质量明显低于对照组,并且会进一步影响患者的心理预期、情绪和社会活动 的各个方面。     

Likelihood of residential aged care use in later life: a simple approach to estimation with international comparison

Objectives: In New Zealand (NZ), place of death among decedents aged 65+ years has been reported as residential aged care (RAC, 38%), acute hospital (34%) or elsewhere (28%). However, lifetime risk of use of RAC (or nursing homes) is unknown. A simple method of estimation is demonstrated for NZ and Australia, with comparisons to other countries. Methods: Deaths of RAC residents in acute hospitals were estimated for NZ from four separate studies and added to deaths occurring in RAC, to derive the likelihood of using RAC after age 65 years. Academic and other sources were searched for comparative reports. Results: An estimated 18% of RAC residents died in acute hospital in NZ. When added to those who died in RAC, the proportion using RAC for late‐life care was estimated at over 47% (66% if aged 85+ years). Of 12 US reports, the median report was 41%. Elsewhere, Finland was 47%, UK 28%, Australia 34% to 53%, and Germany 22% & 26%. Conclusions: Simple estimation using existing data demonstrates that RAC in late life is common. Implications: Late‐life care services will continue to evolve. Monitoring RAC utilisation is necessary for informed debate about palliative care provision in RAC, use of hospital by RAC residents and for planning and policy setting.     

Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis

Tumor metastasis to lymph nodes is a key indicator of patient survival, and is enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting via VEGFR-3 signalling. These targets constitute important avenues for anti-metastatic treatment. Despite this new understanding, clinical observations linking metastasis with tumor depth or location suggest that lymphangiogenic growth factors are not the sole determinants of metastasis. Here we explored the influence of tumor proximity to lymphatics capable of responding to growth factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We found that primary tumor location profoundly influenced VEGF-D-mediated lymph node metastasis: 89 % of tumors associated with the flank skin metastasised, in contrast with only 19 % of tumors located more deeply on the body wall (p < 0.01). Lymphatics in metastatic tumors arose from small lymphatics, and displayed distinct molecular and morphological profiles compared with those found in normal lymphatics. Smaller lymphatic subtypes were more abundant in skin (2.5-fold, p < 0.01) than in body wall, providing a richer source of lymphatics for VEGF-D⁺ skin tumors, a phenomenon also confirmed in human samples. This study shows that the proximity of a VEGF-D⁺ primary tumor to small lymphatics is an important determinant of metastasis. These observations may explain why tumor location relative to the lymphatic network is prognostically important for some human cancers.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.