The role of cytotoxic T-lymphocytes in the prevention and immune surveillance of tumors— lessons from normal and immunodeficient mice

The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer, a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite. Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance. A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the highest incidence, we concluded that in this model the immune system constituted a 'tumor-suppressive factor' delaying and sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic than tumors from normal mice, resulting in a high rejection rate. CD8+ cytotoxic T cells were found to be indispensable for this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating immunogenic tumor cell variants in the incipient tumor. In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations and hypotheses.     

Granulomatous mastitis: a report of seven cases

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.     

Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T₂^* MRI (T₂^* OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T₂^* signal change during OC. [¹⁴C]2-deoxyglucose (2-DG) autoradiography was combined with T₂^* OC to determine metabolic status of T₂^*-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147±32 minutes after stroke, T₂^* signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T₂^*-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T₂^* signal increase of 9.22%±3.9% (mean±s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T₂^* signal change was negligible in ischemic core, 3.2%±0.78% in contralateral regions, and 1.41%±0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.     

Persistent ectopic pregnancy following ipsilateral “salpingectomy”

Persistent ectopic pregnancy (PEP) following ipsilateral “salpingectomy” is a rare occurrence. This report describes this uncommon condition in a 26-year-old woman who presented with a sudden onset of right fossa iliac pain following an earlier salpingectomy. At laparoscopy, a persistent ipsilateral EP in the right fallopian tube stump was found. At the initial laparoscopy, an endoloop was used for salpingectomy, and a tubal stump of about 4 cm was left. This poses the questions: Are salpingectomies performed with endoloops true salpingectomies or partial salpingectomies? Do women managed with endoloops need to have human chorionic gonadotropin (hCG) follow-up, as do those with salpingostomy?     

基于雌激素浅谈逆针灸预防围绝经期女性高血压病的可行性

女性进入围绝经期后,随着雌激素分泌水平的下降,高血压病的患病率逐年升高。鉴于其不可治愈性,对"高血压前期"给予早期有效的干预,控制高血压病的发生发展,是当前预防围绝经期女性高血压病的有效措施。然而指南指出激素替代疗法和雌激素受体调节剂均不应用于围绝经期女性心血管疾病的预防,针灸作为一种既能同时调节血压和雌激素,又没有明显副作用的治疗方式,给围绝经期女性高血压病的预防带来了新的希望。文章通过探讨针灸、雌激素和高血压病三者的关系,阐释逆针灸预防围绝经期女性高血压病的可行性,为临床诊治提供参考。     

大学生饮酒模式调查分析

目的分析影响大学生饮酒模式的因素,针对饮酒教育及酒精政策提出建议。方法采用整群抽样方法,选择来自北京和郑州的530名大学生完成有效问卷调查。采用 Epidata 录入数据,SAS 12.0和 R 2.7.2进行数据描述和分析。结果74.5%的大学生在过去1年内饮过酒,啤酒是饮酒者的主要选择（85.9%）,餐馆和家里是饮酒比较频繁的场所,饮用酒多来自同学/朋友及家庭成员提供,25.3%饮酒者并无特别原因饮酒,各有约1/5的饮酒者是出于社交目的或喜欢饮酒的感觉。认为“饮酒有助于社交暠或“饮酒促进交流暠者、父母及同学/朋友饮酒者、来自农村地区或小城镇者及吸烟者更容易发生饮酒行为（均 P 〈0.05）,男生大学生、规律饮酒者更容易遭遇强迫劝酒场面、更易发生醉酒（均 P 〈0.05）。超过一半饮酒者出现酒后脸红、肌肉软弱无力等生理反应,饮酒对被调查大学生产生的社会心理影响依次是记忆丧失（23.9%）、宿醉（14.6%）、做了后悔的事（低于10%）等。结论目前大学生仍保持着一种低风险饮酒模式。大学生饮酒教育应提供关于饮酒利弊的科学信息,使其对饮酒保持一种现实的期望。应制定针对性酒精政策和教育鼓励和支持低风险且满足社交功能的饮酒模式,控制高风险饮酒模式。     

Field research in humanitarian medical programmes. Treatment of neuropathic pain in Sierra Leone

A pilot study was carried out among 223 war wounded and amputees in Sierra Leone in 2001 to investigate whether an intervention using proven medication for clinically diagnosed neuropathic pain would work in a developing country with limited health services. Compliance with medication was assessed in 79 patients and their pain and mood scores were assessed by questionnaire before medication and 6-10 months later. The pain and mood scores of 33 patients who stopped taking medication were compared for the initial and follow-up assessments indicating that, although the scores showed an improvement at follow-up, there was no significant improvement. Compliance was reasonable in 46 patients who continued with their medication, with 86.5% of possible doses collected although many had difficulty understanding how to take the drugs properly. Their pain and mood scores showed significant improvement at reassessment indicating that pain will be reduced with a longer duration of treatment. This study showed that it is possible to run an effective intervention for neuropathic pain in Sierra Leone with intermittent expert involvement and MSF have been able to develop a protocol for the assessment and treatment of neuropathic pain that may be useful in other difficult settings in which they work.     

Entering the loop: assessing the contribution of pain clinics in northern Britain

A survey of patients attending ten outpatient pain clinics throughout northern Britain was undertaken to identify opportunities for improving the treatment of pain patients. A short data collection form was designed to obtain information at every patient consultation. The patients were found to be a diverse group, many with complex pain problems. For many patients meaningful diagnoses could not be obtained. The focus of the study was altered to address a selected group of patients: those with neurogenic pain. This group was selected because it was comparatively easy to define, and previous studies suggested that nerve damage pain might not always be well managed. Many patients were found not to have had adequate trials of potentially effective therapies prior to attendance at the pain clinics. Some of these therapies, such as antidepressants and anticonvulsants, could have been prescribed by general practitioners. However, there were also substantial differences between the clinics in the proportion of patients receiving particular therapies. Finally, although many patients had psychological morbidity few were offered psychological assessment and management. These studies have shown that the pain clinics provide a range of therapies which patients are unlikely to receive elsewhere. But there is scope for improvement in the management of patients in pain clinics and efforts are currently being directed towards this.     

Effects of intracisternal endothelin-1 injection on blood flow to the lower brain stem.

The central effects of endothelin-1 (Et-1, 10-30 pmol in 2.5 microliters injected intracisternally) have been investigated in the conscious rat. With 10 and 20 pmol Et-1, no significant change in blood pressure was observed. With 30 pmol Et-1, mean arterial blood pressure rose by 40 +/- 10 mm Hg with an accompanying modest, short-lived bradycardia at 2 min post-injection. Cerebral blood flow [( 14C]iodoantipyrine autoradiography), measured simultaneously with the hypertensive response, was markedly reduced throughout the caudal medulla and cerebellum (by up to 85%), while significant hyperaemia was evident in a number of forebrain structures (e.g. an increase of 78% in sensorimotor cortex). These observations have relevance to two distinct scientific areas. Concerning the significant effect of Et-1 in central cardiovascular control, these results caution against drawing conclusions from ventricular application with knowledge only of cardiovascular parameters. These results also illustrate the profound effects of Et-1 which is uniquely capable of overriding cerebral autoregulatory mechanisms.