股动脉粥样硬化的病理学特点探讨

目的通过与冠状动脉、颈总动脉粥样硬化比较,探讨股动脉粥样硬化的病理学特点。方法收集解放军总医院老年尸体解剖病例15例,将每例之两侧股动脉、两侧颈总动脉、左冠状动脉前降支进行连续取材,常规病理检查,选取部分节段行平滑肌肌动蛋白、CD68、bax免疫组织化学SP法染色。结果股动脉粥样硬化与冠状动脉粥样硬化在病变类型、斑块中平滑肌细胞、巨噬细胞的分布方面基本相同。但股动脉粥样硬化的范围较小、狭窄程度较轻,其斑块中的平滑肌细胞相对多,巨噬细胞相对少;bax在巨噬细胞的表达多,在平滑肌细胞的表达少。股动脉粥样硬化与颈动脉粥样硬化的病理学特点相似。结论股动脉粥样硬化与冠状动脉粥样硬化病理特点大体相同,但在某些量化指标上存在差异。     

整合素α5β1与纤连蛋白在人尸检标本动脉粥样硬化斑块局部的表达及意义北大核心CSCD

目的 探讨人动脉粥样硬化斑块局部整合素α5β1与纤连蛋白的表达情况,分析二者与动脉粥样硬化发生发展的关系.方法 收集尸检标本120例,分别取主动脉及冠状动脉.采用免疫组织化学EnVision两步法染色检测CD68、肌动蛋白、整合素α5β1与纤连蛋白在冠状动脉组织中的表达情况.依据弹力纤维染色及美国国立卫生研究院设计的Scion Image（60.1）软件的检测结果确定冠状动脉狭窄程度,并分为A组（0～25%）、B组（26%～50%）、C组（51%～75%）、D组（76%～100%）4组.结果 （1）整合素α5β1可表达于内皮细胞胞质、泡沫细胞胞质、单核巨噬细胞胞质、平滑肌细胞胞质以及钙化灶周边.整合素α5β1在已经穿越内弹力板处的平滑肌细胞的表达高于中膜平滑肌细胞.整合素α5β1在不同狭窄程度冠状动脉平滑肌的表达呈现随着狭窄程度的升高而降低的趋势.（2）纤连蛋白表达于泡沫细胞胞质、单核巨噬细胞胞质、平滑肌细胞胞质（尤其穿过内弹力板处的平滑肌细胞胞质呈现较高表达）及钙化灶周边.（3）整合素α5β1与纤连蛋白表达的相关性：二者在动脉粥样硬化组平滑肌细胞及钙化灶周边的表达均呈明显正相关性（P〈0.01）.结论 动脉粥样硬化发生发展过程中整合素α5β1与纤连蛋白参与调控平滑肌细胞向内膜的迁移,促进动脉粥样硬化斑块局部钙化的发生、发展.动脉粥样硬化后期,整合素 α5β1不参与加重冠状动脉狭窄程度.     

人冠状动脉内半乳糖凝集素3水平与斑块稳定性的相关性研究

目的:探讨人冠状动脉粥样斑块内半乳糖凝集素3(galectin-3)的表达水平与斑块结构及稳定性的关系。方法:收集尸检案例的冠状动脉标本84例,其中动脉粥样硬化但非冠心病猝死者22例(A1组),冠心病猝死但不伴有继发病变者20例(A2组),冠心病猝死且伴有继发病变者24例(A3组),无心脏疾病死亡者18例作为正常对照组(control组)。所有冠状动脉行常规HE染色检测内膜厚度、坏死核心厚度、纤维帽厚度和血管狭窄程度;以单核巨噬细胞表面标志物CD68标记病灶内的单核-巨噬细胞并计数,采用免疫组织化学、Western blot及RT-qPCR法检测冠状动脉组织中galectin-3、CD68和基质金属蛋白酶2(MMP-2)表达,并分析其表达与斑块结构及其稳定性的关系。结果:同正常组比较,病变各组粥样硬化病灶内的内膜和坏死核心增厚,纤维帽变薄,血管狭窄程度增高(P0.05);病灶内泡沫细胞数量增多(P0.05);病灶内galectin-3、CD68和MMP-2蛋白及mRNA水平较正常组显著升高,且在A1组、A2组和A3组中呈递增趋势(P0.05);病灶内galectin-3、CD68和MMP-2的表达与内膜厚度和坏死灶厚度呈正相关,与纤维帽厚度呈负相关。结论:人冠状动脉粥样硬化病灶内galectin-3表达升高,并与斑块结构稳定性相关。     

南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CIMO配体表达、巨噬细胞和平滑肌细胞数量的影响

目的：探讨南蛇藤素对高脂饲养ApoE基因敲除小鼠（ApoE^-/-）主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响。方法：8周龄雄性ApoE^-/-小鼠12只,随机分为南蛇藤素组或二甲基亚砜（DMSO）溶剂对照组,每组各6只。均给以高脂饲养8周,在高脂饲养的后4周,分别给予南蛇藤素2mg·kg^-1·d^-1或相当剂量的DMSO腹腔注射（ip）4周。麻醉处死小鼠后,取小鼠主动脉,以石蜡包埋,行主动脉根部连续切片。免疫组化法检测主动脉粥样硬化斑块内CD40配体、CD68和平滑肌α-actin表达水平,以Image ProPlus6．0软件进行图像分析。结果：与对照组相比,南蛇藤素组主动脉粥样硬化斑块内CD40配体表达显著减少（P〈0．05）;巨噬细胞的阳性率显著降低（P〈0．05）;而两组问动脉粥样硬化斑块内平滑肌细胞的阳性率没有显著差异（P〉0．05）。结论：南蛇藤素可能通过减少ApoE^-/-小鼠粥样斑块内CD40配体的表达和巨噬细胞的聚集,抑制动脉粥样硬化斑块中炎症反应,而发挥稳定动脉粥样硬化斑块的作用。     

南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响

目的:探讨南蛇藤素对高脂饲养ApoE基因敲除小鼠(ApoE-/-)主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响。方法:8周龄雄性ApoE-/-小鼠12只,随机分为南蛇藤素组或二甲基亚砜(DMSO)溶剂对照组,每组各6只。均给以高脂饲养8周,在高脂饲养的后4周,分别给予南蛇藤素2 mg·kg-1·d-1或相当剂量的DMSO腹腔注射(ip)4周。麻醉处死小鼠后,取小鼠主动脉,以石蜡包埋,行主动脉根部连续切片.。免疫组化法检测主动脉粥样硬化斑块内CD40配体、CD68和平滑肌α-actin表达水平,以Image Pro Plus 6.0软件进行图像分析。结果:与对照组相比,南蛇藤素组主动脉粥样硬化斑块内CD40配体表达显著减少(P＜0.05);巨噬细胞的阳性率显著降低(P＜0.05);而两组间动脉粥样硬化斑块内平滑肌细胞的阳性率没有显著差异(P＞0.05)。结论:南蛇藤素可能通过减少ApoE-/-小鼠粥样斑块内CD40配体的表达和巨噬细胞的聚集,抑制动脉粥样硬化斑块中炎症反应,而发挥稳定动脉粥样硬化斑块的作用。     

尸检组织环氧合酶2、妊娠相关血浆蛋白A在冠状动脉的表达与急性冠状动脉综合征发生的关系

目的 检测急性冠状动脉综合征(ACS)发生时尸检标本中环氧合酶2(COX-2)与妊娠相关血浆蛋白A(PAPP-A)在冠状动脉局部的表达情况及两者相关性.方法 从2002-2007年尸检例中筛选出有ACS发生的21例标本作为ACS组,选择未发生ACS的标本21例作为对照组,分别取其左、右冠状动脉.以CD68标记巨噬细胞、α-肌动蛋白标记平滑肌细胞,通过对这两种细胞的标记定位PAPP-A、COX-2的阳性部位.结果 (1)COX-2及PAPP-A的阳性部位均为内皮细胞胞质、巨噬细胞胞质、平滑肌细胞胞质.COX-2在ACS组平滑肌细胞胞质的表达阳性率为28.60%,在对照组平滑肌细胞胞质阳性率为4.76%,结果表明ACS组COX-2表达明显高于对照组(x2=14.13,P<0.05).(2)在ACS发生时,COX-2与PAPP-A在冠状动脉中膜平滑肌的表达有明显的相关性(r=0.88,P<0.05).(3)非斑块处平滑肌表达PAPP-A强度明显强于斑块底部平滑肌(x2=10.36,P<0.05).结论 COX-2、PAPP-A可通过在冠状动脉局部发挥作用来参与ACS的发生.     

冠状动脉粥样硬化的超高速CT检测与病理学对照I-钙化参数与粥样硬化面积之间的相关性

目的;为探讨超高速CT检测的冠状动脉钙化与冠状动脉粥样硬化面积之间的关系。方法从8例(年龄在42—84岁)压力灌注固定后的心脏标本中分离出20支冠状动脉,拉直后,超高速CT扫描;每支冠状动脉分成相应的3mm血管段,组织切片,地衣红染色,Leica图像分析仪上计算粥样硬化面积。结果在血管、心脏水平,总的粥样硬化面积与钙化面积、钙化积分高度相关,在血管段水平,每个标本内粥样硬化面积与钙化面积、钙化积分呈等级相关;有一些粥样斑块的血管段,超高速CT未检测出钙化。结论超高速CT检则的钙化参数与粥样硬化面积在血管、心脏水平高度相关;能检出钙化的血管段,其粥样斑块面积可能有一定的阈值。     

南疆地区汉族与维吾尔族人群冠状动脉粥样硬化多层螺旋CT表现对比分析

目的 探讨新疆南疆地区汉族及维吾尔族健康体检人群多层螺旋CT冠状动脉血管成像(CCTA)中冠状动脉粥样硬化的检出率、斑块性质及管腔狭窄程度的差异。方法 回顾性分析2016年6月—2017年1月喀什地区第一人民医院3 565例维吾尔族及汉族健康人群CCTA资料。3 565例中,男2 271例、女1 294例,年龄25~79(48.13±10.60)岁。其中维吾尔族2 041例,年龄25~79(48.42±10.58)岁,男1 299例、女742例;汉族1 524例,年龄28~75(47.91±10.62)岁,男972例、女552例。对冠状动脉进行曲面重建(CPR)、最大强度投影(MIP)及容积再现(VR),比较汉族及维吾尔族人群冠状动脉粥样硬化的检出率及其所致管腔狭窄程度,以及斑块性质的差异。结果 3 565例健康人群中,冠状动脉粥样硬化CCTA检出率为33.44%(1192/3 565),其中汉族人群检出率为28.41%(433/1 524),维吾尔族人群检出率为37.19%(759/2 041)。共检出不同性质斑块2 657个:汉族人群检出不同性质斑块802个,占总数30.19%(802/2 657),其中钙化斑块551个、混合斑块140个、软斑块111个;维吾尔族人群检出不同性质斑块1 855个,占总数69.81%(1 855/2 657),其中钙化斑块1313个、混合斑块311人、软斑块231个。动脉粥样硬化所致斑块狭窄程度:汉族人群组轻度狭窄者占71.83%(311/433),中度占12.47%(54/433),重度占3.23%(14/433);维吾尔族人群组狭窄程度分别为轻度占58.24%(442/759),中度占20.42%(155/759),重度占3.69%(28/759)。两组冠状动脉粥样硬化检出率、狭窄度差异均有统计学意义(χ²=30.190, Z=-11.396, P值均＜0.05),冠状动脉粥样硬化斑块性质差异无统计学意义(χ²=1.340, P＞0.05 )。结论 新疆南疆地区维吾尔族与汉族健康成人CCTA对冠状动脉粥样硬化的检出率及其所致狭窄度存在差别,动脉粥样硬化斑块性质无明显差异。     

氟伐他汀对兔颈动脉粥样斑块CD68和PCNA的影响

目的探讨氟伐他汀对粥样硬化家兔CD68和增殖细胞核抗原（PCNA）表达的影响。方法采用高脂饮食喂养法建立动脉粥样硬化（AS）模型。将24只家兔随机分为：正常对照组、AS模型组和氟伐他汀组，每组8只。饲养12周后处死，取颈动脉行HE染色，免疫组化染色法检测PCNA和CD68的抗原表达。结果氟伐他汀组血清总胆固醇（TC）、低密度脂蛋白．胆固醇（LDL-C）浓度明显低于AS模型组（P〈0．01）。AS模型组颈动脉斑块中见大量CD68及PCNA阳性细胞，氟伐他汀组对应阳性细胞数显著少于AS模型组（P〈0．01）。结论氟伐他汀治疗可以抑制高胆固醇血症兔颈动脉粥样斑块的形成，减轻斑块内巨噬细胞的浸润并抑制PCNA的产生，从而起到稳定斑块的作用。     

冠状动脉粥样硬化的超高速CT检测与病理学对照:II-钙化参数与管腔狭窄之间的关系

目的 :为探讨超高速 CT检测的冠状动脉钙化与冠状动脉管腔狭窄之间的关系。方法 :从 8例压力灌注固定后的心脏标本中分离出 2 0支冠状动脉 ,拉直后 ,超高速 CT扫描 ;每支冠状动脉分成相应的 3mm血管段 ,组织切片 ,地衣红染色 ,L eica图像分析仪上计算冠状动脉管腔面积狭窄率。结果 :在 4 84个血管段中 ,无粥样病变血管段的钙化率、钙化面积、钙化积分 (0 ,0 ,0 )明显低于有粥样病变的血管段 (2 8% ,1.74 %和 6 .73,P<0 .0 1)和管腔狭窄≥ 75%的血管段 (54.4 % ,5.8和 2 2 .7,P<0 .0 1) ;狭窄程度越大 ,钙化率越高 ;尽管冠状动脉钙化阴性的血管段可能有粥样硬化存在 ,但是只有 8.4 %的血管段属于管腔面积狭窄≥ 75% ;超高速 CT检测管腔面积狭窄≥ 75%的血管段敏感性、特异性分别为 54.4 %、81.5%。结论 :冠状动脉狭窄程度越重 ,粥样硬化内钙化发生率越高 ;冠状动脉钙化阴性有着重要的临床意义 ;CT阈值≥ 130 Hu于国人可能偏高     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.     

Platelet-activating factor receptor and respiratory and metabolic responses to hypoxia and hypercapnia

Activation of the platelet-activating factor receptor (PAFR) regulates neural transmission. A PAFR blocker reduced the peak hypoxic (pHVR) but not hypercapnic ventilatory (HCVR) responses in rats [Am. J. Physiol. 275 (1998) R604]. To further examine the role of PAFR in respiratory control, genotype-verified PAFR -/- and PAFR +/+ adult male mice underwent hypoxic and hypercapnic challenges. HCVR was similar in the two groups (p-NS). However, pHVR was significantly reduced in PAFR -/- mice (38 +/- 13% baseline [S.D.]) compared to PAFR +/+ mice (78 +/- 16% baseline; P < 0.001, ANOVA), with reduced tidal volume recruitments during pHVR. In addition, hypoxic ventilatory depression was attenuated in PAFR -/- mice (P < 0.01), and was primarily due to attenuation of the time-dependent decreases in oxygen consumption during sustained hypoxia (P < 0.01). Thus, PAFR expression/function modulates components of the acute ventilatory and metabolic adaptations to hypoxia but not to hypercapnia. Imbalances in PAFR activity may lead to maladaptive regulation of the tightly controlled metabolic-ventilatory relationships during hypoxia.