Coronary myointimal hyperplasia in freshwater Lake Michigan salmon (genus Oncorhynchus). Evidence for lipoprotein-related atherosclerosis.

The relationship between plasma lipoprotein concentration and histologic myointimal proliferative lesions in the coronary vessels was examined in 37 freshwater Chinook salmon (Oncorhynchus tshawytscha). The fish were obtained during the migrating, schooling, and spawning periods of the fourth year of life. Plasma apoB polypeptides were maximally elevated in the migrating fish in correlation with a high degree of coronary vascular disease. Both the relative incidence and the severity of lesions were greater in migrating salmon as compared with spawning fish. In contrast, plasma apoA polypeptides were maximally elevated in association with reduced levels of plasma apoB in spawning fish in which coronary lesions were reduced in severity and incidence. Simultaneous observations confirmed the relative decrease in circulating thyroid hormone and increase in adrenal cortical hormones characteristic of the maturation process. These data in the mature freshwater Lake Michigan Chinook salmon provide direct support for the hypothesis that coronary proliferative atherogenesis proceeds in parallel with excessive exposure to apoB-containing lipoproteins and that reversal is associated with excessive exposure to apoA-containing lipoproteins. The temporal relationship to altered hormone status is described, but the pathophysiologic significance for atherogenesis cannot be determined from these data.     

The ultrastructure of spontaneous coronary arterial lesions in steelhead trout (Salmo gairdneri).

Electron-microscopic examination of spontaneously occurring coronary arterial lesions in adult spawning steelhead trout showed them to be subendothelial accumulations of modified smooth muscle cells covered by an intact endothelium. Some of the cells in the nodules appeared highly vacuolated and seemed to be associated with varying amounts of collagen and elastin. The internal elastic lamina was often doubled with smooth muscle cells between the layers. The thickness of the internal elastica was altered and, in some lesions, penetrated by smooth muscle cells. In the smallest lesions, smooth muscle cells appeared to be penetrating the internal elastic lamina and were usually close to a highly vacuolated intimal endothelial cell. The underlying medial layer frequently exhibited altered orientation of the cells, with the frequent appearance of increased collagen and amorphous extracellular material. No lipid was present in any lesion. Although vacuolation of endothelial cells suggested some alteration in endothelial cells, at least in developed lesions, no evidence of endothelial denudation over lesions was observed.     

Computed tomography imaging of early coronary artery lesions in stable individuals with multiple cardiovascular risk factors

OBJECTIVES:To investigate the prevalence, extent, severity, and features of coronary artery lesions in stable patients with multiple cardiovascular risk factors.METHODS:Seventy-seven patients with more than 3 cardiovascular risk factors were suspected of having coronary artery disease. Patients with high-risk factors and 39 controls with no risk factors were enrolled in the study. The related risk factors included hypertension, impaired glucose tolerance, dyslipidemia, smoking history, and overweight. The characteristics of coronary lesions were identified and evaluated by 64-slice coronary computed tomography angiography.RESULTS:The incidence of coronary atherosclerosis was higher in the high-risk group than in the no-risk group. The involved branches of the coronary artery, the diffusivity of the lesion, the degree of stenosis, and the nature of the plaques were significantly more severe in the high-risk group compared with the no-risk group (all p < 0.05).CONCLUSION:Among stable individuals with high-risk factors, early coronary artery lesions are common and severe. Computed tomography has promising value for the early screening of coronary lesions.     

Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice.

We have shown that spontaneously occurring, organ-specific autoimmune lesions develop in aged C57BL/6 mice of both sexes, especially in 24-month-old senescent mice. The inflammatory lesions were found in the multiple organs such as salivary gland, kidney, pancreas, lung, and liver, associated with ageing process. Organ-specific autoimmune lesions first appeared in 6-month-old C57BL/6 mice, and were aggravated with advancing age. In contrast, significant inflammatory changes did not develop in the thyroid, stomach, testis, ovary, and prostate in aged C57BL/6 mice. The incidence and severity of organ-specific autoimmune lesions in this strain of non-autoimmune mice increase with advance of age. The most severely affected lesion was sialadenitis developed in the submandibular salivary gland of aged mice, and a significant difference between male and female mice was noted only in the salivary gland. The infiltrating cells within the lesions of multiple organs consisted mainly of Thy 1.2+ and L3T4+ cells. Autoantibodies were detected in the sera of the mice with each corresponding organ-specific autoimmune lesions.     

Comparative pathology of gizzard lesions in broiler chicks fed fish meal, histamine and copper

In order to elucidate the histopathogenesis of gizzard lesions occurring with various diets and in particular with fish meals, comparative studies were made on the gizzard and proventriculus of broiler chicks fed a diet containing 15% of a suspect batch of fish meal (group A), and normal fish meal containing diets to which were added 0.4% of histamine (group B) or 1,000 parts/10(6) of copper (group C). The gizzard lesions in group A were widespread and consisted of thickening and loosening of the lining, frequently with erosions and ulcerations. The lesions in group B were almost identical to those in group A, but were less severe and less associated with erosions and ulceration. The lesions in group C were widespread and consisted of a markedly thickened lining with numerous desquamated surface cells, sometimes with erosions. The surface and chief cells were swollen in most glands of groups A and C and in the cells of those glands under the altered lining in group B. A poorly-staining secretion was shown to be excreted into the lining. The proventriculus in the three experimental groups showed increased secretion in direct proportion to the severity of the gizzard lesions. It was suggested that the gizzard lesions caused by dietary fish meal might have originated from hyperactivity of the gizzard glands, followed by erosion and ulceration.     

老年冠心病患者血清VEGF、NT-proBNP、cTnT与冠状动脉病变程度的相关性

目的 探讨老年冠心病(coronary atherosclerotic heart disease,CHD)患者血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、氨基端脑肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、肌钙蛋白T(cardial troponin T,cTnT)与冠状动脉病变程度的相关性.方法 选取2015年8月~2016年8月南京医科大学附属淮安第一医院收治的113例老年CHD患者为观察组,同期选取64例体检健康老年人为本研究对照组,采用酶联免疫吸附试验(Enzymes linked immunosorbent assay,ELISA)检测所有受试者血清VEGF、NT-proBNP、cTnT水平,分析三者与老年CHD患者冠状动脉病变程度的相关性.结果 观察组血清VEGF、NT-proBNP、cTnT水平均明显高于对照组,差异有统计学意义(P<0.05);冠状动脉3支血管病变组血清VEGF、NT-proBNP、cTnT水平均明显高于2支及1支血管病变组(P<0.05),2支血管病变组血清VEGF、NT-proBNP、cTnT水平均明显高于1支血管病变组(P<0.05);Gensini积分≥30分组血清VEGF、NT-proBNP、cTnT水平均明显高于Gensini积分<30分组(P<0.05);相关性分析结果可见,血清VEGF、NT-proBNP、cTnT水平与Gensini积分呈显著正相关(r=0.772,0.593,0.634,P<0.05).结论 老年CHD患者血清VEGF、NT-proBNP、cTnT与冠状动脉病变程度相关,且随着冠状动脉病变程度增加呈现明显升高趋势.     

Increased atherosclerosis and glomerulonephritis in cynomolgus monkeys (Macaca fascicularis) given injections of BSA over an extended period of time.

A study was conducted to compare the effects of experimental immune complex disease on the development of glomerulonephritis and aortic and coronary artery atherosclerosis. Fourteen adult male macaques (Macaca fascicularis) were fed a mildly atherogenic diet. Ten of these animals were given repeated intravenous injections of bovine serum albumin (BSA), and the remaining 4 were given similar injections of saline. Three of the monkeys given BSA responded with a high antibody titer, 4 with a moderate titer, and 3 with a low level titer to BSA. In all 4 monkeys with the moderate antibody response glomerulonephritis developed, characterized by increased glomerular cellularity, electron-dense deposits in the glomerular capillary basal lamina, and deposits of IgG, IgM, C3, C4, and BSA. Glomerulonephritis was not seen in the other 6 monkeys given BSA or the 4 control monkeys. Aortic lesions seen at necropsy consisted of a few fatty intimal streaks with no differences between test monkeys (given BSA) and control monkeys (given saline). There was no correlation between total serum cholesterol concentration, high-density lipoprotein cholesterol concentration, or BSA antibody levels and the degree of aortic atherosclerosis. Immunochemical stains for immunoglobulins and complement components revealed increased intimal staining when intimal thickness increased. Medial staining for immunoglobulin and complement components appeared to be slightly increased in monkeys with moderately high-level titers of BSA. The extent of atherosclerosis in the coronary arteries of monkeys given BSA was greater than in the control animals. Differences in the extent and severity of the atherosclerotic lesions were most pronounced in the proximal portions of the main coronary arteries, suggesting an increased susceptibility of this site to immune-complex-exacerbated atherosclerosis. In addition to the increased lesion severity in monkeys given BSA, there were numerous granulocytes seen within, attached to, and penetrating into the intima of the coronary lesions. No correlation was seen between the development of glomerulonephritis and either aortic or coronary artery atherosclerosis.     

低骨密度和冠心病Gensini积分的相关性

背景：相关研究已经显示,冠心病和骨质疏松存在共同的病理生理机制,动脉粥样硬化和骨质疏松有明显的相关性。 目的：分析骨质疏松症和冠心病患者冠脉病变严重程度的相关性。 方法：回顾性分析首次行冠脉造影并明确诊断为冠心病的322例患者资料,将其分为骨质疏松组和非骨质疏松组患者,采用多元线性回归模型分析骨质疏松和反映冠脉病变严重程度的Gensini积分间的相关性。 结果与结论：骨质疏松组比非骨质疏松组患者具有较少的冠脉单支病变(P < 0.001),更多的冠脉多支病变(P < 0.001)和更高的Gensini积分(P < 0.001)。在校正可能的影响因素后,多元线性回归显示,骨质疏松是Gensini积分的危险因素(P < 0.001)。相关性分析显示,骨密度和Gensini积分呈负相关关系(r=-0.36, P=0.004)。结果表明,骨质疏松和冠心病冠脉病变严重程度密切相关。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.     

Pathological changes in the brains of mice infected with Toxoplasma gondii: a histological, immunocytochemical and ultrastructural study

The pathological changes in the brains of mice infected with T. gondii were studied at various intervals between 7 days and 22 months post-infection using histology, immunocytochemistry and electron microscopy. Initially, a few single parasites were observed (day 7) but necrotic lesions and microglial and inflammatory nodules rapidly appeared (9-I4 days). The majority of the lesions between days 9 and I4 contained proliferating toxoplasma and early cyst formation but from 2I days onwards the vast majority of nodules contained neither parasites nor Toxoplasma antigen. Intact intracellular cysts persisted throughout the period of study eliciting no host response. A generalized meningoencephalitis developed by day II and persisted with varying degrees of severity throughout the 22 months studied. At first, the inflammatory cells consisted of lymphocytes and monocyte/macrophages but during the chronic phase plasma cells predominated. In chronic infections, the number of microglial/inflammatory nodules was relatively constant with only a few containing toxoplasmic material resulting from recent cyst rupture. A few brains contained small nodules of dystrophic calcification. This study shows that in these asymptomatic animals, the major feature is perivascular cuffing by mononuclear cells and localized microglial/inflammatory nodules. After the development of the chronic state, there is no obvious increase or decrease in the severity of the pathological changes with time.     

Pathology of acute graft-versus-host disease in the dog. An autopsy study of ninety-five dogs.

The morphology of graft-versus-host disease (GVHD) in canine radiation chimeras was studied by examination of autopsy tissue from 95 dogs including: 1) 13 healthy, untreated dogs; 2) 9 dogs given 1200 R total body irradiation and no marrow infusion; 3) 17 dogs given 1200 R and autologous marrow infusion; 4) 25 dogs given 1200 R and hemopoietic cells from dog-leukocyte-antigen (DLA)--identical littermates; and 5) 31 dogs given 1200 R and nonidentical DLA hemopoietic cells. Some of the dogs in Groups 3--5 received a postgrafting methotrexate (MTX) regimen of 0.25--0.5 mg/kg body weight on Days 1, 3, 6, and 11 and once weekly until Day 102. Prominent lesions were found in the small and large intestines, skin, and liver of dogs with allogeneic grafts. Skin lesions consisted of lymphocytic infiltrates of epidermis with necrosis of basal epidermal cells progressing to denudation. Gut lesions consisted of mucosal destruction progressing from crypt abscess formation to denudation. Liver lesions consisted of portal triaditis, plasmacytic and lymphocytic infiltrates, necorsis and atypia of small bile ducts, and scattered individual hepatocyte necrosis. These lesions were differentiated from changes caused by irradiation and MTX and were deemed characteristic of GVHD. The overall severity of GVHD lesions was less in the identical DLA group than in the nonidentical DLA group, and also less in dogs treated with MTX than in those not given MTX. The degree of lymphoid depletion in the lymph nodes, spleen, and intestinal lymphoid tissue was very similar in dogs with autologous and allogeneic grafts at comparable survival times. No specific evidence of pancreatic or renal involvement in GVHD was discovered.     

冠心病患者FFA水平与冠脉病变程度的相关性分析

目的 探讨冠心病(CHD)患者游离脂肪酸(FFA)水平与冠脉病变程度的关系.方法 选取我院接诊的具备完整病例资料的433例CHD患者为研究对象,另纳入我院同期健康体检者90例为对照组,比较不同类型、冠脉不同狭窄支数和不同冠脉病变Gensini积分CHD患者的FFA水平,分析FFA与冠脉病变程度的相关性.结果 CHD组与对照组甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(APOA1)、FFA比较,差异均有统计学意义(P<0.05),不稳定型心绞痛(UAP)、稳定型心绞痛(SAP)和急性心肌梗死(AMI)组FFA水平均显著高于对照组(P<0.05),UAP组和SAP组FFA水平比较,差异无统计学意义(P>0.05);AMI组FFA水平显著高于UAP组和SAP组(P<0.05);FFA水平随着冠脉狭窄支数和冠脉病变Gensini积分的增加而升高(P<0.05);FFA水平与冠脉病变Gensini积分呈正相关(r=0.309,P<0.05);FFA水平与冠脉狭窄支数呈正相关(r=0.265,P<0.05);FFA>0.57mmol/L是冠脉病变的独立危险因素.结论 CHD患者FFA水平与冠脉病变Gensini积分、冠脉狭窄支数呈正相关,FFA>0.57mmol/L是冠脉病变的独立危险因素,治疗过程中应监测和控制FFA水平.     

冠心病冠脉病变严重程度与红细胞分布宽度及尿酸的相关性分析

目的 探讨冠心病冠脉病变严重程度与红细胞分布宽度及血尿酸的相关性。方法 选取中医药大学第一附属南院心血管病区2016年12月~2017年12月因胸痛疑诊冠心病或已明确冠心病患者134例,根据既往或入院后冠状动脉造影结果,左主干、左前降支、左回旋支、右冠状动脉或其主要分支血管直径狭窄≥50％者为冠心病组共96例,上述主要分支血管直径狭窄＜50％者共40例为对照组。根据冠状动脉病变支数分为单支病变组、双支病变组和三支病变组,采用Gensini法分别对冠脉病变进行评分。结果 冠脉病变严重程度与红细胞分布宽度与血尿酸水平呈正相关,尿酸（OR=1.006,P＜0.05）和红细胞分布宽度（OR=2.450,P＜0.05）的升高为冠心病的独立危险因素,且红细胞分布宽度与UA水平随着冠脉病变支数的增加逐渐递增,三支病变组红细胞分布宽度、血尿酸水平高于单支病变组（P=0.004、0.016＜0.05）,三支病变组红细胞分布宽度水平高于双支病变组（P＜0.05）;双支病变组红细胞分布宽度、血尿酸水平高于单支病变组,三支病变组血尿酸水平高于双支病变组,差异无统计学意义（P＞0.05）,考虑与样本量较小及患者用药控制因素有关。结论 冠心病冠脉病变严重程度与红细胞分布宽度及血尿酸呈正相关。     

Ultrastructure of intramural coronary arteries in pigs with hypertrophic cardiomyopathy.

Pigs with hypertrophic cardiomyopathy diagnosed by echocardiographic examination were selected for study from a genetic breeding herd. Under dissecting microscopic examination, intramural coronary arteries in the septum and left ventricular free wall of euthanized pigs were collected for ultrastructural study. The major lesions of wall thickening included degeneration or denudation of endothelium, subendothelial edema, proliferation of collagen fiber, and hyperplasia of smooth muscle cells. Smooth muscle cells proliferated and migrated through the internal elastic lamella into the intima, which caused the early lesion of wall thickening of the intramural coronary arteries. The extent of smooth muscle cell proliferation was related to the severity of endothelial damage. The smooth muscle cells in the intima were identified by immunohistochemical staining (i.e., smooth muscle actin [SMA] stain). Three major types of severe wall thickening with narrow lumen were observed in the intramural coronary arteries. Edema in the intima caused the major lesion of Type I wall thickening. The internal elastic lamella was broken into small interrupted fragments, and fine fragments of elastic fibers surrounded by the cellular processes of smooth muscle were observed in Type I lesions. Many smooth muscle cells proliferated in the intima and media, which constituted the major lesion of Type II wall thickening of the intramural coronary arteries. Many vacuolized, degenerated smooth muscle cells with fewer sarcoplasmic myofilaments could be clearly observed in the Type II lesions. In advanced cases, severe vacuolization and degeneration of smooth muscle cells with the presence of many bizarrely shaped smooth muscle cells in the walls of the intramural coronary arteries could be observed, which caused the major lesion of Type III wall thickening. Pigs with hypertrophic cardiomyopathy, characterized by spontaneously occurring lesions in intramural coronary arteries, may prove a valuable animal model for human disease.     

血脂异常与老年冠心病患者冠脉病变程度的相关性研究

目的 探讨血脂异常与老年冠心病患者冠脉病变程度的相关性。方法 选取2015年5月~2017年1月本院心内科住院的明确诊断为冠状动脉粥样硬化性心脏病（CHD）的150例老年患者设为CHD组。选取同期收治的150例非CHD患者为对照组。比较两组血清中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平,并计算N-HDL-C、LDL-C/N-HDL-C、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值。比较不同冠脉病变支数、不同病情严重程度的CHD患者的血脂及其比值。对血脂与冠脉病变支数、病情严重程度积分进行相关性分析。结果 CHD组患者LDL-C、TG、TC、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值均高于对照组,HDL-C水平低于对照组,差异均有统计学意义（P＜0.05）;不同冠脉病变支数各亚组间的TC、TG、N-HDL-C水平、TC/HDL-C比值差异存在统计学意义（P＜0.05）;TC、TG、N-HDL-C水平、TC/HDL-C比值均与冠脉病变支数均呈正相关（P＜0.05）;不同病情严重程度亚组间的LDL-C、TC、TG、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C比值差异存在统计学意义（P＜0.05）;CHD患者LDL-C、TC、TG、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C比值与冠状动脉病变积分均呈正相关（P＜0.05）。结论 可以通过对血脂指标的监测,并计算N-HDL-C、TC/HDL-C、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值,来评估CHD病情的临床进展。     

Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice

Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen especially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, spontaneously appeared on the face, neck, ears and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasma levels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4+ T cells containing IL-4 necessary for IgE synthesis. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction, which may be triggered by some environmental factor(s).      

Quantitative ultrastructural analysis of coronary atherosclerotic involvement in two macaque species

Ultrastructural analyses were employed to observe and to compare in detail lesions of the coronary artery of cynomolgus and rhesus monkeys. Animals were fed individually with the same atherogenic ration under identical conditions for 4, 8, and 12 months, and controls of each species were fed with a low fat, cholesterol-free ration. Transmission electron microscopic studies of coronary arteries from these animals led to the following conclusions: (1) Synthetic smooth muscle cells (SMC) without lipid and macrophages without lipid appeared more frequently in the cynomolgus lesions than in the rhesus lesions. Furthermore, phenotypic expression of synthetic SMCs in the cynomolgus was more active with greater diversity, while the rhesus showed less phenotypic modulation. Macrophages without lipid appeared frequently in the cynomolgus media. (2) Increased percentages of both synthetic SMCs with lipid and macrophages with lipid were demonstrated in the cynomolgus lesions as compared to those in the rhesus. This indicates that foam cells, including SMC- and macrophage-derived foam cells, are more prevalent in cynomolgus than in rhesus. They are considered to play an important role in atherogenesis. (3) Medial disruption, synthetic SMCs, and macrophages containing lipid appeared more often in cynomolgus media than in rhesus media. (4) There were greater percentages of both synthetic SMCs and macrophages in the intima of the myocardial side of coronary arteries in both species. (5) Approximately 42% of all foam cells in the cynomolgus lesions were derived from SMCs. There were fewer macrophages in rhesus lesions. (6) The difference in expression between the two macaque species reflects different responses of macrophages to medial smooth muscle cell (SMC) components. The configuration of the artery wall could be one of the important indicators of these different expressions.     

The histopathology of the upper airway in the neonate following mechanical ventilation

Laryngotracheobronchial lesions were carefully documented in 26 neonatal autopsies and were classified into two main types. Type I lesions were focal desquamative or ulcerative, asynchronous, and variable in severity involving areas exposed to contact with endotracheal tube or suction catheter. These lesions are most likely due to trauma of artificial ventilation. Type II lesions were diffuse, necrotizing, more synchronous and uniform in severity involving tissues distal to the endotracheal tube and extending to second or third generation bronchi. The early or mild type II lesions consisted of coagulative necrosis of epithelial cells and mucosal oedema. The late or severe type II lesions showed features similar to those of necrotizing tracheobronchitis described by Metley et al. All the cases with type II lesions had been ventilated with 100 per cent oxygen continuously for at least 3 h during life. The use of pure oxygen may be an important factor leading to necrotizing tracheobronchitis.     

S.E.M. study II: Protective effect of ranitidine against gastric and duodenal lesions induced by non-steroidal anti-inflammatory drugs

The effect of Ranitidine on the gastric and duodenal lesions induced by Aspirin or Piroxicam was studied by scanning electron microscopy (SEM). Twelve patients were entered into the study. The first group consisted of 6 patients with normal basic morphology, of which 3 were treated with 1.5 g of Aspirin and Ranitidine 300 mg/day, and 3 with 20 mg of Piroxicam and Ranitidine 300 mg/day, for one month. The second group was composed of 6 rheumatic patients, 3 of which took 1.5 g of Aspirin and the other 3 received 20 mg of Piroxicam per day for at least four months. Ranitidine (300 mg/day) was then administered concomitantly for one month to all these 6 patients. Overall, Ranitidine appeared to have a positive effect in preventing the development of gastroduodenal lesions induced by these anti-inflammatory drugs in the first group of patients. No differences were observed in the ability of Ranitidine to promote the healing of lesions induced by chronic treatment. Ranitidine, however, appeared to be more effective in preventing lesions induced by Aspirin rather than those induced by Piroxicam.     

Toxic effects of theobromine on mature and immature male rabbits

Mature and immature male rabbits were fed for 120 and 20 days, respectively, a commercial diet containing theobromine in amounts of 0, 0.5, 1 and 1.5 per cent. Clinical, haematological, histopathological and histoenzymological examinations were performed. Mortality, which appeared dose- and time-related, was severe and rapid, mostly in the 1 and 1.5 per cent groups and was attributed to cardiac failure. Theobromine administration resulted in marked changes in thymus and testes and the severity of lesions appeared to be related to the amounts of the ingested methylxanthine. The earliest thymic alterations in immature rabbits consisted of a blurring of demarcation between cortex and medulla accompanied, in the more advanced stages, by a decreased lymphocyte density. Similar lesions were observed in mature animals which had died in the earlier phase of the study. Testicular alterations ranged from vacuolation of spermatids and spermatocytes to multinucleated cell formation and oligospermia or aspermia with extensive degeneration of tubule cells. Some necrotic and post-necrotic myocardial foci were also recorded. The increase in testicular activity of beta-glucuronidase in immature rabbits compared to the untreated animals provided further evidence of an early theobromine-induced damage of the testes.