Reginald S.A. Lord

S-100 positive cells in human arterial intima and in atherosclerotic lesions

OBJECTIVE The presence of previously unrecognised cells has been detected during ultrastructural investigations of normal and atherosclerotic human aortic intima. These cells show many of the morphological features of dendritic cells. Because dendritic cells can be stained positively for S-100, the aim of this study was to determine whether S-100 immunoreactive cells can be detected in the arterial wall, and if so, how they are distributed in normal intima and in atherosclerotic lesions. METHODS Paraffin sections of human aorta and carotid artery were stained with S-100 antibody, using an immunoperoxidase technique. RESULTS In areas of the arterial wall without histological signs of atherosclerosis, S-100 positive cells were found but they were relatively few compared with the much greater numbers of S-100 positive cells showing dendritic cell morphology in atherosclerotic lesions. Different atherosclerotic lesions were found to contain different numbers of S-100 positive cells. In fatty steaks and in uncomplicated atheromatous plaques, many S-100 positive cells were present, but in complicated atherosclerotic lesions fewer such cells were found. CONCLUSIONS Although the nature of these S-100 positive dendritic cells needs further clarification, the results suggest that these cells play an important role in the development of atherosclerotic lesions, and may represent antigen presenting dendritic cells in human arteries. If the S-100 positive cells prove to be part of the family of antigen presenting dendritic cells, the findings have important implications for understanding atherogenesis and offer a link between immune mechanisms and atherosclerotic lesion formation.

Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions.

The present study was undertaken to examine the cellular composition of the aortic wall in Takayasus arteritis and to investigate the association of different cell types in the immuno-inflammatory reactions of this disease. Specimens of aortic wall affected by Takayasus arteritis were obtained from 10 patients (five male, five female), aged 32 to 68 years (mean 49.5 years) at elective operation. The mean duration of disease was 6.5 years (range 2 months to 13 years). Specimens were embedded in paraffin and the sections stained with antibodies to CD3 (to identify T cells), CD20 (B cells), S-100 (dendritic cells), CD15 (granulocytes), CD68 (macrophages), alpha-SMA (smooth muscle cells) and von Willebrand factor (endothelial cells). Immunohistochemical examination demonstrated that all specimens showed histological alteration with the replacement of the muscular and elastic layers of the media and adventitia by dense fibrous tissue, and were characterized by varying degrees of inflammatory cell infiltration. In five cases, inflammatory nodules consisting of numerous T cells and B cells were observed in the adventitia. Within the inflammatory nodules, as well as around areas of neovascularization in the deep portion of the intima, lymphocytes were co-localized with dendritic cells. In addition, in the adventitia, the accumulation of a large number of granulocytes was observed. The present study demonstrates that immune inflammation is a typical feature of Takayasus disease, and that the interactions between dendritic cells and lymphocytes may be important in the control of the immune reactions in this vascular pathology.

The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep

PURPOSE This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. METHODS Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, five and six notches of closure. The extent of endothelial injury was assessed by using a dedicated computer assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. RESULTS For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 +/- 0.28 newtons) and four notch (5.68 +/- 0.29 newtons) closure compared with that for five notch (6.19 +/- 0.31 newtons) and six notch (6.61 +/- 0.16 Newtons) closure (p = 0.01). For carotid arteries, three notch (5.68 +/- 0.28 newtons) closure caused less damage than did four notch (7.98 +/- 0.29 newtons), five notch (9.17 +/- 0.40 newtons) and six notch (9.57 +/- 0.64 newtons) closure (P = 0.02). Scanning electron microscopy confirmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. CONCLUSIONS The closing forces generated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood flow.

Prospective Randomized Trial of Polytetrafluoroethylene and Dacron Aortic Prosthesis. I. Perioperative Results

Over a two year period 80 patients were entered into a prospective randomized trial comparing polytetrafluoroethylene (PTFE) and Dacron infrarenal aortic reconstructions. Fifty-four patients were treated for aneurysm (30 single tubed grafts; 24 bifurcation grafts), and 26 patients were treated for occlusive disease (26 bifurcation grafts). The groups were matched for age, sex and preoperative risk factors. Five patients died after operation (6.3%) including two from hemorrhage, but there were no significant differences in mortality and morbidity between the PTFE and Dacron groups. The volume of blood lost at operation (1930 +/- 1340 ml, all patients); the volume of blood transfused (2.98 +/- 2.43 units); the volume of crystalloids infused (3050 +/- 1390 ml); the intraoperative heparin dosage (67.9 +/- 20.5 mg); the clamp time (71.6 +/- 34.5 min); and the total operating time (228.1 +/- 78.3 min) also showed no significant differences between PTFE and Dacron. The ankle systolic pressure index rose more for PTFE (0.96 +/- 0.24) than for Dacron (0.82 +/- 0.20; P less than 0.002) at the time of discharge. This partially reflects a difference in the index between the groups before operation (PTFE 0.79 +/- 0.30; Dacron 0.72 +/- 0.32), but it may also indicate that PTFE is less thrombogenic than Dacron.

The cell adhesion molecule E-cadherin is widely expressed in human atherosclerotic lesions

OBJECTIVE Various cell adhesion molecules are expressed in atherogenesis and the significance of their involvement in atherosclerotic lesion formation is well appreciated. In the present work, we examined whether the Ca(2+)-dependent cell adhesion molecule E-cadherin is also involved in atherogenesis. METHODS Specimens of carotid artery and aorta were obtained at operation. Expression of E-cadherin was studied by an immunohistochemical method. The nature of E-cadherin-expressing cells was examined by comparative analysis of consecutive sections and by a double immunostaining procedure. An immunohistochemical approach was also applied to examine how the accumulation of oxidised low density lipoproteins (LDL) by intimal cells is associated with E-cadherin expression. RESULTS No E-cadherin+ cells were found in normal non-atherosclerotic intima but E-cadherin+ cells were present in 96% of the atherosclerotic lesions. In atherosclerotic intima, E-cadherin was expressed by intimal cells showing varying degrees of transformation into foam cells. These E-cadherin+ cells also contained oxidised LDL in their cytoplasm. Differing numbers of CD68+ foam cells (15% to 60%) expressed E-cadherin but all the CD68+ macrophages without signs of transformation into foam cells were negative for E-cadherin. Neither smooth muscle cells nor foam cells of smooth muscle cell origin (smooth muscle alpha-actin+) were found to be positive for E-cadherin. T-cells (CD3+) and endothelial cells (von Willebrand factor+) were also negative for E-cadherin. Only a few vascular dendritic cells (S-100+) expressed E-cadherin and their expression was weak. We also found that a large proportion (40% to 85%) of E-cadherin+ cells did not stain with any cell-type specific markers. CONCLUSIONS The finding that E-cadherin is expressed in atherosclerotic lesions expands our knowledge of cell adhesion molecules involved in atherogenesis. That E-cadherin is expressed in intimal cells transforming into foam cells suggests that lipid accumulation might be associated with the alteration and reorganisation of cell-to-cell interactions in atherogenesis. The present observations might assist in understanding the mechanisms associated with intracellular lipid accumulation.

VCAM-1 expression and network of VCAM-1 positive vascular dendritic cells in advanced atherosclerotic lesions of carotid arteries and aortas

This study was undertaken to determine whether vascular dendritic cells (VDCs) display VCAM-1 in atherosclerotic lesions. Specimens of carotid artery and aorta were obtained at operation. All the plaques contained VCAM-1+ cells, but VCAM-1 immunoreactivity was irregularly distributed being mainly associated with the zones of neovascularisation in the base of the atherosclerotic plaques. Vascular dendritic cells were identified with DAKO-CD1 a. Alternative parallel sections were stained with either anti-CD1 a or anti-VCAM-1. By comparison of consecutive parallel sections the CD1a+ vascular dendritic cells were located separate from other intimal cells. In some areas networks formed by VCAM-1+ vascular dendritic cells were observed suggesting that cellular networks may mediate a local immune response in atherosclerotic lesions. We speculate that VCAM-1 is involved in the formation of cell-to-cell contacts of vascular dendritic cells in atherogenesis.

55-kD Actin-bundling Protein (p55) Is a Specific Marker for Identifying Vascular Dendritic Cells

Compared with other members of the dendritic cell family, the antigen profile of the recently recognized vascular dendritic cells has received limited attention. This study demonstrates that vascular dendritic cells in the human aorta and carotid arteries express 55-kD actin-bundling protein (p55), a specific marker for blood dendritic cells and Langerhans cells. This finding will facilitate screening of dendritic cells during their isolation from the arterial wall, as well as other investigations.

Accumulation of co-localised unesterified cholesterol and neutral lipids within vacuolised elastin fibres in athero-prone areas of the human aorta

To investigate whether there are alterations of elastin fibres in the arterial intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic aorta were taken soon after death from 13 healthy trauma victims whose ages ranged from 16 to 40 years. Two areas were compared: atherosclerosis-prone (AP) areas localised to the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas from the ventral aorta. Electron microscopic analysis combined with cytochemical staining was applied. Unesterified cholesterol was identified using the filipin-staining technique while neutral lipids were visualised by the OTO-technique. Intimal features were studied by combining the filipin-staining and the OTO-technique. Electron microscopical examination showed that in both AR and AP areas, some elastin fibres in the intima were vacuolised. Unesterified cholesterol was found to be predominantly localised in the musculoelastic layer, in particular, inside the vacuolised elastin fibres. This localisation was seen in all 13 AP areas studied in contrast to the AR areas where it was observed in only four of 13 aortas studied (P < 0.0005, chi2-test). Accumulation of neutral lipids inside vacuolised elastin fibres was found in five out of 13 AP areas but was not observed in any of the AR areas (P=0.01, chi2). A combination of the filipin-staining and OTO-techniques showed that some deposits of neutral lipids and unesterified cholesterol within vacuolised elastin fibres were independently located from each other, but more frequently, neutral lipids were co-located with unesterified cholesterol. The present observations indicate a difference between AP and AR intimal areas which, in particular, relates to the structure of elastin fibres in the musculoelastic layer. The observations suggest that alterations of the extracellular matrix are involved in the trapping and retention of cholesterol and neutral lipids within the intima at an early stage in the development of atherosclerotic lesions.

Ernst Ferdinand Sauerbruch: Rise and Fall of the Pioneer of Thoracic Surgery

Ferdinand Sauerbruch (1875–1951) was a pioneer of thoracic and cardiac surgery and is undoubtedly one of the twentieth centurys most outstanding surgeons. Before 1904 operations on the thorax met with fatal complications due to pneumothorax. Sauerbruch developed a pressure-differential chamber that maintained normal respiration and enabled safe operations to be undertaken on the thorax. Together with von Mikulicz, he initiated intrathoracic operations and later developed various surgical procedures on the mediastinum, lungs, pericardium, heart, and esophagus. The simple yet effective techniques of positive-pressure ventilation replaced the expensive, cumbersome negative-pressure chamber. Sauerbruchs latter years were marred by dementia that adversely affected his personality, intellect, and capacity as a surgeon. The unjustifiable toll of increasing patient morbidity and mortality forced authorities to dismiss him in 1949. He died at the age of 76 in Berlin. After almost a century since the advent of the first safe thoracic surgery, the advances in technique and technology have been enormous. A great deal is owed to the inspiration and contributions of Ferdinand Sauerbruch.

Traveller's venous thromboembolism.

I N T R O D U C T I O N Venous Thromboembolism (VTE) is a serious disorder which may have a fatal outcome in 1 to 2% of the sufferers.1 The annual incidence of VTE in Caucasian populations is 1 to 2 per 1000.2-5 This incidence is age dependant and climbs from virtually zero in children to less than 1 per 10 000 in young adults and 3-5 per 1000 in people over the age of 60 years.6 A serious disabling long-term consequence of deep venous thrombosis (DVT) is postthrombotic syndrome which may present with pain, trophic skin changes and ulceration.7 Approximately 10 to 30% of patients will ultimately develop chronic venous insufficiency after DVT. Fatal pulmonary embolism (PE) occurs in 1-2% of all patients.3