Simon Sevitt

The structure and growth of valve-pocket thrombi in femoral veins

The structure of 50 small thrombi in femoral valve pockets and the microscopic contents of 35 apparently empty pockets were studied in an attempt to ascertain the nature of the microscopic nidi from which thrombi form and their manner of growth to visible thrombi. Sixteen thrombi had little or no cellular invasion. Most of these recent structures had two main regions, red areas restricted distally in the pocket by the vein wall, and larger white regions comprising most of the thrombus length and often covering the red areas. Red areas are the early sites of cellular adhesion and invasion and the likely sites of origin of most thrombi. They were usually dominated by red cells and fibrin. White zones, which represent propagation growth, are characterized by many foci of platelets with fibrin borders (platelet-fibrin units). Some red areas also contained platelet-fibrin units but they were few and tiny; platelets were not seen in others and one small wholly red thrombus was devoid of platelets. Degenerative changes in platelet-fibrin units were observed, and it is postulated that many become purely fibrin structures. There was no significant evidence of preceding intimal damage in the vein wall. Therefore nidi are laid down on normal endothelium probably on the vein wall near the apex of the pocket. Some pockets, empty of thrombi, contained condensed foci of red cells or tiny fibrin fragments surfaced by endothelial cells and considered to be the remnants of aborted thrombi; a few contained clumps of platelets or leucocytes. It is postulated that any of these may represent the nidi from which thrombi grow. Several thrombi also incorporated large fat droplets, numerous in two. Fat embolic globules derived from fractures are their likely source.

Post-traumatic adrenal apoplexy.

The first description of haemorrhage into the adrenal glands is attributed to Griselius, of Vienna, in 1670 (Doran, 1907). In the nineteenth century cases, mostly of obscure aetiology, were described by Rayer (1837), Dickinson (1863), Mattei (1883), Carrington (1885), Churton (1886), and others, and Arnaud (1900) collected and reviewed 79 cases. Since then reports of patients with gross adrenal haemorrhage have been not infrequent, and the two clinico-pathological pictures of adrenal haemorrhage in the newborn and that associated with fulminating meningococcal septicaemia, now known as the Waterhouse-Friderichsen syndrome, have been separated. This has left many cases associated with diverse conditions. In some the haemorrhage has been spontaneous and unassociated with other disorders (e.g., Pearl and Brunn, 1928; Barsoum, 1936; Thorstad, 1942; Falconer, 1953). Occasionally extensive adrenal haemorrhage complicates severe burns (Dudgeon, 1904; Weiskotten, 1919; Harris, 1929; Snelling and Erb, 1935); sometimes it is associated with pregnancy or the puerperium (Hall and Hemken, 1936; Keele and Keele, 1942; Hurter, 1946; Dewhurst, 1951 ; Crawford, 1951); occasionally the condition complicates ulcerative colitis (Dr. P. N. Coleman, 1954, personal communication; Wilson and Roth, 1953), agranulocytosis (Seligman, 1932), leukaemia (Lauckner and Hebbert, 1947), pneumonia, septicaemia, or cellulitis (Lusk and Brumbaugh, 1919; Seligman, 1932; Hall and Hemken, 1936). In other reports chronic visceral disease has been found (Simmonds, 1902), such as chronic pancreatitis (Lavenson, 1908), hydatid hepatic cyst (Godfrey, 1947), tuberculous pyelonephritis (Thorstad, 1942), and secondary carcinoma (Seligman, 1932), and occasionally fatal adrenal haemorrhage is said to complicate an abdominal operation (Taylor, 1930). The first reports of cases following injury were those of Canton (1863) and Mattei (1883), but haemorrhage into the adrenals of guinea-pigs was observed by Brown-Sequard in 1852 after section of the spinal cord. In his review Arnaud con-

Fatal road accidents in Birmingham: Times to death and their causes

Abstract The intervals between injury and death in the 254 fatalities after road traffic accidents in Birmingham during 1969 and 1970 were analysed and correlated with other data. Sixty-three per cent were pedestrians and 23 per cent were passengers and drivers of vehicles. In round figures, about a third of the series died within half an hour, a half by 2 hours, two-thirds by 24 hours, and three-quarters by 2–4 days. The patterns of survival-time could be divided into three phases. There was an early steep decline, with 36 per cent dying during the first half-hour and 44 per cent within 1 hour of the accidents. This was followed by a longer stage during which the rate of dying decreased progressively in logarithmic fashion. The cumulative tolls were 51 per cent by 2 hours, 58 per cent by 4 hours, 68 per cent by 24 hours, and 83 per cent by 7 days. The curve then flattened into a prolonged tail. Between 7 and 28 days another 10 per cent died, making 93 per cent by 28 days. The remaining 7 per cent succumbed during the subsequent weeks and months, 3 patients surviving longer than a year. Fifty-six per cent of vehicle occupants and 40 per cent of pedestrians died within an hour of injury, and the excess of rapid deaths among vehicle occupants was mainly due to a higher proportion of rupture of the aorta. All the ruptured aortae in vehicle occupants occurred after accidents at night or the early hours of the morning. Many of the affected drivers and passengers had consumed alcohol and their injuries were more rapidly lethal than after accidents at other times. Serious cerebral trauma dominated all groups of road users and multiple injuries were common. Included among the fatality tail was a group of subjects, mainly pedestrians, with relatively modest injuries who might have survived had they not developed pulmonary embolism, respiratory infection, or other complications.

Diffuse and focal oxygen pneumonitis: A preliminary report on the threshold of pulmonary oxygen toxicity in man

Utilizing hyaline membranes and proliferative pneumonitis as evidence of pulmonary oxygen toxicity, the lung changes in 21 patients (19 injured, two inhaled smoke) who died after oxygen therapy are correlated with the intensity and duration of oxygen administration. Diffuse pneumonitis inducing hypoxaemia was found in 10 (or 11) subjects, and in nine of them it was associated with the breathing of high concentrations of oxygen (60 to 100%) for at least two days. In at least eight subjects the pneumonitis contributed to death, and two others who survived for weeks had extensively fibrosed lungs. The breathing of 40% oxygen for a sufficient time seems to be a threshold for dangerous lung effects, since one patient developed a diffuse pneumonitis and another a partly-diffuse partly-focal pneumonitis while exposed to this concentration. Those respiring oxygen concentrations between 25 and 40% for days developed either subclinical focal lung lesions or had no relevant lung changes.

Distal Tubular Necrosis with Little or No Oliguria

The clinico-pathological syndrome of acute renal failure following abortion, incompatible blood transfusion, crush injuries, severe trauma, sulphonamide intoxication, and many other conditions including burns is now well known (Bratton, 1941 ; Dunn, Gillespie, and Niven, 1941 ; Bywaters and Beall, 1941 ; Bywaters and Dible, 1942; Lucke, 1946; Bull, Joekes, and Lowe, 1950; Bull and Dible, 1953). Clinically it is characterized by a short onset phase during which the flow of urine rapidly falls. Then follows the period of anuria or severe oliguria. This was defined by Bull as the excretion by an adult of not more than 300 ml. of urine per day and usually considerably less. This state may last up to a week or longer; uraemia develops and commonly proves fatal. Recovery is heralded by a period of diuresis during the early phase of which tubular function is seriously limited. By ordinary histological methods the kidneys show multiple, often discrete necroses of many distal tubules frequently associated with tubular blockage by haemoglobin or other casts. Rupture of tubules and dislocation of casts into the interstitial tissue and veins produce a peritubular and perivenous infiltration of inflammatory cells, tubulo-venous anastomoses, and thromboses. By microdissection of individual nephrons Oliver and his colleagues (Oliver, MacDowell, and Tracy, 1951; Oliver, 1953) have shown that the tubular necrosis is widespread and frequently involves the first convoluted tubu!e. The purpose of this paper is to describe a number of subjects whose kidneys showed either these changes or their residue and in whom oliguria either did not occur or was transient or slight. With one exception all were severely burned. A few died before uraemia could develop, some became uraemic, and in others uraemia did not occur. Thus, in addition to the well-known uraemia-oliguria syndrome, uraemia may occur with an adequate flow of urine. This is important to recognize, because the patients chance of survival has increased with the introduction of high-calorie, low-nitrogen feeding. The finding of one case of post-traumatic uraemia with little or no oliguria indicates that this form of renal failure is not restricted to burned patients. It will be shown that the difference between the uraemic and non-uraemic forms generally has a morphological basis, and that the tubular dysfunction in these uraemic subjects differs from that reported in the oliguric type of acute renal failure (Bull et al., 1950).

Traumatic ruptures of the aorta: a clinico-pathological study

Abstract Thirty-seven subjects with traumatic ruptures of the aorta coming to necropsy between 1958 and 1975 were analysed. All had been involved in road accidents and most had suffered multiple injuries. Most had survived to be admitted to hospital, and 25 lived for up to 13 days. The ruptures can be divided into those in ( a ) the ascending aorta (7 cases), ( b ) the proximal descending aorta (25 cases) and ( c ) the distal descending thoracic aorta (5 cases). Ruptures of the distal thoracic aorta were confined to pedestrians and motor cyclists with local hyperextension dislocations of the spine. Occupants of vehicles suffered ruptures of the proximal descending aorta (15 cases) or the ascending part (2 cases). All tears were transverse and internal, involving intima and media. The adventitia was intact though usually haemorrhagic. Ruptures of the ascending aorta (2 drivers, 5 pedestrians) were supravalvar and 6 were on the posterior wall. With one exception, these ruptures were associated with severe chest trauma from direct impact. Ruptures of the proximal descending aorta were located 1–3 cm beyond the left subclavian artery. The tears were major in 22 subjects, some of which were circumferential, whilst others affected part of the wall. False aneurysms contained by intact adventitia had formed in those surviving more than a day. In most cases haemorrhage had tracked into the mediastinum, finally rupturing into the pleural cavities, usually the left. However, two immediate survivors died later from complications of other injuries. In 3 subjects, only small subclinical tears were present and similar small ones were found near several major ruptures. Most major and minor ruptures are above the ligamentum arteriosum and on the anterior aortic wall, indicating a mechanism involving cranially directed tension on the aorta. Thoracic injury was also common in these, but was absent in 7 cases (including 3 motor cyclists and 2 pedestrians). This suggested that at least some ruptures result from indirect forces such as body deceleration. One rupture seemed due to a blow directed upwards against the lower chest. Analysis of all road traffic deaths in Birmingham over a 2-year period showed that aortic rupture is a major cause of rapid death among vehicle occupants, and that this is related to accidents at night and alcohol consumption.

The Spleen and Blood Eosinopenia

Within a few hours of injury or burning the number of eosinophils in the blood falls progressively to reach low or zero values and this eosinopenia (Fig. 1) lasts up to a few days (Laragh and Almy, 1948; Roche, Thorn, and Hills, 1950; Hardy, 1950; Sevitt, 1951, 1954; Evans and Butterfield, 195 1). The endocrine control of eosinopenia is known to be due to release of adrenocortical hormones through stimulation of the anterior pituitary, but the manner in which the eosinopenia is produced is in doubt. The question has been recently reviewed by Essellier, Jeanneret, and Morandi (1954). Several possible explanations could account for the eosinopenia, viz., (1) inhibited release of

ACUTE HEINZ-BODY ANÆMIA IN BURNED PATIENTS

Abstract Haemolytic anaemia associated with many Heinz bodies and necessitating large blood-transfusions is described in three extensively burned patients, two of whom were young children. It was delayed in onset. Anaemia improved and Heinz bodies disappeared when drugs were discontinued—cloxacillin, probenecid, and aspirin in one case; cloxacillin, ampicillin, aspirin, and digoxin in another; and gentamicin and carbenicillin in the third. Follow-up studies in the two survivors revealed no deficiency in glucose-6-phosphate dehydrogenase or other enzymes concerned with aerobic glycolysis. The burns in two patients were treated locally with silver nitrate, and they became infected with Pseudomonas œruginosa in the three patients. Two patients had episodes of unexplained cyanosis, and methaemoglobinaemia has been found in other burned patients. Though the haemolytic process seems to have been aggravated or precipitated by drugs, multiple factors may have been concerned in predisposing the red blood-cells to oxidative degradation, including the residual effects of heat, bacterial infection, and local therapy with silver nitrate. The condition may be an overt manifestation of a more frequent red-blood-cell disorder induced by burning, complications, and therapy.

Reflections on mortality and causes of death after injury and burns

Abstract The study of mortality and causes of death after injury and burns has both academic value and important practical applications. Knowledge of the main causes of illness leading to death exposes problems requiring solution, whilst statistical analysis of mortality may help to assess the value of new remedies.

Coronary Thrombosis following Injury and Burns

Cases of recent coronary thrombosis, with or without myocardial infarction, are described in injured and burned subjects. Although the thrombi were associated with atheromatous disease, they cannot be set aside as being always or wholly due to natural causes because other cases with little or no coronary atheroma have been reported. Periodic thrombosis in renal arteries and other uninjured vessels strengthens the argument for a connexion between trauma and arterial thrombogenesis in some cases. The appearance of pulmonary microthrombi in most injured and burned cases and of glomerular microthrombi in some subjects indicates that thrombogenesis is a frequent systemic reaction to injury; whilst post-traumatic activation of the coagulation mechanism and a consumptive coagulopathy involving circulating platelets and clotting factors seem underlying mechanisms. Arterial thrombosis in injured or burned subjects may be regarded as a breakdown of the unsteady, post-traumatic equilibrium between thrombogenesis and thrombolysis. Under these circumstances, atherosclerosis could act as a predisposing and localizing factor, whilst thrombosis in coronary arteries would be the most important manifestation.