Repeat Injury Research Articles

Current issues in thrombosis prevention with antiplatelet drugs.

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.

Cutaneous vascular ectasia treated by non-laser infra-red

The use of lasers to treat abnormal vasculature of the skin is proliferating. However there is now considerable evidence that, despite its theoretical advantages, the argon laser causes a rather non-specific thermal burn: the CO2 laser, which vaporizes tissue on contact, has produced satisfactory results in treating port wine stains. This casts doubt on whether laser radiation or specific wavelengths are essential for the results being obtained. The MBB-AT infra-red coagulator is a cheap portable machine which produces non-specific thermal damage. It has a maximal output at 960 nm. We have previously shown that the cosmetic results of treating tattoos in this way compares favourably with other methods. We have now investigated histologically the relationship between the duration of each pulse of infra-red and the depth of injury in pig skin using stains for viable collagen. Between 0.625 s and 1.125 s the relationship was linear. Thus, the coagulator gives a predictable and repeatable injury, and this property has been utilized in man. Using pulses just shorter than those which cause collagen damage we have had most encouraging results in the treatment of vascular ectasia including port wine stains in 10 patients.

Muscle changes during reinnervation after repeated nerve injuries.

Localized freezings of adult rat sciatic nerve, repeated 2 to 5 times at monthly intervals, induced a series of profound changes in the gastrocnemius muscle. In particular, many type IIC fibres were observed one month after the last freezing. However, this muscle transformation was not stable. Our combined cytological, cytochemical and electrophysiological results provide evidence for multiple and polyneuronal innervation of these type IIC fibres.

Endothelial injury and atherosclerosis

In previous work, it has been shown that continued or repeated injury to the intima of arterial vessels in normal rabbits causes a spectrum of atherosclerotic lesions which include raised atheroma-containing plaques, fatty streaks, and fibromusculo-elastic plaques. On removal of the injurious stimulus, these lesions regressed rapidly, the residuum being a non-lipid-containing fibro-musculo-elastic plaque. The development of raised lipid-containing lesions can be markedly inhibited by making the rabbits thrombocytopenic with antiplatelet serum or a combination of Busulphan and antiplatelet serum. This indicates that the thrombotic process which accompanies repeated intimal injury, plays a key part in the development of lipid-containing lesions. Similarly, the fibro-musculo-elastic intimal thickening that follows a single removal of the endothelial layer of the rabbit aorta by balloon embolectomy catheter can also be markedly inhibited by exposing the rabbits to antiplatelet serum which induces severe thrombocytopenia. Taken together, these findings indicate that repeated damage to the endothelium might be an important mechanism by which lipid-containing raised lesions are induced. To examine this more closely in terms of a specific endothelial injury, the endothelium of rabbit aortas was removed six times at 2-week intervals employing a balloon embolectomy catheter. Animals killed at 1, 3, and 7 weeks following the last balloon injury showed preferential accumulation of lipid in intimal plaques covered by regenerated endothelium around aortic branches. In animals killed 6 months or 1 year following the last ballooning, lipid was seen preponderantly where the endothelium had regenerated from the orifices of aortic branches. The lesions resembled human fibro-fatty plaques or fatty streaks. In the areas where endothelial regeneration had not occurred, lipid was infrequently observed. The accumulation of lipid may relate to binding of lipoprotein to proteoglycans formed in the areas where the endothelium is repeatedly removed and regenerates.

Response to experimental implantation of autologous iris tissue and to iris injuries.

Autoimmune disease has been suspected in some cases of human uveitis. The initiating event has been thought to be injury and/or infection. To investigate the effect of injury on the uvea and on the immune apparatus rabbits and guinea pigs were subjected to various repeated iris insults, including implantation of autologous iris tissue into the anterior chamber of the contralateral eye. Of the procedures employed only iridectomy and insertion of iris produced some anterior chamber clouding, which was only slightly increased on repetition of the procedure; 76% of these animals failed to produce circulating CF antibodies. No local CF antibodies in the anterior chamber fluid nor increases in fluorescent antibodes in sections of the eyes could be detected. None of the animals tested developed skin hypersensitivity to homologous uveal antigen. None of the other traumatic procedures, which included repeated insertions of plastic into the anterior chamber, produced uveitis manifested clinically or by histological examination, circulating or local humoral antibodies, nor increases in fluorescent antibodies in the tissues of the eye. Introduction of antiuveal antibody into the anterior chamber also failed to produce uveitis. It can be concluded from these experiments that simple, repeated injury to the iris is not sufficient to elicit an autoimmune response under the conditions tested.

Tracheal basement membrane thickening in rhesus monkeys.

Thickened hyaline tracheal membrane similar to that which occurs with several respiratory conditions in man was seen in Rhesus monkeys. The membrane was eosinophilic and up to 50.4 μm thick. Frequently eosinophils and mast cells were seen in the tracheal mucosa and submucosa. Using fluorescent microscopy, IgG, B1C, B1A and albumin were identified in the membrane. Electron microscopy showed that the membrane was composed of 18.8-nm collagen-like fibrils with occasional periodicity. The cause of the thickened hyaline tracheal membrane could not be determined. The changes probably represent a response to mild repeated or continuous tracheal injury owing to a variety of causes. Delineation of the cause of this process in nonhuman primates may help in the understanding of respiratory diseases in man.

Roentgenographic Manifestations of Unsuspected Trauma in Infancy

Twenty-five cases of unsuspected trauma in young children have been recognized in a 2-year period. They presented characteristic roentgenographic manifestations. Multiple sites of bony involvement were identified, in different stages of healing. The history and clinical aspects were frequently misleading, and the fact of wilful, repeated injury to the child was generally either unrecognized or concealed by the informant. The case of an 8-month-old girl is described. She was admitted twice for treatment of fractures, each time with evidence of repeated injuries. Recognition of these findings becomes important in safeguarding the infant from further injury.

SPECIAL ARTICLE

A major problem of child health today is the prevention of accidents. Part of the answer to this problem lies in the answer to the question of why some children have more than their share of accidents. Although there is an extensive literature on the accident-susceptible or accident-prone adult, there has been but little written on this aspect of the accident-prone child. Much remains to be done in order to identify the respects in which children who have repeated accidents differ from their fellows. In spite of the lack of reported studies of children there has been a tendency to talk about the accident-prone child and to attribute to him the personality characteristics and motivations seen in the adult accident repeater. It was with a desire to do something about it, and not merely to talk about it, that the study, of which this paper is a preliminary report, was begun at the Babies Hospital of the Columbia-Presbyterian Medical Center, New York, in the fall of 1951. The purpose of this investigation was to explore methods for identifying and determining the significance, in relation to the incidence of accidents in children, of parental attitudes, parent-child relationships, environmental accident hazards, personality characteristics and functioning of the child, physical coordination and physical disabilities as these are reflected in the experience of the accident repeater. It was planned to do this through the study of a relatively small number of children of school age and their environment, both personal and physical, comparing a group who have had repeated accidents with a group who have no accident history. Even though the number of children studied would be small some questions might be answered. In addition, leads for further investigations with a larger number of children might emerge. In any event, it would be discovered whether the proposed approach in the study would bring out meaningful information. The plan was to select for investigation 10 or 12 children of average intelligence who had been brought to the Emergency Clinic of the Columbia-Presbyterian Medical Center for treatment of accidental injuries at least 3 times during the 18 month period prior to the outset of the study. Children whose only accidents had been traffic or who had had severe or repeated head injuries were to be included.

Osteochondritis dissecans: Report of cases involving elbow, ankle and metatarsophalangeal joints

1. 1. Three cases of osteochondritis dissecans are reported occurring in joints other than the knee, i.e., elbow, ankle, and metatarsophalangeal joints. 2. 2. The lesion may be produced by traumata varying widely in type and intensity from a single, severe crushing injury to a mild, repeated injury resulting from the forces brought into play by joint movements. 3. 3. The treatment is the surgical removal of the detached fragment.

TERATOMA OF THE TESTICLE: ASSOCIATED WITH REPEATED INJURY AND WITH MISPLACEMENT

TERATOMA OF THE TESTICLE: ASSOCIATED WITH REPEATED INJURY AND WITH MISPLACEMENT

An Investigation of the Physical Nature of Cancer Cells

Introduction In our investigation of the physical nature of cancer cells we have sought evidence in support of the widely held theory that cancer owes its development to some alteration in the cells of the tissues as the result of some mechanical, physical or chemical factor. To this end we have been endeavoring to discover some physical principle which might account for the conversion of normal cells into cancer cells as the result of single or repeated injury; for cancer cells do not originate in uninjured, unchanged tissues, but in tissues which have been subjected to chronic irritation. It is clear that the cancer cell must owe its formation to the operation of existing laws of growth in the host, for cancer originates and lives only in the living. The problem, therefore, is concerned with the struggle for survival between the cancer cell and the normal cell; and the logical point of attack would seem to be the characteristics of the normal cell. We have therefore been trying to discover what physical differences might account for the conversion of differentiated into undifferentiated cells; of cells whose energy is used primarily for function into cells whose energy is used primarily for growth.

SUBCOSTAL NEURITIS AS A CAUSE OF ABDOMINAL PAIN

The condition to which I am calling attention is a clinical entity that seems to be generally unrecognized, though it is of fairly common occurrence and is of practical importance. Traumatic neuritis may be produced by a single or repeated injury to a nerve trunk, and the condition that I present belongs to the latter group. The intercostal nerves are shielded from injury by intact ribs except when they pass beyond the tips of the last few ribs. At this point, the eleventh and twelfth especially, may be injured in various ways. The commonest method of nerve injury to these last two nerve trunks is by the repeated squeezing of the nerve between the tips of the ribs and the wing of the pelvis. This repeated trauma is seen in short waisted persons or in those who have an unusually long eleventh or twelfth rib. The pain is of a