Thorotrast-induced primary cerebral angiosarcoma: case report.

OBJECTIVE: Thorotrast was used as a contrast medium in clinical practice until the 1960s for outlining cerebral abscess cavities and ventricular cavities, and for angiography. Gliosarcomas, meningiomas, and schwannomas have been reported previously, as has Thorotrast-associated angiosarcoma, typically in the liver. A unique case of a primary intracerebral well-differentiated angiosarcoma in a 68-year-old man with a history of colocalized exposure to Thorotrast is described. This may be the first case of a primary angiosarcoma in the brain. CLINICAL PRESENTATION: The patient presented with a progressive left-sided weakness 62 years after initial surgery for a right parietal cerebral abscess, which included the instillation of Thorotrast into the abscess cavity. Computed tomography showed a right parietal tumor. INTERVENTION: An explorative craniotomy showed an intrinsic, infiltrating, very vascular tumor with surrounding calcification. The tumor appeared to arise from a benign cavernous vasoformative lesion intimately associated with a Thorotrast-type granuloma. The patient declined further surgery or radiotherapy. CONCLUSION: The histology, confirmation of radioactivity of the material obtained from within the tumor, and latency period of presentation provide compelling support for tumor induction by the Thorotrast. Primary lesions of the central nervous system associated with Thorotrast are very rarely reported, despite its extensive use in cerebral angiography and management of brain abscess between 1930 and 1960.

Thorium dioxide-related haemangiosarcoma of the liver.

Rare tumours of the liver are occasionally seen; thorium dioxide-related haemangiosarcoma of the liver, with an estimated frequency of 0.14 to 0.25 per million in the normal population, is one of these. Causes, epidemiology and pathobiology are described related to a clinical case of angiosarcoma. A differentiation of hepatic tumours with imaging techniques is presented. Last, a short review on up-to-date treatment of haemangiosarcoma is discussed. Lessons can always be learned from history: will the contrast agent gadolinium be the Th232 of this era?

Ultrastructural studies on the intracellular fate of Chlamydia psittaci (strain guinea pig inclusion conjunctivitis) and Chlamydia trachomatis (strain lymphogranuloma venereum 434): modulation of intracellular events and relationship with endocytic mechanism.

Previous observations on the highly infectious LGV strain 434 of Chlamydia trachomatis and the guinea pig inclusion conjunctivitis (GPIC) strain of C. psittaci (which requires centrifugation of inocula with host cell monolayers for maximum infectivity) indicated that infectivity differences were expressed, not at entry, but at an intracellular stage affecting multiplication. Centrifugation increased the potential of internalized chlamydiae to undergo productive infection. Here, analysis of the intracellular fate of chlamydiae by ultrastructural methods indicates that strain GPIC exhibits two patterns of behaviour depending on the mode of inoculation. Strain GPIC showed limited entry, with 47% of intracellular organisms becoming associated with thorotrast-labelled lysosomes, following static incubation with monolayers. In contrast, with centrifugation, entry was not limited and association with lysosomes was reduced to 12%; strain 434 behaved similarly but independently of the mode of inoculation. The different results for strain GPIC correlated with distinct entry mechanisms. Entry during static incubation was unimpaired either by treatment with cytochalasin D or by temperature reduction to 20 degrees C, suggesting that it was pinocytic. Entry during centrifugation was markedly impaired by both treatments, suggesting that it was phagocytic. The data lead to two novel conclusions: first, that chlamydiae can apparently enter cells by both pinocytic and phagocytic mechanisms; second, that the entry mechanism influences intracellular fate. It is suggested that entry mechanism is linked to selection of the vesicle membrane forming around the internalizing chlamydiae. This, in turn, may influence both intracellular translocation and subsequent inhibition or promotion of multiplication of the internalized parasite.

Chemical blockade of the reticuloendothelial system results in arteriolar spasms: possible role of endothelial cells.

Scattered qualitative studies in the literature suggest that the reticuloendothelial system (RES) interacts with the microcirculation to effect host defense and that chemical or pharmacologic blockade of the RES might compromise the microcirculation. With this possibility in mind, we designed experiments in rats to determine whether colloid and pharmacologic blockade of the RES could alter microvascular tone and reactivity. The effects of colloidal carbon, thorium dioxide, tripalmitin and tetracycline on reticuloendothelial system phagocytic function, mesenteric terminal arteriolar tone and arteriolar reactivity to noradrenaline and acetylcholine were examined in situ at magnifications up to 5000x. Colloidal carbon and thorium dioxide, in the doses utilized, produced complete blockade of the RES. Treatment with tripalmitin and tetracycline produced pronounced RES depression. RES blockade and depression were associated with marked reductions in terminal arteriolar lumen sizes, curtailment of capillary inflow and outflow, hyper-reactivity to the constrictor, noradrenaline, and hypo-reactivity to the dilator, acetylcholine. Close examination of the endothelial linings of the capillaries, postcapillary venules and terminal arterioles of the experimentally-treated animals indicated pronounced uptake of carbon particles in the endothelial cells, different degrees of endothelial cell swelling and often bulging into the microvessel lumens. Our findings suggest that RES-induced alterations in microvascular tone and arteriolar reactivity may be related to injury of the microvascular endothelial cells.

Pseudosecondary antibody response to LPS induced by toxins for macrophages.

A single dose of bacterial lipopolysaccharide, administered 21 days after mice had been treated with the macrophage toxins carrageenan, or microparticulate crystalline silica, resulted in a secondarytype antibody response. The phenomenon of pseudosecondary responsiveness was investigated to determine the mechanism for its generation. The results showed that generating a pseudosecondary response was T cell dependent; but except for this, it followed the same kinetic and genetic patterns as a true, two dose of antigens, secondary response. It was concluded that pseudosecondary responsiveness resulted from priming the mice by the consequential effects of the macrophage toxins; thereafter, secondary responsiveness to LPS was generated in a normal manner.

Effect of scarlet fever toxin on the phagocytic activity of the reticuloendothelial system.

In normal rabbits and mice, one i.v. injection of scarlet fever toxin (ET) (30 000 STD per kg of rabbit weight or 20-g mouse) elicited a similar biphasic change in carbon clearance rate - early depression followed by a stimulating phase - as has been described for Gram-negative endotoxins. Prolonged depression without a subsequent stimulation phase was obtained in mice by raising the ET dose. The reasons of the discrepancy between these findings and those of Hanna and Watson (1965b) are discussed. Pyrogenic tolerance to ET is not accompanied by accelerated carbon clearance and is not impaired by RES blockade. A possible mechanism of ET tolerance is suggested.

Transplacental transmission and fetal parasitosis of Trypanosoma cruzi in outbred white Swiss mice.

Two strains of Trypanosoma cruzi, isolated from humans and assayed for their biological capacity to kill outbred white Swiss mice (HaM/CR-CD) following reticuloendothelial system blockade with thorium dioxide, were used in these experiments: the Maria Cristina strain, which killed all blocked mice at a rate following a rectangular dose-response curve, and the José Cardoso strain, which did not kill blocked mice at comparable dosages. When inoculated into pregnant HaM/CR-CD mice, the non-pathogenic José Cardoso strain did not cross the placental barrier, in either blocked or unblocked mice, to cause fetal parasitosis. The pathogenic Maria Cristina strain did not cross the barrier in non-blocked mice, but in thorium-dioxide blocked mice it produced an incidence of fetal parasitosis of 8.9% (7 of 79 fetuses). These results indicate that the transplacental transmission of T. cruzi was dependent on two restrictions: pathogenicity of the strain of T. cruzi, and blockade of phagocytic activity by thorium dioxide, suggesting that transplacental transmission of T. cruzi is related to interference with the phagocytic activity of the placenta.

Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression.

Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.

Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals.

Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

Experimental bacterial endocarditis. IV. Structure and evolution of very early lesions.

The vegetations of experimental sterile and bacterial endocarditis in rabbits were studied using light, immunofluorescent and electron microscopy. At an early stage, both lesions were composed chiefly of masses of platelets supported in a scaffolding of fibrin strands. In previous studies, this structure has often been described merely as "fibrin". After i.v. injection of Thorotrast, sterile vegetations showed remarkable accumulations of mononuclear phagocytes containing this substance, on surfaces projecting into the bloodstream. Sections fixed 30 min. after i.v. injection of streptococci also showed these phagocytes, which contained large numbers of bacteria. The possibility that BE is initiated by phagocytosis of circulating bacteria has been raised. Smaller numbers of circulating streptococci reached the vegetation by direct adhesion to exposed surfaces. In contrast, a majority of Proteus and Staphylococcus albus adhered directly to vegetations, without phagocytosis. Subsequently, these first settlers multiplied rapidly to form rounded colonies surrounded by capsules of fibrin, which apparently provided protection from phagocytosis. The vegetations grew by accretion of layers of fibrin and platelets, with colonies sandwiched between them. This suggested that a cycle of thrombosis and reseeding by circulating bacteria was a factor in their growth. Colonies showed morphological changes consistent with ageing after two days. Healing occurred by endothelialisation and organisation, and was greatly accelerated by penicillin treatment.

The effect of thorotrast and cortisone on renal cortical fibrinolytic activity in the rabbit.

Previous studies have shown that a single injection of endotoxin inhibits renal cortical fibrinolytic activity in the rabbit. This suggests that the initial injection of endotoxin may prepare for the generalized Shwartzman reaction by depletion of cortical fibrinolytic activity. A fibrin slide technic was used to determine whether Thorotrast(R) and cortisone prepare for the generalized Schwartzman reaction by a similar mechanism. Renal cortical fibrinolytic activity was inhibited following Thorotrast injection, but no inhibition could be detected following cortisone injection. This suggests that Thorotrast, like endotoxin, prepares for the generalized Shwartzman reaction by depletion of cortical fibrinolytic activity. Failure to demonstrate inhibition of lytic activity following cortisone injection may indicate that cortisone prepares for the generalized Shwartzman reaction by another mechanism, or that the fibrin slide technic was unable to detect quantitative changes in lytic activity.