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Brain stem abscess treated surgically. Wtih special note upon the employment of thorium dioxide.

A 10-year-old girl, with congenital heart disease, harboring a brain stem abscess, was recently treated at the UCLA Hospital. Needle aspirations of the abscess was performed through a posterior occipital craniectomy, and thorium dioxide (Thorotrast) was placed within the abscess cavity as a marker. Postoperatively, the patient improved temporarily but died 18 days later. Autopsy examination included radioactive analysis of brain and liver tissue. Radioautographs were superimposed on H&E preparations of the abscess wall to localize the extent of activity of the thorium dioxide. The unusual occurrence of this abscess in a young patient, clinically diagnosed and treated by operation, provided a rare opportunity to assess the problem of the surgical accessibility of brain stem abscess as well as to reevaluate a role for thorium dioxide as a marker for intracranial purulent collections.

Autoradiography

Vascular complications of thorium dioxide.

Vascular complications occurring late after exposure to thorium dioxide (thorotrast) are described in two patients. One patient had both cerebral andmyocardial infarcts and died at age 25 years. Necropsy disclosed both adventitial and intimal fibrosis of the left carotid artery and greater than 75 per cent cross-sectional area luminal narrowing of both the left main and left anterior descending coronary arteries. The other patient, a 33 year old man, had no cerebral symptoms in life but total obstruction of the right carotid artery secondary to a thorotrastoma was found at necropsy. Vascular complications due to thorotrast appear to represent consequences of chronic alpha irradiation.

Adult

Hodgkin's disease following thorium dioxide angiography.

Hodgkin's disease occurred in a 53-year-old man who, 25 years previously, had undergone cerebral angiography, for which thorium dioxide suspension (Thorotrast) was used. Deposits of throium dioxide were noted in reticuloendothelial cells in various locations. An association between thorium dioxide administration and the subsequent development of malignant tumours and neoplastic hematologic disorders has previously been reported.

Autoradiography

Thorotrast (thorium dioxide) granuloma of the neck: Surgical considerations.

Summary--Thorotrast (thorium dioxide) is a contrast material which was first used for angiography about 40 years ago. Its use was discontinued because of the reported incidences of malignancy following injection. Its long-term effects are related to its long half-life and slow excretion rate. Following extravasation into the soft tissues of the neck, the prolonged radiation effect results in tissue breakdown with formation of granulomas. There can also be cranial nerve palsies, occlusion of the major blood channels, laryngeal edema, pharyngeal and esophageal ulceration, and fistula formation. To avoid these late consequences, it is suggested that Thorotrast granuloma in the neck be excised radically. Partial or limited resections are inadequate.

Angiography

Uptake of colloidal thorium dioxide by the mouse connective tissue mast cell.

The ability of the mouse mast cell to phagocytize colloidal thorium dioxide, Thorotrast, was investigated employing the mouse connective tissue air pouch. The connective tissue mast cell of mouse was found to have limited capability to ingest the particulate Thorotrast in comparison to the rat peritoneal mast cell which ingested this material readily. Fibroblasts and macrophages in the connective tissue removed injected Thorotrast very rapidly in contrast to mast cells that demonstrated limited phagocytic capabilities. The tissue mast cell of the mouse, therefore, should not be considered a part of the reticuloendothelial system.

Animals

Thorium dioxide granuloma of the neck with resultant fatal hemorrhage.

A 46-year-old man had a granuloma in the neck that was caused by extravasation of thorium dioxide (Thorotrast) by an angiographic procedure performed about 30 years previously. His chief complaints were dysphagia and dyspnea with mild hoarseness. Parital resection of the tumor was performed, but his symptoms were not ameliorated. The immediate postoperative course was unfavorable. The patient died four months after the operation from massive hemorrhages from the right common carotid artery.

Carotid Arteries

Hepatoma induced by thorium dioxide.

A 74-year-old man complained of anorexia and weight loss. Twenty-six years earlier he had received an injection of Thorotrast. A needle biopsy of the liver showed thorium dioxide granules and periportal fibrosis. On laparotomy, a hepatoma of the left lobe of the liver was discovered. Hepatic malignancy should be suspected in any patient with abnormal results of liver function tests, particularly an elevated level of alkaline phosphatase, who previously has had an injection of Thorotrast.

Aged

Pinocytotic uptake and intracellular distribution of colloidal thorium dioxide by cultured sensory neurites.

Sensory ganglia from 9-day chick embryos were grown on collagen coated coverslips for36 h in the presence of nerve growth factor, producing a profuse neuritic outgrowth. The cultures were then incubated for varying periods in a colloidal suspension of thorium dioxide, and the pinocytotic uptake of this marker was followed by electron microscopy. Following brief exposures (3 min), most of the labelled organelles consisted of smooth surfaced vesicles and vacuoles; with longer exposures, the bulk of the marker accumulated first in cup-shaped pre-multivesticular bodies and ultimately in multivesicular bodies. The marker was also taken up into coated vesicles, dense-cored and electron lucent tubules,dense-cored vesicles and dense bodies of the multi-layered myelin body configuration. In addition, evidence suggestive of exocytosis was also obtained; views of apparent fusion of labelled multivesicular bodies with the plasmalemma involving extrusion of vesiclesand marker particles into the extracellular space were regularly encountered following long exposures.

Animals

[Bone marrow insufficiency and hemangioendothelioma of the liver after thorotrast application: Late effects of thorotrast (thorium dioxide) in man (author's transl)].

The report details with the late effects following administration of thorotrast in two patients: multicentre metastating hemangioendothelioma of the liver respective bone marrow insufficiency developed after application of thorotrast 34 respective 36 years ago. The clinical and autoptical findings are described and attention is drawn to the relevance of this disease at present time.

Alkaline Phosphatase

Thorium dioxide granuloma of the neck: a report of four cases.

Four patients with Thorotrast granuloma are reported. The first patient had a radical neck dissection performed; however, postoperative hemorrhage and fistula occurred with a six-month delay in healing. The granuloma in this patient had totally occluded his carotid system with a greatly enlarged vertebral artery. A second patient presented with spontaneous bleeding in the neck from a granuloma followed by encephalomalacia, hemiparesis and aphasia. The third and fourth patients presented as hoarseness with a hard mass in the neck. All four patients had Thorotrast in the liver and spleen. The latter three had laryngoscopies and incisional neck biopsies as their only surgical treatment. Neck malignancy from Thorotrast is very rare. Despite legal decisions suggesting removal and similar suggestions in the literature, the authors feel only small extravasations have had uncomplicated operations. Neck dissection is rarely indicated. Hoarseness can be improved by vocal cord injection. These patients, of course, must be followed periodically as any other tumor, checking the neck mass, liver, and carotid circulation.

Adult

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.

Animals

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.

Animals