Postoperative use of radioactive phosphorus in stage I ovarian carcinoma.

The addition of intraperitoneal colloidal radioactive chromic phosphorus following total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy in women with Stage I ovarian cancer does not cause significant morbidity. Moreover, our preliminary results suggest that this regimen appears to increase the rate of local control of disease. In 21 unselected patients, there was 1 incident of small bowel obstruction. Fourteen of these patients have been followed for at least 1 1/2 years; all are alive without evidence of disease. These facts suggest that a national prospective study to investigate the efficacy of this treatment for Stage I ovarian cancer is warranted.

Naegleria: another pathogenic ameba studies in germfree guinea pigs.

Free-living amebas of the genus Naegleria, of world-wide distribution and long considered harmless, have been linked etiologically with 57 fatal cases of primary amebic meningoencephalitis during the last decade. Naegleria from cultures derived from one of these fatal cases in Richmond, Virginia, have been inoculated intranasally, intraorally, into the conjunctival sac near the inner canthus of the eyes, and into induced skin lesions in adult germfree guinea pigs. Of 33 animals inoculated intranasally with 18 to 31 amebas, 31 developed a fatal encephalitis. There was considerable destruction of tissues of the cerebellum and the cerebrum and including the olfactory lobes. The meninges were involved to varying degrees in most of the animals. None of the animals inoculated by the three other routes developed either symptoms or lesions.

Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. I. Penetration of the intestinal epithelium by trophozoites.

Germ-free guinea pigs were inoculated intracecally with Entamoeba histolytica and the enteric flora derived from a human patient with acute amebic colitis. Aanimals were killed at post-inoculation intervals of 7 to 12 days. The mode of penetration of cecal epithelium by the ameba was examined by light and electron microscopy. The following sequence was reconstructed from numerous individual observations. When the amebae were in moderately close proximity to the brush, border, the microvilli became shortened, irregular, and sometimes disappeared. Dense material was observed between the amebae and microvilli. When the ameba was very close to the epithelium the apical portion of epithelial cytoplasm projected into the lumen contacting the organism, thus becoming detached from adjoining cells. This produced spaces between epithelial cells through which amebae invaded interepithelial spaces. Initially the ameba penetrated the interglandular epithelium. Later, it penetrated equally the glandular and interglandular epithelium barrier. There were marked alterations of cytoplasmic components of epithelial cells. Polymorphonuclear leukocytes migrated into the epithelium filling these spaces; these often showed a variety of degenerative processes. Amebae, utilizing their pseudopodia, moved further through the intercellular spaces and reached the lamina propria.

Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. II. Early cellular and vascular changes accompanying invasion of the lamina propria.

Early cellular and vascular changes in response to invasion of lamina propria by Entamoeba histolytica were studied sequentially, at the ultrastructural level, in germfree guinea pigs inoculated intracecally with amebae and enteric flora derived from patients with acute amebic colitis. Approximately one week post-inoculation the animals developed acute colitis with mucosal invasion by trophic amebae. Although epithelial cells at the sites of amebic invasion showed progressive cytoplasmic changes and desquamation resulting in microerosions, most mesenchymal elements in the lamina propria appeared normal without cytopathic changes even when in direct contact with invading amebae. Only the polymorpho-nuclear leukocytes (PMN) apposed or topographically close to amebae exhibited degenerative changes which were characterized by condensation of nucleoplasm and cytoplasm, extra-cellular release of cytoplasmic components including granules, and, finally, lysis of cell membranes. Capillaries and venules in the lamina propria showed a variety of changes such as swelling and gap formation at the intercellular endothelial junctions and more rarely at the fenestrae. Blood vessels physically close to amebae showed formation of endothelial cytoplasmic blebs which pinched off into the vascular or extravascular space. Platelet and fibrin thromboses were common in the more severely damaged capillaries and venules. Fragments or clumps of fibrin-like material were found also in the extracellular spaces. Amebic invasion of the lamina propria, then, is accompanied by continued epithelial shedding, PMN degeneration, and changes in both capillaries and venules consisting of endothelial damage and occlusive thrombosis. The vascular changes appeared to be closely related to PMN degeneration resulting from interaction of PMN with invading amebae.

Chemistry for commercial scale production of yttrium-90 for medical research.

Studies were initiated at Oak Ridge National Laboratory (ORNL) in 1982 for the radiolabeling of resin microspheres with yttrium-90 (90Y) for liver cancer therapy. Yttrium-90 is the decay product of strontium-90 (90Sr). Subsequently, 90Y became a major radioisotope of choice for labeling antibodies for therapeutic trials in the treatment of other forms of cancer. A 25-Ci 90Y 90Y generator or 90Sr cow was placed in service to supply the anticipated needs of customers. In vivo use of 90Y required that the 90Sr contamination levels be kept below 10 muCi/Ci 90Y (corrected to preparation time). Also, it was necessary to remove trace metals that interfered in the 90Y antibody radiolabeling process, giving low radiolabeling yields. Di-(2-ethylhexyl) phosphoric acid (HDEHP) in dodecane has been used routinely at ORNL to extract 90Y and thereby give a product that meets the radiochemical purity required with respect to 90Sr. Methods were also developed to remove interfering trace elements to provide acceptable labeling yields.