In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates.

Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities.

Early changes in experimental hydrocephalus.

In acute obstruction of the cerebral spinal fluid (CSF) absorption pathways, fluid is produced more rapidly than it is absorbed, and the ventricles enlarge proximal to the obstructions. Communicating hydrocephalus results from a difference between the rates of production and absorption of cerebrospinal fluid. In animals with chronic communicating hydrocephalus, the initial pathologic changes appear to involve the periventricular tissue near the angles of the lateral ventricles. The present investigation was designed to identify the various changes associated with the production of communicating hydrocephalus in acutely hydrocephalic preparations and to relate these findings to those found in experimental animals with chronic communicating hydrocephalus. The results of this study seem to confirm that the changes noted in the chronically hydrocephalic animals occur as early as 12 hours after the restriction of the normal flow of CSF.

Cerebrospinal fluid pressure alterations in experimental communicating hydrocephalus. Response of cerebrospinal fluid pressure to increase in arterial carbon dioxide tension.

The response of cerebrospinal fluid (CFS) pressure to increased arterial carbon dioxide tension (PCO2) was evaluated in 5 control animals and 7 animals with experimentally induced communicating hydrocephalus. The CSF pressure in control dogs increased moderately in response to PCO2; in dogs with hydrocephalus, an increase in PCO2 produced a pronounced increase in CSF pressure accompanied by a simultaneous decrease in cerebral perfusion pressure. Progression of hydrocephalus can be explained by increased intracranial pressure, periventricular edema and cerebral ischemia.

The ultrastructural basis of periventricular edema: preliminary studies.

The pathophysiology of periventricular lucency (PVL) on CT in primates was evaluated by transmission (TEM) and scanning electron microscopy (SEM). At 100 days after Silastic-induced hydrocephalus, six primate brains showed loss of cilia and ependymal cells over the ventricular surface and abnormal small supraependymal cells. TEM demonstrated communicating pathways between the ventricular lumen and brain parenchyma and the extracellular space was markedly increased. At 1000 days, ependymal changes in two brains were noted at greater distances from the ventricular angle. This study suggests that CT periventricular lucency in patients with hydrocephalus is due to the increased extracellular space. The lack of recognition of PVL by computed tomography in chronic normal pressure hydrocephalus may be due to change in distribution and resolution limits.

Autoradiographic enhancement of mammograms. Investigation of a new dose reduction technique.

Autoradiographic image enhancement using thiourea labeled with 35S was investigated as a means of reducing dose in mammography. It was found that mammograms underexposed as much as tenfold can be autoradiographically intensified so that the enhanced image is comparable with a normal exposure. Limitations to routine use include cost, processing time, and disposal of radioactive solutions.

Evaluation of the central canal of the spinal cord in experimentally induced hydrocephalus.

The central canal of the spinal cord has been proposed as a significant compensatory alternative pathway of cerebrospinal fluid (CSF) flow in hydrocephalus. Ten dogs were made hydrocephalic by a relatively atraumatic experimental model that simulates the human circumstance of chronic communicating hydrocephalus. The central canal was studied by histopathology and compared with 10 normal control dogs. In both groups the central canal of the spinal cord was normal in size, configuration, and histological appearance. In this experimental model dilatation of the canal and increased movement of CSF does not appear to be a compensatory alternative pathway.

The central canal of the spinal cord in experimental hydrocephalus: preliminary results.

The central canal of the spinal cord in certain animal species has been shown to be an alternative pathway of cerebrospinal fluid flow in experimentally induced hydrocephalus. Enlargement and increased movement of cerebrospinal fluid in the central canal has been proposed as a compensatory mechanism in hydrocephalus in humans. The central canal of the spinal cord was normal in 5 dogs and 2 primates made hydrocephalic by a relatively atraumatic experimental model which simulates the human disorder to chronic communicating hydrocephalus. Dilatation of the central canal is apparently not an important compensatory alternative pathway.

Rhinorrhea, ventricular radiopharmaceutical stasis and communicating hydrocephalus: evaluation by serial cisternography.

Spontaneous cerebrospinal fluid rhinorrhea has been known to occur in association with hydrocephalus. The specific pathophysiology which results in a potential communication between the cerebrospinal fluid space (subarachnoid space) and the nasopharynx is unknown. The relationship of CSF movement and rhinorrhea was evaluated in ten random source mongrel dogs. These data suggest that spontaneous CSF rhinorrhea may occur during the early developmental phase of communicating hydrocephalus in dogs. At this time radiopharmaceutical movement showed ventricular entry and clearing. When the lateral ventricles enlarged, ventricular radiopharmaceutical stasis was seen and the rhinorrhea disappeared. This suggests that CSF rkinorrhea may act as a compensatory mechanism which partially protects the CSF compartment to withstand the extra CSF during the early development of communicating hydrocephalus.

Compartmental analysis of cerebrospinal fluid-blood albumin transfer: consideration of kinetics in normal animals and animals with chronic communicating hydrocephalus.

Transfer of radioactively labelled albumin from the cerebrospinal fluid (CSF) to the blood was monitored in 15 dogs with normal cisternograms and in 8 dogs with induced communicating hydrocephalus. Blood concentration curves alone are of limited value and give less than satisfactory information about CSF distribution spaces and were corrected for albumin disappearance from the blood to other compartments. The transit time in animals with hydrocephalus was much greater than in normals and entry into the intravascular compartment was delayed. Mathematical analysis to the indicator movements appears to offer understanding about CSF compartments and transfer of molecules in different types of hydrocephalus.

Natural history of autologous blood clot embolization in swine.

Previous studies of the natural history of embolized clots in dogs have demonstrated rapid lysis, presumably because the canine fibrinolytic system is very active. The fibrinolytic activity in swine, however, is similar to humans, and for this reason the pig was chosen for our study. The gluteal branches of the external iliac artery in nine domestic swine were embolized with either unmodified or modified (heat-formed, Amicar) autologous clot. In addition, three pigs were embolized with unmodified autologous clot to branches of the gastrosplenic artery. The lysis of clot emboli in both groups was followed by serial angiography at 48 hours and 14 days. Clot lysis as assessed by euglobulin lysis and plasmin generation was not activated by the experimental technique. Necropsy was performed on the animals in the second group. Partial or total obstruction of all arteries was present 48 hours after embolization and only 50% of arteries were recanalized at 14 days. At necropsy, organized partially occluding clot was demonstrated in the splenic artery of all 3 embolized swine. It is concluded that: 1)swine provide an excellent animal model for studying the natural history of arterial embolization; 2)Amicar or heat-formed clot shows no advantage over simple autologous clot in retarding intra-arterial clot lysis, and 3)simple autologous clot is an effective material for temporary intra-arterial occlusion.