Effect of IL-1 on experimental bone/bone-marrow metastases.

Bone metastasis is a common event and a major cause of morbidity in cancer patients. The hematopoietic marrow of the bones, rather than the bone tissue per se, is the target organ in bone metastasis. In the bone marrow, IL-1 induces the release of hematopoietic growth factors that may affect tumor-cell growth. We treated groups of mice with rhuIL-1 alpha to examine its role in the establishment of experimental bone/bone-marrow metastasis. We found that injection of 2 micrograms of rhuIL-1 alpha 24 hr prior to, simultaneously with or 24 hr after the injection of 10(4) B16 melanoma cells into the left cardiac ventricle of mice resulted in a 2-fold increase in the average number of colonized bones per mouse. GM-CSF is produced by bone-marrow stromal cells in response to IL-1, and its receptor has been found on tumor cells, including melanoma cells. However, the administration of rmuGM-CSF to mice by either multiple injections or continuous infusion did not affect the number of colonized bones. Many of the biologic effects of IL-1 are mediated by prostaglandins. Treatment of mice with 100 micrograms of indomethacin, a potent inhibitor of prostaglandin synthesis, prior to the injection of rhuIL-1 alpha, prevented the increase in number of bone metastases. To determine whether constitutive productions of IL-1 and/or prostaglandins are involved in the pathogenesis of bone/bone marrow metastasis, we treated mice with antimouse IL-1 alpha neutralizing antibodies, rhuIRAP (an inhibitor of IL-1 activity) or indomethacin. We found no difference in the average number of colonized bones per mouse between treated and control mice. We conclude that exogenous administration of IL-1 enhances experimental bone/bone-marrow metastases, and that this phenomenon is mediated through prostaglandins. However, neither the constitutive production of IL-1 nor that of prostaglandins appear to play a role in the pathogenesis of bone/bone-marrow metastasis in our murine model system.     

Long-term reproducibility of quantitative computed tomography vertebral mineral measurements

Similar methods for measuring bone density using quantitative computed tomography have been proposed by Cann and Genant and by Firooznia et al. This study was done to evaluate the long-term reproducibility of quantitative computed tomography in the clinical setting. An anthropomorphic phantom was evaluated over an 18-month interval. A variation of +/- 2.2% was obtained, substantiating that quantitative computed tomography can be done in a reproducible manner over an extended time interval.     

Alteration in temperature regulation induced by burn injury in the rat

The preoptic anterior hypothalamus (POAH) of rats housed at three ambient temperatures was implanted with perfusion apparatuses. Response of heat production to displacement of POAH temperature was determined for control animals and animals with burns (31% +/- 3% total body surface area). At an ambient temperature of 22 degrees C there was a significant increase in thermosensitivity of the POAH for both control rats and rats with burns compared with thermosensitivity at 32 degrees C. Within ambient temperatures there was no effect on thermosensitivity detected for rats with burns compared with control rats. The threshold temperature for heat production was shifted significantly upward (p less than 0.05) both by a lower ambient temperature and by burn injury. The reference temperature for heat production was also shifted to the right by burn injury (p less than 0.05). The significant shifts to the right for threshold temperature and reference temperature for heat production enhance the organisms's ability to meet the stress of the hypermetabolic response. At a warm ambient temperature (32 degrees C) there are no significant differences in thermoregulation detected in animals with burns or control animals.     

Meningitis as the presenting symptom of pituitary adenomata

We have recently seen two patients, both men in their forties, who presented with a clinical picture of meningitis which was later found to be secondary to infarction of an underlying chromophobe adenoma of the pituitary.     

Nonimmune hydrops fetalis: antenatal diagnosis and management

An 8-year (1975-1982) study of 26 cases of nonimmune fetal hydrops revealed the main causes to be: anomalies (11/26), tachyarrhythmias (4/26), and twin-to-twin transfusion (4/26). The perinatal mortality was 19/26 (76%). Based on this series, and a review of the literature, a plan for the antenatal diagnosis and management of these cases is outlined.