Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

EquiTest modification with shank and hip angle measurements: differences with age among normal subjects

The Sensory Organization Test protocol of the EquiTest system (NeuroCom International, Clackamas Oregon) tests utilization of visual, vestibular, and proprioceptive sensors by manipulating the accuracy of visual and/or somatosensory inputs during quiet stance. In the standard Sensory Organization Test, both manipulation of sensory input (sway-referencing) and assessment of postural sway are based on ground reaction forces measured from a forceplate. The purpose of our investigation was to examine the use of kinematic measurements to provide a more direct feedback signal for sway-referencing and for assessment of sway. We compared three methods of sway-referencing: the standard EquiTest method based on ground reaction torque, kinematic feedback based on servo-controlling to shank motion, and a more complex kinematic feedback based on servo-controlling to follow position of the center of mass (COM) as calculated from a two-link biomechanical model. Fifty-one normal subjects (ages 20-79) performed the randomized protocol. When using either shank or COM angle for sway-referencing feedback as compared to the standard EquiTest protocol, the Equilibrium Quotient and Strategy Score assessments were decreased for all age groups in the platform sway-referenced conditions (SOT 4, 5, 6). For all groups of subjects, there were significant differences in one or more of the kinematic sway measures of shank, hip, or COM angle when using either of the alternative sway-referencing parameters as compared to the standard EquiTest protocol. The increased sensitivities arising from use of kinematics had the effect of amplifying differences with age. For sway-referencing, the direct kinematic feedback may enhance ability to reduce proprioceptive information by servo-controlling more closely to actual ankle motion. For assessment, kinematics measurements can potentially increase sensitivity for detection of balance disorders, because it may be possible to discriminate between body sway and acceleration and to determine the phase relationship between ankle and hip motion.     

Nail grafts for reconstruction

Monkey digits were used experimentally to demonstrate the pathologic anatomy of nail deformities and the results of treatment using full and partial thickness nail matrix grafts. Seventy-five human nail deformities were evaluated and treated. In both the experimental and clinical groups, microscopic hypertrophy of the superficial epithelial elements underlying the deformed nail existed. A follow-up of treatment of nail deformities indicated that nail matrix grafts, both full and partial thickness, are beneficial when the defect involves the sterile matrix and the proximal nail fold.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.     

Gallium-67 lung uptake: conjugate-view technique

A conjugate-view technique is derived for calculation of absolute gallium-67 (Ga-67) uptake from scintillation-camera images. The technique combines counts of posterior and anterior images of the lung with an attenuation correction obtained from cobalt-57 (Co-57) transmission imaging. The formulation is such that the effects of Compton scatter build-up are accounted for. Studies utilizing a canine model indicated that, normally, more activity is located in the chest wall than in the lungs. The quantitative technique must therefore accurately account for a variety of Ga-67 distributions, including that in the chest wall. Calculations were performed using a three-component model comparing results obtained with the conjugate-view approach to the actual uptake. These calculations suggest that an assumption of uniform activity distribution allows an accuracy of approximately +/- 10% over a broad range of body-part thicknesses and uptake by the lungs. It was concluded that the conjugate-view technique is necessarily approximate but can provide clinically useful results.