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.      

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.     

Bacteremic infectability of vascular grafts: the influence of pseudointimal integrity and duration of graft function.

This report describes an experimental study in which dogs with prosthetic graft replacement of the infrarenal abdominal aorta were challenged at progressive time intervals following graft placement with a single intravenous infusion of Staphylococcus aureus in order to determine the duration of susceptibility to graft infection of bacteremic origin. The results demonstrate that the susceptibility of a prosthetic graft to infection by bacteremic seeding virtually was 100 percent up to 1 month following graft placement. The incidence of infection then began to progressively drop but never was eliminated as demonstrated by a 30 percent incidence of graft infection in dogs so challenged 1 year graft placement. Careful scrutiny of the intimal surface of the harvested grafts, 3 weeks following bacteremic challenge, revealed that all grafts in which the pseudointimal coverage was complete were insulated effectively from infection by bacteremic seeding in that their cultures were negative. All grafts that had positive cultures for Staphylococcus aureus were noted to have either an incomplete or absent pseudointimal lining.     

Can survival in pancreatic adenocarcinoma be predicted by primary size or stage?

Evaluation of diagnosis and treatment modalities in pancreas cancer is hampered by the lack of a suitable staging system. The current staging protocol of the American Joint Committee is arranged as follows: intrapancreatic disease (stage I), localized invasion (stage II), positive regional lymph nodes (stage III), and distant metastases (stage IV). Primary size is not taken into account and may represent an important determinant of survival, as it does in other malignancies. Primary size as a criterion of operability may assume increasing importance, given the demonstrated accuracy of sonography and computed tomography. Chart review was undertaken of the 119 consecutive patients with pancreas cancer presenting at Grady Hospital between 1976 and 1981. Ninety-one per cent were histologically confirmed. The presence or absence of metastases continues to be the most important factor predicting survival (P less than 0.001). It was demonstrated, however, that patients with primary lesions less than 5 cm lived significantly longer than those with primaries greater than or equal to 5 cm (P less than 0.02). Using the currently recommended American Joint Committee protocol, there was no difference in survival curves among stages, I, II, and III. The median survival times were 7.5 months, 5 months, and 5 months, respectively. Between combined stages I, II, and III and stage IV (median survival, 1.0 month), there was a significant difference (P less than 0.001) in survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.