Specific dietary interventions. Diabetes, osteoporosis, renal disease

A dietary treatment plan that considers both quality-of-care and quality-of-life issues is most beneficial for elderly patients. Diabetes can be successfully managed in most elderly patients with a liberalized diet that is low in simple sugars and includes variety and moderation in food choices. Although dietary management in osteoporosis may be most compelling in its preventive capacity, clinicians treating elderly patients with osteoporosis are well advised to consider supplementation of the diet with calcium and vitamin D in amounts equal to the RDAs if patients are unable to consume adequate calcium and vitamin D and if exposure to sunlight is minimal. Encouraging calcium intake, moderate exercise, maintenance of desirable body weight, and avoidance of laxative and antacid abuse with patients throughout the life cycle is appropriate preventive advice. The elderly renal failure patient may benefit from dietary modification of protein, potassium, sodium, fluid, vitamins, and minerals when complications associated with these nutrients are present. Because clinicians treat significant numbers of elderly diabetic, osteoporotic, and renal failure patients, and because many skilled nursing facilities are developing specialty and rehabilitation units for such high-acuity level patients, the clinician is well advised to know how to maximize quality of care and quality of life for these patients through appropriate dietary intervention.     

Toxicity of an antitumor ribonuclease to Purkinje neurons

Purkinje cell toxicity is one of the characteristic features of the Gordon phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and tremor that may lead to death (Gordon, 1933). Two members of the RNase superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP (eosinophil cationic protein), cause the Gordon phenomenon when injected intraventricularly into guinea pigs or rabbits. We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The neurotoxic activity of onconase correlates with ribonuclease activity. Onconase modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity of the native enzyme displays a similar decrease in ability to cause the Gordon phenomenon. In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon. A comparison of the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three pancreatic RNA substrates demonstrates that onconase is orders of magnitude less active enzymatically than EDN and RNase A. Thus, another member of the RNase superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post and core reconstruction for fixed prosthodontic restoration

If the previous restorative therapy or dental caries has resulted in substantial loss of tooth structure, the abutment teeth for fixed prosthodontic restorations require a core reconstruction or a post and core. Small dentin defects can be restored with bonded cores; more extensive dentin defects that are often accompanied by previous endodontic treatment generally require additional support for the core material. A direct procedure with a bonded post is a viable treatment method. The decision to use either light-conducting all-ceramic zirconium or titanium as a post material depends on the aesthetic requirements present. The indications for a cast post and core as an indirect procedure for prosthodontic reconstructions appear to be decreasing. The learning objective of this article is to review the past and current post and core materials and techniques. Indications for core reconstruction with vital teeth and posts and cores for pulpless teeth are discussed.     

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.     

The hierarchies of knowledge and the mathematics of discovery

Rather than attempting to characterize a relation of confirmation between evidence and theory, epistemology might better consider which methods of forming conjectures from evidence, or of altering beliefs in the light of evidence, are most reliable for getting to the truth. A logical framework for such a study was constructed in the early 1960s by E. Mark Gold and Hilary Putnam. This essay describes some of the results that have been obtained in that framework and their significance for philosophy of science, artificial intelligence, and for normative epistemology when truth is relative.I am indebted to Kevin Kelly for several years of happy conversation from which the perspective and views of this paper grew, for comments on a draft of the paper, and for constructing some of the illustrations. A fellowship from the John Simon Guggenheim Memorial Foundation provided the liberty to write this paper. It was first presented in the Turing Colloquium, 1990.     

Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.