Publications

The current dilemmas in primary care stem from 1) the unintended consequences of forces thought to promote primary care and 2) the "disruptive technologies of care" that attack the very function and concept of primary care itself. This paper suggests that these forces, in combination with "tiering" in the health insurance market, could lead to the dissolution of primary care as a single concept, to be replaced by alignment of clinicians by economic niche. Evidence already exists in the marketplace for both tiering of health insurance benefits and corresponding practice changes within primary care. In the future, primary care for the top tier will cater to the affluent as "full-service brokers" and will be delivered by a wide variety of clinicians. The middle tier will continue to grapple with tensions created by patient demand and bureaucratic systems but will remain most closely aligned to primary care as a concept. The lower tier will become increasingly concerned with community health and social justice. Each primary care specialty will adapt in a unique way to a tiered world, with general internal medicine facing the most challenges. Given this forecast for the future, those concerned about primary care should focus less on workforce issues and more on macro health care financing and organization issues (such as Medicare reform); appropriate training models; and the development of a conception of primary care that emphasizes values and ethos, not just function.

The gene encoding alanine dehydrogenase (AlaDH; EC 1.4.1.1) from the marine psychrophilic bacterium strain PA-43 was cloned, sequenced, and overexpressed in Escherichia coli. The primary structure was deduced on the basis of the nucleotide sequence. The enzyme subunit contains 371 amino acid residues, and the sequence is 90% and 77% identical, respectively, to AlaDHs from Shewanella Ac10 and Vibrio proteolyticus. The half-life of PA-43 AlaDH at 52 degrees C is 9 min, and it is thus more thermolabile than the AlaDH from Shewanella Ac10 or V. proteolyticus. The enzyme showed strong specificity for NAD(+) and l-alanine as substrates. The apparent K(m) for NAD(+) was temperature dependent (0.04 mM-0.23 mM from 15 degrees C to 55 degrees C). A comparison of the PA-43 deduced amino acid sequence to the solved three-dimensional structure of Phormidium lapideum AlaDH showed that there were likely to be fewer salt bridges in the PA-43 enzyme, which would increase enzyme flexibility and decrease thermostability. The hydrophobic surface character of the PA-43 enzyme was greater than that of P. lapideum AlaDH, by six residues. However, no particular modification or suite of modifications emerged as being clearly responsible for the psychrophilic character of PA-43 AlaDH.