Overview of graduate medical education. Funding streams, policy problems, and options for reform

In this article, we examine the financing mechanisms for graduate medical education (GME) in the United States. In so doing, we identify Medicare as the single largest contributor to GME and the most important barrier to producing a physician workforce that is appropriately sized, balanced, and skilled. Until passage of the 1997 Budget Reconciliation Agreement, the structure of Medicare payments promoted overproduction and skewed production toward training specialists in tertiary settings. We then examine the various reform proposals put forward by major health care organizations and policy bodies. These organizations generally agree on seven policy objectives: Remove incentives that promote expanded resident production; Base the GME subsidy on actual costs and distribute it more uniformly; Focus reductions on specialty residency positions; Provide GME payments for training provided in ambulatory, community, and managed care sites; Decouple Medicare GME reimbursement from payments to health maintenance organizations for patient care; Require all health insurers to contribute to GME; and Ensure that reductions in the GME subsidy do not reduce access to care for low-income persons. A myriad of different mechanisms for achieving these objectives have been recommended, many of which could be melded together to form a comprehensive approach to GME reform. The prospects for meaningful GME reform are dim in the absence of broader Medicare reform. The costs to stake-holders are too concentrated while the benefits to the public are too diffuse for GME reform to stand alone. But the political imperative to deal with the federal budget's short-term deficit and Medicare's long-term solvency will likely create an opportunity for GME reform. An addendum has been added that shows how the 1997 Budget Reconciliation Agreement addresses most of the major reform objectives identified but that several important issues remain unresolved.     

Apolipoprotein E epsilon 4 allele distribution in alcoholic dementia and in Alzheimer's disease in Japan

The apolipoprotein E epsilon 4 allele has been associated with both familial and sporadic Alzheimer's disease (AD). Given its possible role in nerve repair and growth, it is plausible that apolipoprotein E may be a common denominator in the pathogenesis of several dementing diseases. Therefore, we investigated epsilon 4 frequencies in demented and nondemented alcoholics, as well as in patients with sporadic AD and controls in Japan. No significant differences in allele frequencies was found between demented and nondemented alcoholics and controls, while a significant association was demonstrated between AD and the epsilon 4 allele. These results support a specific role of epsilon 4 in the pathogenesis of AD, rather than a more general role for epsilon 4 in dementing illnesses.     

Monoclonal antibodies to a 100-kd protein reveal abundant A beta-negative plaques throughout gray matter of Alzheimer''s disease brains

Methionine metabolism and transmethylation are central to the metabolism and differentiation of all known cells. In enkaryotic organisms, methionine metabolism and transmethylation are of paramount importance in modification and regulation of proteins, lipids, and nucleic acids. The differential methylation of genes regulates their expression in the myriad of cells in eukaryotic organisms. Disruption and abnormalities in methionine metabolism and transmethylation seems to be associated with the major diseases of mankind, including cancer, heart disease, aging, obesity, and Parkinson's disease. In this review, we describe how aberrant and abnormal methionine metabolism and transmethylation are related to these major diseases. Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases.     

Phosphorescence and optically detected magnetic resonance characterization of the environments of tryptophan analogues in staphylococcal nuclease, its V66W mutant, and Delta 137-149 fragment

Phosphorescence and optically detected magnetic resonance (ODMR) measurements are reported on the triplet states of the tryptophan analogues, 7-azatryptophan (7AW), 5-hydroxytryptophan (5HW), and 4-, 5-, and 6-fluorotryptophan (4FW, 5FW, 6FW), when incorporated at position 140 of wild-type Staphylococcal nuclease (7AW-nuclease, etc. ), positions 66 and 140 of its V66W mutant (7AW-V66W, etc.), and the deletion fragment of the latter, Delta 137-149 (7AW-V66W', etc.). These measurements point to the retention of protein structure at position 140 in each of the wild-type nuclease analogues. Substitution of the analogue at both tryptophan sites of V66W leads to structured sites with differentiated triplet-state properties for all analogues except 7AW-V66W, whose structure is destabilized. 5HW-V66W' is the only fragment that apparently lacks structure at position 66. All other V66W' analogues exhibit a structured environment at position 66 (4FW-V66W' was not studied), but in each case this site can be differentiated readily from the corresponding site in intact V66W. 7AW-V66W' is resolved by ODMR into two discrete structures with slightly differing zero field splittings (ZFS). Interaction of the protein with 5HW at position 66 of 5HW-V66W induces a 2-fold increase in the ZFS E parameter, which is reduced to its normal value upon formation of the fragment, 5HW-V66W'. Analogous effects occur for 5FW, but on a smaller scale.     

Transfectable and transplantable postmitotic human neurons: a potential "platform" for gene therapy of nervous system diseases

OBJECTIVE: To evaluate F-18 fluorodeoxyglucose positron emission tomography (PET) in terms of its sensitivity and specificity in diagnosing malignant pulmonary nodules and staging bronchogenic carcinoma. METHODS: A retrospective review of any patient that presented to the VA Palo Alto Health Care System with a pulmonary nodule between 9/94 and 3/96 revealed 49 patients (four female, 45 male) age 37-85 (mean 63) with 54 pulmonary nodules who had: chest CT scan, PET scan; and tissue characterization of the nodule. Characterization of each nodule was achieved by histopathologic (N = 44) or cytopathologic (N = 10) analysis. Of the 49 patients, 18 had bronchogenic carcinoma which was adequately staged. Mediastinal PET and CT findings in these 18 patients were compared with the surgical pathology results. N2 disease was defined as mediastinal lymph node involvement by the American Thoracic Society's classification system. Mediastinal lymph nodes were interpreted as positive by CT if they were larger that 1.0 cm in the short-axis diameter. RESULTS: Sensitivity and specificity for the diagnosis of malignant pulmonary nodules using PET was 93 and 70%, respectively. All nodules (N = 3) that were falsely positive by PET scan were infectious in origin. All nodules (N = 4) that were falsely negative by PET were technically limited studies (outdated scanner, no attenuation correction, hyperglycemia) except for one case of metastatic adenocarcinoma. The sensitivity and specificity of PET in diagnosing N2 disease was 67 and 100%, compared with 56% and 100% for CT scan (not statistically significant). However, one more patient with N2 disease was correctly diagnosed by PET than by CT scan. CONCLUSION: PET is a valuable tool in the diagnosis and management of pulmonary nodules and may more accurately stage patients with bronchogenic carcinoma than CT scanning alone.