Robert R. Kane

The outcome of hospitalization for acute illness in the elderly

The use of acute‐care hospitals by the elderly is rising rapidly, particularly in the age group 75 and older. Any changes that will reduce the length of stay could result in considerable savings in health care costs. It is imperative to look at present policies and explore possible changes that could reduce costs by reducing the total hospital days. A study was conducted in a 290‐bed county‐funded community hospital in California that serves the majority of disadvantaged and poor elderly residing in an area with a population of approximately 300,000 persons. The objective was to determine what demographic, medical, and sociologic characteristics of elderly patients recorded at admission would be of value in predicting those most likely to change their functional status.

Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis

The mechanism of tumor cell killing by OXI4503 was investigated by studying vascular functional and morphological changes post drug administration. SCID mice bearing MHEC5‐T hemangioendothelioma were given a single dose of OXI4503 at 100 mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50% at 1 hr, and reached a maximum level 6–24 hr post drug treatment. Tumor vascular permeability, measured by Evans blue and hemoglobin, increased significantly from 3 hr and peaked at 18 hr. The elevated tumor vessel permeability was accompanied by an increase in vascular endothelial growth factor (VEGF) from 1 hr post drug treatment. Immunohistochemical staining for CD31 and laminin showed that tumor blood vessels were affected as early as 3 hr but more prominent from 6 hr. From 12 hr, the vessel structure was completely destroyed. Histopathological and double immunohistochemical staining showed morphological change and induction of apoptosis in endothelial cells at 1–3 hr, followed by tumor cell necrosis from 6–72 hr. There were no statistically significant changes of Evans blue and hemoglobin contents in liver tissue over the time course. These results suggest that OXI4503 selectively targets tumor blood vessels, and induces blood flow shutdown while it enhances tumor blood vessel permeability. The early induction of endothelial cell apoptosis leads to functional changes of tumor blood vessels and finally to the collapse of tumor vasculature, resulting in massive tumor cell necrosis. The time course of the tumor vascular response observed with OXI4503 treatment supports this drug for development as a stand alone therapy, and also lends support for the use of the drug in combination with other cancer therapies.

Long-term functional status and quality of life after lower extremity revascularization

OBJECTIVE The objective of this study was to assess the longer term (up to 7 years) functional status and quality of life outcomes from lower extremity revascularization. METHODS This study was designed as a cross-sectional telephone survey and chart review at the University of Minnesota Hospital. The subjects were patients who underwent their first lower extremity revascularization procedure or a primary amputation for vascular disease between January 1, 1989, and January 31, 1995, who had granted consent or had died. The main outcome measures were ability to walk, SF-36 physical function, SF-12, subsequent amputation, and death. RESULTS The medical records for all 329 subjects were reviewed after the qualifying procedures for details of the primary procedure (62.6% arterial bypass graft, 36.8% angioplasty, 0.6% atherectomy), comorbidities (64% diabetics), severity of disease, and other vascular risk factors. All 166 patients who were living were surveyed by telephone between June and August 1996. At 7 years after the qualifying procedure, 73% of the patients who were alive still had the qualifying limb, although 63% of the patients had died. Overall, at the time of the follow-up examination (1 to 7.5 years after the qualifying procedure), 65% of the patients who were living were able to walk independently and 43% had little or no limitation in walking several blocks. In a multiple regression model, patients with diabetes and patients who were older were less likely to be able to walk at follow-up examination and had a worse functional status on the SF-36 and a lower physical health on the SF-12. Number of years since the procedure was not a predictor in any of the analyses. CONCLUSION Although the long-term mortality rate is high in the population that undergoes lower limb revascularization, the survivors are likely to retain their limb over time and have good functional status.

Expeditious synthesis of a key C9–C21 subunit of the aplyslatoxine and oscillatoxins

Abstract The C9–C21 portion of the aplysiatoxin/oscillatoxin bluegreen algal metabolites was synthesized as the 9-aldehyde bearing a tert -butyldimethylsilyl ether group on the C11 hydroxyl and a trimethylsilylethoxymethyl ether group on the C20 hydroxyl. Featuring an asymmetric aldol and an asymmetric oxazaborolldine reduction, the synthesis proceeded with high (>90%) stereoselectivity in 13 steps and 5–7% overall yield from commercial starting material.

Synthesis of new building blocks for boron-rich oligomers in boron neutron capture therapy (BNCT). I.

Abstract The synthesis of carborane-containing subunits for use in the construction of boronated oligophosphates via solid phase synthesis is described.

Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4

Combretastatin A-4 disodiumphosphate (CA4P), a prodrug formulation of the natural product combretastatin A-4 (CA4), is currently in clinical investigation for the treatment of cancer. In vivo, CA4P is rapidly enzymatically converted to CA4, a potent inhibitor of tubulin polymerization (IC(50)=1-2 microM), and rapidly causes bloodflow shutdown in tumor tissues. A variety of alkyl and aryl di- and triesters of CA4P have been synthesized and evaluated as potential CA4 prodrugs and/or stable CA4P analogues.

An Evaluation of Rural Health Care Research

This article reviews the state of the art of rural health research and evaluation with par ticular emphasis on the questions of access, health personnel, and financing. The current state of knowledge both in the published and in the unpublished literature in each area is summarized and a series of unresolved issues is proposed. A strategy for further research to include the various types of rural health care programs is described. Major findings suggest that, although rural populations do have somewhat less access to care than do urban populations, our ability to quantify precisely the extent and importance of this discrepancy is underdeveloped. Despite a substantial investment in a variety of rural health care programs there is inadequate information as to their effectiveness. Programs designed to increase the supply of health personnel to rural areas have met with mixed success. Sites staffed by National Health Service Corps personnel show consistently lower productivity than do sites under other sponsorship. Nonphysician personnel (physician assistants and nurse practitioners) offer apromising source of primary carefor rural areas; recent legislation that reimburses such care should increase their utilization. A persistent problem is the expectation (often a mandate) incorporated into many rural health care demonstration efforts that the programs become financially self-sufficient in a finite period of time. Self-sufficiency is a function of utilization, productivity, and the ability to recover charges for services. In many instances stringent enforcement of the self-suf ficiency requirement may mean those those who need the services most will be least likely to receive them.

The effect of HMO status on the outcomes of home-care after hospitalization in a medicare population

OBJECTIVE: The literature suggests that Medicare health maintenance organization (HMO) patients may have poorer outcomes with formal home‐health care than do fee‐for‐service (FFS) patients, but it is unclear whether this is related to case‐mix or quality. Our objective was to compare the home‐health care outcomes for HMO and FFS Medicare patients after hospitalization for stroke, COPD, CHF, hip replacement, or hip fracture with fixation or replacement while controlling for site of discharge and other patient characteristics.

Synthesis and photochemical protein crosslinking studies of hydrophilic naphthalimides

A mixture of 4-alkylamino-1,8-naphthalimides has previously been reported to exhibit potential utility as a photochemical tissue-bonding reagent. In order to determine which constituents of the mixture were responsible for the observed tissue bonding and to facilitate study of the mechanism, we have synthesized each of the primary constituents of the mixture. Each naphthalimide synthesized has been demonstrated to photochemically crosslink proteins.

An α-alkylation/reduction of ketones via radical cyclizations of β-chloroethylsilyl enol ethers

Abstract β-Chloroethyldimethylsilyl enol ether derivatives of five ketones were allowed to react with tributylstannane in the presence of AIBN to yield the products of “reductive α-alkylation,” 1-oxa-2-silacyclohexanes, plus ethyldimethylsilyl enol ether byproducts from direct reduction. The unstable oxasilacyclohexanes were treated with methyllithium to yield, upon workup, γ(trimethylsilyl) alcohols.