Philip Morris's Project Sunrise: weakening tobacco control by working with it.

OBJECTIVE: To analyse the implications of Philip Morris USA's (PM's) overtures toward tobacco control and other public health organisations, 1995-2006. DATA SOURCES: Internal PM documents made available through multi-state US attorneys general lawsuits and other cases, and newspaper sources. METHODS: Documents were retrieved from several industry documents websites and analysed using a case study approach. RESULTS: PM's Project Sunrise, initiated in 1995 and proposed to continue through 2006, was a long-term plan to address tobacco industry delegitimisation and ensure the social acceptability of smoking and of the company itself. Project Sunrise laid out an explicit divide-and-conquer strategy against the tobacco control movement, proposing the establishment of relationships with PM-identified "moderate" tobacco control individuals and organisations and the marginalisation of others. PM planned to use "carefully orchestrated efforts" to exploit existing differences of opinion within tobacco control, weakening its opponents by working with them. PM also planned to thwart tobacco industry delegitimisation by repositioning itself as "responsible". We present evidence that these plans were implemented. CONCLUSION: Sunrise exposes differences within the tobacco control movement that should be further discussed. The goal should not be consensus, but a better understanding of tensions within the movement. As the successes of the last 25 years embolden advocates to think beyond passage of the next clean indoor air policy or funding of the next cessation programme, movement philosophical differences may become more important. If tobacco control advocates are not ready to address them, Project Sunrise suggests that Philip Morris is ready to exploit them.

Understanding Philip Morris's pursuit of US government regulation of tobacco.

OBJECTIVE: To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. DATA SOURCES: Internal Philip Morris documents released as part of the Master Settlement Agreement. METHODS: Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. RESULTS: Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. CONCLUSIONS: Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted.

Thyrotropin levels during hydrocortisone infusions that mimic fasting-induced cortisol elevations: a clinical research center study.

Both short term fasting and administration of high doses of glucocorticoids lead to marked suppression of serum TSH levels in healthy subjects. However, it is not known whether the more mild serum cortisol elevations seen during fasting can account for fasting-induced TSH suppression. To study this question, eight healthy subjects each underwent three 2-day studies: 1) baseline (adlibitum diet), 2) fasting (56 h of total caloric deprivation), 3) hydrocortisone (HC) infusions at a dose and pulsatile pattern that reproduced cortisol levels measured during each subject's fasting study. Subjects required 34-46 mg HC/24 h to achieve these cortisol levels. During each study, blood samples were drawn every 15 min during the final 24 h for serum cortisol and TSH levels. A TRH stimulation test was performed at the end of each study. By design, fasting and HC infusions induced similar mild increases in 24-h serum cortisol levels (32% over baseline), with the most significant increases seen between 1400-0200 h. Fasting decreased 24-h mean and pulsatile TSH levels 65% from baseline, whereas HC infusions decreased mean and pulsatile TSH levels 51% from baseline. Daytime (0800-0200 h) TSH levels were identical in the two studies, whereas nocturnal (0200-0800 h) TSH levels during HC infusions fell midway between baseline and fasting studies. Serum total T3 and TSH responses to TRH were decreased to a similar degree by fasting or HC infusions. These results suggest that mild elevations in endogenous cortisol levels may mediate at least in part fasting-induced changes in TSH secretion and thyroid hormone levels. In addition, these data show that near-physiological doses of HC and resulting changes in serum cortisol levels within the normal range can cause significant decreases in serum TSH levels.

Variability of plasma cortisol levels in extremely low birth weight infants.

Cortisol is secreted by children and adults in a pulsatile pattern of 15-30 peaks and nadirs each day with a circadian rhythm. Newborns are known to lack the circadian pattern, leading to uncertainty about the appropriate time for blood sampling for assessment of adrenal function. Because extremely low birth weight (ELBW) infants may manifest signs of adrenal insufficiency, knowledge of the pattern of cortisol levels is necessary to guide the appropriate timing of blood sampling. To define the pattern of plasma cortisol levels in 14 ELBW infants, we obtained blood specimens every 20 min over a 6-h period at 4-6 days of life. Although cortisol levels in the 14 infants ranged from 2.0-54.5 micrograms/dL, each infant's cortisol levels varied little from his or her own mean cortisol level. The SDs calculated from each infant's mean cortisol level were small, ranging from 0.37-4.12 micrograms/dL. Cluster analysis was applied to the data; only 0.6 cortisol pulses/infant 6-h period were detected. Each infant's plasma cortisol levels were plotted against time, and regression analysis was performed. The slopes of the resulting lines of regression ranged from -0.0284 to 0.0221. Our data indicate that ELBW infants show little variability in their plasma cortisol levels over time; therefore, a single random measurement provides an adequate reflection of the adrenal status of the ELBW infant.

Glipizide-GITS does not increase the hypoglycemic effect of mild exercise during fasting in NIDDM.

OBJECTIVE: This study compared the effect of mild exercise while fasting on plasma glucose concentrations in subjects with NIDDM treated with extended-release glipizide and subjects not taking an oral hypoglycemic agent. RESEARCH DESIGN AND METHODS: Twenty-five moderately obese subjects with NIDDM were randomized to treatment with extended-release glipizide or placebo. After 9 weeks of treatment, they fasted overnight, took their study drug, omitted breakfast, and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide concentrations were measured before, during, and after exercise. RESULTS: On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms. CONCLUSIONS: Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.

Diagnosis of diaphragmatic trauma with helical CT in a swine model.

OBJECTIVE: The purpose of this study was to determine whether diaphragmatic injury can be accurately diagnosed with helical CT in a swine model. The hypothesis of our study was that thin-section helical CT with sagittal and coronal reformations can reliably detect injury of the diaphragm. MATERIALS AND METHODS: The study was performed in a swine model because of the similarity of the swine thorax to the human thorax. Ten swine had a limited abdominal helical CT (enteral contrast; 3-mm collimation; pitch, 1) before and after surgical creation of a 6-cm posterolateral laceration in the left hemidiaphragm. A repeat scan was obtained after 5 cm of gastric fundus was sutured through the laceration. The gastric fundus was used because it is the most commonly herniated viscus in human diaphragmatic injury. No IV contrast was used. Control, laceration, and herniation scans were reconstructed with 1.0-mm overlap and reformated in axial, sagittal, and coronal planes. Three observers scored each reformation as control or injury (defined as laceration or herniation) in a blinded and randomized fashion. RESULTS: Using helical CT, the observers were able to distinguish diaphragmatic injury from controls (p < .0001). The sensitivity and specificity were 92% and 87%, respectively, for sagittal reformations; 85% and 87%, respectively, for coronal reformations; and 73% and 80%, respectively, for axial reformations. Sagittal reformations proved superior to coronal or axial reformations (p = .01). The results were independent of individual observers: We found no significant difference in accuracy among the three observers. CONCLUSION: Helical CT can accurately detect diaphragmatic injury in a swine model.

Renal 11 beta-hydroxysteroid dehydrogenase activity is enhanced by ramipril and captopril.

Changes of renal 11 beta-hydroxysteroid dehydrogenase activity may contribute to variations of sodium excretion by modulating inactivation of cortisol or corticosterone and thus their access to mineralocorticoid receptors. Angiotensin-converting enzyme inhibitors enhance sodium excretion but by mechanisms still incompletely understood. To test the hypothesis that the angiotensin-converting enzyme inhibitors ramipril and captopril act in part by enhancing renal 11 beta-hydroxysteroid dehydrogenase activity, the effects of these agents in slices of rat renal outer medulla were examined. Conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone was 58% greater in tissue from fasted rats than from fed rats (mean +/- SE 2467 +/- 146 vs. 1584 +/- 102 pmol/mg protein.h, P < 0.01). Incubation of tissue from fed rats with physiological concentrations of ramiprilat, the active form of ramipril, enhanced activity (1497 +/- 76) to fasted levels (2323 +/- 120, P < 0.02). Captopril had a similar in vitro effect (1557 +/- 92 to 2109 +/- 116, P < 0.01). Ramipril given in vivo to fed rats also increased activity to fasted levels (1716 +/- 101 to 2737 +/- 396, P < 0.05). Angiotensin II incubated with renal tissue from fasted rats suppressed activity to fed levels, but this effect was prevented by the presence of ramiprilat. Both ramipril and captopril enhance renal 11 beta-hydroxysteroid dehydrogenase activity, and this effect is only partly explained by limitation of endogenous angiotensin II production.

Acute reduction of renal 11 beta-hydroxysteroid dehydrogenase activity by several antinatriuretic stimuli.

The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity of the kidney prevents access of cortisol or corticosterone to the renal mineralocorticoid receptor. Reduction of 11 beta-HSD activity by nutritional, hormonal, or pharmacologic factors might enhance the mineralocorticoid effect of these corticosteroids, thus causing sodium retention. To test this concept, we studied the effect on 11 beta-HSD activity of several antinatriuretic factors given orally to rats or exposed in vitro to rat renal tissue. Renal 11 beta-HSD activity was higher in fasted than fed rats (P < .05). Glucose, ethanol, and Toradol (Syntex Laboratories, Palo Alto, CA) given orally to fasted rats all reduced renal 11 beta-HSD activity by 20% to 40% (P < .05-.005) to levels similar to those observed in fed animals. Incubation of renal tissue from fasted rats with physiologic concentrations of insulin, ethanol, and Toradol also reduced 11 beta-HSD activity by 20% to 40% (P < .05-.01). These findings are consistent with the hypothesis that the antinatriuretic actions of these stimuli are due in part to alteration of renal 11 beta-HSD leading to greater mineralocorticoid effects in kidney.

Personnel requirements for an outpatient chemotherapy admixture service.

Chemotherapy preparation times and personnel requirements for an outpatient chemotherapy admixture service (CAS) were determined in this study. CAS activities and time measurement endpoints were identified by process analysis. Direct time studies were performed over a 2-month period on approximately 400 variable (chemotherapy admixture) activities and on their related fixed (auxiliary) activities. Variable activities were divided into four distinct categories based upon the original formulation of the antineoplastic agent and its complexity of admixture. All CAS activities were performed by a pharmacy technician under the supervision of a pharmacist. Mean preparation times for the different categories of variable and fixed activities were determined. Variable, fixed, and estimated nonproductive time were combined with 8 months retrospective output data to determine total weakly CAS service hours and personnel requirements. Variable activity time varied widely among the four categories of admixtures and had an aggregate mean time of 9.7 minutes per admixture. Variable and fixed activity time comprised 13.5 and 4.5 mean weekly service hours, respectively. Total weekly service time was 18 hours or 0.48 full-time equivalents. These results on elemental times and personnel requirements are similar to those obtained in previous studies.

Cost comparison of seven antibiotic combinations as empiric therapy in a simulated febrile neutropenic patient.

Total costs, drug and supply costs, and personnel costs for 14 days of therapy with seven therapeutically equivalent i.v. antibiotic combinations were calculated for a simulated febrile neutropenic patient. The cost for each antibiotic regimen was calculated using a previously developed computerized model that included the cost elements involved in preparation, administration, and pharmacokinetic monitoring of i.v. antibiotic therapy. Comparative costs for the seven antibiotic regimens were determined by inserting the costs of the individual elements into the model. Total costs for the 14 days of therapy varied greatly among the seven regimens, ranging from $908 to $2543. Antibiotics constituted the greatest percentage of total expenditures for each regimen (64-92%). Costs were increased substantially when a third-generation cephalosporin was included in the regimen. Antibiotic costs correlated strongly with total costs, while personnel costs correlated poorly with total costs and accounted for only 6-30% of the total expenditures. Computerized analysis of all costs involved in antimicrobial therapy for this simulated neutropenic patient showed that total costs varied widely in direct proportion to antibiotic costs. In selecting antimicrobial agents for high-risk patients, costs should be considered along with efficacy.

Tax aspects of outpatient drug transactions in nonprofit hospitals.

Tax issues related to sales of medications to outpatients by pharmacies in nonprofit hospitals are described. Hospitals are increasing their emphasis on development of ambulatory-care programs. Two aspects of the tax implications of such services are (1) whether revenue from sales of medications to ambulatory patients constitutes "unrelated business income" for the nonprofit hospital and thus is taxable and (2) whether engaging in dispensing of medications to ambulatory patients might jeopardize the tax-exempt status of the hospital. Various rulings from the Internal Revenue Service and court cases are reviewed. Sales of medications to members of the general public who are unrelated to the hospital are taxable. Sales of medications for the convenience of hospital patients, and irregular and intermittent sales to the public by a pharmacy that normally serves only "patients," are tax exempt. Sales of medications to the public probably do not jeopardize the tax-exempt status of a hospital so long as the primary purpose of the hospital is consistent with permissible tax-exempt purposes.