You got a problem with that? Exploring evaluators' disagreements about ethics.

A random sample of American Evaluation Association (AEA) members were surveyed for their reactions to three case scenarios--informed consent, impartial reporting, and stakeholder involvement--in which an evaluator acts in a way that could be deemed ethically problematic. Significant disagreement among respondents was found for each of the scenarios, in terms of respondents' views of whether the evaluator had behaved unethically. Respondents' explanations of their judgments support the notion that general guidelines for professional behavior (such as AEA's Guiding Principles for Evaluators) can encompass sharply conflicting interpretations of how evaluators should behave in specific situations. Respondents employed in private business/consulting were less likely than those in other settings to believe that the scenarios portrayed unethical behavior by the evaluator, a finding that underscores the importance of taking contextual variables into account when analyzing evaluators' ethical perceptions. The need for increased dialogue among evaluators who represent varied perspectives on ethical issues is addressed.

Prescription to over-the-counter drug reclassification.

Self-care is becoming increasingly popular among health care consumers. The availability of over-the-counter medications makes it possible for consumers to treat numerous ailments without the supervision of a health care professional. Many of the medications now available without a prescription were previously classified as prescription-only products. The U.S. Food and Drug Administration has procedures in place that allow prescription products to be reclassified as over-the-counter medications if certain criteria are met. Reclassified products have had clinical and economic effects on the U.S. health care system and have led to concerns among health care professionals. Patient education and counseling are particularly important to promote safe and effective use of over-the-counter products.

Comparison of tobramycin pharmacokinetics after administration by CRIS and a traditional intravenous piggyback infusion.

OBJECTIVE: To compare the administration pharmacokinetics of a 30-minute intravenous piggyback (ivpb) infusion of tobramycin with those of controlled-release infusion system (CRIS) using a 20-mL vial at rates of 60 and 120 mL/h. DESIGN: Randomized, controlled, crossover, prospective, open-label trial. SETTING: Medical college-affiliated hospital. PARTICIPANTS: Eight healthy volunteer men between the ages of 22 and 24 years weighing between 60 and 90 kg. INTERVENTIONS: Volunteers received, in random order, tobramycin sulfate 2 mg/kg i.v. on 3 occasions separated by 1 week. The drug was administered using a 50-mL ivpb infusion at 100 mL/h for 30 minutes, and with the CRIS using a 20-mL vial with flow rates of 60 mL/h for 1 hour (slow) and 120 mL/h for 1 hour (fast). MAIN OUTCOME MEASURES: Primary endpoints were area under the time-concentration curve (AUC), time to reach maximum concentration (tmax), and maximum concentration (Cmax). Secondary endpoints were elimination rate constant (ke), clearance (Cl), and half-life (t1/2). RESULTS: Six volunteers successfully completed the trial. The tmax values observed following fast CRIS and ivpb were 28 +/- 8 and 32 +/- 4 minutes, respectively, and not significantly different from each other. Both occurred significantly earlier than the tmax associated with slow CRIS (44 +/- 7 min). The Cmax values observed following ivpb (11.2 +/- 1.5 mg/L) and slow CRIS (10.9 +/- 0.9 mg/L) administration were not significantly different from each other, but both were significantly lower than that of fast CRIS (13.4 +/- 1.5 mg/L). The AUCs of slow and fast CRIS were 29.8 +/- 4.8 and 31.2 +/- 3.8 mg/L.h, respectively, and were not significantly different from each other. The AUC of fast CRIS was significantly greater than that observed with ivpb (27.4 +/- 4.3 mg/L.h). No significant difference in ke (fast CRIS 0.32 +/- 0.03 h-1; slow CRIS 0.33 +/- 0.04 h-1; ivpb 0.34 +/- 0.0 h-1) was observed among any of the methods. CONCLUSIONS: CRIS administration of tobramycin resulted in higher AUCs than did ivpb administration. Compared with ivpb, fast CRIS resulted in a higher Cmax, but the tmax values of fast CRIS and ivpb administration were not statistically different. Compared with ivpb, slow CRIS resulted in a more delayed tmax, but the Cmax values of slow CRIS and ivpb were not statistically different.

Public opinion's tilt against private enterprise.

Drawing on hundreds of identically worded questions, this DataWatch finds that Americans now feel genuine concern for the health status of other people. This is a dramatic development in a country that has encouraged individuals to isolate themselves. The second finding is that necessity has pushed Americans into grudgingly accepting government taxation and regulation as the most feasible way to provide what is by now an expected benefit: secure access to essential health care. Evidence of Americans' concerns and of the tilt away from laissez-faire commitments challenges two of the most sacred conventional assumptions about public opinion in the United States.

Health reform impasse: the politics of American ambivalence toward government.

This paper presents two interrelated arguments: it rethinks conventional understanding of the policy-making process and analyzes an important substantive issue regarding public opinion. The substantive issue involves the public's deep ambivalence toward government reforms: Americans are simultaneously supportive of significant reform and uneasy about expanding government involvement. The critical question is what, if any, impact this public ambivalence will have on policy deliberations. Answering this question requires an analysis of the role of public opinion in policy-making. Investigation of historic as well as contemporary health reform suggests that the impact of public opinion varies, depending on the character of both public opinion and the policy issue. The public's preferences are not especially influential when they are characterized by uncertainty or when an issue is not salient, but strong and sustained sentiment can affect agenda setting, interest group leverage over government officials, and policymakers' formulation of detailed administrative arrangements.

Fiber and colon cancer.

The human evidence that dietary fiber prevents the development of colon cancer has been reviewed. The correlational studies are consistent with a protective effect in 61.9 per cent of reports. However, these studies are all retrospective and largely uncontrolled. The case-control studies provide evidence of a protective effect in only 48 per cent of reports. It is of additional concern that some human studies have found an association between tumor enhancement and some fiber-containing foods. Whereas this is not sufficient evidence to implicate dietary fiber as a promoter of human colon cancer, it does perhaps argue for a more conservative approach to recommending high-fiber diets as a means of cancer prevention. The animal data show that different sources of dietary fiber produce markedly different effects on colon carcinogenesis. Although some fibers exhibit protective properties, others clearly promote tumor development. The mechanisms behind these opposing actions require further investigation. However, one thing is clear and that is that dietary fibers do modulate the carcinogenic process and as such provide a valuable tool for probing the mechanisms and stages of colon tumor development. Dietary fiber appears to play a major role in the regulation of normal intestinal function and in the maintenance of a healthy intestinal mucosa. Although there is some evidence that a fiber-deficient diet predisposes to colon carcinogenesis, it is still not known whether an increase in fiber consumption will prevent the development of colon cancer. This is further complicated by not knowing what constitutes a normal level of fiber intake. In the interim, physicians should perhaps advise their patients to consume a moderate diet that contains vegetables, fruits, and whole grains. This will provide a varied source of fiber-containing foods and if consumed in sufficient quantity will optimize intestinal transit and bulk according to individual needs. Isolated fiber supplements have not been shown to be effective in colon cancer prevention. Further attempts to be more specific about what type of fiber to recommend seem premature at this time. However, an intake in the range of 20 to 35 gm per day of dietary fiber from foods has recently been recommended by an Expert Panel.

Long-term effects of fermentable fibers on rat colonic pH and epithelial cell cycle.

The long-term effects of fermentable fibers on colonic luminal pH and the epithelial cell cycle were compared in 50 male Sprague-Dawley rats fed either a defined basal fiber-free diet or the basal diet supplemented with 10% pectin, cellulose or guar or with 20% oat bran. After 8 mo, in vivo pH measurements revealed that acidification of luminal contents occurred in the cecum and in mid and distal colons of rats fed fiber-supplemented diets when compared with the fiber-free controls (P less than 0.05). Pectin and guar produced the greatest acidification of luminal contents, the largest increase in cecal surface area and the highest percentage of colonic cells in S-phase, as measured by flow cytometry. In the proximal colon of the pectin group 9.2 +/- 0.5% of cells were in S-phase (6.3 +/- 0.8% with the fiber-free group) (P less than 0.05) and in the distal colon of the guar group 10.9 +/- 1.4% were in S-phase (7.1 +/- 0.5% with the fiber-free group) (P less than 0.05). Even though the most fermentable fibers produced the greatest mitogenic response, there was no site-specific correlation between pH and mucosal cell growth except in the cecum. This suggests that fibers may act as colon cell growth factors by some mechanism other than extracellular pH changes.

Fiber supplementation results in expanded proliferative zones in rat gastric mucosa.

The effects of three different fibers on gastric fundic mucosal morphometrics and cytokinetics were compared by feeding defined diets to 40 male Sprague-Dawley rats for 4 wk. Groups of 10 rats each were fed a fiber-free diet as a control or the same diet uniformly diluted with either 20% oat bran, 10% pectin, or 10% guar. Fiber supplementation expanded the zone of proliferating cells by 58% with the guar-supplemented diet (p less than 0.05), 101% with oat bran (p less than 0.05), and 150% with pectin (p less than 0.01) compared with controls. Expansion was due to a downward shift in proliferating cells towards the muscularis mucosa of the oat bran and pectin groups (p less than 0.01) while pectin also expanded the proliferative zone toward the mucosal surface (p less than 0.05). Because expanded proliferative zones have been shown to precede and accompany neoplastic transformation, these data suggest a potentially negative effect of dietary fiber on the gastric mucosa.

Effect of dietary fiber on colonic cell proliferation and its relationship to colon carcinogenesis.

The addition of specific fiber supplements to semipurified diets has been shown to stimulate large bowel cell proliferation in laboratory rodents. Relatively insoluble fibers such as cellulose, which is poorly fermented, the more-soluble oat bran, and inert bulking agents such as kaolin produce little or no effect on cell growth. On the other hand, wheat bran, pectin, guar gum, and degraded carageenan all stimulate large bowel cell proliferation, the greatest growth response tending to occur in the cecum or proximal colon. The proximal large bowel is also the major site for the intestinal fermentation of dietary fiber and any other nonabsorbed carbohydrates. The fermentation of fiber by colonic microorganisms results in the production of short-chain fatty acids and a lower pH of large bowel contents, metabolic events known to be associated with increased epithelial cell growth. In general, factors that stimulate cell growth also enhance tumor development, a concept that holds true in the colon even for dietary fibers such as pectin and guar gum. Wheat bran can also stimulate colon carcinogenesis when fed only during carcinogen exposure. Oat bran and corn bran may stimulate colon carcinogenesis by increasing fecal bile acid excretion, a feature of many soluble fibers, while the acidification of large bowel contents is associated with an increased frequency of chemically induced colonic cancers. A greater understanding of colonic metabolism and cell physiology is needed to define fully the mechanisms by which dietary fibers modify colon cancer development.

Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms.

The relationships between fiber consumption and human cancer rates have been examined, together with an analysis of the effects of individual dietary fibers on the experimental induction of large bowel cancer. The human epidemiology indicates an inverse correlation between high fiber consumption and lower colon cancer rates. Cereal fiber sources show the most consistent negative correlation. However, human case-control studies in general fail to confirm any protective effect due to dietary fiber. Case-control studies indicate that if any source of dietary fiber is possibly antineoplastic then it is probably vegetables. These results may mean that purified fibers alone do not inhibit tumor development, whereas it is likely that some other factors present in vegetables are antineoplastic. Experiments in laboratory animals, using chemical induction of large bowel cancer, have in general shown a protective effect with supplements of poorly fermentable fibers such as wheat bran or cellulose. In contrast, a number of fermentable fiber supplements including pectin, corn bran, oat bran, undegraded carageenan, agar, psyllium, guar gum, and alfalfa have been shown to enhance tumor development. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens and/or promoters contained within the intestinal lumen, the modulation of colonic microbial metabolic activity, and biological modification of intestinal epithelial cells. Dietary fibers not only bind carcinogens, bile acids, and other potential toxins but also essential nutrients, such as minerals, which can inhibit the carcinogenic process. Fermentation of fibers within the large bowel results in the production of short chain fatty acids, which in vivo stimulate cell proliferation, while butyrate appears to be antineoplastic in vitro. Evidence suggests that if dietary fibers stimulate cell proliferation during the stage of initiation, then this may lead to tumor enhancement. Fermentation also lowers luminal pH, which in turn modifies colonic microbial metabolic acidity, and is associated with increased epithelial cell proliferation and colon carcinogenesis. Because dietary fibers differ in their physiochemical properties it has been difficult to identify a single mechanism by which fibers modify colon carcinogenesis. Clearly, more metabolic and physiological studies are needed to fully define the mechanisms by which certain fibers inhibit while others enhance experimental colon carcinogenesis.