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Biomedical subjects

B Jennings

Publications and source records attributed to B Jennings.

At least 55 records · Page 3Linked to original sources

Active euthanasia and forgoing life-sustaining treatment: can we hold the line?

Public sentiment in favor of permitting voluntary active euthanasia creates a dilemma for a bioethics rooted in a libertarian notion of autonomy. At stake in the active euthanasia debate is actually a question of power--the individual's assertion of sovereignty over the timing and circumstances of his or her own death. Also at stake is society's unwillingness to impose a conception of the good--and a good dying--on individuals whose personal values and conceptions of the good may differ. In order both to reject voluntary active euthanasia and to affirm the patient's right to forgo life-sustaining treatment, some societal conception of the good must be developed and agreed upon to counter unbridled claims of individual self-sovereignty over dying. Pragmatic arguments alone, such as the need to maintain confidence in the doctor-patient relationship, will not be sufficient.

Beneficence↗

Possibilities of consensus: toward democratic moral discourse.

The concept of consensus is often appealed to in discussions of biomedical ethics and applied ethics, and it plays an important role in many influential ethical theories. Consensus is an especially influential notion among theorists who reject ethical realism and who frame ethics as a practice of discourse rather than a body of objective knowledge. It is also a practically important notion when moral decision making is subject to bureaucratic organization and oversight, as is increasingly becoming the case in medicine. Two models of consensus are examined and criticized: pluralistic consensus and overlapping consensus. As an alternative to these models, the paper argues that consensus refers to the dialogic aspects of a broader normative conception of democratic moral agency. When the preconditions for that dialogic democratic practice are met, consensus has a justificatory role in ethics; when they are not, consensus, as distinct from mere agreement, does not emerge and can have no moral authority.

Bioethical Issues↗

Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin.

Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.

Administration, Inhalation↗

Toward an expanded vision of clinical ethics education: from the individual to the institution.

This paper advances a new paradigm in clinical ethics education that not only emphasizes development of individual clinicians' skills, but also focuses on the institutional context within which health care professionals work. This approach has been applied to the goal of improving the care provided to critically and terminally ill adults. The model has been adopted by about thirty hospitals and nursing homes; additional institutions will soon join the program, entitled Decisions Near the End of Life. Here, we describe the history and rationale for this approach, its goals, pedagogical assumptions, and design.

Curriculum↗

Low-tension glaucoma.

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Adrenergic beta-Antagonists↗

Bioequivalent doses of budesonide and prednisone in moderate and severe asthma.

We determined the relative antiasthmatic and systemic glucocorticoid potencies of inhaled budesonide (BUD) versus morning-dose oral prednisone (PRED) in 34 adult patients with asthma over a dose range extending from conventional to high and potentially toxic levels, 3.2 mg of BUD or 40 mg of PRED per day. Changes in symptom frequency and severity, FEV1, and peak expiratory flow rate were measured during a double-blind, double-dummy controlled, crossover protocol. The drugs proved equally effective, provided a sufficient dosage was administered. The dose required to eliminate recurrently disabling asthma relapses in these patients was about 2.0 mg of BUD per day or greater than 40 mg of PRED per day. On the average, BUD doses greater than or equal to 1.84 mg/day/70 kg adult (26.3 micrograms/kg/day) exhibited systemic effects on the 8 AM serum cortisol level and blood eosinophil count equivalent to greater than or equal to 15 mg of PRED per day. The latter doses are known to be associated with steroid-induced complications, such as osteoporosis. However, the level of systemic glucocorticoid activity produced by any particular dose of BUD in these patients was consistently much lower than that produced by the dose of PRED needed to achieve an equivalent level of antiasthmatic response. Thus, the use of high-dose inhaled BUD appears clinically reasonable and ethically acceptable in patients with severe asthma in whom the alternative is their continuing dependency on PRED.

Administration, Inhalation↗

The binding of polycyclic aromatic hydrocarbon diol-epoxides to DNA.

Diol-epoxide derivatives of polycyclic aromatic hydrocarbons are the ultimate carcinogenic forms of these compounds encountered in vivo. Using a novel electro-fluorescence apparatus, we report that, like the (+/-)-anti-diol-epoxide of benzo[a]pyrene (BP), the similar diol-epoxides of benzo[a]anthracene (BA) and 3-methylcholanthrene (3MC) also bind to the DNA helix at an inclination of approximately 50 degrees. This compares with the essentially perpendicular, intercalative-type binding generally found with saturated aromatic compounds, such as the native hydrocarbons, and may indicate a systematic behavior in the molecular associations precursive to carcinogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Use of spacers to facilitate inhaled corticosteroid treatment of asthma.

Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.

Administration, Topical↗

Personal observations on the use of inhaled corticosteroid drugs for chronic asthma.

Topically active inhaled corticosteroid (IC) drugs are highly effective for chronic asthma. Formalized conceptions of "high, low or safe" dosages of these drugs may be less appropriate than one of "optimal dosage". It seems reasonable to formulate a specific goal of treatment, and then fit dosage to the individual needs and tolerances of the patient rather than to a conventionalized "safe" limit, based on averaged data from different and perhaps quite dissimilar subjects. The studies reviewed here illustrate some principles applicable to the effective use of IC drugs.

Aerosols↗

Dosing regimen of budesonide and occurrence of oropharyngeal complications.

The influence of the dosing regimen on the occurrence of oropharyngeal complications during a trial of the anti-asthmatic aerosol steroid budesonide was assessed by systematically varying the daily dose (400, 800, 1,600 micrograms), dose frequency (b.i.d. vs. q.i.d.), and dosing schedule (AM vs. AM/PM). Dysphonia was infrequent and was not affected by any features of the treatment regimen. ;Its incidence was unrelated to that of candidiasis. The amount of oropharyngeal candidiasis on the other hand correlated strongly with the daily dose of budesonide and dosing frequency. B.i.d. treatment abolished the effect of increasing budesonide dose on candidiasis, and virtually eliminated any need for nystatin. A 24 h interval between doses (using an AM schedule), or two intervals of about 12 h were both effective in conserving antifungal host defences in the oropharynx. Temporary conversion to b.i.d. dosing can facilitate the control or prevention of thrush, especially when the risk is increased by concomitant antibiotic therapy, as was shown to be the case in these patients. A small, but statistically significant, deterioration in peak expiratory flow occurred during b.i.d. dosing. Thus, despite its ability to virtually eliminate the problem of recurring thrush, b.i.d. dosing should not be continued indefinitely. These considerations probably apply to other topically active steroids currently used to treat asthma.

Aerosols↗

The care of the terminally ill: morality and economics.

Are current expenditures on dying patients disproportionate, unreasonable, or unjust? Although a review of empirical data reveals that care for the terminally ill is very costly, it is not appropriate to conclude that such expenditures represent a morally troubling misallocation of societal resources. Moreover, though efforts to reduce the costs of caring for the dying are not unreasonable, they must be undertaken with great caution. At present, such efforts should concentrate on three basic goals: development of better criteria for admission to intensive- and critical-care units; promotion of patient and family autonomy with regard to decisions to stop or refuse certain kinds of treatment; and promotion of alternative forms of institutional care, such as hospice care. The most difficult moral problems will arise when patients and their physicians seek access to therapies judged only marginally useful. There may be conflict between administrators with broad institutional responsibilities and clinicians committed to particular patients.

Cost-Benefit Analysis↗

Tactics for clinical trials of therapy in patients with chronic asthma.

Asthma can be conceptualized as a disease system ranging from the molecular to the social level. It is important to monitor both subjective and objective indices appropriate to different parts of the system. Objective indices alone are not enough. It is also important to distinguish disability from symptom severity or frequency and pulmonary impairment. The personality of the patient or the duration of follow-up can profoundly affect the perceived outcome of a particular treatment. It is important in controlled trials, and also in clinical practice, to take these factors into account.

Asthma↗