Gerald Logue

Cortisol pharmacodynamics after methylprednisolone administration in young and elderly males

Glucocorticoids are commonly prescribed in the elderly on an empiric basis with little consideration for the age‐related alterations in pharmacologic response. The objectives of this study were to compare the effect of methylprednisolone on cortisol patterns in elderly and young healthy men, to define the relationship between pharmacokinetic parameters of methylprednisolone and pharmacodynamics of cortisol in the elderly and young men. Seven healthy, elderly males (69–82 years old) and five healthy, young males (24–37 years old) participated in a 24‐hour pharmacodynamic trial with randomized assignment to a control period (Phase I) and a methylprednisolone period (Phase II). Serial blood samples were obtained throughout both study periods. Cortisol measurements included the total area under the concentration—time curve (AUC), return AUC, and suppression ratio. During Phase I, a circadian pattern was noted in both groups. After exposure to methylprednisolone (Phase II), a linear decline in serum concentrations of cortisol was observed in both groups. The return AUC of cortisol (425 ± 357 ng·hr/mL [elderly] versus 854 ± 216 ng·hr/mL [young]) and the total AUC 764 ± 340 g·h/mL [elderly] versus 1,230 ± 258 g·hr/mL [young]) were significantly lower in the older men. In addition, a significant decline in total AUC and nadir concentration of cortisol from Phase I to Phase II was noted within both groups. The suppression ratio was significantly greater in the elderly men (mean, 0.38 versus 0.58 in young), which indicates a greater degree of adrenal suppression after administration of methylprednisolone. Exposure to methylprednisolone, as measured by AUC, was 554 ± 215 ng·hr/kg (elderly) and 389 ± 102 ng·hr/kg (young). The greater exposure to methylprednisolone noted in the elderly yielded significant combined correlations for both groups with AUC, return AUC, and suppression ratio of cortisol. A more significant response of cortisol to the exogenous glucocorticoid was apparent in the elderly men. In addition, a slower clearance of methylprednisolone was noted in the elderly group compared with their young counterparts. The effect of reduced clearance of methylprednisolone on the suppression ratio indicates the interrelationship between the disposition of a single dose of an exogenous glucocorticoid and response patterns of cortisol.

Pharmacokinetics of methylprednisolone in elderly and young healthy males

OBJECTIVE: To characterize and compare the pharmacokinetics of a single intravenous dose of methylprednisolone in elderly and young healthy males.

Complement-activating antineutrophil antibody in systemic lupus erythematosus☆

Serum samples from 18 patients with systemic lupus erythematosus (SLE) were tested for neutrophil C3-fixing ability and neutrophil-binding lgG by the binding of radioiodinated monoclonal anti-C3 antibody and staphylococcal protein A to paraformaldehyde-fixed allogeneic neutrophils sensitized with serum. Serum from patients with SLE resulted in the binding of significantly greater amounts of lgG to neutrophils than normal serum, but this lgG binding did not correlate with the degree of neutropenia. In contrast, serum samples from 10 neutropenic patients with SLE resulted in the binding of significantly greater amounts of C3 to neutrophils when compared with serum samples from eight non-neutropenic patients with SLE. Fixation of C3 to neutrophils by serum from patients with SLE appeared to be due to the binding of complement-activating monomeric antineutrophil lgG autoantibody. A significant negative correlation (r = -0.78) between the neutrophil count and the C3-fixing ability of serum from patients with SLE suggested that antineutrophil antibody-mediated activation of complement may be important in the pathophysiology of neutropenia in SLE.

T-lymphocytes escape membrane defect in paroxysmal nocturnal haemoglobinuria

Erythrocytes, granulocytes and platelets from patients with paroxysmal nocturnal haemoglobinuria (PNH) are abnormally sensitive to lysis by complement. We studied T‐lymphocytes from PNH patients for abnormal complement lysis sensitivity. T‐lymphocytes free of other contaminating blood cells were prepared by sedimentation, nylon wool filtration, and density gradient centrifugation. The lymphocytes were then labelled with 51Cr and lysis induced by antithymocyte globulin and rabbit complement. PNH lymphocytes were no more susceptible to complement‐mediated lysis than lymphocytes from normal individuals. The unusual sensitivity of PNH erythrocytes could still be demonstrated when rabbit serum was a source of complement so the lack of any difference in the sensitivity of normal and PNH lymphocytes was probably not attributable to the inability of rabbit serum to elicit the membrane defect. PNH erythrocytes and granulocytes also acquire more membrane‐bound C3 when human complement is activated. Therefore we also searched for increased membrane C3 binding on PNH lymphocytes using anti‐I antibody and human serum as a complement source. C3 binding was measured using 125I labelled monoclonal mouse anti‐human C3. While we verified increased membrane C3 binding on PNH granulocytes during complement activation we were unable to show similar differences between PNH and normal T‐lymphocytes. Thus PNH T‐lymphocytes do not share the membrane abnormalities of PNH erythrocytes and granulocytes.

Ethical issues in health care on the frontiers of the twenty-first century

Dedication. Ethical Issues in Health Care on the Frontiers of the Twenty First Century S. Wear, et al. Preface: The Continued Role of Biomedical Ethics in the Next Millenium J. Naughton. Keynote Address: Bioethics at the End of the Millenium: Fashioning Health Care Policy in the Absence of a Moral Consensus H.T. Engelhardt. Part I: The Dilemma of Funding Health Care. The Dilemma of Funding Health Care S. Wear. Toward Multiple Standards of Health Care Delivery: Takin Moral and Economic Diversity Seriously H.T. Engelhardt, Jr. A Preventive Ethics Approach to the Managed Practice of Medicine: Putting the History of Medical Ethics to Work L.B. McCullough. Saving Lives, Saving Money: Shepherding the Role of Technology E.H. Morreim. Part II: The Human Genome Project. The Human Genome, Difference, and Disease: Nature, Culture, and New Narratives for Medicines Future J.J. Bono. Concepts of Disease After the Human Genome Project E. Juengst. From Promises to Progress to Portents of Peril: Public Responses to Genetic Engineering D. Nelkin. PKU and Procreative Liberty: Historical and Ethical Considerations D.B. Paul. Everybodys Got Something J.D. Moreno. Part III: The Physician/Patient Relationship. The Physician/Patient Relationship G. Logue. A Medicine of Neighbors K. Montgomery. Trust, Institutions, and the Physician-Patient Relationship: Implications for Continuity of Care J.R. Rosenbaum. Can Relationships Heal - At a Reasonable Cost? H. Brody. Values and the Physician-Patient Relationship S. Devito. General Bibliography A. McEvoy. Notes on Contributors. Index.

The Health Care Institution / Patient Relationship

Over the last quarter century, the field of bioethics has proceeded with a primary focus on the sorts of moral problems and quandaries that surface within the individual provider-patient relationship. To be sure, a parallel focus on more systemic issues, such as justice and equity within health care, or the allocation of scarce medical resources, has also occurred. Equally, focus has been given to more extraordinary, “sexy” sorts of issues, e.g., stem cell research and surrogate motherhood. But if one performed a tally of the number of pages produced within bioethics proper over this period, the total count for issues such as informed consent, truth-telling, confidentiality, beneficence and paternalism, and death and dying, cast within the specific frame of the provider-patient relationship, would surely dwarf the number of pages dedicated to the more systemic or extraordinary issues.

Cortisol (C) pharmacodynamics after methylprednisolone (MePn) in young and elderly males

Clinical Pharmacology & Therapeutics (1996) 59, 173–173; doi: 10.1038/sj.clpt.1996.193