The authors explore complexity science, a relatively new field of inquiry, which holds for both clinicians and health care leaders the real possibility of stimulating fresh insights and approaches to health and medical care-both its provision and its organization. Two case studies are presented to illustrate how complexity theory can provide health care leaders with a new perspective on how to address the myriad challenges they confront daily: (1) a patient with dissociative identity disorder; and (2) a physician task group charged to advise on hospital medical staff reorganization and governance. These case studies help clinicians and leaders of health care organizations understand how complexity: (1) may be relevant, even helpful, as they consider difficult challenges in both patient and organizational management; and (2) might emerge as a synthesizing force as they face the extraordinarily complicated task of jointly creating integrated health care systems. A resource section is provided for those who may wish to further pursue the topic.

Adult↗

PubMedDate not supplied

Merging, de-merging, and emerging at Deaconess Billings Clinic.

Complexity theory offers a powerful model for effective mergers of health care organizations that differs substantially from customary approaches. Exploring how Deaconess Billings Clinic in Montana evolved from two separate and very different cultures provides insight into how organizations can apply a complex adaptive system (CAS) model of mergers to create more truly integrated health care systems. DBC's merger illustrates the phenomenon of emergence in complex systems, whereby structures arise that are not a synthesis of the pre-existing cultures or the result of a new culture being imposed. Instead, the merger is understood as an ongoing, self-organizing process appropriately characterized by fits and starts, feelings of uncertainty, and other natural challenges of change and growth. By squarely surfacing the distinct cultures of the organizations through abundant interaction, relationship building, and information flow, differences can be creatively transformed, resulting in deep-seated change and the emergence of a genuine, shared health care system culture.

Ambulatory Care Facilities↗

PubMedDate not supplied

Metabolism of bambuterol in rat liver microsomes: identification of hydroxylated and demethylated products by liquid chromatography mass spectrometry.

The oxidative metabolism of (R,S)-bambuterol in rat liver microsomes was studied. Metabolite fractions were analyzed by thermospray LC-MS. The use of an equimolar mixture of deuterium-labeled and unlabeled bambuterol facilitated the mass spectrometric identification of the metabolites. Six metabolites, formed via hydroxylation, demethylation, and hydrolytic reactions, were identified. The demethylated metabolites were found to be chemically unstable under physiological conditions. It is likely that the complex biotransformation of bambuterol into terbutaline is one factor contributing to the long duration of action of bambuterol.

Animals↗

PubMedDate not supplied

Liver metabolism of budesonide in rat, mouse, and man. Comparative aspects.

The metabolism of budesonide, (22RS)-16 alpha, 17 alpha-butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene- 3,20-dione, was studied in the 9000g supernatant fraction of livers from rat, mouse, and man. The two budesonide C-22 epimers produced different metabolites. This was explained by substrate-selective oxidation of the nonsymmetric 16 alpha, 17 alpha-acetal substituent. Epimer 22R gave 16 alpha-hydroxyprednisolone, while epimer 22S produced a metabolite tentatively identified as 23-hydroxybudesonide. Otherwise, budesonide followed the general metabolic pathways reported for synthetic glucocorticoids. Thus, oxidative metabolism predominated, 6 beta-hydroxybudesonide and delta 6-budesonide being identified in all investigated species. Reductive metabolism, giving 4,5 beta-dihydrobudesonide and 3,4,5 beta-tetrahydrobudesonide, was most pronounced in the rat. Rates and routes of budesonide metabolism were most similar in mouse and human livers. This implies that the mouse is a more relevant species than the rat in studies of the pharmacology and toxicology of budesonide.

Aged↗

PubMedDate not supplied

Metabolic acetal splitting of budesonide. A novel inactivation pathway for topical glucocorticoids.

Topical glucocorticoids usually have a high intrinsic glucocorticoid potency and may, after systemic uptake, induce side effects. The systemic inactivation of budesonide is rapid due to extensive liver biotransformation. The major metabolic pathway, 16 alpha, 17 alpha-acetal splitting, is unique for budesonide within this group of compounds. This biotransformation is catalyzed by microsomal monooxygenases and proceeds via hydroxylation and subsequent rearrangement to an intermediary ester. The ester is cleaved by hydrolysis to 16 alpha-hydroxyprednisolone and butyric acid. The hydrolysis product 16 alpha-hydroxyprednisolone has strongly reduced glucocorticoid activity.

Acetals↗

PubMedDate not supplied

Pharmacokinetics and analgesic effect of pethidine (meperidine) and its metabolites in the rat.

The pharmacokinetics of pethidine (meperidine) and norpethidine (normeperidine) have been investigated after iv administration of pethidine in the rat. The plasma concentration-time curve for pethidine could be described by a triexponential function. The calculated half-lives were 6.0, 18.5, and 64.5 min. Norpethidine, metabolically formed from pethidine, reached maximum plasma concentrations after 30 min and declined biexponentially with half-lives of 66.8 and 301 min. The time course of analgesia after iv administration of pethidine, norpethidine, and p-hydroxypethidine has also been evaluated. When the pharmacokinetic data were compared with the time course of analgesia, the plasma levels of pethidine could be correlated with the analgesic effect after the first rapid distribution phase. The pharmacokinetic constants for pethidine and norpethidine were used to stimulate the plasma levels of these compounds after multiple doses of pethidine. Accumulation of norpethidine was demonstrated to occur, which may be of importance when toxic and analgesic effects of pethidine are evaluated.

Analgesics↗

PubMedDate not supplied

Metabolic pathways of the topical glucocorticoid budesonide in man.

The metabolic pathways of budesonide[(22RS)-16 alpha, 17 alpha-butylidenedioxy-11 beta, 21-dihydroxypregna-1,4-diene-3,20-dione] in human liver 9000g supernatant fraction were studied. A comparison was made between the in vitro metabolite pattern and the metabolite pattern in plasma obtained after iv administration of tritiated budesonide to man. No qualitative difference could be found, which indicates that the in vitro model is useful to predict results in vivo. The two major metabolites formed in vitro were identified by HPLC and mass spectrometry as 6 beta-hydroxybudesonide and 16 alpha-hydroxyprednisolone. Loss of the acetal group was not observed when desonide (11 beta,21-dihydroxy-16 alpha,17 alpha-isopropylidenedioxy-pregna-1,4-diene-3,20-dione) was incubated with human liver 9000g supernatant fraction. Neither could 16 alpha-hydroxyprednisolone be detected after incubation of the (22S)-epimer of budesonide with the same medium. The cleavage of the acetal moiety is therefore suggested to be the result of a substrate-selective metabolic pathway.

Adolescent↗