Anticoagulation in the elderly.

Oral anticoagulation therapy has demonstrated benefit in the treatment and prevention of a variety of thromboembolic disorders. Most individuals who receive oral anticoagulant therapy are elderly patients with nonvalvular atrial fibrillation and acute or recurrent venous thromboembolism. Anticoagulation in elderly patients poses unique challenges for the practicing clinician because they are simultaneously at higher risk for recurrent thromboembolism and major bleeding, including catastrophic intracranial hemorrhage. The pharmacology of warfarin in the elderly is reviewed, including important drug interactions and current dosing recommendations for elderly patients. Evidence of the benefits and risks of oral anticoagulation therapy are reviewed for patients with atrial fibrillation and venous thromboembolism. This information should enable practitioners to better assess the relative risks and benefit of oral anticoagulation therapy to guide treatment decisions in the elderly.

Effects of 17beta-estradiol and testosterone on hepatic mRNA/protein levels and catalytic activities of CYP2M1, CYP2K1, and CYP3A27 in rainbow trout (Oncorhynchus mykiss).

There is growing concern that exposure to chemicals in the environment can disrupt the endocrine systems of wildlife and humans, causing reproductive problems or other adverse effects. The expression of many cytochrome P450s (CYPs) is under hormonal control, hence, levels of these enzymes can be affected by exposure to endocrine-disrupting chemicals. Previous research has reported that treatment of fish and other animals with the estrogenic and androgenic hormones 17beta-estradiol (E2) and testosterone (T) alters the P450 content or enzyme activities in the treated animals. However, the results of many of these studies are either incomplete or in disagreement and in most cases the effect on specific P450 forms has not been determined. Therefore, to better understand the effects of gonadal hormones on the expression of P450s and their associated enzyme activities, it was of interest to undertake a comprehensive investigation of the transcriptional and translational expression of three constitutive hepatic P450s in the rainbow trout (Oncorhynchus mykiss) following hormone exposure. Accordingly, juvenile trout were injected intraperitoneally with propylene glycol vehicle and the most active estrogenic and androgenic hormones E2 (3 mg/kg) or T (3 mg/kg) on days 1, 4, 7, 13, and 15 and euthanized on day 19. After treatment with E2, hepatic microsomes showed significantly lower levels (percentage of control) in total P450 contents (52%), lauric acid hydroxylase (32%), and 6beta-progesterone hydroxylase activities (27%), [(3)H]aflatoxin-DNA binding (31%), and the protein levels of individual cytochrome P450s (CYPs) LMC1 (CYP2M1), LMC2, (CYP2K1), and LMC5 (CYP3A27) (average for three isoforms a reduction to 29% of control values) with only minor differences between sexes. Treatment with T had either no effect or resulted in small increases in total P450 in males (42%), in lauric acid hydroxylase in females (24%), and in 6beta-progesterone hydroxylase activity in males (21%). Biological variabilities among fish were high and a polymorphic or new LMC2-like form was detected at about 52 kDa in some liver microsomal samples after exposure of fish to either hormone. Female liver RNAs were analyzed through Northern blots and an average decrease of 94% in CYP2 M1, CYP2K1, and CYP3A27 mRNA levels occurred in the E2-treated trout. In livers from T-treated trout, the changes of mRNA levels of CYP2M1 and CYP3A27 were negligible, but CYP2K1 mRNA level decreased by about 60%. Additional CYP2K1 cDNA hybridizable mRNAs were seen in some fish as faint bands at about 2.8 kb for both hormone treatments. Results of this study, therefore, indicated that E2 down-regulated while T produced small but variable effects on the hepatic mRNA/protein levels of CYP2K1, CYP2M1, and CYP3A27 in juvenile rainbow trout. This study, therefore, suggests that exposure of fish and other wildlife to environmental endocrine disruptors, especially estrogen mimics, can adversely affect a number of physiological processes through mechanisms involving altered levels of expression of specific P450 isozymes.

Heterologous expression of CYP2K1 and identification of the expressed protein (BV-CYP2K1) as lauric acid (omega-1)-hydroxylase and aflatoxin B1 exo-epoxidase.

LMC2 is the most abundant constitutively expressed hepatic cytochrome P450 found in sexually immature rainbow trout (Onchorynchus mykiss) and is also the isozyme that activates the carcinogen aflatoxin B1 (AFB1). This P450 has been cloned, sequenced, and designated as CYP2K1. The present report describes the heterologous expression of enzymatically active CYP2K1 (BV-CYP2K1) in baculovirus Spodoptera frugiperda (Sf9) insect cells and its catalytic and immunoreactivity characterization in comparison with that of the previously purified LMC2 P450. Homogenates of Sf9 cells expressing the CYP2K1 enzyme and LMC2 both catalyzed the hydroxylation of lauric acid and the epoxidation of AFB1 in the presence of rat NADPH-cytochrome P450 reductase. Both LMC2 and BV-CYP2K1 catalyzed the oxidation of lauric acid primarily at the (omega-1) position plus small amounts at the (omega-2) position. Formation of AFB1 epoxide was shown indirectly by the appearance of an AFB1 epoxide-glutathione conjugate when P450 incubation mixtures contained AFB1, glutathione (GSH) together with mouse liver cytosol or purified rat GSH-transferase. When the AFB1 epoxide-GSH conjugate produced by BV-CYP2K1 and purified LMC2 was analyzed by HPLC using a chiral column, it had a retention time identical to that produced by CYP3A4, a human P450 known to form exclusively the AFB1 exo-epoxide. These results, therefore, confirm that the cDNA-expressed CYP2K1 protein is catalytically and immunologically identical to purified trout LMC2 and that these two enzymes produce primarily the highly carcinogenic stereoisomeric exo-epoxide form of AFB1.

Prenylflavonoids from hops inhibit the metabolic activation of the carcinogenic heterocyclic amine 2-amino-3-methylimidazo[4, 5-f]quinoline, mediated by cDNA-expressed human CYP1A2.

The heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potential human carcinogen found in cooked food that requires initial metabolic activation by cytochrome P450s, primarily CYP1A2. The present study was conducted to examine whether recombinant human CYP1A2 expressed in insect cells mediates the metabolic activation of IQ and whether prenylflavonoids found in hops and beer would modulate the CYP1A2-mediated activation of IQ. The cDNA-expressed human CYP1A2 was found to strongly activate IQ as measured by the Ames Salmonella assay and by the covalent binding of IQ metabolites to calf thymus DNA and protein. Inhibition studies showed that the prenylchalcone xanthohumol and the prenylflavanones 8-prenylnaringenin and isoxanthohumol strongly inhibited the mutagenic activation of IQ mediated by cDNA-expressed human CYP1A2 in the Ames Salmonella assay. The three prenylflavonoids also markedly inhibited the human CYP1A2-mediated binding of IQ to metabolites that bind to DNA. The inhibition of the metabolic activation of IQ was paralleled by the inhibition of acetanilide 4-hydroxylase activity of human CYP1A2. Thus, xanthohumol, isoxanthohumol, and prenylflavanones 8-prenylnaringenin are potent inhibitors of the metabolic activation of IQ and may have the potential to act as chemopreventive agents against cancer induced by heterocyclic amines activated by CYP1A2.

In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus.

1. Several unique flavonoid compounds have recently been isolated from hops, Humulus lupulus, and their presence has been detected in beer. Their chemical structures are similar to other plant-derived compounds, many present in the human diet, that have been shown to have cancer chemopreventive properties due, in part, to inhibition of cytochrome P450 enzymes that activate carcinogens. Additionally, preliminary studies have shown these flavonoids (at 100 microM) to be inhibitory of P450-mediated activation reactions in a variety of in vitro systems. Thus, the in vitro effects of these phytochemicals on cDNA-expressed human CYP1A1, CYP1B1, CYP1A2, CYP3A4 and CYP2E1 were currently examined by the use of diagnostic substrates and the carcinogen AFB1. 2. At 10 microM, the prenylated chalcone, xanthohumol (XN), almost completely inhibited the 7-ethoxyresorufin O-deethylase (EROD) activity of CYP1A1. At the same concentration, other hop flavonoids decreased the EROD activity by 90.8-27.0%. 3. At 10 microM, XN completely eliminated CYP1B1 EROD activity, whereas the other hop flavonoids showed varying degrees of inhibitory action ranging from 99.3 to 1.8%. 4. In contrast, the most effective inhibitors of CYP1A2 acetanilide 4-hydroxylase activity were the two prenylated flavonoids, 8-prenylnaringenin (8PN) and isoxanthohumol (IX), which produced > 90% inhibition when added at concentrations of 10 microM. 5. CYP1A2 metabolism of the carcinogen AFB1 was also inhibited by IX and 8PN as shown by decreased appearance of dihydrodiols and AFM1 as analysed by hplc. IX and 8PN also decreased covalent binding of radiolabelled AFB1 to microsomal protein in a concomitant manner. 6. XN, IX and 8PN, however, were poor inhibitors of CYP2E1 and CYP3A4 as measured by their effect on chorzoxazone hydroxylase and nifedipine oxidase activities respectively. 7. These results suggest that the hop flavonoids are potent and selective inhibitors of human cytochrome P450 and warrant further in vivo investigations.

Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines.

Six flavonoids [xanthohumol (XN), 2',4',6',4-tetrahydroxy-3'-prenylchalcone (TP); 2',4',6',4-tetrahydroxy-3'-geranylchalcone (TG); dehydrocycloxanthohumol (DX); dehydrocycloxanthohumol hydrate (DH); and isoxanthohumol (IX)] from hops (Humulus lupulus) were tested for their antiproliferative activity in human breast cancer (MCF-7), colon cancer (HT-29) and ovarian cancer (A-2780) cells in vitro. XN, DX and IX caused a dose-dependent (0.1 to 100 microM) decrease in growth of all cancer cells. After a 2-day treatment, the concentrations at which the growth of MCF-7 cells was inhibited by 50% (IC50) were 13.3, 15.7 and 15.3 microM for XN, DX and IX, respectively. After a 4-day treatment, the IC50 for XN, DX and IX were 3.47, 6.87 and 4.69 microM, respectively. HT-29 cells were more resistant than MCF-7 cells to these flavonoids. In A-2780 cells, XN was highly antiproliferative with IC50 values of 0.52 and 5.2 microM after 2 and 4 days of exposure, respectively. At 100 microM, all the hop flavonoids were cytotoxic in the three cell lines. Growth inhibition of XN- and IX-treated MCF-7 cells was confirmed by cell counting. XN and IX inhibited DNA synthesis in MCF-7 cells. As antiproliferative agents, XN (chalcone) and IX (flavanone isomer of XN) may have potential chemopreventive activity against breast and ovarian cancer in humans.

Evaluation of chemicals as inhibitors of trout cytochrome P450s.

This study examined the ability of several inhibitors of mammalian cytochrome P450s to affect hepatic P450-mediated monooxygenase activities in microsomes from beta-naphthoflavone (BNF)-treated rainbow trout. Three monooxygenase activities, namely, lauric acid (omega-1)-hydroxylase (LA-OH), 7,12-dimethylbenz[a]anthracene hydroxylase (DMBA-OH), and progesterone 6beta-hydroxylase (PROG-OH) activities were used as functional markers for trout hepatic CYP2K1, CYP1A1, and CYP3A27, respectively. The chemicals that were examined for their inhibitory effects were reversible, quasi-irreversible, or irreversible inhibitors of mammalian P450. At 100 microM concentration, the reversible inhibitors (ketoconazole, miconazole, and clotrimazole) were most potent in inhibiting LA-OH activity. These imidazole compounds, as well as ellipticine, parathion, and alpha-naphthoflavone, were the strongest inhibitors of DMBA-OH and PROG-OH activities. In addition, isosafrole, piperonyl butoxide, gestodene, 17alpha-ethynylestradiol, 1-aminobenzotriazole, and 5,8,11,14-eicosatetraynoic acid strongly inhibited PROG-OH activity. The global inhibitors, metyrapone, chloramphenicol, and allylisopropylacetamide, had very little or no inhibitory effect on trout LA-OH and DMBA-OH activities. Triacetyloleandomycin, a CYP3A inhibitor, did not affect PROG-OH activity catalyzed by trout CYP3A27. Diethyldithiocarbamate was an activator of LA-OH activity. None of the above enzyme activities was selectively inhibited by any of the chemicals when used at a concentration of 100 microM. There was no difference in the inhibition of LA-OH activities by representative P450 inhibitors between liver microsomes from untreated trout and BNF-treated trout. The results of this study suggest that inhibition data from mammalian studies could not be directly extrapolated to trout and likely other fish species and that care must be observed when mammalian P450 inhibitors are used to determine the participation of P450s in the metabolism and toxicity of xenobiotics in nonmammalian species.

Analysis of denatonium benzoate in Oregon consumer products by HPLC.

Denatonium benzoate (DB) is being added to a variety of consumer products as an aversive agent or denaturant. In 1995, Oregon was the first state to mandate the addition of DB to antifreeze and windshield washer fluids regardless of whether the product was marketed in a bottle with a child-proof cap. We have modified published high pressure liquid chromatography (HPLC) methods to measure the concentration of DB and validated it for use in Oregon consumer products. Analysis of standards showed a linear curve in the range of 1.25 to 50 ppm. This makes it useful for most analytical applications as DB usually is added in the 10 to 30 ppm range according to DB's manufacturer. The peak analyzed was collected and verified as DB by mass spectrometry. The method was applied to a variety of commercially-available products with particular emphasis on antifreeze and windshield washer fluids which are required by Oregon law to contain an aversive agent. Products analyzed were purchased in either 1994 or 1996 and showed a wide variation in concentration of DB ranging from below the limit of detection in many of the windshield washer products to above 30 ppm in many of the antifreeze formulations. There was no significant change in levels of DB after storage of antifreeze or windshield washer fluids at room temperature for six months.

Induction of lauric acid hydroxylase activity in catfish and bluegill by peroxisome proliferating agents.

In mammals, sensitivity to peroxisome proliferation by peroxisome proliferating agents (PPAs) appears to be correlated with inducibility of lauric acid hydroxylase activity. Bluegill and catfish have been shown to respond to PPAs by induction of lauric acid hydroxylase immunoreactive proteins (Haasch, 1996). In this investigation, induction of lauric acid hydroxylase activity was confirmed by HPLC and mass spectral analysis of specific hydroxylation products and possible species-specific differences in metabolism were investigated. Male bluegill, channel catfish and rat, were administered the model PPAs, clofibrate (200 mg kg-1, i.p.), ciprofibrate (100 mg kg-1, i.p.), or olive oil as vehicle control (both sexes of catfish), 48 h prior to hepatic, trunk kidney (catfish only) or kidney (rat) microsome preparation. In general, total metabolism of lauric acid was similar in all species, but female catfish metabolize lauric acid to a greater extent than males. Ciprofibrate treatment produced significant induction of omega- and omega-6 hydroxylation in male catfish kidney. In male bluegill liver, omega-, omega-4 and omega-5 hydroxylations were significantly induced by clofibrate treatment. The data indicate that induction of lauric acid hydroxylase cytochrome(s) P450 occurs in PPA-exposed fish which may be a consideration for environmentally-exposed responsive species.

The regiospecific hydroxylation of lauric acid by rainbow trout (Oncorhynchus mykiss) cytochrome P450s.

We have reexamined the hydroxylation of [1-14C]-lauric acid by trout liver microsomes and reconstituted trout P450s using a new HPLC system that gave an improved separation of hydroxylauric acids. Under these conditions, hepatic microsomes from yearling juvenile trout were shown to form omega-, (omega-1)-, (omega-2)-, (omega-3)-, (omega-4)-, (omega-5)-, and (omega-6)-OH lauric acid oxidation products (12-OH, 11-OH, 10-OH, 9-OH, 8-OH, 7-OH, and 6-OH lauric acid, respectively) as verified by GC/MS analysis. Microsomes from male and female juvenile trout liver formed (omega-1)-OH lauric acid as the major metabolite (23-29% of total radioactivity) and no major differences were observed between males and females. By contrast, liver microsomes from 3-year-old sexually mature trout had substantially lower lauric acid hydroxylase activity than juvenile microsomes and produced small quantities of only the (omega-1)-, (omega-2)-, and (omega-6)-hydroxylation products. Moreover, microsomes from sexually mature female trout had markedly lower lauric acid hydroxylase activity than those from the sexually mature male trout. Rat liver microsomes were quite catalytically active but formed mostly the omega- and omega-1 lauric acid oxidation products. Lauric acid metabolism also was analyzed in reconstituted systems containing purified juvenile trout LMC1 (CYP2M1) and LMC2 (CYP2K1) and with hepatic microsomes from juvenile trout in the presence of rabbit polyclonal antibodies raised against the two purified trout P450s. CYP2M1 catalyzed the (omega-6)-hydroxylation of lauric acid while the trout CYP2K1 form produces mainly (omega-1)-OH lauric acid together with a smaller quantity of the (omega-2)-hydroxylation product. All of the trout and rat radiometric lauric acid metabolism results were confirmed by direct mass spectrometric analysis of derivatized lauric acid metabolism mixtures. Use of direct mass spectrometric analysis for the hydroxylated lauric acids offers considerable advantages since the method did not require use of a radioactive fatty acid, completely separated all of the lauric acid hydroxylation products, confirmed identification of each metabolite, and was more sensitive than the radiometric analysis method.

Vessel wall and flow characteristics after carotid endarterectomy: eversion endarterectomy compared with Dacron patch plasty.

OBJECTIVES: Experimental studies have demonstrated that decreases in vessel wall compliance and increases in turbulence may contribute to (re)stenosis. We studied vessel wall and flow characteristics after endarterectomy with Dacron patch plasty and after eversion endarterectomy, and compared those findings with the characteristics of non-stenotic, unoperated carotid arteries (controls). METHODS: Seventy-four patients who underwent 84 carotid endarterectomies were studied postoperatively by ultrasonography (2-24 months) Recorded variables included the diameter of the bulb, strain, elastic modulus (stiffness), and presence of turbulent flow. RESULTS: The vessel wall and flow characteristics of the two groups differed significantly. The diameter was higher and the strain lower in Dacron patch plasty than in controls; eversion endarterectomy did not differ from controls. The elastic modulus was higher (stiffer) in Dacron patch plasty than in eversion endarterectomy; neither Dacron patch plasty nor eversion endarterectomy differed significantly from controls. The stiffness index was not significantly different between the groups. Turbulence was present in Dacron patch plasty and eversion endarterectomy when compared with controls. CONCLUSION: In diameter, strain and stiffness, the operated carotid artery resembles the non-stenotic, unoperated artery more closely after eversion endarterectomy than after Dacron patch plasty.

Using systematic reviews in clinical education.

Traditional educational methods change clinical practice only with considerable effort and difficulty. In particular, the teaching of critical appraisal in the setting of journal clubs does not increase the amount of medical research read by trainees. Experiential learning theory, corroborated by the success of problem-based learning, encourages us to link learning to the numerous medical questions that physicians generate while providing patient care. Systematic reviews can link these questions with the results of research that would otherwise be difficult to locate, read, and appraise. Systematic reviews are a uniquely powerful mechanism for teaching, and they offer teachers a new opportunity to model rational and effective use of information. Systematic reviews should be made available at clinical sites for use during "teachable moments." Resistance to the use of systematic reviews can be reduced by using existing journal clubs to teach about the strengths and limitations of these reviews. The point that systematic reviews are meant to assist, not replace, clinical decision making deserves emphasis in such teaching.

Links between race/ethnicity and cultural values as mediated by racial/ethnic identity and moderated by gender.

Two studies examined whether individualism (orientation toward one's own welfare), collectivism (orientation toward the welfare of one's larger community), and familism (orientation toward the welfare of one's immediate and extended family) are distinct cultural values predicted by race/ ethnicity. The 3 constructs proved to be separate dimensions, although collectivism and familism were positively correlated. In Study 1, persons of color scored higher on collectivism and familism than did Anglos. No differences emerged for individualism. Also, persons of color scored higher than Anglos on racial/ethnic identity, which in turn was a positive predictor of all 3 cultural values. In Study 2, we replicated the group differences on collectivism and familism for men but not for women.

Syncope: current diagnosis and treatment.

The patient with syncope often poses a formidable diagnostic challenge. A large number of underlying causes must be considered, ranging in severity from benign to life-threatening. A careful, systematic clinical evaluation beginning with a history, physical examination, and ECG will establish the diagnosis in most patients, and the judicious use of specialized testing will confirm or uncover the cause in many of the remaining cases. Further basic and clinical research into the pathogenesis and treatment of neurocardiogenic syncope, the role of HUT testing in neurally mediated syncope, and the optimal use of EPS in patients with cardiac disease will markedly improve our management of these patients in the future.

Beta-naphthoflavone induced CYP1A1 and 1A3 proteins in the liver of rainbow trout (Oncorhynchus mykiss).

1. Two CYP1A proteins, designated HAP 1 and HAP 2, were isolated from the liver of the beta-naphthoflavone (BNF)-treated rainbow trout. The proteins were initially resolved by chromatography on a DEAE sepharose column and were further purified by hydroxyl-apatite chromatography. 2. Both HAP 1 and HAP 2 proteins exhibited high 7-ethoxyresorufin, methoxy-resorufin and phenacetin O-dealkylase activities and were good catalysts for the oxidation of 7,12-dimethylbenz[a]anthracene (DMBA). No qualitative difference was observed between the two proteins in their ability to catalyse the formation of the individual metabolites of DMBA. 3. The two purified proteins showed identical amino acid sequence for the first 13 amino acids. However, the 14th amino acid was valine for HAP 1 protein and alanine for HAP 2 protein. 4. Alignment of the amino acid sequences showed that HAP 1 protein was identical to the deduced protein of the previously reported trout CYP1A2 (renamed CYP1A1) gene for the first 24 amino acids at the N-terminal region. HAP 2 protein corresponded to the deduced protein sequence of CYP1A3 gene for the first 14 amino acids. However, unlike the deduced sequences of CYP1A1 and 1A3 the N-terminal methionine was absent in the purified proteins. 5. We conclude that HAP 1 and HAP 2 are the products of the CYP1A1 and CYP1A3 genes respectively, and are found in the liver of the BNF-treated rainbow trout.

In vitro metabolism of 7,12-dimethylbenz[a]anthracene by rainbow trout liver microsomes and trout P450 isoforms.

Liver microsomes from juvenile trout metabolized DMBA to unknown highly polar metabolites (X) and to DMBA-t-5,6-diol, DMBA-t-8,9-diol, 7-OHM-12-MBA, 7M-12-OHMBA, 2-OH-DMBA, 4-OH-DMBA, and trace amounts of DMBA-t-3,4-diol. Treatment of trout with beta-naphthoflavone (BNF) and isosafrole (ISF) increased the formation of these products except for the hydroxymethyl derivatives of DMBA. The production of DMBA-t-3,4-diol, 2-OH-DMBA, and 4-OH-DMBA was much greater in BNF-induced liver microsomes than that in ISF-induced liver microsomes. In contrast, the yield of DMBA-t-8,9-diol and 7-OHM-12-MBA was greater in ISF-induced microsomes than that in BNF-induced microsomes. Trout CYP1A1 (P450 LM4b) purified from BNF-treated trout catalyzed the formation of the same metabolites generated by BNF-induced microsomes in the presence of added human microsomal EH. The constitutive forms of P450 isolated from untreated trout such as P450s LMC3, LMC4, and LMC5, CYP2M1 (P450 LMC1), and CYP2K1 (P450 LMC2) did not produce any of the DMBA metabolites (except for DMBA-t-8,9-diol by CYP2K1) generated by the trout microsomes. Generation of DMBA-DNA and DMBA-protein adducts in vitro was enhanced by treatment of trout with BNF and by ISF to a lesser extent. Formation of adducts and DMBA diols by BNF-induced liver microsomes and by trout CYP1A1 was completely blocked by the CYP1A inhibitor ellipticine (100 microM). These results suggest that the BNF-inducible trout P450 (CYP1A), not the constitutive P450s, is the major catalyst for the biotransformation of DMBA to metabolites that bind to macromolecules.

General internists influence students to choose primary care careers: the power of role modeling.

PURPOSE: To determine whether medical students supervised by general internist attendings during the third-year medicine clerkship are more likely to choose primary care careers than students supervised by subspecialist attendings. METHODS: One hundred forty-four consecutive medical students rotating on the general medicine inpatient service during the 1993-1994 academic year were surveyed about their career choice and professional expectations, both at the beginning and end of the clerkship; an additional 50 students completed a post-clerkship survey only. The cohort of students was surveyed at graduation to determine stability of their career preferences. RESULTS: Both pre- and post-clerkship surveys were completed by 138 of 144 students (96%); post-clerkship surveys were completed by 181/194 (93%); and graduation surveys were completed by 137/188 (73%). Fifty-eight students (32%) designated primary care (general internal medicine, general pediatrics, or family practice) as their career choice post-clerkship; of these, 45 students (78%) also indicated a primary care career choice at graduation. Characteristics associated with choosing primary care post-clerkship were: low income expectation, desire to interact closely with patients, desire to contribute to society, low class rank, female gender, and high educational debt. Having a physician parent was negatively associated with choosing primary care. After controlling for important demographic, academic and attitudinal characteristics, increasing exposure to a general internist attending was associated with choosing primary care (OR = 5.1, comparing highest to lowest amount). Among students choosing primary care, exposure to a general internist attending was associated with choosing general internal medicine in a dose-dependent fashion (OR = 4.2, comparing highest to lowest amount). CONCLUSIONS: Although career choice is clearly related to personal characteristics such as socioeconomic background and humanistic qualities, a high degree of exposure to general internists during the medicine clerkship is associated with choosing primary care. Exposure of students interested in primary care to general internist attendings may also influence them to consider general internal medicine over family practice and pediatrics.

Occupational stress and organizational commitment in nurse administrators.

OBJECTIVE: The authors explore levels of occupational stress (burnout) and organizational commitment (intent to stay), their inter-relationships, and their relationships to personal and organizational factors in nurse administrators. BACKGROUND: Although the concepts of burnout and turnover have been studied and reported for staff nurses, relatively few such studies exist in relation to nurse administrators. METHODS: Consequently, the Maslach Burnout Inventory, the Organizational Commitment Questionnaire, and a personal data sheet were completed by respondents to a mailed survey representing 65.6% of the membership of the state's nurse executive organization and 58.2% of the state's hospitals (N = 78). RESULTS: Scores indicate that half the respondents experience low levels of burnout whereas a third have high levels of burnout. Commitment scores were high for most nurse executives and were correlated inversely with burnout scale scores (depersonalization, personal accomplishment, emotional exhaustion), with the amount or phase of burnout, and with non-nursing management experience. Those with few opportunities to meet with colleagues scored higher on emotional exhaustion and lower on personal accomplishment scales. Intent to stay (high commitment scores) was related positively to perceived organizational support and to religiosity. CONCLUSIONS: Findings are consistent with those reported in other studies; however, the administrative role may require unique approaches to avoid or correct organizational stress. The role of social support, the determination of organizational/individual fit, and the adaptation of traditional organizational development techniques to the administrative role are discussed and proposed as areas for further study.

Nurse executives: leadership motivation and leadership effectiveness.

In a mailed survey, chief nurse officers (N = 92) described their leadership motivation and leadership effectiveness. Leadership motivation scores depicted high needs for affiliation and moderate needs for power. Leadership effectiveness scores reported by chief nurse officer and chief executive officer (n = 59 pairs) were correlated positively. Significant predictors of leadership effectiveness were job satisfaction, education, professional recognition, and experience, respectively. Those motivated by socialized power needs were in the most complex hospitals, whereas those motivated by affiliation were in the least complex settings. Identification of the motivational needs of successful leaders and aspiring leaders is advocated to provide valid and reliable measures for use in assessment centers and to inform curricula.