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Biomedical subjects

M C Henderson

Publications and source records attributed to M C Henderson.

At least 19 recordsLinked to original sources
PubMed1998

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.

Animals↗
PubMed1998

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.

Chromatography, High Pressure Liquid↗
PubMed1998

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.

Animals↗
PubMed1997

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.

Education, Medical↗
PubMed1997

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.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

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.

Arrhythmias, Cardiac↗
PubMed1997

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.

Aged↗
PubMed1997

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.

California↗
PubMed1997

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.

Amino Acid Sequence↗
PubMed1997

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.

Animals↗
PubMed1996

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.

Adult↗
PubMed1996

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.

Adult↗
PubMed1995

Inhibition of in vitro aflatoxin B1-DNA binding in rainbow trout by CYP1A inhibitors: alpha-naphthoflavone, beta-naphthoflavone and trout CYP1A1 peptide antibody.

Rainbow trout cytochrome P450 (CYP)1A detoxifies aflatoxin B1 (AFB1) to aflatoxin M1 (AFM1), whereas CYP2K1 activates AFB1 to AFB1-8,9-epoxide. We report that alpha-naphthoflavone (ANF) and beta-naphthoflavone (BNF) both strongly inhibit CYP1A-mediated ethoxyresorufin O-deethylase (EROD) activity (Ki = 9.1 +/- 0.8 and 7.6 +/- 1.1 nM, respectively). These inhibitors (selective for mammalian CYP1A at low concentrations), as well as rabbit polyclonal antibody to a trout CYP1A1 peptide (residues 277-294), also strongly inhibited trout microsome-catalyzed AFB1-DNA binding and lauric acid (omega-1) hydroxylation in vitro, reactions previously established to be CYP2K1-dependent. ANF at 0.5, 5, 50 and 500 microM inhibited liver microsome-catalyzed AFB1-DNA binding by 22, 58, 84 and 91%, respectively, whereas BNF at the same concentrations inhibited 22, 74, 78 and 81%, respectively. The CYP1A1 peptide and CYP2K1 polyclonal antibodies (10 mg IgG/mg microsomal protein) inhibited AFB1-DNA binding by 84 and 66%, respectively, compared with pre-immune IgG. Lauric acid (omega-1) hydroxylation was inhibited 61% by 5 microM ANF, 69% by 5 microM BNF and 100% by either antibody at 12 mg IgG/mg microsomal protein. These results demonstrate that mammalian CYP1A inhibitors also inhibit trout microsomal AFB1-DNA binding and lauric acid (omega-1) hydroxylation, catalyzed primarily by CYP2K1. In the absence of evidence that trout CYP1A can catalyze AFB1-DNA binding, the results suggest configuration similarities at, or near, the active sites for these two fish enzymes that result in antibody crossreaction and loss of the inhibitor specificity observed with mammalian CYP1A.

Aflatoxin B1↗
PubMed1995

Abnormal uterine bleeding.

Concerns about abnormal menstrual bleeding are a common reason for women to consult a primary care physician. The first step in the evaluation is to determine the patient's ovulatory status. Women with heavy bleeding but normal ovulatory cycles should be evaluated for coagulopathies, structural lesions, and hypothyroidism. In the absence of a systemic or structural cause, menorrhagia can be treated with OCPs or NSAIDs. Intermenstrual bleeding in OCP users may be due to noncompliance or the use of low-dose pills. Encouraging patient compliance and adjustment of the estrogen dose can often solve the problem. If the patient is not on OCPs, intermenstrual bleeding is usually due to a structural or inflammatory lesion. The differential diagnosis for anovulatory bleeding is extensive. Pregnancy, systemic illnesses, and structural lesions should be ruled out by history, physical examination, and laboratory evaluation. Endometrial biopsy is indicated in patients over age 35 and younger patients with risk factors for endometrial cancer, such as chronic anovulation and obesity. Dysfunctional uterine bleeding is a nonspecific term for abnormal uterine bleeding in the absence of systemic or structural disease. It is usually associated with anovulation. Adolescents frequently have dysfunctional uterine bleeding owing to immaturity of the hypothalamic-pituitary-ovarian axis. Perimenopausal women have an increased incidence of irregular bleeding secondary to decreased estrogen production by the ovary. Obesity, polycystic ovary syndrome, stress, crash diets, and vigorous exercise can all disrupt normal ovulatory function. Treatment options for dysfunctional uterine bleeding include oral contraceptives, cyclic progesterone, or hormone replacement with estrogen and progesterone. Patients with structural lesions or those who do not resume normal withdrawal bleeding patterns on hormone therapy should be referred to a gynecologist for further evaluation and treatment.

Adolescent↗
PubMed1995

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.

Educational Status↗
PubMed1994

Personality characteristics of young adult offspring of substance abusers: a study highlighting methodological issues.

Our study sought to demonstrate the importance of attending to methodological issues in the study of personality characteristics of offspring of substance abusers (OSAs). A 4 x 2 factorial design, Parental Mental Health (no known psychological problems, substance abuse, other psychological problems, or dual diagnosis) x Exposure to Abuse/Neglect (present or absent), was used to examine depression proneness, neuroticism, alexithymia, self-esteem, self-concept, and locus of control in young adults. Results of this study demonstrated that in order to determine whether characteristics of OSAs are uniquely related to parental substance abuse, a psychiatric control group is needed. Also, the importance of separating the influences of other family environment variables (e.g., exposure to abuse/neglect) was demonstrated. None of the differences between groups in this study could be attributed to parental substance abuse per se; rather, the concomitants of substance abuse (i.e., exposure to abuse/neglect) were found to be more strongly related to poorer adjustment in OSAs. Finally, it was shown that the proportion of treatment-seeking subjects included in the sample affected the level of pathology observed. These results are discussed in relation to previous findings, and recommendations regarding methodology are made for future studies.

Adult↗