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C Alexander

Publications and source records attributed to C Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1997

Bimodal regulation of ceramidase by interleukin-1beta. Implications for the regulation of cytochrome p450 2C11.

Interleukin 1beta (IL-1beta) induces the hydrolysis of sphingomyelin (SM) to ceramide (Cer) in primary cultures of rat hepatocytes, and Cer has been proposed to play a role in the down-regulation of cytochrome P450 2C11 (CYP2C11) and induction of alpha1-acid glycoprotein (AGP) by this cytokine (Chen, J., Nikolova-Karakashian, M., Merrill, A. H. & Morgan, E. T. (1995) J. Biol. Chem. 270, 25233-25238). Nonetheless, some of the features of the down-regulation of CYP2C11 do not fit a simple model of Cer as a second messenger as follows: N-acetylsphinganine (C2-DHCer) is as potent as N-acetylsphingosine (C2-Cer) in suppression of CYP2C11; the IL-1beta concentration dependence for SM turnover is different from that for the increase in Cer; and the increase in Cer mass is not equivalent to the amount of SM hydrolyzed nor the time course of SM hydrolysis. In this article, we report that these discrepancies are due to activation of ceramidase by the low concentrations of IL-1beta ( approximately 2.5 ng/ml) that maximally down-regulate CYP2C11 expression, whereas higher IL-1beta concentrations (that induce AGP) do not activate ceramidase and allow Cer accumulation. This bimodal concentration dependence is demonstrated both by in vitro ceramidase assays and in intact hepatocytes using a fluorescence Cer analog, 6-((N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-Cer (NBD-Cer), and following release of the NBD-fatty acid. IL-1beta increases both acid and neutral ceramidase activities, which appear to be regulated by tyrosine phosphorylation because pretreatment of hepatocytes with sodium vanadate increases (and 25 microM genistein reduces) the basal and IL-1beta-stimulated ceramidase activities. Since these findings suggested that sphingosine (and, possibly, subsequent metabolites) is the primary mediator of the down-regulation of CYP2C11 by IL-1beta, the effects of exogenous sphingosine and C2-Cer on expression of this gene were compared. Sphingosine was more potent than C2-Cer in down-regulation of CYP2C11 when added alone or with fumonisin B1 to block acylation of the exogenous sphingosine. Furthermore, the suppression of CYP2C11 by C2-Cer (and C2-DHCer) is probably mediated by free sphingoid bases, rather than the short chain Cer directly, because both are hydrolyzed by hepatocytes and increase cellular levels of sphingosine and sphinganine. From these observations we conclude that sphingosine, possibly via sphingosine 1-phosphate, is a mediator of the regulation of CYP2C11 by IL-1beta in rat hepatocytes and that ceramidase activation provides a "switch" that determines which sphingolipids are elevated by this cytokine to produce multiple intracellular responses.

Amidohydrolases↗
PubMed1997

Reflections for action.

This is the second of three articles based on a major report launched by the Foundation of Nursing Studies last year-Reflection for Action-which looked at the dissemination and implementation of research in nursing. This article discusses two of the studies that made up the report.

Clinical Competence↗
PubMed1997

Prescriptive care? Guidelines and protocols.

The first of two articles on the development and implementation of guidelines and protocols describes a series of workshops on research utilisation. The authors also attempt to explain some of the confusing terminology in the area of prescriptive care. The second article, which will appear in the near future, will attempt to answer the questions arising from the workshops described here.

Clinical Nursing Research↗
PubMed1997

Promoting community-based maternal and child health services: a university-health department partnership.

OBJECTIVES: Funded by the Federal Maternal and Child Health Bureau, a partnership between the Johns Hopkins University School of Public Health, Department of Maternal and Child Health (JHU), and the Baltimore City Health Department (BCHD) identifies maternal and child health problems, and develops appropriate interventions. This paper presents the organization and activities of the JHU/BCHD Maternal and Child Community Health Science Consortium as a result of overcoming traditional barriers to collaborative efforts, and discusses what role the Consortium has had in its own collaborative success. METHOD: A review of the literature uncovered a number of barriers to productive interaction. A number of factors contributing to overcoming the barriers was also revealed. The organization and activities of the work of the JHU/BCHD Maternal and Child Community Health Science Consortium has been applied to these barriers and associated factors, and discussed in context of implications for future collaborative efforts. RESULTS: The Consortium has developed a fully integrated administrative structure bridging both the BCHD and JHU. The mission of the Consortium has been translated into four categories of work, each one designed to complement, extend, and augment the other. The infrastructure established in Baltimore, as a direct result of this partnership, has served to overcome traditional barriers to productive academic/agency collaboration, while promoting organizational productivity. This outcome is a result of overcoming the recognized barriers to collaboration. CONCLUSIONS: Health agencies and university public health programs must link resources and collaborate to address public health issues. Commitment to a collaborative approach to the public's health will determine its future.

Child↗
PubMed1997

Hospice and palliative care education in medical school: a module on the role of the physician in end-of-life care.

BACKGROUND: As a part of a program to integrate comprehensive palliative care education at the University of Maryland School of Medicine, a new teaching module was incorporated into the Introduction to Clinical Practice course for freshman medical students. METHODS: The module is entitled "The Role and Responsibility of the Physician in Palliative and End-of-life Care: the Inter-disciplinary Team Approach." The teaching objectives are: 1) describe the value of palliative and end-of-life care as a professional practice; 2) delineate the barriers to physician competence in end-of-life care; 3) describe the concept of hospice and the multidisciplinary approach to the care of the terminally ill; 4) List the fundamental areas of knowledge and skills required for a physician to be an effective member of the palliative care team. The format of the module is a 30-minute didactic/interactive overview of the teaching objectives, followed by a 30-minute videotape "Care Beyond Cure," produced by the National Hospice Organization. The class then breaks up into small groups to discuss, over a two-hour period, a hypothetical illustrative case. RESULTS AND CONCLUSIONS: The module was applied to the freshman medical student class in the 1995-1996 academic year. All freshmen were required to take it. Outcome evaluation utilized tools to assess attitude and cognitive domains. The attitude survey revealed that the majority of the students agreed that care of the dying could be a rewarding experience for the physician (72%) and that the case had helped them to understand the physician's role (93%). Overall, 82% wanted to learn more about the subject. Cognitive assessment tools indicated that the students satisfactorily understood the fundamental definitions of palliative care and hospice.

Attitude to Death↗
PubMed1997

The shortage of rural general practitioners in north-western New South Wales.

The objective of this study was to provide the Tamworth Rural Training Unit with a clear understanding and practical strategic directions for contributing to an equitable distribution of rural general practitioners in the New England Area Health Service. A survey was sent to all 139 general practitioners practising in this region. The best and worst features of rural practice, both professionally and personally, were surveyed, as well as ways to attract more general practitioners to rural areas. It was found that this region required an additional 46 full-time general practitioners in 1995 if equity and social justice principles were to be met. Projecting to the year 2005, the total shortfall of full-time general practitioners in the New England Area Health Service amounts to 90. It is recommended that this critical shortage of rural general practitioners be assessed within two distinct time frames, namely short-term strategies (1996-1998) and medium-term strategies (1999-2005).

Adult↗
PubMed1997

Considering a decision-making approach to youth violence prevention programs.

The unfortunate exception to a general downturn in violent crime involves an upsurge in violence among youth. Violence often results when minor confrontations escalate. As school violence increasingly has become widespread, schools have become the location of many violence prevention efforts, few of which have been evaluated adequately. This paper focuses on enhancing decision-making skills as one approach to increase adolescents' ability to manage interpersonal violence. Adolescents can be considered fairly skilled decision-makers and their unique perspective must be considered in development of effective intervention programs. Data from a pilot study were examined for insights about adolescents' ability to make decisions in situations of interpersonal conflict.

Adolescent↗
PubMed1997

Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers.

In a double-blind and randomized manner, 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate (Cr) or a maltodextrin placebo (P) for 9 days during training. Prior to and following supplementation, subjects performed three 100-m freestyle sprint swims (long course) with 60 s rest/recovery between heats. In addition, subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests. Significant differences were observed among swim times, with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint. There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group. Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance.

Adolescent↗
PubMed1997

Stress, stress reduction, and hypertension in African Americans: an updated review.

This is a comprehensive and integrative review of multiple factors underlying the greater prevalence of hypertension in African Americans compared with whites. Evidence linking stress with hypertension and cardiovascular disease in African Americans is reviewed. A survey of mechanisms of hypertension in African Americans and existing behavioral strategies for the treatment of hypertension is presented. Given that the excess of hypertension may be mediated in part by behavioral factors operating through biological mechanisms, a case is presented for behavioral stress reduction measures. This review of stress reduction techniques especially the Transcendental Mediation program for the treatment of hypertension in African Americans highlights current issues facing the field. New information is provided to help direct future nonpharmacological research and practice in hypertension to prevent morbidity and premature mortality in this underserved population.

Black or African American↗
PubMed1997

[18Fluoro-FDG SPECT for the demonstration of hibernating myocardium: an interim account].

AIM: The present investigation demonstrates an intraindividual comparison of FDG-PET and FDG-SPECT. MATERIAL AND METHODS: Thirty patients with CHD and planed revascularisation underwent both modalities. Myocardial perfusion was evaluated by 99mTc-MIBI SPECT. The myocardium was divided into 25 segments and the results were compared by two experienced observers. RESULTS: Segmental concordance of FDG-PET and -SPECT was 94.1%. PET indicated a higher percentage of hibernating myocardium (8.9% vs. 5.7%) and a lower rate of matched defects (11.5% vs. 16.0%). In 22 cases the need for revascularisation was assessed identically. In the remaining 8 patients FDG-PET and FDG-SPECT required an intervention in 6 and 2 cases, respectively. CONCLUSION: The results of FDG-PET and FDG-SPECT showed a high segmental concordance, but the individual assessment of hibernation worthwhile for revascularisation demonstrated important differences in patient management.

Aged↗
PubMed1996

Reflection for action: the challenge for nurses.

In June, The Foundation of Nursing Studies (FoNS) launched its first position paper, Reflection for Action. This report highlights the key aims of the paper which were to explore national and local research implementation cultures, and to identify barriers, expectations, achievements and opportunities for the future.

Foundations↗
PubMed1996

Fumonisin toxicity and sphingolipid biosynthesis.

Fumonisins are inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase) in vitro, and exhibit competitive-type inhibition with respect to both substrates of this enzyme (sphinganine and fatty acyl-CoA). Removal of the tricarballylic acids from fumonisin B1 reduces the potency by at least 10 fold; and fumonisin A1 (which is acetylated on the amino group) is essentially inactive. Studies with diverse types of cells (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have established that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids; but also, causes sphinganine to accumulate. Some of the sphinganine is metabolized to the 1-phosphate and degraded to hexadecanal and ethanolamine phosphate, which is incorporated into phosphatidylethanolamine. Sphinganine is also released from cells and, because it appears in blood and urine, can be used as a biomarker for exposure. The accumulation of these bioactive compounds, as well as the depletion of complex sphingolipids, may account for the toxicity, and perhaps the carcinogenicity, of fumonisins.

Amidohydrolases↗
PubMed1996

Retrospective analysis of 305 consecutive cases of endometrial ablation and partial endomyometrial resection.

STUDY OBJECTIVE: To assess the efficacy and safety of operative resectoscopy, partial endomyometrial resection, and endometrial ablation in the evaluation and treatment of abnormal uterine bleeding. DESIGN: Retrospective analysis of 305 consecutive cases of endometrial ablation and partial endomyometrial resection. SETTING: Midwestern urban obstetric and gynecology group practice and teaching hospitals. PATIENTS: Three hundred five women (age 30-72 yrs) with abnormal uterine bleeding. Interventions. Partial endomyometrial resection and endometrial ablation. MEASUREMENTS AND MAIN RESULTS: Of the 301 patients who completed surgery and follow-up, 283 (97%) reported improvements in amenorrhea (55%), hypomenorrhea (41%), and eumenorrhea (1%). Ten (3%) failed to report improvement. In 24 (7.9%) women, hysterectomy was performed for various reasons after endometrial ablation, including recurrent bleeding in 4. Four uterine perforations occurred, infection was suspected in one patient, and loss of Laminaria occurred in another; all patients, however, were observed appropriately and discharged the same day of surgery. CONCLUSIONS: Partial endomyometrial resection and endometrial ablation is a safe and effective treatment of abnormal uterine bleeding, and may be an alternative to hysterectomy in selected patients.

Adult↗
PubMed1996

Behavior and injury in urban and rural adolescents.

OBJECTIVES: This study investigates the consistency of factors associated with adolescent injury in separate urban and rural samples. SAMPLES: Adolescents, 11-17 years old, in public schools in urban and rural Maryland (n = 2,712). METHODS: Separate bivariate and logistic regression analyses were conducted for each sample to determine individual and environmental factors associated with major and minor injuries experienced in the previous year. RESULTS: Multivariate analyses revealed that, for both samples, the probability of a major injury was highest for boys and, among both boys and girls, for those who played several team sports. Among rural youth, other significant covariates of both major and minor injuries were a tendency to engage in risky behavior and to use alcohol. For urban youth, being white, carrying a weapon for protection, attending an unsafe school, and working for pay were also significant covariates. Interactions were important and complex. CONCLUSIONS: The consistency of predictive factors, such as multiple sports team participation and risky and aggressive behaviors in completely different physical environments, underscores the need to address the contexts of heightened injury risk that some adolescents create wherever they live by playing sports and/or behaving in an antisocial, aggressive manner. Moreover, the perception of lack of safety in schools and neighborhoods is associated with increased injury rates, suggesting the need for policy interventions to target social environments as well as behavior.

Adolescent↗