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PubMed2005

Sustained Akt/PKB activation and transient attenuation of c-jun N-terminal kinase in the inhibition of apoptosis by IGF-1 in vascular smooth muscle cells.

Characteristics of hVSMC apoptosis and its inhibition by insulin-like growth factor-1 (IGF-1) remain unclear. Also unclear is whether a balance in hVSMCs exists whereby c-Jun N-terminal stress kinases (JNK) promote apoptosis while extracellular signal-regulated (ERK1/2) MAP kinases inhibit cell death. In this study, we examined the involvement of Akt/PKB and its upstream kinase, PDK1 and whether JNK activation correlated with human and rat VSMC apoptosis induced by staurosporine and by c-myc, respectively. We observed a strong, sustained JNK activation (and c-Jun phosphorylation), which correlated with VSMC apoptosis. IGF-1 (13.3 nM), during apoptosis inhibition, transiently inhibited JNK activity at 1 h in a phosphatidylinositol 3-kinase (PI3-K)- and MEK-ERK-dependent manner, as wortmannin (100 nM) or PD98059 (30 muM) partially attenuated the IGF-1 effect. PKC down-regulation had no effect on JNK inhibition by IGF-1. While IGF-1 alone produced a strong phosphorylation of Akt/PKB in hVSMCs up to 6 h, it was notably stronger and more sustained during ratmyc and hVSMCs apoptosis inhibition. Further, whereas transient expression of phosphorylated Akt protected VSMCs from apoptosis by nearly 50%, expression of dominant interfering alleles of Akt or PDK1 strongly inhibited IGF-1-mediated VSMC survival. These results demonstrate for the first time that transient inhibition of a pro-apoptotic stimulus in VSMCs may be sufficient to inhibit a programmed cell death and that sustained anti-apoptotic signals (Akt) elicited by IGF-1 are augmented during a death stimulus. Furthermore, PI3-K and ERK-MAPK pathways may cooperate to protect VSMCs from cell death.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMedDate not supplied

A five-stage model for sustaining a community campaign.

The Sisters Together, Move More Eat Better pilot communication program focuses on young Black women in three inner-city communities to encourage improved nutrition and increased physical activity. The design for Sisters Together is based on an expansion of a public health campaign that combines social marketing with community building efforts. The pilot program design comprises five phases: design, promotion, demonstration, transfer, and sustained activity. The proposed five-stage model holds potential for increasing the life span of a campaign and contributing to community building. Partnerships and coalition development promise to maintain the campaign beyond the limited budget period. This descriptive article illustrates the elements of a hybrid model for the design of a communication program with examples from Sisters Together, Move More Eat Better, a pilot program currently in the last year of implementation.

Adolescent↗
PubMed2004

Current Assessment of Yellow Fever and Yellow Fever Vaccine.

Yellow fever (YF) is a mosquito-borne viral illness that causes hemorrhagic fever in tropical Africa and South America. Although a very safe and efficient vaccine (17D) is available, it is underused. An estimated 200,000 people are still infected annually, and YF remains a major public health concern. This article reviews the recent data on YF epidemiology, virology, and immunity, and analyzes the rare postvaccination adverse effects that have been recently reported. YF vaccine should be included in the expanded program of immunization for children and sustained for people living in or traveling to endemic areas. A surveillance of vaccinated people also should be reinforced. New research programs should be developed to identify molecular markers of YF virus tropism and attenuation, and to understand mechanisms of host responses to virus infection.

Journal Article↗
PubMed1999

Effects of an emergency department-based advocacy program for battered women on community resource utilization.

STUDY OBJECTIVE: The emergency department is often accessed by battered women. Although it is recommended that information about community resources be given to women, there is little information regarding how often women use these resources. The objective of this study was to determine whether an ED-based advocacy program resulted in increased community resource utilization by battered women. METHODS: The study used a before-after trial design at an urban county hospital ED. Before the program, a consecutive sample of 117 women was identified in the ED as having sustained injuries by domestic violence. After the program, a consecutive sample of 105 (57% of the 183 asked) who agreed to meet with an advocate in the ED was identified. Participants in both groups lived in Kansas City, Missouri, and were 18 years of age or older. The outcome measures were the proportion of women with shelter use, shelter-based counseling, police calls, full orders of protection, and repeat ED visits for domestic violence after the index ED visit. RESULTS: After the initiation of the program, shelter use increased from 11% to 28% (P =.003) and shelter-based counseling increased from 1% to 15% (P <.001). There was no change in repeat police calls (25% versus 35%, P =.14), full orders of protection (9% versus 6%, P =. 58), or repeat ED visits for domestic violence (11% versus 8%, P =. 63). CONCLUSION: ED-based advocacy for domestic violence resulted in increased use of shelters and shelter-based counseling.

Adolescent↗
PubMed1997

Promotion of breast cancer screening in communities: a research agenda.

This paper used the National Cancer Institute of Canada (NCIC) cancer control framework to review research on participation in breast cancer screening programs and identify areas for further study. Cancer Lit, MEDLINE, CINAHL, Sociofile, Health and the Public Affairs Information Service databases were searched for literature published from 1990 to 1995. Information was also obtained from provincial breast cancer screening programs and Health Canada. Interventions designed to promote participation in screening programs have not been effective. Involvement of the target community, however, increased success and sustainability. Barriers to initial participation within screening programs include alternative sources of screening and the lack of funds to screen all eligible women. Studies show that participation decreases with successive screening rounds. The priorities for study are development of: a theoretical framework for recruitment strategies, a method to capture all Canadian screening results including those performed through provincial health insurance plans and a mechanism to deliver screening to all eligible Canadian women.

Academies and Institutes↗
PubMed2003

Implementing a community-based oral health care program: lessons learned.

OBJECTIVES: The objective of this paper is to report key findings of a process evaluation that may be useful to other institutions seeking to implement a community-based oral health care program primarily targeting children in dentally underserved communities. By partnering with community-based organizations, public schools, and community health care providers, the Columbia University School of Oral and Dental Surgery (SDOS) established the Community DentCare Network (DentCare) in the Harlem and Washington Heights/Inwood neighborhoods of northern Manhattan. These low-income neighborhoods are characterized by poor oral health and have been designated by the federal government as health professions shortage areas. METHODS: The method used in the process evaluation was open-ended qualitative interviewing by a sociologist with extensive experience in this methodology aided by a participant-observer within the DentCare program. RESULTS: The heterogeneity of the two communities required different strategies and resources to gain trust and acceptance. Fundamental changes were required of SDOS over a 10-year period, beginning with prioritizing community service into a primary mission. Collaborating with medical clinics facilitated the implementation of the network when the partners shared the same philosophical goals. Faculty and staff with different skills were needed during the start-up and the sustained development phases of the program.

Black People↗
PubMed1989

Predictors of inducible sustained ventricular tachyarrhythmias in patients with coronary artery disease.

To determine predictors of inducible sustained ventricular tachycardia or fibrillation by programmed electrical stimulation in patients with coronary artery disease and ventricular tachyarrhythmias, 14 clinical and angiographic variables were analyzed in 60 consecutive patients. All patients had angiographically documented coronary artery disease and symptomatic ventricular arrhythmias (sustained ventricular tachycardia in 21, ventricular fibrillation in 21 and nonsustained ventricular tachycardia in 18). Baseline programmed electrical stimulation while the patient was not taking antiarrhythmic drugs was performed with use of single, double and triple extrastimuli and burst pacing from two right ventricular sites. The variables analyzed were presenting arrhythmia; presence, frequency and complexity of ventricular ectopic activity on baseline 24 h electrocardiographic (Holter) monitoring; greater than or equal to 70% narrowing in either the left anterior descending, proximal left anterior descending, right coronary or circumflex coronary artery (independently assessed); single, double or triple vessel coronary disease; anterior, apical or inferior wall motion abnormalities; segmental dyskinesia and ejection fraction. Thirty-seven patients (62%) had inducible sustained ventricular tachycardia (rate greater than 100 beats/min, duration greater than 30 s or requiring cardioversion) and two patients (3%) had ventricular fibrillation induced. Eleven patients (18%) had nonsustained ventricular tachycardia (duration greater than or equal to 3 beats, less than 30 s) induced and 10 patients (17%) had no inducible arrhythmia (duration less than 3 beats). Multivariate stepwise logistic regression analysis identified three independent variables predictive of inducible sustained ventricular arrhythmias: sustained ventricular tachycardia as the presenting arrhythmia (p = 0.004), proximal left anterior descending artery lesion (p = 0.002) and anterior wall motion abnormality (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2004

Reinventing mass communication: a World Health Organization tool for behavioral change to control disease.

Most of the WHO's vertical programs, because they were ill-conceived, ill-designed, and defectively implemented, have fallen far short of expectations. These limitations have been doggedly ignored by the WHO, although the authorities in India have now realized that such vertical programs are expensive and not sustainable. Launching of Communication for Behavioral Impact (COMBI) appears to mark a desperate effort to revive their performance. It represents yet another deviation from the mandate given to the WHO. In 1983, the then director general warned against motivational manipulation of people to sell health ideas, but the WHO has now brazenly come forward to look for help from the private sector. COMBI uses the jargon and language of the market place to "market" health programs; it calls this "cause-related marketing." The WHO has been most a historical in conceptualizing COMBI, as it has not learned from the failure of UNICEF's earlier venture to market child survival by employing experts in social marketing to bring about "community mobilization." The WHO should have reviewed the large body of literature on work in the health social sciences, health education, and the many programs based on the concept of "information, education, and communication." The pointed neglect of such key issues raises serious moral, ethical, and human rights questions. The COMBI approach amounts to be a breach of trust--a threat to human dignity.

Communication↗
PubMed2004

Microvolt T-wave alternans as predictor of electrophysiological testing results in professional competitive athletes.

BACKGROUND: Several studies have confirmed the equivalence of the microvolt T-wave alternans (mTWA) and the electrophysiology (EPS) tests in cardiac disease. No data are available in populations of competitive athletes with arrhythmias that might jeopardize the pursuit of their professional career. METHODS: We prospectively studied 100 trained competitive athletes, including elite types (72/100), (mean age +/- standard deviation: 26.1 +/- 4.5 years). Forty-eight of them were wholly normal (Group A, mean age: 24.5 +/- 8.5 years) and 52 of them had severe arrhythmias (Group B, mean age: 28.2 +/- 11.5 years) and were symptomatic in 85% of cases for prolonged palpitations and syncope, but lacked any overt structural heart disease at standardized cardiological screening. All athletes were evaluated with the microvolt T-wave alternans exercise-stress test, using the Heart Wave System with Microvolt Sensors. Group B underwent EPS to evaluate inducibility to sustained ventricular tachycardia (VT) during programmed electrical stimulation. RESULTS: In Group A, the mTWA outcome was determinate in 45 subjects (94%) and indeterminate in 3 (6%). No symptomatic event was reported in a follow-up of 36.1 months. In Group B, the mTWA test was positive in 7 symptomatic subjects (15%), indeterminate in 3 (7%), and negative for the remaining 42 subjects (76%). Forty-one of 42 negative mTWA subjects were also negative in the EPS test, without any syncope or sustained VT during 25.3 months of follow-up. In the positive mTWA test subjects, 5 (72%) were positive for inducibility of rapid sustained monomorphic VT in EPS, 1 was positive for severe sustained atrial tachyarrhythmias, and 1 refused EPS. We were able to pronounce a correct diagnosis of lymphocytic myocarditis for only 1 mTWA and EPS-positive subject. For the other 4 positive patients with arrhythmogenic micropathology, severe arrhythmic events were revealed in the follow-up and aggressive hybrid treatment was necessary. CONCLUSION: Microvolt-TWA study seems to be a useful, noninvasive, and feasible tool for evaluating arrhythmic risk in the athletic population. The mTWA test showed a high negative predictive value, using both EPS and the follow-up observation for severe arrhythmic cardiac events as an endpoint. The positive predictive value was present in a limited number of cases that were, however, subjects with a high risk of sudden arrhythmic death.

Adolescent↗
PubMed1984

Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias.

Electrophysiologic studies were performed in 172 consecutive patients for evaluation of documented sustained ventricular tachyarrhythmias. One hundred thirteen patients presented with sustained ventricular tachycardia that was hemodynamically stable, and 59 patients presented with cardiac arrest. Seventy-one patients without previously documented or suspected ventricular arrhythmias were also studied to determine the specificity of our electrophysiologic study protocol. The stimulation protocol included single, double, and triple right ventricular extrastimuli and rapid ventricular pacing at multiple cycle lengths performed at one or more right ventricular sites. Stimulation was performed at one or more left ventricular sites in patients with documented spontaneous arrhythmias when right ventricular programmed stimulation failed to induce sustained ventricular tachycardia. Ventricular tachyarrhythmias were induced in 110 (97%) of the patients who presented with sustained ventricular tachycardia, in 48 (81%) of the patients who presented with cardiac arrest, and in 28 (40%) of the patients without documented spontaneous arrhythmias. Right ventricular triple extrastimuli induced tachycardia in 22% of patients who presented with sustained ventricular tachycardia vs 46% of those who presented with cardiac arrest (p less than .001). Left ventricular stimulation was required for tachycardia induction in 3% of patients with stable tachycardia vs 19% of those with cardiac arrest (p less than .01). Triple extrastimuli induced 57% of tachycardias in the 28 patients without spontaneous arrhythmias, and virtually all of these tachycardias were polymorphic and nonsustained. The cycle lengths of tachycardias induced in each group by double and triple extrastimuli were similar, but the tachycardias induced in patients with cardiac arrest were significantly faster than those induced in the ventricular tachycardia group (mean cycle length 218 vs 291 msec, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

Assessing HCFA's Health Care Quality Improvement Program.

BACKGROUND: In 1992 the Health Care Financing Administration introduced the Health Care Quality Improvement Program (HCQIP), through which quality improvement projects are conducted in partnership with quality improvement organizations (QIOs), hospitals, health plans, or physicians. An evaluation of HCQIP began in May 1996 in response to the QIOs' request for an independent assessment of their activities. METHODOLOGY: The methodology and objectives of the evaluation were determined by an independent panel. The QIOs' full cohort of 970 HQIP projects could not be reviewed in the 10-month time frame available, but two topics were chosen: the management of warfarin or aspirin in patients with atrial fibrillation and the management of community-acquired pneumonia. FINDINGS: Analyses were limited to the 49 of the 68 projects that had progressed to the "improvement plan implemented" stage. However, only 39 of these 49 projects had information on outcomes, organization changes, and/or changes in process of care--and only 20 of the 49 had moved beyond the "improvement plan implemented" phase. Feedback of data led hospitals collaborating on improvement projects to revise or create processes of care. DISCUSSION: Although the assessment is the most comprehensive of its type to date, it should be viewed as a pilot study of some of the methods that could be incorporated in a more extensive and rigorous future evaluation of the impact of the HCQIP projects. Specific recommendations include random sampling of HCQIP projects across all clinical areas, conducting both prospective and retrospective assessments, developing uniform process and outcome program impact measures, and developing sustainable, ongoing automated data abstraction and analysis systems.

Atrial Fibrillation↗
PubMed1990

A quantitative evaluation of refractoriness within a reentrant circuit during ventricular tachycardia. Relation to termination.

Programmed ventricular stimuli introduced during sustained monomorphic ventricular tachycardia frequently reset the tachycardia, resulting in a less than fully compensatory pause. A resetting response curve is generated when the set of return cycles is evaluated as the function of the coupling intervals of the extrastimuli delivered during the ventricular tachycardia. If the stimulated wave front encounters tissue within the tachycardia circuit that is not fully recovered, interval-dependent conduction changes should occur producing an increasing resetting response pattern. We quantified the magnitude of this interval-dependent conduction slowing in 17 morphologically distinct ventricular tachycardias. The slope of the increasing limb of the resetting response curve was determined by linear regression analysis and ranged from -0.30 to -1.14 (mean +/- SD, 0.70 +/- 0.25). Seven of the 17 ventricular tachycardias (41%) terminated during introduction of ventricular extrastimuli. The slope of the resetting response pattern in those ventricular tachycardias that terminated were significantly steeper than in those that did not terminate (-0.85 +/- 0.15 versus -0.61 +/- 0.21, respectively, p = 0.025). Six of the seven ventricular tachycardias terminated with programmed ventricular stimuli had a slope steeper than -0.75, whereas only one of 10 ventricular tachycardias that did not terminate exceeded this value. In conclusion, the slope of the increasing portion of the resetting response curve correlates with ability to terminate uniform sustained ventricular tachycardia by timed extrastimuli. This slope is the quantification of the magnitude of interval-dependent conduction slowing. Additionally, tissue within the reentrant circuit displaying greater degrees of interval-dependent conduction slowing may also have relatively longer effective refractory periods.

Cardiac Pacing, Artificial↗
PubMed2006

A marketing perspective on disseminating evidence-based approaches to disease prevention and health promotion.

Evidence-based disease prevention practice guidelines can provide a rationale for health programming decisions, which should, in turn, lead to improved public health outcomes. This logic has stimulated the creation of a growing number of evidence-based prevention practice guidelines, including the Guide to Community Preventive Services. Few systematic efforts have been made to document the degree of adoption and implementation of these approaches, although the evidence on translation of research into practice in other health fields indicates that the adoption and implementation rate is low. Drawing on the marketing literature, we suggest three approaches to enhance the adoption and implementation of evidence-based approaches: 1) conducting consumer research with prospective adopters to identify their perspectives on how evidence-based prevention programs can advance their organization's mission, 2) building sustainable distribution channels to promote and deliver evidence-based programs to prospective adopters, and 3) improving access to easily implemented programs that are consistent with evidence-based guidelines. Newly emerging paradigms of prevention research (e.g., RE-AIM) that are more attuned to the needs of the marketplace will likely yield a new generation of evidence-based preventive approaches that can be more effectively disseminated. We suggest that the public health community prioritize the dissemination of evidence-based prevention approaches, because doing so is a potent environmental change strategy for enhancing health.

Evidence-Based Medicine↗
PubMed1996

Time- versus frequency-domain analysis in predicting cycle length of inducible ventricular tachycardia after myocardial infarction.

To determine whether time- and frequency-domain analyses differ in their ability to predict sustained ventricular tachycardia (VT) induced by programmed ventricular stimulation, 60 consecutive patients with myocardial infarction and 30 healthy control subjects were evaluated. Programmed ventricular stimulation using three extrastimuli and signal-averaged ECG recordings were performed in patients with myocardial infarction. Of the 60 patients, sustained monomorphic VT (SMVT) with cycle length (CL) > or = 250 ms (slow SMVT) was inducible in 9, and SMVT with CL < 250 ms (fast SMVT) was inducible in 9. The durations of the filtered QRS (f-QRS) at each high-pass filter (25, 40, and 80 Hz) and the low amplitude signal (LAS) at 25-Hz high-pass filtering were significantly longer in the slow SMVT group than in the fast SMVT, no VT, or normal control group. The root-mean-square voltages at 25-Hz and 80-Hz high-pass filters in the slow SMVT group were significantly lower than in the fast SMVT, no VT, or normal control group. There was no significant difference in time-domain variables among fast SMVT, no VT, and normal control groups. The CL of the induced sustained VT was significantly correlated with the durations of f-QRS and LAS. Concerning frequency-domain variables (area ratio and factor of normality), there was no significant difference between slow and fast SMVT groups. Both the slow and fast SMVT groups had a significantly higher area ratio and a significantly lower factor of normality than the group with no VT or the normal control subjects. In conclusion, there were significant correlations between time-domain variables and CL of SMVT, while there was no correlation when using frequency-domain parameters.

Cardiac Catheterization↗
PubMed2004

Consumer involvement in the health technology assessment program.

OBJECTIVES: This study aims to describe a cycle of development leading to sustainable methods for involving consumers in the management of a program commissioning health technology assessment. METHODS: Staff time was dedicated to developing procedures for recruiting and briefing consumers to participate in prioritizing, commissioning, and reporting research. Resources and support were developed in light of early feedback from consumers and those working with them. These were piloted and amended before being used routinely. RESULTS: Over 4 years, procedures and resources have been developed to support six consumers attending seven to eight prioritization meetings a year; thirty to forty-five consumers each year commenting on research need for particular topics; thirty consumers a year commenting on research proposals, and twenty a year commenting on research reports. The procedures include clear job descriptions, induction and development days, clear briefing materials, payment for substantial tasks, and regularly seeking feedback to improve procedures. CONCLUSIONS: Explicit, inclusive, and reproducible methods for supporting consumer involvement that satisfy National Health Service policy recommendations for involving consumers in research require dedicated staff time to support a cycle of organizational development.

Community Participation↗
PubMed2004

Tails and cuts: the role of histone post-translational modifications in the formation of programmed double-strand breaks.

In eukaryotic organisms, various DNA recombination mechanisms have been described that are an integral part of nuclear differentiation processes. In several places, the recombination is initiated by one or more double-strand breaks that result from the action of specific endonucleolytic activities. The importance of chromatin in controlling susceptibility of DNA to various DNA transactions has been recognized for long. Recent literature links post-transcriptional modifications of the amino-terminal part of histones (the tails) to the formation of developmentally regulated DNA double-strand break (the cuts). In this review, I compare the existing data in three different DNA rearrangement-based processes, i.e., genetic recombination associated to meiosis, lymphoid-specific V(D)J recombination and excision of DNA fragments in the nucleus of ciliates. Inspired by some of the concepts established in the field of transcription, models are proposed for molecular mechanisms that sustain the epigenetic control of programmed double-strand break formation.

Animals↗
PubMed2002

Learning from history: morphology's challenges in Germany ca. 1900.

A century ago, Carl Gegenbaur's program of vertebrate evolutionary morphology faced its greatest challenges. The controversy over the evolutionary origin of the vertebrate paired limbs between 1875 and 1906 illustrates the failure of the traditional methods of comparative anatomy and embryology (supported by Haeckel's biogenetic law) to choose between different phylogenetic hypotheses. The controversy over morphology's status as science intensified at the turn of the twentieth century, when the legitimacy of historical explanation itself as a mode of scientific understanding came under fire. Gegenbaur's intellectual grandson, Hermann Braus, sought to defend the legitimacy of phylogenetic reconstruction while updating it to include experimental and causal-analytical approaches, but was unable to sustain a viable synthetic research program. The article concludes with reflections on approaches to the past used by historians and evolutionary morphologists.

Anatomy, Comparative↗
PubMed1996

HLA class II signaling mediates cellular activation and programmed cell death.

The class II human leucocyte antigens (HLA class II) are principally peptide presentation molecules. Signal transduction by these molecules has also been shown to transmit activation signals in both B and T lymphocytes by a pathway including protein tyrosine kinase activation, an intracellular calcium flux, and both the activation and transcriptional regulation of protein kinase C (PKC) isoforms. Apoptosis can also result from human leukocyte antigen class II stimulation. Inhibitors of gene transcription were used to inhibit activation and, therefore, to distinguish the signal transduction pathways important for apoptosis. This approach provided evidence that cellular activation and apoptosis undertook separate signaling pathways, and that PKC and intracellular calcium were shared between the two pathways, while tyrosine kinase activity was essential for cell activation. Further studies using cord blood B cells showed that these cells were incapable of generating a calcium flux after HLA class II ligation and were not subject to cell death. The importance of sustained levels of calcium for programmed cell death (PCD) was underlined since the restoration of a calcium flux enabled PCD of cord blood B cells via HLA class II. These results demonstrate that HLA class II stimulation initiates two distinct signal transduction pathways.

Adult↗