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PubMed1986

Clinical electrophysiology, efficacy and safety of chronic oral cibenzoline therapy in refractory ventricular tachycardia.

The electrocardiographic (ECG) and electrophysiologic (EP) effects, clinical efficacy and safety of oral cibenzoline therapy were evaluated using a twice-daily dosing regimen in patients with refractory ventricular tachycardia (VT). Twenty patients underwent EP studies in the control (drug-free) state and after cibenzoline therapy using an incremental dose-titration protocol. Oral cibenzoline (2.4 to 5.8 mg/kg/day) was administered in doses of 130, 160 or 190 mg at 12-hour intervals. ECG and EP variables, 24-hour ambulatory ECG monitoring and programmed electrical stimulation studies were obtained in the control state and after 11 +/- 4 days of cibenzoline therapy. Cibenzoline therapy prolonged the mean PR interval (from 179 +/- 29 to 201 +/- 36 ms, p less than 0.001), the mean QRS duration (from 107 +/- 21 to 130 +/- 25 ms, p less than 0.001), and the mean QTc interval (from 422 +/- 25 to 460 +/- 42 ms, p less than 0.001). It increased the mean HV interval (from 50 +/- 17 to 65 +/- 20 ms, p less than 0.01) and mean right ventricular effective refractory period (from 245 +/- 24 to 266 +/- 27 ms, p less than 0.01). After cibenzoline therapy, 5 patients (25%) had suppression of inducible sustained VT during programmed electrical stimulation. High-degree atrioventricular block occurred in 2 patients. Chronic cibenzoline therapy (mean follow-up 24 +/- 3 months) remained effective in long-term suppression of VT in 4 patients. Two patients had to discontinue therapy because of gastrointestinal intolerance. Cibenzoline is effective in suppression of refractory VT in selected patients using a twice-daily dosing schedule.

Administration, Oral↗
PubMed1997

Value of a supervised exercise program for the therapy of arterial claudication.

PURPOSE: This study was performed to test the effectiveness of a formal supervised exercise program against a home-based exercise program for both walking ability and quality of life endpoints. METHODS: Patients with arterial claudication were randomized to either a 12-week supervised exercise program (SUPEX) with weekly lectures relating to peripheral vascular disease or to a home exercise group (HOMEX) who attended an identical lecture program and received weekly exercise instruction. The study population included 29 men and 26 women, with a mean age of 69.1 +/- 8.1 years. Forty-seven patients completed the 12-week program, 46 were available for testing at completion, and 38 for 6-month testing. Claudication pain time (CPT) and maximum walking time (MWT) on a progressive treadmill exercise test were assessed at baseline, program completion, and 6 months. The Medical Outcomes Study Short Form-36 (SF-36) was administered at these intervals to assess effects on quality of life. RESULTS: Each group improved (p < 0.001) in both CPT and MWT at the completion of the 12-week program, which was sustained at the 6-month follow-up. Increase in HOMEX CPT from baseline (3.6 +/- 2.73 minutes) to 6-month follow-up (6.6 +/- 3.17 minutes) was less than for the SUPEX group (3.8 +/- 2.74 to 11.2 +/- 4.02 minutes, respectively); similar results were obtained for MWT. At both completion and 6 months, there was a significant intergroup difference for CPT and MWT (p < 0.004) favoring SUPEX. For both groups, measures of health perception based on the SF-36 demonstrated improvement (p < 0.002) in Physical Function Subscale, Bodily Pain Subscale, and Physical Composite Score. There were no between-group differences on the subsets of the SF-36 at the three assessment intervals. CONCLUSIONS: Supervised exercise programs provide superior increased walking ability in the noninterventional therapy of arterial claudication, and both supervised and home based exercise therapy result in improved SF-36 functional measures. The lack of intergroup differences in these measures may be a result of the high degree of interaction with healthcare providers in the HOMEX group. Although a supervised program results in optimal walking benefits, a highly structured home-based program provides similar functional improvement and may be a satisfactory alternative for patients with lesser walking requirements.

Aged↗
PubMed2003

Application of non-market valuation to the Florida Keys marine reserve management.

The quality of the coral reefs in the Florida Keys is essential to sustain nature-based tourism in the Keys. The recently established marine reserves (MR) are expected to improve the reef environment, particularly coral and fish abundance and diversity. In this paper, a combined model of travel cost and contingent behavior was estimated in order to measure the non-market recreational benefits of reef quality improvements. The results indicated that an average visitor would undertake 43-80% more number of trips to the Florida Keys and experience a 69% increase in the use values per trip, as a result of the MR-induced reef quality improvements. The above non-market value estimates were further applied to evaluating alternative management proposals for funding the MR program. It was found that the annual management costs of the MR program would constitute an insignificant portion--only around one to 2%--of the annual recreational benefits that the MR would generate. The results provide a strong economic justification for designing user-based funding mechanisms in order to make the MR program self-sustaining in the future.

Anthozoa↗
PubMed1998

Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter.

BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. METHODS: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. RESULTS: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. CONCLUSION: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.

Animals↗
PubMed1989

Antiarrhythmic effects of desethylamiodarone in dogs with subacute myocardial infarction and inducible ventricular arrhythmias.

To determine if desethylamiodarone (DA), the principal metabolite of amiodarone, has antiarrhythmic activity, DA was administered intravenously (i.v.) as a 5 mg/kg bolus followed by a 2-h infusion of 8 mg/kg/h to 12 dogs with 5-7-day-old myocardial infarction and reproducibly inducible sustained ventricular arrhythmias. Programmed electrical stimulation of the right ventricle was repeated, and plasma DA concentration was determined at 15-min intervals during DA administration. At the end of the infusion, the animals were killed and DA concentration in infarcted and noninfarcted myocardium was measured. Grading and statistical analysis of induced arrhythmias revealed significant amelioration during DA infusion, with partial or complete suppression in 9 of the 12 dogs. Apparent steady-state plasma DA concentration (range 0.8-1.0 micrograms/ml) was achieved and maintained during the final 105 min of infusion. DA concentration in noninfarcted myocardium (62.6 +/- 22.0 micrograms/g) was significantly higher (p less than 0.01) than DA concentration in infarcted myocardium (25.6 +/- 18.6 micrograms/g). We conclude that DA administered i.v. has antiarrhythmic activity in dogs with subacute myocardial infarction and reproducibly inducible sustained ventricular arrhythmias.

Amiodarone↗
PubMed2000

A clinical advancement program: evaluating 10 years of progressive change.

OBJECTIVE: To report the evolution of a clinical advancement program, UEXCEL, at a western teaching hospital and the outcomes associated with evaluation over time. BACKGROUND: The clinical ladder program was initiated in 1989 to provide a professional framework for developing, evaluating, and promoting registered nurses. The program is derived from Benner's Novice to Expert model. Over a 10-year period, the program has undergone three significant revisions. Program evaluation data have been used to guide institutional change. METHODS: Structure and progression of program development and change are outlined. Evaluation data were collected using a 23-item clinical ladder satisfaction scale developed by Strzelecki. Data were collected in 1993, 1994, 1996, and 1998 using standard survey methods after institutional review board approval. Subjects were registered nurses holding clinical positions at the University of Colorado Hospital. Data were trended across units and time periods and were compared with other institutional evaluation data sets. RESULTS: Improvement in nurse satisfaction with the UEXCEL program has been steady and incremental, after low baseline measurement. Satisfaction has improved after each program revision. A significant demographic variable over time is the correlation between higher registered nurse education and program satisfaction. Human resources issues are reported with data results. CONCLUSIONS: Sustaining a clinical advancement program represents a challenge in the current health-care environment. Institutional commitment, staff involvement in revisions, and activities to improve professional nurse development are critical strategies so progress can be achieved.

Career Mobility↗
PubMed2002

Long-term injured purkinje cells are competent for terminal arbor growth, but remain unable to sustain stem axon regeneration.

Long-distance axon regeneration requires the activation of a specific set of neuronal growth-associated genes. Adult Purkinje cells fail to upregulate these molecules in response to axotomy and show extremely weak regenerative properties. Nevertheless, starting from several months after injury, transected Purkinje axons undergo spontaneous sprouting. Here, we asked whether long-term injured Purkinje cells acquire novel intrinsic growth properties that enable them to upregulate growth-associated genes and sustain axon regeneration. To test this hypothesis, we examined axon growth and cell body changes in adult rat Purkinje neurons following axotomy and implantation of embryonic neocortical tissue or Schwann cells into the injury track. Purkinje cells that survived over 6 months after injury/transplantation displayed profuse sprouting in the injured cerebellum and developed extensive networks of terminal branches into embryonic neocortical grafts. In addition, severed Purkinje axons exposed to these transplants 6 months after injury grew faster than their counterparts confronted with the same environment immediately after axotomy. Nevertheless, long-term injured Purkinje cells failed to regenerate stem neurites into Schwann cell grafts, and, under all experimental conditions, they did not upregulate growth-associated molecules, including c-Jun, GAP-43, SNAP-25, and NADPH-diaphorase. These results indicate that the long-term injured Purkinje cells remain unable to activate the gene program required to sustain axon regeneration and their plasticity is restricted to terminal arbor remodeling. We propose that the delayed growth of injured Purkinje cells reflects an adaptive phenomenon by which the severed axon stump develops a new terminal arbor searching for alternative connections with local partners.

Animals↗
PubMed2005

Long-term impact of a district-wide school/community-based substance abuse prevention initiative on gateway drug use.

This study examined long-term effects of a school/family/community substance abuse prevention partnership intervention lead by a Midwestern school district. Previous findings suggested that the program contributed to decreased tobacco and marijuana, but not alcohol, use prior to and after implementation between 1987 and 1991. The current study examined 8th-12th grade student drug use prevalence data from 1991 and 2003 to determine whether previous program effects were sustained. With one exception, reported lifetime and monthly cigarette use decreased below 1991 levels for all grades. Lifetime and monthly alcohol use decreased below 1991 levels for most grades, a result not previously detected. While still below national rates, reported lifetime use of marijuana increased for all grades over time. The intervention was effective in reducing cigarette and alcohol use over time and in suppressing marijuana use levels below national rates; however, these gains tended to erode in later high school grades.

Adolescent↗
PubMed2003

Peer education for HIV prevention in the Socialist Republic of Vietnam: a national assessment.

In 2000, the government of Vietnam conducted the first assessment of its national peer education program for HIV prevention. Twenty (32%) of Vietnam's 61 provinces and urban areas had functioning peer education programs, and program coordinators of all 20 were interviewed regarding their programs. In addition, on-site reviews were done for 10 of the 20 programs, including interviews of peer educators and high-risk persons in each program. The assessment found that a total of 500 peer educators were functioning either independently or as part of one of 79 teams. In the 20 provinces, the peer educators made an estimated 7,000 total contacts per month with high risk persons, but many persons were likely contacted repeatedly. Despite this, coverage was limited: some provinces with high numbers of persons reported with HIV/AIDS had few peer educators. Although most provinces targeted IDU and many targeted CSW, few provinces targeted sex partners of IDU or CSW. The definition of peer education and composition of teams varied substantially by province; only one province included persons living with HIV/AIDS as peer educators. The services provided by peer educators were primarily distributional: delivering information either through word of mouth, pamphlets, or brochures, providing condoms, and sometimes providing clean syringes and needles. Skills building or goal setting interventions aimed at HIV risk reduction were rarely provided. Most provinces had concerns about ongoing funding and sustainability of the programs. Based on the assessment, specific recommendations were provided for strengthening and expanding Vietnam's peer education programs.

Adolescent↗
PubMed1988

Prognosis following sustained ventricular tachycardia occurring early after myocardial infarction.

Eighty-seven patients with sustained ventricular tachycardia (VT) between 3 and 90 days after acute myocardial infarction (AMI) were evaluated to define factors associated with a high risk of arrhythmia recurrence or death. Most patients had poor left ventricular function (mean ejection fraction 29 +/- 12%), multivessel coronary artery disease (71%) and inducible sustained VT with programmed stimulation (87%). During a mean follow-up of 26 months, 36 patients (41%) died and 21 patients had arrhythmia recurrence (with 19 sudden deaths). Factors independently associated with mortality included: (1) treatment before 1981 (p less than 0.01); (2) anterior AMI (p less than 0.05); (3) short time from AMI to first episode of VT (p less than 0.06); and (4) multivessel coronary artery disease (p less than 0.07). Factors independently associated with arrhythmia recurrence were: (1) medical treatment (as opposed to surgical) (p less than 0.01); (2) greater than or equal to 3 episodes of spontaneous VT (p = 0.01); (3) multivessel coronary disease (p less than 0.05); and (4) anterior AMI (p less than 0.07). Medically and surgically treated patients did not differ significantly in overall survival (49 vs 61%, respectively), although short-term (6 month) surgical survival improved from 31% during the first half of the study to 96% in the latter half (p less than 0.01). For patients with sustained VT early after AMI the risk of death and arrhythmia recurrence can be assessed based on clinical and angiographic characteristics; in addition, surgical treatment is associated with a lower incidence of arrhythmia recurrence than medical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The impact of the Postponing Sexual Involvement curriculum among youths in California.

Postponing Sexual Involvement (PSI) is a widely implemented middle school curriculum designed to delay the onset of sexual intercourse. In an evaluation of its effectiveness among seventh and eighth graders in California, 10,600 youths from schools and community-based organizations statewide were recruited and participated in randomly assigned intervention or control groups; the curriculum was implemented by either adult or youth leaders. Survey data were collected before the program was implemented, and at three months and 17 months afterward. At three months, small but statistically significant changes were found in fewer than half of the measured attitudes, behaviors and intentions related to sexual activity; at 17 months, none of these significant positive effects of the PSI program had been sustained. At neither follow-up were there significant positive changes in sexual behavior; Youths in treatment and control groups were equally likely to have become sexually active, and youths in treatment groups were not less likely than youths in control groups to report a pregnancy or a sexually transmitted infection. The evaluation suggests that PSI may be too modest in length and scope to have an impact on youths' sexual behavior.

Adolescent↗
PubMed1986

Improved selection of patients for programmed ventricular stimulation by frequency analysis of signal-averaged electrocardiograms.

Improved selection of patients with suspected sustained ventricular tachycardia (VT) for programmed ventricular stimulation is needed. To determine if frequency analysis detects patients in whom sustained VT might be induced, we first obtained fast-Fourier transforms (FFT) of signal-averaged electrocardiograms (ECGs) from 20 patients with spontaneous sustained VT (group 1) and compared them with the results of programmed ventricular stimulation with single and double extrastimuli during two cycle lengths and burst pacing from two right ventricular sites. The FFT data were expressed as an area ratio that quantified the relative contributions of 20 to 50 Hz frequencies in the terminal QRS and ST segment. A logistic regression with inducibility as the dependent variable was used to help define area ratio values greater than 20 as abnormal. Sustained monomorphic VT was induced in 18 patients, each with an area ratio value greater than 20. Sustained VT was not induced in two patients, each with an area ratio value less than 20. FFT data were then compared prospectively with the results of programmed stimulation in 38 patients (group II) with nonsustained VT (12 patients) or syncope (26 patients) referred for electrophysiologic study. In none of the 26 patients in group II with normal FFT values was VT inducible. Sustained monomorphic VT was induced in five of 12 patients with abnormal FFT values. Thus, the results of FFT analysis correctly predicted the results of programmed ventricular stimulation in 88% of patients studied and in 82% of patients in group II with syncope or nonsustained VT. Moreover, all five patients in group II in whom sustained VT was induced were identified correctly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Guillain-Barré syndrome in the US Army.

Using the US Army's operational reporting system, the medical records of soldiers with Guillain-Barré syndrome were retrieved and compared with reported incidence figures from the 1976 national influenza immunization program. Military personnel sustained an incidence of disease approximatley 50% higher than unvaccinated civilians but less than 25% of the rate attributed to civilian vaccinees.

Adult↗
PubMed2005

The physician-scientist career pipeline in 2005: build it, and they will come.

CONTEXT: Physician-scientists play a unique and critical role in medical research. Nonetheless, a number of trends followed during the 1980s and 1990s revealed that this career pathway was in serious jeopardy. Physician-scientists were declining in number and were getting older. A variety of factors were thought to contribute to this problem, including increasing indebtedness of medical school graduates caused by rapidly rising medical school tuition costs. OBJECTIVE: To evaluate the impact of recently initiated programs from the National Institutes of Health (NIH) and several not-for-profit institutions designed to revitalize the physician-scientist career pipeline. DESIGN: We assessed recent trends in the physician-scientist career pipeline using data obtained from the NIH, the American Medical Association, the Association of American Medical Colleges, and other sources. MAIN OUTCOME MEASURES: Total numbers of physicians performing research, grant application numbers and success rates for MDs, MD-PhDs, and PhDs at various stages in their careers, interest in research among medical students, medical school tuitions and postgraduate salaries, numbers and composition of applicants for NIH loan repayment programs, and gender distribution of young physician-scientists. RESULTS: The number of physician-scientists in the United States has been in a steady state for the past decade, but funded physician-scientists are significantly older than they were 2 decades ago. However, the study of early career markers over the past 7 to 10 years has demonstrated increasing interest in research careers by medical students, steady growth of the MD-PhD pool, and a new burst of activity in the "late bloomer" pool of MDs (individuals who choose research careers in medical school or in residency training), fueled by loan repayment programs that were created by the NIH in 2002. Several recent trends for more established physician-scientists have also suggested improvement. CONCLUSIONS: Although it is too early to assess the impact of these indicators on the long-term career pathway, the recent growth in activity in the physician-scientist career pipeline is an encouraging development. Continued funding of these new programs, coupled with sustained support for physician-scientists committed to the pathway, will be required to maintain these positive trends.

Biomedical Research↗
PubMedDate not supplied

Building capacity through collaborative leadership.

This paper is based upon material from the manuals and training program underpinnings the 'Sustaining community-based initiative' from the Healthcare Forum with the W.K. Kellogg Foundation in the USA. In order to address the problems of American urban communities a new approach is proposed using the concept of 'collaborative empowerment'. This is a planning and organizational method that lets community- and neighbourhood-based organizations design, implement and assess problem-solving strategies that increase their effectiveness at dealing with community issues. The use of organizational management principles and practices in community involvement and strengthening community leadership is illustrated through practical examples.

Community Health Planning↗
PubMed2006

Billing effectively with the new health and behavior current procedural terminology codes in primary care and specialty clinics.

The health and behavior current procedural terminology (CPT) codes introduced in 2003 have gained nationwide acceptance through Medicare and limited acceptance through third party payers. The codes facilitate accurate description and quantification of behavioral medicine services within a primary care or specialty clinic setting. The author reviews their appropriate utilization to enhance reimbursement and facilitate development of self-sustaining behavioral medicine programs. Information is provided on increased use and reimbursement of codes within psychology. Future directions for continued advocacy, increased acceptance, training, and research are discussed.

Behavioral Medicine↗
PubMed2005

Proteome analysis of early somatic embryogenesis in Picea glauca.

Forestry is a valuable natural resource for many countries. Rapid production of large quantities of genetically improved and uniform seedlings for restocking harvested lands is a key component of sustainable forest management programs. Clonal propagation through somatic embryogenesis has the potential to meet this need in conifers and can offer the added benefit of ensuring consistent seedling quality. Although in commercial use, mass production of conifers through somatic embryogenesis is relatively new and there are numerous biological unknowns regarding this complex developmental pathway. To aid in unravelling the embryo developmental process, two-dimensional electrophoresis was employed to quantitatively assess the expression levels of proteins across four stages of somatic embryo maturation in white spruce (0, 7, 21 and 35 days post abscisic acid treatment). Forty-eight differentially expressed proteins have been identified, which display a significant change in abundance as early as day 7 of embryo development. These proteins are involved in a variety of cellular processes, many of which have not previously been associated with embryo development. The identification of these proteins was greatly assisted by the availability of a substantial expressed sequence tag (EST) resource developed for white, sitka and interior spruce. The combined use of these spruce ESTs in conjunction with GenBank accessions for other plants improved the rate of protein identification from 38% to 62% when compared with GenBank alone using automated, high-throughput techniques. This underscores the utility of EST resources in a proteomic study of any species for which a genome sequence is unavailable.

Cell Line↗
PubMed2004

Protecting, promoting, and supporting breastfeeding among women in the labor force.

The need to protect, promote, and support breastfeeding among women in the labor force is an important global issue that requires greater attention. An increasing proportion of women of child-bearing age are employed outside the home. Women who resume full-time work outside the home when their infants are young tend to have shorter durations of breastfeeding and less exclusive breastfeeding. However, evidence indicates that appropriate breastfeeding policy and support programs can help sustain breastfeeding among employed women. Effective strategies include delayed return to work, working part-time, improved conditions at work for breastfeeding, breastfeeding breaks during work hours, milk expression and storage, and access to breastfeeding counseling. In this chapter, we consider the special needs of women working outside the home; provide a brief overview of the literature; and address international policy regarding the protection, promotion, and support of breastfeeding among women who work outside the home.

Adult↗