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PubMed1987

Electrophysiologic consequences of the Mustard repair of d-transposition of the great arteries.

This study describes the electrophysiologic effects of the Mustard repair of d-transposition of the great arteries on the sinus node and on conduction and refractoriness in the atrium, atrioventricular (AV) node and ventricle. Seventy-two electrophysiologic studies were performed on 64 patients after the Mustard operation. Standard rest and 24 hour ambulatory electrocardiograms were evaluated. Catheter endocardial atrial mapping, available in 67 of the 72 studies, revealed that sinus rhythm was present in the atria in 33 patients, ectopic atrial rhythm in 26 and junctional rhythm in 8. Intraatrial conduction delays with very late activation of the low medial, low lateral or low right atrium at the AV junction were present in 53 of 59 patients with atrial or sinus rhythm. Sinus node function was normal in only nine patients. Prolonged refractory periods were found in the right atrial portion of the new right atrium when compared with the left atrial portion of the new right atrium. Forty-one percent of the patients had prolongation of atrial refractoriness with shortening of the paced cycle lengths. Fifty-one percent developed sustained intraatrial reentry with programmed atrial stimulation. Forty-eight percent of these patients with inducible atrial tachycardia have since developed clinical episodes of atrial flutter. In summary, electrophysiologic studies revealed significant abnormalities of sinus node function and atrial conduction and refractoriness. Alone or in combination, these abnormalities, which result in severe bradycardia or rapid atrial arrhythmias, may lead to sudden death. The Jatene or arterial switch procedure may provide an appropriate alternative operation in this group of patients.

Adolescent↗
PubMedDate not supplied

Oncology clinical trials.

In 1971, President Nixon declared a "war on cancer" and initiated substantial funding for the National Cancer Program, which has been sustained through the years with a significant return on investment. Recently released 1998 statistics from the National Cancer Institute (NCI), the Centers for Disease Control and Prevention, and the American Cancer Society show the first real decline in cancer since the 1930s. Still, more than 1.2 million Americans will be diagnosed with cancer this year. New developments in biomedicine and advances in science and technology likely will lead to greater declines in cancer incidence and mortality.

American Cancer Society↗
PubMed2006

Transcriptional regulator Id2 mediates CD8+ T cell immunity.

Transcriptional programs that initiate and sustain the proliferation, differentiation and survival of CD8(+) T cells during immune responses are not completely understood. Here we show that inhibitor of DNA binding 2 (Id2), an antagonist of E protein transcription factors, was upregulated in CD8(+) T cells during infection and that expression of Id2 was maintained in memory CD8(+) T cells. Although Id2-deficient naive CD8(+) T cells recognized antigen and proliferated normally early after infection, effector CD8(+) T cells did not accumulate because the cells were highly susceptible to apoptosis. Id2-deficient CD8(+) T cells responding to infection had changes in the expression of genes that influence survival and had altered memory formation. Our data emphasize the importance of Id2 in regulating gene expression by CD8(+) T cells and the magnitude of effector responses, suggesting a mechanism involving Id protein- and E protein-mediated survival and differentiation of mature T cells.

Adoptive Transfer↗
PubMed1984

Effects of exhaustive, isometric training on lactate accumulation in different muscle fiber types.

Four physically active men took part in a 6-week training program. They performed three sustained leg press contractions at 50% maximal isometric strength (MIS) to exhaustion 3-4 times a week. Before training and following performance of 50% MIS to exhaustion, muscle biopsies were obtained from m. vastus lateralis for subsequent lactate analysis on freeze-dried fiber fragments. Post-training biopsies were taken (a) after a contraction performed at the same tension level and for the same time period and (b) after an exhaustive contraction held at 50% of the post-training MIS. Prior to training, lactate concentration in fast-twitch (FT) and slow-twitch (ST) muscle fibers averaged 29.8 (range 27.9-31.4) and 28.7 (24.0-32.4) mmol X kg-1 w.w, respectively. After training the values were 16.7 (11.0-27.5) (FT) and 14.1 (6.1-26.9) (ST). Lactate concentrations following exhaustive contraction were 21.3 (16.3-27.9) (FT) and 17.8 (11.5-28.0) (ST). Thus, for all situations studied, lactate concentration was greatest in FT fibers, and this difference tended to increase with training, irrespective of whether or not the contraction was maintained until the onset of exhaustion.

Adult↗
PubMed2003

Susceptibility and biomarker knowledge for improvement of environmental health.

At the international level, environmental health problems are usually most serious in countries that have the least resources to deal with the problems. Therefore, international efforts have been initiated to achieve equitable environmental health globally. One approach is to conduct international collaborative studies. This approach has been successful in the building of scientific infrastructure in these countries so that they can address their own environmental health concerns and to sustain the environmental health programs. Using liver and oral cancers as models for discussion, examples of success in the identification of etiology and the mechanisms for the diseases are provided. For example, biomarkers are used to provide early warning signals for the disease. In addition, the application of the collected information for developing disease prevention and intervention programs is presented. Expertise in genetic susceptibility is used to provide a more precise understanding of the cancer process. With the precise knowledge, the information can potentially be used to screen for high-risk individuals and to develop "designer" intervention procedures against specific biochemical defects. Success in disease prevention is dependent upon multidisciplinary collaborations at the local and international levels.

Aflatoxin B1↗
PubMed1981

Maternal locus of control and developmental gain demonstrated by high risk infants: a longitudinal analysis.

The short and long-term effects of a parent-infant training program for biologically handicapped infants was evaluated in terms of maternal locus of control. Twenty-four infants were evaluated on five developmental scales measuring motor, cognitive, and language functioning over a four-year period. Developmental gains on these indices were regressed against maternal locus of control partialing maternal education and socioeconomic status out of the relationship. The results indicated that maternal locus of control accounted for a substantial portion of variance in the developmental gains following the program intervention period. This was especially true for the cognitive and language indices. Locus of control in the mother, however, was not related to the motor indices, nor did it relate to cognitive and language gains achieved during the program intervention period. The results are discussed in terms of the mother's perceived contribution to infant progress in programs designed to produce sustained gains in early infant development.

Adult↗
PubMed1997

At the crossroads: options for financing college health services in the 21st century.

At a time when increasing numbers of uninsured and underinsured students are attending college, many college health programs face formidable challenges in their efforts to sustain services. As financial pressures increase, college health programs must revisit their funding options, including (1) maintaining the current level and source of funding but requiring additional out-of-pocket fees for certain services from students, (2) establishing their own insurance plans, (3) qualifying as a preferred provider organization, or (4) some combination of the above. Whatever strategies are selected and pursued, college health programs must continue to try to provide quality services at a reasonable cost while maintaining an emphasis on prevention, health education, and the provision of services most needed by the college population, including mental health and substance abuse services.

Adolescent↗
PubMed2005

Intensive telephone follow-up to a hospital-based disease management model for patients with diabetes mellitus.

The objective of this study was to evaluate the value of an intensive telephone follow-up as an additional component of a diabetes disease management program already shown to be effective in improving glycemic control, adherence with American Diabetes Association (ADA) standards of care, and health-related quality of life (HRQOL). The study involved a randomized controlled trial. The intervention group received a series of 12 weekly phone calls reinforcing base education and self-management skills. Five hundred and seven consenting patients, age 18 years or older, with type 1 or type 2 diabetes mellitus referred to the hospital- based disease management program who had telephones and were able to complete surveys in English or Spanish were enrolled. Outcomes were evaluated at 3 and 12 months follow- up. Adherence to ADA standards of care, specifically annual eye exams, physician foot exams, foot self-exams, and pneumonia vaccination were significantly better with the added telephone intervention, but there were no differences between the groups on glycemic control, HRQOL, or patient satisfaction. The effectiveness of the disease management program was replicated with sustained improvement in glycemic control, HRQOL, and adherence to ADA standards. The additional telephone intervention further improved adherence to ADA guidelines for self-care and medical care but did not affect glycemic control or HRQOL.

Adult↗
PubMed2004

p53 localization at centrosomes during mitosis and postmitotic checkpoint are ATM-dependent and require serine 15 phosphorylation.

We recently demonstrated that the p53 oncosuppressor associates to centrosomes in mitosis and this association is disrupted by treatments with microtubule-depolymerizing agents. Here, we show that ATM, an upstream activator of p53 after DNA damage, is essential for p53 centrosomal localization and is required for the activation of the postmitotic checkpoint after spindle disruption. In mitosis, p53 failed to associate with centrosomes in two ATM-deficient, ataxiatelangiectasia-derived cell lines. Wild-type ATM gene transfer reestablished the centrosomal localization of p53 in these cells. Furthermore, wild-type p53 protein, but not the p53-S15A mutant, not phosphorylatable by ATM, localized at centrosomes when expressed in p53-null K562 cells. Finally, Ser15 phosphorylation of endogenous p53 was detected at centrosomes upon treatment with phosphatase inhibitors, suggesting that a p53 dephosphorylation step at centrosome contributes to sustain the cell cycle program in cells with normal mitotic spindles. When dissociated from centrosomes by treatments with spindle inhibitors, p53 remained phosphorylated at Ser15. AT cells, which are unable to phosphorylate p53, did not undergo postmitotic proliferation arrest after nocodazole block and release. These data demonstrate that ATM is required for p53 localization at centrosome and support the existence of a surveillance mechanism for inhibiting DNA reduplication downstream of the spindle assembly checkpoint

Ataxia Telangiectasia Mutated Proteins↗
PubMed2005

Person-to-person transmission of hepatitis A virus in an urban area of intermediate endemicity: implications for vaccination strategies.

Developing countries with an increasing hepatitis A disease burden may target vaccination to specific groups, such as young children, as an initial control strategy. To better understand transmission of hepatitis A virus in such countries, the authors prospectively studied household and day-care/school contacts of cases in Almaty, Kazakhstan. Overall, by the time of identification of symptomatic index cases, half of transmission had already occurred, having been detected retrospectively. The odds of household contacts' becoming infected were 35.4 times those for day-care/school contacts (95% confidence interval (CI): 17.5, 71.7). Within households, younger age of either index cases or susceptible contacts elevated the odds of secondary infection among susceptible contacts: The presence of a case under 6 years of age raised the odds 4.7 times (95% CI: 1.2, 18.7); and compared with contacts aged 14 years or older, the odds of infection were increased to 7.7 (95% CI: 1.5, 40.3) and 7.0 (95% CI: 1.4, 34.3) among contacts aged 0-6 years and 7-13 years, respectively. Young children are appropriate targets for sustainable hepatitis A vaccination programs in areas undergoing hepatitis A epidemiologic transition. If vaccine is determined to be highly effective postexposure and if it is feasible, vaccinating household contacts could be a useful additional control strategy.

Adolescent↗
PubMed1994

Cardiac late potentials for diagnosis in heart disease.

In recent years abundant information has been obtained about the relationship of heart disease and cardiac late potentials. Non-invasive recordings of ventricular late potentials are useful in risk stratification of various clinical conditions, in particular, in patients following myocardial infarction. Here a close correlation has been established between cardiac late potentials and spontaneous or induced sustained ventricular tachycardias using programmed electrical stimulation. Cardiac late potentials also appear to be associated with arrhythmic events in patients with cardiomyopathies, and following unsuccessful antitachycardia surgery. Furthermore, recording of abnormal late potentials are associated both with acute rejection after cardiac transplantation and unsuccessful thrombolytic therapy after myocardial infarction. Interestingly, antiarrhythmic drugs have no clear effect on cardiac late potentials.

Arrhythmias, Cardiac↗
PubMed1988

Randomized controlled trial of prophylactic antiarrhythmic therapy in patients with inducible ventricular tachyarrhythmias after recent myocardial infarction.

Survivors of acute myocardial infarction who had inducible sustained ventricular tachyarrhythmias at programmed stimulation 1-4 weeks after infarction were recruited to a randomized pilot trial of Class I antiarrhythmic drugs, in an attempt to determine whether their mortality and risk of spontaneous ventricular tachycardia and fibrillation could be reduced by treatment. Of 136 eligible patients, 96 (71%) joined the trial and 47 were randomized to 'no treatment' and 49 were randomized to 'treatment' (quinidine, disopyramide or mexiletine given to attain 'therapeutic' serum levels). During follow-up, the two groups fared similarly. For the 'treatment' and 'no treatment' groups, the respective 3-year probabilities of remaining incident-free were:cardiac death, 0.91 vs 0.89; instantaneous death + non-fatal ventricular tachyarrhythmias, 0.87 vs 0.87; cardiac death + non-fatal ventricular tachyarrhythmias, 0.83 vs 0.85. The highest risk patients with inducible ventricular tachycardia fared similarly in the 'treatment' and 'no treatment' groups. The respective probabilities of remaining incident-free were: cardiac death, 0.89 vs 0.88; instantaneous death + non-fatal ventricular tachyarrhythmias, 0.79 vs 0.84; cardiac death + non-fatal ventricular tachyarrhythmias, 0.76 vs 0.77. We conclude that prophylactic Class I antiarrhythmic drug therapy with quinidine, disopyramide or mexiletine given to achieve a 'therapeutic' serum level does not appear to alter the prognosis of patients with inducible ventricular tachyarrhythmias after myocardial infarction.

Actuarial Analysis↗
PubMed2003

The Centre for Medical Humanities, Royal Free and University College Medical School, London, England.

The Centre for Medical Humanities is based within the Royal Free and University College Medical School. With a student body of more than 2,000, this large United Kingdom medical school benefits from being a fully integrated component of University College London. With its strong humanities and science faculties, University College London was founded more than 175 years ago to make education available to wider social and religious groups. With this background, it is logistically and ideologically well suited to sustaining a medical humanities program. The Centre's aims are to raise awareness of the field of medical humanities, to develop resources for the academic and teaching communities, and to build a broad and well-grounded educational program supported by sound educational principles and innovative research. Since 1998, the Centre and its predecessor, the Medical Humanities Unit, which was established by a group of medical educators with a diverse range of interests in the arts and humanities, has built interdisciplinary links and collaborative relationships with individuals and institutions within the university and beyond, nationally and internationally. These links and relationships have provided invaluable contributions and stimulus to the Centre's activities. The undergraduate educational program described in this article includes core and optional teaching throughout the curriculum, and a 1-year intercalated Bachelor of Science in Medical Humanities degree. For postgraduates, the Centre offers the United Kingdom's first continuing professional development accredited 2-day course in medical humanities, and an annual residential retreat open only to graduates of the course.

Curriculum↗
PubMed1991

Efficacy and safety of oral poliovirus vaccine and inactivated poliovirus vaccine.

Inactivated poliovirus vaccine (IPV) is the vaccine of choice for protection against paralytic poliomyelitis provided that it is used within the context of a program to increase and sustain the level of uptake to as close to 100% as possible. This means targeting the disadvantaged in society as well as those who have their own pediatrician. The reasons are that enhanced-potency killed polio vaccine is safe, whereas oral poliovirus vaccine (OPV) is associated with a low, but definite, risk of paralysis, especially after the first dose. The immunity, as measured by antibody concentrations, is at least as good as and, in some circumstances, such as in the tropics or for booster doses, better than that provided by OPV. IPV reduces the replication of living poliovirus and produces herd immunity, as exemplified by experience in Sweden and Holland. The immunity, whether induced by OPV or IPV, involves memory cells and is long lasting, as seen by the rapid secondary response to a booster dose. IPV also can be mixed with other vaccine components to provide immunity against an increasing range of childhood infections.

Humans↗
PubMed2006

Imprinting disorders after assisted reproductive technologies.

PURPOSE OF REVIEW: To assess the evidence of an increased risk of imprinting diseases in children born after use of assisted reproductive technologies. RECENT FINDINGS: Imprinting disorders occur when the epigenetic programming during gametogenesis is disturbed, or when this programming is not sufficiently sustained during the process of fertilization and early embryonic development. Ten case or case-reference reports have been published suggesting that compared with reference populations, a higher proportion of children with imprinting diseases were conceived by assisted reproductive technologies. These reports are inconsistent in linking the risk to a specific assisted reproductive technology, and a cytogenetic examination assessing the exact genetic imprinting mechanism was not always provided. Two national systematic follow-up studies on 6052 Danish and 16,280 Swedish in-vitro fertilization children found none and two children with imprinting diseases, respectively. These figures correspond approximately to the expected number of children with imprinting disease from the general population. SUMMARY: The evidence of an increased risk of imprinting diseases in children conceived by assisted reproductive technologies is limited. The published case reports, however, call for a systematic multinational long-term follow-up of children born after assisted reproductive technologies.

Animals↗
PubMed1983

Dissociation of the site of origin from the site of cryo-termination of ventricular tachycardia.

We performed conventional electrogram mapping and cryomapping in dogs with one-week-old experimentally-induced myocardial infarctions and programmed stimulation-induced sustained ventricular tachycardias to assess whether there is a correlation between the "site of origin" and site of cryo-termination of ventricular tachycardia (VT). Electrogram maps showed that 4 of 8 induced sustained VTs were due to macro- and 4 of 8 to microre-entry. Local cooling of the site of origin terminated 4 of 4 microre-entrant VTs, but only 1 of 4 macrore-entrant VTs. In the other 3 macrore-entrant VTs, the sites of cryo-termination were 2, 2.5, and 4 cm distant from the sites of origin. In contrast, cooling of the mid-to-late diastolic portions of the re-entry loops terminated all 8 VTs. These data demonstrate a dissociation of the site of origin from the site of cryo-termination of macrore-entrant VT.

Animals↗
PubMed1986

Effects of different modes of stimulation on the morphology of the first QRS complex following pacing during digitalis-induced ventricular tachycardia: observations in the conscious dog with chronic complete atrioventricular block.

During digitalis-induced, sustained, monomorphic ventricular tachycardia, programmed electrical stimulation was performed and the effect on the first post-pacing QRS morphology was determined. Ventricular tachycardia was induced in nine conscious dogs with chronic complete atrioventricular block by administering digoxin i.v. 0.1 mg/kg given in 1-1 1/2 hour. Spontaneous ventricular tachycardia most frequently had a right bundle branch block morphology and an extreme left axis suggesting an origin in the apex of the left ventricle. Less frequently, a left bundle branch block-like configuration with an intermediate axis was observed, compatible with an origin in the basal part of the right ventricle. Following pacing close to one of these predilection sites, the first post-pacing QRS morphology suggested an origin close to the site of stimulation. Pacing distant from these predilection sites resulted in fusion complexes between electrical activation from these predilection sites and the stimulation site. The amount of fusion depended on interstimulus interval and the number of stimuli. Long interstimulus intervals and few stimuli induced a QRS complex similar to that of the spontaneous tachycardia. The faster and longer the stimulation train, the more the QRS complex became similar to the paced QRS complex. Similar findings were also observed on decreasing the last paced interval only. Our findings suggest that triggered activity is the underlying mechanism for the first post-pacing QRS complex. QRS configuration and the relation between the R-R interval and QRS configuration during tachycardia suggest that triggered activity is also the mechanism for the spontaneously occurring ventricular tachycardia during digitalis intoxication. These observations may have important clinical implications.

Animals↗
PubMed1990

Three-dimensional electrocardiography of cardiac pacing.

Electrocardiographic evaluation of modern pacing systems requires sustained documentation during iterative programming procedures, exercise testing or Holter monitoring. Documentation of a prolonged period of time in standard electrocardiography is based on horizontal compression. The value and limitations of a vertical compression with no change in horizontal chronology and waveform morphology are evaluated. The signal taken from a selected surface lead is introduced into an oscilloscope triggered by an electrocardiographic event along the horizontal axis. A continuous vertical monitoring provides a vertical superimposition of the consecutive cycles. The brightness is proportional to the amplitude of the signal and introduces a third dimension. The three-dimensional technique results in an original image allowing report miniaturization at standard 25 or 50 mm/sec paper speed. Appropriate lead selection and use of the brightness as a marker event allow reliable atrial activity identification. In rate responsive pacing evaluation, the procedure is specifically convenient to full disclosure of the chronotropic response. The main limitation is a high sensitivity to noise during recording. Further developments are to be expected based on computer-assisted electrocardiography.

Cardiac Pacing, Artificial↗