Fetal Cardiology Bioethics: An Innovative New Curriculum for Cardiology Trainees.

Decision-making in fetal cardiology is fraught with ethical issues yet education in bioethics for trainees is limited or nonexistent. In this innovation report, we describe the development of a fetal cardiology bioethics curriculum designed to address this gap. The curriculum was developed to supplement the core curriculum for cardiology fellows and fetal cardiology subspecialty trainees. The series combines didactic and interactive teaching modalities and contains 5 key components: (1) introduction to bioethics and its role in fetal cardiology, (2) counseling and pathways for compassionate terminal care, (3) case vignette-based ethical analysis and discussion cases, (4) fetal counseling considerations for shared decision-making and recommendations, (5) facilitated communications role play. The curriculum was refined using session evaluations from end users. This report describes the innovative curriculum as a starting point for further incorporation and study of bioethical education in pediatric cardiology and fetal training programs.

Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006.

BACKGROUND: Rising incidences of Kawasaki disease (KD) have been reported worldwide. Reported herein are the results of 4 triennial KD surveillances conducted in Ontario. METHODS: Between 1995 and 2006 all hospitals in Ontario were asked on 4 occasions to identify all patients with discharge diagnoses of KD and report incident cases. RESULTS: The latest surveillance identified 697 new KD patients (100% response rate) for a total of 2378 KD patients through all 4 surveillances. Yearly incidence was 26.2/100,000 for <5 years old, 6.7/100,000 for 5-9 years old and 0.9/100,000 for 10-14 years old. KD incidence significantly increased from 1995 to 2006, although the increase seemed to plateau between the 3rd and 4th surveillance. There was an increase in the proportion of patients diagnosed with incomplete KD and a significant reduction in the rate of coronary artery abnormalities, possibly due to better disease recognition and treatment. Hospitals reporting <20 cases per surveillance were found to be more likely to report cases with incomplete KD. These patients were also less likely to be treated with i.v. immunoglobulin and aspirin but were more likely to be treated with antibiotics, suggesting uncertainties regarding diagnosis and management of KD patients in those centers. CONCLUSIONS: The incidence of KD in Ontario is possibly one of the highest outside of Asia and has been rising since 1995. Although the most recent surveillance demonstrated improved cardiac outcomes, treatment delays or absence thereof continue to be a problem. Effective diagnosis and prompt treatment remain critical aspects of KD management.

Outcome and growth potential of left heart structures after neonatal intervention for aortic valve stenosis.

OBJECTIVES: The purpose of this study was to determine trends of growth of left heart structures after intervention for neonatal aortic valve stenosis. BACKGROUND: The growth potential of left heart structures in neonatal aortic valve stenosis after relief of obstruction might influence risk for subsequent outcomes. METHODS: From 1994 to 2004, 53 patients underwent neonatal (< or =30 days old) balloon aortic valve dilation. Factors associated with time-related outcomes (death, reintervention, aortic valve replacement) and longitudinal changes in normalized left heart dimensions were sought. RESULTS: The median age at intervention was 3.5 days (range 1 to 30 days). During a median follow-up of 3.2 years ranging up to 10.9 years, there were 31 reinterventions on the aortic valve in 21 (40%) patients and 7 deaths (13%). The presence of moderate or severe left ventricular (LV) endocardial fibroelastosis was the only independent predictor for time-related mortality (hazard ratio 22.1; p = 0.004), and a smaller initial aortic valve annulus z-score was a significant independent predictor for aortic valve replacement (hazard ratio 0.63 per 1-U change; p = 0.007). Aortic valve annulus, aortic sinus, and LV dimension z-scores significantly increased over time, whereas mitral valve z-scores remained below normal. The structure's initial z-score and concomitant size of other left heart structures were significant independent factors associated with subsequent z-scores. CONCLUSIONS: There is potential catch-up growth of the aortic valve and LV over time for neonates after intervention for aortic valve stenosis. However, the continued hypoplasia of the mitral valve warrants further consideration in the long-term management of these patients.

Cost-effectiveness analysis of a proposed public health legislative/educational strategy to reduce tap water scald injuries in children.

OBJECTIVE: To determine the cost effectiveness of a public health legislative/educational strategy to reduce tap water scalds in children less than 10 years of age. DESIGN: Cost-effectiveness analysis conducted from the government perspective over a 10-year time horizon. POPULATION: Children under 10 years of age in Ontario, Canada INTERVENTIONS: Legislation to set thermostat settings on new domestic water heaters to lower temperatures (maximum 49 degrees C) plus annual educational notices to utility customers versus status quo. MAIN OUTCOME MEASURES: The burden of tap water scalds, healthcare resource utilization, the cost and effectiveness of the proposed intervention, and the probabilities assigned to health outcomes were modeled in a decision analysis based on population-based data, patient charts, and the published medical literature. All costs and health outcomes beyond 1 year were discounted at 3%. RESULTS: An estimated 182 children under 10 require medical care for tap water scald injuries annually in Ontario (13.98 per 100,000). Of these, 65 require emergency department (ED) care only (median cost $C149 per injury), 103 require ED care with clinic follow-up ($C577 per injury), 14 require hospital admission ($C5203 per injury), and two require surgical skin grafting ($C28,526 per injury). The estimated cost of the intervention was $C51,000 annually, with a projected 56% reduction in tap water scald injuries. Over 10 years, the intervention group would show total costs of $C1.17 million and 704 scalds, compared with $C1.65 million and 1599 scalds in the status quo group. Therefore, the intervention would be cost saving, with an incremental ratio of $C531 saved per scald averted. Sensitivity analyses showed that the intervention would remain cost saving through a wide range of variable estimates. CONCLUSIONS: Legislation to lower thermostat settings on domestic water heaters plus annual educational notices to utility customers would generate cost savings while reducing the morbidity from tap water scalds in children.

Association between physical activity, adiposity, and lipid abnormalities in children with familial hyperlipidemia.

BACKGROUND: The benefits of physical activity in children have been studied extensively; however, its role in children with familial hyperlipidemia (FH) is unknown. OBJECTIVE: To determine associations between physical activity, adiposity, and lipid profiles in children with FH. DESIGN: A physical activity questionnaire was completed by 147 children with FH. Correlations between activity levels, body mass index (BMI), and fasting lipid profiles were determined. RESULTS: The mean age of patients was 12.5+/-3.2 years with a mean total cholesterol of 6.17 mmol/l (238 mg/dl), low-density lipoprotein-cholesterol of 4.43 (171), high-density lipoprotein-cholesterol of 1.08 (42), and triglyceride levels of 1.51 (134). Patients had greater weight for height indices than normal, with a mean BMI z score of +0.90+/-1.30 SD (P<0.001 versus normal), and with 21% of the participants being more than 2 SD above normal. Higher BMI z scores significantly correlated with higher triglyceride levels (r=0.33; P<0.0001) and greater time spent in sedentary pursuits (r=0.24; P=0.004), in particular watching television (r=0.26; P=0.003). The increased time that other family members spent in physical activity significantly correlated with a lower BMI z score (r=-0.21; P=0.01) of the patient and greater time spent in physical activity (r=0.24; P=0.003). There was no association between patients' physical activity levels and lipid profile or BMI. CONCLUSION: Similar to the general population, children with FH are also at risk of becoming overweight. Increased adiposity significantly correlated with the greater sedentary activities of the patient, lower physical activities of the family, and higher triglyceride levels. Physical activity levels of the patient correlated with family activity levels.

Outcomes of uncomplicated aortic valve stenosis presenting in infants.

BACKGROUND: The management of uncomplicated aortic valve stenosis presenting with critical obstruction in infants continues to be associated with significant morbidity and mortality. However, not all infants have critical obstruction, and outcomes spanning the broader spectrum of disease severity are less well defined. METHODS: In a 12-year period, 55 infants (<3 months of age) were seen with aortic valve stenosis and with anatomy suitable for biventricular repair. Clinical, echocardiographic, angiographic, management, and outcome data were reviewed. RESULTS: Status at presentation (median age 6 days) included signs of congestive heart failure in 20 patients, cardiovascular collapse in 5 patients, and an asymptomatic heart murmur in 30 patients. The initial echocardiogram showed reduced left ventricular function in 26% of patients, with a mean peak instantaneous gradient of 69 +/- 30 mm Hg in patients with normal function. There were 5 deaths (9%), all in patients with poor ventricular function. The initial intervention was balloon valvotomy in 24 patients and surgical valvotomy in 20 patients, with 11 patients having no intervention to date. The freedom-from-intervention rate was 69% at age 1 week, 58% at 1 month, 36% at 3 months, and 28% at 1 year. Patients without cardiovascular collapse, normal left ventricular function, and gradients <60 mm Hg at presentation (n =1 9) had better survival and longer freedom from intervention than patients with poor ventricular function or gradients >or=60 mm Hg (n = 36, P =.0001). CONCLUSION: Most infants with aortic valve stenosis receive intervention, although this may be safely delayed in selected patients with lower initial gradients and good left ventricular function.

Expression of an artificial polypeptide with a repeated tripeptide glutamyl-tryptophanyl-lysine in Saccharomyces cerevisiae.

AIMS: Artificial genes, which encode 48 or 64 repeats of a tripeptide, glutamyl-tryptophanyl-lysine have been cloned to the yeast expression vector pAM82 containing the PHO5 promoter and expressed in Saccharomyces cerevisiae AH22. METHODS AND RESULTS: When the yeast cells harbouring recombinant plasmids pALTG6-2 and pALTG4-4 were derepressed in Burkholder minimal medium (Toh-e, A., Ueda, Y., Kakimoto, S.I. and Oshima, Y. (1973) Journal of Bacteriology113, 727-738) containing low phosphate (0.03 g l-1 KH2PO4 and 1.5 g l-1 KCl), the expression was the highest after 24 h induction and the artificial polypeptides were synthesized to about 10% (pALTG6-2) and 14% (pALTG4-4) of the total cell protein. CONCLUSIONS: The artificial polypeptides produced in yeast were made to react with the rabbit antiserum against the polypeptide purified from Escherichia coli and found only in the pellet fraction of cell lysates, indicating the formation of inclusion body. Artificial polypeptide consisting of Glu-Trp-Lys may be useful as partial supplement in food and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of single cell enriched with homopolymers of an essential amino acid in yeast might be an important tool of supplementing cereal diets and feed grain rations and could be used as means for improvement of the amino acid profile of single cell protein and production of pharmaceutical peptides.

Optimization of submerged culture conditions for the production of angiotensin converting enzyme inhibitor from Flammulina velutipes.

The angiotensin-converting enzyme (ACE) inhibitory effect was tested in the culture broth from submerged mycelial cultures of 20 basidiomycetes. The ACE inhibitory effect of culture broth from Flammulina velutipes strain 414 was the highest (52.8%), followed by Lentinus edodes strains 2 (44.4%) and 16 (41.3%). Nutritional requirements for the production of ACE inhibitory substance from F. velutipes were studied. Sucrose, ammonium acetate, and glutamic acid were chosen for the maximum production of ACE inhibitory substance. The optimal medium composition was (g/l): sucrose 20, ammonium acetate 5, glutamic acid 2, KH(2)PO(4) 3, MgSO(4).7H(2)O 0.8, and yeast extract 0.5. Under optimal culture conditions, the ACE inhibitory effect was more than 80%.

Focusing through an interface: scanning and localizing the intensity.

Focusing light through an interface leads to an aberrated intensity distribution that is highly extended with a relatively low peak intensity. We present a method, using a well-chosen annular aperture, that can greatly improve the localization of the intensity about a prescribed point on the axis. Also, the intensity at that point can be increased significantly. By continuously varying the annulus radii, we can scan the intensity peak through the second medium. This localization and scanning method has possible applications in three-dimensional imaging and lithography.

[Treatment of hypertension in preventive health care. Experiences from a high-risk strategy in the first cardiovascular examinations]. / Blodtrykksbehandling i det forebyggende helsearbeid. Erfaringer fra en høyrisikostrategi i de første hjerte- og karundersøkelsene.

A subset of the total population aged 35-49 years was screened for elevated blood pressure in three Norwegian counties. As part of a high risk approach in the prevention of risk factors for CVD, the persons identified as having elevated blood pressure were referred for intervention and treatment. The follow-up time varied from three to five years. Even though there was an overall improvement of blood pressure during the follow-up period, a comparison showed no overall significant difference in the magnitude of blood pressure reduction between those that participated in the intervention program and those that did not. The paper raises questions about the quality of the intervention and about the high risk approach in general as a model for prevention.

Purification of anti-ulcer polysaccharides from the roots of Bupleurum falcatum.

A water-soluble crude polysaccharide fraction (BR-1) prepared from the root of Bupleurum falcatum L. (Japanese name = Saiko) prevented HCl/ethanol induced ulcerogenesis in mice significantly. BR-1 was fractionated into four polysaccharide fractions (BR-2, BR-3, BR-4, and BR-5) by the addition of cetyltrimethylammonium bromide, and the strongly acidic polysaccharide fraction BR-2 showed the most potent inhibition of gastric lesion formation. When BR-2 was further fractionated by anion-exchange chromatography, the most potent anti-ulcer activity was observed in the pectin-like polysaccharide, bupleuran 2IIc. Bupleuran 2IIc was homogeneous as determined by electrophoresis and gel filtration. Bupleuran 2IIc was composed mainly of galacturonic acid with small proportions of arabinose, rhamnose, and galactose, and its average relative molecular mass was estimated to be 63,000 d. BR-2 lost most of its activity after treatment with periodate or digestion with endo-polygalacturonase indicating that the polygalacturonan region and/or the molecular mass may contribute to activity.

Race, family income, and low birth weight.

The relations among race, family income, and low birth weight were examined using information obtained from the National Longitudinal Survey of Youth, which conducted yearly interviews with a nationally representative sample of young women identified in the late 1970s. Data were available for these women and their offspring from 1979 through 1988. Maternal education, maternal age, age/parity risk, marital status, and smoking during pregnancy served as covariates in cross-sectional and longitudinal analyses. The risk of low birth weight among births to black women and white women who were poor was at similarly high levels regardless of whether poverty was determined prior to study entrance or during the study period. Longitudinal analyses showed an exceptionally large increase in risk of low birth weight among children born to women whose prior pregnancy ended in a low-birth-weight infant. These two findings emphasize the importance of factors antecedent to the pregnancy in the genesis of low birth weight.

Structural characterization of an anti-complementary pectic polysaccharide from the roots of Bupleurum falcatum L.

An anti-complementary pectic polysaccharide (BR-2-IIb), isolated from the roots of Bupleurum falcatum L., has an average molecular weight of 36,000 (gel filtration), and was subjected to methylation analysis before and after carboxyl-reduction, digestion with endo-polygalacturonase, base-catalysed beta-elimination, and partial acid hydrolysis. BR-2-IIb consisted mainly of galacturonic acid, arabinose, rhamnose, and galactose in the molar ratios 13.0:2.1:1.4:1.0 and contained a large enzyme-sensitive polygalacturonan region. The enzyme-resistant region (PG-1) was rich in neutral sugars and contained a backbone of 4-linked GalA and 2-linked Rha to which a highly branched arabinogalactan was attached to position 4 of some 2-linked Rha units. Partial acid hydrolysis of BR-2-IIb gave Ara-(1----3)-Ara, Ara-(1----4)-Arap, Ara-(1----5)-Araf, Ara-(1----6)-Gal, Gal-(1----4)-Gal, GalA-(1----2)-Rha, GalA-(1----4)-Rha, GalA----Rha----Rha, Gal----Rha----Rha, and GlA-(1----6)-Gal in addition to (1----4)linked oligogalacturonides. The anticomplementary activity of BR-2-IIb was enhanced by de-esterification, but carboxyl-reduction decreased the activity.

Self-reported data: reliability and role in determining program effectiveness.

This study was conducted to assess the reliability of self-reported hospitalization data, as well as the appropriateness of using self-reported data in evaluating the effectiveness of the Maine Ambulatory Diabetes Education and Follow-Up (ADEF) program. A Maine Blue Cross/Blue Shield (BC/BS) inpatient claims file was used as the reference source to verify self-reported hospitalization data. For a sample of 99 BC/BS subscribers who attended the ADEF program, 77% of the study participants accurately self-reported hospitalization patterns over a 12-mo time period before attending the education program, and 81% of the participants accurately self-reported hospitalization patterns during a posteducation follow-up time period. The reference BC/BS claims data documented a reduction in hospitalizations for the study participants similar to that reported using the ADEF self-reported hospitalization data. The Maine Diabetes Control Project used the self-reported hospitalization data in combination with selected reference claims data to secure third-party reimbursement for the Maine ADEF Program.