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Biomedical subjects

Douglas R Rosing

Publications and source records attributed to Douglas R Rosing.

17 recordsLinked to original sources
PubMed2007

Exercise capacity of cardiac asymptomatic hereditary hemochromatosis subjects.

PURPOSE: The exercise capacity of cardiac asymptomatic subjects with hereditary hemochromatosis (HH) has not been well described. In this study, we tested whether the iron overload associated with HH affected exercise capacity with a case control study design. METHODS: Forty-three HH and 21 normal control subjects who were New York Heart Association functional class I underwent metabolic stress testing using the Bruce protocol at the clinical center of the National Institutes of Health. Exercise capacity was assessed with minute ventilation (.VE), oxygen uptake (.VO2), and carbon dioxide production (.VCO2) using a breath-by-breath respiratory gas analyzer. RESULTS: The exercise capacity of HH subjects was not statistically different from that of control subjects (exercise time 564 +/- 135 vs 673 +/- 175 s, P = 0.191; peak .VO2 29.6 +/- 6.4 vs 32.5 +/- 6.7 mL.kg(-1).min(-1), P = 0.109; ventilatory threshold 19.0 +/- 3.4 vs 21.0 +/- 5.0 mL.min(-1).kg(-1), P = 0.099; data are for HH vs control subjects). Ventilatory efficiency was comparable between groups (.VE/.VCO2 slope 23.7 +/- 3.2 vs 23.4 +/- 4.2, P = 0.791). No significant correlation between the markers of iron levels and the markers of exercise capacity was noted. Iron depletion by 6-month phlebotomy therapy in 18 subjects who were newly diagnosed did not affect exercise testing variables (exercise time 562 +/- 119 vs 579 +/- 118 s, P = 0.691; peak .VO2 29.5 +/- 3.7 vs 29.1 +/- 4.7 mL.kg(-1).min(-1), P = 0.600; ventilatory threshold 18.5 +/- 2.8 vs 17.9 +/- 3.8 mL.kg(-1).min(-1), P = 0.651; data are from before and after phlebotomy therapy). Abnormal ischemic electrocardiographic responses and complex arrhythmias were more frequently seen in HH subjects. CONCLUSIONS: The aerobic exercise capacity of asymptomatic HH subjects seems not to be statistically different from that of normal subjects. The iron levels do not seem to affect exercise capacity in asymptomatic HH subjects.

Adult↗
PubMed2006

Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome.

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.

Adult↗
PubMed2006

Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis.

Patients with hereditary hemochromatosis (HH) have been reported to develop diastolic functional abnormalities detectable by echocardiography, but it is unknown whether these occur in asymptomatic subjects. Thus, this study tested whether echocardiographic left ventricular (LV) relaxation abnormalities are detectable in subjects with asymptomatic HH. Forty-three asymptomatic subjects with HH (C282Y homozygosity in the HFE gene) and 21 age- and gender-matched control subjects without known HFE mutations underwent echocardiography with comprehensive diastolic functional evaluations. Subjects with HH were in New York Heart Association functional class I and consisted of 22 newly diagnosed patients (group A) and 21 chronically phlebotomized subjects with stable iron levels (group B). Group A subjects showed significant iron overload compared with group B subjects and controls (group C) (ferritin 1,164 +/- 886 [p <0.05 vs groups B and C], 128 +/- 262, and 98 +/- 76 microg/L and transferrin saturation 79 +/- 19% [p <0.05 vs groups B and C], 42 +/- 21%, and 26 +/- 10% for groups A, B, and C, respectively). Echocardiographic evaluation revealed (1) no statistically significant abnormalities of Doppler LV relaxation in HH groups; (2) significant augmentation of atrial contractile function in subjects with HH compared with controls, which was not correlated with iron levels and treatment status; and (3) the preservation of overall LV systolic function in HH groups. In conclusion, the results of this study suggest that the augmentation of atrial contraction appears to be an early detectable echocardiographic cardiac manifestation of abnormal diastolic function in asymptomatic subjects with HH, which may reflect undetectable subclinical LV relaxation abnormalities.

Atrial Function, Left↗
PubMed2006

Left ventricular systolic function during stress echocardiography exercise in subjects with asymptomatic hereditary hemochromatosis.

There is no information available on left ventricular (LV) systolic function and the response to stress echocardiography in asymptomatic subjects with hereditary hemochromatosis (HH). To evaluate this topic, 43 asymptomatic subjects with HH homozygous for the C282Y HFE gene mutation (22 untreated subjects [group A] and 21 long-term treated subjects [group B]) were compared with 21 age- and gender-matched normal volunteers negative for HFE mutations. Contractile reserve, as a measure of LV systolic function, was assessed using continuous echocardiographic imaging and electrocardiography during supine bicycle exercise. Nineteen subjects in group A had repeat tests after 6 months of induction phlebotomy therapy to assess the effect of iron removal. Exercise performance and hemodynamic variables of supine bicycle exercise were comparable between subjects with HH and controls. LV contractile reserve of asymptomatic subjects with HH was not impaired at either a 75-W submaximal exercise level (mean +/- SD difference in ejection fraction from baseline 13.8 +/- 6.2%, 11.5 +/- 6.8%, and 13.4 +/- 7.8% in groups A, B, and C, respectively; p = NS for all by analysis of variance) or at peak exercise (difference in ejection fraction from baseline 18.9 +/- 6.9%, 18.4 +/- 7.8%, and 20.3 +/- 8.1% in groups A, B, and C, respectively; p = NS for all by analysis of variance). However, the incidence of abnormal ischemic stress electrocardiographic responses was more frequent in subjects with HH as a whole (33%) compared with normal subjects (10%). Stress imaging revealed no regional wall motion abnormalities, suggesting that these were false-positive results. Iron removal by induction phlebotomy did not affect stress echocardiographic performance. In conclusion, LV systolic function during exercise in asymptomatic subjects with HH is preserved, and 6-month induction phlebotomy does not affect stress echocardiographic performance.

Echocardiography, Stress↗
PubMed2006

Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma.

PURPOSE: The histone deacetylase inhibitor depsipeptide (FK228) has activity in patients with cutaneous or peripheral T-cell lymphoma. Electrocardiogram abnormalities, thought to be a class effect, were observed in preclinical animal studies and phase I testing and led to the incorporation of intensive cardiac monitoring in an ongoing efficacy trial. PATIENTS AND METHODS: This report summarizes the cardiac monitoring of 42 patients enrolled and treated on a phase II trial with depsipeptide. Cardiac evaluations included serial electrocardiograms to evaluate T-wave, ST segment, and QT interval effects and serial serum cardiac troponin I levels and left ventricular ejection fraction (LVEF) evaluations to exclude myocardial damage. RESULTS: Cardiac studies from 282 cycles and 736 doses of depsipeptide included 2,051 electrocardiograms and 161 LVEF evaluations. Although T-wave flattening (grade 1) or ST segment depression (grade 2) was observed in more than half of the electrocardiograms obtained posttreatment, these electrocardiogram abnormalities were not associated with elevation of cardiac troponin I or with altered left ventricular function. No significant changes in LVEF were observed, even in 16 patients treated for >or=6 months and regardless of prior anthracycline exposure. Posttreatment electrocardiograms had a mean heart rate-corrected QT interval prolongation of 14.4 milliseconds compared with baseline. Electrolyte replacement has been instituted to mitigate potential untoward effects. CONCLUSION: The data obtained in this study show that the administration of depsipeptide is not associated with myocardial damage or impaired cardiac function. The potential effect of heart rate-corrected QT interval prolongation remains under study.

Adult↗
PubMed2006

Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community-acquired myocarditis.

The purpose of this study was to describe and compare the cardiac magnetic resonance (CMR) characteristics of myocarditis caused by high dose interleukin-2 (7 patients) with community-acquired myocarditis (14 patients). A total of 21 patients with suspected myocarditis and elevated cardiac enzymes underwent cine CMR followed by delayed enhancement. The mean ejection fraction was mildly decreased in both groups. The location, pattern, and extent of DE were similar in both groups of patients. The CMR similarities between these two populations suggest that cytokine-mediated cytotoxicity may play an important role in community-acquired myocarditis.

Aged↗
PubMed2006

Prolongation of the cardiac QTc interval in Turner syndrome.

Anatomic anomalies of the cardiovascular system occur in approximately 50% of individuals with Turner syndrome (TS), with the specific genetic cause(s) for the heart defects still unknown. Because congenital heart disease may be associated with conduction system abnormalities, we compared electrocardiograms (ECGs) in 100 women with TS and 100 age-matched female controls. Women with TS were significantly more likely to demonstrate left posterior fascicular block (p < 0.005), accelerated AV conduction (p < 0.006), and T wave abnormalities (p < 0.006). The PR interval was significantly shorter (137 +/- 17 vs. 158 +/- 18 ms, p < 0.0001) and the rate-corrected QT interval (QTc) significantly longer in women with TS than in controls (423 +/- 19 ms vs. 397 +/- 18 ms; p < 0.0001). Twenty-one women with TS but no controls had a QTc greater than 440 ms. We found no statistically significant relation between body habitus, cardiac dimensions, evidence of congenital heart disease, or metabolic parameters and the incidence of ECG abnormalities or QTc duration in TS. Cardiac conduction and repolarization abnormalities appear to be intrinsic features of TS, suggesting that deletion of the second sex chromosome has more profound effects on the cardiovascular system than previously recognized, and that ECG analysis should be included in evaluating and monitoring patients with Turner syndrome.

Adolescent↗
PubMed2006

Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome.

BACKGROUND: We recently reported that electrocardiographic abnormalities are common in adults with monosomy X (Turner syndrome), but this issue has not been investigated in girls with Turner syndrome. PATIENTS AND METHODS: We analyzed electrocardiograms in 78 girls with Turner syndrome and 50 age-matched control girls. The girls with Turner syndrome had additional cardiac and metabolic evaluations. RESULTS: Girls with Turner syndrome were more likely to demonstrate > or = 1 electrocardiographic findings including right axis deviation, right ventricular hypertrophy, accelerated atrioventricular conduction, T-wave abnormalities, and a prolonged rate-corrected QT interval. The right-sided findings were associated with partial anomalous pulmonary venous connection, but the etiology of the other findings remains unknown. The rate-corrected QT interval was significantly longer in girls with Turner syndrome (431 +/- 22 vs 407 +/- 21 milliseconds). Twenty-eight girls with Turner syndrome but only 2 controls had a rate-corrected QT interval above the reference range. We found no correlation between body habitus, cardiac dimensions, or metabolic parameters and the rate-corrected QT interval duration in girls with Turner syndrome. CONCLUSIONS: Cardiac conduction and repolarization abnormalities seem to affect both young girls and adults with Turner syndrome equally, suggesting that electrophysiologic defects are intrinsic to the syndrome and indicating that electrocardiogram analysis should be included in evaluating and monitoring even the youngest patients with Turner syndrome. Attention to the rate-corrected QT interval is important, because some common medications may further prolong this interval and increase the risk of arrhythmias.

Adolescent↗
PubMed2005

Pediatric Fabry disease.

BACKGROUND: Fabry disease is an underdiagnosed, treatable, X-linked, multisystem disorder. OBJECTIVES: To test the hypothesis that quality of life and sweating are decreased among pediatric patients with Fabry disease, compared with control subjects, and to provide quantitative natural history data and novel clinical end points for therapeutic trials. DESIGN: Prospective, cross-sectional, observational study. SETTING: Referral to the National Institutes of Health. PARTICIPANTS: Twenty-five male children with Fabry disease (mean age: 12.3 +/- 3.5 years) and 21 age-matched control subjects. MAIN OUTCOME MEASURES: Quality of life (measured with the Child Health Questionnaire) and sweating (assessed with the quantitative sudomotor axon reflex test). RESULTS: Quality of life scores for pediatric patients <10 years of age with Fabry disease, compared with published normative values, were 55 +/- 17 vs 83 +/- 19 for bodily pain and 62 +/- 19 vs 80 +/- 13 for mental health. Bodily pain scores for patients > or =10 years of age were 54 +/- 22 vs 74 +/- 23. Sweat volume in the Fabry disease group was 0.41 +/- 0.46 microL/mm2, compared with 0.65 +/- 0.44 microL/mm2 in the control group. Renal function, urinary protein excretion, and cardiac function and structure were normal for the majority of patients. The 3 patients with residual alpha-galactosidase A activity > or =1.5% of normal values were free of cornea verticillata and had normal serum and urinary globotriaosylceramide levels. All other children had glycolipid levels comparable to those of adult patients with Fabry disease. Acroparesthesia and cardiac abnormalities were generally present before anhidrosis and proteinuria. Mapping of the missense mutations on the crystallographic structure of alpha-galactosidase A revealed that the mutations were partially surface-exposed and distal to the active site among individuals with residual enzyme activity. Mutations associated with left ventricular hypertrophy (defined as left ventricular mass index of >51 g/m2.7) were localized near the catalytic site of the enzyme. CONCLUSIONS: Despite the absence of major organ dysfunction, Fabry disease demonstrates significant morbidity already in childhood. We have identified important, potentially correctable or preventable, outcome measures for future therapeutic trials. Prevention of complications involving major organs should be the goal for long-term specific therapy.

Adolescent↗
PubMed2005

Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome.

OBJECTIVES: Turner syndrome (TS) is associated with congenital cardiovascular defects (CCVDs), most commonly bicuspid aortic valve (BAV) and aortic coarctation (COARC), congenital renal anomalies, and fetal lymphedema. It has been theorized that compressive or obstructive effects of fetal lymphedema may actually cause cardiovascular and renal dysmorphogenesis in TS. The objective of this study was to determine whether there is a specific association between a history of fetal lymphedema and CCVDs in monosomy X, or TS, independent of karyotype or general severity of the phenotype. METHODS: This was a prospective study of 134 girls and women who have TS (mean age: 30 years) and were clinically evaluated for evidence of fetal lymphedema, classified as central (signified by the presence of neck webbing) or peripheral (current or perinatal, or dysplastic fingernails). The presence of BAV and/or COARC was detected by magnetic resonance imaging combined with echocardiography, and renal anomalies were determined by ultrasound. RESULTS: There is a strong association between developmental central lymphedema, signified by neck webbing, and the presence of BAV (chi2 = 10) and COARC (chi2 = 8). The association between webbed neck and CCVDs was independent of karyotype. There was, in contrast, no significant association between renal anomalies and webbed neck or CCVDs. CONCLUSIONS: The strong, statistically significant association between neck webbing and the presence of BAV and COARC in TS suggests a pathogenetic connection between fetal lymphatic obstruction and defective aortic development. The presence of neck webbing in TS should alert the clinician to the possibility of congenital cardiovascular defects.

Adult↗
PubMed2004

Graded blood pressure reduction in hypertensive outpatients associated with use of a device to assist with slow breathing.

To study the effects of device-guided breathing on office systolic blood pressure (SBP), five centers randomized 149 untrained hypertensives (50% male, age 59+/-10 years, baseline blood pressure 150+/-9/86+/-9 mm Hg, 77% taking drug therapy). One half received a device to guide slow breathing; all received a home blood pressure monitor and only simple, written instructions. The changes in office SBP (adjusted for office-to-home difference in baseline SBP and accumulated time spent in slow breathing, guided and measured by the device) were significantly (p<0.001 for trend) correlated with accumulated time spent in slow breathing. Greater decreases in SBP (-15.0+/-1.8 vs. -7.3+/-1.9 mm Hg) were observed for those who spent more (vs. less) than 180 minutes over 8 weeks in slow breathing, as well as those who just monitored their blood pressure at home (-9.2+/-1.6 mm Hg). Thus, even without training, hypertensive patients who receive a device to guide slow breathing significantly lowered their office SBP if the total time spent in slow breathing over 8 weeks exceeded a "threshold" value of 180 minutes.

Adult↗