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Biomedical subjects

S E Lipshultz

Publications and source records attributed to S E Lipshultz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea.

Individual cancer patients differ in their nausea/vomiting response to chemotherapy. It is not known why patients receiving the same chemotherapy have different severity of side effects. Several lines of research implicate the autonomic nervous system (ANS) in the development of chemotherapy-induced nausea. We examined the association between autonomic reactivity and the level of nausea experienced following chemotherapy in 20 patients with ovarian cancer treated with cisplatin or carboplatin who received the same antiemetic. We applied eight common non-invasive clinical tests of autonomic function prior to inpatient chemotherapy treatment, 2 h after treatment and again 24 h following treatment. Two hours after chemotherapy and before any nausea was reported by the patients, the nine patients who subsequently experienced high levels of nausea had a greater overall percentage of abnormal clinical ANS tests than the 11 patients who subsequently developed low levels of nausea (P < 0.01). Twenty-four hours after treatment, the overall number of abnormal autonomic tests remained non-significantly higher than at the pretreatment baseline for the high nausea group. Demographic and clinical characteristics were not related to chemotherapy-induced nausea in this sample. Autonomic reactivity appears to be related to the development of nausea following chemotherapy. Further investigation of ANS involvement in chemotherapy-induced nausea could increase understanding of nausea etiology and potentially lead to the prediction of susceptible patients.

Aged↗
PubMed1999

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease.

OBJECTIVES: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Base Sequence↗
PubMed1999

Genetics of neonatal cardiomyopathy.

Cardiomyopathies, primary disorders of the myocardium, are a leading cause of morbidity and mortality in children and adults, and these disorders are responsible for a significant percentage of sudden cardiac deaths and cardiac transplants. Neonatal cardiomyopathies commonly are associated with poor prognosis, and the underlying etiology of this disorder differs considerably from cardiomyopathies in older children, adolescents, and adults with similar phenotypes. In this review, the major causes of neonatal cardiomyopathy are described.

Cardiomyopathies↗
PubMed1999

Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin.

PURPOSE: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. MATERIALS AND METHODS: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. CONCLUSION: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.

Animals↗
PubMed1999

Cardiac complications in children with human immunodeficiency virus infection. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group, National Heart, Lung, and Blood Institute.

OBJECTIVE: Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. METHODOLOGY DESIGN: Prospective cohort (Group I) and inception cohort (Group II) study design. SETTING: A volunteer sample from 10 university and public hospitals. PARTICIPANTS: Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. INTERVENTIONS: According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12- or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. OUTCOME MEASURES: Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) </=25% after 6 months of age, CHF, or treatment with cardiac medications. RESULTS: CARDIAC ABNORMALITIES: In Group I children (older cohort), the prevalence of decreased LV function (FS </=25%) was 5.7% and the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. The prevalence of echocardiographic LV enlargement (LV end-diastolic dimension z score >2) at the time of the first echocardiogram was 8. 3%. The cumulative incidence of LV end-diastolic enlargement was 11. 7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS </=25% after 6 months of age, CHF, or treatment with cardiac medications) in Group I. After excluding these prevalent cases, the 2-year cumulative incidence of cardiac impairment was 19.1% among Group I children and 80.9% remained free of cardiac impairment after 2 years of follow-up. Within Group II (neonatal cohort), the 2-year cumulative incidence of decreased LV FS was 10.7% in the HIV-infected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II infected versus uninfected children (8.7% vs 2.1%). The cumulative incidence of CHF and/or the use of cardiac medications was 8.8% in Group II infected versus 0.5% in uninfected subjects. The 1- and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 12.8%, respectively, with 87.2% free of cardiac impairment after the first 2 years of life. MORTALITY: In the Group I cohort, the 2-year cumulative death rate from all causes was 16.9% [95% CI: 11.7%-22. 1%]. The 1- and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%, respectively. In the Group II cohort, the 2-year cumulative death rate from all causes was 16.3% [95% CI: 8.8%-23.9%] in the HIV-infected children compared with no deaths among the 463 uninfected Group II children. Two of the 4 Group II children with CHF died during the 2-year observation period and 1 more died within 2 years of the diagnosis of CHF. The 2-year mortality rate after the

Adolescent↗
PubMed1998

Prevalence of congenital cardiovascular malformations in children of human immunodeficiency virus-infected women: the prospective P2C2 HIV Multicenter Study. P2C2 HIV Study Group, National Heart, Lung, and Blood Institute, Bethesda, Maryland.

OBJECTIVES: The purpose of the study was to assess the effects of maternal HIV-1 (human immunodeficiency virus) infection and vertically transmitted HIV-1 infection on the prevalence of congenital cardiovascular malformations in children. BACKGROUND: In the United States, an estimated 7000 children are born to HIV-infected women annually. Previous limited reports have suggested an increase in the prevalence of congenital cardiovascular malformations in vertically transmitted HIV-infected children. METHODS: In a prospective longitudinal multicenter study, diagnostic echocardiograms were performed at 4-6-month intervals on two cohorts of children exposed to maternal HIV-1 infection: 1) a Neonatal Cohort of 90 HIV-infected, 449 HIV-uninfected and 19 HIV-indeterminate children; and 2) an Older HIV-Infected Cohort of 201 children with vertically transmitted HIV-1 infection recruited after 28 days of age. RESULTS: In the Neonatal Cohort, 36 lesions were seen in 36 patients, yielding an overall congenital cardiovascular malformation prevalence of 6.5% (36/558), with a 8.9% (8/90) prevalence in HIV-infected children and a 5.6% (25/449) prevalence in HIV-uninfected children. Two children (2/558, 0.4%) had cyanotic lesions. In the Older HIV-Infected Cohort, there was a congenital cardiovascular malformation prevalence of 7.5% (15/201). The distribution of lesions did not differ significantly between the groups. CONCLUSIONS: There was no statistically significant difference in congenital cardiovascular malformation prevalence in HIV-infected versus HIV-uninfected children born to HIV-infected women. With the use of early screening echocardiography, rates of congenital cardiovascular malformations in both the HIV-infected and HIV-uninfected children were five- to ten-fold higher than rates reported in population-based epidemiologic studies but not higher than in normal populations similarly screened. Potentially important subclinical congenital cardiovascular malformations were detected.

Cohort Studies↗
PubMed1998

Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group.

BACKGROUND: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood. METHODS AND RESULTS: A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up. CONCLUSIONS: Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.

AIDS Dementia Complex↗
PubMed1998

Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity.

The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulative doses of doxorubicin (7 mg/kg) that induced only minimal histological alterations in myocytes. Concentrations of cTnT were further elevated, coincident with reduced immunohistochemical staining, in SHRs given 10-12 mg/kg doxorubicin. Thus, monitoring serum levels of cTnT can detect doxorubicin-induced myocyte damage in SHR and may prove useful for the noninvasive evaluation of this toxicity in humans.

Animals↗
PubMed1998

Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia.

PURPOSE: Late anthrocycline cardiotoxicity after treatment for childhood cancer is common and often progressive. A safe anthracycline dose that will not result in late cardiac abnormalities has not been established due to the limited dose ranges used in existing studies. PATIENTS AND METHODS: To determine the relationship between cumulative anthracycline dose and late cardiotoxicity, we performed echocardiograms on 189 survivors of childhood acute lymphoblastic leukemia a median of 8.1 years (range, 2.0 to 23.4) after completion of anthracycline therapy. Patients were treated according to protocols that used widely varying cumulative anthracycline doses, but comparable nonanthracycline chemotherapy. Patients were divided into four groups based on the city of treatment and cumulative anthracycline dose: Copenhagen, 0 to 23 mg/m2 (n = 32); Boston, 45 mg/m2 (n = 17); Copenhagen, 73 to 301 mg/m2 (n = 53); and Boston, 244 to 550 mg/m2 (n = 87). Left ventricular dimension and fractional shortening were adjusted for sex and age or body-surface area through use of a control population (n = 296), and then compared among the four groups. RESULTS: Mean left ventricular dimension was significantly increased in the high-dose Boston group (observed:predicted value, 4.57 cm:4.45 cm; P = .002) and significantly higher than in the two Copenhagen groups. In the three lower-dose groups, there was no significant increase in mean left ventricular dimension, and the groups were not significantly different from each other. Similarly, the mean left ventricular fractional shortening was significantly depressed in the high-dose Boston group (observed:predicted value, 29.0%:33.8%; P = .0001) and significantly lower than in the three lower-dose groups. CONCLUSION: Depressed left ventricular fractional shortening and left ventricular dilatation were uncommon years after treatment of childhood leukemia when cumulative anthracycline doses were < or = 300 mg/m2.

Adolescent↗
PubMed1998

Epidemiology of anthracycline cardiotoxicity in children and adults.

Anthracyclines, potent cytotoxic agents used to treat a broad spectrum of malignancies, are limited in their use by an attendant risk of cardiotoxicity. Malignancies affect all age ranges, and anthracyclines are used in all age ranges, thereby exposing a broad population of patients to the development of heart disease. For some treated patients, anthracyclines affect cardiac muscle, resulting in cardiomyopathy. The type and degree of cardiomyopathy, as well as when during or after treatment the condition occurs, are dependent on what risk factors are present. Age is a major risk factor. Children and adults may develop restrictive and dilated cardiomyopathy. The length of subsequent survival and amount of subsequent somatic growth may influence late anthracycline-associated cardiac outcome. Early cardiotoxicity, occurring during or within 1 year of completion of treatment, is the largest risk factor for the development of late cardiotoxicity, which occurs beyond a year of completion of treatment. Risk factors, which appear to be specific for early cardiotoxicity in children, include black race, trisomy 21, and the use of amsacrine therapy after anthracycline therapy. More cardiotoxic effects are seen in survivors of childhood cancer, the longer from completion of treatment a patient is followed. Cumulative as well as peak anthracycline doses affect adults and children alike, and cardiotoxicity occurs early and late. In adults, left ventricular contractility is affected by anthracyclines. Children may manifest impairment of left ventricular contractility and increased afterload due to thinning of left ventricular walls. Patients with an early presentation of depressed left ventricular contractility are likely to show progression of cardiac disease with time. In addition, female gender appears to affect early and late cardiotoxicity in both adults and children, although this risk factor has been described predominantly in the survivors of childhood cancer. Thus, although anthracycline chemotherapy has improved overall survivorship of patients with cancer, there is a significant risk of cardiotoxicity associated with this class of drugs.

Adult↗
PubMed1997

Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury.

BACKGROUND: Biochemical markers have not been routinely used in children at risk for myocardial damage. Yet, because of somatic growth and the duration of survival, a low level of myocardial damage may ultimately be of more consequence in children than in adults. METHODS AND RESULTS: We investigated the utility of cardiac troponin T (cTnT) blood levels (CARDIAC T ELISA Troponin T, Boehringer Mannheim Corp) in 51 consecutively sampled patients from 1 day to 34 years of age (median=5.7 years) undergoing cardiovascular (n=19) or noncardiovascular (n=17) surgery or who received doxorubicin for acute lymphoblastic leukemia (ALL) (n=15). Minimum detectable cTnT elevations were 0.03 ng/mL. cTnT was measurable in children of all ages with myocyte damage. In patients who underwent cardiovascular surgery, a correlation was noted between a score of increasing surgical severity and the mean level of postoperative cTnT (r=.79, P<.0001). Postoperative cTnT levels were elevated in children who completed cardiovascular surgery with an open chest compared with those with a closed chest (P=.0083). In addition, cTnT levels before cardiovascular surgery predicted postoperative survival (P=.007). cTnT elevations were observed after initial doxorubicin therapy for ALL. The magnitude of elevation predicted left ventricular dilatation (r=.80 when variables were treated as continuous, P=.003) and wall thinning (r=.61, P=.044) 9 months later. CONCLUSIONS: Elevations of blood cTnT in children relate to the severity of myocardial damage and predict subsequent subclinical and clinical cardiac morbidity and mortality.

Adolescent↗
PubMed1997

Nutritional status and cardiac mass and function in children infected with the human immunodeficiency virus.

Malnutrition, skeletal muscle wasting, and changes in cardiac muscle mass and function have been described in children infected with the human immunodeficiency virus (HIV). This report analyzes the relation of nutritional status to cardiac muscle mass and function in HIV-infected children. Thirty-six children with symptomatic HIV infection underwent simultaneous anthropometric and echocardiographic evaluations before antiretroviral therapy or supplemental feedings. Nutritional measurements included weight, height, triceps skinfold thickness, and arm muscle circumference. Cardiac measurements included left ventricular mass, contractility, end-diastolic dimension, fractional shortening, blood pressure, and heart rate. In a cross-sectional analysis, children infected with HIV were significantly below age-adjusted standards for height (P = 0.0001), weight (P = 0.0001), triceps skinfold thickness (P = 0.001), and arm muscle circumference (P = 0.04). Left ventricular mass normalized to body surface area was below standard, but contractility was normal. Correlation analyses found an inverse relation between left ventricular mass and weight z score (r = -0.45, P = 0.01), height z score (r = -0.47, P = 0.006), and arm muscle circumference percentile (r = -0.51, P = 0.003). An inverse relation was also found between heart rate and weight z score (r = -0.47, P = 0.007) and arm muscle circumference percentile (r = -0.46, P = 0.007). In malnourished children with HIV infection, a paradoxical relation exists between nutritional status and cardiac muscle mass. The inverse relation between heart rate and nutritional status may suggest altered metabolic rates with possible increased sympathetic tone.

Anthropometry↗
PubMed1997

Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience.

PURPOSE: To determine the incidence of clinical cardiotoxicity from anthracycline chemotherapy in children with cancer and to identify associated risk factors. PATIENTS AND METHODS: The study population consisted of 6,493 children with cancer who had received anthracycline chemotherapy on Pediatric Oncology Group (POG) protocols from 1974 to 1990. Cardiotoxicity, defined as congestive heart failure not due to other causes, abnormal measurements of cardiac function that prompted discontinuation of therapy, or sudden death from presumed cardiac causes, was determined by a review of protocol records. RESULTS: Cardiotoxicity was confirmed in 106 patients (1.6%): 58 had congestive heart failure, 43 had changes in measures of cardiac function that prompted the discontinuation of therapy, and five died suddenly from presumed cardiac causes. In a multivariate analysis, factors that contributed to the relative risk (RR) of toxicity were a cumulative anthracycline dose > or = 550 mg/m2 of body-surface area (RR = 5.2), maximal dose > or = 50 mg/m2 (RR = 2.8), female sex (RR = 1.9), black race (RR = 1.7), presence of trisomy 21 (RR = 3.4), and exposure to amsacrine (RR = 2.6). Cardiotoxicity within 1 year after the completion of anthracycline treatment (early cardiotoxicity) represented 89.5% of all cases. CONCLUSION: Early clinical cardiotoxicity in children treated with anthracycline is rare. A high maximal dose, or cumulative dose of anthracycline, female sex, black race, presence of trisomy 21, and treatment with amsacrine increase the risk for anthracycline-associated cardiotoxicity.

Adolescent↗
PubMed1996

Clinical approach to genetic cardiomyopathy in children.

BACKGROUND: Cardiomyopathy (CM) remains one of the leading cardiac causes of death in children, although in the majority of cases, the cause is unknown. To have an impact on morbidity and mortality, attention must shift to etiology-specific treatments. The diagnostic evaluation of children with CM of genetic origin is complicated by the large number of rare genetic causes, the broad range of clinical presentations, and the array of specialized diagnostic tests and biochemical assays. METHODS AND RESULTS: We present a multidisciplinary diagnostic approach to pediatric CM of genetic etiology. We specify criteria for abnormal left ventricular systolic performance and structure that suggest CM based on established normal echocardiographic measurements and list other indications to consider an evaluation for CM. We provide a differential diagnosis of genetic conditions associated with CM, classified as inborn errors of metabolism, malformation syndromes, neuromuscular diseases, and familial isolated CM disorders. A diagnostic strategy is offered that is based on the clinical presentation: biochemical abnormalities, encephalopathy, dysmorphic features or multiple malformations, neuromuscular disease, apparently isolated CM, and pathological specimen findings. Adjunctive treatment measures are recommended for severely ill patients in whom a metabolic cause of CM is suspected. A protocol is provided for the evaluation of moribund patients. CONCLUSIONS: In summary, we hope to assist pediatric cardiologists and other subspecialists in the evaluation of children with CM for a possible genetic cause using a presentation-based approach. This should increase the percentage of children with CM for whom a diagnosis can be established, with important implications for treatment, prognosis, and genetic counseling.

Brain Diseases↗