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Biomedical subjects

E Holt

Publications and source records attributed to E Holt.

At least 19 recordsLinked to original sources
PubMed1998

Reduced myocardial Na+, K(+)-pump capacity in congestive heart failure following myocardial infarction in rats.

We examined changes in expression and function of the cardiac Na+, K(+)-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated rats after 6 weeks. In the CHF group the ratio of heart weight to body weight was 70% greater compared to sham (*P < 0.05) and all left-ventricular end-diastolic pressures (LVEDP) were above 15 mmHg. The expression of the alpha 1- and beta 1-subunits (mRNA and protein) of the Na+, K(+)-pump was not significantly different in CHF and sham. As compared to sham the alpha 2 isoform, mRNA and protein levels were lower in CHF hearts by 25 and 55%, respectively, whereas the alpha 3 isoform mRNA was greater by 120% in CHF. The alpha 3 protein was not detectable in sham but a prominent band was seen in CHF. Cell volume of isolated cardiomyocytes was 30% larger in CHF. Cardiomyocytes containing the Na+ sensitive fluorescent dye SBFI were loaded to an intracellular Na+ concentration ([Na+]i] of about 140 mM in a K(+)- and Mg(2+)-free medium (140 mM Na+, free Ca2+ of 10(-8) M). To avoid back leak of Na+ and to ensure no voltage effects on the Na+, K(+)-pump extracellular Na+ was subsequently removed, and 6 mM Mg2+ was added to the superfusate, The Na+, K(+)-pump was then reactivated by 10 mM Rb+. SBFI fluorescence ratio decreased mono-exponentially with a time constant (tau) of 191 +/- 15 s in sham (n = 8) and 320 +/- 38 s in CHF (n = 9) rats (P < 0.01). These changes in fluorescence indicate that the maximum rate of decline of [Na+]i from 100 to 35 mM was 39% (P < 0.005) slower in CHF compared to sham, whereas maximum pump rate per cell was not significantly altered (9.0 +/- 0.7 fmol/s in sham and 7.1 +/- 0.7 fmol/s in CHF cells). The [Na+]i which caused 50% pump activation (k0.5) was also not altered in CHF (40 mM in both groups). We conclude that the number of Na+, K(+)-pumps per cell was maintained in CHF but an isoform switch of the alpha 3-replacing the alpha 2-isoform occurred. However, maximum Na+, K(+)-pump rate in terms of rate of change of [Na+]i was significantly attenuated in CHF, most likely as a result of increased cell size.

Animals↗
PubMed1998

Mechanisms of cardiomyocyte dysfunction in heart failure following myocardial infarction in rats.

Available information regarding the cellular and molecular mechanisms for reduced myocardial function after myocardial infarction (MI) is scarce. In rats with congestive heart failure (CHF), we examined cardiomyocytes isolated from the non-infarcted region of the left ventricle 6 weeks after ligation of the left coronary artery. Systolic left-ventricular pressure was reduced and diastolic pressure was markedly increased in the CHF-rats. The cardiomyocytes isolated from the CHF-hearts had increased resting length, reduced fractional shortening by 31% and a 34% increase in time to 90% relaxation compared to sham cells (P<0.01 for all). Peak L-type calcium currents were not significantly changed, but peak calcium transients measured with fura-2 were reduced by 19% (P<0.01). Moreover, the decline of the calcium transients as measured by the time constant of a monoexponential function was significantly increased by 26% (P<0.01). We also examined the contribution of the Ca2+-ATPase of the sarcoplasmic reticulum (SR) in the removal of cytosolic Ca2+ during relaxation by superfusing cells with 1 microM thapsigargin that effectively inhibits the Ca2+-ATPase. Relaxation time in CHF-cells was significantly less prolonged when this drug was used (P<0.01). This suggests that other mechanisms, probably the Na+-Ca2+ exchanger, contribute significantly to the relaxation rate in CHF. Simultaneous measurements of fura-2 transients and mechanical shortening did not reveal any alteration in the calcium-myofilament sensitivity in CHF. Our study clearly shows reduced shortening and prolonged relaxation in cardiomyocytes isolated from non-infarcted region of the left ventricle in heart failure. Moreover, we were able to relate the observed cardiomyocyte dysfunction to changes in specific steps in the excitation-contraction coupling.

Actin Cytoskeleton↗
PubMed1998

Effectiveness of pediatric practice consultation on missed opportunities for immunization.

OBJECTIVE: To evaluate the effectiveness of pediatric practice consultation in reducing missed-opportunity rates at eight pediatric sites in Baltimore, Maryland. The overarching goal was to decrease the occurrence of missed opportunities from 33% to 15% for the first, second, and third diphtheria and tetanus toxoids and pertussis vaccines during visits at which children were eligible for the vaccines. DESIGN: The effect of an in-office educational program alone at four sites is compared with the educational program and a consultation on office vaccination practices at four matched sites. All eight sites received a small grant ($2,000) to fund practice changes. The medical records of children making visits before and after the interventions were audited to determine missed-opportunity rates. The policies and operations and the knowledge, attitudes, and practices of physicians and nurse practitioners at each site were also assessed. RESULTS: The four education-consultation sites experienced a statistically significant 14% net reduction in the missed-opportunity rate relative to the education-only sites. This positive effect, however, was largely due to an increase in missed opportunities at one education-only site. There was a 10% increase in the missed-opportunity rate among the education-only sites and a 4% decrease among the education-consultation sites; neither change was statistically significant. Two of the three sites that reduced missed opportunities were matched health maintenance organizations (HMOs). Shortly after the interventions, both HMOs implemented tracking and follow-up information systems, which were planned before the interventions. CONCLUSIONS: There is no evidence that either the educational program alone or the educational program and consultation combination reduced missed opportunities. The findings suggest that improved tracking and follow-up data systems and vaccination of children at sick visits may reduce missed opportunities.

Baltimore↗
PubMed1998

Opiate disruption of maternal behavior: morphine reduces, and naloxone restores, c-fos activity in the medial preoptic area of lactating rats.

Morphine significantly impairs maternal behavior; naloxone, an opiate antagonist, restores it. Maternal behavior is associated with c-fos expression, an immediate early gene product, in the medial preoptic area (mPOA) of females. In two experiments, the effects of morphine-alone and morphine plus naloxone on the expression of c-fos were examined. On postpartum day 5, females were injected with morphine or saline (experiment 1), and morphine + naloxone or morphine + saline (experiment 2) and placed back in the home-cage, separated from their pups by a wire-mesh partition. A separate group in experiment 1 was injected but not exposed to pups. Processing for c-fos immunohistochemistry commenced, and c-fos positive cells in a proscribed portion of mPOA were counted. Morphine-treated females had fewer c-fos cells in mPOA compared to saline-treated females, and the presence of pups accounted for a significant increase in c-fos-expressing neurons, whereas in females not exposed to pups, morphine treatment did not significantly reduce baseline c-fos expression (experiment 1). Furthermore, naloxone mitigated the effect as morphine + naloxone-treated females expressed more c-fos cells compared to morphine + saline females (experiment 2). Morphine-treated females, therefore, may exhibit reductions in maternal behavior because of relative opiate-induced inactivation of areas of the brain devoted to the regulation of maternal behavior.

Analgesics, Opioid↗
PubMed1998

Initiating the first DTP vaccination age-appropriately: a model for understanding vaccination coverage.

OBJECTIVE: Our earlier research found that the strongest predictor of not being up to date on the full series of immunizations by 24 months is failure to receive the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on time. To learn more about the relationship between successful vaccination during the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life, inclusive) and an infant's early visit to the physician (before 42 days of life), we quantified children's progression through a sequence of provider visits and outcomes. DESIGN: This study analyzed data from 426 children living in the 57 poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the percentage of times a DTP1-AA vaccination, provider missed opportunity, or deferral for a valid contraindication occurred. Relative and attributable risks were computed to assess associations between DTP1-AA vaccination and early visits and missed opportunities. RESULTS: We found the following: 1) Children who made a visit before 42 days of life were more than twice as likely to receive a DTP1-AA vaccination; 2) the missed opportunity rate for children who did not make an early visit was approximately twice that of the early-visit group; and 3) well visits were more likely to result in DTP1-AA immunization than sick visits. Attributable risk calculations show that DTP1-AA vaccination rates could be increased in this population by one third if all infants had an early visit. CONCLUSIONS: Early in-office visits seem to make DTP1-AA vaccination more likely. These rates may be amenable to intervention by increasing early visits and reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to the recommended series may place more emphasis on early visits and result in increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.

Age Factors↗
PubMed1997

Are immunizations an incentive for well-child visits?

OBJECTIVE: To assess the beliefs of parents and the visit patterns of their children to determine whether immunizations act as an incentive to use well-child care. DESIGN AND METHODS: Medical record audits provided data on immunizations and well-child visits. Two questions from a parent interview were used to identify 4 groups of parents: (1) motivated and (2) unmotivated to keep a well-child care appointment regardless of whether immunizations are scheduled, (3) vaccine-motivated and (4) checkup-motivated (parents who were influenced negatively by the prospect of receiving vaccinations). The percentage of children with a visit at each age window for well-child visits and the percentage up-to-date for their immunizations at given ages were compared across the 4 groups. The 4 groups were also compared for other parental attitudes about immunizations and well-child visits, and on sociodemographic and access characteristics. RESULTS: Most (73.3%) of the 502 parents surveyed were classified as motivated and 5% as unmotivated to keep a well-child care appointment regardless of whether an immunization was scheduled. Only 18.3% were categorized as vaccine-motivated and 3.4% as checkup-motivated. For all 4 groups, there was no discernible difference in attendance between immunization and nonimmunization visits. Attendance in the windows for well-child visits and percentage of children up-to-date on immunizations declined with increasing age. CONCLUSIONS: In this inner-city population, attendance patterns at visits did not support the incentive hypothesis. This finding should reassure clinicians that providing immunizations outside of regular well-child care visits will not necessarily decrease attendance at visits for well-child care.

Baltimore↗
PubMed1997

Electrical stimulation of adult rat cardiomyocytes in culture improves contractile properties and is associated with altered calcium handling.

A major limitation in long-term studies of quiescent adult cadiomyocytes in culture has been the decline in contractile properties of the cells over time. Regular contracting cardiomyocyte cultures may represent a more physiological model. The aim of the present study was to investigate the mechanical properties and calcium handling of myocytes after 24 hours of electrical stimulation at 1 Hz. In a random and blind design, stimulated (S) and unstimulated (U) myocytes were examined using an inverted microscope which allows continuous length recordings and measurements of intracellular Ca2+. Fractional shortening examined at 0.25 Hz was 14.67 +/- 0.51% in S cells and was not significantly different from U cells. However, at higher frequencies we found a significant difference in mechanical properties between the two groups. At 2 Hz fractional shortening was 12.03 +/- 0.67% in S cells, but only 8.07 +/- 0.94% U cells (P < 0.05). We were able to abolish the difference between the two groups by stimulating with the beta-adrenergic agonist isoproterenol. Measurements of Ca2+ transients were made at 1 Hz after loading with fura 2-AM. Peak fura 2 ratio was 25.4% greater in S cell compared to U cells. Resting fura ratios were not significantly different. Caffeine-induced transients were greater in S than in U cells. [3H]-ryanodine-binding and Ca(2+)-ATPase contents were not significantly different. In conclusion, we have found that regular electrical stimulation of adult ventricular myocytes in culture, so that they contract rhythmically, enhances both mechanical properties and calcium transients when compared to quiescent myocytes. These results suggest that regular electrical stimulation is important when studying the function of adult ventricular myocytes in culture.

Adenosine Triphosphate↗
PubMed1997

Increased cardiac expression of endothelin-1 mRNA in ischemic heart failure in rats.

OBJECTIVES: Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ETA and ETB receptor subtypes. METHODS: In rats with ischemic heart failure (left ventricular end-diastolic pressure > 15 mmHg) due to left coronary artery ligation. Northern blot analyses were performed on mRNA isolated from cardiac tissues. RESULTS: A substantial upregulation was revealed in all chambers of the failing hearts. Up to 27-fold upregulation (mean 10.6 +/- 4.0, P = 0.002) of left ventricular ET-1 mRNA levels was measured 1 week after myocardial infarction, whereas only a modest upregulation was detected after 6 weeks (mean 2.7 +/- 0.5, P < 0.05). Ribonuclease protection assay revealed 2.8 +/- 0.4-fold higher levels of ET-1 mRNA in the left ventricular area subjected to myocardial infarction compared to the non-infarcted tissue after 1 week. Left ventricular ET-1 mRNA correlated significantly with left ventricular end-diastolic pressure after 1 week (r2 = 0.86, P = 0.007). The ETA and ETB receptor mRNA levels tended to increase 1 week after myocardial infarction although these changes were not statistically significant. CONCLUSIONS: Cardiac ET-1 mRNA levels are increased in ischemic heart failure and correlate significantly with left ventricular end-diastolic pressure 1 week after myocardial infarction. The increase in cardiac ET-1 mRNA is not accompanied by a decrease in ET receptor mRNA.

Animals↗
PubMed1997

Transient Ca2+ overload alters Ca2+ handling in rat cardiomyocytes: effects on shortening and relaxation.

Transient Ca2+ overload in cardiomyocytes occurs during pathophysiological conditions. The aim of the present study was to investigate the effects of transient Ca2+ overload on shortening and relaxation in isolated rat cardiomyocytes electrically stimulated at 0.5 Hz and to examine whether transient Ca2+ overload induces alterations in Ca2+ handling and myofilament sensitivity. Fractional shortening and shortening velocity fell to 79 +/- 5% (P < 0.05) and 78 +/- 4% (P < 0.01) 2 min after exposure to high Ca2+. A transient decrease in resting length, a reduction in relaxation velocity to 86 +/- 7% (P < 0.05), and a prolonged time of relaxation with 8.3 +/- 4.3% (P < 0.05) were also observed. Systolic fluorescence ratio using fura 2 as the Ca2+ indicator fell by 11.0%, and the decline of the fluorescence ratio was prolonged by 29.8%. By applying caffeine, we observed a significant reduction in sarcoplasmic reticulum Ca2+ content after transient Ca2+ overload. A significant reduction in myofilament sensitivity was also observed. In conclusion, the systolic dysfunction observed after transient Ca2+ overload is the result of both decreased systolic Ca2+ and reduced myofilament sensitivity. The relaxation abnormalities are most likely caused by altered Ca2+ handling, since we observed a reduction in the sarcoplasmic reticulum Ca2+ content and a prolongation of the decline of the fura 2 transient.

Adenosine Triphosphate↗
PubMed1996

Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis.

OBJECTIVE: To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis. METHODS: The design was a randomized, double blinded, placebo-controlled trial of dexamethasone (0.2 mg/kg) vs. placebo given intravenously before antibiotic therapy. Patients were recruited from the patient populations at two missionary hospitals. Primary outcome variables were determined before analysis of data. RESULTS: Seventy-two children with sepsis were enrolled in the study. Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables: survival to discharge (83%, dexamethasone group; 89%, placebo group); hemodynamic stability at 48 h (33%, dexamethasone group; 49%, placebo group); median length of hospital stay (11 days, dexamethasone group; 11 days, placebo group); normal at discharge (90%, dexamethasone group; 75%, placebo group); normal at follow-up (90%, dexamethasone group; 72%, placebo group); and afebrile at 48 to 72 h (61%, dexamethasone group; 44%, placebo group). CONCLUSIONS: These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied.

Adolescent↗
PubMed1996

Defining the roles of parathyroid hormone-related protein in normal physiology.

Parathyroid hormone-related protein (PTHrP) was discovered as a result of a search for the circulating factor secreted by cancers which causes the common paraneoplastic syndrome humoral hypercalcemia of malignancy. Since the identification of the peptide in 1982 and the cloning of the cDNA in 1987, it has become clear that PTHrP is a prohormone that is posttranslationally cleaved by prohormone convertases to yield a complex family of peptides, each of which is believed to have its own receptor. It is also clear that the PTHrP gene is expressed not only in cancers but also in the vast majority of normal tissues during adult and/or fetal life. In contrast to the situation in humoral hypercalcemia of malignancy in which PTHrP plays the role of a classical "endocrine" hormone, under normal circumstances PTHrP plays predominantly paracrine and/or autocrine roles. These apparent physiological functions are also complex and appear to include 1) regulation of smooth muscle (vascular, intestinal, uterine, bladder) tone, 2) regulation of transepithelial (renal, placental, oviduct, mammary gland) calcium transport, and 3) regulation of tissue and organ development, differentiation, and proliferation. In this review, the discovery of PTHrP, the structure of its gene and its cDNAs, and the posttranslational processing of the initial translation products are briefly reviewed. Attention is then focused on a detailed organ system-oriented review of the normal physiological functions of PTHrP.

Amino Acid Sequence↗
PubMed1996

The contribution of missed opportunities to childhood underimmunization in Baltimore.

OBJECTIVE: To determine the community-wide incidence of missed opportunities to vaccinate, to describe the clinical settings in which they occur, and to estimate the impact of missed opportunities on immunization coverage. DESIGN AND METHODS: We abstracted outpatient medical records from a random, community-based sample of 2-year-old children whose residence was inner-city Baltimore. The date of each vaccine and the date, diagnoses, and temperature at each visit were collected for 502 children at 98 different provider sites. MAIN OUTCOME MEASURES: Missed opportunities to vaccinate and up-to-date vaccination status. RESULTS: By 24 months of age, 75% of the children had at least one missed opportunity and only 55% were up-to-date for the 4:3:1 series. Missed opportunities occurred at more than one third of eligible visits for each vaccine, including > 20% of preventative care visits. Diagnoses commonly associated with missed opportunities were "well child," otitis media, upper respiratory infection, gastroenteritis, skin infection, and resolving illness. If no missed opportunities had occurred, 73% of the children would have been up-to-date by 24 months. CONCLUSIONS: Missed opportunities occurred commonly at providers serving inner-city children in Baltimore and represent a major factor in underimmunization. Reduction of missed opportunities by accurate screening at all visits and adherence to the contraindication guidelines is a provider-based, low-cost method to increase immunization coverage.

Baltimore↗
PubMed1996

Parental attitudes do not explain underimmunization.

OBJECTIVE: This article describes the results of a community-based study to determine the effect of family knowledge and attitudes on the immunization rates of a random sample of children younger than 2 years in the poorest census tracts of Baltimore. DESIGN AND METHODS: The two sources of data were (1) parent interviews that provided data on knowledge, attitudes, and beliefs related to immunization and sociodemographic characteristics, and (2) medical record audits from which data on immunization status were obtained. The protection motivation theory, a model of behavioral change, was used to select the variables to assess the relation of parental attitudes with immunization status. A multivariate logistic regression analysis included only variables found to be significantly associated with immunization outcome in the preliminary analysis. RESULTS: Mothers were well informed and generally had favorable attitudes toward immunizations. Immunization status was more strongly associated with the sociodemographic characteristics of the children than with the protection motivation theory variables. Only two protection motivation theory variables were associated with more than one immunization outcome. The children of mothers who perceived that timing of vaccination did not matter were less likely to be immunized than children of care takers who thought that it did matter and children whose parents believed in the safety of multiple immunizations were less likely to be immunized than children whose parents did not hold this belief. CONCLUSIONS: In this study, parents' attitudes and beliefs had little effect on their children's immunization levels. Interventions intended to heighten parental awareness about immunization may have little impact. In poor urban neighborhoods, African-American children whose mothers are young, have multiple siblings, and do not use the Women, Infants and Children program may be at highest risk for delayed immunization.

Adult↗
PubMed1995

The demand for childhood immunizations: results from the Baltimore Immunization Study.

In spite of the net social benefits of childhood vaccines, a substantial proportion of American children do not receive their full complement of immunizations by their second birthday. Designing policies and programs that increase the rate of completed immunizations in preschool children requires an understanding of the factors which contribute to the timely receipt of immunizations. In this paper, we estimate a model of demand for immunizations for preschool children. Our results suggest that household resources, the child's usual source of care, and other "convenience factors" significantly influence the successful completion of the immunization schedule.

Adult↗
PubMed1994

Maternal IgG1 and IgA antibody to V3 loop consensus sequence and maternal-infant HIV-1 transmission.

Maternal-infant transmission of HIV-1 occurs in 13-40% of pregnancies. Studies on transmission of maternal immunity to HIV antigens have used antigens from viruses not representative of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgG1 antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (p = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.

Amino Acid Sequence↗
PubMed1994

Do provider practices conform to the new pediatric immunization standards?

OBJECTIVE: Standards for pediatric immunization practices were issued by the Centers for Disease Control and Prevention, Atlanta, Ga, in May 1992. This article provides baseline data on immunization practices related to eight of the standards. DESIGN: Survey of pediatric providers before publication of the standards. SETTING: Baltimore, Md. PARTICIPANTS: Forty of the 41 health centers, clinics, and private practices serving children in designated high-risk census tracts participated in the survey. One hundred seventy-three of the 251 eligible physicians and nurse practitioners at the sites responded. MAIN OUTCOME MEASURES: Conformity with the eight standards was measured as a percentage of either sites or physicians and nurse practitioners across the sites. RESULTS: Conformity with the standards varied, ranging from nearly universal conformity with the need to educate parents and guardians about immunizations (standard 5) to less than 3% for simultaneous administration of all vaccine doses when a child is first eligible (standard 8). For most of the standards, considerable variability was found between and within public and private sites. CONCLUSIONS: Providers often followed practices that did not conform to the new standards (prior to issuance). Some of the standards are ambiguous and require clarification before they can be fully applied. The impact of the standards on immunization rates and pediatric primary health care has yet to be tested empirically.

Baltimore↗
PubMed1994

Social and psychological costs of preventive child health services in Haiti.

Much of the research on determinants of health service utilization has focused on economic and cognitive variables which influence preventative health behavior. Our ethnographic study of maternal perceptions of the barriers and incentives to immunization use in Haiti underscores the importance of 'hidden' social and psychological costs of utilization, such as embarrassment, fear, child care difficulties, and competing demands on maternal time. Findings from focus group interviews with mothers, individual interviews with health care providers, and observation at health posts identified five categories of maternal factors (competing priorities, low motivation, socioeconomic constraints, fears about health or social consequences, knowledge and folk beliefs) and five categories of system factors (accessibility, acceptability, availability, accommodation, affordability) which can deter immunization completion. The discussion focuses on how these factors influence maternal decision-making regarding use of preventive child health services. More attention is needed on the psychosocial costs of health behavior in developing country settings.

Adult↗