Search PubMed⌕ Search

Biomedical subjects

E Holt

Publications and source records attributed to E Holt.

At least 19 recordsLinked to original sources

Scaling exponent predicts defibrillation success for out-of-hospital ventricular fibrillation cardiac arrest.

BACKGROUND: -Defibrillator shocks often fail to terminate ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OOHCA), and repeated failed shocks can worsen the subsequent response to therapy. Because the VF waveform changes with increasing duration of VF, it is possible that ECG analyses could estimate the preshock likelihood of defibrillation success. This study examined whether an amplitude-independent measure of preshock VF waveform morphology predicts outcome after defibrillation. Methods and Results-Clinical data and ECG recordings from an automated external defibrillator were obtained for 75 subjects with OOHCA in a suburban community with police first responders and a paramedic-based emergency medical system. An estimate of the fractal self-similarity dimension, the scaling exponent, was calculated off-line for the VF waveform preceding shocks. Success of the first shock was determined from the recordings. Return of pulses and survival were determined by chart review. The first shock resulted in an organized rhythm in 43% of cases, and 17% of cases survived to hospital discharge. A lower mean value of the scaling exponent was observed for cases in which the first defibrillation resulted in an organized rhythm (P:=0.004), for cases with return of pulses (P:=0.049), and for cases surviving to hospital discharge (P:<0.001). Receiver operator curves revealed the utility of the scaling exponent for predicting the probability of restoring an organized rhythm (area under the curve=0.70) and of survival (area under the curve=0.84). CONCLUSIONS: -The VF waveform in OOHCA can be quantified with the scaling exponent, which predicts the probability of first-shock defibrillation and survival to hospital discharge.

Aged↗

Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after MI.

Excitation-contraction (E-C) coupling was investigated in rat hearts 6 wk after induction of myocardial infarction (MI) by ligation of the left coronary artery. Heart weight was increased by 74% and left ventricular end-diastolic pressure was 23 +/- 2 mmHg in MI compared with 8 +/- 2 mmHg in sham-operated controls (Sham, P < 0.001). Cell shortening was measured in voltage-clamped myocytes at 36 degrees C. In solutions where Cs(+) had been replaced by K(+), the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells. Verapamil (20 microM) blocked L-type Ca(2+) current and reduced contraction in Sham cells by approximately 50% (P < 0.01) but did not decrease contraction significantly in MI cells at test potentials above +10 mV. Verapamil-insensitive contractions were blocked by Ni(2+) (5 mM). Na(+)/Ca(2+) exchange current was doubled in MI compared with Sham cells at test potentials between -20 and +80 mV (P < 0.05), whereas mRNA and protein expression increased by 30-40%. Finally, voltage dependence of contraction was bell shaped in Na(+)-free solutions, but contraction was significantly increased in MI cells over a wider voltage range (P < 0.05). The insensitivity to Ca(2+) channel block in MI cells may result from an increased contribution of the Na(+)/Ca(+) exchanger to triggering of E-C coupling. These results suggest significant changes in E-C coupling in the hypertrophy and failure that develop in response to extensive MI.

Animals↗

The effect of parental monetary sanctions on the vaccination status of young children: an evaluation of welfare reform in Maryland.

OBJECTIVE: To determine whether financial sanctions to Aid to Families With Dependent Children (AFDC) recipients can be used to improve vaccination coverage of young children. DESIGN: Randomized controlled trial. SETTING: Six AFDC jurisdictions in Maryland. INTERVENTION: Recipients of AFDC were randomized to the experimental or control group of the Primary Prevention Initiative. Families in the experimental group were penalized financially for failing to verify that their children received preventive health care, including vaccinations; control families were not. PARTICIPANTS: Children aged 3 to 24 months from assigned families were randomly selected for the evaluation (911 in the experimental, 864 in the control, and 471 in the baseline groups). MAIN OUTCOME MEASURES: Up-to-date for age for diphtheria and tetanus toxoids and pertussis (DTP), polio, and measles-mumps-rubella (MMR) vaccines; missed opportunities to vaccinate; and number of visits per year. ANALYSIS: Comparisons among baseline and postimplementation years 1 and 2. RESULTS: Vaccination coverage of children was low. Less than 70% of children were up-to-date for age for polio and MMR vaccines; slightly more than 50% were up-to-date for DTP vaccine. Up-to-date rates differed little among baseline, experimental, and control groups. Over time, there was a decrease in missed opportunities, and more children made at least 1 well-child visit; however, neither improvement resulted in a change in vaccination status. CONCLUSIONS: The Primary Prevention Initiative did not contribute to an increase in vaccination coverage among these children. Minimal economic sanctions alone levied against parents should not be expected substantially to affect vaccination rates.

Aid to Families with Dependent Children↗

Thyroid hormone control of contraction and the Ca(2+)-ATPase/phospholamban complex in adult rat ventricular myocytes.

Thyroid hormones may have important long-term effects on cellular Ca2+ handling in the heart. We investigated isolated adult rat cardiomyocytes in a primary culture exposed (T3-cells) or not exposed to (control cells) 10(-8) M triiodothyronine (T3) for 48 h. Northern blot analysis revealed reciprocal alterations in the expression of SERCA2 and phospholamban. The ratio of the SERCA2/phospholamban signal was approximately 10 times higher in the T3-cells as compared with the control cells (P < 0.05). Phospholamban protein content was significantly reduced by 33% but SR-Ca(2+)-ATPase protein content was not significantly altered in T3-cells. These results were associated with functional alterations measured by an inverted microscope equipped to monitor fluorescence at two excitation wavelengths as well as cell shortening by a video edge detection unit. The peak calcium transients as measured by fura-2 acetoxymethyl ester (AM) were increased significantly during stimulation at 0.25 and 0.5 Hz in T3-cells compared with control cells (P < 0.05). The monoexponential decline of the fura-2 transient was significantly faster at all frequencies in the T3-cells as compared with control cells (P < 0.05). Interestingly, we observed blunted responses to both isoproterenol stimulation and post rest potentiation in the T3-cells. The intracellular level of sodium as represented by SBFI-AM was significantly lower in the T3-cells compared with the control cells (P < 0.05). The increased SR-Ca(2+)-ATPase/phospholamban ratio and decrease in phospholamban protein content in T3-treated cells was reflected in a parallel increase of contraction and calcium transients and more rapid Ca2+ reuptake, but the post-rest potentiation and response to isoproterenol were reduced.

Animals↗

The relation of parent and provider characteristics to vaccination status of children in private practices and managed care organizations in Maryland.

OBJECTIVES: This study sought to identify provider practices and policies in private pediatric settings that relate to vaccination status, controlling for the characteristics of the children served. METHODS: Vaccination data came from the medical records of 709 randomly selected 2-year-old children at 18 private practices and managed care organizations in Maryland, family data from 466 telephone interviews with the children's parents, and provider characteristics from 18 site questionnaires and 42 individual physician and nurse practitioner questionnaires. Logistic regression and generalized estimating equations were used to estimate the relation of provider characteristics to vaccination status. Three age-appropriate (AA) and two up-to-date (UTD) vaccination status variables characterized successful vaccination. RESULTS: Approximately 70% of the study children were up-to-date by age 2 years for the full vaccination series, excluding hepatitis B vaccine. Family demographic characteristics were the strongest correlates of undervaccination. Neither parents' knowledge and attitudes about immunization nor the children's insurance coverage was statistically related to vaccination status. Site reminder or follow-up systems and provider perceptions about appointment scheduling and receipt of vaccine information from health departments were positively related to vaccination. Concern for liability was associated with a reduced odds of age-appropriate and up-to-date vaccination. CONCLUSIONS: Family demographics strongly correlate with vaccination status; however, they are generally not modifiable. This study's findings encourage providers to operate a tracking system, to remain current on immunization recommendations, to use all clinical encounters to screen and vaccinate children, and to ensure the availability and convenience of vaccination services.

Age Factors↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗