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Biomedical subjects

L Horton

Publications and source records attributed to L Horton.

At least 19 recordsLinked to original sources
PubMed2004

High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial.

OBJECTIVE: To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects. DESIGN: A multicentre, randomised, double blind, clinical trial. SETTING: Four tertiary neonatal units within Australia. PATIENTS: Infants born less than 30 weeks gestation ventilated for more than 48 hours. INTERVENTIONS: Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management. Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation. MAIN OUTCOME MEASURE: Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or doxapram within seven days of caffeine loading. RESULTS: A total of 234 neonates were enrolled. A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7 (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p = 0.01). No difference in adverse effects was detected in terms of mortality, major neonatal morbidity, death, or severe disability or general quotient at 12 months. CONCLUSIONS: This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life.

Caffeine↗
PubMed2001

Adapting the HCUP QIs for hospital use: the experience in New York State.

BACKGROUND: The Agency for Healthcare Research and Quality developed the Healthcare Cost and Utilization Project (HCUP) quality indicators (QIs) in 1994. The Healthcare Association of New York State (HANYS; Albany), which represents more than 500 nonprofit and public hospitals, long-term care facilities, and home health care agencies, has adapted the HCUP QIs since 1997 to produce annual comparative reports for its member hospitals. Specifically designed for internal use, the reports have been well received and have drawn interest from other hospital associations and state health departments. METHODS: The HCUP QIs were applied to the New York State hospital discharge abstract. A risk adjustment model was constructed for each complication measure. Measures of utilization and access to care were adjusted for differences in patient demographics and payer status by indirect standardization. Data are presented in graphic format. Each hospital receives its own report (in both paper copy and CD-ROM) with comparisons to statewide norms, regional averages, and peer group averages. Report prepared for hospital systems include data for each affiliated hospital. CONCLUSIONS: When used appropriately, the HCUP QIs provide valuable information for individual hospitals to assess quality of care and target potential areas for improvement. The HCUP QIs also give hospitals a broad perspective to look beyond their own institutions and develop community-based quality improvement initiatives. Nevertheless, given the limitations that commonly exist with administrative databases and the lack of standard risk adjustment systems, the HCUP QIs are best used for internal purposes and not for public reporting.

Benchmarking↗
PubMed2001

Bms1p, a novel GTP-binding protein, and the related Tsr1p are required for distinct steps of 40S ribosome biogenesis in yeast.

Bms1p and Tsr1p define a novel family of proteins required for synthesis of 40S ribosomal subunits in Saccharomyces cerevisiae. Both are essential and localize to the nucleolus. Tsr1p shares two extended regions of similarity with Bms1p, but the two proteins function at different steps in 40S ribosome maturation. Inactivation of Bms1p blocks at an early step, leading to disappearance of 20S and 18S rRNA precursors. Also, slight accumulation of an aberrant 23S product and significant 35S accumulation are observed, indicating that pre-rRNA processing at sites A0, A1, and A2 is inhibited. In contrast, depletion of Tsr1p results in accumulation of 20S rRNA. Because processing of 20S to 18S rRNA occurs in the cytoplasm, this suggests that Tsr1p is required for assembly of a transport- or maturation-competent particle or is specifically required for transport of 43S pre-ribosomal particles, but not 60S ribosome precursors, from the nucleus to the cytosol. Finally, Bms1p is a GTP-binding protein, the first found to function in ribosome assembly or rRNA processing.

Amino Acid Sequence↗
PubMed1999

Effect of repeated doses of sucrose during heel stick procedure in preterm neonates.

The purpose of this randomized clinical trial was to test the efficacy of repeated versus single dose sucrose to decrease pain from routine heel stick procedures in preterm neonates. Infants (n = 48) in the first week of life with a mean gestational age of 31 weeks received 0.05 ml of 24% sucrose solution or sterile water by mouth (1) 2 min prior to actual lancing of the heel; (2) just prior to lancing, and (3) 2 min after lancing. The single-dose group received sucrose for the first dose and water for the second and third dose; the repeated-dose group received sucrose three times, and the placebo group received only water. The Premature Infant Pain Profile (PIPP) scores were obtained for five 30-second blocks from lancing. Both sucrose groups had lower PIPP scores (single sucrose pain scores, 6.8-8.2, p = 0.07; repeated sucrose pain scores, 5.3-6. 2, p < 0.01) than water (pain scores 7.9-9.1), and in the last block, the repeated dose had lower scores than the single dose (6.2 vs. 8. 2, p < 0.05).

Analgesics↗
PubMed1999

Multiple pathways of prostate carcinogenesis analyzed by using cultured cells isolated from rats treated with N-methyl-N-nitrosourea and testosterone.

Treatment of rats with N-methyl-N-nitrosourea (MNU) and testosterone results in a high incidence of metastasizing dorsolateral prostate tumors. In previous studies, a high frequency (> or = 70%) of a G35 --> A transition mutation at the second position of codon 12 of the Ki-ras oncogene was found in these tumors. This was confirmed in the study reported here, and the frequency of this mutation appeared similar in tumors induced in four different rat strains, regardless of differences in sensitivity among these strains to the induction of prostate cancers by MNU and testosterone: Wistar Furth (62% incidence of grossly visible prostate tumors) > Lobund Wistar (55%) > Fisher 344 (40%) > Copenhagen (37%). A method was developed to isolate and separately culture epithelial and stromal cells from these rat prostate carcinomas. Of 20 primary cell cultures established from histologically confirmed rat prostate carcinomas, 19 (95%) displayed one or more of the following characteristics: the Ki-ras mutation (17 of 20; 85%), anchorage-independent growth in soft agar at early passage (12 of 20; 60%), or tumorigenicity at later passage (eight of eight; 100%). One epithelial cell culture and all five stromal cell cultures established from prostate tumors had none of these characteristics. Epithelial cultures that had the Ki-ras mutation and grew in soft agar constitute the predominant genotype/phenotype (55%), cultures with the mutation that did not grow in soft agar were less frequent (30%), 10% of the cultures had neither characteristic, and only one grew in soft agar but did not have the mutation. These findings suggest that there are at least two and perhaps more different molecular pathways of prostate carcinogenesis in rats treated with MNU plus testosterone. Furthermore, these data suggest that these pathways and the mechanisms determining strain differences in sensitivity to prostate cancer induction are unrelated.

Animals↗
PubMed1996

Developmental changes in response to heelstick in preterm infants: a prospective cohort study.

Twenty-eight preterm infants of 28 weeks gestational age were observed four times over eight weeks in order to determine changes in their pain response. Both routine and sham heelstick procedures were used. Physiological (heart rate and oxygen saturations) and behavioural parameters (three upper facial actions) were used as outcomes. The responses to real heelstick were significantly greater than to sham heelstick for heart rate and all facial actions except one at 28 weeks gestational age, but not for oxygen saturation. The magnitude of response to both real and sham heelstick increased over time. Thus, the older the infant, the more robust and recognisable the response. Since even the youngest infants showed a differential response to pain, professionals caring for such infants need to be able to recognize their more subtle pain responses.

Child Development↗
PubMed1995

Chemiluminescent detection of DNA probes in forensic analysis.

The conditions for hybridization and detection of enzyme-labeled probes have been optimized in our laboratory for use with oligonucleotides coupled to alkaline phosphatase. We have examined several enzyme-linked probe which are complimentary to commonly used variable number of tandem repeats (VNTR) loci to determine the feasibility of using chemiluminescence for routine application in forensic DNA analysis. It was found that a chemiluminescent detection system employing an alkaline phosphatase activated dioxetane in the presence of chemiluminescent enhancers provides a high degree of sensitivity in hybridization protocols with a significant savings in overall filter processing time. The chemiluminescent system achieved equal or greater sensitivity that observed for 32P-labeled probes in much shorter development times. Furthermore, a new chemiluminescent substrate, Lumi-Phos Plus, has recently been investigated and found to further decrease the filter development time for forensic assays.

Alkaline Phosphatase↗
PubMed1995

Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol.

This study determined the incidence of prostate adenocarcinoma following long-term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats.

Adenoma↗
PubMed1995

Diverting managed care Medicaid patients from pediatric emergency department use.

OBJECTIVE: To evaluate the health outcomes of managed care Medicaid children with non-emergent conditions who were not authorized to be seen in the Pediatric Emergency Department (PED) by their primary care provider. DESIGN: Consecutive case surveillance from 6/29/92 to 2/2/93. SETTING: University based PED (17,500 visits/year) in inner city Baltimore. PARTICIPANTS: Cases were MAC children denied authorization to be seen for non-emergent conditions in the PED. Age and complaint matched MAC children were selected from the university based Pediatric Ambulatory Center (PAC) and from non-emergent PED visits (PED-seen) in order to compare utilization rates after denial. INTERVENTION: The Maryland Access to Care (MAC) Medicaid program (started in 12/91) emphasizes primary care and appropriate health care utilization by incorporating the following elements of managed care: assignment to primary care provider, gatekeeping, mandatory enrollment and fee for service. METHODS: Consecutive case surveillance from 6/29/92 to 2/2/93 was used to evaluate the health outcomes of MAC children denied authorization for non-emergent care in a university based PED. One week following denial, a pediatric nurse practitioner contacted the patient's caretaker and the MAC provider to ascertain health outcome. Medicaid claims data was used to compare the six month health care utilization of the denied group to age and complaint matched children seen in the PED (PED-seen) or in a primary care clinic (PAC). RESULTS: 216 MAC patients were not authorized for a PED visit by their MAC providers. 123 (57%) saw their MAC provider within one week of the denied PED visit. 40 (18%) were not seen because their presenting complaint had resolved completely. No adverse health outcomes occurred because of delay in health care delivery. The subsequent ER utilization rate of the denied group was the same as the PED-seen comparison group, and significantly higher than that of the PAC group (P = .002). The denied group was hospitalized at a significantly higher rate relative to these comparison groups (P = .003). CONCLUSIONS: Diverting Medicaid children classified as non-emergent in an ER to their MAC providers can be a safe practice short-term. However, denial of a PED visit has no impact on subsequent ER utilization by Medicaid participants and may be associated with higher hospitalization rate. Gatekeeping in this setting does not necessarily change the health care seeking behavior of these patients.

Baltimore↗
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

Efficacy of albuterol in the management of bronchiolitis.

OBJECTIVE: To examine the efficacy of albuterol (0.15 mg/kg per dose) in the management of bronchiolitis. DESIGN: Randomized, double-blind, placebo-controlled outpatient clinical trial utilizing four study groups: neubulized albuterol, nebulized saline, oral albuterol, and oral placebo. SETTING: Pediatric emergency department and outpatient clinic at University of Maryland in Baltimore. PATIENTS: Eighty-eight infants (median age 5.5 months) being treated for their first episode of wheezing were randomly assigned to nebulized albuterol (n = 22), nebulized saline (n = 23), oral albuterol (n = 19), oral placebo (n = 24). INTERVENTIONS: The nebulized groups received two nebulizations 30 minutes apart, whereas the oral groups received one oral dose. MAIN OUTCOME MEASURES: Respiratory and heart rates, clinical score, oxygen saturation (Spo2), and the infant's state, ie, asleep, awake, or feeding, were recorded at baseline and at 30 and 60 minutes after treatment. RESULTS: Randomization produced equivalent groups in terms of demographics and baseline measures. There were no statistically significant differences in any outcomes among the four treatments, except for oral albuterol, which produced an increase in heart rate (15 beats per minute, P = .005). No differences in the need for additional treatment or hospitalization were observed. Change in the state of the infant during the trial had significant effects on respiratory rate and clinical score. CONCLUSIONS: Albuterol is as effective as oral placebo in the management of bronchiolitis. Past studies supporting the use of albuterol did not control for effects of change in state of the infant and did not use a truly inactive placebo group. This study underscores the importance of these design components in measuring the efficacy of albuterol in infants.

Administration, Inhalation↗
PubMed1993

Perceptions of vaccine efficacy, illness, and health among inner-city parents.

A resurgence of measles in the past decade has focused attention on the limitations of current immunization programs, particularly for inner-city, low-income populations. As part of a larger study of immunization rates, we discussed perceptions of disease severity and vaccine efficacy, as well as the prioritization of the tasks of parenthood, with 40 parents of infants living in inner-city Baltimore to discover their beliefs about immunization. Vaccines were considered only partly successful; susceptibility to chickenpox after vaccination was repeatedly cited as evidence of vaccine failure. Fever was seen as a primary indicator of illness; thus, vaccines were believed to cause, rather than prevent, illness. Immunization was not considered a high-priority parental responsibility. These findings suggest future interventions be aimed at changing parental perceptions of vaccines as ineffective and of fever after immunization as an indicator of illness. Finally, immunizations should be made easily available, even during clinic visits for a child's illness.

Baltimore↗
PubMed1992

Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding.

Despite the importance of the retinoblastoma susceptibility gene to tumor growth control, the structural features of its encoded protein (pRb) and their relationship to protein function have not been well explored. We constructed a panel of deletion mutants of pRb expression vectors and used a biological assay for pRb that measures growth inhibition and morphologic changes in pRb-transfected Saos-2 cells to correlate structural alterations of the pRb coding region with function. We tested the deleted proteins for the ability to bind to viral oncoprotein E1A and to the transcription factor E2F. We also measured the ability of the mutant proteins to become hyperphosphorylated in vivo and to be recognized as substrates in vitro by a cell cycle-regulatory kinase associated with cyclin A. We identified two regions of pRb that are required for E2F binding and for hyperphosphorylation. E1A binding domains partially overlap but are distinct from both of these other two regions. Biological function of pRb is dependent on retention of the integrity of both of these biochemically defined domains. These data support the model that pRb is a transducer of afferent signals (via the kinase that phosphorylates it) and efferent signals (through transcription factor binding), using distinct structural elements. Preservation of both of these features is essential for the ability of pRb to induce growth inhibition and morphologic changes upon reintroduction into transfected cells.

Adenovirus E1A Proteins↗
PubMed1990

Human tumor and normal tissue reactivity of the anti-(breast cancer) monoclonal antibody BA-Br-3 and its similarity to the anti-(epithelial membrane antigen) monoclonal antibody E29.

A mouse monoclonal antibody (BA-Br-3) raised against the breast carcinoma cell line CAMA-1 was previously shown to react with a greater than or equal to 300-kDa globule-like glycoprotein from human milk fat also expressed in the cytoplasm and on the surface of human carcinoma cells of different histological types. In this report the reactivity of this mAb with a large number of normal and malignant human tissues was analyzed using immunoperoxidase techniques. When tested on sections of both fresh-frozen tissues and formalin-fixed, paraffin-embedded tissues, BA-Br-3 reacted with a formalin-resistant antigenic determinant expressed by normal and malignant epithelial cells. Preferential reactivity was observed at the apical portion of ductal epithelial cells in normal breast and in glandular epithelia distributed in several other organs. Reactivity with mucin-like secretions in the lumina of ducts was also found. BA-Br-3 reacted mostly in heterogenous staining patterns with 88% of 49 breast carcinoma specimens tested, regardless of their histological type or whether they were primary or secondary neoplasms. Testing of epithelial malignant tumors other than breast carcinomas with this antibody showed that 127 of 151 (84%) were also reactive. mAb BA-Br-3 and E29 (a commercially available anti-(epithelial membrane antigen) shared very similar staining patterns and distributions of reactivity with breast and other epithelial tumors. However, BA-Br-3 showed a significantly higher percentage of reactivity with melanoma (33% versus 6%, P = 0.003) and a trend toward a higher percentage of reactivity with sarcoma (55% versus 27%, P greater than 0.05). This antibody, therefore, defines a molecule that is a member of the mucin-like epithelial membrane antigen family. Further studies are warranted to determine its usefulness in antibody-directed cancer diagnosis, prognosis, and immunotherapy.

Antibodies, Monoclonal↗
PubMed1990

Binding and functional properties of a mouse-human chimeric monoclonal antibody of the human IgG1 subclass with specificity for human carcinomas.

Recombinant DNA techniques were utilized successfully to join the coding regions for the variable region of a mouse anti-tumor antibody (BA-Br-1) and the human IgG1 constant region for both the light and heavy chains. After insertion into a mouse myeloma host cell line, the chimeric genes were expressed successfully and the resulting antibody (ING-1) was purified. In this study, we describe biochemical, serological, immunohistochemical, and functional properties of the chimeric ING-1 antibody. Analysis of the synthesized antibody revealed that while it was similar in size to the mouse antibody, it had a different pI as determined by isoelectrofocusing. The flow cytometric binding profiles of the new molecule were found to be essentially identical to the parental mouse immunoglobulin. The specificity of the chimeric ING-1 and mouse BA-Br-1 antibodies were compared by extensive immunohistochemical analysis on human normal and tumor tissues. The chimeric antibody retained the same broad carcinoma binding activity, showing strong reactivity with greater than 90% of epithelial tumor tissues, as was previously observed for the mouse BA-Br-1 antibody. The chimeric and mouse antibodies also recognized the same selected normal tissues: primarily glandular epithelia, gastrointestinal mucosa, bile ducts, and thyroid follicles. Analysis of the biological function of the chimeric antibody revealed that it possessed ADCC activity against antigen-bearing tumor targets in vitro which was absent from the mouse form of the antibody. Competent effector cells could be either PBMCs from normal healthy donors, PBMCs from cancer patients receiving LAK/IL-2 therapy, or LAK cells prepared from cancer patients. Enhanced cytotoxicity even in the presence of LAK cell killing was noted with effector cells from the latter two sources. This contrasts sharply with the absence of activity in the same systems when the native murine antibody was used. The in vitro activation of cell-dependent cytolysis observed with the chimeric antibodies when effector cells from both normal and tumor-bearing donors were used strongly suggests that comparable activity would be observed in vivo. These results, along with the broad carcinoma binding activity and minimal normal tissue reactivity, suggest that the ING-1 chimeric antibody may be useful in cancer therapy. The application of the ING-1 chimeric antibody for treatment of tumors thus offers a promising avenue for future research.

Animals↗