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Biomedical subjects

M C Allen

Publications and source records attributed to M C Allen.

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

Trends and racial differences in birth weight and related survival.

OBJECTIVE: In the past two decades, infant mortality rates in the United States declined in African-American and White populations. Despite this, racial disparities in infant mortality rates have increased and rates of low birth weight deliveries have shown little change. In this study, we examine temporal changes in birth weight distributions, birth weight specific neonatal mortality, and the birth weight threshold for an adverse risk of survival within both racial groups in order to explore the mechanisms for the disparities in infant mortality rates. METHOD: Single live births born to South Carolina resident mothers between 1975 and 1994 and considered White or African-American based on the mother's report of maternal race on the birth certificate were selected for investigation. We define the birth weight threshold for adverse survival odds as the birth weight at which 50% or more of infants in the population died within the first month of life. RESULTS: Despite significant increases in very low birth weight percentages, neonatal mortality rates markedly declined. Birth weight specific neonatal mortality decreased for both races, although greater reductions accrued to White low birth weight infants. By the end of the study period, the birth weight at which over 50% of newborns died within the first month of life was 696 g for Whites and 673 g for African-Americans. DISCUSSION: The ongoing decline in neonatal mortality is mainly due to reductions in birth weight specific neonatal mortality, probably related to high-risk obstetric and neonatal care. Technological developments in these areas may have differentially benefited Whites, resulting in an increasing racial disparity in mortality rates. Moreover, the relatively greater and increasing mortality risk from postmaturity and macrosomia in infants of African-America mothers may further exacerbate the racial gap in infant mortality.

Female↗
PubMed1999

The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage.

The rectal carriage of glycopeptide-resistant Enterococcus spp. (GRE) had been established at approximately 50% in a series of prevalence studies on a busy haematological malignancy unit. The aim of this study was to reduce the chance of patients acquiring GRE. A prospective three-phase sequential study was performed. In Phase 1, the acquisition rate of GRE detectable by rectal swab was measured without any intervention for a period of 4 months. For the following 8 months (Phase 2), the first-line treatment for febrile neutropenic episodes was changed from monotherapy with ceftazidime to piperacillin/tazobactam. In addition, an intense education programme was introduced to improve hygiene to reduce the risk of case-to-case spread. In the final 4 months (Phase 3), ceftazidime was again used as the first-line antimicrobial, while continuing the same level of training in relation to hygiene. The carriage of GRE was measured from rectal swabs done weekly. During the initial 4 months, at any time, 40-50% of patients in the unit were colonized with GRE, and 43 of 75 (57%) new patients initially negative for GRE acquired it within 6 weeks of their admission. In Phase 2, 25 patients out of 129 (19%) acquired GRE, with the acquisition rate falling progressively so that in the last 3 months, only one new patient acquired GRE (logrank comparison of probabilities for cohort 1 vs cohort 2b: P < 0.0001). A return to ceftazidime in Phase 3 was associated with a return of the risk of acquiring detectable GRE colonization, despite continued hygiene teaching and surveillance, with 21 out of 58 patients (36%) acquiring GRE (cohort 1 vs cohort 3: P = 0.08). Glycopeptide usage was not reduced during the period of the study. Clinical cases were seen only in Phases 1 and 3. Although the reduction in the risk of acquiring GRE may have been due in part to hygiene practices as well as to the change in antimicrobial usage, or may have occurred spontaneously for other reasons, the return of the problem with the reintroduction of ceftazidime strongly suggests that this antibiotic was responsible for encouraging the acquisition of detectable GRE.

Adolescent↗
PubMed1998

Agonist and antagonist effects of histamine H3 receptor ligands on 5-HT3 receptor-mediated ion currents in NG108-15 cells.

The ability of histamine H3 receptor ligands to interact with 5-HT3 receptors in NG108-15 cells was studied using the whole cell patch clamp recording technique. Imetit, a histamine H3 receptor agonist, generated inward currents and exhibited weak partial agonist activity at the 5-HT3 receptor (EC50 = 11.8 microM). Imetit-induced currents were slow to desensitize and at a high concentration reduced in size. The histamine H3 receptor antagonists iodophenpropit and thioperamide did not generate inward currents but were able to inhibit 5-hydroxytryptamine (5-HT) responses with an IC50 of 1.57+/-0.3 microM and 13.7+/-3.5 microM, respectively. Thioperamide is probably a non-competitive antagonist which may have more than one binding site on the receptor.

Animals↗
PubMed1998

Inhibition of ligand-gated cation-selective channels by tamoxifen.

The nonsteroidal antioestrogen tamoxifen has been shown to block a number of voltage-gated cation-selective channels but its effect on ligand-gated cation-selective channels has not been studied. We have investigated the action of tamoxifen and the related derivative toremifene on ligand-gated cationic nicotinic acetylcholine and 5-HT3 receptor channels. Tamoxifen and toremifene both inhibited cationic currents of adult-type human muscle nicotinic acetylcholine receptors expressed in Xenopus oocytes with similar IC50 values of 1.2 +/- 0.03 microM (nH = 0.84 +/- 0.02) and 1.2 +/- 0.1 microM (nH = 1.1 +/- 0.1), respectively. Tamoxifen could also block native 5-HT3 receptors in NG108-15 neuroblastoma/glioma hybrid cells with IC50 = 0.81 +/- 0.15 microM and nH of 1.3 +/- 0.3. The characteristics of block by tamoxifen at the 5-HT3 receptor were voltage- and use-independent. The inhibition of the 5-HT-evoked currents were not overcome by increasing concentrations of 5-HT consistent with a noncompetitive mechanism of block.

Animals↗
PubMed1998

Rapid determination of oral pharmacokinetics and plasma free fraction using cocktail approaches: methods and application.

PURPOSE: To apply cocktail approaches for protein binding (PB) and pharmacokinetics (PK) within a discovery program as a means of providing timely systemic exposure (AUC and Cmax) data. METHODS: For PB data, a procedure of cocktail ultrafiltration, mixed matrix sample preparation and single quadrupole atmospheric pressure ionization LC/MS analysis was used. In vivo PK studies consisted of 4 experimental compounds and a control compound dosed orally at 1 mg/kg (5 mg/kg total dose), with plasma samples obtained at 0.5, 1, 2, 4 and 8 h post dose. For PB and in vivo PK analysis, a control compound was tested within each cocktail to ensure consistent reproducibility. RESULTS: Approximately 2 weeks were spent comparing single and cocktail approaches to determine the feasibility of this method for this project. Comparisons of cocktail data with single compound data revealed no significant differences between the approaches. The oral AUC values ranged from 0.01 to 9.28 micrograms.hr/ml and the Cmax values ranged from 0.04 to 2.17 micrograms/ml. Free fractions of the 44 compounds studied ranged from 0.006 to 0.271. Using the free fraction values to correct for free AUC and Cmax results in ranges of 0.001 to 0.473 microgram.hr/ml, and 0.001 to 0.119 microgram/ml, respectively. CONCLUSIONS: All 44 compounds tested had similar potencies in vivo. Thus, these results suggest that a respective 400 and 100-fold range in AUC and Cmax corrected for free fraction exist in the presence of comparable in vivo activity. The ability to generate this type of data in a timely manner allowed the selection of a candidate with low peripheral exposure relative to the effective dose. The free fraction and PK data on the 44 compounds described was collected within three work days by 2 lab scientists.

Administration, Oral↗
PubMed1998

The association between adequacy of prenatal care utilization and subsequent pediatric care utilization in the United States.

OBJECTIVE: To explore the association between adequacy of prenatal care utilization and subsequent pediatric care utilization. DESIGN: A longitudinal follow-up of a nationally representative sample of infants born in 1988. PARTICIPANTS: Nine thousand four hundred forty women who had a live birth in 1988, and whose child was alive at the time of interview, and 8285 women from the original sample who were reinterviewed in 1991. MAIN OUTCOME MEASURE: There were four outcome measures: number of well-child visits; adequate immunization for diphtheria, tetanus, and pertussis; adequate immunization for polio; and continuity of a regular source of care, as measured by the number of sites for pediatric care. RESULTS: Children whose mothers had less than adequate prenatal care utilization had significantly fewer well-child visits, and were significantly less likely to have adequate immunizations, even after income, health insurance coverage, content of prenatal care, wantedness of child, sites of prenatal and pediatric care, and maternal and pregnancy risk characteristics were taken into account. Less than adequate prenatal care utilization was not associated with having more than one pediatric care site. CONCLUSIONS: Prenatal care utilization can be used to identify and target interventions to women who are at risk for not obtaining well-child care or complete immunizations for their children.

Child Health Services↗
PubMed1998

Speech intelligibility in children after cochlear implantation.

OBJECTIVE: This study aimed to evaluate the long-term speech intelligibility of young deaf children after cochlear implantation. STUDY DESIGN: The study design was a prospective study following a large group of consecutively implanted deaf children with up to 5 years' cochlear implant use. SETTING: The study was conducted at a pediatric tertiary referral center for cochlear implantation. PATIENTS: All children in the study were congenitally deaf or deafened before 3 years of age. They each received a Nucleus multichannel cochlear implant before the age of 7 years. Eighty-four subjects were evaluated up to 5 years after cochlear implantation. INTERVENTION: Cochlear implantation followed by an intensive program of local and center-based assessment and rehabilitation was performed. MAIN OUTCOME MEASURES: A speech intelligibility rating scale evaluated the spontaneous speech of each child before and at yearly intervals for 5 years after implantation. RESULTS: After cochlear implantation, the difference between the speech intelligibility ratings increased significantly each year for 4 years (Mann-Whitney U-test). For the first 2 years, the average rating remained "prerecognizable words" or "unintelligible speech." It was not until the 3-year interval that the average intelligibility rating became category 3 (intelligible speech if someone concentrates and lip-reads). At the 4-year interval, 85% of children had some intelligible connected speech. This improvement continued, and at the 5-year interval, the median speech intelligibility was category 4 (intelligible speech to a listener with a little experience of deaf speech) and the mode was category 5 (intelligible speech to all listeners). CONCLUSION: Congenital and prelingually deaf children gradually develop intelligible speech that does not plateau 5 years after implantation.

Cochlear Implantation↗
PubMed1997

Quantitation of 4-cyclohexyl-2-hydroxy-3-(3-methylsulfanyl-2- [2-[(morpholine-4-carbonyl)amino]-3-phenylpropionylamino]propi onylamino ) butyric acid isopropyl ester (CP-80,794), a renin inhibitor, and its hydrolytic cleavage metabolite 2-[(morpholine-4-carbonyl)amino]-3-phenylpropionic acid (CP-84,364) in dog and human plasma by high-performance liquid chromatography.

Simple and precise high-performance liquid chromatographic (HPLC) assays were developed and validated for the determination of a renin inhibitor (RI), 4-cyclohexyl-2-hydroxy-3- (3-methylsulfanyl-2-[2-[(morpholine-4-carbonyl)amino]- 3-phenylpropionylamino]propionylamino)butyric acid isopropyl ester (CP-80,794, I), and its hydrolytic cleavage metabolite, 2-[(morpholine-4-carbonyl)amino]-3-phenylpropionic acid (CP-84,364, II) in dog and human plasma. The internal standard for I, CP-83,092 (III, a carbon-substituted derivative of I) and analyte were extracted by liquid-liquid extraction using n-butyl chloride, cleaved to form a fragment containing a primary amine, and subsequently fluorescently derivatized for measurement by HPLC. Samples were analyzed by reversed-phase HPLC using a Waters C18 column with fluorescence detection at 390 nm excitation/440 nm emission. The quantitation limit of I was 10 ng/ml and the calibration curve was linear over the range of 0.01-1.0 microgram/ml (r2 > 0.99). In dog and human plasma, intra- and inter-assay precision ranged from 2.3 to 16% and 3.0 to 18%, respectively. The average recoveries were similar (> or = 63%) for both I and III and the upper limit of quantification of I can be as high as 4 micrograms/ml. The internal standard for II, CP-96,452 (IV, a methoxy derivative of II) and analyte were extracted by anion-exchange solid-phase extraction and subsequent liquid-liquid extraction using methyl tert.-butyl ether. Samples were analyzed by reversed-phase HPLC using a Waters C18 column with ultraviolet detection at 214 nm. The quantitation limit of II was 20 ng/ml and the calibration curve was linear over the range of 0.02-2.0 micrograms/ml (r2 > 0.99). In dog and human plasma, intra- and inter-assay precision ranged from 2.6 to 13.0% and 1.8 to 20.0%, respectively. The average recoveries were similar (> or = 75%) for both II and IV and the upper limit of quantification of II can be as high as 20 micrograms/ml. The methods described have been successfully applied to the quantification of I and II in about 5000 dog and human plasma samples over a 2 year period.

Animals↗
PubMed1997

Cycling Werner's syndrome fibroblasts display calcium-dependent potassium currents.

Werner's Syndrome (WS) fibroblasts undergo premature senescence. Two hypotheses have been proposed to explain this phenomenon: (i) the phenotype is due to the overexpression of senescence-specific proteins in every cell in the population. Such proteins are known to suppress calcium-dependent potassium currents. (ii) The WS mutation greatly increases the proportion of cells that stop cycling at each generation and become senescent. If hypothesis (i) is correct, such currents should be suppressed in all WS fibroblasts; whereas hypothesis (ii) predicts that they will be retained in the cycling fraction of the population. To distinguish between these hypotheses whole-cell patch-clamp currents were recorded from cycling cells. Slowly activating outward calcium-dependent potassium currents were detected in both cycling WS and control fibroblasts. These findings support hypothesis (ii): the premature senescence of WS fibroblasts is due to an increased rate of transition from cycling to senescence in the total cell population.

Calcium↗
PubMed1997

Using motor milestones as a multistep process to screen preterm infants for cerebral palsy.

Pediatricians often informally use motor milestones to screen infant motor development, and one advantage is that they can be used during sequential office visits, as a multistep screening process. In this study we evaluated six motor milestones (roll prone to supine, roll supine to prone, sit with support, sit without support, crawl and cruise) as a multistep process in screening for cerebral palsy in 173 high-risk preterm infants (<33 weeks gestational age) who had been followed with sequential developmental assessments for at least 18 months. At the 18 to 24 month evaluation, 31 (18%) had cerebral palsy. We found that using the motor milestones as serial screening tests for cerebral palsy was more effective in terms of positive predictive value than any individual milestone alone. Limited community resources can be more efficiently used if preterm infants with delays in more than four motor milestones are referred for further evaluation and early intervention services.

Cerebral Palsy↗
PubMed1997

Using the clinical linguistic and auditory milestone scale for developmental screening in high-risk preterm infants.

Eighty-one preterm infants (mean gestational age 29 weeks, range 24-36 weeks) discharged from The Johns Hopkins Hospital Neonatal Intensive Care Unit were followed up sequentially from birth to 2 years of age by use of the Clinical Linguistic and Auditory Milestone Scale (CLAMS) to evaluate language development. Children were studied during three time intervals: Interval 1: 3-5 months chronologic age (CA); Interval 2: 9-14 months (CA); and Interval 3: 18-24 months (CA). Psychometric test scores were compared with CLAMS Language Quotients (LQ) by use of full, partial (75%, 50%, 25%), and no "correction" for weeks of prematurity to determine whether "correcting" for prematurity would yield a more accurate estimate of eventual cognitive outcome. CLAMS LQ at Interval 1 was highly correlated with CLAMS LQ at Interval 2 and CLAMS LQ at Interval 2 correlated well with CLAMS LQ at Interval 3 (r = 0.57 and 0.64, respectively, P = 0.0001). Correlations indicated that there was an orderly, sequential development of language in the preterm infant. CLAMS evaluations correlated significantly with psychometric test results during Interval 2 and Interval 3 (r = 0.34, P < 0.02 and r = 0.75, P = 0.0001, respectively). The CLAMS proved to be a useful instrument for monitoring preterm language development in the primary pediatric care setting.

Apgar Score↗
PubMed1996

Determination of 1-[5-(2-cyclopropyl-5,7-dimethyl-imidazo[4,5-b] pyridin-3-ylmethyl)thiophen-2-yl]cyclopent-3-enecarboxylic acid (CP-191,166), an angiotensin II antagonist, in dog and rat plasma by high-performance liquid chromatography.

A simple and precise high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of a novel angiotensin II antagonist, 1-[5-(2-cyclopropyl-5,7-dimethyl-imidazo[4,5-b]pyridin-3-ylmethyl) thiophen-2-yl]cyclopent-3-enecarboxylic acid (CP-191,166, I), in dog and rat plasma. The internal standard (II, a saturated derivative of I) and analyte were extracted by liquid-liquid extraction using methyl tert.-butyl ether. Samples were analyzed by reversed-phase HPLC using a Zorbax C8 narrow-bore column with ultraviolet detection at 289 nm. The quantitation limit of I was 10 ng/ml and the calibration curve was linear over the range of 0.01-10.0 micrograms/ml (r2 > 0.99). In dog and rat plasma, intra- and inter-assay precision ranged from 0.00 to 3.36% and 0.00 to 4.95%, respectively. The average recoveries were similar (73%) for both I and II and the upper limit of quantification of I can be as high as 500 micrograms/ml. The method described has been successfully applied to the quantification of I in about 2000 dog and rat plasma samples over a nine-month period.

Angiotensin II↗
PubMed1996

Histamine forming capacity (HFC) and its modulation by H3 receptor ligands in a model of bronchial hyper-responsiveness.

The histamine forming capacity (HFC) of acutely challenged airways from sensitised guinea pigs was investigated. After exposure to nebulised bovine serum albumin (BSA) or normal saline, animals were sacrificed, the pulmonary HFC determined and concurrent in vitro histamine log concentration response curves were constructed for parenchymal strips and tracheal muscle, the latter was field stimulated to record neurogenic responses. Exposure to BSA increased the HFC above controls for 24 hours (p < 0.001) and log concentration response curves for the parenchymal strips were shifted slightly to the left with an increased maximum response. This change appeared 3 hours after exposure and remained elevated at 24 hours. Similar changes did not occur with the trachea. Pre-treatment with thioperamide augmented (p < 0.02) HFC and this increase was inhibited by alpha-methylhistamine (p < 0.05). A possible relationship may exist between increased responsiveness of lower airways to exogenous histamine and a raised endogenous formation, regulated by the H3 receptor.

Animals↗
PubMed1994

Neurocardiogenic syncope in children with a normal heart.

OBJECTIVES: The purpose of this study was to review the results of investigation and management of children with syncope and a structurally normal heart. BACKGROUND: Syncope is a common clinical problem and has many etiologies. Autonomic testing and, in particular, the tilt/orthostatic test have helped to positively diagnose neurocardiogenic syncope in a high proportion of such patients. METHODS: Patient case notes and autonomic test charts were reviewed in 162 children aged 1 to 20 years (mean age 12.8 years) with syncope. The autonomic test consisted of orthostatic maneuver, carotid sinus massage, diving reflex, Valsalva maneuver and dose response to intravenous boluses of isoproterenol and phenylephrine. Serum levels of epinephrine and norepinephrine were drawn during the orthostatic test. After confirmation of neurocardiogenic syncope, treatment was begun with fludrocortisone and salt, and beta-adrenergic blocking agents were used as a second line of therapy when indicated. RESULTS: The orthostatic test was positive for neurocardiogenic syncope in 100 patients (62%) and negative in 62 (38%). Patients in the former group were older, were more often female and had a diminished response to carotid sinus massage, a higher Valsalva ratio and a higher supine epinephrine level. Both groups showed an increase in epinephrine and norepinephrine levels at 5 min of standing. In the orthostatic positive group at the time of syncope, norepinephrine levels decreased, whereas epinephrine levels increased. Patients in this group were also more sensitive to the vasodilating effect of isoproterenol but not to its chronotropic effects. Eleven patients had cardioinhibitory syncope (asystole > or = 3 s). Of these, three had pacemaker implantation. Fludrocortisone and salt used in 84 patients in the orthostatic positive group produced resolution of symptoms in 55 patients (65%) and improvement in 14 (17%). Ten patients received beta-blockers, with resolution in four and improvement in four. CONCLUSIONS: Patients with orthostatic test-proved neurocardiogenic syncope show evidence of autonomic dysfunction. They also show beta-adrenergic hypersensitivity. Treatment initiated on the basis of the protocol was associated with amelioration of symptoms in the majority of patients.

Adrenergic beta-Antagonists↗
PubMed1994

Effect of beta-adrenergic stimulation on the QT interval of children with syncope.

The effect of intravenous bolus doses (0.25, 0.5, 1.0 microgram) of isoproterenol on the QT and RR intervals was reviewed in a group of 34 children undergoing autonomic testing for syncope. Twenty-one patients had a positive orthostatic test and 13 were negative. The two groups (positive and negative) were compared. Baseline QT and RR intervals were similar. The RR interval was shortened by isoproterenol in both groups. Isoproterenol shortened the QT interval in the negative group (as seen in normal persons), but produced QT prolongation in the positive group, although neither reached statistical significance when compared to baseline within the respective group. Comparing the values for RR and QT at each dose of isoproterenol (including baseline) between the two groups showed a significant difference in the QT interval after the 1.0-microgram dose of isoproterenol. Thus children with orthostatic positive neurocardiogenic syncope showed a different QT response to beta-adrenergic stimulation. This lends support to the theory of altered beta-adrenergic sensitivity being present in children with neurocardiogenic syncope.

Adolescent↗
PubMed1994

The CAT/CLAMS assessment for early intervention services. Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale.

The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) is a relatively new test of language, problem-solving abilities, and visual-motor skills for children ages 0 to 36 months of age. This instrument was compared to the Bayley Mental Developmental Index (MDI), the generally accepted standard of infant developmental tests. This study evaluates 328 normal children tested in infancy and then at 18 and 30 months of age. Specificity was excellent (95% to 100%) at both 18- and 30-month levels when compared to the Bayley MDI. Sensitivity, however, was 21% at the 18-month level and 67% at the 30-month level. Predictive validity (.65) and within-test validity (.69) are good. The CAT/CLAMS compares favorably with the Bayley MDI assessment of children between 18 and 30 months of age and can be used for clinical assessment of toddlers referred for development assessment prior to admission to early intervention programs.

Animals↗
PubMed1994

CAT/CLAMS. A tool for the pediatric evaluation of infants and young children with developmental delay. Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale.

The American Academy of Pediatrics recommends regular developmental screening as a part of routine child health supervision. However, the pediatrician has a limited number of tools available to further evaluate a child who is found to be suspect or abnormal on a developmental screening test. The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was therefore developed to provide pediatricians with a technique to assess infants and toddlers with suspected developmental delay. The CAT/CLAMS demonstrated strong psychometric properties. Concurrent validity with the Bayley Scales of Infant Development (BSID) was demonstrated in 43 children ages 12 to 19 months who were tested on three occasions with both instruments (correlation coefficient ranging between 0.63 and 0.87; P < .001). Predictive validity 6 and 12 months later was also demonstrated in this population with correlation coefficients ranging between 0.73 and 0.77, significant at the P = .001 level. Utilizing the CAT/CLAMS as part of the pediatrician's evaluation of children with developmental concerns would allow the pediatrician to compare language and nonlanguage problem-solving abilities and, therefore, aid in diagnosis and appropriate referral.

Developmental Disabilities↗