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Biomedical subjects

E Owens

Publications and source records attributed to E Owens.

12 recordsLinked to original sources

Activity profiles of developmental toxicity: design considerations and pilot implementation.

The available literature was searched for quantitative test results from both in vitro and in vivo assays for developmental toxicity for five model compounds: cyclophosphamide, methotrexate, hydroxyurea, caffeine, and ethylenethiourea. These compounds were chosen on the basis of their extensive utilization in a variety of assay systems for developmental toxicity as evidenced by their representation in the ETIC database (each generally has 100-500 citations encompassing multiple test systems). Nine cellular-based assays, six assays using whole embryos in culture, as well as Segment II and abbreviated exposure tests for mammalian test species are included in the database. For each assay, the critical endpoints were identified, each of which was then provided a three-letter code, and the criteria for extraction of quantitative information were established. The extracted information was placed into a computerized reference file and subsequently plotted such that the qualitative (positive/negative) and quantitative (e.g., IC50, highest ineffective dose (HID), lowest effective dose (LED] results across all test systems could be displayed. The information contained in these profiles can be used to compare qualitative and quantitative results across multiple assay systems, to identify data gaps in the literature, to evaluate the concordance of the assays, to calculate relative potencies, and to examine structure-activity relationships.

Animals

Preparation and biological evaluation of 18F-labeled benzamide analogs as potential dopamine D2 receptor ligands.

Three 18F-labeled benzamide derivatives were prepared and evaluated as potential ligands to study the dopamine D2 receptor phenomenon. The compounds are analogs of iodobenzamide, eticlopride and raclopride and are labeled with an N-2-[18F]fluoroethyl functionality on the pyrrolidine ring. The compounds were tested in vitro for binding affinity and found to exhibit somewhat lower affinity than the non-fluorinated analog. In vivo distribution studies revealed that all compounds were more highly bound to plasma proteins than was raclopride. In addition, compartmentation of radioactivity demonstrated nonspecific binding to be the predominate retention in the brain as reflected by the low caudate to cerebellum ratios for these compounds. These three 18F-labeled benzamide derivatives are inferior to raclopride and iodobenzamide for studies of the D2 receptor system using positron emission tomography.

Animals

Kinetic analysis of 3-quinuclidinyl 4-[125I]iodobenzilate transport and specific binding to muscarinic acetylcholine receptor in rat brain in vivo: implications for human studies.

Radioiodinated R- and S-Quinuclidinyl derivatives of RS-benzilate (R- and S-125IQNB) have been synthesized for quantitative evaluation of muscarinic acetylcholine receptor binding in vivo. Two sets of experiments were performed in rats. The first involved determining the metabolite-corrected blood concentration and tissue distribution of tracer R-IQNB (active enantiomer) and S-IQNB (inactive enantiomer) in brain 1 min to 26 h after intravenous injection. The second involved the measurement of brain tissue washout over a 2-min period after loading the brain by an intracarotid artery injection of the ligands. Various pharmacokinetic models were tested, which included transport across the blood-brain barrier (BBB), nonspecific binding, low-affinity binding, and high-affinity binding. Our analysis demonstrated that the assumptions of rapid equilibrium across the BBB and rapid nonspecific binding are incorrect and result in erroneous estimates of the forward rate constant for binding at the high-affinity receptor sites (k3). The estimated values for influx across the BBB (K1), the steady-state accumulation rate in cerebrum (K), and the dissociation rate constant at the high-affinity site (k4) of R-IQNB were independent of the specific compartmental model used to analyze these data (K1 approximately 0.23 ml/min/g, K approximately 0.13 ml/min/g, and k4 approximately 0.0019 min-1 for caudate). In contrast, the estimated values of k3 and the efflux rate constant (k2) varied over a 10-fold range between different compartmental models (k3 approximately 2.3-22 min-1 and k2 approximately 1.6-16 min-1 in caudate), but their ratios were constant (k3/k2 approximately 1.4). Our analysis demonstrates that the estimates of k3 (and derived values such as the binding potential) are model dependent, that the rate of R-IQNB accumulation in cerebrum depends on transport across the BBB as well as the rate of binding, and that uptake in cerebrum is essentially irreversible during the first 360 min after intravenous administration. Graphical analysis was consistent with compartmental analysis of the data and indicated that steady-state uptake of R-IQNB in cerebrum is established within 1-5 min after intravenous injection. We propose a new approach to the analysis of R-IQNB time-activity data that yields reliable quantitative estimates of k3, k4, and the nonspecific binding equilibrium constant (Keq) by either compartmental or graphical analysis. The approach is based on determining the free unbound fraction of radiolabeled ligand in blood and an estimate of K1.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms

Hearing aid evaluation for persons with postlingual hearing levels of 90 to 100 dB.

Of 20 subjects with profound (90 to 100 dB) hearing loss who underwent a careful hearing aid evaluation, 16 were able to benefit from hearing aid use. With the recommended aids, all subjects could detect speech at levels within the normal conversational range; 75% had some understanding of spondee words; and 56% successfully accomplished tasks in phoneme identification. Two subjects succeeded on a standard speech discrimination test. Ear-level instruments, five binaural, were recommended for 13 of the 16 subjects. Microphones were front-facing in the majority of instances; none were directional. Seven aids used amplitude compression. Subjects were encouraged to relate their subjective impressions, and home trial was an important part of the evaluation. In the majority of instances, lipreading scores were markedly better with hearing aid use than without.

Adolescent

Hearing performance inventory.

The Hearing Performance Inventory (HPI) was developed to assess hearing performance in problem areas experienced in everyday listening. It consists of six sections: (1) Understanding Speech, (2) Intensity, (3) Response to Auditory Failure, (4) Social, (5) Personal, and (6) Occupational. A self-report response style is used. Sentences were written to describe a number of listening situations covering a variety of talker characteristics and communication processes. The development, current status, and clinical implications of the HPI are presented.

Attitude to Health

Hearing aid evaluations for persons with total postlingual hearing loss.

To answer the question whether persons with total postlingual hearing loss can benefit from hearing aid use, hearing aid evaluations were carried out for 18 subjects. Nonstandardized listening tasks were necessitated because none of the subjects could discriminate speech. Subjective considerations played an integral role in the evaluation procedure. The results of the evaluations were as follows: (1) six subjects became new hearing aid users; (2) two retained the aids they were already wearing; (3) one improved when the hearing aid was changed to the opposite ear; (4) one obtained a satisfactory replacement for an inadequate instrument; and (5) eight were unable to use an aid to advantage. Thus, it is important that all persons with total postlingual hearing loss be afforded the opportunity of a careful hearing aid evaluation.

Adult

Two years of a program in hearing-aid-related services.

A program of hearing-aid-related services is described in which a dispenser of hearing aids visits an audiology facility on a regular basis as a supplier. Surveys to assess the program were conducted during a two-year period. Of the 128 patients who participated in the study, 89% continued wearing their hearing aids during the first year and 86% during the second year. The adjustment period of about 30 days with an accompanying orientation program was crucial. Ear mold considerations and use of the hearing aid during noisy situations constituted two major problem areas. Five aids were returned to the factory during the adjustment period, six during the first year, and 15 during the second year. Group work in hearing aid evaluation and orientation was a positive factor.

Audiology

Consonant errors and remediation in sensorineural hearing loss.

An analysis of consonant errors for hearing-impaired subjects in a multiple-choice format revealed that about 14 consonants caused most of the difficulty in consonant recognition. For a given consonant, error probability was typically lower in the initial position of the stimulus word than in the final position. When errors were made, the substitutions were limited typically to two or three other consonants, with a greater variety occurring for consonants in the final position. Substitutions tended to be the same over a wide range of pure-tone configurations. Place errors were predominant, but manner errors also occurred. In only a few instances did specific relationships occur between particular stimulus consonants and pure-tone configurations. With knowledge of the error consonants and typical substitutions, auditory recognition of consonants can be improved by programmed instruction methods. Shaping can be accomplished by a manipulation of the response foils (choices). Since it has been shown that visual recognition of consonants can also be improved, advantage can be taken of both the visual and auditory modalities in remedial procedures. Frequency of usage in the language should be considered in the ordering of consonants for retraining purposes. Work in consonant recognition should be beneficial to the hearing-impaired patient as part of a total rehabilitation program.

Hearing Loss, Sensorineural

Therapy of heavy drinking during pregnancy.

A survey of patients registering at the Boston City Hospital Prenatal Clinic had demonstrated that 9 percent were heavy drinkers. To reduce the health hazards to mothers and children, treatment of heavy alcohol use was integrated with prenatal care. A pediatric neurologist independently examined 322 offspring, including 42 whose mothers were heavy drinkers. Frequency of congenital anomalies, growth retardation, or functional abnormalities among these 42 was twice that of infants born to abstinent or moderate drinking mothers P less than .001). Within that group of 42, there were 15 whose mothers were able to abstain or reduce alcohol intake during the third trimester. These 15 demonstrated fewer abnormalities than those 27 whose mothers had continued heavy drinking (P less than .001). Since pregnant women can be motivated to reduce heavy drinking, treatment programs can benefit both mothers and infants.

Abnormalities, Drug-Induced

Development of the California Consonant Test.

A 100-item, multiple-choice test for consonant identification labeled the California Consonant Test (CCT) has been developed expressly for use with hearing-impaired patients. A computer-assisted analysis was obtained for the test responses of 550 patients with sensorineural hearing loss. The test seems highly sensitive to configurations of high-tone loss, but the correlation with degree of loss, especially in the instance of flat configurations, is somewhat low (-0.40). Test-retest correlation is 0.96. A correlation of 0.35 with a W-22 list indicates that the two tests are measuring different aspects of speech reception. In addition to its usefulness in identifying consonant confusions for rehabilitation purposes, the CCT may prove helpful in ranking hearing aids. For the latter purpose, two 50-item subforms, designed for equivalence, have been under observation for possible use when time is a critical factor. Repetitions of the 100-item list offer greater stability, however.

Auditory Perception

Intraductal "noninfiltrating" carcinoma of the breast.

We are reviewing 40 patients with noninvasive intraductal carcients; 10% developed oppostie breast cancer of the invasive variety. Twenty-one patients underwent radical mastectomy in which one patient was found to have a positive axillary node. The 19 remaining patients had total mastectomy alone. No recurrence of death attributed to intraductal carcinoma was found in 39 patients available for follow-up.

Adenofibroma