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Biomedical subjects

R H Wilson

Publications and source records attributed to R H Wilson.

At least 19 recordsLinked to original sources

Colorectal cell kinetics.

The assessment of cell proliferation in colorectal tissue may provide information with both prognostic and therapeutic implications. A variety of methods are available, including flow cytometric estimations of S phase fraction, immunohistochemical and autoradiographic visualization of exogenous and endogenous proliferation proteins, and morphological and stathmokinetic techniques. There is some correlation between Dukes stage and proliferation state features, and there is increased proliferative activity throughout the adenoma-carcinoma sequence. Data on cell proliferation rates are difficult to obtain. When correctly applied, the metaphase arrest technique remains the 'gold standard' of measuring proliferation, but its usefulness in clinical practice is limited. Recent studies have employed dual measurement flow cytometry and double labelling techniques to produce rate data.

Biomarkers

Identification performance by right- and left-handed listeners on dichotic CV materials.

Normative data from 24 right-handed and 24 left-handed subjects were obtained for the dichotic consonant-vowel (CV) materials (pa, ta, ka, ba, da, and ga) recorded on the Veterans Affairs (VA) compact disc (CD) Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0. Identification performance by the two subject groups was significantly different. With the right-handed subjects, identification performances on the materials presented to the right ear (RE) were better than performances on the materials presented to the left ear (LE) by (1) 16.3 percent for simultaneous onsets (RE = 72.8%; LE = 56.5%), (2) 11.3 percent for the 90-msec right-ear lag (RE = 86.3%; LE = 75.0%), and (3) 8.7 percent for the 90-msec left-ear lag condition (RE = 85.8%; LE = 77.2%). In comparison to the right-handed subjects, the left-handed subjects exhibited a smaller right-ear advantage and more inter-subject variability. With the left-handed subjects, identification performances on the materials presented to the right ear also were better than performances on the materials presented to the left ear by (1) 1.7 percent for simultaneous onsets (RE = 62.9%; LE = 61.1%), (2) 2.8 percent for the 90-msec right-ear lag (RE = 75.0%; LE = 72.2%), and (3) 3.1 percent for the 90-msec left-ear lag condition (RE = 75.9%; LE = 72.9%). The results are similar to previous dichotic CV data and indicate that the CVs recorded on the VA-CD provide valid estimates of identification performance on the dichotic CV materials.

Adult

Nuclear texture measurements in normal colorectal glands.

OBJECTIVE: To examine differences in epithelial cell nuclear texture along the length of normal, well-oriented colorectal glands. STUDY DESIGN: Histologically normal mucosa was obtained from four patients who had a family history of cancer and no hyperproliferation as assessed by bromodeoxyuridine immunohistochemistry. Serial sections were stained using the Feulgen technique and viewed to identify glands that were sectioned along their entire length. Two glands were sampled from each patient. Each gland was divided into three compartments based on epithelial cell counts along the length of the gland. Within each compartment, 10 nuclei were randomly selected and their nuclear texture features measured using computerized image analysis. RESULTS: Analysis of variance demonstrated that significant differences exist in the nuclear texture of cells in the different compartments of the gland. Discriminant analysis selected three variables that were important and independent in the quantitative discrimination of the gland compartments. These features were related to the elliptical shape, optical density distribution and cooccurrence structure of the chromatin texture within the epithelial nuclei. CONCLUSION: It is clear that these differences are associated with the spatial variation in proliferation and differentiation status found within colorectal mucosal glands. Nuclear measurements from colorectal epithelium with near-normal architecture should therefore be stratified in relation to position within the gland. Nuclear texture and size measurements within defined compartments may provide a sensitive means of detecting early malignant transformation.

Cell Nucleus

Three-dimensional computerised analysis of epithelial cell proliferation in the gastrointestinal tract.

This study describes a new technique for the visualisation and quantitation of glandular epithelial cell proliferation in gastrointestinal mucosa using computerised three-dimensional reconstruction. The tissue used in this study was colorectal biopsy tissue infiltrated in vitro with bromodeoxyuridine (BrdU), although the method could be applied to any gastrointestinal site labelled with any specific marker for cell proliferation. The method is as follows. Five-micron-thick serial sections (> 100) were cut from colorectal biopsies infiltrated in vitro with BrdU. After labelling all the sections for BrdU-positive cells using standard immunohistochemistry, colorectal glands were identified which were completely sectioned within the series. Each microscopic image of the sectioned gland was orientated, digitised and stored using a Kontron image analyser. On each of the stored images, the crypt profile, the positive cells and the negative cells were interactively marked and digitally stored. Using three-dimensional (3-D) reconstruction software, the outer surface of the crypt, the total positive and the total negative fractions could be viewed in three dimensions. The total BrdU-positive cell number could be automatically calculated for the complete crypt or, alternatively, compartmental analysis of the labelling pattern within the crypt could be obtained. This represents a powerful technique: it does not require orientation, it can be carried out on complex glandular structures and is not affected by the biases involved in measuring labelling indices from single tissue sections.

Bromodeoxyuridine

High-frequency audiometric monitoring strategies for early detection of ototoxicity.

Therapeutic drugs such as the aminoglycoside antibiotics (AMG) and the chemotherapy agent cisplatin (CDDP) are known to cause irreversible hearing loss, typically affecting highest frequency hearing first with progression of loss to the lower frequency regions. Conventional (0.25-8 kHz) and high-frequency (9-20 kHz) serial hearing threshold monitoring was done in 123 hospitalized patients (222 ears) administered AMG or CDDP. Of ears showing a decrease in sensitivity corresponding with treatment, 62.5% demonstrated initial hearing loss solely in the high-frequency range, 13.5% first showed loss only in the conventional-frequency range, and 24.0% showed loss in both frequency ranges concurrently. Thus, if only high frequencies had been monitored, early change in auditory sensitivity would have been detected in 86.5% of these patients. Further analysis revealed a range of five frequencies, specific to each individual's hearing threshold configuration, in which initial ototoxicity appeared most likely to be detected. Testing only these five frequencies would have identified 89.2% of ears that showed change. The results of this study confirm the need to serially monitor auditory thresholds, especially in the high-frequency range, of patients receiving ototoxic drugs. A shortened five-frequency monitoring protocol is presented and suggested for use with patients unable to tolerate lengthy audiometric testing procedures.

Aminoglycosides

The need for closer control of warfarin therapy.

Warfarin therapy is associated with a variety of haemorrhagic complications. We report a representative series of six cases of warfarin-induced bleeding in non-cerebral sites admitted to one unit. In all of these cases, there was inadequate control of anticoagulation, resulting in major morbidity and one death. In particular, closer attention must be paid to the indications for and duration of warfarin treatment.

Aged

Department of Veterans Affairs compact disc recording for auditory perceptual assessment: background and introduction.

Materials for use in auditory perceptual assessment of central auditory problems are widely divergent in quality, usefulness, and complexity. These circumstances make interpreting results a highly provincial affair. Comparison of results between different clinics and laboratories is often difficult or impossible. Norms by which to judge an individual's performance are often applicable for only one version of a given test and may not be appropriate for another version of the "same" test. The pressing need for standardization of a battery of central auditory tasks that is useful in clinical endeavors and in laboratory experiments is obvious. If that battery could encompass a wide range of complexity, and if the items in it were produced with very high quality, then its value would increase. The materials previewed in this introductory article and in seven other articles in this journal edition were developed to address some of these issues. Monotic, diotic, and dichotic materials using speech and tone stimuli were created. They were produced on compact disc under the sponsorship of the Department of Veterans Affairs and with the assistance of many institutions and individuals in the United States. In the articles that follow this one, data generated from their use with young, normal listeners are presented.

Adolescent

Masking-level difference for spondaic words in 2000-msec bursts of broadband noise.

One protocol developed for the Tonal and Speech Materials for Auditory Perceptual Assessment audio compact disc was the masking-level difference (MLD) for spondaic words in which the words and broadband noise were mixed and recorded at 16 selected signal-to-noise ratios. Four words were recorded at each level. Because it was impossible to monitor the word presentations at negative signal-to-noise ratios, a different paradigm was devised in which the spondaic words were embedded in 2000-msec bursts of noise. Before the materials were finalized for the compact disc, two experiments studied the perceptual characteristics of the paradigm. Experiment I was performed to determine the characteristics of the MLD for spondaic words in 2000-msec bursts of noise at 70 dB SPL. An unexpected finding was that the mean SoNo thresholds were at signal-to-noise ratios 3-4 dB lower than previously reported spondaic word thresholds in continuous broadband noise. Experiment II examined this discrepancy with the spondaic words embedded in continuous noise and in the 2000-msec noise bursts. The results confirmed the 3-4 dB difference between thresholds for the two masker conditions. Based on the pilot data, the spondaic words embedded in 2000-msec bursts of broadband noise at signal-to-noise ratios of 0 dB to -30 dB were recorded on the compact disc in the S pi No paradigm. In the compact disc trials, which involved 120 subjects with normal hearing, the MLDs for the spondaic words recorded on the compact disc were measured on 60 subjects at each of two noise levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation

Dichotic listening to musical chords: background and preliminary data.

One test of dichotic listening utilizing nonverbal stimuli is included on the VA-CD Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0. It is a test using three tone complexes that meet the definition of musical chords. The dichotic chords were included as a complement to the three dichotic speech procedures on the VA disc because musical chords may depend on right hemisphere brain function in a manner at least related to the way speech depends on left hemisphere organization/activity. Normative data were obtained from 120 normal-hearing listeners at nine testing centers in the United States. The three tone chords were presented dichotically under two onset time conditions, simultaneous and 90-msec onset time stagger, and three presentation levels, 70, 80, and 90 dB SPL. In general, subjects could identify the dichotically presented chords about 60 percent of the time in each ear. In addition, onset time relationships and presentation levels did not greatly affect accuracy. Overall, subject performance was similar to that noted by others and at levels that should allow lesion effects to be sought.

Auditory Perception

Dichotic listening to speech: background and preliminary data for digits, sentences, and nonsense syllables.

Three tests of dichotic listening utilizing speech signals as stimuli are included on the VA-CD Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0. They include a dichotic monosyllabic digits task, a dichotic synthetic sentences task, and a dichotic nonsense syllable (CV) task. Since the materials were specially recorded or created and recorded for use on the VA-CD, normative data were collected at nine universities/medical centers in the United States involving 120 young listeners. Data revealed that these listeners had little difficulty correctly identifying digits or synthetic sentences when they were presented at 50-70 dB HL in a dichotic format requiring two responses to each trial. At the same presentation levels and under two onset-time conditions (0- and 90-msec onset stagger), correct responsiveness was less frequent when the stimuli were dichotic CVs. However, scores fell in ranges consistent with previous studies and useful for seeking lesion effects. Although careful definition of stimuli, standardization of materials, and the relative stability offered by audio compact disc technology were prime reasons for making the VA-CD, another goal was to offer the clinician-researcher a range of difficulty among the procedures on the disc. Data from the normative trials using dichotic speech signals suggest that the goal has been accomplished.

Compact Disks

Word recognition with segmented-alternated CVC words: compact disc trials.

The Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0 audio compact disc contains a set of consonant, vowel-nucleus, consonant speech materials that have been segmented at the approximate phoneme boundaries so that the carrier phrase and consonant segments of a word can be presented to one ear and the carrier phrase and vowel segment of the word presented to the other ear. In this manner, consonant and vowel information are presented to different ears using a binaural fusion paradigm in which the temporal sequence of the word is maintained. The purpose of the compact disc trials was to document the recognition performance of 120 young adults with normal hearing under the following three conditions: (1) the consonant segments presented monaurally at 40, 50, and 60 dB HL; (2) the vowel segment of the words presented monaurally at 20, 30, and 40 dB HL; and (3) the binaural condition at 0 to 30 dB Hl in which the consonant segments were presented to one ear and the vowel segments were presented to the other ear. Recognition performance under the binaural fusion paradigm was identical to recognition performance on the same materials unaltered.

Adult

Low- and high-pass filtered Northwestern University Auditory Test No. 6 for monaural and binaural evaluation.

Two protocols developed for the Tonal and Speech Materials for Auditory Perceptual Assessment audio compact disc are low- and high-pass filtered versions of the Northwestern University Auditory Test No. 6 (female speaker). Two experiments were performed on subjects with normal hearing to determine the needed filter characteristics of the words. In Experiment I, word-recognition performance was determined at 70 dB SPL for four low-pass cut-offs (800 to 1700 Hz) and for four high-pass cut-offs (1700 to 3000 Hz). Based on the data from Experiment I, the low-pass (1500-Hz cut-off) and high-pass (2100-Hz cut-off) conditions were selected for inclusion on the compact disc. In Experiment II, psychometric functions were obtained in quiet for the two filter conditions with lists 3 and 4 included on the compact disc. Because the high-pass filtered words were recorded on channel 1 and concurrently the corresponding low-pass filtered words were recorded on channel 2, a binaural fusion paradigm is also available on the compact disc. For the compact disc trials, which involved 120 subjects with normal hearing, psychometric functions were generated for monaural low-pass, monaural high-pass, and binaural spectral fusion (low- and high-pass) conditions, with each of the subjects providing data at one of six levels for each of three conditions.

Acoustic Stimulation

Effects of time compression and time compression plus reverberation on the intelligibility of Northwestern University Auditory Test No. 6.

The Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0 audio compact disc developed in 1992 includes several sets of degraded speech materials, two of which, time compression and reverberation, are described in this paper. The digital techniques used to compress the NU No. 6 materials (female speaker) on an 80386-based computer are described, along with a series of experiments on subjects with normal hearing that document the effects of the time compression on recognition performance. Experiment I examined at 70 dB SPL the effect on word recognition of 45, 55, 65, 70, and 75 percent compressions. Experiment II developed psychometric functions for the 45, 65, and 75 percent time-compression conditions. Experiment III defined the effects that time-compression degradation (45% and 65%) plus reverberation degradation (0.3 sec) had on the recognition performance on the NU No. 6 materials. Based on the experiments, four conditions (45% compression, 65% compression, 45% compression plus 0.3-sec reverberation, and 65% compression plus 0.3-sec reverberation) were selected and recorded on the compact disc. In the compact disc trials, normative data on the four conditions were developed from 120 listeners with normal hearing.

Compact Disks

Adjuvant therapy for colorectal cancer--is there a place for a Northern Ireland study?

Survival from colorectal cancer has not improved over the last four decades despite advances in surgery and anaesthesia. The answer to the question whether adjuvant chemotherapy and radiotherapy will improve survival from the disease can only come from randomised, controlled trails. In the future, immunotherapy and gene therapy may be of benefit but these are still many years from the clinical arena. We believe that current evidence suggests that patients with Dukes B and C colorectal cancer should be entered into trials of adjuvant therapy. This evidence is reviewed below among with estimates of the impact that adjuvant therapy would have on the outcome from this disease in Northern Ireland.

Antimetabolites, Antineoplastic

Development and use of auditory compact discs in auditory evaluation.

Two audio compact discs have been developed by the Department of Veterans Affairs for use in the assessment of auditory function. This report focuses on 1) the development of the first compact disc, which contains speech materials used in routine audiologic evaluations, and 2) an introduction to the second compact disc, which contains tonal and speech materials used in more elaborate auditory evaluations. The first disc (Speech Recognition and Identification Materials, Disc 1.1), which is in its second generation, contains spondaic words, several monosyllabic word tests (Rush Hughes PB-50s, CID W-22, Maryland CNCs, and Northwestern University [NU] No. 6), and the Synthetic Sentence Identification materials. The second disc (Tonal and Speech Materials for Auditory Perceptual Assessment), which was produced in conjunction with the Dartmouth-Hitchcock Medical Center, contains spondaic words in the MLD paradigm, dichotic materials (chords, nonsense syllables, digits, and sentences), segmented/alternated CNCs, high-pass and low-pass NU No. 6 materials, 45% and 65% compressed NU No. 6 materials, the same 45% and 65% compressed materials compounded with 0.3-s reverberation, frequency tone patterns, and duration tone patterns.

Compact Disks