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Biomedical subjects

T Nicol

Publications and source records attributed to T Nicol.

At least 19 recordsLinked to original sources
PubMed2002

Abnormal neural encoding of repeated speech stimuli in noise in children with learning problems.

OBJECTIVES: This study investigated whether neurophysiologic responses to repeated speech stimuli, presented in quiet and noise, differed between normal children (NL) and children with learning problems (LP). METHODS: Subjects were normal-hearing, school-age children. NL subjects scored significantly better than LP subjects on measures of reading, spelling and speech sound discrimination. Stimuli (40 ms /da/) were presented to the right ear at 80 dB SPL. Stimuli were presented in trains of four, separated within trains by 360 ms. The interval between trains was 1060 ms. Stimuli were presented in quiet and in white noise (S/N+15). Cortical responses were recorded from an electrode placed along the midline at Cz. RESULTS: Correlations between the first and 4th responses were lower in noise than in quiet for LP subjects only. Response correlations in quiet were no different between groups. There were no root-mean-square (RMS) amplitude differences between groups. CONCLUSIONS: Response correlation in noise suggested that the LP population consisted of two subgroups, one whose responses appeared relatively normal, and another whose responses were severely degraded by repetition in noise. Response correlations in noise were related to behavioral measures of auditory processing and spelling. These findings suggest that abnormal, asynchronous, auditory cortical encoding may underlie some language-based learning problems.

Acoustic Stimulation↗
PubMed2002

Interdigitating dendritic cell sarcoma: a rare malignancy responsive to ABVD chemotherapy.

Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm of which fewer than 25 cases have been reported in the world literature. This malignancy is difficult to diagnose because of its rarity, and because of the subtle histopathologic features that distinguish IDCS from similar tumors arising from reticular cells. To date, there exists no consensus on a standard chemotherapeutic regimen for IDCS. Patients with this malignancy have been treated with chemotherapy regimens used against non-Hodgkin's lymphomas. Responses to these regimens have been variable, but mostly unsuccessful. In this article we describe a case of IDCS occurring in a 44 year old female who presented with abdominal pain and inguinal adenopathy. Staging of the tumor with CT scan, PET scan, and bone marrow biopsy demonstrated inguinal and abdominal lymphadenopathies, a large mass encasing the small bowel, and extensive liver infiltration. Morphologic and cytochemical analysis of biopsies from the abdominal mass and inguinal node were consistent with a diagnosis of IDCS, and immunohistochemical stains of the lymph node were positive for CLA, Kp-1, S-100, while negative for CD1a, CD3, CD20, CKER, and HMB45. Treatment of this patient with ABVD chemotherapy resulted in rapid clinical improvement with a marked decrease in tumor burden after two cycles of ABVD, and a complete response after six cycles of therapy.

Adult↗
PubMed2001

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Biopsy, Needle↗
PubMed2001

Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors.

Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear. Here we present the identification of a specific and highly polymorphic homopolymeric C stretch (D310), located within the displacement (D) loop, as a mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors analyzed harbored somatic deletions/insertions at this mononucleotide repeat. Moreover, these alterations were also present in head and neck preneoplastic lesions. We further characterized the D310 variants that appeared in the lung and head and neck tumors. Most of the somatic alterations found in tumors showed deletion/insertions of 1- or 2-bp generating D310 variants identical to constitutive polymorphisms described previously. Sequencing analysis of individual clones from lymphocytes revealed that patients with D310 mutations in the tumors had statistically significant higher levels of D310 heteroplasmy (more than one length variant) in the lymphocyte mtDNA as compared with the patients without D310 mutations in the tumor mtDNA. On the basis of our observations, we propose a model in which D310 alterations are already present in normal cells and achieve homoplasmy in the tumor through a restriction/amplification event attributable to random genetic drift and clonal expansion.

Carcinoma, Squamous Cell↗
PubMed2001

Molecular detection of cervical intraepithelial neoplasia and cervical carcinoma by microsatellite analysis of Papanicolaou smears.

Carcinoma of the uterine cervix is one of the most common malignancies worldwide, yet it is clearly preventable by population screening. The Papanicolaou (Pap) smear has proved to be the most successful test for the detection of precancerous lesions and is largely responsible for the reduction of cervical cancer mortality and morbidity rates. However, the Pap smear is not perfect; false-negative results of various rates are reported. To improve the diagnostic efficacy of cervical cytology, we performed microsatellite analysis on paired Pap smear samples from cervical lesions. Nine microsatellite markers were chosen from chromosomal regions commonly displaying loss of heterozygostity (LOH) in cervical cancer and those displaying microsatellite instability (MI) in other squamous cell cancer. Microsatellite alterations were detected in 16/21 (76%) Pap smear DNA samples including 11 of 13 (85%) smears from invasive squamous cell carcinomas (SCCs) and 5 of 8 (63%) from squamous intraepithelial lesions (SILs). Microsatellite alterations detected in the Pap smear DNA were identical to those identified in seven paired primary tumors available for analysis. Moreover, this molecular approach detected genetic alterations in two cases apparently negative by cytologic examination. None (0/25) of the control patients displayed microsatellite alterations in paired Pap smears. Microsatellite analysis of cervical cytologic samples may provide a complementary method to analyze suspicious but not diagnostic cytologic samples further.

Adenocarcinoma↗
PubMed2001

Gas chromatography/combustion/isotope ratio mass spectrometry to control the misuse of androgens in breeding animals: new derivatisation method applied to testosterone metabolites and precursors in urine samples.

A new derivatisation reaction applied to the analysis of steroids by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) was studied. The trimethylsilylated steroids were characterised by well-resolved chromatographic signals, no peak tailing, reproducible 13C/12C measurements (0.32 per thousand, n = 28), good signal-to-noise ratio and absolute intensity (5 x 10(-9) A, 20 ng), and a slow degradation of copper oxide pellets in the combustion furnace. In addition, two new metabolites and one precursor of testosterone in bovine have been brought into consideration and used for GC/C/IRMS measurements, namely, 3beta-hydroxy-5alpha-androstan-17-one (epiandrosterone), 3beta,17alpha-dihydroxy-5alpha-androstane, and 3beta,17alpha-dihydroxy-5-androstene. The new findings have been applied to an elimination study in bovine of testosterone metabolites after an intramuscular injection of testosterone enanthate. Significant differences (up to 4 per thousand) between testosterone metabolites and precursor were detectable at least three weeks after administration.

Agriculture↗
PubMed2001

Neurobiologic responses to speech in noise in children with learning problems: deficits and strategies for improvement.

OBJECTIVES: Some children with learning problems (LP) experience speech-sound perception deficits that worsen in background noise. The first goal was to determine whether these impairments are associated with abnormal neurophysiologic representation of speech features in noise reflected at brain-stem and cortical levels. The second goal was to examine the perceptual and neurophysiological benefits provided to an impaired system by acoustic cue enhancements. METHODS: Behavioral speech perception measures (just noticeable difference scores), auditory brain-stem responses, frequency-following responses and cortical-evoked potentials (P1, N1, P1', N1') were studied in a group of LP children and compared to responses in normal children. RESULTS: We report abnormalities in the fundamental sensory representation of sound at brain-stem and cortical levels in the LP children when speech sounds were presented in noise, but not in quiet. Specifically, the neurophysiologic responses from these LP children displayed a different spectral pattern and lacked precision in the neural representation of key stimulus features. Cue enhancement benefited both behavioral and neurophysiological responses. CONCLUSIONS: Overall, these findings contribute to our understanding of the preconscious biological processes underlying perception deficits and may assist in the design of effective intervention strategies.

Adolescent↗
PubMed2000

Aging affects hemispheric asymmetry in the neural representation of speech sounds.

Hemispheric asymmetries in the processing of elemental speech sounds appear to be critical for normal speech perception. This study investigated the effects of age on hemispheric asymmetry observed in the neurophysiological responses to speech stimuli in three groups of normal hearing, right-handed subjects: children (ages, 8-11 years), young adults (ages, 20-25 years), and older adults (ages > 55 years). Peak-to-peak response amplitudes of the auditory cortical P1-N1 complex obtained over right and left temporal lobes were examined to determine the degree of left/right asymmetry in the neurophysiological responses elicited by synthetic speech syllables in each of the three subject groups. In addition, mismatch negativity (MMN) responses, which are elicited by acoustic change, were obtained. Whereas children and young adults demonstrated larger P1-N1-evoked response amplitudes over the left temporal lobe than over the right, responses from elderly subjects were symmetrical. In contrast, MMN responses, which reflect an echoic memory process, were symmetrical in all subject groups. The differences observed in the neurophysiological responses were accompanied by a finding of significantly poorer ability to discriminate speech syllables involving rapid spectrotemporal changes in the older adult group. This study demonstrates a biological, age-related change in the neural representation of basic speech sounds and suggests one possible underlying mechanism for the speech perception difficulties exhibited by aging adults. Furthermore, results of this study support previous findings suggesting a dissociation between neural mechanisms underlying those processes that reflect the basic representation of sound structure and those that represent auditory echoic memory and stimulus change.

Acoustic Stimulation↗
PubMed2000

Reconstruction of complex cranial wounds with demineralized bone matrix and bilayer artificial skin.

Complex wounds involving loss of both cranium and scalp are difficult to reconstruct. Current solutions include both autogenous and alloplastic materials. Tissue engineering provides interesting alternatives for reconstruction of missing bone and soft tissue. Demineralized bone matrix and Integra, artificial bilayer skin substitute, have been used successfully to reconstruct bone and skin as isolated defects, but never in combination. This study investigates the possibility of using demineralized bone matrix in a gel carrier and Integra for combined cranial and scalp defects. The study was divided into two parts. In the first, demineralized bone matrix in the forms of Grafton Flex (n = 12) and Grafton putty (n = 12) was used to reconstruct 15-mm critical size cranial defects in female adult New Zealand White rabbits. In the control group (n = 6), the defect was left empty. The second part of the study investigated the use of Integra and Grafton Flex to reconstruct a 15-mm cranial defect with an overlying full-thickness scalp defect (n = 6). The first study revealed bony healing of the critical-size cranial defect with demineralized bone matrix. The second study demonstrated successful reconstitution of scalp and cranium with both demineralized bone matrix and Integra. We conclude that complex cranial defects involving bone and soft tissue may be successfully reconstructed with their tissue-engineered substrates, demineralized bone matrix (Grafton) and Integra artificial skin.

Absorptiometry, Photon↗
PubMed2000

Speech-evoked neurophysiologic responses in children with learning problems: development and behavioral correlates of perception.

OBJECTIVES: To evaluate the maturational progression of speech-evoked P1/N1/N2 cortical responses over the life span, determine whether responses are distinctive in clinical populations experiencing learning problems and elucidate the functional significance of these responses. DESIGN: The P1/N1/N2 complex was measured in 150 normal subjects (5 to 78 yr) and 86 subjects with learning problems (LP) (8 to 15 yr) to a synthetic CV syllable. Analyses included description and comparison of the developmental time course in both groups and evaluation of the relationship between P1/N1/N2 and children's performance on speech discrimination tasks and standardized learning measures. RESULTS: Findings revealed significant changes in waveform morphology, latency and amplitude as a function of age. Maturational patterns in the group of children with learning problems did not differ from the normal group. P1/N1/N2 parameters were significantly correlated with standardized tests of Spelling, Auditory Processing and Listening Comprehension in the LP group. Moreover, there was a predictive relationship between Auditory Processing and N2 latency. CONCLUSIONS: The P1/N1/N2 complex changes throughout life from school-age to old age. The developmental sequence throughout the school-age years is similar in normal and LP children. Thus, differences in the rate of P1/Nl/N2 latency and amplitude development do not appear to be distinctive in these two populations. The relationship between P1/N1/N2 parameters and standardized measures of learning (particularly between Auditory Processing and N2 latency) provides new information about the role of these responses in hearing and highlights the potential value in characterizing auditory processing deficits.

Adolescent↗
PubMed1999

Thalamic asymmetry is related to acoustic signal complexity.

Hemispheric asymmetries in response to speech sounds are well documented. However, it is not known if these asymmetries reflect only cortical hemispheric specialization to language or whether they also reflect pre-conscious encoding of signals at lower levels of the auditory pathway. This study examined differences in neural representations of signals with acoustic properties inherent to speech in the left versus right side of the thalamus. Specifically, 2000 Hz tone bursts, clicks and synthesized forms of the phoneme /da/ were presented to anesthetized guinea pigs. Evoked responses were recorded simultaneously from aggregate cell groups in the left and right medial geniculate bodies. Results showed an asymmetric response to complex auditory stimuli between the left versus right auditory thalamus, but not to the simple tonal signal. Moreover, asymmetries differed in male versus female animals.

Acoustic Stimulation↗
PubMed1999

Comparative microsatellite analysis in discerning origin of disseminated tumor: the case of a patient with malignant ascites and a history of multiple tumors.

The origin of metastatic carcinoma is now always easily resolved on the basis of conventional dinical and pathological parameters, particularly in patients with more than 1 primary tumor. When 1 of the tumors is a renal cell carcinoma, the clinical picture is further confounded by the tendency of these tumors to be locally silent, to metastasize to unusual sites, and to disseminate long after removal of the primary tumor. We compared tumors for loss (ie, deletion) of loci on chromosomal arms 3p, 5q, 11q, and 18q in a patient with a malignant ascites fluid, a remote history of renal and colonic neoplasms, and a strong clinical suspicion of disseminated gastrointestinal adenocarcinoma. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. Even though the clinical picture suggested a gastrointestinal origin, comparison of genetic alterations clearly showed that the malignant ascites represented recurrence of the renal cell carcinoma. The malignant ascites and the primary renal cell carcinoma showed identical patterns of allelic loss at all loci tested. In contrast, the malignant ascites and colonic adenoma showed discordant patterns of allelic loss. Comparative microsatellite analysis provides a rapid genetic approach for discerning the origin of metastatic tumor spread. This may be a useful diagnostic adjunct when tumor origin is not clear on clinical or morphological grounds. In some instances, it may even provide a reasonable alternative to an extensive and costly conventional work-up.

Adenoma↗
PubMed1997

Is it really a mismatch negativity? An assessment of methods for determining response validity in individual subjects.

Mismatch negativity (MMN) responses were collected from 86 normal school-age children in response to synthesized speech syllables, /wa/and two variants of /ba/. Waveform characteristics and statistical properties of the responses were analyzed across stimulus conditions in order to assess methods for determining response validity in individuals. Methods were compared using signal detection theory techniques. Criteria based on measurements of response area, onset latency, and duration were the best indicators of response validity. Also a promising indicator of validity was the interval of significance based on Z transformations determined by considering the variance of the underlying noise distribution. Correlations of individual responses with the grand average and integral calculations of the response negativity showed somewhat lower d' values. Statistical methods which utilized response subaverages were the poorest indicators of response validity. Likely the methods are limited primarily by the signal to noise ratio of the MMN compared to the underlying physiologic noise. Improvement of the signal to noise ratio remains a significant factor in the interpretation of MMN for individual subjects.

Acoustic Stimulation↗
PubMed1996

Acoustic elements of speechlike stimuli are reflected in surface recorded responses over the guinea pig temporal lobe.

Auditory evoked potentials measured from the guinea pig temporal lobe surface reflect acoustic elements of synthesized speech syllables. Eliciting stimuli included a four formant anchor stimulus /ba/, with a 40-ms formant transition duration. The other stimuli differed from /ba/ along simple acoustic dimensions. The /pa/ stimuli differed on a VOT continuum; /da/ stimuli had a higher frequency F2 onset; /wa/ had a longer (80 ms) formant transition duration; and /bi/ differed in three vowel formant frequencies. The /ba/ and /da/ onset response latencies decreased systematically with increasing F2 onset frequency. The response to the /pa/ voicing increased in latency with increasing VOT and showed a physiologic discontinuity at VOT of 15-20 ms. Responses to /ba/ and /wa/ showed similar onset morphology but significant amplitude differences at latencies corresponding to vowel onset. Significant amplitude differences in /ba/ and /bi/ responses corresponded in latency to both consonant and vowel portions of the syllables. Similar to previous reports in the awake monkey for VOT, these results demonstrate in the anesthetized guinea pig that acoustic elements essential to speech perception are reflected in aggregate response of ensembles of cortical neurons.

Animals↗
PubMed1995

Acoustic features and acoustic changes are represented by different central pathways.

The central processing of acoustic stimulus changes can be observed neurophysiologically in the mismatch negativity auditory evoked potential (MMN). Stimuli differing in interaural phase were used to investigate the contributions of the primary and non-primary auditory pathways to the encoding of binaural stimuli and to investigate passively elicited measures of binaural processing in experimental animals. In guinea pigs, the MMN was obtained in response to 1000 Hz tones embedded in white noise (S:N = 2 dB). Using a modified oddball paradigm (that is, two stimuli presented in a series, each with a different probability of occurrence), stimuli were presented binaurally with both the tone and noise in-phase to the two ears (S0N0) as the standard stimulus ans the tone 180 degrees out-of-phase (S(PI)N0) as the deviant stimulus. The MMN, by definition, should occur only in response to a change, or 'mismatch,' between the standard and deviant stimuli. The response to the deviant stimulus in the oddball paradigm was compared to the response to the same stimulus when presented in a series alone. The responses to S0N0 and S(PI)N0 collected in a series alone, termed the intrinsic responses, were also compared. Responses were recorded from two surface epidural electrodes - one at the posterior midline and one over the left temporal lobe. AEPs from these locations have been shown to reflect the activity of primary and non-primary thalamo-cortical pathways respectively. A significant MMN was observed at the midline electrode, but no MMN was observed over the temporal lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1995

Speech-evoked cognitive P300 potentials in cochlear implant recipients.

The cognitive P300 evoked potential was elicited by speech stimuli in successful cochlear implant recipients, and the resulting P300 morphology was remarkably similar to that of normal-hearing individuals. The P300 was elicited by the synthesized speech pair/da/and/di/ presented using an oddball paradigm to nine "good" Nucleus cochlear implant users and nine age-matched normal-hearing subjects (34-81 yr old). There were no significant differences in P300 amplitude and latency between the two groups. Moreover, the N1 and P2 potentials occurred at similar latencies in the two groups, although the N1 amplitude was significantly smaller in the cochlear implant users. The P300 was absent in one "poor" cochlear implant user. The results suggest that the P300 may serve as a useful tool for evaluating the cognitive aspects of auditory processing in cochlear implant recipients, and that it may aid in assessing the success of cochlear implantation.

Acoustic Stimulation↗
PubMed1994

Binaural response patterns in subdivisions of the medial geniculate body.

Auditory evoked potentials (AEPs) to binaural click stimulation were examined in the ventral (MGv) and caudomedial (MGcm) subdivisions of the medial geniculate body (MG) in guinea pigs. Binaural stimulation caused a decrease in amplitude for the response component recorded from the MGv, but an increase in amplitude for the AEP component recorded from the MGcm. Findings suggest that the evoked responses recorded from MGv and MGcm are functionally distinct. The inhibitory binaural response (BR) pattern seen in MGv was similar to that of the middle latency response (MLR) component recorded over the temporal cortex, while the additive BR pattern typical of the MGcm was similar to that of the surface midline MLR component. Furthermore, these data imply that the binaural response patterns seen in the primary and non-primary auditory cortex may be processed and encoded at the thalamic level. It is concluded that the distinct BR patterns noted for the two MG subdivisions reflect the predominant type of binaurally responsive neurons within the respective pathways.

Acoustic Stimulation↗