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Biomedical subjects

M J Hewitt

Publications and source records attributed to M J Hewitt.

16 recordsLinked to original sources
PubMed2000

The use of whole rat embryo culture as a technique for investigating potential serum toxicity in recurrent miscarriage patients.

Previously, the rat embryo model has been used as an experimental technique in investigations of the aetiology of idiopathic recurrent miscarriage. The aim of the present study was to validate it as a tool in the investigation of the aetiology of this condition. Subjects (n = 36) with a history of recurrent miscarriage were recruited from two dedicated recurrent miscarriage clinics and compared with control women with at least one previous pregnancy resulting in a live birth (n = 23). Serum from each woman was used as culture medium in the rat embryo model. Cultured embryos were scored for growth and differentiation. No statistical difference was found in any parameter between the two groups. Furthermore, patients from the recurrent miscarriage group whose serum demonstrated a trend towards lower scores, subsequently conceived and underwent uncomplicated pregnancies.

Abortion, Habitual↗
PubMed1995

A computer model of dorsal cochlear nucleus pyramidal cells: intrinsic membrane properties.

Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] studied "simple spiking," pyramidal cells of the dorsal cochlear nucleus (DCN) maintained in vitro. Response profiles to hyperpolarizing and depolarizing current pulses were generated. Hyperpolarization of the cell membrane followed by depolarization produced markedly different response profiles from those generated when no prehyperpolarization was imposed. By manipulating the magnitude of the hyperpolarizing and depolarizing pulses, "chopper," "pauser" and "build-up" response patterns, similar to those in vivo, could be generated by individual cells. Manis concluded that the different response profiles resulted from the modulation of intrinsic membrane conductances by the prehyperpolarizing pulses. Here a computer model is used to show that (a) steady-state hyperpolarization can influence cell responding to subsequent depolarization in a manner consistent with the data reported by Manis; and (b) the effects reported can be generated by the addition of a modeled transient potassium conductance to the standard Hodgkin-Huxley model of spike generation [A. L. Hodgkin and A. F. Huxley, J. Physiol. 117, 500-544 (1952)]. The model will be of use to those who wish to consider the role of various excitatory and inhibitory inputs to pyramidal cells and to establish their functional role within the DCN.

Cochlear Nucleus↗
PubMed1994

A computer model of amplitude-modulation sensitivity of single units in the inferior colliculus.

A computer model is presented of a neural circuit that replicates amplitude-modulation (AM) sensitivity of cells in the central nucleus of the inferior colliculus (ICC). The ICC cell is modeled as a point neuron whose input consists of spike trains from a number of simulated ventral cochlear nucleus (VCN) chopper cells. Input to the VCN chopper cells is provided by simulated spike trains from a model of the auditory periphery [Hewitt et al., J. Acoust. Soc. Am. 91, 2096-2109 (1992)]. The performance of the model at the output of the auditory nerve, the cochlear nucleus and ICC simulations in response to amplitude-modulated stimuli is described. The results are presented in terms of both temporal and rate modulation transfer functions (MTFs) and compared with data from physiological studies in the literature. Qualitative matches were obtained to the following main empirical findings: (a) Auditory nerve temporal-MTFs are low pass, (b) VCN chopper temporal-MTFs are low pass at low signal levels and bandpass at moderate and high signal levels, (c) ICC unit temporal-MTFs are low pass at low signal levels and broadly tuned bandpass at moderate and high signal levels, and (d) ICC unit rate-MTFs are sharply tuned bandpass at low and moderate signal levels and flat at high levels. VCN and ICC units preferentially sensitive to different rates of modulation are presented. The model supports the hypothesis that cells in the ICC decode temporal information into a rate code [Langner and Schreiner, J. Neurophysiol. 60, 1799-1822 (1988)], and provides a candidate wiring diagram of how this may be achieved.

Animals↗
PubMed1993

Regularity of cochlear nucleus stellate cells: a computational modeling study.

This article reports on a computational modeling study designed to investigate the generation of the transient chopper response of cochlear nucleus stellate cells. The model is based on a simulation of the auditory periphery which feeds a generic stellate-cell model. Physiological recordings of transient chopper units in response to short, best frequency, tone bursts show a brief initial period (typically < 10 ms) of rapid rate adaptation as evidenced by a rapid rise in mean interspike interval. Associated with this rate adaptation is a significant increase in firing irregularity. The changes in rate and irregularity have recently been attributed to the activation of noisy inhibitory inputs on the cell [e.g., Banks and Sachs, J. Neurophysiol. 65, 606-629 (1991)]. However, the results show that the transient chopper response pattern can be generated without the need for inhibitory inputs. The transience of the initial chopping pattern is sensitive to the following model parameters: (a) the firing threshold of the cell, (b) the number of excitatory inputs that converge on the cell, and (c) the magnitude of the current delivered to the cell for each active input. The response was also found to be relatively insensitive to changes in the degree of dendritic filtering imposed on the auditory-nerve input. The results of each simulation can be explained by considering the pattern of depolarization the cell receives during the course of a tone burst.

Acoustic Stimulation↗
PubMed1993

Hydration of the fat-free body mass in children and adults: implications for body composition assessment.

Previous studies have shown that children have a higher aqueous fraction of the fat-free body mass (FFM) than young adults. In older adults, methodological differences among studies limit evaluation of potential age-related differences in the water content of the FFM (W/FFM). Therefore, we determined W/FFM in 28 healthy white prepubescent children (age = 5-10 yr), 31 young adults (age = 22-39 yr), and 62 older adults (age = 65-84 yr), using 2H2O dilution to estimate total body water and a multicomponent approach based on body density, total body water, and regional bone mineral density to estimate FFM. To quantify the extent to which variation in W/FFM affects percent fat estimation error, differences in percent fat between our multicomponent approach and the Siri two-component model were related to W/FFM. Prepubescent children (72.7 +/- 1.6%) and older adults (72.5 +/- 1.4%) were found to have significantly higher (P < 0.01) mean W/FFM than young adults (70.8 +/- 1.2%). Differences in percent fat between the multicomponent and two-component models ranged from -10 to 6% fat and were significantly associated with W/FFM (r = -0.62, P < 0.0001). We conclude that prepubescent children and older adults, on average, have a higher W/FFM than young adults, and that, in adults, individual differences in W/FFM account for a substantial portion of the percent fat estimation errors associated with the use of two-component body composition models.

Adipose Tissue↗
PubMed1992

Modeling the identification of concurrent vowels with different fundamental frequencies.

Human listeners are better able to identify two simultaneous vowels if the fundamental frequencies of the vowels are different. A computational model is presented which, for the first time, is able to simulate this phenomenon at least qualitatively. The first stage of the model is based upon a bank of bandpass filters and inner hair-cell simulators that simulate approximately the most relevant characteristics of the human auditory periphery. The output of each filter/hair-cell channel is then autocorrelated to extract pitch and timbre information. The pooled autocorrelation function (ACF) based on all channels is used to derive a pitch estimate for one of the component vowels from a signal composed of two vowels. Individual channel ACFs showing a pitch peak at this value are combined and used to identify the first vowel using a template matching procedure. The ACFs in the remaining channels are then combined and used to identify the second vowel. Model recognition performance shows a rapid improvement in correct vowel identification as the difference between the fundamental frequencies of two simultaneous vowels increases from zero to one semitone in a manner closely resembling human performance. As this difference increases up to four semitones, performance improves further only slowly, if at all.

Acoustics↗
PubMed1992

A computer model of a cochlear-nucleus stellate cell: responses to amplitude-modulated and pure-tone stimuli.

A computer model of a ventral-cochlear-nucleus (VCN) stellate cell with chop-S type response properties is presented and evaluated. The model is based on a simplified model of spike generation preceded by a stage that simulates dendritic low-pass filtering. Input to the model is in the form of simulated auditory-nerve spikes produced by a model of the auditory periphery [Meddis and Hewitt, J. Acoust. Soc. Am. 89, 2866-2882 (1991)]. Outputs from the stellate-cell model are shown to qualitatively replicate a wide range of typical in vivo responses. These include: (a) realistic onset and steady-state rate-level functions, (b) "chopper"-type post-stimulus time histogram responses; (c) typical "chop-S"-type neuron responses characterized by a low coefficient of variance (CV less than 0.3) of interspike intervals as a function of time; (d) level-dependent amplitude-modulation transfer functions; (e) intrinsic oscillations in responses to pure-tone stimuli; (f) amplitude-modulation encoding over a wide dynamic range; and (g) frequency-limited phase locking to pure tones. It is shown that these responses can be explained primarily by the membrane properties of the cells. More specifically, how the model encodes signal amplitude modulation was studied and an explanation was suggested for the generation of the bandpass modulation transfer functions. Such functions are observed neurally in response to amplitude-modulated stimuli presented at moderate to high signal levels.

Animals↗
PubMed1991

An evaluation of eight computer models of mammalian inner hair-cell function.

Eight computer models of auditory inner hair cells have been evaluated. From an extensive literature on mammalian species, a subset of well-reported auditory-nerve properties in response to tone-burst stimuli were selected and tested for in the models. This subset included tests for: (a) rate-level functions for onset and steady-state responses; (b) two-component adaptation; (c) recovery of spontaneous activity; (d) physiological forward masking; (e) additivity; and (f) frequency-limited phase locking. As models of hair-cell functioning are increasingly used as the front end of speech-recognition devices, the computational efficiency of each model was also considered. The evaluation shows that no single model completely replicates the subset of tests. Reasons are given for our favoring the Meddis model [R. Meddis, J. Acoust. Soc. Am. 83, 1056-1063 (1988)] both in terms of its good agreement with physiological data and its computational efficiency. It is concluded that this model is well suited to provide the primary input to speech recognition devices and models of central auditory processing.

Animals↗
PubMed1981

Coronary sinus atrial pacing: radiographic considerations.

Transvenous atrial pacing via an electrode placed in the coronary sinus has become an increasingly frequent procedure during the past 10 years for both diagnosis and therapy of cardiac arrhythmias. The coronary sinus has five major venous tributaries, any one of which can be entered by a pacing catheter. A catheter in the middle cardiac vein can mimic the usual ventricular pacemaker position, while an electrode in the coronary sinus or in a persistent left superior vena cava may be mistaken for myocardial perforation. A persistent left superior vena cava may also be catheterized. This anomaly is associated with a tenfold increased incidence of congenital atrioventricular conduction abnormalities and, therefore, is surprisingly common in patients having coronary sinus pacers placed because of cardiac arrhythmias.

Adult↗
PubMed1980

Calyceal calculi simulating gallstones.

Multiple faceted stones can develop in any sacular structure. Five cases of renal stones are described, four cases with calculi in calyceal diverticuli and one case with calculi in a hydronephrotic sac. Emphasis is on the remarkably similar radiographic appearance these cases of renal stones have with gallstones.

Adult↗
PubMedDate not supplied

Cellular proliferation in the placenta in normal human pregnancy and pregnancy complicated by intrauterine growth restriction.

OBJECTIVE: To determine the incidence of cellular proliferation in the placenta throughout the three trimesters of normal pregnancy, and in the third trimester of pregnancy complicated by intrauterine growth restriction (IUGR). METHODS: Placental samples were obtained from 17 first-trimester pregnancies, 9 second-trimester pregnancies, 33 uncomplicated third-trimester pregnancies, and 21 third-trimester pregnancies complicated by IUGR. These samples were then stained by immunohistochemical technique, using the monoclonal antibody MIB-1. RESULTS: The incidences of cellular proliferation in the four groups were as follows: first trimester (n = 17): 11.8% of cells (8.51-17.04); second trimester (n = 9): 9.88% of cells (5.04-10.99); normal third trimester (n = 33): 3.15% of cells (2.07-3.7); IUGR third trimester (n = 21): 3.7% of cells (3.02-4.85). The decline in cellular proliferation throughout the three trimesters of pregnancy was statistically significant (P < .0001 Kruskall-Wallis test). The Spearman rank correlation for proliferative index against gestational age had a P value less than .0001 (Rho corrected for ties = -0.81). There was no statistically significant difference in the incidence of cellular proliferation between normal third-trimester and IUGR third-trimester samples. CONCLUSION: The incidence of cellular proliferation in the placenta declines as pregnancy progresses, a finding that agrees with previous work by others. The incidence of cellular proliferation was not altered in cases of IUGR.

Adolescent↗
PubMedDate not supplied

Image-guided biopsy in women with breast cancer presenting with peritoneal carcinomatosis.

When women with a history of breast cancer present with peritoneal carcinomatosis, the differential diagnosis lies between recurrent breast cancer or a new primary tumor. This scenario is of particular relevance to women with a BRCA gene mutation, who have a genetic predisposition to develop second primary tumors of the ovary, fallopian tube, and peritoneum. We describe the use of image-guided core biopsy as an alternative to laparoscopy or exploratory laparotomy in providing minimally invasive diagnosis in this increasingly common clinical dilemma.

Adenocarcinoma↗
PubMedDate not supplied

The detection of microsatellite instability in blind endometrial samples--a potential novel screening tool for endometrial cancer in women from hereditary nonpolyposis colorectal cancer families?

Microsatellite instability (MSI) is the phenotypic molecular characteristic of the majority of tumors associated with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC). Women in this group have an increased risk of endometrial cancer (EC). This study aimed to determine whether MSI could be demonstrated in blind endometrial samples from women with EC, HNPCC kindreds undergoing screening for EC, and women with normal endometrium. Twenty-four women with EC, 20 women from HNPCC kindreds, and 20 women undergoing gynecological surgery for benign indications underwent blind sampling. MSI analysis was performed by conventional polymerase chain reaction using fluorescent-labeled primers and automated analysis. Twelve microsatellites were studied with MSI defined as evident when novel alleles were seen in endometrial biopsy samples compared to genomic DNA. Of the 24 EC samples obtained, sufficient DNA for analysis was extracted in 17 cases. Three cases had evidence of MSI in at least 7/12 loci. None of the endometrium from the two other study groups revealed evidence of MSI. This is the first demonstration of MSI in blind endometrial biopsies. The ability to demonstrate MSI in heterogeneous endometrial samples suggests potential for the development of a novel EC screening tool for women in HNPCC kindreds.

Adult↗