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Biomedical subjects

S Leeman

Publications and source records attributed to S Leeman.

At least 19 recordsLinked to original sources
PubMed1999

Actions of intrathecal diphtheria toxin-substance P fusion protein on models of persistent pain.

Substance P (SP) plays a central role in the transduction of second messenger signals from primary afferent nociceptive terminals to second-order neurons in the spinal cord. We have tested a recombinant engineered diphtheria toxin/SP fusion protein (DAB389SP) in acute and chronic pain models in the rat. DAB389SP binds to the SP receptor (SPR) and is internalized and kills SPR-expressing cells by blocking cellular protein synthesis. DAB389SP delivery was by intrathecal infusion, of varying duration, at the lumbar level. In the chronic constriction injury model of neuropathic pain a significant reduction in mechanically induced hyperalgesia was obtained. This effect was less marked in an acute carageenan inflammation model. Although other pain characteristics (mechano-allodynia, cold-allodynia, and heat-hyperalgesia) showed some improvement, these were less pronounced. Immunocytochemistry revealed a toxin-induced reduction in lamina I, of SPR and of NMDA NR1 subunit receptor expressing neurons, and of c-Fos, an inducible molecular marker of persistent nociceptive activity. The use of cytotoxic fusion proteins to target specific cell types may be of considerable benefit in the study of nociception and the treatment of chronic pain.

Acute Disease↗
PubMed1995

Periodontal disease activity: a development strategy for its investigation by means of accurate 3-dimensional clinical measurement.

The central problem in all previous approaches to clinical assessment of periodontal disease activity is the use of unidimensional measurement, which implies a number of unjustifiable assumptions. In addition, the use of unidimensional probing measurement has established that there are several distinct problems of validity and reliability in currently available techniques. The present paper begins with an analysis of these matters, leading to an approach to accurate clinical measurement of periodontitis in 3 dimensions, with the possibility of future development of a valid system for assessing the nature of disease activity.

Connective Tissue↗
PubMed1994

Nonparametric estimation of ultrasound pulses.

An algorithm for nonparametric estimation of 1-D ultrasound pulses in echo sequences from human tissues is derived. The technique is a variation of the homomorphic filtering technique using the real cepstrum, and the underlying basis of the method is explained. The algorithm exploits a priori knowledge about the structure of rf line echo data and can employ a number of adjacent rf lines from an image. The prime application of the algorithm is to yield a pulse suitable for deconvolution algorithms. This will enable these algorithms to properly take into account the frequency dependence of the attenuation and its variation within a patient and among patients. It is also possible to use the estimated pulse for attenuation estimation, and the consistency of the assumptions underlying the proposed technique is demonstrated by its ability to recover low variance attenuation estimates in the normal liver from in vivo pulse-echo data. Estimates are given for eight different patients.

Adult↗
PubMed1991

Assessment of hybrid speckle reduction algorithms.

A consequence of employing coherent detection methods in medical ultrasound imaging systems is the occurrence of interference effects in the received echo field, which produce the speckle artefact. Speckle can severely degrade the information content of the image, and its efficient removal from ultrasound pulse-echo images is the focus of a number of research projects. Traditionally, the approach towards speckle reduction in pulse-echo images has been based on two classes of technique, either employing some form of spatial/frequency compounding or a data (image) filter. Both approaches have inherent shortcomings, and two alternative techniques are suggested here: 'local frequency diversity' and 'frequency differencing'. These algorithms deterministically identify where speckle occurs, and correct for speckle only within short, localized, corrupted segments of the A-line. This provides the potential for real-time implementation. Simulated and clinical in vivo images have been obtained, and the capabilities of the alternative speckle reduction algorithms are assessed against the more conventional approaches.

Algorithms↗
PubMed1991

[Lipedema].

An overall view of the clinical findings in lipedema is given and of its treatment. Lipedema is shown to be a distinct illness, and not just a disturbance of the distribution pattern of subcutaneous fatty tissue. The diagnosis is based on an accurate history and specific criteria on clinical examination and palpation.

Adipose Tissue↗
PubMed1989

Substance P and neurokinin A in the cat carotid body: localization, exogenous effects and changes in content in response to arterial pO2.

In the present work we studied the occurrence of substance P (SP) and neurokinin A (NKA) in the carotid bodies of cats by means of immunocytochemistry and radioimmunoassay (RIA). We also compared the exogenous effects of SP and NKA on carotid body sensory discharge. SP- and NKA-like immunoreactivities (SP-LI; NKA-LI) were seen in many glomus cells and in a sparse plexus of fine fibers. The SP-LI containing glomus cells and fibers also exhibited NKA-LI, suggesting that both these tachykinins coexist in the carotid body. Chemoreceptor discharge increased both by SP and NKA in a dose-dependent manner. The peak excitation produced by SP and NKA was the same when the effects were compared on an equimolar basis. The tachykinin content of the carotid bodies varied with changes in arterial pO2. During normoxia, SP and NKA levels were 57 +/- 8 and 85 +/- 14 fmol/mg, respectively. When the animals were exposed for 1 h to 100% O2, SP content was unchanged (51 +/- 4 fmol/mg), whereas NKA levels were significantly lower than during normoxia (29 +/- 3 fmol/mg, P less than 0.01). Following 1 h of hypoxia, SP content of the carotid body was 146 +/- 20 fmol/mg, a value higher than that obtained during normoxia and hyperoxia. NKA levels, on the other hand, were not significantly different from normoxic values. These results indicate that the cat carotid body (1) contains both SP and NKA, (2) both peptides augment neural discharge of the carotid body and (3) their levels in the carotid body are substantially altered by arterial oxygen, the natural stimulus to the chemoreceptors.

Action Potentials↗
PubMed1989

Reflections on tissue characterisation.

Theoretical predictions that absorption and velocity dispersion, in addition to characteristic acoustic impedance mismatch, mediate the reflectivity of a planar interface are explored. A technique to measure the frequency dependence of the reflectivity is described: a special hydrophone, purpose-built to this end, is utilised in order to show that perspex/water and neoprene/water reflectivities are not inconsistent with the general predictions of the theory. An approach towards displaying, simultaneously, both the temporal and spectral properties of ultrasound pulses is described, and its potential utility in both reflectivity measurement and investigation of non-linear propagation is proposed.

Acoustics↗
PubMed1989

Phasing out speckle.

It is demonstrated that the instantaneous frequency of a backscattered echo sequence can be used to pinpoint the location of destructive interference effects. These interference artefacts, which are generally interpreted as speckle in the image, are generally removed by stochastic averaging or filtering methods applied to the acquired image. The method proposed here can detect such artefacts within individual A-lines, and thus differs from conventional techniques. Where speckle is recognised within each A-line, the artefact can be corrected on a local basis by the application of the frequency diversity technique. Because it relies only on A-line processing, the approach points the way towards a speckle reduction technique which can realistically be implemented on a real-time basis. In this paper, the principles of the technique are illustrated using a simple two-reflector model.

Computer Simulation↗
PubMed1989

Quantitative sonography of muscle.

Ultrasound imaging allows detection of pathologic change in muscle on the basis of increased strength of echoes. With current commercial equipment, however, there is no method of quantitation of the echoes representing muscle, and there is lack of uniformity in scanning methodology. We describe a specially constructed scanning system, designed to access the raw echo data directly from the ultrasound transducer, and allow display and measurement of the echo signals on a computer. In a study of 38 boys with Duchenne muscular dystrophy, aged 1 to 11 years, who had an ultrasound scan of the thigh muscle, 32 (84%) had abnormality on quantitation of the ultrasound echoes. The quantitative techniques we describe could easily be incorporated into the design of ultrasound scanners.

Adolescent↗
PubMed1988

Acute reduction of brain substance P induced by nicotine.

Ten minutes after a single injection of 0.8 mg/kg nicotine SC (free base) the level of substance P-like immunoreactivity (SPLI) was reduced by 61-73% in rat caudate-putamen, nucleus accumbens, and olfactory tubercle, with smaller and not significant reductions in the frontal cortex, substantia nigra, and ventral tegmental area. The nicotinic receptor antagonist mecamylamine (1.0 mg/kg IP) prevented the reductions in SPLI. The rapidity and the degree of the changes in SPLI after nicotine exceed those previously reported for other agents and implicate substance P neurotransmission as a major component of nicotinic action.

Animals↗
PubMed1986

Noninvasive evaluation of hepatic fibrosis using frequency demodulation of ultrasound signals.

A new ultrasound image can be produced by frequency demodulation (FM) of the conventional ultrasound signal. This new FM image appeared to produce a more accurate representation of the fine structure of the liver. The individual features of the FM image were correlated with hepatic portal fibrosis and cirrhosis on liver biopsy in 34 patients with minimal hepatic fat and sinusoidal collagen. An overall ultrasound score correlated with portal fibrosis (r = 0.788; P less than 0.001). We conclude that the FM image may be helpful in measuring and following the progression of hepatic fibrosis in patients with chronic liver disease.

Biopsy↗
PubMed1986

Frequency-demodulated US: evaluation in the liver. Work in progress.

Frequency modulated (FM) imaging is a new ultrasound (US) modality that uses pulse-echo signal instantaneous frequency in addition to the conventional envelope information. Eight features of the FM image in nondiseased livers are described. The technique is evaluated in a study of 34 patients with biopsy-proved diffuse liver disease. Visual grading of FM US image features shows good correlation with levels of biopsy-graded hepatic fibrosis. Patients with diffuse parenchymal liver disease often exhibit evidence of the abnormality when FM liver imaging is used, while such evidence is not as well demonstrated with conventional envelope (AM) imaging.

Humans↗
PubMed1986

The instantaneous frequency of a sinewave squelched bandlimited signal.

We study the instantaneous frequency of a signal which is formed by the summation of a sinewave and a bandlimited signal. We refer to the composite signal as a sinewave squelched or simply a squelched signal. We study the behavior of the squelched signal at its real zeros and extrema. In particular when the sinewave frequency is equal to the largest frequency in the signal's spectrum and its amplitude is greater than the signal's maximum amplitude, the analytic signal corresponding to this resultant signal (hereafter abbreviated as RZ signal) has only real zeros which contain all of the bandlimited signal's information. FM systems often use zero crossing techniques in the demodulation process. For a process with a normal amplitude distribution, we derive a relationship between the zero crossing density of an RZ converted signal and that of the original signal. One application of these analyses is in ultrasonic FM imaging. We give an explanation for the behavior of the FM imaging system as a function of amplitude and frequency of the added cosine.

Image Processing, Computer-Assisted↗
PubMed1984

Attachment of fibroblasts following hyperthermia and ultrasound.

The rate of cell attachment to the culture substratum is reduced in mouse L cells by hyperthermia at 44 degrees C. The time for 50 per cent attachment of the cells increases rapidly with increasing time of heating immediately before assay. The rate of attachment after 44 degrees C does not show a linear correlation with clonogenic survival, ruling out the use of attachment as a rapid assay of clonogenic survival. The attachment process is less sensitive to heat in cells made thermally tolerant by a prior heat treatment. In contrast, ultrasound irradiation at 37 degrees C and below the cavitational threshold (1.5 MHz, 2.2 W/cm2, 15 min) did not alter the rate of attachment, but at 44 degrees C, ultrasound decreased both clonogenic survival and the rate of attachment to a much greater extent than 44 degrees C alone. As the temperature increase caused by the ultrasound was less than 0.5 degrees C, the data provide evidence of a non-thermal component of ultrasound damage.

Animals↗
PubMed1982

Ultrasound imaging in the diagnosis of muscle disease.

A comparative study has been done of the static B-scan ultrasound appearance of the quadriceps muscle of the thigh in 60 new patients attending our muscle clinic and in 60 control children. In the control subjects there was good visualization of bone and fascia, which stood out clearly against the background of echo-free muscle tissue. Striking change was found in children with neuromuscular disease. Muscular dystrophies were associated with an increase in the intensity of echo reflected from the muscle substance, with corresponding loss of bone echo. Spinal muscular atrophies and neuropathies also showed an increase in muscle echo along with atrophy of the muscle and increase in depth of subcutaneous tissue. Various congenital myopathies also showed changes. Infants with hypotonia from nonneuromuscular causes had normal scans. Severity of change on the scan did not relate to functional disability, and some children had good function yet strikingly abnormal scans. Three degree of change on the scan correlated with the degree of disruption of muscle architecture on biopsy. Ultrasound imaging has proved to be a useful, noninvasive screening tool in the investigation of children with neuromuscular disease.

Adolescent↗
PubMed1981

Peptide and amine transmitter effect on embryonic chick sensory neurons in vitro.

It has been known for some time that NE and ACh can affect voltage-sensitive channels in the heart but it has only recently been appreciated that neurotransmitters (and certain peptides) can modulate voltage-sensitive channels in neurons. In addition to the effect on the action potential of embryonic chick sensory neurons described here, NE decreases the duration of spikes in rat superior cervical ganglion neurons (7). Serotonin prolongs action potentials recorded in Aplysia sensory neurons (9) and an as yet unidentified transmitter decreases an inward Ca++ current in the same cells (20). In the heart, one important consequence of the effect of NE and ACh on the action potential is a change in the strength and/or duration of contraction. In neurons, attention has been focused on the possibility that modulation of voltage-sensitive channels might result in a change in transmitter release. In Aplysia, the 5-HT induced prolongation of sensory neuron some spikes is associated with a dramatic augmentation of transmitter release at sensory nerve-motorneurone synapses (9) and the decrease in some inward Ca++ current is associated with presynaptic inhibition (20). Enkephalin, NE, GABA, and 5-HT can inhibit the evoked release of Substance P from cultured embryonic chick sensory neurons. These same drugs decrease ICa, apparently by decreasing the number of the conductance of voltage-sensitive Ca++ channels. The two phenomena may be related. It is significant in this regard that the same variability (between platings) in the ability of enkephalin to reduce Substance P release was also observed in the effect of enkephalin on action potential duration. Cells that released normal amounts of Substance P in the presence of enkephalin also exhibit spikes of normal duration in the presence of the peptide.

Acetylcholine↗
PubMed1980

Detection of pathological change in dystrophic muscle with B-scan ultrasound imaging.

A comparative study of the ultrasound appearances of the thigh with the static B scan showed consistent differences in 10 children with muscular dystrophy compared with 40 healthy controls. This non-invasive technique could be useful in assessing the extent of pathological change in dystrophic patients and could prove a valuable diagnostic aid.

Adolescent↗