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Biomedical subjects

W F Walker

Publications and source records attributed to W F Walker.

At least 19 recordsLinked to original sources
PubMed2000

A method of imaging viscoelastic parameters with acoustic radiation force.

Acoustic radiation force has been proposed as a method of interrogating the mechanical properties of tissue. One simple approach applies a series of focused ultrasonic pulses to generate an acoustic radiation force, then processes the echoes returned from these pulses to estimate the radiation-force-induced displacement as a function of time. This process can be repeated at a number of locations to acquire data for image formation. In previous work we have formed images of tissue stiffness by depicting the maximum displacement induced at each tissue location after a finite period of insonification. While these maximum displacement images are able to differentiate materials of disparate mechanical properties, they exploit only a fraction of the information available. In this paper we show that the time-displacement curves acquired from tissue mimicking phantoms exhibit a viscoelastic response which is accurately described by the Voigt model. We describe how the viscous and elastic parameters of this model may be determined from experimental data. Finally, we show phantom images that depict not only the maximum local displacement, but also the viscous and elastic model parameters. These images offer complementary information about the target.

Acoustics↗
PubMed1999

Cellular and molecular studies in muscle and cultures from patients with multiple mitochondrial DNA deletions.

In the last decade, several mitochondrial encephalomyopathies have been pathogenically associated with large-scale mitochondrial DNA deletions that are sporadic, or with point mutations that are maternally inherited. The mutations were also demonstrated in cultures of muscle satellite cells obtained from the patients. Subsequently, multiple deletions in mitochondrial DNA were found in several families. The affected members had progressive external ophthalmoplegia, cataracts and limb weakness, inherited as an autosomal dominant trait, or progressive external ophthalmoplegia with neurogastrointestinal encephalomyopathy or with cardiomyopathy, inherited as an autosomal recessive trait. To better understand the developmental pathobiology and localization of the multiple deletions, we performed comparative molecular genetic studies in muscle and cultures from patients. Whereas multiple deletions were found in muscle fragments from which muscle satellite cells were removed by enzymatic digestion, no deletions were found in the satellite cells or their cultured progeny. Our results suggest that multiple mitochondrial DNA deletions arise as somatic mutations during later stages of muscle development, or in terminally differentiated myofibers.

Adolescent↗
PubMed1999

Internal deformation of a uniform elastic solid by acoustic radiation force.

Tissue elasticity estimation is a growing area of ultrasound research. One proposed approach would apply acoustic radiation force to displace tissue and use ultrasonic motion tracking techniques to measure the resultant displacement. Such a technique might allow noninvasive imaging of tissue elastic properties. The potential of this method will be limited by the magnitude of displacements which can be generated at reasonable acoustic intensity levels. This paper presents methods for estimating the internal displacements induced in an elastic solid by acoustic radiation force. These methods predict displacements on the order of 400 microns in the human vitreous body, 0.008 micron in human breast, and 0.020 micron in human liver at an acoustic intensity of 1.0 W/cm2 (in water) and an operating frequency of 10 MHz. While the displacement generated in the vitreous should be readily detectable using ultrasonic methods, the displacements generated in the breast and liver will be much more difficult to detect. Methods are also developed for predicting the time dependent temperature increases associated with attenuated acoustic fields in the absence of perfusion. These results indicate promise for radiation force imaging in the vitreous, but potential difficulties in applying these techniques in other parts of the body.

Elastic Tissue↗
PubMed1997

Mitochondrial mobility in differentiating muscle heterokaryons.

Ragged-red fibers, a morphological hallmark of many patients with mitochondrial encephalomyopathies who harbor mitochondrial DNA (mtDNA) mutations, usually contain varying ratios of mutated and wild-type mtDNAs. Deficient respiratory function in muscle is almost invariably segmental. To investigate whether this observation may be explained by restricted lateral movement of mitochondria within myofibers, we studied the spatial and temporal behavior of two different mitochondrial populations within multinucleate myotubes. We co-cultured normal human and mouse myoblasts, allowed them to fuse into muscle heterokaryons and investigated whether the mitochondria remained segregated, or migrated and intermixed. Human and mouse nuclei were identified by their differential staining pattern with the dye Hoechst 33 258 and mitochondria were distinguished immunologically and by in situ hybridization. Although we observed some territoriality at very early time points after myoblast fusion, there was rapid intermixing of the mitochondrial populations, as early as 48 h after myoblast fusion. We conclude that mitochondria, unlike many other muscle components, lack territorial organization in cultured, differentiating heterokaryons.

Animals↗
PubMed1997

Speckle coherence and implications for adaptive imaging.

Tissue speed of sound inhomogeneities cause significant degradation of medical ultrasound images. In certain cases these inhomogeneities can be modeled as a thin, spatially varying time delay screen located at the face of the transducer. Correction of such aberrators requires the addition of compensating time delays to the normal system focusing delays. These compensating delays are estimated from the arrival time differences between echoes received on different array elements. The accuracy with which these arrival time differences can be estimated is limited by the level of correlation between received speckle signals. This paper derives analytical expressions predicting the correlation between speckle signals acquired by a pulse echo system with either point or larger receive elements in the presence of near-field phase aberrations. Simulations are presented which are in good agreement with theoretical predictions. Similarities between the derived expressions and the Van Cittert-Zernike Theorem are discussed. These results indicate that near-field phase aberration correction may be far more difficult than previous analyses suggest because of the low correlation between echoes received by adjacent elements in elevation in 1.5-D arrays. Transmit aperture amplitude apodization and a new translating aperture technique are presented as methods for improving speckle correlation.

Algorithms↗
PubMed1997

Deficient muscle carnitine transport in primary carnitine deficiency.

Primary carnitine deficiency is associated with deficient blood and tissue carnitine concentrations. The clinical syndrome is dominated by heart and skeletal muscle symptoms, and the clinical response to oral carnitine supplementation is life-saving. Carnitine uptake has been shown to be defective in cultured skin fibroblasts and leukocytes obtained from patients with this condition. We report a new case of primary carnitine deficiency and offer direct evidence consistent with an impairment of carnitine uptake in differentiating muscle culture. The patient presented with severe and progressive cardiomyopathy and moderate proximal limb weakness. Plasma and muscle carnitine levels were very low, and the maximal rate of carnitine transport in cultured fibroblasts was deficient. An asymptomatic sister with intermediate levels of carnitine in plasma showed partially deficient carnitine uptake in fibroblasts, indicating heterozygosity. The patient's condition improved dramatically with oral carnitine therapy. Further studies were performed in cultured muscle cells at different stages of maturation, which demonstrated deficient maximal rates of carnitine uptake. Our findings are consistent with the concept that primary carnitine deficiency is the result of a generalized defect involving carnitine transport across tissue membranes.

Biological Transport↗
PubMed1995

A novel ultrasonic technique for differentiating cysts from solid lesions: preliminary results in the breast.

The feasibility of a new ultrasonic technique to distinguish cysts from solid lesions is explored. High intensity pulses are used to induce acoustic streaming in cyst fluid, and this motion is detected using Doppler techniques. Acoustic streaming cannot be generated in solid lesions, therefore, its detection would indicate a cyst. In six of seven breast cysts motion was clearly generated and detected in vivo. Ultrasonic pulses with intensities up to 4.4 W cm-2 (I(spta) in water) were focused on the cysts for 10 s. Lesion diameters ranged from 0.6 to 2.5 cm; induced flow velocities were less than 4.0 cm s-1.

Breast Neoplasms↗
PubMed1995

Myoblast fusion and innervation with rat motor nerve alter distribution of acetylcholinesterase and its mRNA in cultures of human muscle.

To elucidate the mechanisms underlying acetylcholinesterase (AChE) localization, we analyzed the distribution of AChE and Ache mRNA during myogenesis in cocultures of human muscle and fetal rat spinal cord. We observed a temporal coincidence in alterations of AChE localization and nuclei expressing the message, suggesting developmental regulation at the mRNA level. Nonuniform mRNA staining among nuclei suggests asynchronous regulation, also supporting an earlier proposal that transcription proceeds intermittently. Asynchrony seems to be overridden by generally acting factors during myoblast fusion, when message is up-regulated, and at the onset of muscle contractions, when it becomes restricted to some nuclei in the junctional region and focal patches of AChE appear near nerve contacts. Coincidence of mRNA down-regulation and synthesis of stable basal lamina-bound AChE suggests coordinated adaptation, so that sufficient enzyme may be derived from low message levels.

Acetylcholinesterase↗
PubMed1993

Analysis of dystrophin expression after activation of myogenesis in amniocytes, chorionic-villus cells, and fibroblasts. A new method for diagnosing Duchenne's muscular dystrophy.

BACKGROUND: DNA analysis of peripheral-blood leukocytes is routinely used to demonstrate mutations in the dystrophin gene in patients with Duchenne's or Becker's muscular dystrophy. In approximately 35 percent of patients, DNA studies are not informative; in these patients immunochemical analysis of a muscle-biopsy specimen can determine whether dystrophin, the protein product of the gene for Duchenne's dystrophy, is present at reduced levels or absent. DNA analysis can be performed in amniocytes or chorionic-villus cells to identify mutations of the dystrophic gene prenatally, but immunochemical testing for dystrophin cannot be performed because the protein is not expressed in these cells. METHODS: To circumvent this limitation in prenatal diagnosis, we induced myogenesis in 21 cultures of skin fibroblasts, 49 amniocyte cultures, and 6 chorionic-villus cell cultures by infecting the cells with a retrovirus vector containing MyoD, a gene regulating myogenesis. Transfection of MyoD into cells that do not normally develop into muscle cells results in the production of a protein that switches on myogenesis. We performed immunocytochemical analysis for dystrophin in the MyoD-converted muscle cells. RESULTS: We found that 60 of 61 myotube cultures from subjects with no family history of Duchenne's dystrophy expressed dystrophin. Both myotube cultures from the two patients with Becker's dystrophy also expressed dystrophin, but all cultures from nine patients and two fetuses with Duchenne's dystrophy were dystrophin-deficient. CONCLUSIONS: Immunocytochemical analysis of dystrophin in genetically altered non-muscle cells is feasible and may be applicable to the prenatal and postnatal diagnosis of Duchenne's muscular dystrophy when conventional DNA analysis is not informative.

Amniotic Fluid↗
PubMed1988

Amputation for peripheral vascular disease: the case for level selection.

One hundred major lower limb amputations were performed for end stage peripheral vascular disease over a 15-month period. Selection of amputation level was made on the basis of laboratory criteria using skin blood flow and infrared thermography data. Eighty-one amputations were performed at the below-knee level with six failures. This resulted in a final below-knee: above-knee amputation ratio of 3:1. It is clear that there are still many centres in the UK where above-knee amputation is the accepted operation, despite the inherent drawbacks to this procedure. We recommend that more attention is given to achieving higher below-knee amputation rates to improve the chances of amputee mobility and therefore quality of life.

Amputation, Surgical↗
PubMed1988

Sibling incest.

Explore the source record for details and available documents.

Child↗
PubMed1988

Further experience in the healing rate of lower limb amputations.

Results of lower limb amputation in the Tayside Region in the years 1981-1985 have been analysed. Three-hundred and twenty-four amputations were performed on three-hundred and eight patients. Two-hundred and thirty-six amputations were attempted at the below-knee level. Only 19 required proximal revision. Prior to amputation, all patients should have a detailed vascular assessment, and the operation should be performed by experienced amputation surgeons using meticulous technique.

Adult↗
PubMed1987

Fate of the vascular patient after below-knee amputation.

50 below-knee amputations were carried out in 45 patients (25 men and 20 women), mean (SD) age 73 (10.5) years. The mean survival time was 22(16) months after the operation. In each patient the healing potential of a below-knee amputation was determined preoperatively by segmental pressure studies and thermographic delineation of skin perfusion. 33 of the stumps healed by first intention, in 14 healing was delayed but occurred without the need for further surgery, and 3 stumps healed after local wedge excision. The initial mobilisation rate was 90%. Thus, there are no grounds for carrying out an initial above-knee amputation to save the patient a further operation.

Aged↗
PubMed1987

Role of oxygen in the production of human decompression sickness.

In the calculation of decompression schedules, it is commonly assumed that only the inert gas needs to be considered; all inspired O2 is ignored. Animal experiments have shown that high O2 can increase risk of serious decompression sickness (DCS). A trial was performed to assess the relative risks of O2 and N2 in human no-decompression dives. Controlled dives (477) of 30- to 240-min duration were performed with subjects breathing mixtures with low (0.21-0.38 ATA) or high (1.0-1.5 ATA) Po2. Depths were chosen by a sequential dose-response format. Only 11 cases of DCS and 18 cases of marginal symptoms were recorded despite exceeding the presently accepted no-decompression limits by greater than 20%. Analysis by maximum likelihood showed a shallow dose-response curve for increasing depth. O2 was estimated to have zero influence on DCS risk, although data variability still allows a slight chance that O2 could be 40% as effective as N2 in producing a risk of DCS. Consideration of only inert gases is thus justified in calculating human decompression tables.

Decompression Sickness↗
PubMed1986

Oxygen inhalation induced changes in the skin as measured by transcutaneous oxymetry.

Transcutaneous oxygen (PtcO2) measurements were made on 46 patients with severe ischaemia of the lower limbs and on 17 age-matched controls. Values breathing air, 100 per cent oxygen and the rate of change of PtcO2 breathing oxygen were recorded. Of 29 below knee amputations there were 4 failures; 16 had PtcO2 values less than 35 mmHg, but 12 of the 16 healed. When the rate of change of PtcO2 during oxygen inhalation was greater than 9 mm Hg/min all below knee amputations healed; all 4 failures were found to have values less than 9 mm Hg/min while only one patient with a value of less than 9 mm Hg/min healed a below knee amputation. This study shows that low PtcO2 values are a poor indication of healing potential. A more reliable index of skin viability is provided by the dynamic measurement of PtcO2 changes during oxygen inhalation. The addition of an oxygen inhalation test, when making PtcO2 measurements, greatly enhances the applicability of the technique in the assessment of the oxygen supply to the skin.

Aged↗
PubMed1986

Arterial systolic pressures in critical ischemia.

Segmental systolic pressures were measured in a group of patients with clinically irreversible ischemia. There was a good relationship between the level of pressure in a limb and the eventual outcome, but a particular level of pressure was found to be a poor indicator of a specific level of viability. These results support previous concern about the limitations of systolic pressure measurements in determining the level of limb viability. We suggest that local intrinsic regulation of the microcirculation plays a major role in the ultimate survival of tissues in an ischemic limb.

Aged↗
PubMed1986

pH changes in the dermis during the course of the tuberculin skin test.

The response of six healthy young adults to tuberculin skin testing was studied. Five subjects developed a typical delayed-type hypersensitivity reaction to PPD with a local rise in skin temperature, and the sixth showed a less intense response; a considerable increase in blood flow velocity was seen in all reactions. All subjects showed a fall in pH in the dermis during the course of the reaction: in four subjects the pH minimum occurred at the time when the changes of erythema and induration were most prominent, in one subject the pH fall preceded the maximal clinical changes, and in the remaining subject a substantial fall in pH occurred with only transient erythema. It was concluded that the local tissue acidosis had resulted from the greatly increased metabolic demand of the lymphocytes and monocytes attracted into the dermis as part of the type IV delayed-type hypersensitivity reaction, and that the concurrent reactive hyperaemia was insufficient to clear the acidic metabolic products of the greatly increased cell population.

Adult↗