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Biomedical subjects

S Rees

Publications and source records attributed to S Rees.

17 recordsLinked to original sources

Obstruction in extracardiac ventriculopulmonary conduits: value of nuclear magnetic resonance imaging with velocity mapping and Doppler echocardiography.

OBJECTIVES: This study was designed to investigate the value of noninvasive imaging modalities for the detection of obstruction in extracardiac ventriculopulmonary conduits. BACKGROUND: the diagnosis of obstruction in a conduit by noninvasive methods can be difficult. Obstruction may be silent and its progression unnoticed. Nuclear magnetic resonance imaging (NMR) with velocity mapping is a new noninvasive technique that can provide high resolution images and has been shown to be a reliable method of measuring blood flow velocity. METHODS: Two-dimensional echocardiography, pulsed wave Doppler echocardiography and NMR spin echo imaging were used in 52 patients with an extracardiac ventriculopulmonary conduit. Continuous wave Doppler echocardiography was used in 30 of these, Doppler color flow mapping in 26 and NMR velocity mapping in 12. Cardiac catheterization data were available in 27 patients and operative or autopsy findings in 11. RESULTS: The conduit could be assessed by two-dimensional and pulsed wave Doppler echocardiography in only 17% of patients. Doppler color flow and continuous wave echocardiography provided technically satisfactory data in 19% and 83%, respectively. The anatomy of the conduit was adequately displayed by NMR imaging in 90%. A minimal diameter less than 18 mm indicated conduit obstruction, although failure to detect calcification resulted in obstruction being missed in some patients. Calculated gradients in obstructed conduits derived from NMR velocity mapping correlated well with results of continuous wave Doppler echocardiography and gave an accurate localization of the site of obstruction as well as a measure of its severity. CONCLUSION: NMR imaging with velocity mapping is the most effective noninvasive method of assessing obstruction in ventriculopulmonary conduits and can obviate the need for invasive investigation before an interventional procedure is performed.

Adult

The structural and neurochemical development of the fetal guinea pig retina and optic nerve in experimental growth retardation.

In this study we have examined structural and neurochemical aspects of retinal and optic nerve development in experimentally growth-retarded fetal guinea pigs following maternal unilateral artery ligation. Eye weight (n = 4) and total retinal area (n = 6) at 62 days gestation (term approximately 66 days) were both relatively spared when expressed as a percentage of body weight but in absolute terms were significantly reduced by 18% (P less than 0.001) and 13% (P less than 0.05) respectively when compared with age-matched controls. The numerical density of neurons in the ganglion cell layer was significantly higher at both 52 days (n = 4) and 62 days (n = 4) in growth-retarded fetuses compared with controls. However, there was no difference between the groups in the total number of neurons in this retinal layer at either age, since retinal areas are reduced in growth retardation. The area of neuronal somata in the ganglion and inner nuclear layers was significantly reduced in growth-retarded fetuses compared with controls. There was a concomitant reduction in the width of the cellular layers in the retina and also in the plexiform (synaptic) and photoreceptor layers. The growth of the outer segments of the photoreceptor layer was particularly affected in peripheral retina. The higher packing density of cells and the reduced growth of the plexiform layers suggests a reduction in the growth of the neuropile in growth-retarded fetuses compared with controls. The radial bundling of ganglion cell axons coursing across the retina to enter the optic nerve head was poorly defined in growth retardation. In addition myelination was delayed in the optic nerve with the numerical density of myelinated axons being significantly reduced (P less than 0.005) in growth-retarded fetuses compared with controls. There was a significant reduction (P less than 0.01) in the number of amacrine cells in the inner plexiform layer expressing Substance P-like immunoreactivity in growth-retarded fetuses compared with controls. Glutamate-like immunoreactivity was most intense in the five laminae of the inner plexiform layer and in the outer plexiform layer and less pronounced in photoreceptors, ganglion cells and their axons. There was no qualitative difference in glutamate immunoreactivity between control and growth-retarded fetuses in any of these structures. Thus we have shown that intrauterine growth retardation has specific effects on the development of the fetal guinea pig retina, reducing the growth of several types of neurons and their processes and affecting the expression of the neuropeptide substance-P in amacrine cells.

Animals

Expression of SV-40 T antigen in the small intestinal epithelium of transgenic mice results in proliferative changes in the crypt and reentry of villus-associated enterocytes into the cell cycle but has no apparent effect on cellular differentiation programs and does not cause neoplastic transformation.

The mouse intestinal epithelium represents a unique mammalian system for examining the relationship between cell division, commitment, and differentiation. Proliferation and differentiation are rapid, perpetual, and spatially well-organized processes that occur along the crypt-to-villus axis and involve clearly defined cell lineages derived from a common multipotent stem cell located near the base of each crypt. Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene were used to establish three pedigrees of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells situated in the uppermost portion of small intestinal crypts and in already committed, differentiating enterocytes as they exited these crypts and migrated up the villus. T antigen production was associated with increases in crypt cell proliferation but had no apparent effect on commitment to differentiate along enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel-immunocytochemical studies plus RNA blot hybridization analyses suggested that the differentiation programs of these lineages were similar in transgenic mice and their normal littermates. This included enterocytes which, based on the pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating nuclear antigen expression, had reentered the cell cycle during their migration up the villus. The state of cellular differentiation and/or TAg production appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase to M-phase cells (collected by metaphase arrest with vincristine) and of the intensities of labeling of nuclei by [3H]thymidine indicated that the duration of S phase was longer in differentiating, villus-associated enterocytes than in the less well-differentiated crypt epithelial cell population and that there may be a block at the G2/M boundary. Sustained increases in crypt and villus epithelial cell proliferation over a 9-mo period were not associated with the development of gut neoplasms--suggesting that tumorigenesis in the intestine may require that the initiated cell have many of the properties of the gut stem cell including functional anchorage.

Animals

Prenatal development of cutaneous afferent connections in the spinal cord of fetal sheep. A physiological and neurochemical study.

In this study we have examined the physiological and neurochemical development of the cutaneous afferent pathways from the hindlimb to the spinal cord in fetal sheep. We have shown that somatosensory input from the hindlimb evokes activity in DRG neurons at 87d gestation and in cells in the dorsal horn at 92d (term, 146d). There is evidence of immunoreactivity for substance P, calcitonin gene-related peptide and glutamine several days prior to this at 77-80 days. The implication of these findings are discussed.

Afferent Pathways

The effects of intrauterine growth retardation on the development of neuroglia in fetal guinea pigs. An immunohistochemical and an ultrastructural study.

The effects of intrauterine growth retardation on the development of myelinating oligodendrocytes and astrocytes in the brain and spinal cord of the fetal guinea pig have been examined using immunohistochemical and ultrastructural techniques. As judged by immunoreactivity for myelin basic protein, the extent of myelination in the spinal cord, cerebral cortex, corpus cellosum and cerebellum was reduced in the growth-retarded fetuses compared with controls at both 52 (n = 4) and 62 days (n = 5) of gestation. As assessed by immunoreactivity for glial fibrillary acidic protein, there were no marked differences between control and growth-retarded brains in the extent or distribution of radial glial cells or astrocytes at 52 or 62 days in the cerebellum. However, in the cerebral cortex at 62 days there was a striking proliferation of astrocytes surrounding cortical blood vessels in growth-retarded fetuses. Ultrastructural studies showed that at 52 days, myelination of the corticospinal tract had begun in the control but was virtually absent in growth-retarded fetuses. At 62 days, the total number of myelinated fibres in growth-retarded fetuses was significantly reduced by 56% (P less than 0.01) compared with control fetuses; however, there was no difference between the groups in the total number of fibres in the corticospinal tract. Where fibres were myelinated the myelin sheath was disproportionately reduced relative to axon diameter. Thus, in intrauterine growth retardation there is a delay in the initiation and in the extent of myelination. This could be due to a reduction in the number of myelinating glia formed and the restricted capacity of those which do form to generate myelin.

Aging

Membranous neuronal and neuroglial inclusions produced by intracerebral injection of Suramin.

A single intracerebral injection of 5 micrometer of the trypanocidal drug Suramin, into the left hemisphere of young rats, resulted in the formation of membranous inclusion bodies within the perikarya and processes of neurones and neuroglia. These inclusion bodies were round or oval in shape and 0.5-3.0 micrometer in their longest diameter. They were bounded by a single trilaminar membrane and contained closely packed membranes in concentric, curved or parallel arrays. The inclusions were distributed throughout the cerebral cortex and underlying hippocampus at the injection site, and in reduced numbers up to 1 mm anteriorly and posteriorly from it. They formed within 22 hr of the injection and had increased in numbers and in the complexity of their arrays 3 days after injection. Within 14 days, the inclusions were markedly reduced in number. As Suramin is known to inhibit lysosomal hydrolases required for the degradation of proteins, glycolipids and mucopolysaccharides, the membranous inclusions could form as a result of the accumulation of these substances within lysosomes. These experiments indicate a possible experimental model for storage diseases. It is hoped that the extension of this paradigm to other enzyme inhibitors will provide a new means of identifying some of the unusual inclusions that can be found in neurones and neuroglia (Rees 1975).

Animals

The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome).

In a quantitative electronmicroscopic study, autopsy samples from the frontal and temporal lobes of two severely defective mongoloid brains were examined for the presence of abnormalities in the ultrastructure of the cerebral cortex. Particular attention was paid to the occurrence of atypical neuronal and glial inclusions similar to those which occur in small numbers (1 in 5000 mu2 of cortex) in neurologically normal brain (Rees, 1975). An area of 3.6 x 10(5) mu2 of cortex was examined from each brain. Within the cortical parenchyma, there was no gliosis, neuronal death or areas of degeneration. Atypical neuronal and glial inclusions were observed in both of the retarded brains, but they did not occur in substantially different numbers from normal brains. There were no inclusions or structural abnormalities peculiar to the retarded brains. Thus, in these two defective brains, it has not been possible to demonstrate any specific abnormalities in the ultrastructure of the cortex.

Adolescent

A quantitative electron microscopic study of the ageing human cerebral cortex.

A recent quantitative electron microscopic study of biopsy samples of the cerebral cortex of neurologically normal individuals, aged between 15 and 54 years, has shown that atypical inclusions are present in neuronal and glial processes in small but appreciable numbers (Rees). It would be of interest to know whether these inclusions accumulate with age. This study therefore applied the same quantitative methods used in the previous study, to autopsy samples of frontal and temporal cortex from 3 non-demented ageing human brains (70-76 years). The results showed that in the areas of cortex examined, the number of inclusions in neuronal processes did not increase with age. However, the number of dense deposits in the cell bodies and processes of oligodendrocytes did increase significantly with age. In agreement with previous studies corpora amylacea were found in astrocytic processes. Senile plaques were not observed.

Aged

The watershed: a factor in coronary vein graft occlusion.

In 50 patients with one or more aortocoronary saphenous vein grafts investigated by angiography the patency rate of grafts inserted into arteries with a total proximal occlusion was significantly higher than of those inserted into arteries with a proximal stenosis. The interval between operation and investigation in the two groups was similar. In 10 patients with double grafts, one to an occluded and one to a non-occluded artery, there were 7 with one blocked graft, in each case to the non-occluded artery. In the other 3 both grafts were patent. A watershed was shown at angiography in one patient with a graft inserted into a stenosed artery; the distal run-off appeared good, but reflux of the contrast up the coronary artery into the aorta occurred when injecting into the graft, and vice versa. This watershed may operate to a minor degree in all grafts inserted into non-occluded arteries, and by causing stasis at the anastomosis, could explain the higher incidence of graft occlusion in this group. Ligation of the coronary artery proximal to the anastomosis may therefore be necessary to achieve the highest patency rate.

Adult

A quantitative electron microscopic study of atypical structures in normal human cerebral cortex.

Biopsy samples of the cerebral cortex from four normal human brains were examined in the electron microscope for the presence of abnormalities related to neurones and neuroglia. Atypical forms of axons, axon terminals and dendrites, many of them similar to those described in a variety of pathological and experimental material, were found to occur in small but appreciable numbers. Neuroglia exhibiting atypical inclusions occurred but were much less common. Physiologically altered neuronal perikarya were not encountered apart from one neuronal death. An area of 3.6 x 10(5) mu2 was scanned from each brain and atypical structures were categorised and counted. The possible implications of the presence of these structures in normal brain in discussed and the need for neuropathologists and neuroanatomists to be aware of the existence of atypical forms of neuronal processes in normal human and animal brains is emphasised.

Adolescent

Cardiac flow measurement by ultrafast CT: validation of continuous and pulsatile flow.

To gauge the accuracy of ultrafast CT in measuring cardiac output and myocardial perfusion in humans, measurements of continuous and pulsatile flow were made in a large asymmetrical phantom. The variation in the relationship between Hounsfield number and contrast concentration was assessed in a human thorax phantom. Radiopaque contrast medium was injected during perfusion of the phantom at a range of flow rates between 1.5 and 8 L/min. The phantom was scanned in two modes (50 and 100 ms) during continuous and pulsatile flow and with the phantom surrounded by air and by water. Flow in the tubes was calculated using indicator dilution theory, and flow in the tissue-equivalent chamber was calculated by applying first-pass distribution principles. The standard deviation of the difference between calculated and measured flow varied from 0.2 to 0.6 L/min, giving 95% limits of agreement from 0.4 to 1.2 L/min. The constant (K) relating Hounsfield unit number to iodine concentration varied widely both in different locations within the phantom and under different scan conditions (17.2-27.6 HU/mg I). Within a human thorax phantom, K varied from 14.15 to 23.18 HU/mg I and was dependent on location within the thorax phantom, the scan mode, and the cross-sectional diameter of the phantom. These data suggest that though the ultrafast CT scanner can measure continuous and pulsatile flow accurately in tubes, precise measurements of cardiac output in humans will require K to be assessed for each subject. Measurements of flow in tissue should be possible.

Cardiac Output