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Biomedical subjects

M A Bell

Publications and source records attributed to M A Bell.

At least 19 recordsLinked to original sources

The Charcôt-Bouchard aneurysm controversy: impact of a new histologic technique.

For over a century a controversy has existed about the prevalence and significance of Charcôt-Bouchard (C-B) aneurysms, especially regarding their relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B aneurysms by staining thick brain sections from 35 hypertensives and 20 normotensives with the alkaline phosphatase (AP) endothelial stain followed by light microscopy and high-resolution microradiography. Charcôt-Bouchard aneurysms were conspicuously absent in both groups which included four cases of hypertensive ICH. The three-dimensional perspective and enhanced ability to trace vessels with these techniques helped to identify arteriolar coils and twists that can be mistaken for aneurysms when demonstrated by injection methods. Routine brain pathologic sections from 2,800 autopsies over a decade showed rare examples of parenchymal aneurysms. We conclude that elimination in our study of a) injection artifacts and b) misinterpretations shows that C-B aneurysms are uncommon and have little relationship to ICH. Despite this, and in view of the original contribution of Charcôt and Bouchard, the occasional examples of brain parenchymal aneurysms should continue to bear their names.

Aged

The relations between frontal brain electrical activity and cognitive development during infancy.

The relations between changes in the scalp-recorded electroencephalogram (EEG) and the development of the ability to perform successfully 2 cognitive tasks attributed to frontal lobe functioning were examined in 13 infants from 7 to 12 months of age. Infants successful in performing the A-not-B task with increasingly longer delays across the second half of the first year of life showed changes in power in scalp-recorded brain electrical activity in the frontal region and an increase in anterior/posterior EEG coherence. Infants with rapid mastery of object retrieval did not differ in frontal EEG development from infants who exhibited the normal developmental progression in object retrieval performance. In a task examining inhibition of reaching to a novel toy, there were no differences in frontal EEG as a function of performance. Results from a cross-sectional sample revealed similar findings. These data confirm work with nonhuman primates on the importance of maturation of frontal cortex in the successful performance on certain tasks (A-not-B), but do not confirm nonhuman primate data on the importance of frontal cortex for other tasks (object retrieval). The data also suggest that the electroencephalogram may be useful as a noninvasive measure of central nervous system development during the first year of life.

Brain

Does tortuosity in cerebral arterioles impair down-autoregulation in hypertensives and elderly normotensives? A hypothesis and computer model.

A mathematical model of pressure/flow relationships in straight and tortuous intracerebral arterioles is presented. Using this model, it is predicted that patients with severe tortuosity would never be able to tolerate an appreciable decrease in MAP. This morphological alteration may explain the inability of a few hypertensive and normotensive elderly patients to tolerate periods of mild reductions in blood pressure. The alkaline phosphatase histochemical staining technique is potentially an excellent method of establishing the identity of deep white matter signal alterations seen on MRI because of its ability to trace the vascular supply from the brain surface to the lesion.

Aging

Brain microemboli during cardiac surgery or aortography.

We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium-sized arterioles. Two other patients had a small number of the same microvascular changes following proximal aortography. Thirty-four patients and 6 dogs not undergoing cardiopulmonary bypass had none. (A 35th patient who had not undergone cardiopulmonary bypass or aortography showed a small number of dilatations; mediastinal air was a suggested source.) Some of the dilatations exhibited various forms of birefringence. Because most of the dilatations appear empty, we speculate that they are the sites of gas bubbles or fat emboli that have been removed by the solvents used in processing. These microvascular events, occurring only in conjunction with major arterial interventions, may be the anatomical correlate of the neurological deficits or moderate to severe intellectual dysfunction seen in at least 24% of patients after cardiac surgical procedures assisted by cardiopulmonary bypass.

Adult

Electrophysiological indices of frontal lobe development. Relations to cognitive and affective behavior in human infants over the first year of life.

Over the past 8 years we have been involved in a study of the psychophysiological correlates of cognitive and affective behaviors during the first year of life. We have utilized recordings of brain electrical activity (the EEG) to describe differences in regional activation as well as, more recently, changes in regional connectivity. Our studies have indicated an important role for the frontal region in the expression of positive and negative emotions and in the regulation of emotional distress. In addition, individual differences in frontal EEG maturation seem to be associated with improved performance on tasks known to involve specific regions of frontal cortex. The corroborative data from different areas of study (studies of brain-damaged adults; studies of lesions in nonhuman primates) give us confidence that our measures of regional electrical activity are indeed reflecting true brain processes. Our continuing task is to understand the skills that are involved in these complex behaviors (such as AB performance or expression of affect) so as to better understand these important brain-behavior relationships.

Aging

Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study.

In an ongoing study of brain microvasculature in humans at autopsy, we had the opportunity to analyze the overall scheme of this vascular supply. The native endothelial membrane enzyme, alkaline phosphatase, is used to precipitate black lead sulfide salt in the vessel wall, rendering the brain microvasculature visible by both light microscopy and microradiography. There are six distinct patterns of intraparenchymal afferent blood supply to the supratentorial brain: short arterioles from a single source (e.g., those in the cortex); short- to intermediate-length arterioles, single source (anterior two-thirds of the corpus callosum); short- to intermediate length arterioles and arteries, dual source (subcortical U fibers); intermediate-length arterioles and arteries, triple source (extreme/external capsule and claustrum); long arteries and arterioles, single source (centrum semiovale); and large, long muscular arteries, single source (thalamus and basal ganglia). The nature of this arrangement offers some protection to certain regions of the cerebrum from circulatory challenges such as hypotension, while leaving other areas vulnerable. The distal arterioles supplying two of these protected regions, the U-fiber area and the extreme/external capsule and claustrum area, also exhibit the feature of interdigitation, which can offer additional collateral potential from one arteriolar territory to the next. Aging, hypertension, diabetes mellitus, and atherosclerosis can have a significant impact on brain microcirculation. The way in which vascular patterns dictate the distribution of these effects is discussed. The ability to stain the cerebral microvessels and demonstrate the finer points of their patterns in sections and microradiographs has enabled us to resolve some long-standing questions about vascular connections and directions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Microdialysis-perfusion sampling for the investigation of phenol metabolism.

In vivo methods provide several advantages for the study of metabolism relative to the commonly used in vitro techniques. The integrity of the organism and actual physiological conditions are maintained to reflect more accurately the processes occurring on exposure to a xenobiotic compound. Experimental precision is improved because each animal serves as its own control and can be used to generate a complete pharmacokinetic experiment. This may result in the added benefit that fewer experimental animals will be needed for a metabolic investigation using in vivo techniques. The technique of microdialysis perfusion was characterized for the in vivo study of the hepatic metabolism of phenol and conjugation by glutathione. In this study, in vivo experiments were conducted by implanting a microdialysis probe into the intact, in-place liver of a killed rat. These results were compared to in vitro experiments using liver homogenate and liver-microsomal protein. Substantial differences were observed between the in situ experiments and those performed in vitro.

Animals

Lucilia cuprina induced hyperammonaemia and alkalosis associated with pathology in sheep.

Gross and microscopical examinations were done in 12 sheep infested with Lucilia cuprina larvae. All the sheep became hyperammonaemic and alkalotic. Six sheep died and 6 survived, one being moribund before euthanasia. Necropsy revealed severe acute dermatitis and congestion of the liver, heart, kidney, spleen and lungs. Ecchymotic haemorrhages were present in the heart, kidneys and adrenal glands of severely infested sheep. Microscopical examination showed mild to severe vacuolation of the central nervous system in all sheep. In severely infested sheep, skin, lung, heart, kidney, and liver tissues were infiltrated by mononuclear cells, neutrophiles or lymphocytes. Fibrin thrombi were present in vessels. Elevated concentrations of lipid soluble ammonia in blood were positively correlated with tissue abnormality and early death.

Alkalosis

Changing practice habits of King County obstetricians.

In 1987, all practicing King County, Washington obstetricians (N = 181) were surveyed to determine the impact of rising malpractice premium rates and the threat of litigation on their obstetric practices. Six percent of respondents anticipated closing their practices over the next year, which means an additional 520 deliveries will have to be absorbed into existing obstetric practices. Of the 71% who increased their professional fees in 1986, 90% attributed the increase to higher malpractice premiums and increased risk of litigation.

Adult

Localized fibrous tumour of serosal surfaces. Immunohistochemical and ultrastructural evidence for a type of mesothelioma.

It is uncertain whether localized lesions of serosal membranes have a kinship to mesotheliomas or are truly fibromatous in nature. Ultrastructural and immunohistochemical investigations were carried out on 12 localized benign and malignant pleural and peritoneal tumours from 10 patients. Electron microscopic findings, including the consistent and non-fibroblastic cellular organization of localized neoplasms, the presence of some form of intercellular junctions in 7 of 10 cases, basal lamina deposition in 3 cases, and polarized microvilli in one case indicated a form of mesothelial differentiation. Using monoclonal and polyclonal antibodies, positive immunostaining of tumour cells for cytokeratin peptides was detected in one case, while antibody to vimentin stained four cases. Light microscopic, ultrastructural and immunohistochemical features of one benign localized serosal tumour, with a unique blend of epithelial and spindle cells, provided further evidence for a histogenic link between localized serosal tumours and diffuse epithelial mesotheliomas. On the basis of the current findings and reports in the literature, it would appear that the majority of localized tumours of serosal membranes are a subset of mesothelioma, while a minority are fibromas.

Adult

The correlation of vascular capacity with the parenchymal lesions of Alzheimer's disease.

Hippocampal capillary and arteriolar measurements showed a significant reduction in capacity with normal aging. Alzheimer's dementia was not associated with any further reduction; in fact regional variations suggested that the zones of Ammon's horn most severely affected by tangles and granulovacuoles retained the best vascular capacity. The arterial system supplying the hippocampus, from the posterior cerebral artery to the series of small hippocampal arteries, was also assessed. Its capacity, as judged by arterial diameters, was similarly found to decrease significantly with age; the arterial diameters of Alzheimer cases were (insignificantly) greater than those of the normal old. Calcarine capillary and arteriolar measurements also indicated a marked reduction of capacity with normal aging, and, as before, in Alzheimer's dementia there was no further significant change. All three phases of the study thus suggest that cerebrovascular capacity in Alzheimer's dementia is at least as good as in the normal old, if not better. Senile (neuritic) plaques with amyloid cores and their relationship to the microvasculature were examined in the calcarine cortex. In both normal old and Alzheimer cases the plaques tended to congregate where capillaries were densest. Their correlation with capillary density was however better in the normal old, raising the question of whether their pathogenesis might differ in the two conditions.

Adult

Encephalic microvascular abnormalities in hypertension. A light and X-ray microscopic study.

Brain and cervical spinal cord removed at autopsy from hypertensive humans have been subjected to 4 levels of microscopic study, 3 being first histochemically prepared so as to stain the arterial and capillary system. Thick (100 microns) sections for light microscopy and thicker (500-1000 microns) for x-ray microscopy facilitate the study of long, complex anatomic units. Arterial and arteriolar microaneurysms have not been found. In addition to the usual age related vascular changes in normal people we have found: moniliform capillary dilatations, focal segments of arteriolar narrowing, état pre-criblé, and lacunar infarcts. Few changes have been encountered in the corpus callosum. While the segmental arteriolar narrowing occurs in the cortex as well as deep white matter, the effects of resultant poor perfusion might be expected to be more profound in the deep white matter.

Animals

Laminar variation in the microvascular architecture of normal human visual cortex (area 17).

Diameters and densities of arterioles and capillaries were measured in thick alkaline phosphatase-stained sections of human visual cortex from normal young adults. Values were compared between laminae. Capillary diameters ranked: IV greater than V-VI greater than II-III greater than I; capillary densities ranked: IV greater than II-III greater than V-VI greater than I. The striking capillary density of lamina IV overlaps the stria Gennarii and, like it, is limited to area 17. The data suggest correlations with similar laminar distributions of some neurotransmitters and of certain common neuropathological lesions.

Adolescent

A morphometric study of intrafascicular vessels of mammalian sciatic nerve.

Intrafascicular vessel profiles were measured with a Quantimet image analyzer in 1-micron transverse sections of sciatic nerves of rats and compared with those of ("white") skeletal muscle. Blood vessels occupy the same percentage of the total tissue area in nerve and muscle tissues. The nerve, however, has much larger capillaries (about 1.7 X) spaced farther apart (about 2.5 X). Comparison of 3 1/2 month with 1-year-old rats showed that muscle capillaries increased in diameter (slightly, but significantly) at maturity, but those of the nerve decreased (also significantly). Vascular percentages of total tissue areas did not change. Nerve and muscle samples from monkey, rabbit, mouse, and cat show that the same striking pattern of large, widely spaced vessels distinguishes the nerve from other tissues. Minor interspecies variations exist. The nerve may contain as much blood as the muscle but its angioarchitecture suggests a lower exchange capacity.

Age Factors

Staining for microvascular alkaline phosphatase in thick celloidin sections of nervous tissue: morphometric and pathological applications.

Alkaline phosphatase enzyme is active in the endothelium of capillaries (and often arterioles) in the central and peripheral nervous systems of many animals including man. A modified metallic stain for this enzyme applied to thick (50-500 micron) sections of brain or nerve produces a striking picture of the microvascular system. Preparations may be examined by light microscopy or microfocal radiography. Thick sections (particularly at 100 micron) are suitable for vascular morphometry at the light microscopic level. Celloidin embedding of the material permits storage of the specimen and ensures that cohesive sections can be cut serially, labeled, and handled with ease. Counterstaining permits normal and pathological features of the parenchyma to be demonstrated in relation to the vessels. Techniques of preparation and morphometry are described. Examples are drawn from current studies of the hippocampal and calcarine microvasculatures and their relation to senile plaques in normal aging and senile dementia of the Alzheimer type.

Alkaline Phosphatase

A descriptive study of the blood vessels of the sciatic nerve in the rat, man and other mammals.

The gross blood supply and internal vascular organization of the sciatic nerve in the rat (and other mammals including man) have been studied by injection, dissection, and microradiographic methods, in thick sections stained for alkaline phosphatase and semithin sections, and by electron microscopy. In the rat, an anastomotic vascular connection from the arteria comitans to the medial femoral circumflex artery is illustrated. In all species studied, the microvascular network of the nerve has an unusually large calibre and wide spacing, particularly when compared with that of skeletal muscle. Arterioles and venules are present within fascicles; the arterioles are thin-walled, with only rudimentary internal elastic laminae. Endoneurial capillaries are large, continuous and nonfenestrated, with prominent (often multiple) basal laminae and an unusually complete pericyte investment. Endothelial junctions appear to vary in type; not all are tight. Pinocytosis is common. The extensively interconnected vascular network of the nerve fascicle may act as an adaptable in situ reservoir for blood in the precise maintenance of the endoneurial milieu.

Alkaline Phosphatase

Pre-operative localisation of parathyroid tumours using neck vein catheterisation and radioimmunoassay for parathyroid hormone: the Glasgow experience.

Reliable pre-operative localisation of parathyroid tumours can be of value in surgery for primary hyperparathyroidism, and particularly so where re-exploration of the neck is required. Neck vein catheterisation and parathyroid hormone radioimmunoassay have been suggested as a sensitive means of tumour localisation, and we report our experience of the technique over the last five years. A total of 46 patients with primary hyperparathyroidism had 50 studies performed with positive localisation and a pre-operative prediction made on 38 occasions (76%). Forty-two operations were carried out and a parathyroid tumour confirmed in 39 cases for a localisation efficiency of 69 per cent. No negative neck exploration followed a positive localisation. Twelve studies were performed in patients with renal osteodystrophy and localisation to a single site was achieved on only three occasions. It is concluded that neck vein catheterisation and parathyroid hormone assay can correctly localise parathyroid tumours in most cases of primary hyperparathyroidism, but it is suggested that its use be restricted to selected cases such as those subjects with previous negative neck exploration or patients for whom prolonged or repeated surgery may be a particular hazard.

Adenoma