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Biomedical subjects

C P Case

Publications and source records attributed to C P Case.

34 records · Page 2Linked to original sources

Death after proximal femoral fracture--an autopsy study.

We reviewed 22,486 consecutive autopsy reports in a single District General Hospital, from 1953 to 1992. Five hundred and eighty-one patients with fractures of the proximal femur (hip fracture) were identified. Causes of death were correlated with timing of surgery and change of clinical practice. Thromboembolic and haemorrhagic potential were analysed. The principal causes of death after hip fracture were bronchopneumonia, cardiac failure, myocardial infarction and pulmonary embolism. Surgical intervention, within 24 h of injury significantly reduced death from bronchopneumonia and pulmonary embolism. Early mobilization reduced death from bronchopneumonia. Pulmonary embolism may be reduced by prophylactic anticoagulation, but 17 per cent of patients are at risk of haemorrhage, and mechanical methods seem safer in this population.

Aged↗

Neurofibrillary tangles in Niemann-Pick disease type C.

Post-mortem neuropathological examination of five cases of Niemann-Pick disease type C revealed neurofibrillary tangles in many parts of the brain. Tangles were a consistent finding in the hippocampus, hypothalamus, substantia innominata, midbrain pons and medulla. Other regions of the brain in which tangles were present included neocortex, basal ganglia, thalamus, cerebellar cortex in one case, and dentate nucleus in another. The tangles were argyrophilic, fluoresced under ultraviolet light when stained with thioflavin S, and reacted strongly with antibody to tau protein. Some of the tangles could be immunostained for ubiquitin. Electron microscopy, performed in one of the cases, showed the tangles to consist of paired helical filaments ultrastructurally identical to those of Alzheimer's disease. The distribution of the tangles in the central nervous system as a whole and also within many individual neurons corresponded fairly closely with that of the abnormal storage material. Both the tangles and the storage material extended into, and distended, the proximal parts of many dendrites and axons. No A4/beta protein, either in the form of plaques or in the walls of blood vessels, was detected in any of the cases. Our findings suggest that neurofibrillary tangles are a common feature of Niemann-Pick disease type C and that their formation may be a reaction to the abnormal storage material.

Adolescent↗

Ossifying fibromyxoid tumour of soft parts--a new tumour of the parotid/zygomatic arch region.

The ossifying fibromyxoid tumour of soft parts was first described as recently as 1989 by Enzinger has not been previously reported in the maxillofacial literature. This tumour has a proven record of recurrence and a potential in a few cases to become malignant and to metastasise. Being such a rare and relatively newly described tumour it has proved to be difficult to diagnose and manage. In order to illustrate these difficulties we describe a case in which such a tumour occurred in the parotid/zygomatic arch region and recurred three times following surgical removal over a period of 24 years. Since the tumour has a pseudo-capsule containing nests of tumour cells, we recommend that it could be removed from the head and neck region with a wide margin of excision.

Adult↗

Widespread dissemination of metal debris from implants.

In a post-mortem study, we compared subjects with metal implants with and without visible wear with an age-matched control group to determine the extent and effects of dissemination of wear debris. In subjects with stainless-steel and cobalt-chrome prostheses metal was found in local and distant lymph nodes, bone marrow, liver and spleen. The levels were highest in subjects with loose, worn joint prostheses and the main source of the debris was the matt coating. Metal levels were also raised in subjects with implants without visible wear and, to a less extent, in those with dynamic hip screws. Necrosis of lymph nodes was seen in those cases with the most wear, and potential damage to more distant organs such as the bone marrow, liver and spleen in the long term cannot be discounted. The consequences for the immune system and the role of metal dissemination in the possible induction of neoplasia are discussed.

Aged↗

Changing the light intensity of the visual environment results in large differences in numbers of synapses and in photoreceptor size in the retina of the young adult rat.

A quantitative light- and electron-microscopic study has been made of the retinae of rats which were exposed to different lighting conditions for between one and 15 weeks in young adulthood, having been reared in identical conditions during development. The width of the inner and outer segments of the photoreceptors and the width of the outer plexiform layer varied inversely with the light intensity under diurnal lighting conditions of 10 h light/14 h dark. Linear regression analysis showed that the widths were inversely related to the fourth root of the light intensity as measured in lux. Both central and peripheral areas of retina showed a similar change. No change was seen in the widths of the inner plexiform layer, or of the inner and outer nuclear cell layers. Nor was there a difference in the packing density or size of the nuclei in the nuclear cell layers. The number of ribbon synapses in the outer plexiform layer also varied inversely with the intensity of diurnal light. Linear regression analysis showed that the number of synapses was inversely correlated with the fourth root of the light intensity and was positively correlated with the width of the outer plexiform layer. The number of ribbon synapses was increased by up to two and a half times in constant darkness compared to diurnal light of 35 lux. The increase was present but not maximal after one week of exposure. The length of synaptic ribbons was unchanged. The nerve terminals forming such synapses were increased in size but not in number. After one week, there was little or no additional change in the retinal widths and number of synaptic ribbons with time. However, there was a progressive increase with time in nerve terminal size (two-fold in area) in constant darkness. There was some evidence of a slight decrease in nerve terminal number and increase in size of retinal nuclei with age. It is concluded that the adult retina responds to a different lighting environment by a relatively rapid change in the size of photoreceptor segments, by a progressive and large change in number of ribbon synapses and by a slower progressive and large change in the size of photoreceptor nerve terminals. The response is quantitatively determined by the strength of the stimulus but not in a linear fashion. These results are compared with the effects of environmental stimulation of other areas of the nervous system.

Animals↗

Systemic distribution of wear debris after hip replacement. A cause for concern?

The production of particulate wear debris is a recognised complication of joint arthroplasty, but interest has concentrated on local tissue reactions and a possible association with implant loosening. The fate of wear products in the body remains unknown, although some of the metals used in the construction of orthopaedic implants are known to have toxic and oncogenic properties. We report histological and electron-microscopic evidence from two cases which shows that metallic debris can be identified in the lymphoreticular tissues of the body distant from the hip some years after joint replacement. The increase in the use of total arthroplasty in younger patients, the development of new alloys and the use of porous coatings must raise concern for the long-term effects of the accumulation of wear debris in the body.

Aged↗

Neurotrophic activities of normal and motor neurone disease patient skeletal muscle extract on cultured rat spinal neurones.

Cultured foetal rat spinal neurones, grown in serum-free medium from day 3, respond to neuronotrophic factors present in adult human skeletal muscle extracts. Levels of total protein, neurofilament protein and choline acetyltransferase (ChAT) activity are all increased approx. 2 to 3-fold at 200 micrograms extract/ml medium. Culture survival is also extended from an average of 21 days to more than 30 days. Extracts prepared from skeletal muscle biopsies of motor neurone disease (MND) patients do not differ significantly from non-MND patient muscle extracts in their ability to boost the parameter levels or survival of the cultures. The results show no evidence that neuronotrophic factors are lacking in the skeletal muscle of MND patients.

Animals↗

Vascular innervation in human skeletal muscle with and without neuromuscular disease. A quantitative ultrastructural study with references to the effects of age and different blood pressure.

A quantitative ultrastructural study has been made of the innervation of 461 arterioles in 114 skeletal muscle biopsies of patients with or without neuromuscular disease excluding diabetes and autonomic neuropathy. In 18 controls the number of nerves and Schwann cells around each vessel was related to the size of the vessel, whether the vessel was within a muscle fascicle or between muscle fascicles. The innervation of arterioles increased with increased diastolic blood pressure. There was no statistically significant change in innervation with increased systolic blood pressure or with age, from 4 to 85 years. In 96 cases of neuromuscular disease and especially in motor neurone disease, axonal varicosities in cross section tended to be larger, more often contained no vesicles or only a few and had altered satellite cell cover depending on the location of the arteriole. Whilst the numerical density of Schwann cells did not change with disease, fewer varicosities were identified within Schwann cells in motor neurone disease, metabolic myopathy and neuropathy and myopathy due to toxins or vascular disease. Preterminal axons in nerve fascicles adjacent to arterioles were lost in polymyositis and muscle disease due to toxins or vascular disease. In polymyositis, metabolic myopathy and motor neurone disease there was some evidence of compensatory nerve sprouting, either in the nerve fascicles or in the adventitia of the arterioles. These structural changes may be related to the changes in blood flow or vascular reactivity described by others in motor neurone disease, polymyositis and metabolic myopathy. It is concluded that the ultrastructure of the vascular innervation of human skeletal muscle is similar to that in other mammals and is changed more with increased diastolic blood pressure and neuromuscular disease than with age.

Adolescent↗

Intramuscular nerves in motor neurone disease. A quantitative ultrastructural study.

The ultrastructure of human intramuscular nerves at biopsy has been compared in motor neurone disease with that in other neuromuscular disease including muscular dystrophy and in controls. Myelinated axons appeared to be lost in control patients aged over 50 years, but this varied both between and within nerve fascicles. Even in two boys aged 3 1/2 and 9 years, but with Duchenne's dystrophy, examples were found of nerve fascicles with few or no axons. In motor neurone disease additional nerve fibres were lost, but there was little change in the size distributions of axons and myelin sheaths within the muscle. In both preterminal and terminal fascicles there was an increase of Schwann cell cytoplasm in association with unmyelinated axons, which was compatible with nerve sprouting. It is concluded that intramuscular nerves are likely to be lost with age as well as motor neurone disease. The results are discussed in relation to the stage of the disease process at biopsy.

Adolescent↗

Outgoing synapses of small granule-containing cells in the rat superior cervical ganglion after post-ganglionic axotomy.

Small granule-containing cells are intrinsic and interneurone-like in the rat superior cervical ganglion, being innervated by preganglionic axons and giving outgoing synapses of asymmetrical type to the principal neurones. A quantitative ultrastructural investigation has been made of the effect on these outgoing synapses of axotomy of the major post-ganglionic nerve trunks 18.5 h-390 days previously. Cutting, or cutting and ligating, the internal and external carotid nerves 2-3 mm from the ganglion in rats aged 1.5-5.5 months resulted in a statistically significant mean loss of up to 85% of the asymmetrical synapses given by small granule-containing cells in the injured ganglion. The reduction of synapses was maximal 5-9 days post-operatively, and thereafter the incidence of synapses showed significant signs of progressive recovery. The time course and magnitude of the change in incidence of these synapses resembled those found earlier (Matthews & Nelson, 1975) for the loss of preganglionic synapses to principal neurones in the same ganglia, and after an identical post-ganglionic lesion. Control experiments showed that there was no loss of outgoing synapses from the small granule-containing cells as a result of surgical stress or of simple ageing. Older rats (5.5 and 13 months) showed a small but significant increase in the incidence of these synapses. Unilateral post-ganglionic axotomy produced the same reaction in the injured ganglia as did bilateral lesions. Uninjured ganglia contralateral to unilateral axotomies, however, also showed some deficit of outgoing synapses from small granule-containing cells, but this was slight, amounting to 9.9% over-all in comparison to normal values in young rats, and this difference did not reach statistical significance. Cutting the cervical sympathetic trunk to produce preganglionic denervation 2 days before surgical removal of ganglia for analysis did not alter the incidence of outgoing synapses of the small granule-containing cells, either in ganglia post-ganglionically axotomized 5-128 days earlier or in contralateral ganglia, indicating that at no stage was any significant proportion of these synapses given to preganglionic axons. These findings suggest that most of the outgoing synapses from the intra-ganglionic small granule-containing cells are directed to principal neurones whose axons leave with the injured branches, the internal and external carotid nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Incoming synapses and size of small granule-containing cells in a rat sympathetic ganglion after post-ganglionic axotomy.

A quantitative ultrastructural study has been made of the reaction of the incoming synapses of small granule-containing cells after axotomy of the major post-ganglionic branches of the superior cervical ganglion of the young adult rat. These cells are intrinsic and interneurone-like in this ganglion, receiving a preganglionic input and giving outgoing synapses to principal post-ganglionic neurones. Unlike their outgoing synapses, which are lost after post-ganglionic axotomy (Case & Matthews, 1986), the incoming synapses of the small granule-containing cells in axotomized ganglia increased in incidence post-operatively. The increase first became clearly evident 5-7 days post-operatively and was greater, being both more sustained and progressive, after bilateral than after unilateral axotomy. After bilateral axotomy the incidence of incoming synapses rose to more than four times that of normal ganglia and was still elevated at 128 days post-operatively, but was within normal limits at 390 days. After a unilateral lesion, increases of similar extent and time course to those in the axotomized ganglia were seen in the incoming synapses of small granule-containing cells in the uninjured contralateral ganglia. The incoming synapses of the small granule-containing cells are multifocal, i.e. show several points or active foci of synaptic specialization. The increase in synapses expressed itself both through an increased incidence of these synaptic active foci per nerve terminal and through an increase in the number of presynaptic nerve terminal profiles associated with the cells. Control observations indicated that the increase in synapses was not due to surgical stress, nor was it attributable solely to post-operative ageing. The nerve terminals which were presynaptic to the small granule-containing cells post-operatively were all of preganglionic origin: no incoming synapses or presynaptic nerve terminals remained at 2 days after a preganglionic denervation of axotomized or contralateral ganglia, at whatever stage this was performed throughout the range of survival intervals. There was some evidence that the synapses had increased by sprouting, including terminal sprouting, of the preganglionic nerve fibres. In the shorter term there was an increase in the proportion of small nerve terminal profiles. In the longer term the mean size of the terminal profiles increased, and very large terminals of unusual form were seen. After post-ganglionic axotomy, and in particular after a bilateral lesion, the small granule-containing cells became hypertrophied.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A quantitative study of structural features, synapses and nearest-neighbour relationships of small, granule-containing cells in the rat superior cervical sympathetic ganglion at various adult stages.

Groups and sub-groups (clusters) of small granule-containing cells ("small cells") were analysed at 3 and 6 micron intervals and in serial sections, in rats aged 2-13 months. Fully intraganglionic clusters of small cells were all found to receive an incoming ("afferent") innervation, of the order of 3-6 afferent terminals per cell, derived from axons of preganglionic type via multifocal, symmetrical, mainly axosomatic synapses. No evidence was obtained of sharing of preganglionic inputs between small cells and principal neurones. Intraganglionic clusters also regularly gave outgoing ("efferent") synapses of the asymmetrical type, of the order of 2-6 per cell, to intraganglionic nerve elements; 30-50% of these synapses were given from somata, 50-70% from processes of the small cells. Whenever the postsynaptic structure was identifiable these synapses were all found to be given to postganglionic neurones or their dendrites, principally to spine-like processes or slender twigs. In some ganglia a few efferent synapses to other small cells were observed; these were of the symmetrical type. Efferent synapses to nerve profiles resembling chemosensory axon terminals, also of the symmetrical type, were extremely infrequent (fewer than 1% of all efferent synapses) in intraganglionic small cell groups and appeared virtually restricted to glomus-like clusters of small cell, which lay intracapsularly, or in and near the bases of nerves entering or leaving the ganglion. Almost all groups and clusters of small cells were located near to fenestrated capillary vessels, which are not found elsewhere in the ganglion. The implications of possible non-synaptic release of material from small cells via membrane regions not covered by satellite cell cytoplasm, were explored in a nearest-neighbour analysis. These "exposed" regions comprised 1-3% of the small cell surface, a proportion comparable with those engaged in receiving afferent synapses or in giving efferent synapses. The majority of such regions faced toward other nerve profiles (axons and dendrites) ensheathed in satellite cytoplasm (mean 30%), intraganglionic tissue spaces wider than 3 micron (mean, 30%) or other small cells (mean, 14%); 25% faced toward blood vessels, but of these vascularly directed regions, only one fifth (or 5% of the total) on average faced directly toward fenestrated endothelium, the rest being non-fenestrated and/or separated by pericyte processes from the exposed regions of small cell membrane. Thirty-three percent of the small cells in a sample of 242 lay within 2 micron of the nearest blood vessel.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

A suprasellar subarachnoid pouch; aetiological considerations.

A child with hydrocephalus treated by a valved shunt was reinvestigated after developing a shunt infection. A pouch was discovered invaginating the floor of the third ventricle and filling slowly with CSF from the region of the interpeduncular cistern. Histology and mechanisms of this pouch formation are discussed.

Arachnoid↗