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Biomedical subjects

D K Dastur

Publications and source records attributed to D K Dastur.

At least 37 records · Page 2Linked to original sources

The pathology and pathogenesis of tuberculous encephalopathy and myeloradiculopathy: a comparison with allergic encephalomyelitis.

The pathology and pathogenesis of tuberculous encephalopathy are reviewed. They confirm the findings in a smaller series previously published. The main features were: diffuse brain edema and myelin pallor in the majority of specimens; microvascular distension or necrosis with perivascular macrophage reaction and greater demyelination; focal glial nodules in the white matter; less frequently, hemorrhagic lesions in the presence of mild-to-moderate tuberculous meningitis (TM), but in the virtual absence of the commoner brain-damaging mechanisms. Focal demyelinating lesions in the nerve roots are now added to the above pathology in the brain in some of the cases of spinal tuberculous meningitis. In addition, a picture similar to that in human postinfectious allergic or experimental allergic encephalomyelitis (EAE) has emerged. The spinal cords from one case of the former condition and from four animals with EAE are described to illustrate this similarity. The pathogenesis of tuberculous encephalopathy and myeloradiculopathy is believed, as before, to be due to delayed hypersensitivity, i.e., cell-mediated immunity (CMI) to tuberculoprotein. Experimental confirmation of this demyelination as a nonspecific consequence of CMI to various forms of tubercle bacillus proteins has recently been published. In a proportion of our cases, where two episodes of TM had occurred, the possibility of a hypersensitivity reaction to the brain's own myelin protein is also considered.

Adolescent↗

Pleomorphism of fine structure of rabies virus in human and experimental brain.

Identification of the Negri bodies in the brain of an 8-year-old boy who died 8 days after a paralytic illness and 20 days after a dog bite, and who had received 9 injections of Semple's anti-rabies vaccine, provided evidence that he died of acute rabies encephalitis and not of post-vaccinal allergic encephalomyelitis. The Negri bodies in the human subject and those seen in the inoculated mouse differed in their morphological structure: the former consisted of a matrix of very fine granular material bearing larger granules or strands of higher electron-density resembling nucleic acids and representing products of host cell-virus interaction; and the latter showed better defined areas of granular matrix containing tubular, bullet-shaped and elongated forms of viral structures, and nucleocapsids or capsule-deficient cores, representing the virions, emerging from them. Fine structural examination of the patient's brain and of the inoculated mouse has provided evidence of the pleomorphism of the Negri bodies and the various stages of formation of viral material and virions in them, the animal alone showing the mature virions of rabies, and proving the infectivity of the Negri bodies of the human brain.

Animals↗

Fine structure of cellular and vascular reaction in brain tuberculomas: a model for phagocytosis in the CNS.

The fine structure of cells of the mononuclear phagocyte series (MPS) and a few other cells with phagocytic capacity, has been critically evaluated, mainly from an electronmicroscopic examination of the reactive border zone of 11 human brain tuberculomas, which provide ideal material for the study of macrophages. Most of them appeared to be blood monocyte-derived epithelioid cells of various forms and stages. The cytoplasm of these cells showed either more rough ER representing protein synthesising activity; or more frequently, phagosomes, phagolysosomes, dense bodies or empty vacuoles, representing various stages of ingestion and digestion of necrotic material. Often such material, which was more or less osmiophilic, was seen abundantly between the cells. These actively phagocytic cells occasionally undergoing, mitosis, are referred to as "epithelioid macrophages" and were morphologically similar to the "activated microglia" described in other conditions. They also showed a tendency to be closely adjacent to each other and occasionally fuse to form giant cells. There were also a number of lymphocytes and plasma cells. The latter showed various stages of active and granular or depleted and distended rough ER tubules, phagocytic activity and tendency to fuse. Expected vasculitis and small vessel necrosis formed part of this granulomatous reaction. Constituents of oedematous or necrosed brain tissue were seen immediately around the reactive zone of these tuberculomas, the most frequent being reactive astrocytes, many of which showed membrane-bound vacuoles. It is conceivable that the excessive pleomorphic cellular, vascular and necrotic reaction in these brain tuberculomas could have resulted from a delayed type of hypersensitivity to a very small quentity of antigenic tuberculoprotein, which probably initiates the chain of immunologic responses.

Adolescent↗

Experimental neurotoxicity of the anorectic fenfluramine. I. A fine structural model for cerebral lysosomal storage and neuroglial reaction.

Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8-19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic "reactive microglia" were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.

Animals↗

Changes in atrial biopsies in chronic rheumatic heart disease. I: Cellulo-vascular and mesenchymal reaction.

The cellular, vascular and connective tissue changes were studied in 32 atrial biopsy specimens from patients with chronic rheumatic heart disease (RHD). 15 of these 32 specimens showed some inflammatory reaction, 7 with small mononuclear cells only and 8 with macrophage reaction amidst increased but necrotic collagen, especially in the subepicardial and subendocardial regions. Most cellulonecrotic foci were histologically consistent with a stage of Aschoff nodule. Acid phosphatase activity in frozen sections was seen in the cytoplasm of the macrophages. Fine structural examination showed membrane-bound vacuoles and lipofuscin bodies rather than ingested material in the macrophages. By light and electronmicroscopy, these macrophages were not different from those encountered in other granulomatous or necrotic conditions. There was moderate proliferation of blood vessels, with prominence of endothelial cells and pinocytotic vesicles, or fibrosis of media, or proliferation of basal laminae. The presence of Aschoff nodules in the right atrium, the least affected chamber in RHD, suggests a diffuse and smouldering pathology on the basis of a persistent subclinical cell-mediated immune (CMI) reaction.

Adolescent↗

Changes in atrial biopsies in chronic rheumatic heart disease. II: Muscle fibre reaction.

Myocardial fibres were studied in the right atrial biopsies from 32 patients with chronic rheumatic heart disease (RHD). Paraffin and, particularly, araldite sections showed many muscle fibres well preserved, and others with large hyperchromatic nuclei, or with depleted myofibrils and increased mitochondria. With the SDH and ATPase reactions, there was no type difference in the myocardial fibres, and the former showed the reaction predominantly in the centre while the latter showed it mainly at the periphery of the fibres. At electronmicroscopy, fibres with intact myofibrils were found close to "degenerating" fibres with variable degrees of myofibrillar and myofilament disorganisation and loss, mitochondrial proliferation, occasionally with degeneration of cristae, and accumulation of lipofuscin in varying amounts, and irregularly tortuous or loosened intercellular junctions. This study has revealed more severe muscle changes than expected, even in the clinically less affected right atrial chamber in chronic RHD. It is speculated that this might be due to subclinical involvement of the tricuspid valve, known to be frequent in Indian patients, and the resulting "back pressure" on the right atrium might lead to changes in its myofibres.

Adolescent↗

Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia.

A review and a reappraisal are presented of earlier data on cerebral circulatory and metabolic studies in normal active elderly men (Group I) of mean age 71 years, compared with normal young subjects of mean age 21 years, conducted at the National Institutes of Health, Bethesda, MD, U.S.A., during 1956-1958. There was no significant difference in the mean CBF and cerebral metabolic rate for oxygen (CMRO2) values between the two populations; i.e., these important parameters did not fall with chronological aging per se. There was significant depression in the mean cerebral metabolic rate for glucose (CMRG) value (by approximately 23%) in the aged compared with the young. Newer methods using positron emission tomography and appropriate isotopes have confirmed these findings in normal aging in human subjects and experimental animals. As expected, MABP and cerebral vascular resistance (CVR) were significantly elevated in the normal aged. MABP was even more elevated in elderly hypertensive subjects, and the CVR more elevated in the subjects with arteriosclerosis (Group II), who also showed a small but significant fall in CBF and in internal jugular venous PO2. The CBF showed a more pronounced fall in senile aged patients with chronic brain syndrome (Group III), in whom the CMRO2 also showed a marked drop (by approximately 22%); the CMRG fell still further (approximately 40% of that in the young). Of the few aged subjects followed up after a lapse of 11 years by a repeat estimation of the same physiological and psychological parameters and of the EEG, most showed clear worsening, together with a fall in overall physical and intellectual performance, probably related to a rise in CVR and an increase in atherosclerosis with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Meningoceles and neurological involvement.

The term meningocele is used in this communication to include all lesions presenting as swellings associated with spina bifida, when neural tissue is not exposed on the surface. 144 meningoceles were operated on during an 18-year period. The stalk of the meningocele was connected with the neural tissue in 113 of them. Two distinct types of lesions have been noted in these patients and have been designated "meningocele with tethered cord" (52) and "meningocele with tethered roots" (56). In both conditions about half the number of cases presented clinically before the age of 3 months, when paraplegia was evident in only 5 of the 26 infants with tethered cord and 3 of the 25 with tethered roots. In contrast, all or the majority of babies reporting after the age of one year, had paraplegia. Hence, a case is made out for an early operation in all these patients. At surgery the main lesion was a fatty mass in 29 babies with tethered cord, and a cystic mass in 30 with tethered roots. While hydrocephalus was virtually absent in these babies, there were 5 others who manifested obstructive hydrocephalus with meningocele. "Meningomyelocele", the commonest lesion associated with spina bifida, presents with an exposed spinal cord at birth, is associated with communicating hydrocephalus, and can be clearly distinguished from the meningocele.

Diagnosis, Differential↗

Megacystis, microcolon, intestinal hypoperistalsis syndrome: possible pathogenesis.

Two cases of "Megacystis-microcolon-intestinal hypoperistalsis syndrome" are described. These appear to be the seventh and eighth cases in published literature. Consistent with the two published reports, both our patients were newborn female infants who manifested a large bladder, associated with unused colon and functional intestinal obstruction. While the earlier published reports mention a full complement of normal mature ganglion cells in all parts of the bowel, the two cases described here showed " dysganglionosis " to some extent, in the form of fewer and shrunken neurones along with other mature-looking neurones in some parts of the bowel. The bladder was available for histologic examination only in the second case and showed apparently normal innervation. Hence, it is felt that the intestinal obstruction in these cases could have been due to a disturbance in bowel innervation.

Colon↗

Neurosurgically relevant aspects of pathology and pathogenesis of intracranial and intraspinal tuberculosis.

In view of the persisting high prevalence (though somewhat reduced compared to 20 years ago) of various forms of neurotuberculosis , especially in economically underpriviledged and undernourished urban paediatric populations of the world, some aspects of the neuropathology relevant to neurosurgeons, are briefly presented and discussed. The most conspicuous of these is the development of brain tuberculomas, which act as both space-occupying and inflammatory masses that result in severe oedema or direct destruction of brain parenchyma. The cellular reaction in the border zone of these tuberculomas is identical to that in tuberculous meningitis and consists of specialized large mononuclear cells-the epitheloid cells-which undertake a phagocytic function and also fuse with one another to form giant cells, as seen by both light and electron microscopy. These cells together with others like lymphocytes and plasma cells, also infiltrate the walls of small blood vessels, constituting vasculitis, and these vessels may undergo necrosis, in both the intracranial (mainly basal) and spinal leptomeningeal exudate. The latter is more frequent in young adults than in children, and may be the primary event in the CNS or secondary to extension downwards of the basal meningitis. The quantity and nature of the spinal exudate vary in duration and severity, the more common being extensively "tubular" and subacute, producing radiculopathy and myelopathy by compression of these structures, and rarely infiltration. The damage to the cord, mainly the white matter, occurs through oedema and ischaemia, rather than frank infarction, the larger arteries being rarely involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pathology and pathogenesis of predilective sites of nerve damage in leprous neuritis. Nerves in the arm and the face.

A very brief review of the literature on the clinicopathological aspects of leprosy is given; mainly through references. The salient features of the two main types of leprosy--tuberculoid and lepromatous--are presented in a Table. The surgical and pathological findings are briefly described and the pathogenesis of involvement of the facial nerve (a motor nerve) is discussed. On the basis of (i) the severe histopathologic changes (degeneration) of the most distal part of the zygomatic branch of the facial nerve (innervating the orbicularis oculi), with sparing of the roots of all branches and the trunk of the nerve; (ii) the concurrent loss of cutaneous sensations in the territory of the maxillary division of the trigeminal nerve (the region of the zygoma and the lower eyelid); and (iii) the close approximation or even anastomoses occurring between the ultimate branches of these two nerves, it is postulated that paralysis of orbicularis oculi occurs secondarily to the sensory nerve damage, i.e. due to spread of infection from the sensory branches of the trigeminal to the motor branches of the facial nerve. The surgical and pathological findings of the nerves in the arm, especially the ulnar and the median and their branches are described, in tuberculoid and lepromatous leprosy. The forms of nerve degeneration, the occasional axon regeneration, and the role of the Schwann cell in harbouring the bacilli, are illustrated. The lysosomal enzyme activity in the Schwann cells of nerve fibres, particularly of unmyelinated fibres which preferentially phagocytose the M. leprae, and their role, albeit not very successful, in degrading the bacilli and controlling the infection, are also stressed, through light and electronmicrographs. The constellation of secondary factors of the terrain operating to produce further damage to primarily diseased nerves, is discussed. These factors include indirect compression from unyielding fibroosseous tissues, minor traumata, stretching of the nerves, and their exposure to lower temperatures in subcutaneous tissues.

Facial Nerve↗

Von Recklinghausen's disease with a malignant meningeal, cerebral and optic nerve tumour and bilateral vagal schwannomas. Possible mesenchymal histogenesis on light and electron microscopy.

The clinical, histopathologic and fine structural features of multiple unusual tumours detected in a 20-year-old patient with von Recklinghausen's disease, who died within a year of onset of symptoms of a rapidly expanding intracranial tumour, are described. The tumour was found to involve the falx cerebri, the basal leptomeninges and dura mater, both olfactory and optic nerves, both frontal lobes, the right temporal lobe and middle cerebral peduncle, both middle cerebellar peduncles, and with a metastasis in a cervical node. On light and electron microscopy this tumour appeared to be a fibroblastic meningeal sarcoma with giant cells, mitotic figures, a rich reticulin matrix throughout, and tumour cells full of rough ER but without any glial filaments. Also very unusual was the involvement of both vagus nerves in their cervical and intrathoracic portions, by a schwannomatous benign tumour and with a non-chromaffin paraganglioma at its termination in the oesophagus. One of the few cutaneous "neurofibromas" was also schwannian, containing tumour cells with a basement membrane on electron microscopy. Most, if not all, of these tumours appeared mesenchymal in origin, more aggressive in behaviour and carrying a graver prognosis in von Recklinghausen's disease.

Adult↗

Cerebral ganglioglio-neuroblastoma: an unusual brain tumour of the neuron series.

The pathology of an unusual intracranial neuroectodermal tumour of the neuron series in described and its possible histogenesis discussed. The tumour, in a child aged 5 years with an enlarged head since infancy, presented as a large solid intra-cerebral mass. Histological examination showed four types of cells; (i) the stroma, forming the bulk of the tumour, was astrocytomatous; (ii) lobules of ill defined cells bearing small circular nuclei, representing immature neuroblasts: (iii) the same of other lobules containing neurons in various stages of development; and (iv) dense clusters of cells with hyperchromatic nuclei attempting rosettes, representing an overtly malignant neuroblastoma. This tumour was designated "ganglioglio-neuroblastoma" and probably originated from a slow growing ganglioglioma.

Astrocytes↗