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Biomedical subjects

D K Dastur

Publications and source records attributed to D K Dastur.

At least 73 records · Page 4Linked to original sources

Nature of muscular change in osteomalacia: light- and electron-microscope observations.

Thirteen muscle biopsy specimens (mainly the gluteus maximus) from 12 patients with laboratory confirmation of osteomalacia and proximal muscle weakness in 10 were examined by light and electron microscopy. Light microscopy revealed mild diffuse non-specific atrophy of the muscle fibres in 10 cases, severe generalised atrophy in one and patchy group atrophy in one. There was no myopathic change in specimens from cases with either a nutritional aetiology, or a mixed aetiology. The former, mostly women gave a history of severe chronic malnutrition often accompanied by repeated pregnancies and prolonged lactation; those with a mixed aetiology gave, in addition, evidence of a metabolic or endocrine disorder such as hyperparathyroidism, hyperthyroidism, uraemia, or treatment with anti-epileptic drugs or were of uncertain origin. Electron-microscope examination of muscle from the nutritional group showed atrophic changes in the fibres, such as loss of myofibrils, prominence of mitochondria and glycogen, loosening and folding of the basement-membrane but good preservation of the remaining myofibrils. In contrast muscle from cases of mixed aetiology showed, in addition to the atrophic features, clear degenerative changes in the myofibrils and the mitochondria, accumulation of amorphous material at the site of myofibrillar loss and of lipofuscin in muscle fibres, vascular endothelium and satellite cells. The earliest degenerative change was in the "I" band, involving actin filaments and "Z" line. The triads were generally preserved but the sarcoplasmic reticulum appeared affected in a patient with tetany and severe mitochondrial degeneration. In a patient with thyrotoxicosis, proliferation of central nuclei, "Z" line streaming and formation of "T" tubular aggregates were seen. In one patient with hyperparathyroidism and hypercalcaemia, severe myofibrillar degeneration and mitochondria showing osmiophilic deposits, possibly of calcium phosphate, were encountered. It is concluded: (1) that all osteomalacic muscle weakness is not myopathic but a non-specific atrophy occurring probably on the basis of disuse and malnutrition, and (2) patients with an added metabolic or endocrinological disorder show in addition to the atrophy, degenerative changes in the muscle fibre and its sub-cellular components consistent with myopathy, and these patients should be clearly distinguished from those with a background of malnutrition only.

Adolescent↗

Dual infections of mice: visceral larva migrans and sublethal infection with Japanese encephalitis virus.

Experiments in 3 weeks old albino mice with Toxocara canis and sublethal infection with JE virus established a marked synergestic effect in dually infected mice. The results are discussed to indicate the possible role of visceral larva migrans in creating exploxive outbreaks of "acute encephalopathy syndrome" in individuals having simultaneous infection with a virus (es) which, alone, might produce only mild illness. The nature of the possible mechanisms involved yet remains to be understood.

Animals↗

Interrelationships between the B-vitamins in B12-deficiency neuromyelopathy. A possible malabsorption-malnutrition syndrome.

Five patients presenting clinically with a form B12-deficiency neuromyelopathy, with cord involvement in all and proximal muscle weakness in two of them, were investigated for their neurologic, hematologic and vitamin status. Megaloblastosis and achlorhydria were present in all, and impaired absorption of 57Co vitamin B12 and of D-xylose was detected in four. Total cyanide extracted vitamin B12 (A) was lowered in all cases and noncyanide extractable (B) in four of the five, being zero in three. All five responded to injections of hydroxocobalamin. In two patients sequential estimations showed that both A and B, especially the latter, rose steeply initially, normalizing at 50% of A after some weeks. Moiety B is suggested to be physiologically the more active and dissociable form of vitamin B12. Markedly elevated initial serum folate levels, and their subsequent fall under treatment with B12, indicated the operation of the "methyltetrahydrofolate trap". Blood levels of thiamin, nicotinic acid and pantothenic acid were within normal limits. However, serum riboflavin (B2) total vitamin B6 and pyridoxal were reduced in all where tested. Vitamin B6 deficiency could have resulted from its own malabsorption and have contributed to be B12 deficiency. Vitamin B2 and B6 levels also corrected themselves on B12 therapy. The B-vitamin deficiencies in our patients probably resulted from intestinal malabsorption, with a possible factor of malnutrition consequent to their strictly vegetarian diet.

Achlorhydria↗

Possible neurogenic factor in muscular dystrophy: its similarity to denervation atrophy.

Muscle biopsy specimens from 179 cases of muscular dystrophies and from 140 cases of anterior horn cell disorders (from a total of 1,348 biopsied patients) were examined histologically. There were 72 cases of Duchenne type muscular dystrophy (DMD), five of Becker type MD, four girls with myopathy resembling DMD, 40 with limb-girdle, 10 with facioscapulohumeral, seven with late onset, 13 with congenital, and 28 with unclassifiable muscular dystrophies. Groups of small atrophied muscle fibres were encountered in 42 (23%) of the cases in this group, most frequently in patients with limb-girdle, facioscapulohumeral, and least frequently with DM dystrophy. In the second group there were 25 cases of infantile, 38 of juvenile, and 39 of adult spinal muscular atrophy (SMA); there were 21 patients with motor neurone disease (MND), six with poliomyelitis, and 11 with an unclassifiable type of anterior horn cell disorder. Pseudomyopathic changes were encountered in 43 (30%) of all cases in this group. They were most frequently present among patients with juvenile and adult SMA and in those with MND. The presence of group atrophy in muscular dystrophy is considered significant myopathological evidence of a denervation process. On the other hand, pseudomyopathic changes, variation in fibre size, rounding, central nuclei, and increase in connective tissue occurring in various anterior horn cell disorders are seen not to be specific `myopathic' changes. Thus there was an overlap of pathological reactions in muscles from the dystrophies and the neurogenic atrophies. Comparably atrophied fibres (much less than 2 SDs below the normal mean diameter) and hypertrophied fibres (much more than 2 SDs above the normal mean diameter) were encountered in both dystrophy and neurogenic atrophy, considering the large muscles of the limb. Likewise, the mean fibre diameters were comparable in DMD and in juvenile SMA. The fourth evidence of a neurogenic factor in muscular dystrophy was derived from an examination of SDH preparations of muscle. There was a preponderance of type I muscle fibres in dystrophic muscles compared with specimens from controls, suggesting depletion of type II fibres. It appears that the concept of muscular dystrophy as a primary muscle disease needs to be re-examined.

Adolescent↗

Effect of vegetarianism and smoking on vitamin B12, thiocyanate, and folate levels in the blood of normal subjects.

Vitamin B(12), thiocyanate, and folate levels in the blood were estimated in 69 apparently normal subjects, of whom 26 were non-vegetarian non-smokers, 19 non-vegetarian smokers, 15 vegetarian non-smokers, and nine vegetarian smokers. The serum total (cyanide-extracted) B(12) level (value A) ranged from 105 to 728 pg/ml, with a mean of 292 pg/ml. The highest values were found in non-vegetarian non-smokers and the lowest in vegetarian smokers. There was no significant difference in value A between smokers as a group and non-smokers as a group. On the other hand, in vegetarians value A was very significantly lower than in non-vegetarians regardless of their smoking habits.It is suggested that A may represent both the protein-bound and free forms of vitamin B(12) in the blood, and B mainly the free B(12), which may be the physiologically active form. The plasma thiocyanate level varied from 1.0 to 15 mumol/100 ml, being, as expected, much higher in smokers (mean 8.20 mumol/100 ml) than in non-smokers (mean 2.02 mumol/100 ml). There was a rough correlation between falling B(12) levels and rising thiocyanate levels. The serum folate level ranged from 2.75 to 15.75 ng/ml, and was slightly but significantly higher in vegetarians (mean 6.60 ng/ml) than in non-vegetarians (mean 4.79 ng/ml), reflecting the greater content of folate in a vegetarian diet.

Cyanides↗

Role of vegetarianism, smoking, and hydroxocobalamin in optic neuritis.

Only 20 patients with optic neuritis of unknown aetiology could be collected in Bombay over a period of two and a half years. Only six of them were smokers and only three (one a non-smoker) had bilateral centrocaecal scotomata similar to those found in tobacco amblyopia. In 11 untreated patients the serum vitamin B(12) and plasma thiocyanate levels were estimated and found to show no significant differences from those in normal control subjects. Treatment with hydroxocobalamin in the majority of cases and with cyanocobalamin, corticotrophin, or prednisolone in the rest showed equally good results; spontaneous improvement was seen in one case.No significant role could be assigned to smoking (cyanide) or to vegetarianism in the production of optic neuritis in these patients; nor was there any evidence of depletion of total (cyanide-extracted) B(12) or of an increase in the proportion of non-cyanide-extracted B(12) in the serum.

Adolescent↗

Arthrogryposis multiplex congenita. I. Clinical and electromyographic aspects.

Sixteen cases with arthrogryposis multiplex congenita were examined clinically and electromyographically; three of them were re-examined later. Joint deformities were present in all extremities in 13 of the cases; in eight there was some degree of mental retardation. In two cases, there was clinical and electromyographic evidence of a myopathic disorder. In the majority, the appearances of the shoulder-neck region suggested a developmental defect. At the same time, selective weakness of muscles innervated by C5-C6 segments suggested a neuropathic disturbance. EMG revealed, in eight of 13 cases, clear evidence of denervation of muscles, but without any regenerative activity. The non-progressive nature of this disorder and capacity for improvement in muscle bulk and power suggest that denervation alone cannot explain the process. Re-examination of three patients after two to three years revealed persistence of the major deformities and muscle weakness noted earlier, with no appreciable deterioration.

Adolescent↗

Arthrogryposis multiplex congenita. 2. Muscle pathology and pathogenesis.

Pathological findings are reported on 34 specimens from 16 cases of arthrogryposis multiplex congenita (AMC), including initial observations on paraffin sections from 28 muscles, and subsequent observations on six additional specimens from three of these cases studied both histologically and histochemically. Thirteen of the 34 specimens (from 11 cases) were histologically normal, probably on account of an unaffected muscle being sampled. The most constant pathological feature in the remaining specimens was a disorganization of the muscle fibres and fascicles by severe fibrosis; only three specimens (from two cases) did not show this. Very thin faintly striated muscle fibres embedded in this matrix were encountered in 10 specimens from nine cases. An attempt at grouping of these atrophic or ill-developed fibres was noticed in four specimens; but this may not be denervation atrophy. Two specimens (from two cases) showed `myopathic' features. Repeat biopsy after two to three years was carried out on two affected muscles each from three patients. Case 3 showed well preserved but uniformly small fibres. Case 4 showed extremely few and scattered small rounded fibres. Case 14 showed pronounced variation of fibre size in both, with both atrophic and hypertrophied fibres. Normal nerves and spindles were seen in all these six specimens irrespective of the state of the muscle, and excessive fibro-fatty tissue in cases 4 and 14. Histochemical examination for oxidative enzymes, ATPase, and phosphorylase in these six specimens revealed a normal checkerboard pattern and ratio of type I and type II fibres, in case 3 only. The muscles of case 4 showed a preponderance of type I fibres. One specimen from case 14, showed the same fibres reacting for both oxidative enzymes and phosphorylase, suggesting a lack of development of fibres. The intrafusal fibres were mainly of type I in all. Two possible pathogenetic mechanisms operating in early embryonic life, which may lead to the characteristic changes of AMC, are discussed: (1) a defect in the development of the muscle whereby the full recruitment of myoblasts from the mesenchyme of the limb-bud does not take place and muscles do not form adequately; (2) a lack of innervation of the muscles on account of arrested growth of anterior horn cells. The combined operation of both these mechanisms is also considered. Fibrous tissue replaces the muscle tissue that is lacking, and contractures and deformities ensue. The evidence gathered on our material, such as the very thin smooth muscle fibres, the large numbers of well-formed nerves and spindles especially in the repeat biopsies, and the above-mentioned histochemical feature, would appear to favour the hypothesis of ill-developed muscles in the production of AMC in the majority; in the rest denervation playing either a major or concurrent role.

Adenosine Triphosphatases↗

Distribution and fate of 54Mn in the monkey: studies of differnnt parts of the central nervous system and other organs.

The fate and distribution of isotopic manganese administered as a single carrier-free dose of 200 muCi of maleate-(54)Mn to 12 rhesus monkeys was studied at different time periods from the 6th hr to the 278th day. Whole-body activity was measured, and all body organs and tissues and different parts of the central nervous system (CNS) were evaluated for specific activity, exponential analysis, and relative retention. Exponential analysis revealed a pattern of discharge with a fast and a slow component for the whole body and for many of the viscera. All parts of the CNS and, to a lesser degree, the thyroid and muscle showed an almost steady state of activity after the initial uptake. While the whole body and most organs and tissues appeared to discharge their radioactivity with the passage of time, first rapidly and then gradually, the CNS, endocrine glands, and muscle tissues showed persistent levels of specific activity. All components of the brain exhibited increasing relative retention, the lentiform nucleus and the cerebellum showing this more. It is suggested that the selective vulnerability of the brain in manganese miners might result from this inability on the part of the CNS to discharge the (54)Mn with time. This investigation confirms and amplifies our earlier similar study on the rat.

Animals↗