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Biomedical subjects

A K Sharma

Publications and source records attributed to A K Sharma.

At least 325 records · Page 18Linked to original sources

Morphological abnormalities in the sural nerve from patients with peripheral vascular disease.

The present paper has been written in order to determine the morphological alterations in the sural nerve from patients with chronic arteriosclerotic occlusive disease. Eight patients with Peripheral Vascular Disease (PVD) and six age-matched control subjects were studied. Morphometric data revealed two groups of patients, one of them with mild disease (n = 5), and the other one with severe damage (n = 3), consisting in loss of myelinated fibres and increase in the number of small fibres (p less than 0.05). Teased nerve fibres and electron microscopic studies also showed two types of patients, with respect to the myelin or the axonal alterations. The unmyelinated fibre population was affected equally in both groups. In conclusion, this study supports the idea that ischemia is able to cause structural alterations in the peripheral nerve, and that it can play a role in the development of neuropathy.

Aged↗

Spontaneous gastrointestinal perforation in the neonate.

Twenty seven cases of spontaneous gastro-intestinal perforation were treated from 1981 to 1990. Four perforations were in the stomach, 17 in the small bowel and seven in the large bowel. One of them had dual perforation, one in the stomach and another in the duodenum. The exact etiology remained obscure. Various factors observed were maternal obstetric complications, prematurity and perinatal asphyxia. Stress should be laid on early diagnosis by following up 'at risk neonates' thus, giving a better overall survival rate.

Female↗

Limited proteolysis of gamma II-crystallin from calf eye lens. Physicochemical studies on the N-terminal domain and the intact two-domain protein.

Gamma II-crystallin from calf eye lens consists of two homologous domains, connected by a six-residue linker peptide. In order to study the intrinsic properties of the domains and their mutual stabilization, limited proteolysis was applied. Optimum conditions providing a homogeneous 10-kDa fragment at high yield were pepsin cleavage in 0.1 M NaCl/HCl pH 2.0, in the presence of 3.0 M urea. Determination of the N-terminus and the C-terminal sequence showed that cleavage occurred at the Phe88-Arg89 peptide bond, giving rise to the complete N-terminal domain including the connecting hexapeptide. The C-terminal part of the polypeptide chain is cleaved to small fragments. Comparing the spectral properties of the isolated N-terminal domain and intact gamma II-crystallin proved the structure of the fragment to be closely similar to that of the native domain. Small differences in absorbance, fluorescence emission and circular dichroism point to alterations caused by the increase in surface area as a consequence of domain separation. The resistance of the 10-kDa fragment toward thermal and alkaline denaturation, as well as unfolding in the presence of urea or guanidine . HCl is decreased, due to the lack of domain interactions stabilizing the intact protein. Unfolding/folding kinetics of the 10-kDa fragment coincide with the second phase of the bimodal transition of intact gamma II-crystallin, in agreement with independent sequential folding and modular assembly of the domains within the native molecule.

Animals↗

Effects of posture on metabolic and hemodynamic predischarge exercise response after acute myocardial infarction.

Predischarge exercise testing after acute myocardial infarction (AMI) is an important noninvasive modality for risk stratification. To study the impact of position on cardiopulmonary exercise response, 30 patients performed symptom-limited upright treadmill and supine bicycle ergometry exercise an average of 8 days after an AMI. The exercise sequence was randomly assigned with a minimum 4-hour interval between tests. Exercise time and peak oxygen consumption were significantly greater in the upright position (7.0 +/- 2.0 vs 5.6 +/- 2.0 minutes; p less than 0.001 and 14.9 vs 12.0 ml/min/kg; p less than 0.001, respectively). Compared to the supine position, exercise in the upright position was associated with a significant increased incidence of ischemic exercise-induced ST-segment depression (33 vs 20%; p less than 0.03), and chest pain (20 vs 10%; p less than 0.04). Thus, position is an important determinant of myocardial ischemic response and exercise tolerance in patients who perform symptom-limited exercise tests early after AMI.

Adult↗

Neurofibromatous neuropathy.

Three cases of chronic distal sensorimotor neuropathy are described in patients with neurofibromatosis. One had type 2 or central neurofibromatosis with a chromosome 22 deletion; the precise form of the disease was not established in the other two. A striking clinical feature was a diffuse nodular enlargement of the peripheral nerves. Nerve biopsies from all three cases demonstrated the presence of neurofibromatous pathology. Neurofibromatous neuropathy constitutes a rare manifestation of neurofibromatosis, related to diffuse neurofibromatous changes in the peripheral nerves.

Adult↗

Hypoxic neuropathy: relevance to human diabetic neuropathy.

Clinical and neurophysiological studies were conducted in 47 patients with chronic obstructive airways disease and compared with 46 age-matched control subjects. Symptomatic neuropathy was reported in 13% and ankle jerks were absent in 45% of hypoxic patients. Peroneal and median nerve conduction velocities and median and sural sensory nerve amplitudes were significantly reduced in hypoxic patients (p less than 0.01). Six hypoxic patients underwent biopsy of the sural nerve, soleus muscle and overlying skin. Nerve glucose, sorbitol, fructose and myo-inositol concentrations were normal. Detailed light and electronmicroscopy revealed both nerve fibre and microvascular pathology. Segmental demyelination (32%) and unmyelinated fibre degeneration were found to be prominent lesions. The sural nerve perineurium was thickened due to an increase in the number of perineurial lamellae and an increase in intraperineurial space. Basement membrane thickening was observed in capillaries of nerve, muscle and skin. Endothelial cell hyperplasia and hypertrophy were observed in nerve and muscle capillaries but not in skin capillaries. In conclusion, this study has provided neurological, neurophysiological and neuropathological evidence of a neuropathy in hypoxic patients with chronic obstructive airways disease. These findings may be of relevance to some aspects of the aetiology of human diabetic neuropathy.

Action Potentials↗

Duodenal tuberculosis: a review of the clinicopathologic features and management of twelve cases.

A retrospective analysis of twelve cases of duodenal tuberculosis is presented herein. The average age of the patients was 31.4 years with a male to female ratio of 2:1. The presenting complaints were duodenal obstruction in six patients and subacute intestinal obstruction in three. None of the patients had associated pulmonary tuberculosis. Eight patients had isolated duodenal tuberculosis, two of whom were successfully treated with antitubercular drugs. In four patients, the diagnosis was established at laparotomy by the presence of tubercles over the duodenum. Five patients required a bypass procedure for obstruction caused by the duodenal tuberculosis and one patient was operated on for uncontrollable bleeding from a tubercular duodenal ulcer. All patients remained symptom free after treatment, whether medical or surgical. Thus, in areas where tuberculosis is endemic, even in the absence of pulmonary tuberculosis, duodenal tuberculosis should be suspected in patients with upper gastrointestinal obstruction or in patients with peptic ulcer like symptoms not responding to medical therapy.

Adult↗

Ultrastructural abnormalities of myelinated fibres in the tibial nerve of streptozotocin-diabetic rats.

In this paper we have examined the ultrastructural changes in myelinated fibre structure after the administration of streptozotocin to Sprague-Dawley rats which had passed the rapid growth period. Myelinated fibre size in the tibial nerve was found to be less in diabetic animals 4 and 6 months after the induction of diabetes, when compared to age-matched controls, but not less than onset. The relative contributions of axon and myelin to this reduction in fibre dimensions were examined. When myelin area was plotted against axon area (derived from perimeter) it showed that the pathological insult of diabetes had a greater effect on the rate of myelin production. The incidence of axonal glycogenosomes was also assessed. These results are discussed in detail.

Analysis of Variance↗

Immunotherapeutic effects of a vaccine based on a saprophytic cultivable mycobacterium, Mycobacterium w in multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w was given in addition to chemotherapy in 54 multibacillary, lepromin negative patients belonging to BB, BL and LL types of leprosy. Thirty-seven patients with similar types of diseases received chemotherapy and placebo injections. The 'vaccine' was repeated every 3 months. Bacterial clearance was more rapid in the vaccinated patients. Two lepromatous leprosy patients with initial bacterial index (BI) of 1.8 and 2.8 became bacteriologically negative in 1 year. One LL patient with BI of 6.0 had a BI fall to 0.16 after four doses of the vaccine. None of the LL patients belonging to placebo group during the same time period became bacteriologically negative. Rapid bacterial clearance was accompanied by distinct signs of clinical improvement. One hundred percent of BB, 85.7% of BL patients and 61.5% of LL patients converted to lepromin positivity after four doses of the vaccine. A significant number of vaccinated patients demonstrated an upgrading in skin lesions histopathologically.

Bacterial Vaccines↗

Interaction between Eimeria uzura infection and aflatoxicosis in Japanese quail (Coturnix coturnix japonica).

The clinical signs and gross lesions caused by Eimeria uzura (10(5) oocysts) in Japanese quail (Coturnix coturnix japonica) exhibited little or no influence in the face of intercurrent dietary aflatoxicosis (1 p.p.m. of aflatoxin B1 from Day 0 to 55). Similarly, no significant differences in the mucosal morphology of the intestine were evident histologically between the two groups of Japanese quail. The nervous signs of ataxia, leg weakness, incoordination of movement, torticollis and terminal opisthotonos were toxin-induced manifestations. In the aflatoxic quail, hypoplastic changes and selective depletion of lymphocytes were more prominent in the bursa of fabricius. Increased relative mean weights of liver, kidney, spleen, crop, proventriculus and gizzard were observed in birds due to aflatoxin sensitivity. The combination of E. uzura infection and aflatoxicosis in Japanese quail may cause significant weight loss, and increased oocyst production and reproductive potential.

Aflatoxin B1↗

Folding of an all-beta protein: independent domain folding in gamma II-crystallin from calf eye lens.

gamma II-crystallin from calf eye lens consists of two homologous domains, each composed of two similar "Greek key" motifs. As a consequence of the bilobal structure, a biphasic transition is seen upon unfolding by urea at low pH (monitored by circular dichroism, fluorescence emission, and ultracentrifugal analysis). In 3.3 +/- 0.5 M urea, a stable intermediate is formed at equilibrium, whereas 5.5 M urea causes maximum denaturation. Unfolding/folding kinetics display a complex pattern characterized by two kinetic phases. Both reactions exhibit strong dependence on the urea concentration; in the range of the respective transition, their rates are extremely slow (k approximately 1 x 10(-4)s-1). The kinetic mechanism of unfolding and refolding may be described by a three-state model: native in equilibrium intermediate in equilibrium denatured. The rate-determining steps are domain folding rather than domain pairing or proline isomerization. Kinetic analysis of the unfolding/folding of the intermediate populated in 3.0 M urea, pH 2.0, reveals that the kinetic and the equilibrium intermediates have similar structures. Limited proteolysis of gamma II-crystallin by pepsin in 3 M urea, pH 2, allows the NH2-terminal domain of the protein to be isolated. Unfolding/refolding of the fragment parallels the second transition in the above scheme, thus proving that the intermediate contains the COOH-terminal domain in its random state, whereas the NH2-terminal domain is still in its native conformation. In conclusion, folding of gamma II-crystallin proceeds through the independent sequential structuring of the domains.

Animals↗

Vagus nerve morphology in diabetic gastropathy.

Two patients were treated with gastroenterostomy and vagotomy for intractable vomiting due to diabetic gastropathy. A morphometric examination of nerve fibres and capillaries in their resected abdominal vagi was performed and the results were compared with findings from two diabetic and two non-diabetic patients undergoing gastroenterostomy and vagotomy for duodenal ulceration. All four diabetic patients had pathological changes of a similar character: reduced myelinated fibre density, degeneration and regeneration of unmyelinated fibres, and capillary basement membrane thickening. Abnormalities were more pronounced in the two diabetic patients with gastropathy but intact and regenerating nerve fibres were still present. The findings support the view that vagal neuropathy could be a causal factor in diabetic gastropathy but imply that severe gastropathy with vomiting is not simply a consequence of autovagotomy. The morphological observations indicated that structural changes can occur in the autonomic nerves of diabetic patients who do not develop autonomic symptoms or have easily detectable abnormal autonomic physiology.

Adult↗

Association of painful and painless diabetic polyneuropathy with different patterns of nerve fiber degeneration and regeneration.

We evaluated neuropathological abnormalities in sural nerve biopsies from 6 nondiabetic control subjects and 16 age-matched diabetic patients with different syndromes of sensory polyneuropathy (6 with chronic painful neuropathy [CPN], 4 with newly presenting painful neuropathy [NPN], and 6 with painless neuropathy associated with recurrent neurotrophic foot ulcers [RFU]). Although all but one of the evaluated features of myelinated and unmyelinated fiber pathology could be found in every diabetic patient, certain myelinated fiber abnormalities were associated with the clinical characteristics of the neuropathy. Thus, myelinated fiber density was severely reduced, "empty" Schwann tubes (an index of myelinated fiber degeneration) were increased, and early regeneration (bands of Büngner [BB], nonmyelinated axons) was pronounced in the RFU group. Progression from BB to regenerating myelinated fiber cluster (myelination and maturation) was more successful in patients with CPN and NPN than in those with RFU, and the finding of fibers with disproportionately large Schwann cells (cytoplasm and myelin) relative to axon caliber was exclusive to patients with neuropathic pain. We concluded that 1) unequal rates of successful fiber regeneration may underlie the apparent difference in the extent of myelinated fiber loss between painful and painless diabetic polyneuropathy; 2) myelinated and unmyelinated fiber degeneration and regeneration per se are probably not the cause of neuropathic pain in diabetic polyneuropathy, because each occurred in patients with RFU; and 3) axonal atrophy may be involved in neuropathic pain generation.

Adolescent↗

Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy.

Endoneurial capillary abnormalities have been assessed quantitatively in sural nerve biopsies from diabetic patients with different syndromes of sensory polyneuropathy: chronic painful neuropathy, newly presenting painful neuropathy, and painless neuropathy associated with neurotrophic foot ulceration. Comparisons were made with age-matched nondiabetic control subjects. The diabetic groups showed no abnormality in capillary density or mean endoneurial area per fascicle. Compared with control subjects, all diabetic patients had an increase in mean capillary diameter, capillary wall thickness, and outer tunic (basement membrane and pericytes) thickness. The increase in wall thickness was most pronounced in patients with painless neuropathy (200%) and less marked in similar patients with painful neuropathy (100%). The pericyte volume fraction of the outer tunic was reduced in all diabetic patients, implying that basement membrane hypertrophy and reduplication were responsible for outer tunic thickening. There was evidence of endothelial cell hyperplasia rather than hypertrophy. There was a correlation between the degree of basement membrane thickening and the severity of myelinated fiber abnormality assessed neurophysiologically and morphologically. This study shows a link between the degree of endoneurial capillary basement membrane thickening, the type of neuropathology, and the clinical expression of neuropathy in diabetes mellitus.

Biopsy↗

Effects of stage of lactation and pregnancy and their interactions on milk yield and constituents.

Effects of stage of lactation and pregnancy and their interactions on 17 milk yield and constituent traits of Holsteins and Jerseys were studied. Data were 11,120 Jersey and 11,092 Holstein daily milk samples. After adjustment for all other known and systematic genetic and environmental effects, stage of lactation influenced all traits and accounted for 11.8 to 26.3% of variation in yields and .2 to 9.9% in percentages. In general, yields declined and percentages increased after about 3 mo of lactation. Chloride percentage showed an initial decline and then a rise after 2 mo. Stage of pregnancy accounted for small but significant variation in most traits; variation was .2 to .4% and less than .1 to 3.0% in yields and percentages for Holsteins, and less than .1 to .2% and .1 to 1.1% for Jerseys. Interactions between stage of lactation and pregnancy were investigated by response surface methodology and found to be very small.

Animals↗