Biomedical subjects
A K Sharma
Publications and source records attributed to A K Sharma.
Nonspecific jejunitis--a challenging problem in children.
An acute enteric infection with the pathological feature of a severe necrotising jejunitis is an uncommon condition which mainly affects young people. It is characterized by severe abdominal pain of acute onset, copious bilious vomiting, and foul smelling loose stools containing blood. Exploration revealed varying degree of ischemic changes in the small bowel (mainly the upper jejunum) ranging from mucosal ulceration to frank gangrene of the bowel. The exact etiology is not known; the condition may be due to toxins produced by gram-negative bacilli or due to a localized allergic reaction. The disease had a progressive but self-limiting course. Mortality is around 40% and considerable morbidity continuing for 2-3 wk. Presentation bears similarity to Darmbrand of Germany, Pig-bel of New Guinea, and ischemic enteritis of Thailand.
Omental injury in a hernial sac.
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The effect of insulin treatment on myelinated nerve fibre maturation and integrity and on body growth in streptozotocin-diabetic rats.
Diabetes mellitus was produced in rats by the administration of streptozotocin and observations made over a period of 2 months. Four groups of animals were studied: onset and end controls, untreated diabetic rats and rats treated daily with a long-acting insulin preparation. Body weight increased in the end controls and insulin-treated diabetic animals to a similar degree over the observation period but was reduced in the untreated diabetic rats. Skeletal growth, assessed by measurements of tibial length, was also reduced in the untreated diabetic rats and partially corrected by insulin treatment. Myelinated fibre diameter in the tibial and sural nerves increased over the observation period in the controls, but the increase was less in the untreated animals and the growth deficit was not corrected by insulin treatment. Myelinated fibre numbers did not alter in the tibial or sural nerves between the onset and end controls. Numbers were significantly less in the tibial nerves of both the untreated and insulin-treated diabetic rats as compared with the two control groups; in the sural nerves, fibre numbers did not differ significantly between the four groups. Finally, the number of degenerating axons, assessed in teased fibre preparations, was very small in the control and untreated diabetic animals but was significantly increased in the insulin-treated group. Measurements of plasma glucose concentrations did not suggest that the axonal degeneration could be related to hypoglycaemia. The explanation for this paradoxical effect of insulin therapy is uncertain. It may be dependent upon fluctuations in blood glucose levels or other metabolic actions of insulin apart from its hypoglycaemic effect.
Ultrastructure of leprous phlebitis.
An ultrastructural study on vein biopsies from six lepromatous leprosy patients was carried out. The results showed that a) the lumen-lining bacillated cells were endothelial in origin due to the presence of specific Weibel-Palade endothelial cell granules; b) endothelial cells released Mycobacterium leprae into the lumen by exophagocytosis; c) M. leprae were able to grow and multiply in the endothelial and smooth muscle cells; and d) smooth muscle cells did not show any evidence of reaction due to the presence of M. leprae in their cytoplasm.
An enzyme immunoassay titrating IgM antibody against phenolic glycolipid for diagnosis of lepromatous leprosy.
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Ultrastructural observations on myelinated fibres in the tibial nerve of streptozotocin-diabetic rats: effect of insulin treatment.
Four groups of male Sprague-Dawley rats aged 11 weeks and weighing approximately 450 g were studied over 16 weeks: onset and end controls, untreated diabetics and diabetics treated with a daily subcutaneous injection of Ultralente insulin. Good metabolic control was achieved in the insulin-treated group as judged by daily blood glucose estimations, glycosylated haemoglobin levels (HbA1c) and body weight. Cross-sectional myelinated fibre area significantly increased between onset and end controls; growth thus occurred. In the untreated diabetic rats the values were significantly less when compared with age matched controls and not different to onset controls. The values for the insulin-treated diabetic group did not show a significant increase when compared with untreated diabetics and onset controls and were intermediate between end controls and untreated diabetics without any significant difference when compared with either group. Cross-sectional axonal area was significantly less in the untreated diabetic group as compared with age matched controls and this was corrected by insulin therapy, as there was no difference between end controls and insulin-treated diabetic group. Insulin treatment corrects the reduction in axon size but total myelinated fibre size is not normalised. It seems that in addition to the axon, the myelin sheath and Schwann cells are also affected and these may be less influenced by insulin therapy.
Truncus arteriosus. Surgical approach.
Between mid-1979 and December, 1983, 23 patients with various types of truncus arteriosus underwent total surgical correction at Royal Children's Hospital, Melbourne, Australia. Nineteen patients had primary total repair and four had secondary repair, three having survived banding done prior to 1978. Sixteen patients were less than 1 year of age. Repair was performed with circulatory arrest in infants and cardiopulmonary bypass with core cooling in older patients. Patients were electively ventilated preoperatively. In the postoperative period, pulmonary artery pressure was monitored very closely and any rise was treated with hyperventilation and vasodilators. Two patients under 1 month of age, who were severely acidotic and anuric preoperatively, died of low output syndrome. Among the rest of the infants there was only one death, probably because of pulmonary hypertensive crisis that might have been prevented. From our experience, we think that patients with truncus arteriosus should have total correction during infancy, preferably at 2 to 3 months of age, as it can be performed with a very low risk and also avoids the development of pulmonary vascular disease, which occurs very rapidly in these infants.
Diabetic gastroparesis from autonomic neuropathy: surgical considerations and changes in vagus nerve morphology.
Two cases with intractable vomiting due to gastroparesis, a rare feature of diabetic autonomic neuropathy, are described. Both required surgical treatment. In the first a gastroenterostomy was complicated by reflux gastritis requiring a revision operation; in the second a gastrojejunostomy was successful. Electron microscopic studies of the vagus nerve in one of the cases showed a severe reduction in the density of unmyelinated axons, the surviving axons tending to be of small calibre. The severity of the abnormalities supports the view that diabetic gastroparesis is related to vagal denervation.
Normal numbers of T6 positive epidermal langerhans cells across the leprosy spectrum.
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Inhibition of interleukin-2 production by adherent cell factors from lepromatous leprosy patients.
Twenty-four hour supernatants (MoF) were obtained from monocyte rich 2 h adherent cells of 19 leprosy patients and four healthy contacts. MoF from borderline and lepromatous patients produced 52-61% inhibition of human interleukin-2 (IL-2) production by a PHA conditioned T cell line (Jurkat). Non-adherent cell supernatants and MoF from tuberculoid and healthy individuals had little effect on IL-2 production. The suppression effected by MoF was in the first 12 h of initiation of PHA stimulated Jurkat cell cultures. Suppressive MoF did not interfere with (1) IL-2 release, (2) IL-2 utilization by Con A-induced T cell blasts or (3) constitutive proliferation of Jurkat cells. Such MoF were released spontaneously from adherent cells of bacilliferous leprosy patients but required in vitro antigen triggering in long term treated lepromatous patients. It is possible that the unresponsiveness associated with lepromatous leprosy is related to the inhibition of IL-2 production by suppressive factors, thereby, preventing the further expansion of antigen reactive T cells.
Sampling schemes for estimating nerve fibre size. I. Methods for nerve trunks of mixed fascicularity.
Using the tibial nerves of diabetic rats, alternative sampling schemes have been compared for estimating the sizes of fibres in nerve trunks of mixed fascicularity. The merits of each scheme were evaluated by comparing their reliability, precision, cost in time, and efficiency with 'absolute' values obtained by first measuring every fibre. The external diameter of all myelinated fibres was measured in each of six nerves (c. 2900 fibres/nerve). Total measurement time was about 29 hours. All sampling schemes produced group means within +/-4% of the absolute value of 5.52 micron. The most efficient schemes were those in which only 6% of all fibres were selected for measurement. For these the measurement time was 2 hours or less. Results are discussed in the general context of measurement of the sizes of nerve fibres. It is concluded that future studies should place more emphasis on sampling fewer fibres from more animals rather than on measuring all fibres very precisely. These considerations are likely to be of special concern to those wanting to analyse specimens with large fibre complements and those screening large numbers of specimens.
Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks.
The total number of myelinated fibres in four unifascicular tibial nerves from diabetic rats has been counted and measured in order to assess the merits of various schemes for estimating group mean fibre diameter. The average nerve trunk contained some 2960 fibres which were measured in just under five hours. With different sampling designs, the average measurement time per nerve was reduced to between 17 and 69 minutes, with little consequent loss of reliability or precision of estimated mean fibre size. The most efficient schemes were those taking systematic samples of squares or sectors. A modification of a method relying on complete strips across two diameters of each nerve was the least efficient sampling approach. It had the additional disadvantage of introducing systematic errors which could affect the accuracy of measurements made on nerve trunks with heterogeneous spatial distributions of fibre size and number. This paper completes an investigation into random sampling errors influencing morphometric estimates of fibre size based on uni- or multifascicular nerve trunks.
Evidence for the presence of M. leprae reactive T lymphocytes in patients with lepromatous leprosy.
Evidence for the presence of Mycobacterium leprae reactive T cells in many lepromatous leprosy (LL) patients was obtained using in vitro antigen-induced lymphoproliferative responses. (1) Co-cultures of T enriched cells from LL patients when combined with 2 h adherent cells (AC) from HLA-D compatible tuberculoid leprosy individuals showed significant levels of 3H-thymidine incorporation in the presence of soluble and integral M. leprae antigens. (2) More interestingly, autologous T cell + AC co-cultures also showed significant improvement in antigen-induced lymphoproliferation in nine of 16 lepromatous patients. Insignificant improvement was observed in similar co-cultures of tuberculoid leprosy patients. (3) Addition of exogenous, purified human interleukin-2 (IL-2) to antigen stimulated PBMC from some lepromatous patients showed the best improvement in terms of overall 3H-thymidine incorporation, indicating that lepromatous patients possess T cells which can differentiate to an IL-2 responsive state. Significantly, the level of proliferation varied within the group. A proportion of clinically similar lepromatous patients failed to show improvement by any of the above methods.
Differences in predominant T cell phenotypes and distribution pattern in reactional lesions of tuberculoid and lepromatous leprosy.
The nature and histological pattern of the cutaneous infiltrates of 17 leprosy patients in reversal reactions (Type I) and erythema nodosum leprosum (Type II, ENL) were compared with tissues from 18 non-reactional borderline leprosy (BT, BL) and lepromatous leprosy (LL) patients using monoclonal antibodies and immunofluorescence. Reactional BT lesions showed a mild increase in OKT11+ pan T cells as compared to non-reactional tissues and a significant influx of OKT8+ (suppressor/cytotoxic) cells which were peripherally localized in the lymphocyte mantle surrounding the epithelioid cells. The Leu 3a+ (helper/inducer) cells were scattered amongst the lymphocytes and macrophages. The mean ratio (+/- s.d.) of Leu 3a+/OKT8+ cells was 1.88 +/- 0.64 in Type I BT reactions as compared to 2.95 +/- 0.95 in BT lesions. In contrast, lesions of BL reversal reactions and ENL showed a more marked increase in pan T cells with a preponderance of the helper/inducer subset, Leu 3a+/OKT8+ ratio being 2.26 +/- 0.61 and 0.93 +/- 0.57 in BL reactional and non-reactional lesions, respectively. Interestingly, this increase in the numbers of the T cells reached levels observed in BT lesions. The distribution pattern of OKT8+ cells was similar to Leu 3a+, both being diffusely scattered amongst the bacilli laden macrophages. Ia like antigens were present in all granulomas and were abundant on lymphocytes and macrophages and less conspicuous on epithelioid cells. T6+ Langerhans cells were uniformly increased in all reactional lesions. It would appear that the changes observed in both Type I and Type II reactions are similar in the lepromatous group of patients. They differ significantly from the BT reversal reaction in terms of the dominant T cell subset and the microanatomical distribution of the OKT8+ cells in the lesions.
Effects of fungal metabolites on the germination of sweet fennel (Foeniculum vulgare Mill.) seeds.
The metabolites of some test fungi adversely affected the seed germination. The maximum reduction was caused by a culture filtrate of Penicillium citrinum followed by Fusarium moniliforme and F. equiseti, while the minimum was caused by Mucor sp. A gradual increase in effective metabolite production was observed by all the fungi up to 15 days.
Squamous cell carcinoma complicating chronic discoid lupus erythematosus (CDLE).
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Inter-animal variation and its influence on the overall precision of morphometric estimates based on nested sampling designs.
This paper provides additional experimental evidence that biological variation between individuals is likely to be the major factor influencing the overall precision and efficiency of nested sampling schemes for morphometric analysis of thin sections. Four distinct experimental systems (two based on nervous tissue and two on epithelia) have been investigated. Morphometric estimates were obtained from measurements made on micrographs generated by sampling tissues at several levels. Sources of sampling variation were isolated so that the contributions to overall variance made by inter-animal differences could be evaluated. In each case, biological variation was the cardinal component of total observed variance between animals. Relative contributions ranged from 53% to 78%. Examining more animals would be the most efficient way of reducing the variance of the group mean in these sampling designs.