Biomedical subjects
Publications and source records attributed to Ishwar Singh.
The cis opening of glycal epoxides with arylaluminum reagents provides strict stereocontrol in C-glycosylation. beta-Aryl-C-2-deoxynucleosides are obtained from known glycals by an epoxidation-glycosylation-deoxygenation sequence.
BACKGROUND: Spindle cell carcinoma (SpCC) is a rare microscopic type of cancer of the mouth and oropharynx. Although SpCC is thought to arise from squamous cell carcinoma (SCC), it carries a worse prognosis. AIM: To find out the difference in immunohistochemical expression of cytokeratin, vimentin and smooth-muscle actin, and mutational alterations in the K-ras oncogene between the two tumours, in an attempt to characterise SpCC. METHODS: Immunohistochemical analysis was performed by standard avidin-biotin complex method in 35 cases each of SpCCs and SCCs. DNA extracted from paraffin wax-embedded tumours was used for PCR followed by single-strand conformation polymorphism for mutational analysis of K-ras exon 1 and exon 2. RESULTS: In the SpCC group, cytokeratin positivity was significantly higher in epithelial areas (52.2%) than in spindle cell areas (16.1%), whereas vimentin was more positive in spindle cell areas (18.7%) than epithelial areas (2.7%). Cells intermediate between epithelial and spindle cell areas were consistently positive for both cytokeratin and vimentin. Cytokeratin was found to be significantly more positive in SCC (72.6%) than the squamous component and spindle cell component of SpCC. In this study, no mutation was detected in the K-ras gene of either the SpCC or SCC group. CONCLUSIONS: The spindle cell component of SpCC is intermixed with cells that are morphologically mesenchymal but express dual antigen-positivity characteristic of epithelial (cytokeratin) and mesenchymal (vimentin) cells. These, possibly, are cells in transition suggesting that SpCC may be a sarcomatous metaplasia of SCC.
Pseudoaneurysm of the carotid artery is a potentially life-threatening complication of deep neck space infection. It clinically manifests by pulsatile neck swelling, lower cranial nerve palsy, and Horner's syndrome. There may be sentinel bleed from nose or oral cavity before the massive haemorrhage, from carotid artery rupture. We present a case of pseudoaneurysm of the internal carotid artery (ICA) following parapharyngeal and retropharyngeal space infection in an 8-month-old infant. Emergency carotid artery ligation was performed and the infant recovered well without any neurological sequelae.
We encountered an extremely unusual presentation of proptosis in a 7-yr-old boy due to psammomatoid juvenile ossifying fibroma of frontoethmoidal region. The tumor also led to development of mucocele in the frontal sinus not yet fully developed as on opposite side.
OBJECTIVE: Glutamate plays a critical role in the hypoxic ischaemic neuronal death. Two mechanisms of glutamate- induced neuronal death have been identified. One is rapid cell death that occurs in minutes and the second is delayed cell death that occurs over hours and is initiated principally by the activation of the N-methyl D-Aspactate (NMDA) receptor. Magnesium (Mg) is an NMDA receptor blocker. Systemic administration of Mg after a simulated hypoxic ischaemic insult has been shown to limit neuronal injury in several animal models. However, before embarking on to the use of Mg for neuronal protection in the human neonate it is important to study the safety and side effects of Mg administration. METHODS: Forty terms, appropriate for gestational age babies with severe birth asphyxia (1 min Apgar score < 3 and 5 min Apgar score < 6), were randomly assigned to either the study group or the control group. Infants in both groups were treated as per unit protocol except that babies in the study group received intravenous injection of magnesium sulphate 250 mg/kg within half an hour of birth and subsequently 125 mg/kg at 24 and 48 hours of life. RESULTS: The mean cord blood serum Mg levels were 0.78 (+/- 0.047) mmol/L in the control group and 0.779(+/-0.045) mmol/L in the study group. The serum Mg levels at 3, 6, 12, 24, 48 and 72 hours of life were 1.87(+/-0.6), 1.65(+/-0.059), 1.468 (+/-0.91), 1.881 (+/- 0.053), 1.916 (+/- 0.053) and 1.493 (+/- 0.084) mmol/L respectively in the study group. All these values were significantly higher than those obtained in the control group (p< 0.001). No significant alterations in heart rate, respiratory rate, oxygen saturation and mean arterial pressure were seen, following magnesium infusion with either 250 mg/kg or 125 mg/kg dose. The serum Mg levels in the study group ranged between 1.493 (+/- 0.084) and 1.916(+/-0.053) mmol/L, which are considered to be in the neuroprotective range. CONCLUSION: Injection MgSO4 administered in a dose of 250 mg/kg and 125 mg/kg as an intravenous infusion is safe and the Mg levels obtained are in the range considered to be neuroprotective.
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A case of angiolymphoid hyperplasia with eosinophilia (ALHE) is reported. It is a rare and new disease for an otolaryngologist. The difference between the Kimura's disease and ALHE has been discussed. Though it is rare, ALHE should be kept in differential diagnosis for an auricular swelling.
We previously demonstrated that exposure to febrile-range hyperthermia (FRH) accelerates pathogen clearance and increases survival in murine experimental Klebsiella pneumoniae peritonitis. However, FRH accelerates lethal lung injury in a mouse model of pulmonary oxygen toxicity, suggesting that the lung may be particularly susceptible to injurious effects of FRH. In the present study, we tested the hypothesis that, in contrast with the salutary effect of FRH in Gram-negative peritonitis, FRH would be detrimental in multilobar Gram-negative pneumonia. Using a conscious, temperature-clamped mouse model and intratracheal inoculation with K. pneumoniae Caroli strain, we showed that FRH tended to reduce survival despite reducing the 3 day-postinoculation pulmonary pathogen burden by 400-fold. We showed that antibiotic treatment rescued the euthermic mice, but did not reduce lethality in the FRH mice. Using an intratracheal bacterial endotoxin LPS challenge model, we found that the reduced survival in FRH-treated mice was accompanied by increased pulmonary vascular endothelial injury, enhanced pulmonary accumulation of neutrophils, increased levels of IL-1beta, MIP-2/CXCL213, GM-CSF, and KC/CXCL1 in the bronchoalveolar lavage fluid, and bronchiolar epithelial necrosis. These results suggest that FRH enhances innate host defense against infection, in part, by augmenting polymorphonuclear cell delivery to the site of infection. The ultimate effect of FRH is determined by the balance between accelerated pathogen clearance and collateral tissue injury, which is determined, in part, by the site of infection.
The HG-AAS technique was used to estimate the soil selenium status of the agricultural lands of northern parts of India. The drier lands where lesser rains were received or where less irrigation water was available in Rajasthan and southern parts of the Haryana states had above normal soil selenium levels. These soils were also found to be alkaline. Punjab, Himachal Pradesh and northern parts of the Haryana states had normal levels of selenium in their soils, except with slightly lower selenium levels in a few areas that were affected by floods along the river Yamuna. The results were also confirmed using the ICP-OES technique.
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Deep neck abscesses (DNAs) continue to be commonly encountered in developing countries like India. This study was conducted to determine the changing trends within our population with respect to presentation, aetiology, location and microbiology of DNAs. Fifty-four patients with DNAs who were managed at the Department of ORL and H&N Surgery in our hospital between May 2002 and December 2002 formed the basis of the study. We observed that the high incidence of DNAs could be attributed to lack of awareness, illiteracy and poverty among patients, along with the poor primary health infrastructure. We also recommend early surgical intervention in these cases to decrease the prevalence of complications.
Low voltage energy source is not free from danger. An exceptionally rare and peculiar mode of facial blast injury is reported. The blast took place silently in the mouth of a 15-year-old boy, due to short-circuiting of wires connected to a12-volt car battery while peeling off insulation with the intent of running a musical instrument. Airway compromise due to soft tissue injury produced further problem during tracheostomy. Emergent airway management is discussed. Post-healing sequel resulted in loss of voice and prevented normal oral feeding. The case report emphasizes need for education to public in handling low voltage energy source.
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The quantitative structure-activity relationship (QSAR) studies conducted by us earlier revealed the cardinal role of the pyran ring carbonyl group in the acetoxy polyphenolic compounds for the acetoxy polyphenol:protein transacetylase (TAase) activity. Hence, an attempt was made to examine whether such substrate analogues of benzopyran acetates which lack in the pyran ring carbonyl group, such as 7-acetoxy-2,3-dihydro-2,2-dimethylbenzopyran (BPA), cetachin pentaacetate (CPA) and hematoxylin pentaacetate (HPA) could inhibit the 7,8-diacetoxy-4-methylcoumarin (DAMC):protein (glutathione-S-transferase) transacetylase activity. These compounds were indeed found to remarkably inhibit the TAase activity in a concentration dependent manner and exerted their inhibitory action very rapidly. Further BPA, CPA and HPA were found to abolish the TAase mediated activation of NADPH cytochrome C reductase as well as the inhibition of liver microsome catalyzed aflatoxin B(1) (AFB(1))-DNA binding by DAMC very effectively. These results strongly suggest that the acetoxybenzopyrans merit as potent inhibitors of TAase.
Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.
Eleven (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins have been synthesised in two steps starting from the coupling of cinnamic acid/substituted cinnamic acid with appropriate phenols, followed by acetylation in 50-83% overall yields. All hydroxy- and acetoxycoumarins were unambiguously identified on the basis of their spectral data. Candida antarctica lipase-catalysed deacetylation of these racemic acetoxydihydrocoumarins in dioxane occurred with moderate enantioselectivity. This is one of the rare examples of resolution using phenolic ester moiety as a remote handle for chiral recognition by a lipase.
The carotid erosion occurs most commonly in patients receiving radiotherapy for head and neck cancer and is associated with high mortality. We report a case of carotid blow out in a 4-year-old child who presented with massive parapharyngeal space abscess. The common carotid artery (CCA) was ligated and child recovered without any neurological sequel.