Search PubMed⌕ Search

Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 361 records · Page 20Linked to original sources

Cyanoacrylate tissue adhesive augmented tenoplasty: a new surgical procedure for bilateral severe chemical eye burns.

PURPOSE: To report on cyanoacrylate tissue adhesive augmented tenoplasty, a new surgical procedure for bilateral severe chemical eye injuries. METHODS: A 26-year-old man presented with bilateral severe (grade IV) chemical burns involving the eye, periorbital tissues, face, and neck. Despite adequate medical therapy, corneal, limbal, and scleral ulceration progressed in both eyes. Secondary Pseudomonas keratitis necessitated therapeutic penetrating keratoplasty in the right eye. Tenoplasty and glued-on rigid gas permeable contact lens were unsuccessful to arrest progression of corneolimboscleral ulceration in the left eye. We applied n-butyl cyanoacrylate tissue adhesive directly on the ulcerating corneal, limbal, and scleral surface to augment tenoplasty. RESULTS: The left ocular surface healed with resultant massive fibrous tissue proliferation and symblepharon on the nasal side. Ocular surface rehabilitation resulted in a vascularized leukomatous corneal opacity with upper temporal clear cornea. The patient achieved visual acuity of 6/36 in the left eye. CONCLUSION: We suggest that cyanoacrylate tissue adhesive-augmented tenoplasty can be undertaken to preserve ocular integrity and retain visual potential in a severe chemical eye injury.

Adult↗

Role of angiotensin in cardioprotective effect of ischemic preconditioning.

This study was designed to investigate the role of angiotensin (Ang II) in the cardioprotective effect of ischemic preconditioning. Isolated perfused rat heart was subjected to global ischemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically by using triphenyl tetrazolium chloride (TTC) staining. Four episodes of ischemic/Ang II preconditioning markedly reduced LDH and CK release in the coronary effluent and decreased myocardial infarct size. The cardioprotective effect of Ang II preconditioning was abolished by CV 11974, AT1-receptor antagonist, whereas no such effect was noted with CV 11974 in ischemic preconditioning. PD 123319, AT2-receptor antagonist, produced no marked effect on Ang II preconditioning and ischemic preconditioning induced reduction in myocardial injury. On the basis of these results, it may be concluded that activation of AT1 receptors may be involved in angiotensin-induced pharmacologic preconditioning. But it may not be involved in the cardioprotective effect of ischemic preconditioning in isolated rat heart.

Angiotensin II↗

Cortical auditory evoked potential correlates of categorical perception of voice-onset time.

The goal of this study was to examine the neural encoding of voice-onset time distinctions that indicate the phonetic categories /da/ and /ta/ for human listeners. Cortical Auditory Evoked Potentials (CAEP) were measured in conjunction with behavioral perception of a /da/-/ta/ continuum. Sixteen subjects participated in identification and discrimination experiments. A sharp category boundary was revealed between /da/ and /ta/ around the same location for all listeners. Subjects' discrimination of a VOT change of equal magnitude was significantly more accurate across the /da/-/ta/ categories than within the /ta/ category. Neurophysiologic correlates of VOT encoding were investigated using the N1 CAEP which reflects sensory encoding of stimulus features and the MMN CAEP which reflects sensory discrimination. The MMN elicited by the across-category pair was larger and more robust than the MMN which occurred in response to the within-category pair. Distinct changes in N1 morphology were related to VOT encoding. For stimuli that were behaviorally identified as /da/, a single negativity (N1) was apparent; however, for stimuli identified as /ta/, two distinct negativities (N1 and N1') were apparent. Thus the enhanced MMN responses and the morphological discontinuity in N1 morphology observed in the region of the /da/-/ta/ phonetic boundary appear to provide neurophysiologic correlates of categorical perception for VOT.

Adult↗

Role of the amino-terminal region of Porphyromonas gingivalis fimbriae in adherence to epithelial cells.

Porphyromonas gingivalis fimbriae elicit many responses in eukaryotic cells, including mitogenicity, cytokine production, epithelial cell invasion, and cellular immune response. Specific domains of the major fimbrial protein (FimA) have been shown to be important in triggering some of these functions. The goal of the present study was to identify the domain(s) of P. gingivalis FimA responsible for specific interaction with human mucosal epithelial cells. Fimbriated P. gingivalis strains have been shown to bind to buccal epithelial cells, whereas nonfimbriated strains bind at low levels or not at all. This and other studies provide evidence that FimA mediates the adherence of P. gingivalis to oral epithelial cells. To determine the specific region(s) of P. gingivalis FimA involved in epithelial cell binding, specific antipeptide antibodies were used to inhibit the binding of iodinated purified fimbriae as well as the binding of P. gingivalis cells to epithelial cells. Antibodies directed against peptides 49 to 68 (VVMANTAGAMELVGKTLAEVK) and 69 to 90 (ALTTELTAENQEAAGLIMTAEP) were found to highly inhibit both the binding of fimbriae and the binding of P. gingivalis cells to epithelial cells. The antibody against FimA peptides 69 to 90 also reacted with P. gingivalis fimbriae in immunogold labeling and immunoblot analysis, thereby indicating that this peptide domain is exposed on the surface of fimbriae. Our results suggest that the amino-terminal domain corresponding to amino acid residues 49 to 90 of the fimbrillin protein is a major epithelial cell binding domain of P. gingivalis fimbriae.

Amino Acid Sequence↗

The NeuroD1/BETA2 sequences essential for insulin gene transcription colocalize with those necessary for neurogenesis and p300/CREB binding protein binding.

NeuroD1/BETA2 is a key regulator of pancreatic islet morphogenesis and insulin hormone gene transcription in islet beta cells. This factor also appears to be involved in neurogenic differentiation, because NeuroD1/BETA2 is able to induce premature differentiation of neuronal precursors and convert ectoderm into fully differentiated neurons upon ectopic expression in Xenopus embryos. We have identified amino acid sequences in mammalian and Xenopus NeuroD1/BETA2 that are necessary for insulin gene expression and ectopic neurogenesis. Our results indicate that evolutionarily conserved sequences spanning the basic helix-loop-helix (amino acids [aa] 100 to 155) and C-terminal (aa 156 to 355) regions are important for both of these processes. The transactivation domains (AD1, aa 189 to 299; AD2, aa 300 to 355) were within the carboxy-terminal region, as analyzed by using GAL4:NeuroD1/BETA2 chimeras. Selective activation of mammalian insulin gene enhancer-driven expression and ectopic neurogenesis in Xenopus embryos was regulated by two independent and separable domains of NeuroD1/BETA2, located between aa 156 to 251 and aa 252 to 355. GAL4:NeuroD1/BETA2 constructs spanning these sequences demonstrated that only aa 252 to 355 contained activation domain function, although both aa 156 to 251 and 300 to 355 were found to interact with the p300/CREB binding protein (CBP) coactivator. These results implicate p300/CBP in NeuroD1/BETA2 function and further suggest that comparable mechanisms are utilized to direct target gene transcription during differentiation and in adult islet beta cells.

Animals↗

Frequent amplification of C-erbB2 (HER-2/Neu) oncogene in cervical carcinoma as detected by non-fluorescence in situ hybridization technique on paraffin sections.

Sixty primary untreated squamous cell carcinomas were studied for C-erbB2 gene amplification by non-fluorescence in situ hybridization technique. Amplified tumour cells showed intranuclear dark brown, often paired signals under light microscopy. Twenty-two out of 60 tumours (36.6%) showed signs of amplification of different degree (+ to +). Considerable heterogeneity of C-erbB2 amplification per cell was seen within each amplified tumour. The proportion of amplified cells ranged between 10 and 90% in these tumours. The arrangement of C-erbB2 in clusters in most amplified tumours suggests that C-erbB2 amplification occurs intrachromosomally. No significant difference in the frequency of amplification was observed according to clinical stage or the histological patterns of the tumours. The results of the present study showed frequent amplification of C-erbB2 in cervical carcinoma on paraffin sections. This technique was found to be more sensitive than the Southern blot technique which could detect amplification in 14% of the tumours of the same cohort.

Carcinoma, Squamous Cell↗

Pharmacokinetics and pharmacodynamics of avitriptan during intravenous administration in healthy subjects.

Avitriptan, a selective 5-HT1-like receptor agonist, is an effective compound for the treatment of migraine headaches with a prolonged duration of response. A double-blind, placebo-controlled, parallel-group, ascending-dose study in 24 healthy subjects was designed to assess the safety, tolerance, pharmacokinetics, and pharmacodynamics of avitriptan. This antimigraine drug was administered as two consecutive constant-rate IV infusions at three dose levels (12.7, 25.3, and 38.0 mg), which were targeted to produce plasma concentrations in and above the therapeutic range. The best fitting of the plasma concentration-time data was obtained by using a triexponential function yielding a terminal t1/2 of 8 hours. The areas under the plasma concentration versus time curves were proportional to dose, indicating linear pharmacokinetics. Moreover, the clearance and steady-state volume of distribution values were independent of the dose. The change in pulse rate and supine systolic and diastolic blood pressure was determined as pharmacodynamic effects of avitriptan. A "threshold log-linear" model, which accounts for the linear increase in pharmacodynamic effect with the log of plasma concentrations when the latter was higher than a certain threshold value, adequately described the pharmacodynamic data. The threshold plasma drug concentrations for the pulse rate and the diastolic and systolic blood pressure were 14, 74, and 161 ng/ml, respectively. Overall, avitriptan has consistent, linear pharmacokinetics and increases systolic and diastolic blood pressure in a predictable manner at a higher plasma concentration. However, this drug does not produce a significant change in pulse rate at the dose levels (12.7-38 mg) evaluated in this study.

Adult↗

Pressure sore prevention in hospital patients: a clinical audit.

Pressure sores cause significant mortality and morbidity as well as being a financial burden on health-care services. Reduction of pressure sore incidence is a Department of Health priority. Pressure sores are accepted as largely preventable complications of illness and disability and the means to achieve prevention are available. The aim of this clinical audit was to identify potential contributing factors to pressure sore acquisition in an acute hospital setting. The results suggest that substantial changes in the approach to clinical management may be needed.

Adult↗

Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis.

BACKGROUND: Neutrophils from patients with localized juvenile periodontitis (LJP) exhibit decreased binding and responsiveness to various chemotactic agents, including N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP). This altered reaction of neutrophils is thought to account in part for the increased susceptibility of LJP patients to infections by periodontal organisms. Receptors for FMLP are involved in the activation and the subsequent response to certain chemotactic stimuli. METHODS: In order to determine if this decreased response is due to a genetic variation in the receptor, we directly compared DNA encoding the FMLP receptor from controls matched for gender and race and LJP patients by single-strand conformation polymorphism analysis (SSCP). RESULTS: Using this technique, we observed a characteristic SSCP pattern in 29 out of 30 patient samples in the FMLP receptor DNA. This pattern differed from those obtained from the 20 control subjects as well as 31 patients with adult periodontitis. DNA sequencing of 30 patients indicated single nucleotide polymorphisms (SNPs) in the FMLP receptor DNA from the LJP patients when compared to 20 controls (P = 0.0005). Two single nucleotide base alterations were consistently seen: either a thymine to cytosine substitution at base 329 in 17 LJP patients or a cytosine to guanine substitution at base 378 in 5 LJP patients. A combination of both alterations were seen in 7 LJP patients. Both alterations resulted in amino acid changes in the second intracellular loop of the receptor, specifically phenylalanine to serine at residue 110 and cysteine to tryptophan at residue 126. This region of the FMLP receptor has recently been shown to play a role in ligand binding and G-protein activation. CONCLUSIONS: This study suggests that a molecular alteration in the second intracellular loop of the FMLP receptor molecules in LP patients may play a role in the decreased chemotactic activity reported for some LJP patients.

Adult↗

The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration.

Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. After 90% pancreatectomy (Px), the adult pancreas regenerates in a process recapitulating embryonic development, starting with a burst of proliferation in the epithelium of the common pancreatic duct. In this model, IDX-1 mRNA was detected by semiquantitative reverse transcription-polymerase chain reaction in total RNA from isolated common pancreatic ducts at levels 10% of those of isolated islets. The IDX-1 mRNA levels were not significantly different for common pancreatic ducts of Px, sham Px, and unoperated rats and did not change with time after surgery. By immunoblot analysis, IDX-1 protein was only faintly detected in these ducts 1 and 7 days after Px or sham Px but was easily detected at 2 and 3 days after Px. Similarly, IDX-1 immunostaining was barely detectable in sham or unoperated ducts but was strong in ducts at 2-3 days after Px. The increase of IDX-1 immunostaining followed that of BrdU incorporation (proliferation). These results indicate a posttranscriptional regulation of the IDX-1 expression in ducts. In addition, islets isolated 3-7 d after Px showed higher IDX-1 protein expression than control islets. Thus, in pancreatic regeneration IDX-1 is upregulated in newly divided ductal cells as well as in islets. The timing of enhanced expression of IDX-1 implies that IDX-1 is not important in the initiation of regeneration but may be involved in the differentiation of ductal cells to beta-cells.

Animals↗

Presence of M. leprae in tissues in slit skin smear negative multibacillary (MB) patients after WHO-MBR.

This study looked for M. leprae in the lymph node, nerve and skin of multibacillary (MB) leprosy patients who become slit skin smear negative after the completion of WHO-MBR. Twenty-five WHO-MBR-treated multibacillary leprosy patients were studied; borderline lepromatous (BL) leprosy (n = 11) and lepromatous (LL) leprosy (n = 14)). Fifteen patients had reaction (erythema nodosum leprosum 11, upgrading reaction 4) either at presentation or during therapy. All patients attained slit skin smear negativity after WHO-MBR (range 24-39 months. Sixteen (64%) patients with multibacillary leprosy showed fragmented bacilli in skin and nerve biopsy or lymph node aspirates after WHO-MBR. Lymph node aspirates alone revealed M. leprae in seven patients, followed by nerve in two and skin in one patient. Four cases showed M. leprae at all sites followed by nerve and skin or lymph node in one case each. A pretreatment bacteriological index (BI) of 4+ or more was significantly associated with the presence of M. leprae at the end of treatment. Also, significantly more lymph node aspirates contained M. leprae in comparison with nerve or skin biopsies. All seven cases in whom treatment was extended beyond 24 months showed M. leprae in tissues even after attaining slit smear negativity. In conclusion, M. leprae persist in tissues after 2 years of WHO-MBR and patients with an initial BI of 4+ or more need to be closely followed up after stopping MDT.

Adolescent↗

Contrasts between the cardiovascular concomitants of tests of planning and attention.

Physiological response stereotypy is a well-established psychophysiological construct. Unfortunately, specifying parameters of tasks that evoke differing physiological responses has proved difficult. We have recorded cardiovascular activity while subjects carried out executive and attentional tasks that differed not only psychologically but also in their sensitivity to brain pathology and to pharmacological manipulations. Finapres recordings were made of 30 healthy, normal subjects (mean age 24 years) performing two tasks involving differing aspects of sustained attention and two tasks involving differing aspects of spatial working memory and planning. Measures of heart rate and blood pressure, heart rate and blood pressure variability, and their spectral derivatives revealed differing patterns of cardiovascular adjustment between the "attentional" and "planning" tasks. Each test raised blood pressure, but changes in blood pressure and heart rate variability were confined to the attentional tasks. These findings suggest distinct brain mechanisms subserving different forms of arousal.

Adult↗

Influence of arrhythmias on gated SPECT myocardial perfusion and function quantification.

UNLABELLED: Despite the importance of R-wave gating myocardial perfusion tomography for ventricular function assessment, neither prevalence of gating errors nor their influence on quantified cardiac parameters has been studied. METHODS: Arrhythmia-induced anomalies in curves of counts versus projection angle for each R-wave segment were detected visually and algorithmically. Arrhythmia prevalence was tabulated for 379 patients (group 1) with prospective coronary artery disease (mean age 63+/-13 y, 47% male). Myocardial counts were analyzed from all reconstructed cinematic midventricular slices to assess arrhythmia effects on percentage of systolic count increase, generally assumed to equal percentage of wall thickening. In a separate retrospective analysis of 41 patients (group 2), with coronary artery disease (mean age 64+/-12 y, 68% male) having no significant arrhythmias, 36 of whom also underwent equilibrium radionuclide angiography, original projection data were altered to simulate arrhythmia-induced aberrant count patterns to evaluate effects on ventricular function and perfusion measurements. RESULTS: Group 1 patients consisted of 26% without gating errors, 32% with count losses only in the last R-wave interval due to inconsistent transient increase of heart rate, 24% with count decreases in several late intervals due to consistently variable rates, 8% with early interval count increases paired with late interval count decreases due to ectopic beats and 9% with erratic count changes due to atrial fibrillation. Observed count patterns were strongly associated (P < 10(-3)) with arrhythmias detected by electrocardiogram monitoring. In group 2 simulations, ventricular volumes changed by only 2%+/-9% and ejection fraction (EF) by only 1%+/-4% from control values and correlated linearly (r> or = 0.96) with control values for all simulated arrhythmias. SPECT and equilibrium radionuclide angiography EFs correlated similarly (r = 0.85-0.89) for control and all simulations. Percentage changes from control in perfusion defect extent and severity were larger than processing reproducibility limits, the largest change being for atrial fibrillation. Control wall thickening was 38%+/-17%, significantly lower (P < 10(-6)) than for simulated arrhythmias, reflecting similar observations for group 1 patients. CONCLUSION: Even though ventricular volumes and EFs were affected minimally by arrhythmias, both perfusion analysis and wall thickening were compromised. Consequently, quality assurance of gating may be critically important for obtaining accurate quantified parameters.

Aged↗

An evaluation of myelography with non-ionic water soluble contrast medium-iohexol.

Iohexol myelography was performed in 25 cases of suspected spinal cord compression. Out of these, 24 cases gave optimally informative myelogram, while one case showed quasi-informative myelogram. Myelographic efficacy regarding the level of lesion was correct in all cases. On final evaluation 15 cases were diagnosed as extradural lesions, 9 cases as intradural extramedullary type and one case as diastematomyelia. Only single case which was diagnosed as intramedullary lesion on myelography was, in fact, an extradural lesion. There were only minor side-effects in the form of headache and paraesthesia in the lower limb. It was concluded that iohexol is a safe contrast medium with high efficacy and minimal side-effects for the total examination of spinal canal.

Contrast Media↗

Pseudomonas aeruginosa (GRC1) as a strong antagonist of Macrophomina phaseolina and Fusarium oxysporum.

A plant growth promotory bacterial strain, isolated from the potato rhizosphere, was characterized as Pseudomonas aeruginosa (GRC1). The isolate produced an hydroxamate type of siderophore after 48 h of incubation on tryptic soy medium under iron deficient conditions. The in vitro antifungal activity of P. aeruginosa was tested against two soil-borne plant pathogens, Macrophomina phaseolina and Fusarium oxysporum. The antagonistic behaviour of the isolate was tested by dual culture technique. The growth inhibition of M. phaseolina and F. oxysporum was 74.1% and 70.5%, respectively, after 5 days of incubation. The production of hydrocyanic acid and indole acetic acid was also recorded under normal growth conditions.

Fusarium↗