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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 37 records · Page 2Linked to original sources
PubMed2006

Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity.

BACKGROUND: The surgical treatment of obesity in the high-risk, high-body-mass-index (BMI) (>60) patient remains a challenge. Major morbidity and mortality in these patients can approach 38% and 6%, respectively. In an effort to achieve more favorable outcomes, we have employed a two-stage approach to such high-risk patients. This study evaluates our initial outcomes with this technique. METHODS: In this study, patients underwent laparoscopic sleeve gastrectomy (LSG) as a first stage during the period January 2002-February 2004. After achieving significant weight loss and reduction in co-morbidities, these patients then proceeded with the second stage, laparoscopic Roux-en-Y gastric bypass (LRYGBP). RESULTS: During this time, 126 patients underwent LSG (53% female). The mean age was 49.5 +/- 0.9 years, and the mean BMI was 65.3 +/- 0.8 (range 45-91). Operative risk assessment determined that 42% were American Society of Anesthesiologists physical status score (ASA) III and 52% were ASA IV. The mean number of co-morbid conditions per patient was 9.3 +/- 0.3 with a median of 10 (range 3-17). There was one distant mortality and the incidence of major complications was 13%. Mean excess weight after LSG at 1 year was 46%. Thirty-six patients with a mean BMI of 49.1 +/- 1.3 (excess weight loss, EWL, 38%) had the second-stage LRYGBP. The mean number of co-morbidities in this group was 6.4 +/- 0.1 (reduced from 9). The ASA class of the majority of patients had been downstaged at the time of LRYGB. The mean time interval between the first and second stages was 12.6 +/- 0.8 months. The mean and median hospital stays were 3 +/- 1.7 and 2.5 (range 2-7) days, respectively. There were no deaths, and the incidence of major complications was 8%. CONCLUSION: The staging concept of LSG followed by LRYGBP is a safe and effective surgical approach for high-risk patients seeking bariatric surgery.

Body Mass Index↗
PubMed2006

CCL19 reduces tumour burden in a model of advanced lung cancer.

Epstein-Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To mimic therapy in late-stage disease, 3-month-old transgenic mice were treated with recombinant CCL19 (0.5 microg dose(-1)) by intranodal (axillary lymph node region) injection three times per week for 4 weeks. CCL19 treatment led to a marked reduction in tumour burden with extensive mononuclear infiltration of the tumours compared to diluent treated controls. Flow cytometric analyses showed significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-beta. Our findings show that CCL19 may serve as a potential immune stimulator and provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2006

Critical behavior at the isotropic-to-nematic phase transition in a bent-core liquid crystal.

Magnetic birefringence and dynamic light scattering measurements of orientational order parameter fluctuations at the isotropic-nematic phase transition of a bent-core liquid crystal reveal a pretransitional temperature dependence consistent with the standard Landau-deGennes mean field theory. However, as follows: the transition in the bent-core compound is more weakly first order (TNI-T* approximately 0.4 degrees C), the leading Landau coefficient is approximately 30 times lower, the viscosity associated with nematic order fluctuations is approximately 10 times higher, and the density change is approximately 10 times lower, than typically observed in calamitic (rod-shaped) liquid crystals. One consistent explanation for these anomalies is an optically isotropic phase composed of microscopic complexes or "clusters" of bent-core molecules.

Journal Article↗
PubMed2006

Euler buckling-induced folding and rotation of red blood cells in an optical trap.

We investigate the physics of an optically driven micromotor of biological origin. When a single, live red blood cell (RBC) is placed in an optical trap, the normal biconcave disc shape of the cell is observed to fold into a rod-like shape. If the trapping laser beam is circularly polarized, the folded RBC rotates. A model based on geometric considerations, using the concept of buckling instabilities, captures the folding phenomenon; the rotation of the cell is rationalized using the Poincaré sphere. Our model predicts that (i) at a critical power of the trapping laser beam the RBC shape undergoes large fluctuations, and (ii) the torque that is generated is proportional to the power of the laser beam. These predictions are verified experimentally. We suggest a possible mechanism for the emergence of birefringent properties in the RBC in the folded state.

Animals↗
PubMed2006

Dynamic, electronically switchable surfaces for membrane protein microarrays.

Microarray technology is a powerful tool that provides a high throughput of bioanalytical information within a single experiment. These miniaturized and parallelized binding assays are highly sensitive and have found widespread popularity especially during the genomic era. However, as drug diagnostics studies are often targeted at membrane proteins, the current arraying technologies are ill-equipped to handle the fragile nature of the protein molecules. In addition, to understand the complex structure and functions of proteins, different strategies to immobilize the probe molecules selectively onto a platform for protein microarray are required. We propose a novel approach to create a (membrane) protein microarray by using an indium tin oxide (ITO) microelectrode array with an electronic multiplexing capability. A polycationic, protein- and vesicle-resistant copolymer, poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG), is exposed to and adsorbed uniformly onto the microelectrode array, as a passivating adlayer. An electronic stimulation is then applied onto the individual ITO microelectrodes resulting in the localized release of the polymer thus revealing a bare ITO surface. Different polymer and biological moieties are specifically immobilized onto the activated ITO microelectrodes while the other regions remain protein-resistant as they are unaffected by the induced electrical potential. The desorption process of the PLL-g-PEG is observed to be highly selective, rapid, and reversible without compromising on the integrity and performance of the conductive ITO microelectrodes. As such, we have successfully created a stable and heterogeneous microarray of biomolecules by using selective electronic addressing on ITO microelectrodes. Both pharmaceutical diagnostics and biomedical technology are expected to benefit directly from this unique method.

Electrodes↗
PubMed2006

Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation.

While external ionizing radiation has been used for treating non-small cell lung cancer (NSCLC), improved efficacy of this modality would be an important advance. Ectopic expression of the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in NSCLC cells facilitated concentration of iodide in NSCLC cells, which markedly induced apoptosis in vitro and in vivo. Pre-incubation of the NIS/TPO-modified NSCLC cells in iodide followed by ionizing radiation generates bystander tumoricidal effects and potently enhances tumor cell killing. This iodide-induced bystander effect is associated with enhanced gap junction intercellular communication (GJIC) activity and increased connexin-43 (Cx43) expression. Thus, iodide may serve as an enhancer to markedly improve the efficacy of radiation therapy in combined therapeutic modalities.

Apoptosis↗
PubMed2006

The 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins. Workshop review: assays and detection.

The development of diagnostic tests for the botulinum neurotoxins is complicated by their extremely high potencies and the considerable diversity observed within the neurotoxin family. Current approaches for the detection of the toxins and the organism include amplified immunoassays and PCR techniques. Assays which exploit the biological activities within the botulinum toxins are also in development. These are based on both antibody and mass spectrometric techniques which measure the endopeptidase activities of the neurotoxins. This overview of the Assays and Detection Workshop of the 5th International Conference of on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins discusses recent progress in the development of these assay systems and the issues that need to be overcome prior to their implementation.

Animals↗
PubMed2006

Involving users in the design of a system for sharing lessons from adverse incidents in anaesthesia.

In this qualitative study using observation and interviews, 10 anaesthetists from five Departments of Anaesthesia in the North-West region of England were enlisted to participate in the design of an online system to allow the sharing of critical incidents. Respondents perceived that existing schemes had differing and sometimes conflicting aims. Reporting was used for reasons other than simply logging incidents in the interests of promoting patient safety. No existing scheme allowed the lessons learned from incidents to be shared between members of the professional group from which they arose. Using participants' suggestions, we designed a simple, secure, anonymous system favouring free-text description, intended to enable the on-line sharing and discussion of selected incidents. Seven incidents were posted during the 6-month pilot period. The practitioners in our study valued the opportunity to share and discuss educational incidents 'horizontally' within their community of practice. We suggest that large-scale reporting systems either incorporate such a function or allow other systems that permit such sharing to co-exist.

Anesthesia↗
PubMed2006

Total serum immunoglobulin E levels in a case-control study in asthmatic/allergic patients, their family members, and healthy subjects from India.

BACKGROUND: Total immunoglobulin E (IgE) is an important indicator of allergic disorders. However, its role in allergic patients in India has not been evaluated in relation to atopic status for a reference range as compared with healthy subjects. OBJECTIVE: The aim of the study was to establish serum IgE levels in a diseased group, study its relationship with atopy, and to compare the same with healthy volunteers in Indian subjects. METHODS: Four hundred and eighty asthmatics/allergic patients, 100 first-degree relatives of asthmatics, and 120 unrelated normal healthy volunteers from Delhi region were recruited for the study. Atopy was established by family history and skin test to common indigenous allergens and, total and specific IgE measurements. Statistical analysis was performed with the help of SPSS software program. RESULTS: The mean IgE levels were the highest in asthmatic patients and the lowest in the control healthy group. IgE was significantly high in the male than the female healthy volunteers (P<0.05), but not in the diseased group. Prosopis juliflora among pollen allergens and Alternaria alternata among fungal allergens were important sensitizers in allergic patients with 34.7% and 17.7% skin positivity, respectively. Atopic status and asthma were found to be the best predictor of IgE, which was highly significant (r(2)=0.239, P<0.00001). However, at 95% confidence interval as many as 50% of asthmatic patients had their IgE values in the normal range. CONCLUSION: The IgE levels in Indian allergic patients is significantly related to atopy, but due to wide overlap of IgE levels in patients and healthy subjects, its diagnostic significance in Indian population seems to be limited.

Adult↗
PubMed2006

Correlates of Type 2 diabetes mellitus in children, adolescents and young adults in north India: a multisite collaborative case-control study.

AIMS: In this study we describe the clinical, anthropometric and biochemical characteristics of patients with early onset Type 2 diabetes mellitus (T2DM) (< 30 years of age) and compare them with healthy, non-diabetic individuals. METHODS: In this multisite collaborative study, 51 patients with T2DM (40 male, 11 female) and 69 non-diabetic individuals of similar age and gender distribution (controls) as the cases (46 male and 23 female) were investigated. The following parameters were measured; anthropometry [body mass index (BMI), waist circumference, waist-hip ratio (WHR) and skin-fold thickness at four sites], percentage body fat (%BF) and lipid profile. RESULTS: The mean (SD) age of diagnosis of T2DM was 21.4 (6.1) years. A significantly higher number of cases had a history of T2DM in first-degree relatives as compared with controls (82.3 vs. 23.2%, P < 0.001). The mean values and the prevalence of abnormal values of measures of generalized obesity (BMI and %BF) and abdominal obesity (waist circumference and WHR) were significantly higher in cases as compared with controls. Hypertriglyceridaemia [OR (95% CI): 4.6 (1.1-20.0)], high WHR [7.9 (2.5-24.4)] and family history of T2DM [7.3 (2.3-23.0)] were independently associated with T2DM. Age and gender adjusted odds ratios of T2DM were 23.3 (5.2-103.6), 37.7 (9.0-158.5) and 86.4 (17.0-438.5), respectively, with the following set of risk factors; hypertriglyceridaemia and high WHR, hypertriglyceridaemia and family history of T2DM, and high WHR and family history of T2DM. Finally, the presence of all three risk factors increased the odds of T2DM to 112.1 (10.8-1164.7). CONCLUSIONS: Early identification of the simple clinical, anthropometric and biochemical parameters which are strongly associated with early onset T2DM in young Asian Indians may be useful for primary prevention.

Adolescent↗
PubMed2006

Studies on low molecular mass phytocystatins purified from Phaseolus mungo (Urd).

In the present study two phytocystatins (thiol protease inhibitors) have been isolated and purified to homogeneity from Phaseolus mungo by a simple two-step procedure using ammonium sulfate fractionation and gel filtration on Sephacryl-100 HR. The latter procedure yielded two peaks of the inhibitors (PMC I and PMC II). The pH optimum of both phytocystatins was pH 7.0; the temperature optima for PMC I and PMC II were 65 and 70 degrees C, respectively. The molecular masses of the purified phytocystatins were 19 and 17 kD, respectively, as determined by SDS-PAGE and mass spectrometry. Antibodies raised against the purified cystatins gave a single precipitin line in Ouchterlony double immunodiffusion. Kinetics of inhibition showed that PMC I and PMC II strongly inhibit papain and ficin but not trypsin and chymotrypsin. Binding stoichiometry of PMC I and PMC II with both papain and ficin was 1 : 2. The effect of urea on PMC I and PMC II was analyzed by fluorescence and circular dichroism spectroscopy. The CD results suggest an unfolding of PMC I and PMC II accompanying a decrease in the amount of extended (hydrated) coil structure and an increase in sheet-like structure. FTIR results show that PMC I is structurally similar to PMC II. Hydrophobic interactions are observed over a long time scale (5-150 min). Furthermore, fluorescence spectroscopy results were found to be in accordance with CD results, by showing quenching of fluorescence intensity of PMC I and PMC II, although to different extents, due to perturbations of the environment of aromatic residues in the protein. Both cystatins showed strong inhibitory activity against Escherichia coli and Staphylococcus aureus.

Circular Dichroism↗
PubMed2006

Effect of polyols and salts on the acid-induced state of human placental cystatin.

Polyols (glycerol and sorbitol) and salts (magnesium sulfate, sodium sulfate, and magnesium chloride) have been used to study the refolding of the acid-induced state of human placental cystatin (HPC), which is a low molecular weight (12,500 daltons) thiol proteinase inhibitor, in terms of CD spectroscopy, binding of hydrophobic dye 1-anilinonaphthalene-8-sulfonic acid (ANS), and intrinsic fluorescence measurements. The helical content of acid-denatured HPC increased with increase in glycerol concentration (0-80%). At 80% glycerol concentration, the secondary structural features observed in the far UV-CD region are similar to those of the native state (pH 6.0). The intrinsic fluorescence and near UV-CD studies showed that this 80% glycerol-induced state has a significant amount of tertiary structure with decreased ANS binding compared to the acid-denatured state. It was found that glycerol is more effective in stabilizing the acid-denatured state of HPC as compared to sorbitol. Among salts the stability effect was more for MgCl(2) (used up to concentration of 3 M) compared to MgSO(4) and Na(2)SO(4) (used up to the concentration of 1.5 M due to restricted solubility of HPC at higher sulfate salt concentrations) as determined by CD studies and fluorescence measurements, which showed secondary and tertiary structural resemblance of this MgCl(2)-induced state close to native state and showed overall spectral features in between the native state and the acid-denatured state. This MgCl(2) (3 M)-induced state showed decreased ANS fluorescence as compared to the acid-denatured state but more than that of the native state. The results taken together suggest that the acid-denatured state of HPC in the presence of 80% glycerol or 3 M MgCl(2) has a conformation in between that of the native state (pH 6.0) and the acid-induced state at pH 2.0.

Circular Dichroism↗
PubMed2006

Physiological left ventricular hypertrophy or hypertrophic cardiomyopathy in an elite adolescent athlete: role of detraining in resolving the clinical dilemma.

The differentiation of physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) can prove challenging for even the most experienced cardiologists. The case is presented of a 17 year old elite swimmer who had electrocardiographic and echocardiographic features that were highly suggestive of HCM. However, indices of diastolic function were normal and cardiopulmonary exercise testing revealed high peak oxygen consumption in keeping with physiological LVH. To resolve the diagnostic dilemma, the patient underwent detraining for eight weeks, after which, there was complete resolution of the changes seen on electrocardiogram and echocardiogram, indicating physiological LVH rather than HCM.

Adolescent↗
PubMed2006

Chronic kidney disease management--what can we learn from South African and Australian efforts?

BACKGROUND: The prevalence of chronic kidney disease is on the rise. Our objective is to describe two programs to improve the awareness and management of hypertension, renal disease, and diabetes in remote Australian Aboriginal and urban and periurban South African communities. We focus on how the Australian Aboriginal and South African Chronic Disease Outreach Programs have worked together. METHODS: The establishment of prevention programs in developing countries is a challenge. The paper evaluates these challenges, including accessing international aid. The programs advocate that regular integrated checks for chronic disease and their risk factors are essential elements of regular adult health care. Programs should be run by primary health workers, following algorithms for testing and treatment, and a backup provided by nurse coordinators. Constant evaluation is essential to develop community health profiles and adapt program structure. RESULTS: Both programs are discussed, including how they are organized to deliver preventative and treatment strategies. The challenges and adaptations required are outlined. CONCLUSIONS: It is the aim of the international kidney community to prevent chronic kidney disease. The South African and Australian groups highlight the need for a systematic and sustained approach to the management of chronic diseases to achieve this goal.

Australia↗