Is surgery still the preferred option for coronary revascularisation in diabetics with multivessel coronary disease?
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Cohort Studies↗
Biomedical subjects
A Kapur
Publications and source records attributed to A Kapur.
Prandial glucose regulation--its implication in clinical practice.
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Blood Glucose↗
Relevance of glycemic index in the management of post-prandial glycemia.
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Blood Glucose↗
Positive ion electrospray ionization mass spectrometry of double-stranded DNA/drug complexes.
Positive ion electrospray ionization mass spectra of 16 base-pair double-stranded (ds)DNA have been obtained with essentially no ions from single-stranded DNA present. Single-stranded DNA was minimized by: (1) careful choice of DNA sequences; (2) the use of a relatively high salt concentration (0.1 M ammonium acetate, pH 8.5), and, (3) a low desolvation temperature (40 degrees C). Similarly, ESI-MS complexes of dsDNA with cisplatin, daunomycin and distamycin were obtained that contained only negligible amounts of single-stranded DNA. The complexes with daunomycin and distamycin were more stable to strand separation in the gas phase than dsDNA alone. This is in agreement with solution studies and with other recent gas phase results. These data contrast with many earlier ESI-MS studies of dsDNA and DNA/drug complexes in which ions from ssDNA are also normally observed.
Cisplatin↗
High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey.
AIMS/HYPOTHESIS: There has been no reported national survey of diabetes in India in the last three decades, although several regional studies show a rising prevalence of diabetes. The aim of this study was to assess the prevalence of diabetes and impaired glucose tolerance in six major cities, covering all the regions of the country. METHODS: Using a stratified random sampling method, 11216 subjects (5288 men; 5928 women) aged 20 years or above, representative of all socio-economic strata, were tested by OGTT. Demographic, anthropometric, educational and social details were recorded using a standard proforma. Physical activity was categorised using a scoring system. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Glucose tolerance was classified using the 2-h values (WHO criteria). Prevalence estimations were made taking into account the stratified sampling procedure. Group comparisons were done by t-test or analysis of variance or Z-test as relevant. Univariate and multiple logistic regression analyses were used to study the association of variables with diabetes and impaired glucose tolerance. RESULTS: Age standardised prevalences of diabetes and impaired glucose tolerance were 12.1% and 14.0% respectively, with no gender difference. Diabetes and impaired glucose tolerance showed increasing trend with age. Subjects under 40 years of age had a higher prevalence of impaired glucose tolerance than diabetes (12.8% vs 4.6%, p < 0.0001). Diabetes showed a positive and independent association with age, BMI, WHR, family history of diabetes, monthly income and sedentary physical activity. Age, BMI and family history of diabetes showed associations with impaired glucose tolerance. CONCLUSIONS/INTERPRETATION: This national study shows that the prevalence of diabetes is high in urban India. There is a large pool of subjects with impaired glucose tolerance at a high risk of conversion to diabetes.
Adult↗
Hippocampal mossy fiber activity evokes Ca2+ release in CA3 pyramidal neurons via a metabotropic glutamate receptor pathway.
Mossy fiber activity can evoke Ca2+ release from internal stores in CA3 neurons, but the physiological conditions under which this occurs and the mechanisms underlying the release are not understood. Using rat hippocampal slices we report here that short trains of mossy fiber stimulation activate group I metabotropic glutamate receptors (mGluRs) on CA3 pyramidal neurons and elicit waves of Ca2+ release from inositol 1,4,5-trisphosphate (IP3) sensitive internal stores that propagate from stratum lucidum to the soma and in some cases distally out the dendrites. Activation of mGluR1,5 receptors by an agonist trans-azetidine-2,4-dicarboxylic acid (tADA) applied to stratum lucidum was also sufficient to induce waves of Ca2+ release. This release was blocked by internal heparin, but not by dantrolene, suggesting the involvement of IP3 rather than ryanodine receptors in not only the initial release but also in the maintenance of the propagating waves. Release could be facilitated by Ca2+ influx through voltage-gated Ca2+ channels, which is consistent with the known Ca2+ sensitivity of IP3 receptors.These results provide insight into the mechanisms and conditions of Ca2+ release in CA3 neurons and demonstrate the powerful influence mossy fiber input can have on these neurons.
Action Potentials↗
Comparison of RTP dose distributions in heterogeneous phantoms with the BEAM Monte Carlo simulation system.
Therapeutic treatment plan evaluation is often based on examining the radiotherapy treatment planning (RTP) system dose distributions in the target and surrounding normal structures. To study the effects of tissue inhomogeneities on photon dose distributions, we compared FOCUS RTP system dose distributions from the measurement-based Clarkson and model-based MultiGrid Superposition (MGS) algorithms with those from the BEAM Monte Carlo code system in a set of heterogeneous phantoms. The phantom inhomogeneities mimic relevant clinical treatment sites, which include lung slab, lung-bone slab, bone-lung slab, mediastinum, and tumor geometries. The benchmark comparisons were performed in lung densities of 0.20 and 0.31 g/cm3, and a bone density of 2.40 g/cm3 for 5x5 cm2 and 10x10 cm2, 6- and 15-MV photon beams. Benchmark comparison results show that the MGS model and BEAM doses match better than 3% or 3 mm, and the MGS model is more accurate than the Clarkson model in all phantoms. The MGS model, unlike the Clarkson model, predicts the build-down and build-up of dose near tissue interfaces and penumbra broadening in lung associated with high energy beams. The Clarkson model overestimates the dose in lung by a maximum of 10% compared to BEAM. Dose comparisons suggest turning-off the effective path length inhomogeneity correction in the Clarkson model for lung treatments.
Algorithms↗
DiabCare Asia--India Study: diabetes care in India--current status.
AIM: To investigate the relationship between diabetes control, management and late complications in a subset of urban Indian diabetes population treated at tertiary diabetes care centres and measure the quality of management to set benchmarks for future improvement. METHODOLOGY: The study population consisted of 100 consecutive review patients treated for more than one year at each of the 26 participating centres. HbA1c was estimated centrally by Bio-Rad Variant method. The methods used to diagnose diabetic complications varied among centres, depending on the doctor's standard clinical examination. A more detailed methodology was eschewed for reason of brevity of the data collection form, and lack of standardisation of methods. Similarly, the assessment of renal function was performed via a variety of methods, namely dipstick proteinuria, a 24 hour urinary excretion assay, presence of microalbuminuria and serum creatiine concentration; retinopathy was detected using fundoscopy. Data was collected in a standardized data collection form, entered into an SAS database, validated and descriptive analysis performed. RESULTS: A total of 2,269 subjects with valid relevant data formed the study population. Subjects had a mean age of 53.3 +/- 13 years. The mean age at onset of diabetes was 43.6 +/- 12.2 years, with a mean diabetes duration of 10.0 +/- 6.9 years. Type 2 diabetics constituted 90.6% of the patients. Approximately half the patients had poor control (HbA1c > 2% points above upper limit of normal and FBG > 139 mg/dl). Mean HbA1c (central laboratory) was 8.9 +/- 2.1% and FBG 150 +/- 59 mg/dl. Over 54% patients had severe late complications, apart from a high frequency of associated hyperlipidemia. Mean HbA1c level and frequency of complications was higher in patients with longer diabetes duration. Frequency of self-monitoring was low. Only 4% of patients were on diet therapy, 53.9% were receiving oral hypoglycemic agents (OHAs), 22% were receiving insulin and 19.8% a combination of insulin and OHAs. Frequency of insulin usage was higher amongst patients with longer diabetes duration. CONCLUSIONS: This large multi-centre collaborative observational study shows that type 2 diabetes begins at an early age amongst Indians. With increasing duration of diabetes, glycemic control deteriorates leading to late complications. Diabetes care in India leaves much to be desired. Concerted efforts to increase awareness amongst health professionals to improve diabetes care are urgently needed. The study by increasing awareness about the current status of diabetes care provides a useful benchmark to plan future improvements.
Adult↗
Annulation reactions of allene-derived 1,3-dipole with 3-substituted-chromones: unusual recognition of 4pi-component in 3-(N-Aryliminomethyl)chromones through
All-carbon dipole derived by the interaction of triphenylphosphine with allenic ester is able to locate the polarized 2pi-component in 3-formylchromones through a regioselective [2 + 3] addition to the C2-C3 pi-bond, which is followed by deformylation leading to novel 3a,9a-dihydro-1-ethoxycarbonyl-1-cyclopenteno[5, 4-b]benzopyran-4-ones. On the contrary, the dipole recognizes azadiene in 3-(N-aryliminomethyl)chromones through [4 + 3] annulation and initially formed adducts undergo tandem rearrangements to afford novel N-aryl-2, 3-dihydro-4-ethoxycarbonylchromano[2,3-b]azepine-6-ones in good yield.
Journal Article↗
Unusual
All-carbon 1,3-dipoles derived from allenic esters/ketones, by catalytic interaction with triphenylphosphine, undergo an unusual [8 + 2] annelation with tropone, leading to 8-oxa-9-(ethoxycarbonyl/acylalkylidene)bicyclo[5.3.0]deca-1,3,5-trienes. Dipoles derived from allenic ketones as well as an alpha-methyl-substituted allenic ester display high reactivity and selectivity.
Journal Article↗
Photon beam characterization and modelling for Monte Carlo treatment planning.
Photon beams of 4, 6 and 15 MV from Varian Clinac 2100C and 2300C/D accelerators were simulated using the EGS4/BEAM code system. The accelerators were modelled as a combination of component modules (CMs) consisting of a target, primary collimator, exit window, flattening filter, monitor chamber, secondary collimator, ring collimator, photon jaws and protection window. A full phase space file was scored directly above the upper photon jaws and analysed using beam data processing software, BEAMDP, to derive the beam characteristics, such as planar fluence, angular distribution, energy spectrum and the fractional contributions of each individual CM. A multiple-source model has been further developed to reconstruct the original phase space. Separate sources were created with accurate source intensity, energy, fluence and angular distributions for the target, primary collimator and flattening filter. Good agreement (within 2%) between the Monte Carlo calculations with the source model and those with the original phase space was achieved in the dose distributions for field sizes of 4 cm x 4 cm to 40 cm x 40 cm at source surface distances (SSDs) of 80-120 cm. The dose distributions in lung and bone heterogeneous phantoms have also been found to be in good agreement (within 2%) for 4, 6 and 15 MV photon beams for various field sizes between the Monte Carlo calculations with the source model and those with the original phase space.
Models, Theoretical↗
Monte Carlo verification of IMRT dose distributions from a commercial treatment planning optimization system.
The purpose of this work was to use Monte Carlo simulations to verify the accuracy of the dose distributions from a commercial treatment planning optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented clinically to improve and verify the accuracy of radiotherapy dose calculations. Further modifications to the system were made to compute the dose in a patient for multiple fixed-gantry IMRT fields. The dose distributions in the experimental phantoms and in the patients were calculated and used to verify the optimized treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT dose distributions agreed with the measurements to within 2% of the maximum dose for all the beam energies and field sizes for both the homogeneous and heterogeneous phantoms. The dose distributions predicted by the Corvus system, which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte Carlo simulations and measurements to within 4% in a cylindrical water phantom with various hypothetical target shapes. Discrepancies of more than 5% (relative to the prescribed target dose) in the target region and over 20% in the critical structures were found in some IMRT patient calculations. The FSPB algorithm as implemented in the Corvus system is adequate for homogeneous phantoms (such as prostate) but may result in significant under or over-estimation of the dose in some cases involving heterogeneities such as the air-tissue, lung-tissue and tissue-bone interfaces.
Computer Simulation↗
Electron beam modeling and commissioning for Monte Carlo treatment planning.
A hybrid approach for commissioning electron beam Monte Carlo treatment planning systems has been studied. The approach is based on the assumption that accelerators of the same type have very similar electron beam characteristics and the major difference comes from the on-site tuning of the electron incident energy at the exit window. For one type of accelerator, a reference machine can be selected and simulated with the Monte Carlo method. A multiple source model can be built on the full Monte Carlo simulation of the reference beam. When commissioning electron beams from other accelerators of the same type, the energy spectra in the source model are tuned to match the measured dose distributions. A Varian Clinac 2100C accelerator was chosen as the reference machine and a four-source beam model was established based on the Monte Carlo simulations. This simplified beam model can be used to generate Monte Carlo dose distributions accurately (within 2%/2 mm compared to those calculated with full phase space data) for electron beams from the reference machine with various nominal energies, applicator sizes, and SSDs. Three electron beams were commissioned by adjusting the energy spectra in the source model. The dose distributions calculated with the adjusted source model were compared with the dose distributions calculated using the phase space data for these beams. The agreement is within 1% in most of cases and 2% in all situations. This preliminary study has shown the capability of the commissioning approach for handling large variation in the electron incident energy. The possibility of making the approach more versatile is also discussed.
Algorithms↗
Regulation of phosphatidylcholine homeostasis by calcium-independent phospholipase A2.
Phosphatidylcholine (PtdCho) is the most abundant phospholipid in mammalian cell membranes and is essential for cell viability. The levels of this lipid must be tightly controlled to maintain homeostasis. Therefore, changes in the rate of PtdCho synthesis are generally balanced by changes in PtdCho catabolism and vice versa. It is commonly accepted that the rate of PtdCho synthesis is regulated by CTP:phosphocholine cytidylyltransferase (CT). However, it is not certain if PtdCho mass is regulated by specific catabolic enzyme(s). Our goal is to determine if PtdCho homeostasis is regulated by a phospholipase A2 (PLA2). To this end, we have prepared Chinese hamster ovary (CHO) cell lines that overexpress CT. CT activity is 7-10-fold higher in the transfected cells than in parental CHO cells. This increase in CT activity is associated with increases in both PtdCho synthesis and PtdCho catabolism. Glycerophosphocholine is the PtdCho catabolite that accumulates in the transfected cells, which suggests that PtdCho turnover is mediated by a phospholipase A2 (PLA2). Indeed, higher levels of calcium-independent PLA2 activity are measured in the cytosols of the CHO cells that overexpress CT, compared to parental CHO cells. The elevated calcium-independent PLA2 activity is associated with increases in the expression of the 80-kDa calcium-independent PLA2 (iPLA2). Together, these data suggest that the 80-kDa iPLA2 may be modulated in response to changes in PtdCho levels and therefore is involved in the regulation of PtdCho homeostasis in CHO cells.
Animals↗
Observation of daunomycin and nogalamycin complexes with duplex DNA using electrospray ionisation mass spectrometry.
The noncovalent binding of the antitumour drugs daunomycin and nogalamycin to duplex DNA has been studied using electrospray ionisation mass spectrometry (ESI-MS). The conditions for the preparation of drug/duplex DNA complexes and for their detection by ESI-MS have been optimised. Ions corresponding to these complexes were most abundant relative to free DNA when prepared in the pH range 8-9, and using gentle ESI interface conditions. Self-complementary oligonucleotides, 5'-d(GGCTAGCC)-3' or 5'-d(CGGCGCCG)-3', annealed in the presence of a 5-fold molar excess of either nogalamycin or daunomycin gave ESI mass spectra in which the most intense ions corresponded to three molecules of drug bound to duplex DNA, with some evidence for four drug molecules bound. For binding to 5'-d(TGAGCTAGCTCA)(2)-3', complexes containing up to four nogalamycin and six daunomycin molecules were observed. These data are consistent with the neighbour exclusion principle whereby intercalation occurs between every other base pair such that up to four bound drugs would be expected for the 8 mers and up to six for the 12 mer. Competition experiments involving a single drug in an equimolar mixture of two oligonucleotides (5'-d(TGAGCTAGCTCA)(2)-3' with either 5'-d(CGGCGCCG)(2)-3' or 5'-d(GGCTAGCC)(2)-3') showed ions arising from complexes of drug/5'-d(CGGCGCCG)(2)-3' were more intense than complexes of drug/5'-d(GGCTAGCC)(2)-3', relative to those from the 12 mer in each mixture. While this suggests ESI-MS has the potential to detect differences in sequence selectivity, more detailed experiments involving a comparison of the relative ionisation efficiency of different oligonucleotides and a wider range of intercalators are required to establish this definitively. ESI mass spectra from experiments in which both drugs were reacted with the same oligonucleotide were more complex, such that a clear preference for one drug could not be established.
Antibiotics, Antineoplastic↗
Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism.
We investigated long-term potentiation (LTP) at mossy fiber synapses on CA3 pyramidal neurons in the hippocampus. Using Ca2+ imaging techniques, we show here that when postsynaptic Ca2+ was sufficiently buffered so that [Ca2+]i did not rise during synaptic stimulation, the induction of mossy fiber LTP was prevented. In addition, induction of mossy fiber LTP was suppressed by postsynaptic injection of a peptide inhibitor of cAMP-dependent protein kinase. Finally, when ionotropic glutamate receptors were blocked, LTP depended on the postsynaptic release of Ca2+ from internal stores triggered by activation of metabotropic glutamate receptors. These results support the conclusion that mossy fiber LTP and LTP at other hippocampal synapses share a common induction mechanism involving an initial rise in postsynaptic [Ca2+].
Animals↗
Stopping-power ratios for clinical electron beams from a scatter-foil linear accelerator.
Restricted mass collision stopping-power ratios for electron beams from a scatter-foil medical linear accelerator (Varian Clinac 2100C) were calculated for various combinations of beams, phantoms and detector materials using the Monte Carlo method. The beams were of nominal energy 6, 12 or 20 MeV, with square dimensions 1 x 1 cm2 to 10 x 10 cm2. They were incident at nominal SSDs of 100 or 120 cm and inclined at 90 degrees or 30 degrees to the surface of homogeneous water phantoms or water phantoms interspersed with layered lung or bone-like materials. The broad beam water-to-air stopping-power ratios were within 1.3% of the AAPM TG21 protocol values and consistent with the results of Ding et al to within 0.2%. On the central axis the stopping-power ratio variations for narrow beams compared with normally incident broad beams were 0.1% or less for water-to-LiF-100, graphite, ferrous sulfate dosimeter solution, polystyrene and PMMA, 0.5% for water-to-silicon and 1% for water-to-air and water-to-photographic-film materials. The transverse variations of the stopping-power ratios were up to 4% for water-to-silicon, 7% for water-to-photographic-film materials and 10% for water-to-air in the penumbral regions (where the dose was 10% of the global dose maximum) at shallow depths compared with the values at the same depths on the central axis. In the inhomogeneous phantoms studied, the stopping-power ratio correction factors varied more significantly for air, followed by photographic materials and silicon, at various depths on the central axis in the heterogeneous regions. For the simple layered phantoms studied, the estimation of the stopping-power ratio correction factors based on the relative electron-density derived effective depth approach yielded results that were within 0.5% of the Monte Carlo derived values for all the detector materials studied.
Electrons↗