Diabetes care in developing countries.
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Data Collection↗
Biomedical subjects
Hitesh Patel
Publications and source records attributed to Hitesh Patel.
Reliability of echocardiographic indices of dyssynchrony.
BACKGROUND: Echocardiographic indices of dyssynchrony are increasingly used to select candidates for cardiac resynchronization therapy. For widespread screening of heart failure patients, such variables need to be comparable when evaluated by different operators using different equipment. OBJECTIVE AND METHODS: To evaluate the reproducibility and obtainability of echocardiographic indices of mechanical dyssynchrony, we studied 40 subjects stratified according to QRS morphology and systolic function. Two echocardiograms were performed on each patient by different sonographers on different machines and each study was analyzed by two observers. RESULTS: All blood-pool and tissue Doppler indices of dyssynchrony were obtainable in over 97% of cases. Blood-pool Doppler measures were the most reproducible indices of intraventricular dyssynchrony (aortic ejection delay) and interventricular dyssynchrony (aortopulmonary difference in ejection delay). For annular tissue Doppler delays, the time to peak velocity was consistently more reproducible than the time to velocity onset. CONCLUSION: Differences in the reliability of echocardiographic indices may affect their suitability as screening tests for dyssynchrony.
Arrhythmias, Cardiac↗
Trends in the prescription and cost of diabetic medications and monitoring equipment in England 1991-2004.
BACKGROUND: To report the trend in prescriptions and cost of antidiabetic drugs and glucose monitoring equipment in England from 1991 to 2004. METHODS: We analysed data on all community antidiabetic drug prescriptions in England collated from the Prescription Cost Analysis system. RESULTS: The total number of diabetes prescriptions (medicines and monitoring) rose from 7,613,000 (1991) to 24,325,640 (2004) (>300% increase). Meanwhile, total costs increased by 650%. Insulins are the biggest contributor to cost followed by monitoring equipment and then oral medications. Three times as many items of oral tablets are prescribed than insulins. Metformin accounts for 40% of all diabetic drug dispensations but only 7% of the costs. More is spent on glitazones now than on either metformin or sulphonylureas. CONCLUSIONS: There has been a substantial increase in the cost of managing diabetes in the community. Costs are likely to continue to rise in the future, as the prevalence of diabetes increases and through more aggressive identification and management of patients with diabetes in the hope of reducing the even more costly complications. The cost implications of glucose monitoring merits further study.
Administration, Oral↗
Detection of myocardial scar by contrast-enhanced cardiac magnetic resonance imaging in patients with troponin-positive chest pain and minimal angiographic coronary artery disease.
Patients who present with chest pain and elevated serum troponin levels may have minimal angiographic coronary artery disease, leading to diagnostic confusion. We investigated patients with troponin-positive acute coronary syndromes and minimal coronary artery disease (CAD) using contrast-enhanced cardiac magnetic resonance imaging to assess for myocardial scar. Twenty-three patients (54 +/- 8 years of age) who presented with chest pain, high troponin I level, and minimal angiographic CAD were included. Patients with a clinical pericarditis/myocarditis, tachyarrhythmia at presentation, previous myocardial infarction, or an alternative explanation for increased troponin I level were excluded. Myocardial scar was assessed with delayed-enhancement inversion-recovery imaging after administration of gadolinium. Hyperenhancement consistent with myocardial scar was seen in 7 of 23 patients (30%) and was located primarily in the right coronary artery distribution. Peak troponin level, clinical characteristics, and volumetric parameters were similar in patients with or without hyperenhancement. One patient had mid-myocardial enhancement that suggested undiagnosed myocarditis. There was a linear relation between the mass of myocardial scar and peak serum troponin level. In follow-up, subsequent cardiac events were more frequent in patients with hyperenhancement (43% vs 12.5%). In conclusion, patients with troponin-positive acute coronary syndromes may have significant myocardial scar even when minimal CAD is found on angiography.
Adult↗
Calcium regulates scallop muscle by changing myosin flexibility.
Muscle myosins are molecular motors that convert the chemical free energy available from ATP hydrolysis into mechanical displacement of actin filaments, bringing about muscle contraction. Myosin cross-bridges exert force on actin filaments during a cycle of attached and detached states that are coupled to each round of ATP hydrolysis. Contraction and ATPase activity of the striated adductor muscle of scallop is controlled by calcium ion binding to myosin. This mechanism of the so-called "thick filament regulation" is quite different to vertebrate striated muscle which is switched on and off via "thin filament regulation" whereby calcium ions bind to regulatory proteins associated with the actin filaments. We have used an optically based single molecule technique to measure the angular disposition adopted by the two myosin heads whilst bound to actin in the presence and absence of calcium ions. This has allowed us to directly observe the movement of individual myosin heads in aqueous solution at room temperature in real time. We address the issue of how scallop striated muscle myosin might be regulated by calcium and have interpreted our results in terms of the structures of smooth muscle myosin that also exhibit thick filament regulation.
Actins↗
A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis.
Increased intracellular H(+) efflux is speculated to be an evolutionarily conserved mechanism necessary for rapid assembly of cytoskeletal filaments and for morphological polarity during cell motility. In Dictyostelium discoideum, increased intracellular pH through undefined transport mechanisms plays a key role in directed cell movement. We report that a developmentally regulated Na-H exchanger in Dictyostelium discoideum (DdNHE1) localizes to the leading edge of polarized cells and is necessary for intracellular pH homeostasis and for efficient chemotaxis. Starved DdNHE1-null cells (Ddnhe1(-)) differentiate, and in response to the chemoattractant cAMP they retain directional sensing; however, they cannot attain a polarized morphology, but instead extend mislocalized pseudopodia around the cell and exhibit decreased velocity. Consistent with impaired polarity, in response to chemoattractant, Ddnhe1(-) cells lack a leading edge localization of F-actin and have significantly attenuated de novo F-actin polymerization but increased abundance of membrane-associated phosphatidylinositol 3,4,5-trisphosphate (PI((3,4,5))P(3)). These findings indicate that during chemotaxis DdNHE1 is necessary for establishing the kinetics of actin polymerization and PI((3,4,5))P(3) production and for attaining a polarized phenotype.
Actins↗
Na(+)/H(+) exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes.
The plasma membrane Na(+)/H(+) exchanger NHE1 has an established function in intracellular pH and cell volume homeostasis by catalyzing electroneutral influx of extracellular Na(+) and efflux of intracellular H(+). A second function of NHE1 as a structural anchor for actin filaments through its direct binding of the ezrin, radixin, and moesin (ERM) family of actin-binding proteins was recently identified. ERM protein binding and actin anchoring by NHE1 are necessary to retain the localization of NHE1 in specialized plasma membrane domains and to promote cytoskeleton-dependent processes, including actin filament bundling and cell-substrate adhesions. This review explores a third function of NHE1, as a plasma membrane scaffold in the assembly of signaling complexes. Through its coordinate functions in H(+) efflux, actin anchoring, and scaffolding, we propose that NHE1 promotes protein interactions and activities, assembles signaling complexes in specialized plasma membrane domains, and coordinates divergent signaling pathways.
Animals↗
The cyclase-associated protein CAP as regulator of cell polarity and cAMP signaling in Dictyostelium.
Cyclase-associated protein (CAP) is an evolutionarily conserved regulator of the G-actin/F-actin ratio and, in yeast, is involved in regulating the adenylyl cyclase activity. We show that cell polarization, F-actin organization, and phototaxis are altered in a Dictyostelium CAP knockout mutant. Furthermore, in complementation assays we determined the roles of the individual domains in signaling and regulation of the actin cytoskeleton. We studied in detail the adenylyl cyclase activity and found that the mutant cells have normal levels of the aggregation phase-specific adenylyl cyclase and that receptor-mediated activation is intact. However, cAMP relay that is responsible for the generation of propagating cAMP waves that control the chemotactic aggregation of starving Dictyostelium cells was altered, and the cAMP-induced cGMP production was significantly reduced. The data suggest an interaction of CAP with adenylyl cyclase in Dictyostelium and an influence on signaling pathways directly as well as through its function as a regulatory component of the cytoskeleton.
Actins↗
Evaluation of the symmetric model for myosin-linked regulation: effect of site-directed mutations in the regulatory light chain on scallop myosin.
Regulatory myosins are controlled through mechanisms intrinsic to their structures and can alternate between activated and inhibited states. However, the structural difference between these two states is unclear. Scallop (Pecten maximus) striated adductor myosin is activated directly by calcium. It has been proposed that the two heads of scallop myosin are symmetrically arranged and interact through their regulatory light chains [Offer and Knight (1996) J. Mol. Biol. 256, 407-416], the interface being strengthened in the inhibited state. By contrast, vertebrate smooth-muscle myosin is activated by phosphorylation. Its structure in the inhibited state has been determined from two-dimensional crystalline arrays [Wendt, Taylor, Trybus and Taylor (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 4361-4366] and is asymmetric, requiring no interaction between regulatory light chains. Using site-directed mutagenesis of the scallop regulatory light chain, we have tested the symmetric model for scallop adductor muscle myosin. Specifically, we have made myosin hybrid molecules from scallop (P. maximus) myosin, in which the normal regulatory light chains have been replaced by expressed light chains containing mutations in three residues proposed to participate in the interaction between regulatory light chains. The mutations were R126A (Arg126-->Ala), K130A and E131A; made singly, in pairs or all three together, these mutations were designed to eliminate hydrogen bonding or salt linkages between heads, which are key features of this model. Functional assays to address the competence of these hybrid myosins to bind calcium specifically, to exhibit a calcium-regulated myofibrillar Mg-ATPase and to display calcium-dependent actin sliding were performed. We conclude that the symmetrical model does not describe the inhibited state of scallop regulatory myosin and that an asymmetric structure is a plausible alternative.
Animals↗
Agreement between insurance claim and self-reported hospital and emergency room utilization data among persons with diabetes.
As part of a retrospective evaluation of a diabetes management program, the agreement between self-reported and insurance claim data on hospitalization and emergency room utilization was examined. Data agreement on hospitalization or emergency room visits between the two collection modes was evaluated through the use of simple agreement proportions and the kappa agreement statistic. A total of 1,230 participant responses were studied. The proportions of patients with hospitalization or emergency room visits were indistinguishable between the self-reported and medical claims data, and kappa statistics also indicated good-to-excellent agreement between data sets. The percentages of participants whose self-reported hospitalization and emergency room utilization exactly matched data derived from insurance claims were high (89.1% and 87.2%, respectively). Furthermore, the kappa statistics of agreement for the number of hospitalizations (0.6366) and emergency room visits (0.5390) indicate good agreement between self-reported and insurance claim data. The results of this study suggest either self-reported or insurance claims data can be used to evaluate the impact of health care interventions on hospital or emergency room utilization.
Aged↗
Clearance of circulating tumor cells after excision of primary colorectal cancer.
OBJECTIVE: To establish whether the prevalence of positive reverse transcriptase-polymerase chain reaction (RT-PCR) results decreased during the first 3 months after colorectal cancer excision, and to assess whether persistence of RT-PCR positivity after primary colorectal cancer excision was related to tumor stage or locally advanced and metastatic disease. METHODS: Systemic venous blood was collected from patients with colorectal cancer before and at intervals up to 12 weeks after surgery. RNA was extracted from the mononuclear cell fraction of the blood samples and subjected to RT-PCR using specific primers for carcinoembryonic antigen mRNA and cytokeratin-20 mRNA. Healthy individuals with no history of cancer were used as controls. RESULTS: The results of RT-PCR were positive in 81 of 116 patients with colorectal cancer before surgery, with no significant differences in preoperative prevalence by Dukes stage or presence of locally advanced or metastatic disease. There was a significant decrease in the prevalence of RT-PCR positivity at 24 hours after surgery compared with before surgery. On subgroup analysis by Dukes stage, only the decrease in Dukes A and B patients reached significance. Seven of the 143 controls were RT-PCR positive. CONCLUSIONS: Circulating tumor cells were present before treatment in most patients with colorectal cancer regardless of tumor stage or metastases. Clearance of circulating tumor cells within 24 hours of colorectal cancer excision was greatest in tumors with the best prognosis.
Adenocarcinoma↗
Reference interval for troponin I on the ACS:Centaur assay: a recommendation based on the recent redefinition of myocardial infarction.
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Adult↗