Objective. To investigate the use of magnetic resonance imaging (MRI) and P‐31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with ...amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM.
Methods. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P‐31 MRS, by determining concentrations of phosphate metabolites during rest and exercise.
Results. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest.
Conclusion. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.
Dermatomyositis is an autoimmune disease characterized by an erythematous rash and severe muscle weakness. 31P Magnetic resonance spectroscopy (MRS) provides quantitative data for longitudinal ...monitoring of disease status and responses to immunosuppressive therapy. A disease variant, amyopathic dermatomyositis, presents with a typical rash but no clinical muscle weakness. However, metabolic abnormalities in the oxidative capacity of muscles of amyopathic patients during exercise were detected with 31P MRS. Because MRS provided the best quantitative data for evaluating dermatomyositis, the 31P metabolic parameters derived from the MR spectra were further processed using an artificial neural network (XERION). The neural network analyses provided additional clinical information from the weighted correlations of multiple 31P parameters, namely, inorganic phosphate, phosphocreatine, ATP, phosphodiesters, and selected ratios. This investigation analyzes the relative importance of the various metabolic parameters for accurate patient characterization and provides insights into the pathogenesis of the disease.
Stability analysis of linear systems can be studied by root-locus technique, Nyquist criterion and Routh Hurwitz's stability testing. Stability study of nonlinear systems can be done by describing ...function method, phase-plane analysis, numerical integration, and Lyapunov's second method. In this paper, neural network approach to predict the stability of nonlinear systems is presented. This approach is illustrated with an example.
Coordinatively unsaturated double‐stranded helicates (H2L)2Eu2(NO3)2(H2O)4(NO3)4, (H2L)2Tb2(H2O)6(NO3)6, and (H2L)2Tb2(H2O)6Cl6 (H2L=butanedioicacid‐1,4‐bis2‐(2‐pyridinylmethylene)hydrazide) are ...easily obtained by self‐assembly from the ligand and the corresponding lanthanide(III) salts. The complexes are characterized by X‐ray crystallography showing the helical arrangement of the ligands. Co‐ligands at the metal ions can be easily substituted by appropriate anions. A specific luminescence response of AMP in presence of ADP, ATP, and other anions is observed. Specificity is assigned to the perfect size match of AMP to bridge the two metal centers and to replace quenching co‐ligands in the coordination sphere.
One AMP is enough: A coordinatively unsaturated double‐stranded dinuclear europium(III) helicate shows adenosine monophosphate (AMP)‐specific luminescence response even in the presence of highly charged adenosine di‐ or triphosphate (ADP or ATP).
Three imidazolium-based ionic liquid (IL) monomers, namely, 3-(1-ethyl imidazolium-3-yl)propylmethacrylamido bromide (IL-1), 2-(1-methylimidazolium-3-yl)ethyl methacrylate bromide (IL-2), and ...2-(1-ethylimidazolium-3-yl)ethyl methacrylate bromide (IL-3), and methacrylic acid (MAA) were polymerized by the reversible addition fragmentation chain transfer (RAFT) process in methanolic solutions at 70 °C, using either 2-cyanopropyl dithiobenzoate (CTA-1) or (4-cyanopentanoic acid)-4-dithiobenzoate (CTA-2) as chain transfer agents (CTAs). Under these conditions, polymers exhibited molar masses predetermined by the initial molar ratio of the monomers to the dithioester precursor, as evidenced by 1H NMR spectroscopy from chain ends analysis. These hydrophilic polymers were subsequently used as macro-CTAs in chain extension experiments in aqueous or in alcoholic solutions, affording IL-based double hydrophilic block copolymers (DHBCs) of the type PIL-1-b-PAm, PMAA-b-PIL-2 and PMAA-b-PIL-3, where PAm and PIL stand for polyacrylamide and polymeric ionic liquid. These DHBCs could be further manipulated and made to self-assemble in micelle-like structures in water by exchanging the bromide (Br−) counteranion of IL blocks for −N(SO2CF3)2. This anion exchange indeed turned the solution properties of the PIL blocks from hydrophilic to hydrophobic, as verified on the corresponding IL-based homopolymers which were immiscible with water after the anion switch. Investigations by 1H NMR evidenced that the diblock copolymers exhibited salt-responsive behavior in aqueous solutions: anion exchange induced the formation of water-soluble micellar aggregates consisting of hydrophobic − N(SO2CF3)2-based IL blocks at the core stabilized by water-soluble PAm or PMAA at the shell.
Background & Aims: The temporal association between diabetes mellitus and pancreatic cancer is poorly understood. We compared temporal patterns in diabetes prevalence in pancreatic cancer and ...controls. Methods: We reviewed the medical records of pancreatic cancer cases residing within 120 miles or less of Rochester, Minnesota, seen at the Mayo Clinic between January 15, 1981, and July 9, 2004, and approximately 2 matched controls/case residing locally. We abstracted all outpatient fasting blood glucose (FBG) levels for up to 60 months before index (ie, date of cancer diagnosis for cases) and grouped them into 12-month intervals; 736 cases and 1875 controls had 1 or more outpatient FBG levels in the medical record. Diabetes was defined as any FBG level of 126 mg/dL or greater or treatment for diabetes, and was defined as new onset when criteria for diabetes were first met 24 or fewer months before index, with at least 1 prior FBG level less than 126 mg/dL. Results: A higher proportion of pancreatic cancer cases compared with controls met the criteria for diabetes at any time in the 60 months before index (40.2% vs 19.2%, P < .0001). The proportions were similar in the −60 to −48 ( P = .76) and −48 to −36 ( P = .06) month time periods; however, a greater proportion of cases than controls met criteria for diabetes in the −36 to −24 ( P = .04), −24 to −12 ( P < .001), and −12 to 0 ( P < .001) month time periods. Diabetes was more often new onset in cases vs controls (52.3% vs 23.6%, P < .0001). Conclusions: Diabetes has a high (40%) prevalence in pancreatic cancer and frequently is new onset. Identification of a specific biomarker for pancreatic cancer–induced diabetes may allow screening for pancreatic cancer in new-onset diabetes.
Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model ...that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. A phase 1 discovery study (
= 20), a phase 2a validation study (
= 189), and a second phase 2b validation study (
= 537) revealed that concentrations of plasma thrombospondin-2 (THBS2) discriminated among all stages of PDAC consistently. The receiver operating characteristic (ROC) c-statistic was 0.76 in the phase 1 study, 0.84 in the phase 2a study, and 0.87 in the phase 2b study. The plasma concentration of THBS2 was able to discriminate resectable stage I cancer as readily as stage III/IV PDAC tumors. THBS2 plasma concentrations combined with those for CA19-9, a previously identified PDAC marker, yielded a c-statistic of 0.96 in the phase 2a study and 0.97 in the phase 2b study. THBS2 data improved the ability of CA19-9 to distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the phase 2b study. A THBS2 and CA19-9 blood marker panel measured with a conventional ELISA may improve the detection of patients at high risk for PDAC.
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