Guiding early revascularization using [15O]H2O PET myocardial perfusion imaging - Impact of atrial fibrillation.

AIMS: Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated whether atrial fibrillation (AF): 1) reduces global hyperemic myocardial blood flow (MBF) and 2) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. METHODS AND RESULTS: We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD and AF-CAD. Hyperemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way ANOVA p<0.0001]. In multiple linear regression ongoing AF was independently associated with reduced hyperemic MBF. Every 0.1 mL/min/g decrease in hyperemic MBF was associated with a 23% increase in odds of early revascularization. ROC-analysis of vessel specific hyperemic MBF to predict early revascularization yielded the following areas under the ROC curve (AUC): SR-noCAD: 0.95 (p<0.0001); AF-noCAD: 0.79 (p<0.0001); SR-CAD: 0.78 (p<0.0001); AF-CAD: 0.88 (p<0.0001). CONCLUSION: Ongoing AF is associated with 19-25 % reduced global hyperemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel specific hyperemic MBF still predicts early revascularization in patients with AF.

Prevalence of muscle dysfunction concomitant with osteoporosis in a home-dwelling Danish population aged 65-93 years - The Copenhagen Sarcopenia Study.

INTRODUCTION: As life expectancy increases, a growing percentage of older individuals with age-related diseases such as osteoporosis and sarcopenia are expected. Patients with both conditions, i.e. patient with osteosarcopenia, are suggested to have a higher risk of fall and fracture compared to individuals with either condition. AIM: To investigate the potential relationship between low bone mineral density (BMD) and muscle dysfunction in a Danish cohort of older home-dwelling individuals. Furthermore, to examine the prevalence of osteosarcopenia and alterations in prevalence depending on cut-off values chosen. METHOD: Measures of BMD, relative appendicular lean mass and hand grip strength were assessed in 529 individuals aged 65+ from the population-based cross-sectional Copenhagen Sarcopenia Study (CSS). Osteoporosis was diagnosed according to the World Health Organization guidelines. Sarcopenia was diagnosed in accordance with the guidelines from the European Working Group on Sarcopenia in Older People (EWGSOP2) with application of cut-off values from the EWGSOP2 paper compared to cut-off values derived from a local cohort (CSS). RESULTS: 19.2% had osteoporosis (66 women and 35 men), whereas 2.7% (6 women and 8 men) and 4.2% (7 women and 15 men) had sarcopenia with application of EWGSOP2 and CSS cut-off values, respectively. Using the EWGSOP2 cut-off values, 1.5% (4 women and 4 men) were diagnosed with osteosarcopenia compared to 1.4% (4 women and 3 men) using CSS cut-off values. In the osteoporosis sub-population, 8% (EWGSOP2) and 7% (CSS) had sarcopenia and within the sarcopenia sub-population, 61.5% (EWGSOP2) and 33.3% (CSS) had osteoporosis. At all sites, BMD was lower among individuals with sarcopenia and sarcopenia increased the risk of osteoporosis (odds ratios: EWGSOP2: 7.3 (p < 0.001) and CSS: 2.2 (ns)). CONCLUSION: Osteosarcopenia was present in 1.5% of a group of healthy home-dwelling older individuals. Notably, individuals with sarcopenia had lower BMD and a higher risk of osteoporosis, whereas the opposite (prevalence of sarcopenia in individuals with osteoporosis) was not as frequent. Our data indicate that screening for sarcopenia and osteoporosis should be performed simultaneously in older individuals at high risk of falls and fractures. However, further studies with outcome-related results are needed to identify optimal measures of osteosarcopenia and cut-off values for sarcopenia.

Vertebral fracture assessment by DXA is inferior to X-ray in clinical severe osteoporosis.

UNLABELLED: Spine fractures are diagnosed by X-ray or vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) scanning. The use of VFA evaluation by DXA is still debated. We demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine and therefore with a reduced diagnostic performance in detecting fractures. INTRODUCTION: Vertebral fracture assessment (VFA) by DXA has been evaluated for many years, and its use in clinical practice is still debated. In a cross-sectional setting, we aimed to compare VFA with traditional radiography in vertebral fracture (VF) diagnosis in severe osteoporotic patient. METHODS: A total of 207 patients referred to the outpatient clinic for teriparatide treatment were screened, out of whom 35 (16.9 %) severe osteoporotic patients were identified (mean age 67.5 ± 11.3 years and median T-score -3.2 interquartile range (IQR) (-1.9 to -3.7). VF diagnosis was performed independently using VFA and X-ray in accordance with the semiquantitative (SQ) approach. The same technician performed the primary interpretation on both sets of images, after which a radiologist and an endocrinologist reviewed the evaluation for a conclusive judgement. RESULTS: In total, 180 radiographic fractures were detected, corresponding to 5.1 fractures per individual. Using VFA, 18.5 % of vertebrae were considered unreadable, compared to 2.0 % on X-ray. The accuracy of VFA in VF detection using X-ray as a reference resulted in sensitivity and specificity of 75.5 and 86.7 %, respectively. Sensitivity decreased from the lumbar to thoracic level. Nevertheless, VFA only identified fractures consistently between Th11 and L3. CONCLUSION: Our data, based on a severe osteoporotic population, demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine, resulting in vertebrae not being assessable for analysis and a reduced diagnostic performance in detecting fractures. Improvements in DXA techniques are needed for it to be comparable with X-ray in VF diagnosis.

Characterization of the radical product formed from the reaction of nitric oxide with the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate.

Previously, 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) has been used in combination with electron paramagnetic resonance (EPR) spectrometry to trap nitric oxide (NO(*)). The reaction between DBNBS and NO(*) yields a radical product which gives rise to an EPR signal consisting of three lines with an A(N) = 0.96 mT, but the structure of this product is unknown. A two-stage high-performance liquid chromatography fractionation was performed to isolate the radical product from the other components in the DBNBS/NO(*) reaction mixture. The fractions containing the radical product were identified by the presence of the three-line EPR signal, and then these fractions were analyzed by negative ion fast atom bombardment-mass spectrometry (FAB-MS). Collectively, the FAB-MS data suggested that the radical product is the monosodium electrostatic complex with the dianion, bis(2,6-dibromo-4-sulfophenyl) nitroxyl. Analysis of the Gaussian and Lorentzian linewidths of the EPR signal suggested that bis(2,6-dibromo-4-sulfophenyl) nitroxyl molecules may group together to form micelles. Further studies also indicated that significant amounts of nitrogen and nitrate were produced during the reaction between DBNBS and NO(*). A reaction scheme consistent with these results is presented.

Simultaneous analysis of nitrite, nitrate and the nicotinamide nucleotides by capillary electrophoresis: application to biochemical studies and human extracellular fluids.

A simple but rapid capillary electrophoresis method was developed for the measurement of nitrite and nitrate in human extracellular fluids and other aqueous solutions. The capabilities of the method were demonstrated by the measurement of endogenous nitrite and nitrate in plasma and serum samples from healthy volunteers, and serum and synovial fluid samples from rheumatoid arthritis patients. Furthermore, this method was used to simultaneously measure nicotinamide adenine dinucleotide, reduced (NADH), nicotinamide adenine dinucleotide (NAD+), nitrite, and nitrate, when studying the nitrite reductase activity of xanthine oxidase. The stability of nitrite was also investigated and it was found that when whole blood was spiked with nitrite and then processed, the nitrite was more stable in the plasma than in the serum. Our findings may help to explain the variations in basal nitrite concentrations reported in the literature.

Nitrite determination in human plasma and synovial fluid using reactions of nitric oxide with 3, 5-dibromo-4-nitrosobenzenesulphonate (DBNBS).

DBNBS (3,5-dibromo-4-nitrosobenzenesulphonate) reacts with nitric oxide (NO) produced from nitrite ions in acid solution to give a radical with a characteristic electron spin resonance spectrum, attributable to a 'DBNBS-NO' product, and comprising a triplet with alphaN=0.96 mT. This is identical with the spectrum obtained when NO, introduced from the gas phase, reacts with DBNBS. Under certain conditions, an additional signal is observed, attributable to oxidation of DBNBS to the radical cation, DBNBS*+ (a triplet with alphaN=1.32 mT). Conditions are described for the determination of nitrite, which avoid this DBNBS oxidation. The height of the low-field signal from the DBNBS-NO product is directly proportional to the nitrite concentration up to about 0.08 mM nitrite. The method has been applied to the measurement of nitrite concentrations in whole blood, plasma and synovial fluid taken from rheumatoid arthritis patients. In order to avoid the oxidation of DBNBS when analysing biological samples of this type, it is necessary to treat the specimen by ultrafiltration as soon as possible after collection and before addition of DBNBS.

Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk.

Outbred NMRI mice were sensitized for high IgE production either by subcutaneous injections of low doses of untreated bovine milk or homogenized bovine milk in combination with intraperitoneal injections of Freund's Complete Adjuvant or by oral administration of untreated or homogenized bovine milk without adjuvant. When analysed in murine passive cutaneous anaphylaxis test both types of milk resulted in production of reaginic antibodies against bovine milk proteins when given subcutaneously. When given orally, homogenized milk resulted in reagin production in 10 out of 14 mice, whereas untreated milk resulted in reagin production in only one out of 12 mice. The sensitized mice, and control mice, were orally challenged with either untreated milk, homogenized milk or 0.9% NaCl. Examination of the intestines 40 min after oral administration revealed that homogenized milk, contrary to untreated milk or 0.9% NaCl, resulted in a large increase in the mass of the proximal gut segment of mice sensitized orally with homogenized milk compared with control mice orally challenged with saline (P less than 0.001), and only mice both sensitized and challenged orally with homogenized milk showed degranulation of mast cells in the intestinal wall. By contrast, subcutaneously sensitized mice or mice sensitized orally with untreated bovine milk showed no significant intestinal reaction upon oral challenge with either homogenized or untreated bovine milk. These observations may indicate that the route of sensitization is of great importance when intestinal reactions are to be studied, and that homogenization of bovine milk may render the milk more aggressive with respect to its ability to induce intestinal reactions. The study indicates that mice may be an attractive experimental animal model for mimicking the intestinal anaphylactic reactions of cow milk-allergic humans.

Reagin production in mice: effect of subcutaneous and oral sensitization with untreated bovine milk and homogenized bovine milk.

Subcutaneous and oral sensitization with untreated bovine milk and homogenized bovine milk in mice was analyzed in two different sensitization schemes--a low dose and a high dose scheme. Homologous murine passive cutaneous anaphylaxis test was used to measure the titres of reagins (IgE and IgG1). Subcutaneous and oral sensitization with low doses of homogenized milk induced production of higher titres of IgE than sensitization with high doses of homogenized milk. By contrast, sensitization with both low and high doses of untreated bovine milk resulted in very low or undetectable IgE titres. The results indicate that homogenization of milk increases the efficacy of inducing IgE production in mice. Some possible implications of these results with respect to clinical allergy are discussed.

Kinetic evaluation of the pool sizes and proliferative response of neutrophils in bacterially challenged aging mice.

Clinical observations during infection suggest that in aged patients, the kinetic or proliferative responses of neutrophils to infection may be deranged. To test this hypothesis, the neutrophil responses of 6-month-old and 30-month-old mice were compared. After intrapulmonary injection of Escherichia coli, young mice exhibited neutrophilia and diminution of the neutrophil storage pool (NSP) by a mean of 6.4 x 10(6) neutrophils/two femurs. This was accompanied by an increase in the pool of CFU-GM from a control value of 1.1 x 10(5) cells/two femurs (range 0.7 to 1.4) to 1.5 x 10(5) (1.1 to 1.9) (P less than .05) and the thymidine suicide (relative proliferative rate) of CFU-GM rose from 27% (19 to 42) to 51% (31 to 61) (P less than .05). Furthermore, the CFU-GM of infected young mice displayed enhanced differentiation to the neutrophil series. In contrast, old mice exhibited a greater mean diminution of the NSP: 12.8 x 10(6) neutrophils. Also, old mice experienced a reduction in CFU-GM from 2.3 x 10(5) (1.0 to 3.9) (controls) to 1.3 x 10(5) (1.2 to 1.5)/two femurs (P less than .05), a reduction in the proliferation of CFU-GM and reduced differentiation of CFU-GM to neutrophils. These experiments establish that the neutrophil response of infected old mice is disordered, with exaggerated depletion of the NSP and lack of stimulus-driven granulocytopoiesis as reflected by a paradoxical reduction in the number and proliferative rate of precursors. This defect may be compounded by decreased differentiation of precursors to neutrophils.