The utility of a 'non-significant' coronary angiogram.

BACKGROUND: Coronary angiography is the gold standard for assessing coronary artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50% stenosis) is found. It is uncertain whether this 'non-significant' result influences management and outcomes. We reviewed characteristics and outcomes in a contemporary cohort of chest pain referrals who had mild or absent CAD on coronary angiography. METHOD: All patients undergoing coronary angiography at Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983). Of these, 12.3% (n = 366) underwent coronary angiography for evaluation of chest pain and were found to have absent or mild CAD. These patients were followed up for 2.3 ± 0.6 years. RESULTS: Mean age was 60.0 ± 12.3 years, 56.1% were female. The ECG was abnormal in 55.0% of patients. Stress testing for inducible ischaemia was undertaken in 40.7% of patients and was abnormal in 57.7%. Following angiography, 43.2% had no changes to cardiac medications. Additional drug therapy (aspirin, statin, beta-blockers, ACE-inhibitor) was commenced in around 14.2-22.1% of cases. These drugs were discontinued in 4.1-8.2% of patients. Rates of major adverse cardiovascular events and readmissions with chest pain were 0.3% (1) and 1.9% (7) respectively at 30 days, and 1.9% (7) and 6.0% (22) at 1 year. CONCLUSION: Although even non-obstructive atheroma may justify medical therapy to limit disease progression, our findings may suggest that in these cases, invasive coronary angiography, may not lead to the patient/physician reassurance justified by historical data.

Evolution of the normal state of a strongly interacting Fermi gas from a pseudogap phase to a molecular Bose gas.

Wave-vector resolved radio frequency spectroscopy data for an ultracold trapped Fermi gas are reported for several couplings at T(c), and extensively analyzed in terms of a pairing-fluctuation theory. We map the evolution of a strongly interacting Fermi gas from the pseudogap phase into a fully gapped molecular Bose gas as a function of the interaction strength, which is marked by a rapid disappearance of a remnant Fermi surface in the single-particle dispersion. We also show that our theory of a pseudogap phase is consistent with a recent experimental observation as well as with quantum Monte Carlo data of thermodynamic quantities of a unitary Fermi gas above T(c).

Verification of universal relations in a strongly interacting Fermi gas.

Many-body fermion systems are important in many branches of physics, including condensed matter, nuclear, and now cold atom physics. In many cases, the interactions between fermions can be approximated by a contact interaction. A recent theoretical advance in the study of these systems is the derivation of a number of exact universal relations that are predicted to be valid for all interaction strengths, temperatures, and spin compositions. These equations, referred to as the Tan relations, relate a microscopic quantity, namely, the amplitude of the high-momentum tail of the fermion momentum distribution, to the thermodynamics of the many-body system. In this work, we provide experimental verification of the Tan relations in a strongly interacting gas of fermionic atoms by measuring both the microscopic and macroscopic quantities in the same system.

Comparison of coronal bacterial leakage between immediate versus delayed post-space preparation in root canals filled with Resilon/Epiphany.

AIM: To compare the sealing ability of Resilon/Epiphany after immediate versus delayed post-space preparation using an ex vivo bacterial leakage model. METHODOLOGY: Eighty extracted, decoronated, single-rooted human maxillary teeth were randomly divided into two experimental groups and two control groups (n = 20). Root canals were prepared in a standard manner with Sequence nickel-titanium rotary files to a final apical size of 50, .06 taper. Root canals in the experimental groups were filled with Resilon/Epiphany using a warm vertical compaction technique. In group 1, the post-space was prepared immediately and in group 2 the post-space was prepared 5 days later. Positive controls were filled with Resilon master cones without sealer. The negative controls were not obturated but the entire root surface including the orifices and foramina were sealed with fingernail polish. Leakage was examined at different time intervals using a dual-chamber bacterial microleakage model. The marker microorganism used was Streptococcus mutans. RESULTS: All positive controls leaked within 3 days. All negative controls showed no leakage at each time interval. All experimental specimens leaked within 14 days. Statistical analysis showed that there was no difference in microleakage between the two experimental groups at each time interval. CONCLUSION: In this ex vivo study, there was no significant difference between immediate and delayed post-space preparation using Resilon/Epiphany. Both groups failed to provide an adequate apical seal regardless of the timing of the post-space preparation.

Using photoemission spectroscopy to probe a strongly interacting Fermi gas.

Ultracold atomic gases provide model systems in which to study many-body quantum physics. Recent experiments using Fermi gases have demonstrated a phase transition to a superfluid state with strong interparticle interactions. This system provides a realization of the 'BCS-BEC crossover' connecting the physics of Bardeen-Cooper-Schrieffer (BCS) superconductivity with that of Bose-Einstein condensates (BECs). Although many aspects of this system have been investigated, it has not yet been possible to measure the single-particle excitation spectrum (a fundamental property directly predicted by many-body theories). Here we use photoemission spectroscopy to directly probe the elementary excitations and energy dispersion in a strongly interacting Fermi gas of (40)K atoms. In the experiments, a radio-frequency photon ejects an atom from the strongly interacting system by means of a spin-flip transition to a weakly interacting state. We measure the occupied density of single-particle states at the cusp of the BCS-BEC crossover and on the BEC side of the crossover, and compare these results to that for a nearly ideal Fermi gas. We show that, near the critical temperature, the single-particle spectral function is dramatically altered in a way that is consistent with a large pairing gap. Our results probe the many-body physics in a way that could be compared to data for the high-transition-temperature superconductors. As in photoemission spectroscopy for electronic materials, our measurement technique for ultracold atomic gases directly probes low-energy excitations and thus can reveal excitation gaps and/or pseudogaps. Furthermore, this technique can provide an analogue of angle-resolved photoemission spectroscopy for probing anisotropic systems, such as atoms in optical lattice potentials.

p-Wave Feshbach molecules.

We have produced and detected molecules using a p-wave Feshbach resonance between 40K atoms. We have measured the binding energy and lifetime for these molecules and we find that the binding energy scales approximately linearly with the magnetic field near the resonance. The lifetime of bound p-wave molecules is measured to be 1.0+/-0.1 ms and 2.3+/-0.2 ms for the ml=+/-1 and ml=0 angular momentum projections, respectively. At magnetic fields above the resonance, we detect quasibound molecules whose lifetime is set by the tunneling rate through the centrifugal barrier.

Potential energy of a 40K Fermi gas in the BCS-BEC crossover.

We present a measurement of the potential energy of an ultracold trapped gas of 40K atoms in the BCS-BEC crossover and investigate the temperature dependence of this energy at a wide Feshbach resonance, where the gas is in the unitarity limit. In particular, we study the ratio of the potential energy in the region of the unitarity limit to that of a noninteracting gas, and in the T=0 limit we extract the universal many-body parameter beta. We find beta=-0.54_{-0.12};{+0.05}; this value is consistent with previous measurements using 6Li atoms and also with recent theory and Monte Carlo calculations. This result demonstrates the universality of ultracold Fermi gases in the strongly interacting regime.

Probing pair-correlated fermionic atoms through correlations in atom shot noise.

Pair-correlated fermionic atoms are created through dissociation of weakly bound molecules near a magnetic-field Feshbach resonance. We show that correlations between atoms in different spin states can be detected using the atom shot noise in absorption images. Furthermore, using time-of-flight imaging we have observed atom pair correlations in momentum space.

Assay for the simultaneous determination of acetaminophen-caffeine-butalbital in human serum using a monolithic column.

A fast and sensitive high performance liquid chromatography (HPLC) assay was developed on a C18 monolithic column for the simultaneous determination of acetaminophen-caffeine-butalbital in human serum. Serum samples were treated with a solid phase extraction procedure. The analytes were separated using a mobile phase of 95:5 (v/v) 0.1M potassium phosphate monobasic (pH 2.41)-acetonitrile on the C18 monolithic column with detection at 220 nm. Benzoic acid was used as the internal standard (IS). The method was validated over the range of 1.25-100 microg/ml for each drug and found to be linear (r > 0.995, n = 12) with RSD less than 8.3%. The method proved to be accurate (percent bias for all calibration samples varied from -14.6 to -1.3%) and precise (ranged from 2.9 to 13.4%). The mean percent absolute recoveries from serum were 89.7 +/- 3.6 for acetaminophen, 95.5 +/- 4.5 for caffeine, 99 +/- 5.2 for butalbital and 83.4 +/- 3.9% for the internal standard.

Determination of degradation products of sumatriptan succinate using LC-MS and LC-MS-MS.

Acid, base, heat, oxidation and UV irradiation stress methods were applied to study the stability of the bulk drug form of sumatriptan succinate. Liquid chromatography coupled with mass spectrometry (LC-MS and LC-MS-MS) was used to analyze the degraded samples and tentative structural identifications were assigned based upon known reactivity of the drug, molecular weight measurements and MS-MS fragmentation patterns. Sumatriptan succinate was found to be stable to exposure of acid, base, oxidation and UV irradiation at ambient conditions, but was found to degrade under acidic, basic and oxidative conditions when heated to 90 degrees C.

Determination of gatifloxacin in human plasma by liquid chromatography/electrospray tandem mass spectrometry.

Gatifloxacin is an advanced-generation, 8-methoxyfluoroquinolone that is active against a broad spectrum of pathogens, including antiobiotic resistant Streptococcus pneumoniae. Development of a rapid, sensitive and selective method for the determination of gatifloxacin in human plasma is essential for understanding the pharmacokinetics of the drug when administered orally or intravenously. Solid phase extraction (SPE) using Oasis HLB was used to extract gatifloxacin and the internal standard ciprofloxacin from plasma. A method based on liquid chromatography/electrospray tandem mass spectrometry (LC/ESI-MS/MS) was developed and validated to quantitate gatifloxacin in human plasma. The precursor and major product ions of the analyte were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Mechanisms for the formation of collision-induced dissociation products of gatifloxacin are proposed. Linear calibration curves were generated from 10--1000 ng/mL with coefficients of determination greater than 0.99. The interday and intraday precision (%RSD) was less than 6.0% and accuracy (%error) was less than 5.4% for gatifloxacin. The limit of detection (LOD) for the method was 500 pg/mL based on a signal-to-noise ratio of 3.

Stability and dissolution of lozenge and emulsion formulations of metronidazole benzoate.

Chicken flavored glycerinated gelatin candy-based lozenges and oil-in-water emulsions of metronidazole benzoate were prepared for veterinary use. The stability and dissolution of the lozenges and emulsions were investigated via a high-pressure (performance) liquid chromatography (HPLC) assay. The separation and quantitation of metronidazole benzoate were achieved on a Phenomenex IB-SIL 5 C8 column (250 x 4.6 mm,id) at ambient temperature, with a 55:45 v/v pH 7.0 phosphate buffer-acetonitrile mobile phase at a flow rate of 1.0 mL/min. Tinidazole was used as the internal standard. A sample of metronidazole benzoate form the lozenge and emulsion was prepared for assay by dissolving one lozenge or 1g of the emulsion in 50:50 v/v methanol-water solution, and that sample was filtered through a 0.2 micrometer membrane filter before assay. The chromatogram was monitored with ultraviolet detection at 230 nm. The HPLC separation of metronidazole benzoate was achieved in less than 10 minutes; sensitivity was in the rage of 10 ng/mL. This method can be used to separate metronidazole and benzoic acid, which are degradation products of metronidazole benzoate, and demonstrated linearity for metronidazole benzoate in the range of 0.01 to 100 micrograms/mL. Accuracy and precision were less than 1.0% and less than 0.54%, repectively. The limit of quantitation was 10 ng/mL, and the limit of detection was 0.01 ng/mL, based on a signal-to-noise ratio of 3 and a 20 microliter injection. The recoveries of metronidazole benzoate from the lozenge and emulsion were 98% +/- 4% and 99% +/- 2%, respectively. Stability testing of the new formulations was performed at ambient temperature and at 4 deg C. Dissolution testing used the USP paddle method at 37 deg C and 100 rpm in simulated gastric fluid without pepsin. Both formulations were stable at ambient temperature and at 4 deg C. Metronidazole benzoate is completely released from the lozenge and emulsion formulations based on dissolution T50% values of 4.2 and 24 minutes and T90% values of 12.8 and 83 minutes, repectively.

Stability of Ephedrine Sulfate at Ambient Temperature and 4 deg C in Polypropylene Syringes.

The stability of 5 mg/mL ephedrine sulfate in 0.9% sodium chloride in 10-mL polypropylene syringes stored at ambient temperature and at 4 deg C for up to 60 days was investigated. Concentration levels of ephedrine sulfate were determined by means of a high-performance liquid chromatography stability-indicating assay at 0, 1, 4, 7, 14, 30, 45 and 60 days after preparation of the syringes. Benzyl alcohol, which was added as a preservative, did not interfere with the assay. The injections in polypropylene syringes were stable for up to 60 days at both ambient temperature and at 4 deg C. The pH of the ephedrine sulfate injections did not change appreciably in a particular direction during the 60-day study period. These data support the stability of ephedrine sulfate under the storage conditions investigated in this study.

Determination of ondansetron and its hydroxy metabolites in human serum using solid-phase extraction and liquid chromatography/positive ion electrospray tandem mass spectrometry.

Ondansetron and its hydroxylated metabolites were determined in human serum using solid-phase extraction (SPE) and liquid chromatography/positive ion electrospray tandem mass spectrometry. Pyrimethamine was used as the internal standard. The analytes were eluted from the SPE cartridge using 2 x 1 ml of methanol containing 0.5% triethylamine, evaporated under vacuum and the residue was reconstituted in the mobile phase. The liquid chromatographic separation was achieved on a silica column using a mobile phase of aqueous 20 mM ammonium acetate (pH 4.7)-acetonitrile (85 : 15, v/v) at a flow-rate of 0.4 ml min(-1). The method was linear over the range 1-500 ng ml(-1) for ondansetron and each of the metabolites in human serum. The intra-day accuracy was better than 9.1% and the precision was <10.3%; the inter-day accuracy was better than 9.5% and the precision was <12.6%. The limit of detection was 250 pg ml(-1) based on a signal-to-noise ratio of 3. The absolute recovery from serum for all analytes was >90%.

Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry.

Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synthase (NOS) and is important in the regulation of vascular tone, neurotransmission and host defense. N,N-Dimethyl L-arginine (asymmetric dimethylarginine, ADMA) and N-monomethyl L-arginine (MMA) are endogenous inhibitors of NOS. N,N'-Dimethyl L-arginine (symmetric dimethylarginine, SDMA), the inactive enantiomer of ADMA is also known to be present endogenously. A simple, sensitive and fast LC-MS-MS method was developed to extract and quantitate ADMA, SDMA, MMA and ARG from human plasma. 13C6-ARG was used as the internal standard for the assay. Protein precipitation using acetonitrile gave good recoveries of all the compounds from plasma. The compounds were separated by HPLC in less than 15 min using a silica column. The limits of detection for this method were found to be approximately 1 ng/ml for ARG, ADMA and SDMA and 2.5 ng/ml for MMA. The total LC-MS-MS analysis time is less than 15 min making this the fastest and most specific method reported to date. The use of an isocratic liquid chromatographic separation makes this method optimal for high sample throughput. The inter- and intra-day precision (% RSD) and accuracy (% error) for this assay were less than 15%. The average concentrations of ARG, ADMA, SDMA and MMA in plasma from 20 human subjects were found to be 10.9+/-4.1 microg/ml, 25.1+/-9.4 ng/ml, 33.2+/-13.1 ng/ml and 19.6+/-3.8 ng/ml, respectively.

HPLC determination of guaifenesin with selected medications on underivatized silica with an aqueous-organic mobile phase.

A high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin pseudoephedrine-dextromethorphan and guaifenesin-pseudoephedrine in commercially available capsule dosage forms and guaifenesin-codeine in a commercial cough syrup dosage form. The separation and quantitation are achieved on a 25-cm underivatized silica column using a mobile phase of 60:40%) v/v 6.25 mM phosphate buffer, pH 3.0 - acetonitrile at a flow rate of 1 ml min(-1) with detection of all analytes at 216 nm. The separation is achieved within 10 min for each drug mixture. The method showed linearity for the guaifenesin-pseudoephedrine-dextromethorphan mixture in the 50-200, 7.5-30 and 2.5-10, microg ml(-1) ranges, respectively. The intra- and inter-day RSDs ranged from 0.23 to 4.20%, 0.18 to 2.85%, and 0.13 to 5.04% for guaifenesin, pseudoephedrine, and dextromethorphan, respectively. The guaifenesin pseudoephedrine mixture yielded linear ranges of 25-100 and 3.75-15 microg ml(-1) and intra- and inter-day RSDs ranged from 0.65 to 4.18% and 0.23 to 3.00% for guaifenesin and pseudoephedrine, respectively. The method showed linearity for the guaifenesin-codeine mixture in the 25-100 and 2.5-10 microg ml(-1) ranges and RSDs ranged from 0.37 to 4.25% and 0.14 to 2.08% for guaifenesin and codeine, respectively.