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.

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.

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.

Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone.

Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent. To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted.

Mechanisms of exercise limitation in hypertrophic cardiomyopathy.

To assess the relation of exercise capacity to indexes of systolic and diastolic function in hypertrophic cardiomyopathy, 81 patients underwent two-dimensional echocardiography, technetium-99m equilibrium radionuclide angiography acquired in list mode and maximal, symptom-limited, treadmill exercise testing with measurement of maximal oxygen consumption (VO2 max). VO2 max for the group was 13.9 to 49.3 (mean 25.4) ml/min per kg. Thirty-six patients (44%) achieved less than or equal to 70% of age-predicted VO2 max. Patients with such a degree of limitation were more likely to be in New York Heart Association functional class II or III (23 of 36 vs. 14 of 45; p = 0.005); there was no such relation between VO2 and the incidence and magnitude of rest left ventricular outflow tract pressure gradient greater than 30 mm Hg (11 of 36 vs. 11 of 45; p = NS and 58 +/- 24 vs. 65 +/- 19 mm Hg; p = NS). In the 22 patients with a left ventricular outflow tract gradient, the ratios of peak ejection to peak filling rate and of atrial contribution to left atrial dimension were related to percent of the age-predicted VO2 max (r = 0.49, p = 0.02 and r = 0.54, p less than 0.02). These ratios reflect impaired left ventricular systolic performance and atrial systolic failure, respectively. Stepwise discriminant analysis revealed these two ratios to be the two strongest predictors (p = 0.0001) of patients with a left ventricular outflow tract gradient whose VO2 max was less than or equal to 70% of the age-predicted value (sensitivity 90%, specificity 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in chronic coronary artery occlusion.

OBJECTIVES: This study was conducted to determine the procedural success rate, complication rate and long-term outcome of percutaneous transluminal coronary angioplasty in chronically occluded coronary arteries. BACKGROUND: Coronary angioplasty of chronically occluded vessels has a lower success rate than has angioplasty of nonoccluded vessels, but it is frequently considered safe because the target vessel is already occluded. The purpose of this study was to determine the reliability of these assumptions at our institution, with the objectives stated above. METHODS: We identified from the angioplasty data base at our institution 100 consecutive coronary angioplasty procedures performed between 1987 and 1991 for chronic total occlusion, defined as complete occlusion (Thrombolysis in Myocardial Infarction [TIMI] grades 0 and 1 flow) for > or = 3 months. The records of the 95 patients who underwent these procedures were reviewed to determine procedural outcome and medium-term results. RESULTS: Procedural success was obtained in 47 occluded vessels (47%). Significantly fewer successes were obtained in the right coronary artery (26.8%) than in either the left anterior descending (57.1%) or the left circumflex (45%) coronary artery (p < 0.05). A procedural failure without serious adverse consequences occurred in 45 procedures (45%), but in eight patients (right coronary artery in five, left anterior descending artery in three) attempted recanalization was complicated by extensive coronary dissection with acute myocardial ischemia, and one of these patients died. There were no emergency operations, but elective coronary artery bypass surgery was undertaken in 26 patients (in 3 after extensive dissection, in 7 after an apparently good result and in 16 in whom the procedure failed). At 12 months after the procedure, 64.1% of those with a procedural success were event free compared with 32.6% of those whose procedure was both unsuccessful and uncomplicated (p < 0.025) and 25% of those in whom it was unsuccessful and complicated by coronary dissection (p < 0.025). CONCLUSIONS: In this series of recanalization of chronically occluded coronary arteries, there was a low procedural success rate, particularly for the right coronary artery. However, when procedural success was obtained, the long-term outlook was good. The overall risk of coronary dissection was comparable to the risk in nonoccluded vessels but was particularly high in the right coronary artery (13%).

Early noninvasive identification of failed reperfusion after intravenous thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: This study sought to evaluate a biochemical approach to the early noninvasive assessment of reperfusion. BACKGROUND: In patients with an acute myocardial infarction, a rapid noninvasive method of detecting failure of intravenous thrombolytic therapy to restore early Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery (IRA) is needed. METHODS: Serial blood samples were collected to assay creatine kinase-MB fraction (CKMB mass), cardiac troponin T and myoglobin concentrations in 105 patients with a myocardial infarction who underwent early angiography after intravenous streptokinase. The ratios of the 60- and 90-min concentrations to prethrombolytic values were used to determine an index that could identify failure to achieve TIMI grade 3 flow in the IRA at 90 min. RESULTS: Significant increases in serum concentrations of markers at 60 min were more likely with TIMI grade 3 flow (59 patients) than with TIMI grade 0 to 2 flow (46 patients). Ratios < or = 5 at 60 min after thrombolysis detected failure to achieve 90-min TIMI grade 3 flow with 92% to 97% sensitivity, 43% to 60% specificity and 63% to 76% positive and 86% to 94% negative predictive values. Ratios < or = 10 at 90 min showed 88% to 95% sensitivity, 49% to 65% specificity and 61% to 69% positive and 86% to 94% negative predictive values for TIMI flow grade < 3. The overall predictive values were thus similar for all three markers. CONCLUSIONS: In acute myocardial infarction treated with intravenous streptokinase, a simple measurement of increased serum concentrations of CKMB mass, cardiac troponin T or myoglobin at 60 and 90 min can accurately predict failure to achieve TIMI grade 3 flow in the IRA at 90 min.

Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy.

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Heat production by the human left ventricle: measurement by a thermodilution technique.

STUDY OBJECTIVE - The aim was to study the feasibility of measuring heat production by the human left ventricle with a view to using this variable as an index of left ventricular mechanical efficiency. DESIGN - The transcoronary temperature difference was derived from catheter mounted thermistors placed percutaneously in the aortic root and coronary sinus. Left ventricular blood flow was measured by continuous thermodilution in the coronary sinus, and heat removal by coronary venous blood was calculated from blood flow and the transcoronary temperature difference. Diffusional heat loss was measured using temperature/time curves recorded in aorta and coronary sinus after a bolus injection of cold saline into pulmonary artery. The heat loss from the system into the endothermic reactions of haemoglobin was calculated from left ventricular oxygen extraction using an assumed respiratory quotient. The energy released by left ventricular myocardial metabolism (EEO2, calculated from oxygen extraction), was compared to measured left ventricular heat production, and the mechanical efficiency of the left ventricle was calculated by the formula: Efficiency = (EEO2 - HLV)/EEO2. PATIENTS - Fifteen conscious patients with anginal chest pain were studied at the time of cardiac catherisation and coronary arteriography. MAIN RESULTS - The transcoronary temperature difference was in the range 0.10-0.32 (mean 0.21) degrees C. Total left ventricular heat production, equal to the sum of heat removed by the blood stream, diffusional loss and endothermic reactions (HLV) was in the range 1.5-4.6 (mean 2.7) watts. The values of EEO2 obtained were in the range 2.4-6.5 (mean 4.0) watts, and the calculated mechanical efficiency of the left ventricle was 0.24-0.55 (mean 0.34). CONCLUSIONS - The measurement of heat production by the human left ventricle is safe and practical. This technique promises to be of value in the clinical investigation of the relationship between myocardial function and energy utilisation.

Left ventricular energetics: heat production by the human heart.

OBJECTIVE: The aim was to examine the effect of coronary artery disease on human left ventricular energetics by a comparison of left ventricular oxygen consumption and heat production. The usefulness of measurement of left ventricular heat production for the detection of the expected change in left ventricular energetics produced by atrial pacing to a faster heart rate was also assessed. METHODS: Forty six patients (mean age 57 years; 31 men) undergoing cardiac catheterisation and coronary arteriography for the investigation of chest pain were studied. Normal left ventricular function and normal coronary arteries were present in eight and 38 had atheromatous coronary artery disease. Left ventricular heat production was calculated from coronary blood flow, the coronary arteriovenous (aorta-coronary sinus) temperature difference, and the areas under thermodilution curves recorded in the aorta and coronary sinus after injection of cold saline into the pulmonary artery. Mean external left ventricular power was calculated from mean arterial blood pressure and cardiac output. Left ventricular mechanical efficiency was derived from heat production and the energy value of myocardial oxygen use, assuming aerobic metabolism. In 27 patients studies were repeated during atrial pacing from the coronary sinus. RESULTS: At rest under basal conditions left ventricular heat production was 2.4(SD 1.0) W in patients with normal hearts and 3.1(1.4) W in patients with coronary disease (NS). Mechanical efficiency was 44.2(9.7)% in the normal patients and 30.7(10.9)% in those with coronary disease (p = 0.003). During atrial pacing to a faster heart rate left ventricular energy supply increased from 4.6(2.7) W to 5.9(3.3) W (p < 0.0005), and heat production increased from 3.0(1.6) W to 4.6(2.4) W (p < 0.0005), but mean external power was not altered. As the extra energy used during pacing was "wasted" as heat, there was a significant fall in left ventricular mechanical efficiency with pacing from 33.9(13.5)% to 18.9(15.2)% (p < 0.0005). CONCLUSIONS: These results show the effect of coronary artery disease on the energetics of left ventricular function. They also show that the method and equipment can detect the expected alteration in left ventricular energetics produced by atrial pacing. The measurement of left ventricular heat production and oxygen consumption allows assessment of the total left ventricular energy flux, and may be useful for the evaluation of drug treatment with such as inotropes and vasodilators, and for the investigation of the functional consequences of left ventricular disease.

Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose.

The pharmacokinetics of bupropion (BUP) and its three major basic metabolites (the erythroamino alcohol [EB], the threoamino alcohol [TB], and the hydroxy [HB] metabolites) were characterized after a single, oral, 200 mg dose of BUP in six healthy men. Twenty-one sequential plasma samples for analysis by HPLC were drawn from each subject over the 56-hour period after dosing. Pharmacokinetic analyses were by noncompartmental methods. The mean elimination t1/2 values of BUP, TB, EB, and HB were 9.8, 19.8, 26.8, and 22.2 hours, respectively. The mean plasma AUCs of TB and HB were 2.4 and 10.3 times greater, respectively, than that for BUP. Because of the substantial presence of these metabolites in systemic circulation, further studies are recommended to understand further their roles in the clinical profile of this new antidepressant.

Carbamazepine treatment of a patient with Klüver-Bucy syndrome.

A 20-year-old man developed Klüver-Bucy syndrome with rage attacks following a motor vehicle accident. Several symptoms, including the attacks, responded dramatically to carbamazepine. Carbamazepine may be a useful agent in the treatment of this unusual syndrome.

Bipolar illness following traumatic brain injury: treatment with lithium and carbamazepine.

A case is described of a 22-year-old woman in whom bipolar disorder developed after a traumatic brain injury. Her symptoms initially responded well to lithium carbonate, but she eventually relapsed. Carbamazepine was added to her treatment regimen with good results.

Aggressive behavior in Huntington's disease: treatment with propranolol.

Episodic aggressive behavior that responded poorly to neuroleptics was reduced by a carefully titrated dose of propranolol in three patients with advanced Huntington's disease. The optimal doses were 180, 30, and 30 mg/day, respectively.

Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects.

In a relatively small pilot study, the half-life of elimination of hydromorphone in six subjects was 2.64 +/- 0.88 hours and the drug had a high volume of distribution, 1.22 l./kg. In addition, the drug was rapidly but incompletely absorbed after oral administration. An equation to predict the plasma concentration of hydromorphone on oral administration was developed from the data of these six subjects.

Plasma levels of clobazam after 10-, 20-, and 40-mg tablet doses in healthy subjects.

It is evident that substantial intersubject and intrasubject varition in the bioavailability of clobazam exists following ingestion of 10, 20 and 40 mg doses in these 12 volunteers. Peak concentrations and area under the plasma level-time curve were directly proportional to the dose of clobazam and the mean plasma half-life of clobazam was about 18 hours regardless of dose administered. The t1/2 value was less than that previously reported, as the current results allow differentiation of parent drug from metabolites. This 18 hr t1/2 compares favorably with the half-life of other benzodiazepines.

Plasma levels of clobazam after three oral dosage forms in health subjects.

As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.