Young Accreting Compact Objects in M31: The Combined Power of NuSTAR, Chandra, and Hubble.

We present 15 high-mass X-ray binary (HMXB) candidates in the disk of M31 for which we are able to infer compact object type, spectral type of the donor star, and age using multiwavelength observations from NuSTAR, Chandra, and the Hubble Space Telescope. The hard X-ray colors and luminosities from NuSTAR permit the tentative classification of accreting X-ray binary systems by compact object type, distinguishing black hole from neutron star systems. We find hard-state black holes, pulsars, and non-magnetized neutron stars associated with optical point-source counterparts with similar frequency. We also find nine non-magnetized neutron stars coincident with globular clusters and an equal number of pulsars with and without point-source optical counterparts. We perform spectral energy distribution (SED) fitting for the most likely optical counterparts to the HMXB candidates, finding seven likely high-mass stars and one possible red helium-burning star. The remaining seven HMXB optical counterparts have poor SED fits, so their companion stars remain unclassified. Using published star formation histories, we find that the majority of HMXB candidates-X-ray sources with UV-bright point-source optical counterpart candidates-are found in regions with star formation bursts less than 50 Myr ago, and three are associated with young stellar ages (<10Myr). This is consistent with similar studies of HMXB populations in the Magellanic Clouds, M33, NGC 300, and NGC 2403.

Reinfarction after thrombolytic therapy for acute myocardial infarction followed by conservative management: incidence and effect of smoking.

A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infarction associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months. Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator (rt-PA) to 141 patients. Reinfarction rate and risk factors for reinfarction were assessed. Management after thrombolysis was conservative; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis. Coronary artery surgery or angioplasty was performed in only 3.7% of patients during the first 30 days after thrombolysis and in only 8.6% by 1 year. Most patients (79%) underwent coronary arteriography. Twenty-six patients (5.7%) exhibited signs of threatened reinfarction at 1 month after thrombolytic therapy as did 43 patients (9.4%) by 1 year. Reinfarction was prevented in four of these patients by early readministration of thrombolytic therapy. Multivariate analysis of possible risk factors for reinfarction identified at the time of initial infarction showed current cigarette smoking to be the only predictive factor (reinfarction occurred in 12.5% of smokers versus 6.3% of nonsmokers, p = 0.04). A second analysis of risk factors identified 3 weeks after initial infarction, including the severity of residual stenosis at coronary arteriography and exercise test variables, again showed continued cigarette smoking to be the only factor predictive of reinfarction. Twenty percent of patients who continued to smoke developed reinfarction compared with 5.1% of those who stopped (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.

OBJECTIVES: This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction. BACKGROUND: Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown. METHODS: To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later. RESULTS: At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo). CONCLUSIONS: Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.

Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow.

OBJECTIVES: To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal. BACKGROUND: The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described. METHODS: A total of 493 patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/-0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow. RESULTS: There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts > 27 had fewer hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p=0.036). CONCLUSIONS: Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.

Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location.

Alpha-interferon (alpha-IFN) therapy is an effective agent in early chronic phase (ECP) chronic myeloid leukemia (CML), achieving hematologic control in the majority and major cytogenetic response (MCR) (reduction in Ph' +ve metaphases to < 35%) in a substantial minority. Currently no pretreatment markers exist to ascertain likelihood of meaningful response. The site of breakpoint in M-bcr and relationship to prognosis is controversial. Studies have been hampered by variation in definition of breakpoint and difference in treatment protocols. In this study of ECP CML patients, Southern analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to determine breakpoint location. Patients received alpha-IFN (9 x 10(6) units/day) and dose-adjusted hydroxyurea (HU) to maintain granulocyte count between 1.0-2.0 x 10(9)/l for 6 months or more. Twelve of 31 patients entered on the study achieved a MCR. The Sokal index did not predict for cytogenetic response to alpha-IFN. Eight of 11 patients with 5' breakpoint achieved MCR compared to only four of 20 patients with 3' breakpoint (P = 0.007). These results suggest site of M-bcr rearrangement may be predictive of response to alpha-IFN therapy. If verified by further study, this may allow more appropriate use of alpha-IFN with respect to other modalities such as allogeneic transplant.

Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and stenosis severity.

Because 24% to 30% of patent infarct-related arteries occlude in the year following thrombolytic therapy for acute myocardial infarction, angiographic factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame count which may predict abnormal infarct-artery flow, require definition. We examined changes in coronary flow and infarct-artery lesion severity by computerized quantitative angiography over 1 year in 154 patients with a patent infarct-related artery 4 weeks after myocardial infarction. These patients were randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg dipyridamole, or placebo. All angiograms were interpreted blind in our core angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year, respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame count and stenosis severity were predictive of late abnormal infarct-artery flow (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks was highly correlated with infarct-artery flow at 1 year.

Association of angiographically detected coronary artery disease with low levels of high-density lipoprotein cholesterol and systemic hypertension.

The prevalence of risk factors for atherosclerosis in 488 consecutive patients undergoing cardiac catheterization for the investigation of chest pain was compared with that in 868 subjects from a population sample. The presence and severity of angiographic coronary artery disease (CAD) (defined as mean diameter stenosis > 50%), total and high-density lipoprotein (HDL) cholesterol, triglycerides, history of systemic hypertension, smoking, diabetes mellitus, family history and drug therapy were assessed. Low HDL cholesterol (< 0.9 mmol/liter [35 mg/dl]) was more prevalent in patients with CAD than in the population sample in both men (44% [95% confidence interval 38 to 48] vs 21% [12 to 28]; p < 0.01) and women (12% [9 to 15] vs 1% [0 to 3]; p < 0.01). There were no differences in total cholesterol levels between these 2 groups. Total:HDL cholesterol ratios were significantly greater in patients with CAD. History of systemic hypertension was more prevalent in both men and women with CAD than in the population sample (47% [37 to 57] vs 20% [16 to 25] for men, and 31% [26 to 36] vs 21% [17 to 26] for women; p < 0.01). The prevalence of other risk factors was not significantly different between the 2 groups. In patients with CAD, the severity of disease was inversely correlated with levels of HDL cholesterol in both men and women (p < 0.01), and positively correlated with total cholesterol in men aged < 55 years (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of needle gauge in Mantoux skin testing.

STUDY OBJECTIVE: To determine the influence of needle gauge in Mantoux skin testing for tuberculosis. DESIGN: Randomized selection of either a 27- or 30-gauge needle for Mantoux skin test placement; observer-blinded. SETTING: Annual hospital employee screening. PARTICIPANTS: Six hundred twenty-five employees working in clinical and laboratory research environments. RESULTS: Blinded observers found that the use of 27-gauge needles caused increased bleeding and bruising compared with 30-gauge needles (p < or = 0.007 for each). However, the 27-gauge needle produced larger blebs and less leakage of tuberculin solution (p < or = 0.0003). CONCLUSION: Smaller gauge needles could potentially cause false-negative screening results because of decreased antigen delivery. Use of needle gauges smaller than 27 gauge should be avoided until their reliability is validated.

Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction.

OBJECTIVE: To assess whether the 90 minute corrected thrombolysis in myocardial infarction frame count (CTFC) in the infarct related artery predicts left ventricular function at 48 hours in patients with myocardial infarction treated with aspirin, streptokinase, and either heparin or Hirulog. DESIGN AND SETTING: Analysis of 251 patients with acute myocardial infarction enrolled in the international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial, who underwent both 90 minute coronary angiography and 48 hour left ventriculography. MAIN OUTCOME VARIABLES: The CTFC was determined in the infarct related artery 90 minutes after starting intravenous streptokinase (1.5 x 106 U over 30 to 60 minutes), and compared with indices of left ventricular function assessed by contrast ventriculography at 48 hours. RESULTS: A CTFC of 2 SD below normal (37% v 51%, p = 0.005), and trends towards higher left ventricular ejection fractions (60.9% v 58.2%, p = 0.11) and lower end systolic volumes (50.1 ml v 55.9 ml, p = 0.23). A CTFC of 2 SD below normal (41% v 52%, p = 0.025), a smaller end systolic volume (49.1 ml v 59.3 ml, p = 0.02), and a higher left ventricular ejection fraction (60.4% v 56.5%, p = 0.03). CONCLUSIONS: The 90 minute CTFC predicts left ventricular function at 48 hours following streptokinase. The CTFC associated with better ventricular function may be higher than values determined from a non-infarct population.

Use of creatine kinase isoforms for diagnosis of infarct artery patency after thrombolytic therapy with streptokinase.

BACKGROUND: We investigated whether the proportion of creatine kinase (CK) MM3 to total MM isoform, measured in a single blood specimen taken at 3 hours after starting intravenous administration of streptokinase to patients with developing myocardial infarction, would give reliable information on patency or occlusion of the infarct-related coronary artery. METHODS: Fifty-nine patients received streptokinase 1.5 x 10(6) U intravenously within 6 hours of onset of prolonged chest pain and ST-segment elevation. Patency of the infarct-related coronary artery was assessed by arteriography at 2.6 +/- 0.3 (SD) hours after starting streptokinase. Creatine kinase MM isoforms were measured by chromatofocusing in blood taken at 3 hours after streptokinase. RESULTS: A proportion of CKMM3 to total CKMM of greater than 50% was present in 34 of 34 patients (100%) with a patent, infarct-related artery at arteriography and whose peak total CK activity reached twice the upper normal limit for our laboratory (600 U/L). CKMM3/total CKMM was less than 50% in 14 of 18 patients (78%) in whom the infarct-related artery was occluded. In five of six patients with a nondiagnostic total CK rise (peak < 600 U/L), 3-hour CKMM3/total CKMM was less than 50% despite a patent artery. CKMM3 was not measurable in one patient. CONCLUSIONS: A proportion of CKMM3/total CKMM of greater than 50% is highly sensitive for prediction of infarct artery patency at 3 hours after administration of streptokinase. However, the test used in this way is not reliable for patients with "prevented" myocardial infarction. Also, positive tests do occur in patients with angiographically occluded arteries, possibly signifying intermittent reperfusion and occlusion.

Clinical trial of a low-fluoride toothpaste for young children.

In this double-blind trial, the anticaries effectiveness of a test toothpaste formulated for young children with 550 ppm F was compared with that of a positive control toothpaste containing 1055 ppm fluoride. More than 3000 2-year-old children were enrolled in the study and after 3 years of toothpaste use, 2177 (72 per cent) were examined. From a clinical and radiographic assessment, more than half the children were found to be caries free and only 32 (1.5 per cent) had evidence of rampant caries. There appeared to be little or no difference between children who had used test or control pastes, either in caries or in plaque levels. On the basis of this clinical trial the experimental toothpaste with 550 ppm fluoride would appear to have a similar anticaries efficacy to that of the control toothpaste. Differences were seen in relation to sex of the child and to social class. Girls had lower levels of plaque than boys but more carious teeth. Children from families in higher social classes had fewer carious teeth and lower levels of plaque.

Streptokinase and lifestyle outcome in survivors of myocardial infarction.

Clinical and lifestyle parameters were assessed in 145 patients who were randomised in a double blind study comparing streptokinase or placebo given within four hours of the onset of ischaemic chest pain. Sixty-six percent of patients were in paid employment at the time of their infarct and 79% returned to paid employment. Patients who received streptokinase returned to work 17 days earlier (p less than 0.05) and returned to sport and leisure activities 33 days earlier (p less than 0.05) than those who received placebo. Those who had received streptokinase also tended to leave hospital earlier (0.8 days, p = 0.07). There were no differences in angioplasty or coronary surgery rates or the incidence of reinfarction in the first year (8%). Total community costs were reduced in the patients who received thrombolytic therapy. These findings have important implications in the benefit:cost analysis of thrombolytic therapy.

Comparison of aspirin with a thromboxane antagonist for patients with prolonged chest pain and ST segment depression.

AIM: To compare a thromboxane antagonist (GR3219) with aspirin in patients with prolonged chest pain and ST segment depression to see if the frequency of attacks of chest pain was reduced. METHODS: The trial was part of a study comparing GR3219 with aspirin, and streptokinase with placebo and comprised the GR3219/aspirin leg. Thirty one patients were randomly assigned to GR3219 80 mg twice daily and 28 to aspirin 300 mg daily. The patients were under the age of 76 and admitted to a coronary care unit within 6 hours of continuous chest pain. The ECG showed at least 1 mm of flat or down-going ST segment. The patients kept diaries of their pain over the subsequent 31 days. RESULTS: Seventy percent of patients developed further chest pain. There was no difference between the pattern of recurrent chest pain according to which drug was used. CONCLUSIONS: The hypothesis that specific thromboxane A blockade with GR3219 would be more efficacious than aspirin was not supported by these results.

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN: Cohort follow up study. SETTING: The four coronary care units in Auckland, New Zealand. SUBJECTS: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.

Efficacy of intravascular catheter lock solutions containing preservatives in the prevention of microbial colonization.

There is little published evidence regarding whether heparin lock solutions containing preservatives prevent catheter-related infections. However, adverse effects from preservative-containing flushes have been documented in neonates, leading many hospitals to avoid their use altogether. Infection control records from 1982 to 2008 at St. Jude Children's Research Hospital (SJCRH) were reviewed regarding the incidence of catheter-related infections and the use of preservative-containing intravenous locks. In addition, the antimicrobial activities of heparin lock solution containing the preservatives parabens (0.165%) or benzyl alcohol (0.9%), and 70% ethanol were examined against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa and Candida albicans, and compared with preservative-free saline with and without heparin. Growth was assessed after exposure to test solutions for 0, 2, 4 and 24h at 35 °C. The activities of preservatives were assessed against both planktonic (free-floating) and sessile (biofilm-embedded) micro-organisms using the MBEC Assay. Infection control records revealed two periods of increased catheter-related infections, corresponding with two intervals when preservative-free heparin was used at SJCRH. Heparin solution containing preservatives demonstrated significant antimicrobial activity against both planktonic and sessile forms of all six microbial species. Ethanol demonstrated the greatest antimicrobial activity, especially following short incubation periods. Heparin lock solutions containing the preservatives parabens or benzyl alcohol, and 70% ethanol demonstrated significant antimicrobial activity against both planktonic and sessile micro-organisms commonly responsible for catheter-related infections. These findings, together with the authors' historical infection control experience, support the use of preservatives in intravenous lock solutions to reduce catheter related infections in patients beyond the neonatal period.