Percutaneous coronary revascularization reduces plasma N-terminal pro-B-type natriuretic peptide concentration in stable coronary artery disease.

OBJECTIVES: The purpose of this work was to assess the effect of percutaneous coronary revascularization (PCR) on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. BACKGROUND: Left ventricular (LV) dysfunction is associated with increased plasma natriuretic peptide concentrations. The effect of ischemia resolution on plasma natriuretic peptide is not known. METHODS: Twenty-six patients with stable angina, normal LV systolic function, and isolated stenoses of the left anterior descending (LAD) coronary artery were studied. All patients had angiographically and physiologically significant lesions defined by cine-angiography and intracoronary pressure wire. RESULTS: After revascularization, 24 patients demonstrated significant decrease in mean plasma NT-proBNP 8 weeks after PCR (from 177.2 +/- 190.8 pg/ml to 105.0 +/- 92.4 pg/ml, p = 0.03). The mean decrease in log NT-proBNP was 0.533, corresponding to geometric mean decrease of NT-proBNP by a factor of 59% (95% confidence interval 48.2% to 71.4%, p < 0.00005). Reduction in NT-proBNP was independent of change in LV systolic function. CONCLUSIONS: This study demonstrates that removal of fixed LAD stenosis reduces plasma NT-proBNP concentration. This has implications for interpretation of natriuretic peptide levels in clinical settings and as screening tool for LV systolic dysfunction.     

Hemodynamic correlates of echocardiographic aortic root motion. Observations on normal subjects and patients with idiopathic hypertrophic subaortic stenosis

In ten normal subjects, we observed an initial hump in the aortic root echocardiogram after the onset of the QRS complex, following which a sharp anterior motion was noted. The onset of the anterior motion of the aortic root coincided with the onset of the upstroke of the aortic root pressure pulse and the onset of the velocity signal in five of seven patients with coronary arterial disease; in the other two, the anterior aortic motion followed the onset of the pressure and velocity signal by 10 msec. The aortic root echocardiogram was abnormal in patients with idiopathic hypertrophic subaortic stenosis; the slope (normalized for the scales of time and depth) in early systole was steeper and in the latter part of systole was flatter than normal in these patients. The slope in early diastole was flatter and the slope due to atrial contraction was steeper in the patients with idiopathic hypertrophic subaortic stenosis than in the normal subjects. These features were consistent with rapid ejection in early systole and slow filling in the early phase of ventricular diastole in idiopathic hypertrophic subaortic stenosis. Fourier analysis of the wave form of the aortic root allowed separation between patients with idiopathic hypertrophic subaortic stenosis and normal subjects.     

Selection of women at high risk of breast cancer for initial screening

Selective breast cancer screening refers to the intentional restriction of screening to only a high-risk subgroup of the total population of women at risk. Using data from the Canadian National Breast Screening Study, we explored methods of defining such subgroups. Discriminants were based on risk factor information collected prior to screening and were constructed using a training group of 77 cases and 400 controls. They were then tested on a separate group of 38 cases and 200 controls. Both simple risk factor counts and logistic models were utilized and separate analyses were performed for pre- and post-menopausal women. Using a logistic model, we were able to define a high-risk subgroup encompassing less than 40% of the test controls and over 85% of the test cases. Such a selection strategy, if implemented, might reduce initial visit mammography rates by up to 60% with only a small reduction in case detection. Other uses as determining the optimal age for initiation of screening are also discussed.     

Safety and efficacy of abciximab use in conjunction with intracoronary urokinase in patients requiring angioplasty.

Abciximab decreases ischemic complications during angioplasty. Intracoronary urokinase lyses intracoronary thrombus. We studied the combination of both drugs. Twenty-six consecutive patients with acute coronary syndromes and intracoronary thrombus underwent intervention with abciximab and intracoronary urokinase. All received aspirin and IV heparin. The dose of abciximab was a weight-adjusted bolus and a 12-hr infusion. The dose of urokinase was 250,000 to 633,000 units. Hemorrhagic complications were classified according to the TIMI study group. Hemoglobin and platelet counts were measured before and 12 and 48 hr after the procedure. Procedural success was achieved in 24 patients. There were no deaths or repeat interventions. No patient had a major bleeding complication. Only two had minor complications. One patient needed blood transfusion. None had a stroke or thrombocytopenia. The use of abciximab and intracoronary urokinase in the presence of intracoronary thrombus is associated with encouraging efficacy and few complications. Cathet. Cardiovasc. Intervent. 49:113-116, 2000.     

Sparing effect of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S at physiologic ligand saturations.

Recent interest in therapies for sickle cell anemia based on elevating fetal Hb has made accurate estimates of the sparing effect of fetal Hb (Hb F) and other non-sickle Hbs on sickle Hb (Hb S) polymerization essential. We have developed a technique, using HbCO as surrogate for HbO2, that enables us to assess the solubility of Hb S as a function of ligand saturation under conditions that mimic those of the sickling disorders. Equimolar mixtures of unliganded Hb S with Hb F or normal Hb A2 were isosoluble. Solubilities for equimolar mixtures with normal (Hb A) or abnormal (Hb C) Hbs were also identical but were lower than in the prior case. Thus, the sparing effect of both Hb F and Hb A2 should be considered in therapeutic strategies designed to modify Hb S polymerization. Hemolysates, stripped of 2,3-bisphosphoglycerate, from sickle cell disease patients with Hb (F + A2) levels varying from 6 to 25%, as well as from a sickle trait individual, were used to evaluate equilibrium solubility as a function of ligand saturation over the range of pathophysiologic interest (25-70%). Our results show that the sparing effect of Hb (F + A2) increases relative to that of Hb A as ligand saturation increases, and that in the absence of ligand, approximately 30% Hb (F + A2) is essentially isosoluble with the 60% Hb A of sickle trait. Although detailed knowledge of expected therapeutic benefits is confounded by the heterogeneity of Hb F distribution and other variables, these data should provide a framework for estimating likely clinical benefit from pharmacologic efforts to modulate globin gene expression.     

Impact of a Rapid-Access Ambulatory Psychiatry Encounter on Subsequent Emergency Department Utilization

The authors sought to determine whether providing a rapid-access ambulatory psychiatry encounter correlated with emergency department utilization during a 6-month follow-up period. Electronic medical records of patients who accessed ambulatory psychiatric care through an urgent care psychiatry clinic that offers treatment exclusively on a walk-in basis over a 1-year period (N?=?157) were reviewed retrospectively to track emergency department encounters with and without a psychiatric chief complaint in the 6 months before and after the initial psychiatry evaluation. Among patients who had not previously received ambulatory psychiatric care (N?=?88), emergency department utilization decreased from 0.68 visits per patient to 0.36, and this difference was statistically significant (p?= 0.0147). No statistically significant differences were found between the average number of emergency department encounters in the 6 months before and after the rapid-access ambulatory psychiatry encounter, regardless of chief complaint, when all patients were included in the analysis. Providing a rapid-access ambulatory psychiatry encounter may reduce subsequent emergency department utilization among patients who have not previously received ambulatory psychiatric care.

     

Quantitative PCR analysis of HbF inducers in primary human adult erythroid cells

The development and evaluation of drugs to elevate fetal hemoglobin in the treatment of the genetic diseases of hemoglobin would be facilitated by the availability of reliable cell assays. We have used real-time, quantitative polymerase chain reaction (PCR) analyses of globin messenger RNA (mRNA) levels in a biphasic, erythropoietin-dependent primary culture system for human adult erythroid cells in order to assay compounds for their ability to modulate levels of adult (beta) and fetal (gamma) globin mRNA. Complementary DNA synthesized from total RNA extracted at timed intervals from aliquots of cells were assayed throughout the period that the culture was studied. gamma-globin mRNA levels were found to be much lower (less than 1%) than beta-globin mRNA levels. At concentrations of agents chosen for minimal effect on cell division, we find that the 3 drugs studied, 5-azacytidine (5 micromol/L), hydroxyurea (40 micromol/L), and butyric acid (0.5 mmol/L), significantly increase gamma-globin mRNA levels. Interestingly, hydroxyurea also had a small stimulatory effect on beta-globin mRNA levels, while butyric acid caused a twofold inhibition of beta-globin mRNA levels, and 5-azacytidine had little effect on beta-globin mRNA levels. The net result of all 3 drugs was to increase the gamma/(gamma + beta) mRNA ratios by threefold to fivefold. These data suggest that the mechanism is distinct for each drug. The profile of butyric-acid-induced changes on globin gene expression is also quite distinct from changes produced by trichostatin A, a known histone deacetylase inhibitor. Quantitative PCR analyses of human erythroid cells should prove useful for studying the mechanism(s) of action of known inducers of gamma-globin and identifying new drug candidates.