Early autologous and allogeneic peripheral blood stem cell transplantation for adult patients with acute B and T cell precursor neoplasms: a 12-year single center experience.

Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.

Bone marrow may be the preferable graft source in recipients homozygous for HLA-C group 2 ligands for inhibitory killer Ig-like receptors.

HLA class I molecules participate in natural killer cell regulation by acting as ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may express one or more inhibitory KIR lacking the corresponding HLA ligand. The role of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains controversial and depends on incompletely defined transplant variables. We have retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264 PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59; P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68; P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4 favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger studies are required to reassess whether BMT should be preferred to PBSCT as an option for C2/C2 recipients.

Granzymes A and B serum levels in allo-SCT.

Activated cytotoxic T lymphocytes and natural killer cells, which are involved in the pathogenesis of GVHD and viral infections after SCT produce granzymes (Grs). This study performed an ELISA in the serum of 86 patients at various time points before and after Allo-SCT to investigate GrA and GrB levels as potential markers for these serious complications. The increase in Gr levels from the day of transplantation until the appearance of the complication was highly predictive. If GrA increased to three times its pretransplant level, the cumulative incidence of developing acute GVHD was 73% and for CMV infection 68%, in comparison with 45 and 35%, respectively, for patients without these complications. A strong increase in GrA level correlated with clinical severity of acute GVHD. No correlation was observed with early relapse or long-term overall survival. In addition to clinical parameters, a strong increase in GrA levels was identified as an independent marker for the occurrence of acute GVHD as well as for CMV infection. Similar effects were observed with GrB. In conclusion, Gr protein levels can also be used as a marker for complications after Allo-SCT.

T-cell precursor frequencies and long-term outcome following unrelated hematopoietic stem cell transplantation.

Functional assays measuring alloreactivity of donor cells are desired to detect either cryptic epitopes inducing graft-vs.-host disease (GvHD) after human leukocyte antigen (HLA)-identical hematopoietic stem cell transplantation (HSCT) or permissible HLA mismatches. However, their value in predicting GvHD and survival is still limited. We determined the cytotoxic and helper T-cell precursor (CTLp and HTLp) frequencies by limiting dilution analysis (LDA) in 40 unrelated recipient/donor combinations. The median observation period at the time of this writing was 4.44 years (range from 0.1 to 11.28). Better overall survival was observed in patients with rather low host-specific CTLp and HTLp frequencies, whereas a trend toward high CTLp frequencies was seen in patients with higher incidence of acute GvHD, especially in patients mismatched in HLA-C. CTLp and HTLp frequencies did not correlate with the incidence of chronic GvHD and relapse. In conclusion, we detected a trend toward better overall survival of patient/donor pairs with low CTLp and HTLp frequencies, however, recommend to use LDA as an additional tool for identifying the most suitable donor when more than one fully HLA-matched stem cell donor is available.

Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation.

To define the role of quantitative graft composition and donor killer-cell immunoglobulin-like receptor (KIR) genotype in clinical outcome following unmanipulated peripheral blood stem cell transplantation (PBSCT) from human leucocyte antigen (HLA)-identical siblings, 43 consecutive transplants for haematological malignancies were analysed retrospectively. Twenty-four patients underwent myeloablative conditioning and 19 received busulphan/fludarabine-based reduced intensity conditioning (RIC). In patients with acute myelogenous leukaemia or myelodysplastic syndrome (AML/MDS; n = 18), no relapse occurred following transplants meeting both a high (above median) natural killer (NK) cell count and missing HLA-ligand(s) to donor's KIR(s), compared to all other AML/MDS patients (0% versus 44%; P = 0.049). Missing HLA-B and/or HLA-C ligand combined with missing HLA-A3/11 (KIR3DL2 unblocked) predicted for reduced relapse incidence regardless of diagnosis or conditioning type (P = 0.028). Moreover, in AML/MDS patients, this constellation predicted superior overall survival (OS) (P = 0.046). Transplants with more than two different activating donor KIRs were associated with an increased risk for non-relapse mortality (NRM), both by univariate and multivariate analysis. Quantitative graft composition had a significant impact exclusively in RIC transplants. Here, a trend towards reduced relapse incidence was found in patients receiving high numbers of NK cells (16% versus 54%; P = 0.09). In patients receiving high versus low T cell numbers, OS was superior (83% versus 37%; P = 0.01), due mainly to reduced NRM (0% versus 33%; P = 0.046). By multivariate analysis, relapse risk was decreased significantly in patients receiving high NK cell numbers (P = 0.039). These data suggest that both the number of transplanted NK cells and the donor KIR genotype play a role in graft-versus-malignancy mechanisms in HLA-identical PBSCT.

Dendritic cells in allogeneic hematopoietic stem cell transplantation.

In allogeneic hematopoietic stem cell transplantation (SCT), dendritic cells (DCs) as the most potent antigen-presenting cells play a central role in the development of acute and chronic graft-vs-host disease (GVHD), in graft-vs-leukemia or -malignancy reactions and in fighting infectious complications. Functional maturity and distribution of DC sub-types (DC1 and DC2) differ between the different stem cell sources used (bone marrow, granulocyte colony-stimulating factor-mobilised peripheral blood and cord blood) resulting in various rates of graft-vs-host disease and graft-vs-leukemia activity. Although DC recovery following stem cell transplantation is prompt, graft-vs-host disease and the use of immunosuppressive drugs result in qualitative and quantitative disturbances in DC homeostasis and have been observed for up to 1 year after transplantation. Complete donor DC chimerism seems to be a pre-requisite for the development of chronic GVHD and for graft-vs-leukemia activity, at least following reduced-intensity transplants, although in the early phase of acute graft-vs-host disease the presence of host antigen-presenting cells is essential. Preliminary data show promising results with DC-based immunotherapy for treatment of viral and fungal infections and of leukemic relapse following allogeneic stem cell transplantation. More information on the mechanisms and interactions between dendritic cells and regulatory T cells is needed for DC vaccination concepts for modulation of graft-vs-host disease.

Comparative in vitro study of the immunomodulatory activity of humanized and chimeric anti-CD25 monoclonal antibodies.

Humanized or chimeric monoclonal antibodies (MoAbs) directed against the interleukin-2 (IL-2) receptor alpha-chain, CD25, are promising immunosuppressive agents due to improved pharmacokinetic profiles and less toxicity. These MoAbs have been used effectively in preventing and/or treating rejection in solid organ transplantation and are currently under investigation for prevention/treatment of graft-versus-host disease (GvHD) in stem cell transplantation. We analysed the in vitro activities of the chimeric anti-CD25 MoAb basiliximab and the humanized anti-CD25 MoAb daclizumab in various test systems for alloimmune response and T cell activation in comparison to cyclosporin A (CsA) and prednisolone. Anti-CD3- and alloantigen-induced T cell proliferation were decreased significantly by the anti-CD25 MoAbs in a dose-dependent fashion. At a concentration of 10 ng/ml daclizumab and CsA synergistically decreased T cell proliferation of mixed lymphocyte cultures, whereas basiliximab showed only subadditive activity. Simultaneous addition of the anti-CD25 MoAbs and prednisolone did not result in combined activity. Addition of exogenous IL-2 completely overcame the inhibitory effect on T cell proliferation of both anti-CD25 MoAbs, but not that of CsA and prednisolone. Anti-CD25 MoAbs inhibited the generation of antigen-specific cytotoxic T lymphocytes in a limiting dilution assay, whereas they showed no effect on the cytolytic activity of established antigen-specific T cell clones. This in vitro study demonstrates strong immunosuppressive activity by both chimeric and humanized MoAbs against CD25. The combined activity with CsA justifies their early use for prevention rather than treatment of GvHD.

Single site experience with high-speed coronary rotational atherectomy.

This report describes a single site experience as part of a multicenter clinical trial with high-speed rotational atherectomy in human coronary arteries. A total of 108 patients with 143 lesions had interventions, were grouped by success or failure, and were analyzed by patient, lesion, and procedural variables. Satisfactory results were achieved in 131 of 143 lesions (92%) and 99 of 108 (92%) patients. Neither patient-related variables (age, gender, diabetes, hypertension, cigarette use, restenosis, previous myocardial infarction, and left ventricular function) nor lesion characteristics (length, ostial or bifurcation location, calcification, lesion classification, and coronary location) were predictive of poor outcome. Tears, acute closure, percentage stenosis after rotational atherectomy and after adjunctive balloon angioplasty were the procedural variables that were statistically associated with outcome by univariate methods. Multivariate analysis isolated postintervention residual stenosis as the only variable that was statistically different between groups. Serious complications included one death in the catheterization laboratory, one Q-wave myocardial infarction, three non-Q myocardial infarctions, and three emergency coronary bypass operations for sustained vessel closure. One patient required emergency surgery for a pacing wire perforation not related to the use of the device. The potential benefits of high-speed rotational atherectomy include increased safety in complex lesions, the ability to address lesions not amenable to balloon techniques, and the possibility of reducing the incidence of restenosis.

Noninvasive determination of left ventricular output and wall stress in volume overload and in myocardial disease by cine magnetic resonance imaging.

The current study used cine magnetic resonance imaging to determine the effect of increasing severity of valvular regurgitation on systolic wall stress and to demonstrate that wall stress was disproportionately increased in relation to the severity of regurgitation in patients with myocardial disease. A total of 39 patients with predominantly mitral (n = 22) or aortic (n = 17) regurgitation with (n = 13) and without (n = 26) myocardial disease and 10 normal volunteers were examined with cine magnetic resonance imaging (MRI) at 1.5 T. Left ventricular (LV) cardiac output (CO) and peak systolic (PS) wall stress (WS) and end-systolic (ES) WS were calculated from blood pressure recordings, carotid pulse tracings, and wall thickness (h) and diameter (D) measurements obtained from cine MRI. Patients were classified into three degrees of severity according to their LV regurgitant volume (RV). Myocardial disease was defined by an ejection fraction (EF) of less than 40%. Mean LV EF was 61 +/- 3% in normal volunteers, 64 +/- 3% in patients with regurgitation, and 25 +/- 2% in patients with myocardial disease. LV CO was directly related to RV in patients without myocardial disease, whereas it was disproportionately low in relation to RV in patients with myocardial disease. PS WS was significantly higher in severe mitral and/or aortic regurgitation compared with moderate, mild, and no mitral and/or aortic regurgitation. Compared with the degree of regurgitation, PS WS was disproportionately higher in patients with myocardial disease. Thus LV CO and WS rise progressively with increasing severity of regurgitation. Disproportionately high systolic WS relative to RV indicates the presence of myocardial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial volume determination by biplane two-dimensional echocardiography: validation by cine computed tomography.

Left atrial (LA) volume measurements have been made by the application of the method of discs (modified Simpson's rule) to orthogonal biplane atrial echocardiographic images. Validation of the technique has been suboptimal due to deficiencies of the reference standard, levophase angiography. To define the accuracy of echocardiography, we compared LA end-systolic volume by echocardiography in 27 patients with volumes by cine computed tomography (Cine CT), a highly accurate and validated method of measuring cardiac chambers. Echocardiographic tracings were made in the apical long-axis two- and four-chamber views. In patients with atria less than 300 ml, 14 had echoes performed prospectively, with optimization of LA size, while the remaining 10 were analyzed retrospectively. The volume of each slice was calculated and was then summated to obtain total volume. The correlation coefficient between two-dimensional echocardiography and Cine CT was r = 0.98, and it was r = 0.82 when patients with atria greater than 300 ml (n = 3) were excluded. Echocardiography underestimated Cine CT measurements by 23%. The slope of the prospective group was closer to unity than the slope of the retrospective group (p less than 0.001), and the correlation with Cine CT was slightly better for the prospective group (r = 0.88 versus r = 0.77). LA volume by two-dimensional echocardiography correlates closely with Cine CT, a more accurate method of volume determination, and gives valid measurements of LA volume. Efforts to maximize LA size during scanning limit inaccuracies of echocardiographic measurements of the left atrium.

Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava.

To evaluate a simple noninvasive means of estimating right atrial (RA) pressure, the respiratory motion of the inferior vena cava (IVC) was analyzed by 2-dimensional echocardiography in 83 patients. Expiratory and inspiratory IVC diameters and percent collapse (caval index) were measured in subcostal views within 2 cm of the right atrium. Parameters were correlated with RA pressure by flotation catheter within 24 hours of the echocardiogram (38 were simultaneous). Correlations between RA pressure (range 0 to 28 mm Hg), expiratory and inspiratory diameters and caval index were 0.48, 0.71 and 0.75, respectively. Of 48 patients with caval indexes less than 50%, 41 (89%) had RA pressure greater than or equal to 10 mm Hg (mean +/- standard deviation, 15 +/- 6), while 30 of 35 patients (86%) with caval indexes greater than or equal to 50% had RA pressure less than 10 mm Hg (mean 6 +/- 5). Sensitivity and specificity for discrimination of RA pressure greater than or equal to or less than 10 mm Hg were maximized at the 50% level of collapse. Thus, IVC respiratory collapse on echocardiography is easily imaged and can be used to estimate RA pressure. A caval index greater than or equal to 50% indicates RA pressure less than 10 mm Hg, and caval indexes less than 50% indicate RA pressure greater than or equal to 10 Hg.

[Three-dimensional analysis of the regional contractility of the normal and the cardiomyopathic left ventricle using cine-magnetic resonance imaging]. / Dreidimensionale Analyse der regionalen Kontraktilität des normalen und kardiomyopathischen linken Ventrikels mit Cine-Magnet-Resonanz-Imaging.

The left ventricular regional contractile pattern, global function and mass of normal subjects and patients with idiopathic dilated cardiomyopathy was compared using cine magnetic resonance imaging (MRI) in a short-axis imaging plane. Left ventricular ejection fraction and mass were 64.3 +/- 2.5% and 115 +/- 10 g in normal hearts and 23.5 +/- 3.1% and 194 +/- 20 g in dilated cardiomyopathic hearts (p less than 0.001 and p less than 0.002). Left ventricular end-diastolic wall thickness was homogeneous in normal hearts except for the posterior wall at the basal level, which was significantly thinner compared to the anterolateral wall and the septum (p less than 0.02). End-diastolic wall thickness in the cardiomyopathic group was significantly more heterogeneous and was thinner at the apical compared to the basal level (p less than 0.02) as well as in the segment of the posterior compared to the anterolateral and septal wall (p less than 0.005 and p less than 0.03). In normal hearts, left ventricular end-systolic wall thickness was progressively greater from base to apex for the anterolateral (p less than 0.01) and posterior wall (p less than 0.02) and the septum (p less than 0.02). Such a uniform gradient of end-systolic wall thickness was not present in hearts with dilated cardiomyopathy. It was even reversed for the anterolateral wall with decreasing thickness from base to apex (p less than 0.03). Left ventricular mean systolic wall thickening increased progressively from base to apex (p less than 0.005) in normal hearts, whereas there was no significant gradient from base to apex in hearts with dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic accuracy and estimation of the severity of valvular regurgitation from the signal void on cine magnetic resonance images.

Anomalous blood flow caused by valvular regurgitation can be visualized as a narrowly defined area of signal loss in contrast to the high intensity of the blood pool on repetitive gradient refocused magnetic resonance (MRI) (cine MRI) views. In order to assess the accuracy of identification and measurements of the signal void in the evaluation of mitral (MR) and aortic regurgitation (AR), the cine MRI studies of 62 patients with regurgitation and of 20 normal volunteers were retrospectively analyzed in a blinded study of three independent reviewers. Accuracy for detection of MR was greater than 0.96 and for AR was greater than 0.91 for all three reviewers. The total volume of the signal void associated with regurgitation was measured on cine MRI images of 58 patients by two independent observers. The patients were divided into three groups of severity based upon assessment of severity of regurgitation by two-dimensional echocardiography and/or angiography. The total volume of signal loss was 9.0 ml (+/- 0.94 SEE; n = 18) for mild MR, 30.7 ml (+/- 5.3 SEE; n = 11) for moderate MR, and 83.4 ml (+/- 17.4 SEE; n = 5) for severe MR. In patients with AR, the calculated signal void was 27.3 ml (+/- 3.2 SEE; n = 24) in mild, 49.7 ml (+/- 2.9 SEE; n = 7) in moderate, and 75.8 ml (+/- 5.7; n = 6) in severe cases. The differences in the volume of the signal void were significant among the three groups of severity (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance.

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease.

To determine the feasibility of noninvasive determination of right ventricular systolic pressure (RVSP) during a graded-exercise protocol, saline contrast-enhanced Doppler echocardiography of tricuspid insufficiency was performed in 36 patients with chronic lung disease and 12 normal controls. In the patients with chronic pulmonary disease, symptom-limited, incremental supine bicycle exercise and pulse oximetry were performed on and off high-flow oxygen. Technically adequate Doppler studies were initially obtained in 20 patients (56%) at rest and 14 (39%) on exercise; these numbers increased to 33 (92%) and 32 (89%), respectively, after enhancement with agitated saline (both p less than 0.001). In 10 patients with chronic lung disease who had simultaneous hemodynamic monitoring during exercise, the correlation between Doppler and catheter measurements of pulmonary artery systolic pressure was close (r = 0.98). Among controls, RVSP increased from 22 +/- 4 at rest (mean +/- SD) to 31 +/- 7 mm Hg at peak exercise. In patients with chronic lung disease, RVSP increased from 46 +/- 20 to 83 +/- 30 mm Hg (both p less than 0.001 vs. controls). Despite normal resting values for RVSP in 28% of study patients, nearly all showed abnormal increases in RVSP during supine bicycle exercise. Increases in RVSP during exercise were greatest in patients who showed oxyhemoglobin desaturation. The short-term administration of oxygen significantly blunted the increase in RVSP during exercise. Saline contrast-enhanced Doppler evaluation of tricuspid insufficiency seems a potentially valuable noninvasive method of determining the exercise response of RVSP in patients with chronic pulmonary disease.

Inferior vena cava plethora with blunted respiratory response: a sensitive echocardiographic sign of cardiac tamponade.

To assess the diagnostic and prognostic value of the respiratory behavior of the inferior vena cava in pericardial effusions, clinical and two-dimensional echocardiographic data of 115 consecutive patients with a moderate or large effusion, including 33 who had cardiac tamponade, were reviewed. Echocardiograms were reviewed for effusion size, inferior vena cava diameter before and after deep inspiration and presence of right atrial and ventricular collapse. For the 83 patients (72%) with less than 50% decrease in inferior vena cava diameter after deep inspiration ("plethora"), inferior vena cava diameter decreased from 2.0 +/- 0.3 to 1.6 +/- 0.4 cm after inspiration (mean +/- SD) (mean decrease 18%). For the 32 patients (28%) without plethora, the diameter decreased from 1.6 +/- 0.5 to 0.6 +/- 0.3 cm (mean decrease 63%). Patients with plethora had significantly higher values for heart rate (111 +/- 21 versus 98 +/- 20 beats/min), pulsus paradoxus (24 +/- 15 versus 12 +/- 4 mm Hg), jugular venous distension (14 +/- 5 versus 8 +/- 3 cm H2O) and right atrial pressure (17 +/- 6 versus 12 +/- 6 mm Hg) and lower values for systolic blood pressure (109 +/- 22 versus 132 +/- 27 mm Hg) (all p less than 0.05) than did patients without plethora. Plethora was present in 58 (92%) of 63 patients who underwent a pericardial drainage procedure, 14 (88%) of 16 who developed constrictive physiology and 11 (92%) of 12 of those whose hospital death was related to pericardial effusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of infarct coronary artery recanalization after intravenous thrombolytic therapy.

Clinical assessment of patients with evolving acute myocardial infarction may suggest recanalization of the infarct coronary artery if chest pain, electrocardiographic ST-segment elevation and reperfusion arrhythmia are diminished. These 3 criteria, however, have not been correlated with immediate coronary angiography. Determination of which patients will achieve myocardial reperfusion after intravenous fibrinolytic therapy would allow for appropriate triage; those in whom it fails may be considered for mechanical or surgical recanalization. Fifty-six patients were studied: 28 received intravenous streptokinase and 28 intravenous recombinant tissue-type plasminogen activator. None of these clinical criteria, considered separately, was predictive of infarct artery recanalization status. Using the presence or absence of all 3 criteria, the specificity and predictive value increased to 100%. However, only 9% of patients in the series had all 3 criteria present (all had a patent infarct artery) and 34% had no criteria present (all had an occluded vessel). Noninvasive clinical markers are simple and practical, but only concordance of all 3 major criteria, when present, accurately predicts results of thrombolytic therapy.

Pluronic F-68: a promising new skin wound cleanser.

Pluronic F-68 is a new skin cleanser that has been approved by the Food and Drug Administration for use in humans. In experimental studies, this nonionic detergent prevented the development of infection with no discernible toxicity. We have used Pluronic F-68 clinically in wounds in more than 1,000 patients without demonstrable side effects. As a result of this experience, Pluronic F-68 has replaced all other commercially available scrub solutions for use as a skin wound cleanser in our medical center.