C-reactive protein in the monitoring of acute rejection after heart transplantation

OBJECTIVE: To measure short duration sounds (L(PEAK)) in the neonatal intensive care unit and describe their intensity, incidence, and periodicity in relationship to activities within the unit. STUDY DESIGN: We measured 1-minute L(PEAK) at four locations within the intensive care unit, accumulating 48 hours of data for each weekday. RESULTS: Thirty-one percent of the L(PEAK) exceeded 90 dB. For further analysis, the data were transformed to the proportion exceeding 90 dB. These values varied significantly with day, week, location, and time of day. During physician rounds, there was a 16% relative increase in L(PEAK). CONCLUSION: These data demonstrate the intensity, incidence, and periodicity of short duration sounds in the intensive care nursery. Short duration sounds are known to affect the infant's physiological and behavioral states and should be addressed in future recommendations for sound control and reduction strategies.     

Heart rate variability as an assessment of acute rejection after heart transplantation

BACKGROUND: Orthotopic heart transplantation is currently a widely accepted treatment for end-stage heart disease. Early detection and adequate therapy of acute rejection increases the survival rate. Currently, the most reliable technique for the detection of acute cardiac rejection (ACR) is endomyocardial biopsy (EMB), which is an invasive procedure with some intrinsic problems. The purpose of this study was to assess heart rate variability (HRV) as a noninvasive procedure for frequent monitoring of ACR. METHODS: Six consecutive orthotopic cardiac transplant recipients were prospectively recruited into this study. The follow-up periods ranged from seven to 359 days (median; 146 days). A precordial electrocardiograph (ECG) of 288 seconds was recorded at 5:00 PM before the patient underwent EMB. The results from the frequency domain analysis of the ECG signals were evaluated to correlate with the findings from EMB. RESULTS: Of 48 EMBs, 42 (87.5%) showed no evidence of rejection, four showed mild focal ACR (EMB grade 1A), one mild diffuse ACR (1B) and one moderate plurifocal ACR (3A). There was no moderate focal ACR (2), severe diffuse ACR (3B) or severe ACR (4). Correlation between ACR (3A) and a significant increase in HRV with a corresponding 'broad-band' or bell-shaped pattern on the power spectrum was noted. CONCLUSIONS: Our study in consecutive cardiac transplant recipients indicates that the changes in HRV provide clinicians with a new concept for heart transplant monitoring. Further study is needed to verify clinical utility.     

Treatment of humoral rejection after heart transplantation

BACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.     

Detection of acute rejection by 133Xe radiospirometry after single lung transplantation in an experimental porcine model

153 regional lymph nodes obtained during surgical operations because of cancer of various cites from 50 cancer patients were studied. Failure of local immunity is explained by the following factors: 1) depletion of T-cell population with a decrease of activated lymphocyte-killers; 2) high activity of B-cell population able to block T-cell cytotoxic effect; 3) deficiency of T-suppressors and T-helpers; 4) a decrease of macrophages-monocytes of phagocytic capacity; 5) high activity of dendritic reticular cells stimulating transformation of B-lymphocytes and low activity of interdigitating reticulocytes determining T-cell immunity stimulation.     

Reproducibility of color Doppler imaging in orbital vessels

The purpose of this study was to evaluate the short-term reproducibility, the long-term reproducibility, and the reproducibility of the measurements made between two different examiners of blood-flow velocity in extraocular vessels using color Doppler imaging (CDI). In a group of 10 healthy volunteers, measurements of the peak-systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) in the ophthalmic artery and the central retinal artery as well as one lateral and one medial short posterior ciliary artery were performed. The best intraindividual reproducibility, expressed as the relative error, was found for the PSV and RI measured in the ophthalmic artery (OA; PSV 5.9%, RI 3.1%) and the central retinal artery (CRA; PSV 7.7%, RI 4.7%). The PSV and RI determined in the posterior ciliary arteries were less reproducible but as much so as the EDV measured in the OA (11.8%) and CRA (19.9%). No systematic trend could be found between the first and second measurements. However, the long-term fluctuation was considerable high. Measurements of PSVs showed good concurrence between the two observers in all four vessels measured. The EDVs and RIs differed statistically significantly between the two observers. This difference was most pronounced in the posterior ciliary arteries.     

Power Doppler imaging of carotid artery stenosis. Comparison with color Doppler flow imaging and angiography

BACKGROUND AND PURPOSE: Power Doppler imaging (PDI) is a new sonographic technique that has recently been introduced for vascular application. Since the technical principles of PDI may provide increased sensitivity to visualize the continuity of blood flow in arterial stenoses, we investigated the diagnostic significance of PDI and the intermethod relationship for the measurement and classification of internal carotid artery (ICA) stenosis in comparison with both color Doppler flow imaging (CDFI) and angiography. METHODS: One hundred patients with a total of 128 ICA stenoses (50% to 69%, n = 37; 70% to 79%, n = 27; 80% to 99%, n = 64) and 12 ICA occlusions were consecutively investigated by means of PDI, CDFI, and intra-arterial angiography (n = 48). Reduction of the intrastenotic lumen was measured on longitudinal and transverse views of PDI and CDFI for the calculation of the degree of diameter and area stenosis, respectively. Angiographic stenosis was determined with the use of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and common carotid (CC) methods. RESULTS: PDI provided significantly more excellent or good (92% versus 79%; P < .01) displays of the intrastenotic lumen than CDFI, particularly in complicated high-grade stenosis. While linear regression analysis demonstrated a high overall correlation between PDI and CDFI for diameter (r = .88; P < .001) and area stenosis (r = .79; P < .001), categorization of ICA stenosis revealed best agreement for 80% to 99% area stenoses. Since angiography frequently either underclassified (NASCET method) or overclassified (ECST, CC methods) the degree of ICA stenosis in comparison to both PDI and CDFI, the sonographic-angiographic correlation was only moderate (regression coefficients ranged from .62 to .70; P < .001). CONCLUSIONS: PDI further improves the assessment of ICA stenosis by providing better visualization of the stenotic vascular lumen than CDFI. Sonographic imaging of the stenotic plaque on both PDI and CDFI provided a direct measurement of the local degree of stenosis, while the angiographic grade of stenosis essentially depended on the method used for evaluation.     

Comparison of regional myocardial velocities assessed by quantitative 2-dimensional and M-mode color Doppler tissue imaging: influence of the signal-to-noise ratio of color Doppler myocardial images on velocity estimators of the Doppler tissue imaging system

M-mode color Doppler imaging of the myocardium affords a greater sampling rate and signal-to-noise (S/N) ratio than 2-dimensional (2D) imaging. In this study, we compared myocardial velocities assessed by 2D and M-mode Doppler tissue imaging (DTI) at the same site and evaluated the influence of the S/N ratio on velocity estimates of the currently used DTI systems. In patients with and without impaired regional left ventricular function, myocardial velocities assessed by 2D DTI were lower than those obtained with M-mode DTI. The difference between regional velocities derived from both imaging techniques was positively correlated with the extent of the "black zone," which could be considered as indirectly reflecting the S/N ratio for each frame. Thus in the clinical setting and on currently used echocardiographs, 2D DTI may provide underestimated regional myocardial velocities when compared with M-mode, mainly because of the influence of the lower sampling rate and S/N ratio on velocity estimators of the imaging system.     

Evaluation of breast tumors with color Doppler imaging: a comparison with image-directed Doppler ultrasound

Preclinical experience has shown that it is possible to maintain and expand hematopoietic cells in liquid culture systems by provision of optimal combinations of colony-stimulating factors (CSF). Ex vivo hematopoietic cell expansion (HCE) would be expected to reduce harvesting time and effort and could also decrease the infusion dose necessary for hematopoietic reconstitution after bone marrow transplantation. In addition, ex vivo expanded cells might be of value for therapeutic gene transfer. The central question in ex vivo HCE is whether the CSF combinations employed provide not only amplification of the late progenitor pools, but also maintenance or expansion of the stem cell compartment to ensure long term engraftment. Choice of CSF and experimental parameters in the culture system appear to be the most critical factors influencing the outcome of strategies for ex vivo HCE. Moreover, it is essential to define the goal of HCE and to adapt the experimental conditions to obtain the required cell populations. In future work, it remains to test the potential applicability of ex vivo expanded cells and to carefully monitor the possibility of the expansion of tumoral cells in ex vivo proliferation systems.     

Results of transplantation for acute and chronic hepatic allograft rejection

B-chronic lymphocytic leukemia (CLL) is characterized by an accumulation of long-lived, resting B cells expressing the Bcl-2 protein. However, less than 10% of the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional Southern blotting analysis. In the present study, rearrangement of the bcl-2 gene in CLL cells was studied by pulsed-field gel electrophoresis (PFGE). With this method, large DNA fragments (> 50-10,000 kb) could be analyzed. Blood CLL cells from 9 of 9 patients and 2 of 2 CLL cell lines showed rearranged bcl-2 gene. In comparison, healthy blood B cells and lymphoblastoid cell lines (LCLs) established from normal peripheral blood lymphocytes of the patients showed only germ line configuration. Thus, the possibility of restriction fragment length polymorphisms (RFLPs) in this gene could be excluded. The primary cell involved in CLL might be a progenitor B cell that has accidentally rearranged the bcl-2 gene. As a consequence, such cells express stable amount of Bcl-2 protein and do not enter apoptosis. During prolonged survival, such cells may acquire secondary changes including chromosomal translocations and mutations.     

Routine surveillance endomyocardial biopsy: late rejection after heart transplantation

BACKGROUND: Transplant programs use routine surveillance endomyocardial biopsies (RSEMB), which are performed at preset intervals to diagnose cardiac rejection. This retrospective study determined the incidence of graft rejection detected by RSEMB. METHODS: The records of 95 patients who underwent heart transplantation between 1987 and 1995 were reviewed. Rejection incidence was recorded for 80 patients who survived at least 30 days, with a mean follow-up of 35 months. RESULTS: One thousand five hundred sixteen total biopsies were performed; 1,170 were RSEMB. Four hundred seventy-five total rejection episodes occurred and 269 (56%) were diagnosed by RSEMB. Two distinct patient groups were identified. The majority (70 patients), had a decline in the incidence of rejection and no rejection episodes were identified by RSEMB after 36 months. In contrast, the high rejection group (10 patients) had a significantly higher ongoing rejection rate (p < or = 0.04 to p < or = 0.001) throughout their postoperative course up to 72 months. CONCLUSIONS: The majority of our transplant patients demonstrate a decrease in rejection with time and do not require RSEMB beyond 30 months. We identified a group of patients who exhibited a higher rate of rejection and need continued RSEMB.     

Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus

A noninvasive assessment of left ventricular (LV) diastolic performance by tissue Doppler imaging was performed in 56 patients (8 patients with atypical chest pain, 42 with coronary artery disease with a previous myocardial infarction, and 6 without a previous myocardial infarction) who underwent cardiac catheterization. Mitral annular velocity (MAV) during early ventricular diastole was obtained by M-mode color tissue Doppler imaging at the posterior corner of the mitral annulus. In each patient, the negative peak of the first derivative of LV pressure decay (peak -dP/dt) and a time constant of LV relaxation (tau) were calculated from the LV pressure waves obtained by a catheter-tip micromanometer. LV end-systolic volume index was measured from contrast left ventriculography. MAV during early diastole was significantly correlated with tau (r = -0.73, p <0.001), peak -dP/dt (r = 0.58, p <0.001), and LV end-systolic volume index (r = -0.63, p <0.001). On multivariate regression analysis with MAV during early diastole, tau and LV end-systolic volume index were selected as prime determinants (r = 0.80, p <0.001). These findings suggest that MAV during early diastole has a direct relation to LV elastic recoil as well as to LV relaxation. MAV during early diastole gives important information regarding LV behavior in late systole to early diastole where LV early diastolic performance is determined.     

Conventional color Doppler velocity sonography versus color Doppler energy sonography for the diagnosis of acute experimental torsion of the spermatic cord

OBJECTIVE: We compared color Doppler velocity sonography and color Doppler energy sonography for the diagnosis of spermatic cord torsion in a canine model and determined the degree of torsion necessary to acutely halt testicular blood flow. MATERIALS AND METHODS: Spermatic cord torsion was created in five dogs by exposing and rotating the ipsilateral testis 0 degree, 180 degrees, 270 degrees, 360 degrees, 450 degrees, and 540 degrees. Detorsion followed. The testicles were scanned at each torsion stop using both color Doppler velocity sonography and color Doppler energy sonography. Doppler parameters were optimized (by phantom and test scans) and maintained at a tolerable noise level throughout the experiment. Readers who were unaware of the degree of torsion compared flow in the rotated and contralateral control testes. RESULTS: Flow became undetectable by color Doppler velocity sonography and color Doppler energy sonography at 450 degrees in four of five cases and at 540 degrees in one of five cases. We found no significant difference between the velocity and the energy techniques for detecting this absence of flow (p > .05, Wilcoxon test). We found a significant difference in degree of flow for both techniques when comparing controls and all degrees of torsion combined (p < .006, Mann-Whitney test), but significance was achieved at lesser degrees of torsion with the velocity technique than with the energy technique (180 degrees and 360 degrees, respectively, Wilcoxon test). CONCLUSION: Color Doppler energy sonography was not significantly more sensitive than color Doppler velocity sonography for the diagnosis of spermatic cord torsion in this model. Complete occlusion of arterial inflow occurred at 450-540 degrees of torsion.     

Comparison of myocardial velocities by tissue color Doppler imaging in normal subjects and in dilated cardiomyopathy

The authors studied 35 normal subjects (41 +/- 6 years) and 22 patients with idiopathic dilated cardiomyopathy 48 +/- 7 years; ejection fraction: 31 +/- 12%) in order to determine normal values of myocardial velocities and to demonstrate the sensitivity of Doppler tissue imaging in detecting a significant decrease in myocardial velocities in patients with abnormal left ventricular contractility. Interventricular septal and left ventricular posterior wall velocities were recorded by M mode long axis parasternal views. In normal subjects, a velocity gradient in the posterior wall was observed, higher in the endocardium than in epicardium, in systole (5.1 +/- 1.5 versus 2.8 +/- 1 cm/s, p < 0.01), and early diastole (13.7 +/- 3.5 versus 5.7 +/- 2 cm/s, p < 0.001) and late diastole at the time of atrial contraction (2.7 +/- 2.1 versus 1.8 +/- 1.7 cm/s, p < 0.01). Moreover, the velocities are higher in the posterior wall than in the interventricular septum throughout the cardiac cycle. Finally, the velocities are higher in early diastole than in systole, both in the interventricular septum and posterior wall. In the group of patients with idiopathic dilated cardiomyopathy, the intramyocardial velocities were lower than in normal subjects. In addition, the velocity gradient in the posterior wall was absent in 15 of the 22 patients. The authors conclude that Doppler tissue imaging provides new information in the analysis of myocardial function both in systole and diastole.