PubMed Health⌕ Search

Biomedical subjects

K Kanter

Publications and source records attributed to K Kanter.

At least 19 recordsLinked to original sources
PubMed1997

Apoptosis of mononuclear cell infiltrates in cardiac allograft biopsy specimens questions studies of biopsy-cultured cells.

During acute rejection, CD4 and CD8 T cells infiltrate the myocardium and cause myocyte death and dropout. CD4 and CD8 cells use a number of cytotoxic mechanisms, including fas-fas ligand interactions, which lead to apoptotic death. Since fas is expressed on myocytes, we investigated endomyocardial biopsy specimens from cardiac transplant patients to determine whether apoptosis is one of the mechanisms of cell death in acute rejection. Serial sections of individual endomyocardial biopsy specimens from patients histologically diagnosed as having grade 3A rejection (n=22 biopsy specimens), biopsy specimens showing a typical "Quilty effect" (n=10), and specimens with concurrent grade 3A rejection and the Quilty effect (n=6) were evaluated using the C-terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique for frequency of apoptosis in myocytes and mononuclear cell infiltrates. None of the examined sections showed detectable evidence of apoptotic myocytes, even within regions clearly showing myocyte damage. Of interest was our consistent finding that 85-98% of mononuclear cell infiltrates within biopsy specimens scored as having grade 3A rejection had undergone apoptosis. In marked contrast, 9 of the 10 specimens with Quilty lesions showed <5% apoptotic mononuclear cells in the endomyocardial infiltrates. Of further interest was our finding of 85-98% apoptotic mononuclear cell infiltrates within Quilty lesions associated with biopsy specimens scored as having grade 3A rejection. The frequency of apoptotic cells determined by the TUNEL technique was confirmed by histological examination of the morphology of the cells and with a technique that involves detection of c-jun. These results prompt a note of caution in the interpretation of data on the phenotype, cytokine profile, Vbeta T cell receptor repertoire, and donor specificity of mononuclear cells cultured and propagated from such cardiac biopsy specimens. The possible reasons for apoptosis of graft-infiltrating mononuclear cells are discussed.

Adult↗
PubMed1997

Effects of dual-chamber pacing for pediatric patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The effects of both temporary and permanent dual-chamber pacing (DCP) were evaluated in symptomatic pediatric patients with hypertrophic obstructive cardiomyopathy (HOCM) unresponsive to medications. BACKGROUND: Permanent DCP pacing can reduce left ventricular outflow tract (LVOT) gradient and relieve symptoms in adult patients with HOCM. METHODS: Ten patients (mean [+/-SD] age 11.1 +/- 6 years, range 1 to 17.5) with HOCM and a Doppler LVOT gradient > or = 40 mm Hg were studied. The seven patients showing hemodynamic improvement during temporary pacing at cardiac catheterization underwent surgical implantation of a permanent DCP system. The effects of permanent pacing were evaluated using a questionnaire, Doppler evaluation, treadmill testing and repeat cardiac catheterization. RESULTS: At initial cardiac catheterization, three patients failed to respond to temporary pacing (inadequate pace capture in two; congenital mitral valve abnormality in one). The remaining seven patients (70%, 95% confidence interval 38.0% to 91.7%, mean age 13 +/- years, range 4 to 17.5) showed a significant reduction (p < 0.05) in LVOT gradient, left ventricular systolic pressure and pulmonary capillary wedge pressure. After pacemaker implantation, these seven patients reported a significant reduction in dyspnea on exertion and exercise intolerance. Serial Doppler evaluation showed a significant reduction in LVOT gradient. Follow-up catheterization at 23 +/- 4 months in six patients (one patient declined restudy) showed a persistent decrease in LVOT gradient (53 +/- 13 vs. 16 +/- 11 mm Hg), left ventricular systolic pressure (149 +/- 16 vs. 108 +/- 14 mm Hg) and pulmonary capillary wedge pressure (18 +/- 2 vs. 12 +/- 4 mm Hg) versus preimplantation values. CONCLUSIONS: Permanent DCP is an effective therapy for selected pediatric patients with HOCM. Rapid atrial rates and intrinsic atrioventricular conduction, as well as congenital mitral valve abnormalities, may preclude effective pacing in certain patients.

Adolescent↗
PubMed1996

In vitro flow experiments for determination of optimal geometry of total cavopulmonary connection for surgical repair of children with functional single ventricle.

OBJECTIVES: This study sought to evaluate the effect of offsetting cavopulmonary connections at varying pulmonary flow ratios to determine the optimal geometry of the connection. BACKGROUND: Previous investigators have demonstrated energy conservation within the streamlined contours of the total cavopulmonary connection compared with that of the atriopulmonary connection. However, their surgical design of connecting the two cavae directly opposite each other may result in high energy losses. Others have introduced a unidirectional connection with some advantages but with concerns about the formation of arteriovenous malformation in the lung excluded from hepatic venous return. Thus, an optimal surgical design has not been determined. METHODS: In the present models, the caval connections were offset through a range of 0.0 to 2.0 diameters by 0.5 superior cava diameter increments. Flow ratios were fixed for superior and inferior cavae and varied for right and left pulmonary arteries as 70:30, 60:40, 50:50, 40:60 and 30:70 to stimulate varying lung resistance. Pressure measurements and flow visualization were done at steady flows of 2, 4 and 6 liters/min to stimulate rest and exercise. RESULTS: Our data show that the energy losses at the 0.0-diameter offset were double the losses of the 1.0 and 1.5 diameters, which had minimal energy losses. This result was attributable to chaotic patterns seen on flow visualization in the 0.0-diameters offset. Energy savings were more evident at the 50:50 right/left pulmonary artery ratio. Energy losses increased with increased total flow rates. CONCLUSIONS: The results strongly suggest the incorporation of caval offsets in future total cavopulmonary connections.

Child↗
PubMed1996

Management of biliary tract stones in heart transplant patients.

OBJECTIVE: The authors report their experience with biliary tract stones in adult and pediatric heart transplant patients, and review the current literature relative to this problem. SUMMARY BACKGROUND DATA: Prior studies in adults have noted that heart transplant patients frequently have cholelithiasis, but offer no consensus about treatment strategy. Few studies exist for pediatric heart transplant patients. A higher rate of hemolysis and cyclosporine-induced changes in bile metabolism may contribute to lithogenesis in this population. METHODS: A chart review was conducted for 211 patients who had heart transplants between January 1988 and September 1994 to determine prevalence of biliary tract stones, management strategies used, and outcome. RESULTS: Of 175 long-term heart transplant survivors, 52 (29.7%) had stones detected: 32.8% of adults (47/143) and 15.6% of children (5/32). The majority of patients (31) were diagnosed 4 months (mean) after transplantation; cholelithiasis developed in 10 of these patients (32%) within 11 months (median) after a negative ultrasound. Symptoms developed in 45% of patients. All patients underwent either elective (36) or urgent (6) cholecystectomy via an open (32) or laparoscopic (10) approach, or endoscopy for common bile duct stones (2). There were no deaths or complications during a follow-up period of up to 7 years. CONCLUSION: Heart transplant patients have a high prevalence of symptomatic biliary tract stone disease. They can be treated safely via an open or laparoscopic approach after transplantation. The authors recommend routine gallbladder ultrasound screening and elective cholecystectomy in the post-transplant period if stones are detected.

Adolescent↗
PubMed1995

Frequency of hypoxanthine guanine phosphoribosyltransferase (HPRT-) T cells in the peripheral blood of cardiac transplant recipients. A noninvasive technique for the diagnosis of allograft rejection.

BACKGROUND: Histological evaluation of serial endomyocardial biopsies performed at fixed time intervals after cardiac transplantation is the universal method used for the detection of cardiac rejection and assessment of the adequacy of antirejection therapy. No noninvasive methodology thus far investigated has achieved a high enough sensitivity and predictive accuracy to be considered as a potential replacement for endomyocardial biopsy in the detection of rejection in adults. The present study exploited the finding that the rate of spontaneous mutation in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene is higher in proliferating human T cells than in resting cells. Thus, it was reasoned that in the posttransplantation setting, the frequency of HPRT- cells in peripheral blood may provide an indirect measure of alloactivated T lymphocytes. METHODS AND RESULTS: This study consisted of determining the clonal frequency of HPRT- mutant cells (FMC/10(6) peripheral blood mononuclear cells [PBMCs]) within a total of 293 peripheral blood samples representing various numbers of sequential samples from each of 27 transplant recipients. These sequential samples represented time periods when endomyocardial biopsy specimens showed either (1) no evidence of rejection (n = 5 patients), (2) a single initial episode after transplantation of early (< 1 year) or late (> 1 year) rejection (n = 12 patients), or (3) multiple rejection episodes (n = 10 patients). Statistical analyses were used to quantify the time profiles of FMC/10(6) PBMCs in serial samples among transplant recipients and to determine the association of these profiles with both the onset of first rejection episodes and, in appropriate patients, the recurrence of rejection episodes. Data showed that PBMCs from patients with no evidence of rejection uniformly gave low values of < 6 FMC/10(6) cells, a frequency similar to that seen in healthy nontransplanted volunteers. In contrast, 19 of the 22 PBMC samples that were obtained from patients whose corresponding biopsy sample was diagnosed with a histological rejection grade of > or = 3 gave values of > 6 FMC/10(6) cells, 11 of which gave values > 50/10(6) cells (range, 146 to 46,982 FMC/10(6) cells). A significant association between the onset of first rejection and an increased rate of FMC/10(6) values was noted (P = .0001). The ability of a rising trend in FMC/10(6) values to correctly identify the onset of rejection was 81.8% and to correctly identify no rejection, 100%. In addition, a significant association between recurrent rejection episodes and persistence of high FMC/10(6) values in the weeks after treated rejection episodes was noted (P = .0003). The ability of a persistently elevated trend in values of FMC/10(6) cells to correctly identify recurrent rejection was 90% and to correctly identify no rejection, 100%. CONCLUSIONS: Increasing frequencies of HPRT- mutant cells in peripheral blood correlated with the onset of first rejection, and persistently elevated HPRT- mutant cells in the weeks after a treated rejection episode correlated with recurrent rejection. This quantitative noninvasive assay may thus serve as a useful adjunct to endomyocardial biopsy for monitoring post-cardiac transplantation patients, and its use as a prospective diagnostic tool merits further study.

Adolescent↗
PubMed1994

The absence of constitutive and induced expression of critical cell-adhesion molecules on human cardiac myocytes. Its role in transplant rejection.

Fetal human cardiac myocytes (FHCM) and a cell line derived from FHCM, termed W1, constitutively express low levels of MHC class I antigens and significant levels of ICAM-1 (CD54), and LFA-3 (CD58) but do not express LFA-1 alpha (CD11a), LFA-1 beta (CD18), GMP-140 (CD62), BB1-B7, VCAM-1, and ELAM-1. In vitro incubation of FHCM or the W-1 cell line for varying periods with varying concentrations of IFN-gamma, TNF-alpha, Poly IC, LPS, IL-alpha, IL-1 beta, PMA, PDBu, and supernatant fluids from Con A-activated PBMC or allogeneic MLR cultures failed to induce cell adhesion molecules (CAMs) or costimulatory molecules that are not constitutively expressed on these cells except for MHC class II antigens. In addition, IFN-gamma, Con A, and MLR supernatant fluids (in order of biological activity) not only induced MHC class II antigens but also markedly increased the mean density of expression per cell of MHC class I and ICAM-1. Analysis of the stability of MHC class I/II molecules using agents like brefeldin-A and Western blot analysis of MHC class II molecules suggest that these ligands are very stably expressed on myocytes. Our previous studies have documented the failure of MHC-expressing FHCM to induce an alloproliferative response. The results of the present studies show that this failure is not secondary to the absence of ICAM-1 or LFA-3 or the presence of unstable MHC molecules but is most likely due to the absence of other CAMs/costimulatory molecules that are critically required for inducing allogeneic activation.

Cell Adhesion Molecules↗
PubMed1994

Patterns of myocardial cell adhesion molecule expression in human endomyocardial biopsies after cardiac transplantation. Induced ICAM-1 and VCAM-1 related to implantation and rejection.

Conflicting patterns of myocardial cell adhesion molecule expression associated with cardiac rejection have emerged from numerous studies of randomly selected cardiac biopsies. We designed a prospective, longitudinal study which reports both qualitative and quantitative levels of myocardial ICAM-1, VCAM-1, E-selectin, and P-selectin expression in sequential human cardiac allograft biopsies. Intense ICAM-1 and VCAM-1 staining was found in all biopsies during the first three weeks after transplant and coincided with elevated serum levels of troponin T, a sensitive marker of ischemic myocyte injury. Baseline ICAM-1 and VCAM-1 expression returned within three to four weeks, as did serum troponin T levels in all patients who did not develop rejection. All 29 rejection episodes encountered were associated with intense ICAM-1 staining, while 24 of the 29 (83%) had intense VCAM-1 staining. Increased ELAM-1 and CD62 staining was only rarely observed. Persistence of increased ICAM-1 and VCAM-1 staining after treated rejection episodes predicted a recurrent rejection episode within two months (75% positive and 100% negative predictive value). Objective quantitative measurements by radioimmunoassay (RIA) confirmed these patterns of induced ICAM-1 and VCAM-1 expression. Thus, longitudinal monitoring of serial biopsies for myocardial ICAM-1 and VCAM-1 expression could be useful in the early detection of rejection episodes and monitoring the efficacy of immunosuppressive therapy.

Adult↗
PubMed1993

Host T-cell primary allosensitization to MHC class-I- and class-II-expressing human cardiac myocytes requires the presence of a second signal.

Normal FHCMs, or transformed cell lines derived from FHCMs, such as W1, even after induction of MHC antigens by pretreatment with IFN-gamma, failed to induce proliferation of allogeneic human PBMCs in vitro. To test the hypothesis that antigen-specific T-cell activation and proliferation require not only the binding of the TCR with its ligand, the MHC molecule, but also a second signal that involves the interaction of T-cell surface molecules with their natural ligands on the stimulating cells, a mAb against CD28 was used. Cocultures of allogeneic PBMCs with IFN-gamma-pretreated irradiated FHCMs or the W1 cell line in microtiter plates containing immobilized anti-CD28 mAb induced marked stimulator cells MHC class-II-specific proliferative responses. The W1 cell line and FHCMs failed to express detectable levels of the BB1/B7 molecule (the natural ligand for CD28) as determined by flow microfluorometry or mRNA levels coding for BB1/B7 as determined by RT-PCR. These data suggest that one of the probably reasons for the failure of MHC-expressing cardiac myocytes to induce allogeneic activation is the absence of costimulatory signals.

Base Sequence↗
PubMed1991

Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease.

OBJECTIVE: --Oxidative phosphorylation (OXPHOS) deficiency due to hypoxemia or other causes was hypothesized to increase oxygen radical generation, damage mitochondrial DNA (mtDNA), and reduce adenosine triphosphate synthesis, resulting in compensatory OXPHOS gene induction. Therefore, we investigated the levels of mtDNA damage and OXPHOS transcripts in normal and ischemic hearts, and then in other forms of heart disease. DESIGN: --DNA was extracted from the heart and the levels of the common 4977 base pair mtDNA deletion were quantitated as an index for mtDNA damage. Total RNA was extracted from hearts and analyzed for OXPHOS transcript levels. RESULTS: --In control hearts, the 4977 base pair mtDNA deletion appeared at age 40 years and reached a maximum deletion of 0.0035%. Much higher levels were found in ischemic hearts (0.02% to 0.85%), as well as in three of 10 cases with other types of heart disease (0.017% to 0.16%). The OXPHOS transcripts were increased in all diseased hearts. CONCLUSION: --Ischemic hearts have increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency. Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease.

Adenosine Triphosphate↗
PubMed1991

Influence of cytokines and immunosuppressive drugs on major histocompatibility complex class I/II expression by human cardiac myocytes in vitro.

Human cardiac myocytes do not express detectable levels of major histocompatibility complex (MHC) class II antigens and express low levels, if any, of MHC class I antigens. During rejection episodes, cardiac biopsies show massive increases of MHC antigens, which are thought to be induced by cytokines released by donor-sensitized recipient mononuclear cells. In efforts to determine the nature of the cytokines that induce MHC expression on cardiac myocytes, human fetal cardiac myocyte cultures were established. Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-1, IL-2, IL-3, IL-4, and tumor necrosis factor (TNF)-alpha were added to these cultures and dose/kinetics of MHC class I/II induction quantitated. Data show that IFN-gamma induces both MHC class I and II expression, and all the other cytokines (except IL-2) induce only MHC class I but not class II. Cytokines used in combination showed that IFN-alpha with TNF-alpha was the only combination that induced MHC class II expression. Addition of immunosuppressive drugs such as cytoxan, azathioprine, cyclosporine-A, and FK-506, even when added at the initiation of the cultures, did not appreciably affect the ability of the appropriate cytokines to induce MHC expression by the myocytes in vitro.

Antibodies, Monoclonal↗
PubMed1990

Characterization of human cardiac infiltrating cells posttransplantation: II. CD4+ cloned T-cell lines with "anti-idiotype"-like reactivity.

CD4+ T cells were cultured from posttransplant cardiac biopsies placed on irradiated feeder cells of autologous cloned donor major histocompatibility complex class II-specific T-cell lines cultured and grown from previous biopsies. Fourteen of the CD4+ T-cell cultures were expanded and cloned using the same feeder cells. Two of the 14 cloned T-cell lines were examined in detail for their ability to proliferate in vitro. Clones 7E4 and 8G2 proliferated (as determined by primed lymphocyte testing) only when cocultured with a series of distinct autologous cloned T-cell lines from previous biopsies that were specific for donor-specific HLA-DR3 and HLA-DR4, respectively. In addition, when HLA-DR-specific T-cell lines were established using recipient peripheral blood mononuclear cells and a series of HLA-DR-expressing homozygous typing cells, clone 7E4 only responded to the series of distinct HLA-DR3-specific autologous cloned T-cell lines but not to autologous HLA-DR2 and -DR4, and clone 8G2 responded to 3 of 8 distinct autologous HLA-DR4-specific T-cell lines, but not HLA-DR2-specific T-cell lines. These data demonstrate that cardiac biopsies contain CD4+ T cells of recipient origin which show anti-idiotype-like reactivity against T-cell receptors specific for donor-specific major histocompatibility complex class II molecules.

Biopsy↗
PubMed1989

Aortico-right ventricular tunnel and critical pulmonary stenosis: diagnosis by two-dimensional and Doppler echocardiography and angiography.

An infant with aortico-right ventricular (AO-RV) tunnel and critical pulmonary stenosis presented with severe distress at birth. We present the clinical, echocardiographic, and angiographic features, correlated with autopsy findings. Also we discuss the differentiation from other AO-RV communications and a theory for the embryogenesis. AO-RV tunnel should be considered in the differential diagnosis of a critically sick newborn with cyanosis, a "to and fro" murmur, and signs of right heart failure. The correct diagnosis can be made echocardiographically by demonstrating the two ends of the tunnel connecting the aorta and a dilated RV, two normal coronary arteries, and obtaining high-velocity systolic and diastolic Doppler flow signals in the tunnel. Surgical repair of this lesion is possible, and early diagnosis and a modification of the surgical procedure may help survival.

Angiography↗
PubMed1988

Echocardiography-guided endomyocardial biopsy. A 5-year experience.

The number of cardiac transplant procedures performed each year continues to increase and may exceed 1,600 procedures in 1987. In these patients, the diagnosis of rejection is obtained from serial endomyocardial biopsy. The absence of clinical symptoms associated with allograft rejection with cyclosporine therapy has necessitated a predetermined routine biopsy frequency that averages 10-15 biopsies per patient in the first posttransplant year. Traditionally, fluoroscopy has been used to guide the biopsy, but this technique has a number of negative features, including cumulative radiation exposure in the physician and the patient, limited portability, and the limited area of access (intraventricular septum) for biopsy. In contrast, echocardiography provides greater portability and flexibility for location of procedure performance, eliminates radiation exposure, provides important information about cardiac function, and safely allows biopsy of any area of the right ventricle, including the free wall and apex. We performed over 4,700 individual biopsies for evaluation of rejection in 58 patients who underwent orthotopic cardiac transplantation. Fluoroscopy was not required for any of the echocardiography-guided biopsies, and only two complications occurred in 4,700 biopsies. We propose, therefore, that echocardiography is a useful alternative or adjunct to fluoroscopy for guiding endocardial biopsy and is a technique that can be learned easily by anyone now performing biopsies.

Antilymphocyte Serum↗
PubMed1986

Anatomic correction of double-outlet right ventricle with subpulmonary ventricular septal defect (the "Taussig-Bing" anomaly).

Seven patients with double-outlet right ventricle and subpulmonary ventricular septal defect (the Taussig-Bing anomaly) underwent anatomical repair at the arterial level with transfer of the coronary arteries. At the time of operation, patient ages ranged from 6 weeks to 33 months (mean 14.1 months) and weight ranged from 3.7 to 11.5 kg (mean 7.0 kg). Four patients had prior pulmonary artery banding: Two of these four also had coarctation repairs, and one had a Blalock-Hanlon septectomy. Three different patterns of coronary artery distribution were encountered. Five patients had side-to-side great arteries, and two had more or less anteroposterior great arterial relationships. There was one operative death (14.3%: 70% confidence limits 1.9 - 40.7%) resulting from muscular subvalvular right ventricular outflow tract obstruction (RVOTO). There have been no late deaths in the six survivors followed 6 to 31 months postoperatively (mean 14.8 months). One patient required closure of a residual ventricular septal defect (VSD) and infundibular resection for RVOTO 4 months postoperatively. All other survivors are functionally NYHA Class I. Five of the six survivors have undergone postoperative catheterization (mean interval 5.8 months). There was no aortic insufficiency and good ventricular function in all patients. In addition to the patient with the residual VSD, two other asymptomatic patients had mild or moderate RVOTO. Compared with alternative surgical procedures for this anomaly, anatomic correction has the advantages of acceptable operative mortality, use of the left ventricle as the systemic ventricle, no need for extracardiac conduits, and applicability to patients with all variations of coronary artery and great artery anatomy.

Child, Preschool↗
PubMed1985

Morphological observations following "anatomical correction" for abnormal ventriculo-arterial connection.

Seven postmortem hearts from children who underwent anatomical correction for complete transposition (6 cases) and double outlet right ventricle (1 case) were examined in order to gain a better understanding of the pathological morphology in relation to the surgical procedure. Associated malformations were ventricular septal defect in all, patient arterial duct in 4 and aortic coarctation in 3. In all hearts the coronary arteries arose from the facing aortic sinuses and were relocated into the facing sinuses of the pulmonary trunk with minimal displacement. The orifices of the coronary arteries were reduced in caliber in one case. The sinus node artery arising from a lateral atrial artery was transected in one case. The Lecompte maneuver was performed in 4 cases and tension on the pulmonary trunk was observed in 2 cases. Potential right ventricular outflow tract obstruction was evident in all (including one in which it had been resected during surgery). The substrates of obstruction were anomalous parietal insertion of the outlet septum (2 cases), anomalous muscular trabeculation (1 case), rightward displacement of the outlet septum (1 case), parietal insertion of the outlet septum (1 case) and restrictive muscular infundibulum (1 case--DORV). In addition, all the complete transposition cases had hypertrophy of the parietal right ventricular wall. This study highlighted the anatomical features which could lead to poor results in the anatomical correction procedure. Some of the potential problems could be avoided by minor modifications to the technique.

Female↗