Biomedical subjects

M Zembala

Publications and source records attributed to M Zembala.

At least 19 recordsLinked to original sources

PubMed2006

Polyelectrolyte adsorption layers studied by streaming potential and particle deposition.

Adsorption of a cationic polyelectrolyte, polyallylamine hydrochloride (PAH), having a molecular weight of 70,000 on mica was characterized by the streaming potential method and by deposition of negative polystyrene latex particles. Formation of PAH layers was followed by determining the apparent zeta potential of surface zeta as function of bulk PAH concentration. The zeta potential was calculated from the streaming potential measured in the parallel-plate channel formed by two mica plates precovered by the polyelectrolyte. The experimental data were expressed as the dependence of the reduced zeta potential zeta/zeta0 on the PAH coverage Theta(PAH), calculated using the convective diffusion theory. It was found that for the ionic strength of 10(-2) M, the dependence of zeta/zeta0 on Theta(PAH) can be reflected by the theoretical model formulated previously for surfaces covered by colloid particles. The electrokinetic measurements were complemented by particle deposition experiments on PAH-covered mica surfaces. A direct correlation between the polymer coverage and the initial deposition rate of particles, as well as the jamming coverage, was found. For ThetaPAH > 0.3 the initial deposition rate attained the value predicted from the convective diffusion theory for homogeneous surfaces. The initial deposition rates for surfaces modified by PAH were compared with previous experimental and theoretical results obtained for heterogeneous surfaces formed by preadsorption of colloid particles. It was revealed that negative latex deposition occurred at surfaces exhibiting negative apparent zeta potential, which explained the anomalous deposition of particles observed in previous works. It was suggested that the combined electrokinetic and particle deposition methods can be used for detecting adsorbed polyelectrolytes at surfaces for coverage range of a percent. This enables one to measure bulk polyelectrolyte concentrations at the level of 0.05 ppm.

Journal Article↗

PubMed2005

Usefulness of stanford scale of intimal hyperplasia assessed by intravascular ultrasound to predict time of onset and severity of cardiac allograft vasculopathy.

BACKGROUND: The purpose of this study was to assess the prognostic value of a single IVUS result described by the Stanford scale to predict CAV development. METHODS: Inclusion criteria were heart transplantation (OHT) before 1997 and at least one IVUS performed before 1998. IVUS studies were performed in 37 patients at 37 +/- 26 months after OHT. Based on the Stanford scale, were divided patients into Four groups: group I (grade 0 or 1): n = 4, 42 +/- 19 years, 2 men/2 women; group II (grade 2): n = 10, 44 +/- 15 years, 9 men/1 woman; group III (grade 3): n = 11, 48 +/- 11 years, 11 men; and group IV (grade 4): n = 12, 46 +/- 8 years, 12 men. We compared the incidence and time of onset of clinically significant CAV, namely significant coronary lesions, myocardial infarction and death caused by CAV. RESULTS: There was no CAV diagnosed in group I. The rates of CAV in coronary angiograms in groups II, III and IV were: 80%, 36%, and 75%, respectively. Significant CAV was found in 30%, 9%, and 50% of patients, respectively. Average times of onset of any CAV in groups II, III and IV were 4.9, 5.6, and 3.3 years, and for significant CAV were 4.1, 3.6, and 5.5 years, respectively. Deaths in groups I to IV were 1, 4, 2, and 5, respectively. CAV was the reason for death in 1 patient from group III, and 3 patients from group IV. CONCLUSIONS: Extreme grades on the Stanford scale (0, 1, and 4) describing a single IVUS study in OHT recipients appear useful to stratify patients with the lowest versus the highest risk of CAV development.

Cardiomegaly↗

PubMed2005

Usefulness of pulmonary hypertension reversibility test with sodium nitroprusside in stratification of early death risk after orthotopic heart transplantation.

AIM: To assess the prognostic value of a PH reversibility test with NPS to predict early death risk after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We analyzed the results of 94 consecutive OHT procedures performed from 2002 to 2003. Pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) were assessed as part of the routine pre-OHT evaluation. PH was excluded in 57 patients (61%, group A); TPG > or = 12 mmHg and/or PVR > 2.5 Wood units were observed in 37 patients (39%). Sixteen patients underwent a PH reversibility test with NPS: 9 patients (group B) achieved normal TPG and PVR without a drop in systolic arterial pressure (BP(s) > 85 mmHg), while a marked decrease of BP(s) (< 85 mmHg) during NPS infusion was observed in 7 patients (group C). Then, 21 patients were selected for OHT despite PH without any reversibility test. We compared the number of early deaths after OHT among groups (chi-square test). RESULTS: The 30-day death rate was 7% in group A, 11% in group B, 71% in group C, and 29% in group D. (A vs C, P = .0001 and A vs D, P = .03). Right ventricle or biventricular failure was the cause of death in 1 patient in group A, 1 patient in group B, 5 patients in group C, and 6 patients in group D (A vs C, P < .0001 and A vs D, P = .0012). CONCLUSION: PH reversibility revealed with NPS does not increase the risk of early death after OHT unless there is an absence of marked fall in systemic pressure.

Adult↗

PubMed2005

Prognostic risk factors in patients with interstitial lung disease referred for lung transplantation.

The aim of the study was to identify prognostic factors that would differentiate patients with interstitial lung disease between those with and without a chance to survive until lung transplantation. A retrospective study was performed in patients with interstitial lung disease referred for lung transplantation between September 1999 and April 2005. The analysis included the demographic data, the time from referral to transplantation, the functional tests (FVC, FEV1, FEV1%VC, the PaO(2) at rest and after oxygen supplementation via a nasal catheter), the count of NYHA functional classes, the left ventricular ejection fraction (EF), the distance covered during a 6-min walk test, and the pathogens in the respiratory tract. The patients were divided into two groups: Group 1 - lung transplant candidates who survived until the successful procedure and Group 2 - lung transplant candidates who died while on the waiting list. There were statistical differences between the two groups in PaO2 after supplementation (P=0.005), EF (P=0.002), and the 6-min walk distance (P=0.001). It appears that simple functional tests of the cardiorespiratory system may define survival of patients with interstitial lung disease waiting for lung transplantation.

Adult↗

PubMed2005

Current status of lung transplantation in Poland: experience of the Silesian Center for Heart Diseases.

Until the year 2001, lung transplantation was not available in Poland, as the only one among other kinds of solid organs transplantation. In 2001, in the Silesian Center for Heart Diseases the first successful combined heart-lung-one-block transplantation was performed. In 2003 and 2004, a successful single lung transplantation in Poland was performed in our center. Here the authors presented their experience with lung transplantation including the indications for specific types of transplantation, the immunosuppressive regimen, the management of early and late stages after lung transplantation, the infection complications, and the current problems with lung transplantation progress.

Bacterial Infections↗

PubMed2004

Characterization of polyelectrolyte multilayers by the streaming potential method.

Polyelectrolyte multilayer adsorption on mica was studied by the streaming potential method in the parallel-plate channel setup. The technique was calibrated by performing model measurements of streaming potential by using monodisperse latex particles. Two types of polyelectrolytes were used in our studies: poly(allylamine) hydrochloride (PAH), of a cationic type, and poly(sodium 4-styrenesulfonate) (PSS) of an anionic type, both having molecular weight of 70,000. The bulk characteristics of polymers were determined by measuring the specific density, diffusion coefficient for various ionic strengths, and zeta potential. These measurements as well as molecular dynamic simulations of chain shape and configurations suggested that the molecules assume an extended, wormlike shape in the bulk. Accordingly, the diffusion coefficient was interpreted in terms of a simple hydrodynamic model pertinent to flexible rods. These data allowed a proper interpretation of polyelectrolyte multilayer adsorption from NaCl solutions of various concentrations or from 10(-3) M Tris buffer. After completing a bilayer, periodic variations in the apparent zeta potential between positive and negative values were observed for multilayers terminated by PAH and PSS, respectively. These limiting zeta potential values correlated quite well with the zeta potential of the polymers in the bulk. The stability of polyelectrolyte films against prolonged washing (reaching 26 h) also was determined using the streaming potential method. It was demonstrated that the PSS layer was considerably more resistant to washing, compared to the PAH layer. It was concluded that the experimental data were consistent with the model postulating particle-like adsorption of polyelectrolytes with little chain interpenetration. It also was concluded that due to high sensitivity, the electrokinetic method applied can be effectively used for quantitative studies of polyelectrolyte adsorption, desorption, and reconformation.

Adsorption↗

PubMed2004

Induction of intracellular cytokine production in human monocytes/macrophages stimulated with ligands of pattern recognition receptors.

OBJECTIVE: This study addressed the role of the pattern recognition receptors (PRR), which recognize different molecular structures present on microorganisms, apoptotic, senescent and tumor cells, in the stimulation of human monocyte and monocyte-derived macrophages (MDM) for the production of intracellular cytokines. MATERIALS AND METHODS: Monocytes and MDM were stimulated with different ligands of scavenger receptors (SR) and mannose receptor (MR). Production of intracellular cytokines: tumor necrosis factor alpha (TNF alpha), interleukin 10 and 12 (IL-10, IL-12) was determined by flow cytometry following staining with anti-cytokine monoclonal antibodies (mAbs). RESULTS: The ligands of SR type A: fucoidan, polyguanylic acid (polyG), chemically modified low density lipoproteins (LDL), ligands of SR-B: native and chemically modified LDL, and ligand of mannose receptor (MR)-mannan induced strong expression of intracellular TNF alpha and weaker IL-10 in monocytes, while phosphatidylserine (PdS) was without effect. IL-12 was stimulated only by fucoidan and polyG. The induction of cytokine m-RNA generally followed the pattern and the magnitude of intracellular cytokine production. In MDM, intracellular TNF alpha and IL-12 expression was induced by mannan, native and modified LDL, but not other ligands. Expression of IL-10 was less pronounced and occurred following stimulation with fucoidan, polyG and modified, but not native, LDL. CONCLUSIONS: These results suggest that some PRR ligands may be involved in activation of monocytes/MDM for the production of mainly proinflammatory cytokines (TNF alpha, IL-12) implicating their role in the response to microbial and tumor invasion.

Cell Differentiation↗

PubMed2004

Pentoxyfylline in and prevention and treatment of chronic lung disease.

The anti-inflammatory effects of pentoxfylline are associated with a number of clinical benefits. These include reduction in mortality in patients who have undergone bone marrow transplants or suffer peritonitis. In infants with sepsis, a reduction in mortality has also been associated with pentoxyfylline administration. The anti-inflammatory effects of pentoxyfylline, as well as its bronchodilator, diuretic and respiratory muscle stimulant effects suggest it may have a useful role in BPD. Interim analysis of a prophylactic trial suggests pentoxyfylline may reduce treatment requirements after the neonatal period and that, in established BPD, pentoxyfylline and dexamethasone may be of similar efficacy.

Chronic Disease↗

PubMed2003

Pathologic assessment of cardiomyocytes in heart transplant recipients treated with rapamycin or cyclosporine.

The aim of this study was to compare cardiomyocytes and stromal pathology in heart transplant recipients treated with rapamycin (RAPA) versus cyclosporine (CyA). We analyzed elective biopsies obtained during first 3 months after heart transplantation in four patients treated with RAPA (24 biopsies) and seven patients receiving CyA (49 biopsies). Additional medications in both groups consisted of mycophenolate mofetil or azathioprine and prednisone. The intensity of rejection was assessed using the ISHLT scale; it was comparable in both groups based upon the number of results showing significant rejection and the average biopsy scores. Each slide was also examined under high-power magnification to sarcoplasmic and nuclear changes. Sarcoplasmic vacuolation, premyocytolysis and myocytolysis, nuclear staining, stromal fibrosis and edema, presence of vasculopathy, and lymphocytes infiltrating the myocardium occurred more frequently in the CyA group. The difference in the degree of hyperchromasia of the nuclei was highly significant (67% versus 10%, P <.00001). Our findings suggest that despite comparable levels of rejection as assessed using the ISHLT scale, patients treated with RAPA display fewer signs of cardiomyocytic alterations early after heart transplantation.

Biopsy↗

PubMed2003

Limited utility of cyclosporine C2 monitoring in heart transplant recipients receiving ketoconazole.

The aim of the study was to compare 2 hours postdose concentration (C2) of CyA in stable patients receiving ketoconazole concomitantly late after heart transplantation (OHT) with patients not receiving ketoconazole. Routine C2 and C1 (1 hour postdose concentration) of CyA monitoring (FPIA, AxSYM, Abbott) along with C0 (trough level) were performed in 64 elective patients. The KETO group consisted of 29 patients receiving 200 mg of ketoconazole daily along with CyA; the remaining 35 patients were included into the control group. Patient characteristics (KETO vs control group) were as follows: age, 49 +/- 11 versus 48 +/- 12 years; percentage of male patients, 93 versus 80; follow-up post-OHT, 4.3 +/- 2 versus 5.3 +/- 2 years. Target C0 of CyA was 175 to 225 ng/mL; CyA doses remained stable for at least 1 month. We compared maintenance doses of CyA, C0, C1, C2 of CyA, number of biopsy-proven acute cellular rejection (AR) during the one year and after the first year post-OHT, and creatinine in both groups. Statistical significance was assessed using Mann-Whitney U test. Results were as follows (KETO versus control group): CyA dose, 53 +/- 30 versus 216 +/- 69 mg, P <.000001; C0, 181 +/- 77 versus 160 +/- 53 ng/mL, NS; C1, 406 +/- 78 versus 803 +/- 317 ng/mL, P =.000001); C2, 397 +/- 174 versus 689 +/- 284 ng/mL, P =.000001, AR during the first year after OHT, 2.8 +/- 1.9 versus 2.3 +/- 1.6, NS; AR beyond first year after OHT, 0.2 +/- 0.5 versus 0.7 +/- 0.9, P =.03); creatinine, 181 +/- 50 versus 160 +/- 114 micromol/L NS. In conclusion; C2 monitoring in stable heart transplant recipients receiving cyclosporine and ketoconazole concomitantly late after procedure does not seem to be sufficient to estimate the immunosuppressive effect of this combination.

Adult↗

PubMed2003

Deterioration of renal function after replacement of cyclosporine with sirolimus in five patients with severe renal impairment late after heart transplantation.

A retrospective analysis of all cases when cyclosporine (CyA) was replaced with sirolimus (SIR) to avoid the renal toxicity of CyA late after heart transplant (OHT) was discontinued due to advanced renal impairment in all five heart transplant recipients (four men, 1 women; age 41 years, range 38-45; time after OHT 5 years, range 4-14). The serum creatinine level at the time of SIR introduction, which was 298 micromol/L (range 217-676), had remained stable for the 6 months prior to conversion. Target SIR trough levels were 12-20 ng/mL. In four patients the last dose of CyA was immediately followed by the first dose of SIR, whereas in one patient CyA was tapered gradually in the presence of low-dose SIR. Deterioration of renal function with signs of fluid overload and increased serum creatinine levels (Delta: 77, 33-150 micromol/L) was observed in all patients. Two patients required dialysis during SIR treatment including one case of pulmonary edema requiring emergency hemodialysis. None of four biopsies showed significant rejection. Four patients were converted back to low-dose CyA (including the two patients requiring dialysis during SIR therapy); one was maintained on mycophenolate mofetil. The creatinine level at the time of SIR discontinuation was (range 250-753) micromol/L, 448. Eventually, all patients required dialysis. In conclusion, replacement of cyclosporine with sirolimus in heart transplant recipients with severe renal impairment late after transplantation may accelerate renal failure.

Adult↗

PubMed2003

Postinfarction ventricular septal defect closure with Amplatzer occluders.

OBJECTIVE: Postinfarction ventricular septal defect (PIVSD) is a rare and life-threatening complication with high risk of both surgical and medical treatment. Another option available now is transcatheter closure. The purpose of this paper is to report the results of such treatment with Amplatzer occluders. METHOD: Seven patients aged from 51 to 71 years were included. The procedure was performed between 2 and 10 weeks after myocardial infarction. One patient had double residual VSD (2 months after previous surgery) and another, coexisting critical stenosis of right coronary artery (RCA). All patients were in III/IV NYHA class, on intropes, one patient on aortic balloon counterpulsation. Venous jugular approach was used to close the VSD in six patients, venous transfemoral in one patient. Implantation of six Ampaltzer atrial septal occluders (ASO) and one muscular Amplatzer VSD occluder (VSO) were performed. RESULTS: All procedures but two were finished successfully. In one patient, the defect could not be entered neither from the venous nor the arterial side due to unusual oblique course (which was confirmed during subsequent operation). In the second patient (2 weeks after MI), the reason was unstable position of 24 mm ASO (probably due to necrotic borders of VSD). Immediate significant clinical improvement was achieved in all patients, in whom PIVSD was closed with Amplatzer occluders. In one postsurgical patient, two ASO were used; in another patient, prior to VSD closure, PTCA and stent implantation to RCA was performed. The stretched diameter of PIVSD ranged from 8 to 22 mm, the size of implanted Amplatzer occluders from 12 to 24 mm. Fluoroscopy time was 60 min (18-120). During the procedure, ventricular fibrillation requiring defibrillation was observed in three patients. One patient died 1 week after the procedure because of multiorgan failure and increasing mitral incompetence (MI). CONCLUSIONS: Despite some technical problems, implantation of Amplatzer occluders, is an attractive option of treatment of patients with subacute PIVSD.

Aged↗

PubMed2002

Inflammatory components in endarterectomy lesions: an immunohistological study.

The aim of this study was to characterize the immunohistological components of chronic inflammation in endarterectomy lesions. Therefore, in 24 patients endarterectomy specimens were obtained from coronary arteries during CABG surgery (16 from RCA and 8 from LCA) and immunohistologically analyzed using avidin-biotin method (LSAB(R)/AP) with monoclonal antibodies. Macrophages and CD3 lymphocytes were counted under 200x magnification but MHC class II and ICAM-1 adhesion molecules were analyzed semi-quantitatively (scale from 0 to 3+). The mean macrophages density was 47.8+/-9.8 cells per mm2 and mean CD3 lymphocyte density was 1.3+/-0.6 cells per mm2. Lack or weak expression of HLA-DR (0-1+) on macrophages was found in 17 of 24 cases (70.8%). In the remaining seven cases (29.2%) there was a moderate and strong expression (2+ and 3+) of HLA-DR antigens. Similarly, no or weak ICAM-1 expression on macrophages was detected in 19 cases (79.2%). These cells were positively stained for ICAM-1 in only five cases (20.8%). Our data suggest that in advanced primary atherosclerotic lesions chronic inflammation is still present. On the other hand, the small number of activated inflammatory cells and the absence of positively stained endothelium suggests that inflammatory process tends to be burnt-out.

Antibodies, Monoclonal↗

PubMed2002

The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas.

BACKGROUND: Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding. AIM: To correlate these two phenomena with morphological features and survival in advanced gastric cancer. METHODS: We examined 76 cases of resected sporadic, advanced gastric cancer by means of routine morphology and a panel of microsatellite markers. Sixty-six cases were screened for presence of cancer cells circulating in blood prior to the surgery using combined morphological and immunocytochemical approach. RESULTS: Twenty-one (27.6%) cases demonstrated microsatellite instability in at least one locus. Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12) examined loci, and they were therefore designated as replication error positive (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability and in 11/47 remaining cases (difference not significant). The survival of the microsatellite instability cases was significantly better. The presence of circulating cancer cells did not correlate with survival. CONCLUSION: It is possible that the microsatellite instability status, but not circulating cancer cells, constitutes a prognostic predictive factor in advanced gastric carcinoma. Confirmation of this hypothesis requires continuation of patient follow-up.

Adult↗

PubMed2002

Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD).

Intracellular expression of several cytokines was assessed in lymphocytes and monocytes of children with transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). THI was characterized by an increased frequency of CD3+/CD4+ lymphocytes expressing tumour necrosis factor alpha (TNF-alpha), TNF-beta and interleukin 10 (IL-10), while in SIgAD elevated numbers of these cells containing TNF-alpha and interferon gamma (IFN-gamma) were observed. No changes in the number of CD4+ T cells expressing IL-4 in both diseases were noted. The proportion of CD33+ monocytes containing TNF-alpha both in THI and SIgAD was unchanged. The secretion of IL-12 by peripheral blood mononuclear cells (PBMCs) of patients with THI and SIgAD was significantly elevated and associated with an increased frequency of IL-12 expressing monocytes in THI but not in SIgAD. IL-18 secretion was slightly, but not significantly, elevated in both diseases. Intracellular Th1 and Th2 type cytokines within CD3+/CD4+ lymphocytes were also determined in the normal blood donors that showed high or low production of IgG and IgA in vitro. In low producers of IgG an increased proportion of CD3+/CD4+ cells expressing TNF-alpha and IFN-gamma was found, while in low IgA responders only elevated TNF-alpha positive CD3+/CD4+ cells were observed. These results suggest that THI and SIgAD may represent diseases with an excessive Th1 type response that is associated with an up-regulation of IL-12 secretion and, at least in THI, elevated numbers of monocytes expressing intracellular IL-12. Up-regulation of IL-12 may be the essential factor in the patomechanism(s) of these diseases as already described in common variable immunodeficiency (CVID).

Agammaglobulinemia↗

PubMed2002

CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies.

The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. The aim of the study was to evaluate monocyte expression of human leucocyte antigen (HLA)-DR and Fc receptor III (FcR III) (CD16) in neonates and small children with high risk of sepsis (hospitalized at the intensive care unit). The reduced proportion of CD14+HLA-DR+ monocytes was observed in all patients at the intensive care unit, while the increase of CD16 expression on monocytes was observed in the course of sepsis. The measurement of CD16 expression on monocytes also proved to be more useful for monitoring patient. The proportion of both CD14dimCD16+ and CD14highCD16+ monocytes increased during sepsis; however, monocytes showed reduced ability to phagocytose Escherichia coli, compromised ability to cooperate with T cells and reduced CD86 expression in parallel to HLA-DR depression. The reduced interleukin (IL)-1 but rather increased IL-10 production was associated with sepsis. The differences between CD14+CD16+ monocytes of healthy donors and patients with sepsis are discussed.

Child, Preschool↗

PubMed2001

Cross-talk between human monocytes and cancer cells during reactive oxygen intermediates generation: the essential role of hyaluronan.

Human monocytes exhibit considerable cytocidal activity against tumor (but not normal cells) associated, at least partly, with the generation of reactive oxygen intermediates (ROIs). The present study examined the role of surface determinants and hyaluronan (HA) in the induction of ROI production by human monocytes stimulated with cancer cells, as measured by luminol-enhanced chemiluminescence (CL). The inhibitory effect of monoclonal antibodies (MAbs) indicated the engagement of CD18, CD29 and CD44 adhesion molecules. Preincubation of monocytes and tumor cells, expressing CD44 determinants, with either anti-CD44 MAb or HA inhibited CL generation. Addition of HA to monocytes decreased the expression of CD44 and induced CL response. Supernatants from the cultures of tumor cells stimulated CL response of monocytes, an effect that was abolished by treatment of the supernatants with hyaluronidase (HAase) or by preincubation of monocytes with an anti-CD44 MAb. These results indicate that several surface molecules of monocytes, including CD44, are required to trigger the generation of ROI after their contact with tumor cells, whereas HA overexpressed on some cancer cells may allow monocytes (via CD44) to distinguish between transformed and normal cells. However, blocking of CD44 on monocytes by free HA dampens their response to tumor cells. Taken together, these observations suggest that the presence of HA in the tumor stroma may modulate effector functions of infiltrating macrophages and their interactions with cancer cells in situ.

CD18 Antigens↗

PubMed2001

Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results.

BACKGROUND: Previous studies have shown disappointing results for immunosuppressive treatment in patients with dilated cardiomyopathy. Therefore, we studied the effectiveness of such therapy in patients with HLA upregulation on biopsy. METHODS AND RESULTS: Of 202 patients with dilated cardiomyopathy, 84 patients with increased HLA expression were randomized to receive either immunosuppression or placebo for 3 months; they were then followed for 2 years. After 2 years, there were no significant differences in the primary end point (a composite of death, heart transplantation, and hospital readmission) between the 2 study groups (22.8% for the immunosuppression group and 20.5% for the placebo). The secondary efficacy end point included changes in ejection fraction, end-diastolic diameter, end-diastolic volume, end-systolic volume and NYHA class; left ventricular ejection fraction increased significantly in the immunosuppression group compared with the placebo group (95% CI, 4.20 to 13.12; P<0.001) after 3 months of follow-up. The early favorable effects of immunosuppressive therapy on left ventricular volume, left ventricular diastolic dimension, and New York Heart Association class were also present. This improvement was maintained in the immunosuppression group at 2 years (ejection fraction: 95% CI, 6.94 to 19.04; P<0.001). In addition, on the basis of the protocol-specified definition of improvement, 71.8% patients in the immunosuppression group versus 20.9% patients in the placebo group met the criteria of improvement after 3 months (P<0.001). At the end of the follow-up period, 71.4% patients from the immunosuppression group versus 30.8% patients from the placebo group were improved (P=0.001). CONCLUSIONS: These data demonstrate a long-term benefit of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA upregulation on biopsy specimens. Thus, restoration of immunosuppressive therapy for such patients should be considered.

Adult↗