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Biomedical subjects

S M Kang

Publications and source records attributed to S M Kang.

At least 19 recordsLinked to original sources

Experience with steroid-free maintenance immunosuppression in simultaneous pancreas-kidney transplantation.

INTRODUCTION: Steroid avoidance is possible in simultaneous pancreas-kidney transplantation with the use of newer immunosuppressive agents and induction therapy. We undertook a retrospective consecutive case review of patients treated at a university tertiary referral center. METHODS: Medical records of 44 consecutive patients receiving a pancreas-kidney transplant from November 2000 to September 2002 were reviewed. The immunosuppression protocol used in this series of patients consisted of thymoglobulin induction, combined with mycophenolate mofetil, tacrolimus, and sirolimus for maintenance immunosuppression. Steroids were used only while thymoglobulin was given and were typically discontinued by postoperative week 1. Main outcome measures included graft and patient survival rates, rejection rates of the kidney or pancreas, infection rates, and surgical complication rates. RESULTS: All 44 patients received a kidney-pancreas transplant with systemic venous anastomosis and enteric drainage of the pancreas. Patient kidney, and pancreas survival rates were 95.6%, 93.2%, and 88.7%, respectively. Biopsy-proven pancreas rejection rates at 1 and 6 months posttransplant were 2.3% and 2.3%. Kidney rejection rates at 1 and 6 months were 2.3% and 4.6%. Reasons for patient loss included one death from sepsis and one cardiovascular death. Reasons for kidney loss besides death included a thrombotic microangiopathy. Reasons for pancreas loss included three thromboses, one mild rejection/infection, and one duodenal segment leak with infection. All patients who have been free of rejection have been off steroids for the duration of follow-up. CONCLUSIONS: Newer immunosuppression protocols without maintenance steroids are possible with minimal rejection in the first 3 months and equivalent patient and graft survival rates compared with earlier protocols utilizing steroids. The potential beneficial long-term impact of steroid avoidance will require further study.

Cause of Death↗

Effects of left atrial compliance on left atrial pressure in pure mitral stenosis.

In mitral stenosis (MS), left atrial (LA) pressure is commonly elevated because of increased LA afterload. There is a wide spectrum of LA pressure in patients with MS, however, despite a similar mitral valve orifice area. LA compliance is an important determinant of both cardiovascular performance and pathological physiology. Few data are available, however, regarding the effects of LA compliance on LA pressure. We hypothesized that LA pressure may be higher in patients with decreased LA compliance. We analyzed the right heart and transseptal catheterization data in 47 patients (41 female, mean age 40 +/- 10 years) with pure MS and sinus rhythm. The magnitude of LA a and v waves was measured from transseptal catheterization. Fick's method was used to determine cardiac output. LA compliance was calculated by dividing the systolic rise in LA pressure (DeltaP(LA) = P(LA(v)) - P(LA(x))) into the stroke volume. LA size, mitral valve area (MVA), mean diastolic pressure gradient (MG), left ventricular (LV) end-diastolic and end-systolic dimensions were obtained by using two-dimensional and Doppler echocardiography. Multiple regression analysis was performed to identify independent factors determining LA pressure. The mean MVA was 0.95 +/- 0.22 cm(2). MG and LA dimension were 11.2 +/- 5.2 mm Hg and 50.6 +/- 5.2 mm, respectively. The mean LA pressure and cardiac output obtained by cardiac catheterization were 23.4 +/- 8.4 mm Hg and 4.3 +/- 1.5 L/min, respectively. The calculated LA compliance was 4.9 +/- 2.8 cm(3)/mm Hg. Univariate analysis showed that factors associated with increased LA pressure were smaller MVA (r = -0.33, P < 0.05), higher MG (r = 0.69, P < 0.01) and lower LA compliance (r = -0.55, P < 0.01); among them, MG (beta coefficient 0.59, SE 0.19, P < 0.01) and LA compliance (beta coefficient -0.26, standard error 0.34, P < 0.05) were the strongest predictors of LA pressure. In conclusion, LA compliance, along with MG that reflects the severity of MS, is an important contributing factor determining LA pressure in patients with pure MS and sinus rhythm.

Adult↗

Posttraumatic concerns: a patient-centered approach to outcome assessment after traumatic physical injury.

BACKGROUND: Approximately 2.5 million Americans are admitted to the hospital after traumatic physical injury each year. Few investigations have elicited patients' perspectives regarding posttraumatic outcomes. OBJECTIVE: To identify and categorize physically injured trauma survivors' posttraumatic concerns. RESEARCH DESIGN: Prospective longitudinal investigation; trauma survivors were interviewed during the post-injury hospitalization and again 1, 4, and 12 months after the trauma. SUBJECTS: Ninety-seven, randomly selected, English speaking, hospitalized survivors of motor vehicle-crashes or assaults. MEASURES: At the end of each interview patients were asked, "Of all the things that have happened to you since you were injured, what concerns you the most?" Using an iterative process and working by consensus, investigators categorized patient concerns in content domains. Concern domains were then compared with established measures of posttraumatic stress disorder (PTSD) symptoms and limitations in physical functioning. RESULTS: Seven categories of posttraumatic concerns were identified. During the course of the year, 73% of patients expressed physical health concerns, 58% psychological concerns, 53% work and finance concerns, 40% social concerns, 10% legal concerns, 10% medical concerns, and 20% uncodable concerns. Rater agreement on concern categorization was substantial (kappa = 0.72). The mean number of concerns expressed per patient gradually decreased over time (1 month mean = 1.51; 12 month mean = 1.26) and resembled the trajectories of PTSD symptoms and functional limitations. CONCLUSIONS: The concerns of physically injured trauma survivors are readily elicited and followed up during the course of the year after injury. Open-ended inquiry regarding posttraumatic concerns may complement standardized outcome assessments by identifying and contextualizing the outcomes of greatest importance to patients.

Adult↗

A combination analysis of p53 and p21 in gastric carcinoma as a strong indicator for prognosis.

We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to investigate the clinical significance of p53-p21 pathway in this disease. One hundred sixty-four primary gastric carcinoma specimens were immunohistochemically stained for p53 and p21 protein, and clinicopathological features of the cases were examined. P53 was stained negatively, while p21 was stained positively in each normal stomach epithelium. P53, and p21 positive staining was observed in 82 (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21 pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less aggressive characteristics, and no recurrent disease after curative resection. While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in 32.9% of the tumors, displayed significantly more aggressive characteristics, poorer survival and higher recurrence rate than the tumors demonstrating other staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The combined evaluation of p53 and p21 expression in gastric carcinoma tissues is suggested to have clinical importance by indicating not only the malignant potential of each tumor, but also the prognosis of this disease.

Adenocarcinoma↗

Laparoscopic live donor nephrectomy at the University of California San Francisco.

Laparoscopic donor nephrectomy is quickly becoming the preferred technique for kidney retrieval, since it removes many of the disincentives of kidney donation. Our experience at UCSF has confirmed that the procedure is safe, with excellent donor recovery. The transplanted kidney appears to function as well as any kidney retrieved using an open technique, at least in the short-term. Development of a successful laparoscopic donor program is best done initially with a team approach, utilizing the skills of an advanced laparoscopic surgeon, and with careful patient selection. With time, the technique can be done well by properly trained transplant surgeons with basic laparoscopic skills, with or without a hand-assist technique. As experience grows, this procedure can be applied to virtually every potential donor, and hopefully will improve live kidney donation rates.

Academic Medical Centers↗

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants.

BACKGROUND: Fas ligand (FasL) mediates apoptosis of susceptible Fas-expressing lymphocytes, and may contribute to the maintenance of peripheral tolerance. In transplantation models, however, artificial expression of FasL on cellular as well as islet transplants results in accelerated rejection by neutrophils. The mechanism of the neutrophilic response to FasL expression is unknown. FasL, like other members of the tumor necrosis factor family, is cleaved to a soluble form by metalloproteases. We tested the hypothesis that soluble FasL (sFasL) was responsible for neutrophil migration by creating a non-cleavable mutant of FasL. METHODS: Three mutants of FasL with serial deletions in the putative proteolytic cleavage site of human FasL were made using inverse polymerase chain reaction. The relative fractions of sFasL and membrane-bound FasL were assessed by Western blot and immunoprecipitation, as well as by cytotoxicity assay using Fas-expressing target cells. The fully non-cleavable mutant was transduced into murine islets as well as myoblasts and tumor cell lines, and tested in a murine transplantation model. RESULTS: Serial deletions in the putative metalloprotease site of FasL resulted in a fully non-cleavable mutant of FasL (ncFasL). Expression of ncFasL in tumor lines induced higher levels of apoptosis in Fas bearing targets than wild-type FasL. Transplantation of ncFasL-expressing islets under the kidney capsule of allogenic mice resulted in accelerated rejection identical to that seen with wild-type Fas ligand-expressing islets. Myoblasts and tumor cell lines expressing ncFasL also induced neutrophil infiltration. CONCLUSIONS: Membrane-bound Fas ligand is fully capable of inducing a neutrophilic response to transplants, suggesting an activation by Fas ligand of neutrophil chemotactic factors.

Animals↗

Is the left atrial v. wave the determinant of peak pulmonary artery pressure in patients with pure mitral stenosis?

A large left atrial (LA) v. wave can be observed in patients with pure mitral stenosis (MS) because of decreased LA compliance. Few data are available regarding the relation between the magnitude of the LA v wave and pulmonary artery pressure in MS. We hypothesized that pulmonary artery pressure may be higher in patients with decreased LA compliance and thus a large v. wave. We analyzed the right-sided cardiac and transseptal catheterization data in 113 patients (16 men and 97 women, mean age 39 years) with pure rheumatic MS in sinus rhythm. Peak systolic, diastolic, and mean pulmonary artery pressures were measured with right-sided cardiac catheterization. The magnitude of LA a and v. waves were measured through transseptal catheterization. Two-dimensional and Doppler echocardiography were also performed to measure LA size, mitral valve area, mean mitral gradient, and valvular regurgitation. Multiple regression analysis was performed to identify the most important factor in the determination of pulmonary artery pressure. A large v wave, defined if peak v wave height exceeded the mean LA pressure by > or =10 mm Hg, was observed in 43 of 113 patients (38%). Increased pulmonary artery systolic pressure (> or =50 mm Hg) was observed in 38 patients (34%). Univariate analysis showed that the factors associated with increased pulmonary artery systolic pressure were smaller mitral valve area, higher mean mitral gradient, higher mean LA pressure, and higher LA v. wave; among them, LA v wave (p <0. 001) and mean mitral gradient (p<0.001) were significant independent factors for pulmonary artery systolic pressure in multivariate analysis. In conclusion, in patients with pure MS and sinus rhythm, the magnitude of the LA v. wave is strongly associated with pulmonary artery pressure. This finding may suggest that LA compliance is a major contributing factor determining pulmonary artery pressure in pure MS.

Adult↗

A dendritic cell line genetically modified to express CTLA4-IG as a means to prolong islet allograft survival.

BACKGROUND: Dendritic cells are potent antigen-presenting cells that bind allogeneic T cells. They are thus candidates for targeting immunoregulatory molecules to the alloreactive T cell compartment and suppressing the alloimmune response. METHOD: A dendritic cell line derived from the BALB/c mouse (H2d) was genetically modified to express the immunoregulatory molecule CTLA4-Ig. The ability of these dendritic cell transfectants to downregulate the alloimmune response was tested in an islet transplant model. Allogeneic C57Bl/6 (H2b) mice were rendered diabetic with streptozocin, and they received BALB/c islet (H2d) transplants. Mice were administered 25 million untransfected or CTLA4-Ig-transfected D2SC/1 cells i.v. on the day of islet transplantation and 6 days later[fnc]. RESULT: Mice treated with CTLA4-Ig-transfected D2SC/1 cells demonstrated prolonged allograft survival (mean = 20 days, median = 17 days, SD = 9.39) compared with mice treated with untransfected D2SC/1 cells (mean = 12 days, median = 11 days, SD=2.74) or untreated control mice (mean = 11 days, median = 11 days SD = 1.41). Third party allograft survival was not prolonged in mice receiving similar treatment. CONCLUSIONS: These results demonstrate that a genetically modified dendritic cell line can suppress the alloimmune response and prolong islet allograft survival in an allospecific manner. The findings also suggest that genetically modified dendritic cells may be useful in targeting alloreactive T cells and prolonging allograft survival.

Abatacept↗

Enhanced detection of left atrial spontaneous echo contrast by transthoracic harmonic imaging in mitral stenosis.

BACKGROUND: Spontaneous echo contrast (SEC) of the left atrium is associated with increased risk of thromboembolism in patients with mitral stenosis (MS). The determination of the presence and severity of left atrial (LA) SEC is of prognostic importance in these patients. Harmonic imaging (HI), a novel echocardiographic technique that differs from conventional fundamental imaging (FI) in that it involves transmitting ultrasound at one frequency and receiving at twice the transmitted frequency, produces better endocardial border definition and myocardial opacification. However, there are no data about its value for the detection of LA SEC. The purpose of this study was to investigate the utility of transthoracic noncontrast tissue HI in the detection of LA SEC in patients with MS. METHODS: Seventy-four consecutive patients with MS (49 women, mean age 51 years) underwent standard transthoracic echocardiography (TTE) in both HI and FI modes and transesophageal echocardiography (TEE) to determine the presence and severity of LA SEC. Left atrial SEC was graded by TEE as either mild (only seen at high gain) or severe (visible in the entire left atrium at normal gain control of the equipment). The control group comprised 30 patients randomly selected from patients who did not have LA SEC at the TEE examination. RESULTS: Atrial fibrillation was found in 46 patients (62.2%). The mean mitral valve area and mean mitral gradient were 1.0+/-0.3 cm(2) and 8.2+/-4.1 mm Hg, respectively. Nine patients (12.2%) had episodes of systemic embolism; 8 had stroke, and 1 had peripheral embolism. Left atrial thrombus was found in 11 patients (14.9%) by TEE. Left atrial SEC was present in all but one patient by TEE (mild in 35 patients, severe in 38). Fundamental imaging with TTE, however, revealed LA SEC in only 5 (6.8%) of the 73 patients. In contrast, with HI, LA SEC could be detected in 63 (86.3%) patients. In the detection of severe LA SEC, the sensitivities of FI and HI were 13.2% (5/38) and 100% (38/38), respectively. Left atrial SEC was not observed in control subjects by either FI or HI. CONCLUSIONS: Transthoracic HI significantly enhances the detection of LA SEC in patients with MS.

Adolescent↗

Patients with recognized psychiatric disorders in trauma surgery: incidence, inpatient length of stay, and cost.

BACKGROUND: Although psychiatric disturbances are highly prevalent among traumatically injured inpatients, few investigations have assessed the impact of these disorders on surgical length of stay (LOS) and cost. METHODS: The authors identified all trauma-registry recorded psychiatric diagnoses among patients admitted to University of California Davis Medical Center between January 1993 and December 1996. Linear and logistic regressions were used to assess the unique effects of psychiatric diagnoses on inpatient LOS and cost. RESULTS: A total of 29% of patients had one or more registry-recorded psychiatric diagnosis. Patients with alcohol abuse diagnoses demonstrated 10% to 12% decreases in LOS and cost (p < 0.01), whereas patients with stress disorders, delirium, and psychoses demonstrated 46% to 103% increases in LOS and cost (p < 0.01). CONCLUSION: Patients with recognized psychiatric disorders uniquely impact inpatient trauma surgery LOS and cost. Additional investigations of the processes and outcomes of care could lead to cost-effective performance improvement efforts that target the amelioration of comorbid psychiatric disorders among physically injured trauma survivors.

Adolescent↗

Assessment of elastic properties of the descending thoracic aorta by transesophageal echocardiography with acoustic quantification in patients with a stroke.

Previous studies have described the use of transesophageal echocardiography (TEE) with acoustic quantification (AQ) in assessing aortic elastic properties. We hypothesized that patients with a prior history of stroke (ST) may have a higher risk of atherosclerotic change in great vessels compared to nonstroke subjects (NST) and thus have decreased elastic properties. We assessed the elastic properties of the descending thoracic aorta (DTA) by TEE in ST patients and compared them with data in NST patients. Subjects included 31 with ST without any evidence of emboli originating from the heart (age 51 +/- 10 years, M:F = 20:11) and 25 age-matched NST (M:F = 8:17). Patients with significant valvular heart disease including aortic and mitral regurgitation, left ventricular dysfunction (ejection fraction < 55%), and congenital heart disease were excluded. Compliance (C), distensibility (D), and stiffness index (SI) were measured using AQ and M-mode measurement at a level of the left atrium. We scored atherosclerotic risk factors (ARF) such as a history of diabetes, hypertension, smoking, hypercholesterolemia, and the presence of atheroma of DTA. There was no evidence of atheroma of DTA in NST. There were no significant differences in heart rate and systolic and diastolic blood pressure between ST and NST patients. Fractional area change (FAC) of DTA was significantly lower in ST than in NST patients (3.2 +/- 1.6 vs 5.4 +/- 2.5%, P = 0.000). ST patients had significantly lower C (1.2 +/- 0.4 vs 1.5 +/- 0.7 x 10(-3) cm2 mmHg(-1), P = 0.039), lower D (0.8 +/- 0.3 vs 1.5 +/- 0.8 x 10(-3) mmHg(-1), P = 0.000), and higher SI (10.3 +/- 8.8 vs 5.3 +/- 2.9, P = 0.006) than NST patients. ST patients without atheroma of DTA (n = 21) also had significantly lower C (1.1 +/- 0.4 vs 1.5 +/- 0.7 x 10(-3) cm2 mmHg(-1), P = 0.038) and lower D (3.5 +/- 1.4 vs 4.8 +/- 2.4 x 10(-3) mmHg(-1), P = 0.021) than NST patients. There was a significant positive correlation between SI and the score of ARF (r = 0.51, P = 0.000). The regional elastic properties of DTA measured by TEE with AQ and M-mode method were abnormal in ST. Therefore, TEE with AQ technique may have a possible clinical application for the detection of early atherosclerotic changes such as alteration of elastic properties in morphological normal DTA.

Acoustics↗

Expression of osteopontin in calcified coronary atherosclerotic plaques.

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

Aged↗

Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: potential role in intimal neovascularization.

Neovascularization of the adventitial vasa vasorum with extension into the intima of atherosclerotic lesions is frequently observed, but its pathophysiological significance is still subject to debate. Recently, leptin, the product of the Ob gene, was identified. Leptin, via activation of the endothelial receptor (Ob-R), generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We hypothesized that a high concentration of leptin within vasa vasorum and plaque itself, may influence inflammatory and vascular neovascularization coupling with functional upregulation of the vascular endothelial growth factor (VEGF). Microscopic computerized tomography was utilized for the spatial distribution of vasa vasorum and intimal neovascularization from atherosclerotic human coronary arteries. Atherosclerotic coronary arteries showed a dense plexus of microvessels in the adventitia and plaque itself. Microscopic analysis from human atherosclerotic aortas revealed an increase in the intimal thickness with neovascularization. The immunoreactivity for Ob-R, VEGF and matrix metalloproteinase (MMP) increased in atherosclerotic plaque, predominantly in the endothelial lining of the intimal neovessel and macrophages/foam cells. Our observation of a prominent colocalization between Ob-R, VEGF and MMP supports this hypothesis and these factors participate in the neovascularization of atherosclerotic lesions. The present study is the first report on vascular tissue and it opens a promising perspective concerning future investigations of leptin-dependent modulation of atherogenesis and vascular neovascularization under pathophysiolgical conditions.

Adult↗

Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions.

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.

Animals↗

A case of endobronchial aspergilloma.

Pulmonary aspergillosis may be classified under three categories, depending upon whether the host is atopic or immunocompromised: invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma. However, it is not always possible to effectively categorize this disease. We experienced a case of endobronchial aspergilloma, which was difficult to categorize, in a healthy male patient. The chest X-ray and computed tomography showed an ill-defined nodule mimicking lung cancer. Fiberoptic bronchoscopy revealed an aspergilloma without cavity formation in the left lower laterobasal segmental bronchial orifice. The aspergilloma was removed and the patient's symptoms were relieved. We present this unusual case with a review of the literature.

Adult↗

Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Solid tumors require neovascularization for growth and metastasis. Vascular endothelial growth factor (VEGF) is a well-characterized inducer of angiogenesis, while, thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the expressions of these antigens and their relationship with microvessel density, and determined their prognostic significance. One hundred specimens resected from patients with colorectal adenocarcinoma were examined using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were VEGF-positive and TSP-1-negative than in other tumors. Patients with VEGF-positive tumors had a significantly worse prognosis than did those with VEGF-negative tumors, and TSP-1 expression was inversely correlated with prognosis. The frequency of hepatic recurrence was significantly higher in patients with tumors that were VEGF-positive and TSP-1-negative than in all other patients. In conclusion, VEGF and TSP-1 are important regulators of tumor angiogenesis, and combined analysis of VEGF and TSP-1 may be useful for predicting recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗

Apoptosis in dilated cardiomyopathy.

OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.

Adult↗