Prognostic impact of multiple fragmented QRS on cardiac events in idiopathic dilated cardiomyopathy.

AIMS: To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR' patterns in ≥2 contiguous leads representing the anterior (V1-V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8-6.2), 31 (11%) patients experienced hard cardiac events. Kaplan-Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07-4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P < 0.001). CONCLUSION: Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.

Morphological analyses of nephrin expression in progressive glomerulonephropathy of common marmosets.

In this study, we focused on nephrin, one of the key molecules within the slit diaphragm of podocytes, as although there have been reports on its expression in humans and rats, their presence in common marmosets has not been reported. We investigated nephrin expression and changes in glomeruli, depending on the development of spontaneous progressive glomerulonephropathy in common marmosets. Nineteen common marmosets at two to ten years of age were evaluated. The kidney was examined by microscopy with hematoxylin and eosin and immunohistochemical staining for nephrin. The lesions were classified into three grades according to a renal lesion grading system reported previously. The nephrin-positive area was measured by morphometric analysis, and the nephrin-positive ratio was calculated. Nephrin expression was observed along the glomerular capillary loop in a continuous linear pattern in renal lesion grades 0 to 2 and either discontinuous linear or coarse granular pattern in grade 3. Nephrin expression tended to decrease significantly depending on the grade of renal lesions. Alteration in nephrin expression has been suggested to play an important role in the progression of renal lesions.

Immunohistochemical Characteristics of Thymomas and Hyperplastic Lesions in Wistar Hannover Rats.

Previously, we investigated the higher incidence of hyperplastic lesions and thymomas and histopathological resemblance of cortex-medullary structures between thymomas and normal thymuses in Wistar Hannover (WH) rats. Thymomas had pale-staining cell foci (PA) similar to medulla but without lymphocytes. Here, we focused on the differences in cytokeratin (CK) expression in the thymic epithelia of the cortex and medulla and compared the structures of thymomas and normal thymuses. Thymomas, hyperplastic lesions, and normal thymuses obtained from background studies of WH rats were stained with antibodies against CK14, CK18, and CD20. In normal thymuses, the epithelial cells were positive for CK14 in the medulla and subcapsular area and for CK18 in the cortex, B-cells were positive for CD20 in the medulla. In thymomas, the epithelial cells were positive for CK14 in the medullary differentiation (MD) areas and for CK18 in the cortex-like lymphocyte rich and PA, and B-cells were positive for CD20 in the MD areas.

Prognosis and Clinical Characteristics of Dilated Cardiomyopathy With Family History via Pedigree Analysis.

BACKGROUND: The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25-16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022). CONCLUSIONS: DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.

A spontaneous middle ear adenocarcinoma characterized by abundant eosinophilic matrix in a young male Crl:CD(SD) rat.

A mass was detected in the right tympanic cavity of a 15-week-old male Crl:CD(SD) rat. Histological examination revealed papillary or tubular proliferations of epithelial cells including ciliated cells that produce mucus and have an abundant eosinophilic matrix. The malignancy of this tumor was revealed by its destructive proliferation, cellular polymorphism, and high proliferative activity. The tumor was diagnosed as a middle ear adenocarcinoma due to its location and histological characteristics. This is the first report of a middle ear adenocarcinoma in rats and the first middle ear tumor accompanied by eosinophilic matrix observed in either humans or animals. The eosinophilic matrix was positive for periodic acid-Schiff and periodic acid-silver methenamine stains and for laminin and collagen Type IV, immunohistochemically, but negative for Congo red, which suggested that this matrix was a basement membrane substance.

Small Hyperintensities in the Area of the Perforating Arteries in Patients with Seizure.

BACKGROUND/AIM: We previously observed spotty hyperintense lesions in the region of the perforating arteries on peri-ictal diffusion-weighted imaging (DWI); however, no report has formally described these findings. The aim of this study was to investigate focal intensities on peri-ictal DWI, and to evaluate the clinical significance of these lesions. METHODS: We conducted a retrospective review of 677 consecutive patients with seizure who completed peri-ictal DWI within 24 h after seizure onset. Patients were grouped according to the presence or absence of diffusion hyperintense lesions (DHLs) in the region of the perforating arteries. We compared clinical and imaging characteristics between these 2 groups. RESULTS: Among 677 patients, 23 patients (3.4%) had DHLs. Analyses of apparent diffusion coefficient values and fluid attenuated inversion recovery images suggested that DHLs were acute or subacute ischemic lesions that had appeared prior to seizure onset. Patients with DHLs were more likely to be older in age, have atrial fibrillation, and coronary artery disease, and have more severe deep white matter hyperintensity or leukoaraiosis compared to patients without DHLs. CONCLUSION: DHLs detected on peri-ictal DWI may represent incidental acute cerebral microinfarcts in the aging brain, especially in patients with small vessel disease.

Relationship Between Immunoglobulin Deposition and Early Lesions of Progressive Glomerulonephropathy in Young Common Marmosets.

The authors previously investigated progressive glomerulonephropathy in 2- to 11-year-old common marmosets and characterized age-related changes of the renal glomeruli and development of tubulointerstitial lesions. In this study, immunoglobulin deposition and ultrastructural changes of the glomeruli were investigated in 5 young marmosets from 6 months to 3 years of age with pre-onset or early glomerulonephropathy. In all animals, the foot processes of podocytes were effaced, and IgM was deposited into the glomeruli. In glomeruli without glomerular basement membrane (GBM) alteration, IgM was the only immunoglobulin type deposited in the glomeruli. In cases with more advanced lesions of reticulation and thickening of GBM, IgA and IgG deposits were also observed. Therefore, the authors conclude that IgM may be the primary or earliest immunoglobulin deposited in this nephropathy, whereas IgA and IgG deposition may be connected to the progression of the glomerular lesions. IgM deposition and foot process effacement of podocytes occur early in the life of affected marmosets.

Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia.

Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient.

Erratum to: Preoperative brain magnetic resonance imaging and postoperative delirium after off-pump coronary artery bypass grafting: a prospective cohort study.

Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0327-x. In the published version, the first name of the third author is incorrect and should read Naoaki Yamada as given in this erratum. The publisher apologizes most sincerely for this error.

Preoperative brain magnetic resonance imaging and postoperative delirium after off-pump coronary artery bypass grafting: a prospective cohort study.

BACKGROUND: Delirium after cardiac surgery is a serious complication, increasing morbidity and mortality. Despite its high expectations, off-pump coronary artery bypass grafting (OPCAB) has largely failed to reduce the incidence of postoperative neurological complications. To further investigate the reasons for this failure, we used perioperative brain magnetic resonance imaging (MRI) to determine the relation between MRI findings and postoperative delirium. METHODS: Altogether, 98 patients undergoing elective OPCAB were enrolled in this prospective observational study. Patients underwent brain MRI and magnetic resonance angiography (MRA) before and after surgery to identify cerebral infarction, white matter lesions, and intracranial artery stenosis. Postoperative delirium in the intensive care unit was measured using the delirium rating scale. The relation between postoperative delirium and MRI findings was examined using logistic regression. RESULTS: Magnetic resonance imaging and MRA was completed in 88 (90%) of the patients. New ischemic lesions were present in seven (7.9%) patients. Delirium rating scale scores of 0, 1-7, and ≥ 8 were found in 25 (31%), 48 (60%), and seven (9%) patients, respectively. Multivariate logistic regression analysis revealed that new ischemic lesions (odds ratio [OR] 11.07, 95% confidence interval [CI]: 1.53 to 80.03; P = 0.017), carotid artery stenosis (OR 7.06, 95% CI: 1.59 to 31.13; P = 0.010), history of myocardial infarction (OR 3.78, 95% CI: 1.05 to 13.65; P = 0.043), and deep subcortical white matter hyperintensity (OR 3.04, 95% CI: 1.14 to 8.12; P = 0.027) were significantly associated with postoperative delirium. CONCLUSIONS: Magnetic resonance imaging findings of new cerebral ischemic lesions, carotid stenosis, and deep subcortical white matter hyperintensity correlated significantly with postoperative delirium in patients who had undergone OPCAB surgery.

Detectability of ischemic lesions on diffusion-weighted imaging is biphasic after transient ischemic attack.

BACKGROUND: Experimental studies of transient focal ischemia indicate biphasic detectability of lesions by diffusion-weighted imaging (DWI); poorly detectable phase exists at 1-12 hours after reperfusion. The present study aimed to clarify whether poorly detectable phase also exists in DWI of transient ischemic attack (TIA) patients. METHODS: A retrospective study was conducted in 144 consecutive TIA patients who underwent magnetic resonance imaging (MRI) within 2 weeks after carotid TIA. Patients were classified into 9 groups according to time from disappearance of TIA symptoms to DWI: intraischemic period, 0-1 hour, 1-12 hours, 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA. RESULTS: Lesions were detected in 33 of 144 patients (22.9%). The frequency of positive lesions was 20% in the intraischemic period and 30.8% at 0-1 hour after the end of TIA; it markedly decreased to 8.7% at 1-12 hours after end of TIA. Thereafter, it increased to 21.7%, 30.8%, 36.4%, 37.0%, 38.5%, and 30% at 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA, respectively. In 7 patients, MRI was repeated twice, at 1-12 hours and then at 5-13 days after the end of TIA. Lesions were never detected on the first MRI but were clearly demonstrated in 4 of 7 patients on the second MRI. CONCLUSIONS: The detectability of ischemic lesions may be biphasic after TIA as indicated by experimental studies.

Morphometric analysis of progressive changes in hereditary cerebellar cortical degenerative disease (abiotrophy) in rabbits caused by abnormal synaptogenesis.

We previously investigated rabbit hereditary cerebellar cortical degenerative disease, called cerebellar cortical abiotrophy in the veterinary field, and determined that the pathogenesis of this disease is the result of failed synaptogenesis between parallel fibers and Purkinje cells. In this study, longitudinal changes in the development and atrophy of the cerebellum of rabbits with hereditary abiotrophy after birth were morphometrically examined (postnatal day [PD] 15 and 42) using image analysis. Although development of the cerebellum in rabbits with abiotrophy was observed from PD 15 to PD 42, the growth rate of the cerebellum was less than that in normal rabbits. In rabbits with abiotrophy, the number of granular cells undergoing apoptosis was significantly higher at PD 15 and dramatically decreased at PD 42. The number of granular cells did not increase from PD 15 to 42. The synaptogenesis peak at PD 15 occurred when the largest number of apoptotic granular cells in rabbits with abiotrophy was observed. Although 26% to 36% of parallel fiber terminals formed synaptic junctions with Purkinje cell spines, the remainder did not at PD 15 and 42. The rate of failure of synaptogenesis in the present study might be specific to this case of abiotrophy. Morphometric analysis revealed detailed changes in development and atrophy in animals with postnatal cerebellar disease occurring soon after birth.

Spontaneous and bilateral necrosis of the femoral head in a young experimental beagle dog.

This report describes the pathological characterizations of a rare case of necrosis of the femoral head that was spontaneous, bilateral, avascular and nontraumatic. A 14-month-old beagle dog was presented with pain in the hind limbs. At necropsy, the articular surface in the bilateral femoral head was markedly irregular. There were no gross abnormalities other than in the hip joints. Microscopically, a wide range of trabecular bone necrosis localized in the subchondral area was observed in both femoral heads. In the right femoral head, fibrosis and proliferative vessels were noted in the subchondral area. The articular cartilage was thickened irregularly, but there was no evidence of cartilage necrosis. The bone marrow adjacent to the affected area showed severe depression. In the metaphysis, atrophic bone marrow, but not bone necrosis, was observed. This was a rare case of spontaneous necrosis of the femoral head in an experimental beagle dog.

Proliferative lesions in thyroid follicular cells of dwarfs derived from Wistar Hannover GALAS rats.

We observed spontaneous dwarfism among Wistar Hannover GALAS rats, caused by primary hypothyroidism. The dwarf (D) rats showed markedly high serum thyroid-stimulating hormone (TSH) values. In this study, we investigated the incidence and histopathological characteristics of the proliferative lesions of the thyroid follicular cells in our D rats. Gross enlargement of thyroid and histological vacuolar change of the thyroid follicular cells with age-related progression suggesting diffuse hypertrophy/hyperplasia were seen in all the D rats. In addition, focal proliferative lesions-namely hyperplasias, activated hyperplasias, adenomas, and adenocarcinomas--were seen in D rats aged over 50 weeks. Taken together, these results suggested that the sustained stimulation of elevated levels of serum TSH caused and enhanced diffuse hypertrophy of thyroid follicular cells and subsequent development of focal proliferative lesions.

Relationship between carotid artery remodeling and plaque vulnerability with T1-weighted magnetic resonance imaging.

BACKGROUND: The aim of this study was to validate the relationship between carotid artery remodeling defined as the carotid remodeling index (CRI) and plaque vulnerability by comparing the degree of outward remodeling calculated using 3-dimensional inversion recovery-based T1-weighted imaging (magnetization-prepared rapid acquisition gradient echo [MPRAGE]) with the symptomatology and histology of plaques extracted during carotid endarterectomy. METHODS: Sixty-one patients with 50% stenosis or more (North American Symptomatic Carotid Endarterectomy Trial criteria) were included. The average rate of stenosis was 79.8%. The CRI was determined by measuring the external cross-sectional vessel area (CSVA) at the maximum stenosis of the internal carotid artery (ICA) and dividing it by the external CSVA at the distal ICA (unaffected by atherosclerosis) using MPRAGE imaging. RESULTS: The CRI was significantly higher in symptomatic patients compared with asymptomatic patients (1.98±.26 versus 1.68±.24, P<.0001). A higher CRI positively correlated with the necrotic core area (r=.57, P<.0001) and negatively correlated with the fibrous cap thickness (r=-.33, P=.01). It was also significantly associated with severe intraplaque hemorrhage (P<.0001) and the prevalence of cap inflammation with macrophage (P=.03) and lymphocyte (P=.01) infiltration. CONCLUSIONS: The larger outward remodeling of the carotid artery on MPRAGE imaging had symptomatic carotid plaques and histologically vulnerable plaques. This study indicates that MPRAGE imaging is useful for the assessment of carotid artery remodeling.

Panmedullary edema with inferior olivary hypertrophy in bilateral medial medullary infarction.

Bilateral medial medullary infarction (MMI) is a rare type of stroke with poor outcomes. Inferior olivary nucleus hypertrophy results from a pathologic lesion in the Guillain-Mollaret triangle. The relationship between inferior olivary nucleus hypertrophy and the medullary lesion is obscure. To the best of our knowledge, only 1 autopsy case with unilateral medial medullary infarction that was associated with ipsilateral inferior olivary nucleus hypertrophy has been reported. We describe a rare case with acute infarction in the bilateral medial medulla oblongata accompanied by subacute bilateral inferior olivary nucleus hypertrophy and panmedullary edema. The hypertrophy appeared to have been caused by local ischemic damage to the termination of the central tegmental tract at the bilateral inferior olivary nucleus.

Histological characteristics of the regression of corpora lutea in wistar hannover rats: the comparisons with sprague-dawley rats.

We examined the ovaries of 44 Wistar Hannover (RccHan(TM):WIST) (WH) and 30 Sprague-Dawley (SD) rats at 32-weeks of age to determine whether the ovarian structure and formation/regression of the corpora lutea (CLs) differ between the two strains. The average ovary weight was higher in WH rats. The average number of all CLs, including currently formed and previously formed CLs, was higher in WH rats in all cycles; however, no appreciable difference was detected in the number of newly or currently formed CLs between the two strains. CLs regression characterized by degeneration and necrosis of luteal cells began to appear in diestrus in both strains; however, the distribution of degenerated/necrotic cells in CLs differed. Necrotic cells were scattered in SD rats but were focally observed in the center of the CL in WH rats. The reduction in size of previously formed CLs accompanied by regression started about 2 or more stages later in WH rats than in those of SD rats. In conclusion, the higher number of CLs in WH rats is considered to be due to slow CL regression compared with in SD rats.

Factors associated with early recanalization failure following intravenous rt-PA therapy for ischemic stroke.

BACKGROUND: Although intravenous recombinant tissue-type plasminogen activator (rt-PA) therapy can be effective for ischemic stroke, a considerable percentage of patients do not receive any benefit as a result of early recanalization failure. We aimed to investigate the factors associated with early recanalization failure following intravenous rt-PA therapy. METHODS: Patients with acute ischemic stroke and internal carotid artery (ICA) or middle cerebral artery occlusion on initial magnetic resonance angiography (MRA) who received intravenous rt-PA therapy within 3 h of stroke onset and underwent follow-up MRA within 8 h after treatment were enrolled. Baseline characteristics, stroke features, onset to treatment time, initial National Institutes of Health Stroke Scale (NIHSS) score, initial Alberta Stroke Programme Early CT Score on diffusion-weighted imaging-ASPECTS (Alberta Stroke Program Early Computed Tomography Score), the presence of ICA or M1 origin (the residual length <5 mm) (ICA/M1 origin occlusion), initial vital signs, and laboratory findings were recorded. Early recanalization on the follow-up MRA within 8 h was evaluated by modified Mori grade: grade 0, no reperfusion; grade 1, movement of thrombus; grade 2, partial recanalization, and grade 3, complete recanalization. RESULTS: Seventy subjects (35 women, 77 ± 12 years) were enrolled. The median (interquartile range: IQR) NIHSS score was 18 (12.5-24), and the mean onset to treatment time was 141 ± 54 min. ICA was occluded in 29%, M1 origin in 17%, M1 middle in 13%, M1 distal in 26% and M2 in 15%. The median (IQR) pretreatment diffusion weighted imaging-ASPECTS was 8 (6-9), and follow-up time of MRA was 65 min (59-70) after rt-PA therapy. Thirty-two subjects (46%) showed modified Mori grade 0; 10 (14%), grade 1; 9 (13%), grade 2, and 19 (27%), grade 3. Multivariate analyses revealed ICA/M1 origin occlusion (OR 3.71, 95% CI 1.03-14.87, p = 0.044), and C-reactive protein (per 0.1-mg/dl increment, OR 1.19, 95% CI 1.03-1.44, p = 0.013) were independently associated with subjects with no recanalization (grade 0-1), whereas age (per years old, OR 0.93, 95% CI 0.86-0.99, p = 0.014) and high-density lipoprotein cholesterol (per 1-mg/dl increment, OR 0.94, 95% CI 0.89-0.98, p = 0.004) were inversely associated with those. CONCLUSION: ICA/M1 origin occlusion and C-reactive protein were positively and high-density lipoprotein cholesterol was negatively associated with early recanalization failure.

Detection of high-risk atherosclerotic plaques by magnetic resonance imaging.

The goal of coronary plaque burden assessment is to detect vulnerable or high-risk atherosclerotic plaques that are prone to rupture and to stabilize them through pharmacologic and other types of interventions before the development of acute coronary syndrome. In this regard, a reliable, reproducible, and less invasive imaging modality capable of identifying plaque characteristics associated with plaque vulnerability would be immensely useful for evaluating plaque status and predicting future cardiovascular events. Recently, magnetic resonance imaging (MRI) has emerged as a novel modality for atherosclerotic plaque detection and characterization. This review will cover the developments in MRI for characterizing atherosclerosis in carotid and coronary arteries and its use in clinical diagnoses and longitudinal studies to understand the pathophysiology of atherosclerosis.

Morphological study of progressive glomerulonephropathy in common marmosets (Callithrix jacchus).

Spontaneous progressive glomerulonephropathy often occurs in common marmosets. However, there are few detailed reports concerning the age-related progressive process of glomerular changes. We discuss the glomerular changes in the early stage and the progressive changes in the advanced stage of nephropathy. We investigated the kidneys of common marmosets (2-11 years old; 9 males and 12 females) using hematoxylin and eosin, periodic acid-Schiff, periodic acid-methenamine-silver, and Masson's trichrome (MT) stains and a transmission electron microscope. There was no remarkable change in urine cytology, hematology, or blood chemistry. In the early stage of nephropathy, effacement of podocyte foot processes was observed ultrastructurally even though there were no marked glomerular lesions in the light microscopy. Subsequently, mesangial proliferation occurred from the hilar to peripheral side along the tuft. In the middle stage, red deposits were visible at the glomerular basement membrane (GBM) and the mesangial region directly under the GBM (paramesangial area) with the MT stain. Electron dense deposits were seen at the same area. In the advanced stage, the irregularity became prominent with or without dense deposits. It is necessary to investigate in detail whether the change of podocyte in the early stage was immuno-mediated or due to podocyte failure.