Recurrent membranous nephropathy with a possible alteration in the etiology: a case report.

BACKGROUND: Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient's clinical course. CASE PRESENTATION: A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission. CONCLUSIONS: This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.

[A CASE OF UNRESECTABLE METASTATIC RENAL CARCINOMA SUCCESSFULLY TREATED BY COMBINED MODALITY THERAPY WITH NIVOLUMAB AND SURGERY].

The patient was a 65-year-old male who was referred with right renal mass (8 × 6.7 cm) and swelling of para-aortic lymph nodes in CT in April, 20XX. Additional examinations revealed inferior vena cava invasion, multiple lung metastases and left iliac bone metastasis and he was diagnosed with a renal cell carcinoma (cT4N1M1b). Pazopanib was administered as the first line treatment for an unresectable renal cancer. Nivolumab was then administrated as the 2nd line therapy due to the disease progression evaluated in (late) June, 20XX. However, immediately after the first administration of nivolumab, the patient have a difficulty in walking resulting from low-back pain, and MRI showed multiple lumbar vertebral metastases and L2 compression fracture. He was transferred to another hospital for combined modality therapy including right femoral head replacement and palliative radiotherapy in August, 20XX. Nivolumab was resumed since he had stable disease after his return to our hospital, and a total of 20 cycles of nivolumab treatment was performed. A follow-up CT showed 70% decrease in an initial primary tumor and tumor decrease or disappear in metastatic lung and bone tumors. The primary tumor was considered surgically resectable, and a radical nephrectomy was performed in August 20XX +1. Histopathological examination showed with a marked effect of neoadjuvant therapy and no evidence of viable tumor cells. We report a case of unresectable carcinoma that was successfully treated with nivolumab.

HOXA10 expression profiling in prostate cancer.

BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.

Heart Failure With Preserved Ejection Fraction　- Time for a Paradigm Shift Beyond Diastolic Function.

At present, heart failure with preserved ejection fraction (HFpEF) is a commonly accepted condition in HF patients. In contrast to HF with reduced EF (HFrEF), HFpEF is strongly associated with aging, and vascular, metabolic, neurohormonal, and systemic inflammatory comorbidities. Two major hypotheses explain the pathophysiology of HFpEF (stages C,D in the American College of Cardiology Foundation/American Heart Association HF staging system): (1) impaired active relaxation and increased passive stiffness of the left ventricular (LV) myocardium during diastole (left atrial [LA]-LV coupling); and (2) LV and arterial stiffening during systole (LV-arterial coupling). Cardiac structural and functional abnormalities can be evaluated using non-invasive measures, such as 2-D, flow velocity Doppler, and tissue Doppler echocardiography, to estimate LV filling pressure and afterload mismatch. The clinical application of 2-D speckle-tracking echocardiography (2D-STE) is feasible for earlier diagnosis of functional abnormalities of the LA, LV, and elastic arteries in asymptomatic patients with cardiovascular risk factors (stages A,B). The goal of this review is to highlight the role of 2D-STE to detect impairment of LA-LV-arterial coupling beyond diastolic function earlier, because it may provide important information on the pathophysiology and prevention of HFpEF.

Challenges for 'diastology': contributions from Japanese researchers.

Diastology is a study to treat diastole of the heart. Transmitral flow and pulmonary venous flow velocities recorded by pulsed Doppler echocardiography provide more important information about left ventricular (LV) diastolic dysfunction [left atrial (LA)-LV coupling] than cardiac catheterization in clinical practice; however, these waveforms are influenced by loading conditions, particularly preload. The early diastolic mitral annular and LV wall motion indices measured by tissue Doppler echocardiography can evaluate LV relaxation abnormality and filling pressure by being relatively preload independent. In addition, the role of concomitant systolic longitudinal dysfunction is well characterized in asymptomatic patients and in patients with heart failure and preserved ejection fraction. Two-dimensional speckle tracking echocardiography is an angle-independent method, and has the potential to evaluate the contraction and relaxation abnormalities in the longitudinal, circumferential, and radial directions of the LV myocardium as well as LV torsion/untwisting and, moreover, deformation of the LA myocardium and large arterial wall. As a result, this new technique can facilitate the early detection of impaired LA-LV-arterial coupling in patients before occurrence of overt heart failure symptoms.

Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer.

BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3ß and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.

Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography.

Left atrial (LA) structural and functional abnormalities are vital steps on the pathway toward heart failure with preserved ejection fraction in asymptomatic patients. The purpose of this study was to assess the relationship of LA function, particularly reservoir function, with LA structural remodeling related to the left ventricular (LV) dysfunction in asymptomatic patients with hypertension (HT) using conventional, tissue Doppler, and 2-D speckle-tracking echocardiography. Fifty age-matched healthy individuals and 140 patients with HT, including 75 with LA volume index (LAVI)<29 ml/m2 (normal LA group) and 65 with LAVI≥29 ml/m2 (large LA group), were enrolled. We defined peak early diastolic transmitral flow velocity/peak early diastolic mitral annular motion velocity (E/e')/peak systolic LA strain (S-LAs) as LA diastolic stiffness. The LV mass index, relative LV wall thickness, peak atrial systolic transmitral flow velocity, LA total, active, and passive emptying volume indexes, and E/e'/S-LAs were greatest, and S-LAs, peak early diastolic LA strain, peak systolic LV longitudinal strain and circumferential strain rate, and peak early diastolic LV radial strain rate were lower in the large LA group compared with control and/or normal LA group. Multivariate linear regression analysis revealed that aging, LA remodeling, and LV systolic and diastolic dysfunction are defined as strong predictors related to increased LA diastolic stiffness in the large LA group. HT alters LA dynamics significantly, with resultant increased LA volume and diastolic stiffness related to LV diastolic and systolic dysfunction, even in asymptomatic patients. Earlier treatment with renin–angiotensin system inhibitors may improve abnormal LA-LV interaction in this patient population.

Influence of comorbid cardiovascular risk factors on left atrial-left ventricular interaction in asymptomatic patients: clinical application of two-dimensional speckle-tracking echocardiography.

Previous studies have examined the negative impacts of individual cardiovascular risk (CVR) factors on left atrial (LA)-left ventricular (LV) interaction, whereas the combined effects of these risk factors are insufficiently elucidated. We studied 176 asymptomatic patients with CVR factors and age-matched 50 healthy individuals by conventional and 2-dimensional speckle-tracking echocardiography. The patients were classified into 2 groups according to the number of CVR factors: one risk factor (single) group (n = 79) and 2 or more risk factors (comorbid) group (n = 97). The peak early diastolic transmitral flow velocity (E)/peak early diastolic mitral annular motion velocity (e')/peak systolic LA strain (S-LAs) was used as a surrogate for LA stiffness during ventricular systole. The E/e'/S-LAs was greatest in the comorbid group. The peak systolic LV circumferential and radial strains, peak early diastolic LV radial strain rate, and peak early diastolic LA strain and strain rate were lower in the comorbid group than in the single group. Multivariate regression analysis identified age, body mass index, systolic blood pressure, end-systolic LV diameter, peak systolic mitral annular motion velocity (s'), and peak systolic LV radial strain in the comorbid group, and peak atrial systolic transmitral fl ow velocity and s' in the single group, as independent predictors of E/e'/S-LAs. Subtle LA and LV dysfunction with individual CVR factors were more aggravated with the comorbid conditions in asymptomatic patients.

Contribution of obesity to left atrial and left ventricular dysfunction in asymptomatic patients with hypertension: A two-dimensional speckle-tracking echocardiographic study.

Hypertension and obesity each are well known to result in heart failure with preserved ejection fraction. Therefore, it is clinically important to clarify the mechanisms of further deterioration of left atrial (LA)-left ventricular (LV) interaction in asymptomatic patients with obesity in the presence of hypertension. Data on conventional and two-dimensional speckle-tracking echocardiography (2DSTE) were obtained from 134 asymptomatic hypertensive patients. The study sample was divided into two groups: non-obese (n = 80; body mass index [BMI] <25 kg/m(2)] and obese (n = 54; BMI ≥25 kg/m(2)). The end-diastolic LV diameter, ratio of early transmitral flow to mitral annular motion velocity (E/e'), peak systolic LV circumferential strain rate, and E/e'/peak systolic LA strain (S-LAs) were greater in the obese group. Among the significantly correlated variables with BMI and E/e'/S-LAs in univariate analyses, multivariate analyses revealed that BMI is independently associated with end-diastolic LV diameter and peak systolic LV radial strain in all hypertensive patients, and that age, systolic blood pressure, relative LV wall thickness, peak systolic mitral annular motion velocity (s'), peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate are identified as independent predictors related to E/e'/S-LAs in the obese patients, whereas only s' contributes to the E/e'/S-LAs in the non-obese patients. Impaired LA-LV interaction was accelerated with obesity in the presence of hypertension. Assessment of the LA and LV function using 2DSTE provided additional information to the negative effects of cardiovascular risk factors on the LA and LV function in patients without clinical symptoms.

The impact of hypertension as a road to heart failure with preserved ejection fraction: diagnostic value of two-dimensional speckle tracking echocardiography for the early impairment of left atrial-left ventricular-arterial coupling.

Heart failure with preserved ejection fraction (HFPEF) is a syndrome that frequently occurs in older people and patients with cardiovascular risk factors, particularly hypertension. This syndrome is not a specific disease process, whereas is associated with high morbidity and mortality in patients with heart failure with reduced ejection fraction (HFREF) as well. Therefore, a "one size fits all" diagnosis strategy is unlikely to operate for patients with HFPEF. Assessment of left atrial (LA)-left ventricular (LV)-arterial coupling seems to have a clinical impact on hypertensive patients, because HF signs and symptoms have been found to be significantly related to inappropriate LA-LV interaction during diastole and LV-arterial interaction during systole. Two-dimensional speckle tracking echocardiography (2DSTE) is a new tool that may have a role in earlier detecting the impaired LA, LV, and arterial function in asymptomatic patients. This review explored the impact of LA-LV-arterial coupling in understanding the pathophysiology of hypertension as a road to HFPEF, and the possibilities of clinical application by using 2DSTE.

Procalcitonin as a useful marker to decide upon intervention for urinary tract infection.

BACKGROUND: Because the use of procalcitonin has been advocated as a marker of bacterial infection, this study was carried out to determine the usefulness of serum PCT as an early marker to decide upon intervention for urinary tract infection. METHODS: The subjects were 68 patients with urinary tract infection (UTI) in whom we measured serum procalcitonin concentration at the start of treatment. RESULTS: There were 47 patients with nonobstructed UTI and 21 with obstructed UTI. All patients with obstructed UTI were subjected to intervention. There were significant differences in procalcitonin, white blood cells, and creatinine levels between patients with nonobstructed and obstructed UTI (P < 0.05). CONCLUSION: Although this retrospective study comprised a small number of patients, we found that procalcitonin was a useful marker to decide upon urinary intervention.

[Granulocyte-colony stimulating factor-producing urothelial carcinoma of the renal pelvis : a case report].

A 43-year-old woman was referred to our hospital for fever, general fatigue and left flank abdominal pain during the last two weeks. A blood test showed severe inflammation, and computed tomography (CT) study of the abdomen with intravenous contrast revealed swelling and irregular enhancement in the upper left kidney. Initially, we diagnosed it as xanthogranulomatous pyelonephritis and treated it with antibiotics. A percutaneous renal biopsy was performed because the white blood cell count remained elevated after the treatment. Histopathologic examination revealed a carcinoma. Therefore, we performed left nephroureterectomy. The diagnosis was high grade urothelial carcinoma of the renal pelvis, and it stained positive by immunohistochemical staining using anti-granulocyte-colony stimulating factor (G-CSF). The serum G-CSF level was also elevated on the same day. The patient received chemotherapy but, died 9 months after surgery. A G-CSF-producing urothelial carcinoma of the renal pelvis is known to have a poor prognosis in the Japanese literature. It is important to closely monitor a G-CSF producing tumor, when a patient shows severe inflammation, but no infection.

Clinical outcome of incidentally discovered small renal cell carcinoma after delayed surgery.

BACKGROUND: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery. METHODS: We reviewed the clinical records of 34 patients with SRMs ≤ 4 cm at diagnosis, who underwent delayed surgical intervention during surveillance from January 2000 to December 2011. Radiographic evaluations using computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at least every 6 months, and the tumor size was determined at least twice. RESULTS: The mean follow-up time was 26.6 ± 18.6 months and mean tumor doubling time was 23.4 ± 16.0 months. Histopathological analysis revealed that 32 of the 34 patients were malignant in pT1aN0M0. Only one patient showed tumor recurrence, who subsequently died due to tumor progression. CONCLUSION: The growth rate of the small renal mass was slow in the majority of our patients. Delayed intervention does not have a detrimental effect on cancer-specific outcomes.

Survey on lower urinary tract symptoms and sleep disorders in patients treated at urology departments.

OBJECTIVES: This study examined the association between sleep disorders and lower urinary tract symptoms in patients who had visited urology departments. METHODS: This was an independent cross-sectional, observational study. Outpatients who had visited the urology departments at the Kinki University School of Medicine or the Sakai Hospital, Kinki University School of Medicine, between August 2011 and January 2012 were assessed using the Athens Insomnia Scale and the International Prostate Symptom Score. RESULTS: In total, 1174 patients (mean age, 65.7 ± 13.7 years), with 895 men (67.1 ± 13.2 years old) and 279 women (61.4 ± 14.6 years old), were included in the study. Approximately half of these patients were suspected of having a sleep disorder. With regard to the International Prostate Symptom Score subscores, a significant increase in the risk for suspected sleep disorders was observed among patients with a post-micturition symptom (the feeling of incomplete emptying) subscore of ≥1 (a 2.3-fold increase), a storage symptom (daytime frequency + urgency + nocturia) subscore of ≥5 (a 2.7-fold increase), a voiding symptom (intermittency + slow stream + hesitancy) subscore of ≥2 (a 2.6-fold increase), and a nocturia subscore of ≥2 (a 1.9-fold increase). CONCLUSION: The results demonstrated that the risk factors for sleep disorders could also include voiding, post-micturition, and storage symptoms, in addition to nocturia.

Early predictors of alterations in left atrial structure and function related to left ventricular dysfunction in asymptomatic patients with hypertension.

Our aim was to investigate the relationships between left atrial (LA) structural and functional changes and left ventricular (LV) dysfunction related to LV pressure overload in asymptomatic patients with hypertension. One hundred and twenty-six asymptomatic patients with hypertension and LV ejection fraction (EF) ≥ 60% were studied. Conventional, pulsed and tissue Doppler, and two-dimensional speckle-tracking echocardiography (2DSTE) were performed to seek the independent determinants for alterations in LA structure and function. LA volume index (LAVI) correlated with age, body mass index (BMI), end-diastolic ventricular septal thickness (VSth), end-diastolic LV posterior wall thickness, relative LV wall thickness (RWT), LV mass index, peak A velocity of transmitral flow, E/e', and peak systolic and early diastolic LA strains and strain rates. Peak LA strain during ventricular systole (S-LAs) correlated with age, BMI, heart rate (HR), end-systolic LV diameter, LAVI, VSth, RWT, LVEF, e', E/e', peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate. Multivariate regression analyses indicated that LV mass index, peak A velocity, E/e', and S-LAs are defined as strong predictors related to LAVI, and that BMI, HR, LAVI, and peak systolic LV radial strain are defined as strong predictors related to S-LAs. In conclusion, 2DSTE demonstrated that alterations in LA structure and function are mainly associated with LV diastolic and systolic dysfunction, respectively, in preclinical patients with hypertension.

Negative impact of cardiovascular risk factors on left atrial and left ventricular function related to aortic stiffness--new application of 2-dimensional speckle-tracking echocardiography.

BACKGROUND: The aim of the present study was to detect earlier the negative effect of cardiovascular risk (CVR) factors on left atrial (LA) and left ventricular (LV) function related to abdominal aortic (AAO) stiffness using 2-dimensional speckle-tracking echocardiography (2DSTE) in asymptomatic patients. METHODS AND RESULTS: One hundred and twelve patients with CVR factors and 56 healthy individuals were studied. 2DSTE data were acquired for determination of LA and LV myocardial and AAO wall deformations. LA volume index, LV mass index, ratio of early diastolic transmitral flow to mitral annular velocity (E/e')/peak systolic LA strain (S-LAs), and AAO stiffness were greater, and peak early diastolic LV longitudinal strain rate (SR-LVe) was lower in the patient group. Among the significantly correlated variables with AAO stiffness on univariate analysis, multivariate linear regression analysis identified SR-LVe and (E/e')/S-LAs in the patient group, and only age in the healthy group, as independent predictor of AAO stiffness. CONCLUSIONS: Structural and functional changes in the LA and LV and AAO stiffening were accelerated with CVR factors, and higher AAO stiffness was associated with deteriorated LA compliance and impaired LV relaxation in asymptomatic patients with CVR factors. 2DSTE has a potential for earlier detection of abnormal LA and LV function related to increased AAO stiffness.

Effect of an increase in left ventricular pressure overload on left atrial-left ventricular coupling in patients with hypertension: a two-dimensional speckle tracking echocardiographic study.

BACKGROUND: Two-dimensional speckle tracking echocardiography (2DSTE) has recently been applied to evaluate left atrial (LA) function in addition to left ventricular (LV) function. However, whether 2DSTE can provide insight into LA-LV interaction related to an increase in LV pressure overload remains unknown. METHODS: One hundred five asymptomatic patients with hypertension were studied by conventional, pulsed and tissue Doppler, and 2DSTE. Hypertensive patients were classified into 2 groups according to the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow: E/A ≥ 1 (n = 37) and E/A < 1 (n = 68). We used (E/peak early diastolic mitral annular motion velocity [e'])/peak systolic LA strain (S-LAs) and E/e', as parameters of LA stiffness during ventricular systole and LV diastolic stiffness, respectively. RESULTS: The peak early diastolic LV longitudinal strain rate, and peak early diastolic LA strain and strain rate were lower in the E/A < 1 group than in the E/A ≥ 1 group. The E/e'/S-LAs and E/e' were greater in the E/A < 1 group. In the E/A < 1 group, systolic blood pressure (SBP) correlated with LV wall thickness parameters, A, e', E/e', peak early diastolic LV longitudinal strain rate, and E/e'/S-LAs. Multivariate regression analysis indicated that A, E/e', and E/e'/S-LAs were defined as strong predictors related to SBP. CONCLUSION: In patients with hypertension, an elevation in SBP leads to increased LA stiffness during ventricular systole and LV diastolic stiffness, in association with continued and further advanced LV diastolic dysfunction. 2DSTE is considered a sensitive tool for detecting abnormal LA-LV coupling related to an increased LV pressure overload.

A case of severe ganciclovir-induced encephalopathy.

BACKGROUND: Ganciclovir, a drug against cytomegalovirus (CMV) infection, is generally well tolerated, but can cause neurotoxicity such as encephalopathy. Although ganciclovir-induced encephalopathy has been described in several reports, a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy. Symptoms usually include confusion and disturbed consciousness, which mimic CMV encephalitis. Prompt and accurate diagnosis is thus sometimes difficult, and is derived solely from accumulated clinical information of definite cases, since ganciclovir concentrations, not routinely measured, become available after several days or a few weeks. CASE PRESENTATION: Here, we summarize clinical information of all patients with definite ganciclovir-induced encephalopathy including our own patient, who had severe symptoms, with the highest reported trough concentration of ganciclovir in the blood, and underwent therapeutic dialysis with complete recovery. CONCLUSION: Our summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses.

Vascular aging of common carotid artery and abdominal aorta in clinically normal individuals and preclinical patients with cardiovascular risk factors: diagnostic value of two-dimensional speckle-tracking echocardiography.

Increased arterial stiffness is becoming an increasing health care problem as the population ages. Our aim was to detect the vascular aging of common carotid artery (CCA) and abdominal aorta (AAO) more easily and earlier using two-dimensional speckle-tracking echocardiography, and to evaluate the regional differences in mechanical properties related to changes in aging between the two arteries in preclinical patients. Twenty-nine clinically normal individuals and 68 preclinical patients with cardiovascular risk factors were examined. The peak circumferential strains were measured from the short-axis views of the CCA and AAO, and each stiffness ß was determined. The CCA and AAO diameters increased with advanced age, and the latter diameter was widely distributed in patients of 50 years or older. The mean strain and stiffness index of the AAO were greater and lower, respectively, than those of the CCA at all ages. The CCA and AAO strains decreased with age, expressing dramatic declines before the fifth decade of life. The CCA and AAO stiffness indices increased with age, expressing rapid ascents after the fifth decade of life, particularly in the AAO. The best markers of subclinical arterial aging were strain in younger persons and stiffness in older individuals. Two-dimensional speckle-tracking echocardiography is a new tool that can be used to directly and easily evaluate arterial function.

The efficacy of EBER in situ hybridization (ISH) stain in PTLD (malignant diffuse large B-cell lymphoma) about 4 years after ABO-incompatible kidney transplantation: a case report.

Post-transplant lymphoproliferative disease (PTLD) is a well-known late complication of organ transplantation which incidence has increased after the introduction of more powerful immunosuppressive agents. A 58-year-old man performed ABO-incompatible living kidney transplantation in June, 2008. At 3 years and 9 months after the transplantation, the patient complained of general fatigue and dyspnea and was hospitalized with renal dysfunction. The clinical data in hospital showed acute rejection, but soluble IL-II exceeded 21700U/ml, and HE staining kidney graft showed a massive infiltration of atypical lymphocytes. Atypical lymphocytes were positive for L-26 and negative for CD3 immunochemical stein, and the EBER in situ hybridization stain for EBV was negative in renal graft. We diagnosed diffuse large B-cell lymphoma in the kidney graft. However, he died due to multiple organ failure (MOF). We described a fatal case of diffuse large B-cell lymphoma without EBV infection occurring 3 years 9 months after ABO-incompatible kidney transplantation. Unfortunately, post-mortem autopsy using EBER-ISH stain does not show whether EB virus infection was a cause.