How Topographic Diffusion-Weighted Imaging Patterns can Predict the Potential Embolic Source.

PURPOSE: To develop an imaging prediction model for patients with embolic stroke of undetermined source (ESUS), we investigated the association of topographic diffusion-weighted imaging (DWI) patterns with potential embolic sources (PES) identified by transesophageal echocardiography. METHODS: From a total of 992 consecutive patients with embolic stroke, 366 patients with the ESUS group were selected. ESUS was defined as no atrial fibrillation (Af) within 24h from admission and no PES after general examination. Clinical variables include age (> 80years, 70-80 years), sex, vascular risk factors and left atrial diameter > 4 cm. Age, sex and vascular risk factors adjusted odds ratio of each DWI for the different PESs were calculated. DWI was determined based on the arterial territories. Middle cerebral arteries were divided into 4 segments, i.e., M1-M4. Moreover, M2 segments were subdivided into superior and inferior branches. RESULTS: The 366 patients consisted of 168 with paroxysmal Af (pAf), 77 with paradoxical embolism, 71 with aortic embolism and 50 with undetermined embolism after transesophageal echocardiography. The variables adjusted odds ratio (OR) of internal carotid artery (OR: 12.1, p = 0.037), M1 (4.2, p = 0.001), inferior M2 (7.5, p = 0.0041) and multiple cortical branches (12.6, p < 0.0001) were significantly higher in patients with pAf. Striatocapsular infarction (12.5, p < 0.0001) and posterior inferior cerebellar artery infarcts (3.6, p = 0.018) were significantly associated with paradoxical embolism. Clinical variables adjusted OR of multiple small scattered infarcts (8.3, p < 0.0001) were significantly higher in patients with aortic embolism. CONCLUSION: The associations of DWI with different PES have their distinctive characteristics and DWI along with clinical variables may help predict PES in patients with ESUS.

The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study.

BACKGROUND: The comprehensive measurement of autoimmune disease-related antibodies (Abs) before immune checkpoint inhibitor (ICI) treatment may be useful for predicting the development of immune-related adverse events (irAEs); however, the clinical utility is not well known. MATERIALS AND METHODS: We retrospectively analyzed patients with advanced solid tumors treated with ICI monotherapy or doublet combination therapy between July 2014 and December 2020 at single institute. Anti-nuclear antibody (ANA), anti-thyroglobulin (Tg) Ab, anti-thyroid peroxidase (TPO) Ab, anti-glutamic acid decarboxylase (GAD) Ab, anti-acetylcholine esterase receptor (AchR) Ab, and platelet-associated immunoglobulin G (PA-IgG) Ab were comprehensively measured for the screening before ICI therapy. RESULTS: Of 275 registered patients (median age, 70 years; male, 64.4%; Eastern Cooperative Oncology Group performance status of 0 or 1, 88.7%; and prior regimen of 0-1/≥2, 88.7%/11.3%), 128 non-small-cell lung cancer, 35 gastric cancer, 33 head and neck cancer, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal cancer, 5 malignant mesothelioma of pleura, 2 endometrial cancer, and 4 other cancer were included. The number of patients with positive ANA, Tg, TPO, PA-IgG, GAD, and AchR Abs was 52 (24.9%), 38 (14.5%), 11 (10.1%), 6 (3.5%), 5 (2.0%), and 1 (0.5%), respectively. There was no association between the development of any irAEs and Abs positivity, while thyroid dysfunction developed more frequently among patients with than without Tg Ab or TPO Ab (39.5% versus 12.5%, P < 0.01; 45.5% versus 14.3%, P = 0.02). CONCLUSIONS: The clinical utility of comprehensive measurement of autoimmune disease-related Abs before introduction of ICI therapy was limited for predicting irAE. However, Tg and TPO Abs were risk factors as regards the development of ICI-induced thyroid dysfunction.

Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems.

OBJECTIVE: In a rat monoiodoacetic acid (MIA)-induced arthritis model, the amount of MIA commonly used was too high, resulting in rapid bone destruction. We examined the effect of MIA concentrations on articular cartilage and infrapatellar fat pad (IFP). We also established an original system for "macroscopic cartilage and bone score" and "IFP inflammation score" specific to the rat MIA-induced arthritis model. DESIGN: Male Wistar rats received a single intra-articular injection of MIA in the knee. The amount of MIA was 0.1, 0.2, 0.5, and 1 mg respectively. Articular cartilage was evaluated at 2-12 weeks. IFP was also observed at 3-14 days. RESULTS: Macroscopically, low MIA doses induced punctate depressions on the cartilage surface, and cartilage erosion proceeded slowly over 12 weeks, while higher MIA doses already induced cartilage erosion at 2 weeks, followed by bone destruction. MIA macroscopic cartilage and bone score, OARSI histological score, and Mankin score increased in a dose- and time-dependent manner. The IFP inflammation score peaked at 5 days in low dose groups, then decreased, while in high dose groups, the IFP score continued to increase over 14 days due to IFP fibrosis. CONCLUSIONS: Punctate depressions, cartilage erosion, and bone destruction were observed in the MIA-induced arthritis model. The macroscopic cartilage and bone scoring enabled the quantification of cartilage degeneration and demonstrated that MIA-induced arthritis progressed in a dose- and time-dependent manner. IFP inflammation scores revealed that 0.2 mg MIA induced reversible synovitis, while 1 mg MIA induced fibrosis of the IFP body.

[(18) F]-Fluorodeoxy-d-glucose uptake-positive seborrhoeic keratosis on positron emission tomography may result from high expression of glucose transporter.

[(18) F]-Fluorodeoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) is known to be highly accurate in differentiating benign lesions from malignant lesions. In rare cases, benign tumours, viral infections and sarcoidosis of the skin have been reported to show FDG uptake, but the mechanism remains unclear. Here we report the first documented case of seborrhoeic keratosis (SK) showing increased FDG uptake. FDG PET-CT can be used to detect enhanced glycolysis of tumour cells by measuring increased levels of glucose transporters (GLUTs) indicative of higher glucose uptake. GLUT1 and GLUT3 expression in this case was compared with that in PET-negative SK and two normal skin samples using quantitative polymerase chain reaction with paraffin-embedded tissue. The expression of GLUT1 and GLUT3 was higher in PET-positive SK than in PET-negative SK or normal skin. More specifically, the expression of GLUT3 was observed only in the PET-positive case. This study revealed that high GLUT1 and GLUT3 expression in SK might be associated with the uptake of FDG.

Glucose tolerance status and risk of dementia in the community: the Hisayama study.

OBJECTIVE: We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia. METHODS: A total of 1,017 community-dwelling dementia-free subjects aged ≥60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia. RESULTS: The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of <6.7 mmol/L, the multivariable-adjusted HRs of all-cause dementia and AD significantly increased in subjects with 2-hour PG levels of 7.8 to 11.0 mmol/L or over, and the risk of VaD was significantly higher in subjects with levels of ≥11.1 mmol/L. CONCLUSIONS: Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD.

Spin susceptibility of noncentrosymmetric heavy-fermion superconductor CeIrSi3 under pressure: 29Si Knight-shift study on single crystal.

We report 29Si NMR study on a single crystal of the heavy-fermion superconductor CeIrSi3 without an inversion symmetry along the c axis. The 29Si Knight-shift measurements under pressure have revealed that the spin susceptibility for the ab plane decreases slightly below T(c), whereas along the c axis it does not change at all. The result can be accounted for by the spin susceptibility in the superconducting state being dominated by the strong antisymmetric (Rashba-type) spin-orbit interaction that originates from the absence of an inversion center along the c axis and it being much larger than superconducting condensation energy. This is the first observation which exhibits an anisotropy of the spin susceptibility below T(c) in the noncentrosymmetric superconductor dominated by strong Rashba-type spin-orbit interaction.

Body mass index in male patients with COPD: correlation with low attenuation areas on CT.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by the presence of airflow limitation caused by loss of lung elasticity and/or airway narrowing. The pathological hallmark of loss of lung elasticity is emphysema, and airway wall remodelling contributes to the airway narrowing. Using CT, these lesions can be assessed by measuring low attenuation areas (LAA) and airway wall thickness/luminal area, respectively. As previously reported, COPD can be divided into airway dominant, emphysema dominant and mixed phenotypes using CT. In this study, it is postulated that a patient's physique may be associated with the relative contribution of these lesions to airflow obstruction. METHODS: CT was used to evaluate emphysema and airway dimensions in 201 patients with COPD. Emphysema was evaluated using percentage of LAA voxels (LAA%) and airway lesion was estimated by percentage wall area (WA%). Patients were divided into four phenotypes using LAA% and WA%. RESULTS: Body mass index (BMI) was significantly lower in the higher LAA% phenotype (ie, emphysema dominant and mixed phenotypes). BMI correlated with LAA% (rho = -0.557, p<0.0001) but not with WA%. BMI was significantly lower in the emphysema dominant phenotype than in the airway dominant phenotype, while there was no difference in forced expiratory volume in 1 s %predicted between the two. CONCLUSION: A low BMI is associated with the presence of emphysema, but not with airway wall thickening, in male smokers who have COPD. These results support the concept of different COPD phenotypes and suggest that there may be different systemic manifestations of these phenotypes.

Physiochemical properties of generic formulations of tacrolimus in Mexico.

Tacrolimus is an important immunosuppressive agent used to prevent allograft rejection after transplantation. Tacrolimus has a narrow therapeutic index; therefore, it is essential that the physicochemical properties of generic formulations be identical to the brand-name formulation, Prograf. In this study, the physicochemical properties of generic tacrolimus formulations were compared with Prograf. The drug dissolution profiles of generic formulations of tacrolimus were different from that of Prograf. Tacrobell and T-Inmun exhibited faster dissolution than Prograf, and Tenacrine, Framebin, and Talgraf showed slower and incomplete drug dissolution, releasing 24% to 51% of tacrolimus within 2 hours. Generic formulations of tacrolimus demonstrated decreased solubility compared with Prograf. The solubility of Prograf was 35.7 microg/mL at 2 hours and 29.5 microg/mL at 24 hours. The solubility of Tenacrine, Framebin, and Talgraf at 2 hours was 5.5, 12.6, and 7.8 microg/mL, respectively, and the solubility decreased to 0.5, 2.3, and 2.1 microg/mL, respectively, at 24 hours. Whereas Prograf demonstrated content uniformity, the content of the generic tacrolimus formulations varied widely. The standard deviation of content for Tenacrine, Tacrobell, and T-Inmun were high at 29.3, 6.9, and 5.6, respectively. Furthermore, the mean percentage of labeled amount of T-Inmun was 84.2% with a relative standard deviation of 6.7% (minimum value; 72.7%; maximum value; 100.7%). These results indicate that generic formulations of tacrolimus tested in this study are not bioequivalent to Prograf, which suggests that their use may be of potential risk to transplant patients.

Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation.

BACKGROUND: The association between gastro-oesophageal reflux disease (GORD) and chronic obstructive pulmonary disease (COPD) exacerbation has so far remained unclear. OBJECTIVE: To prospectively establish the clinical significance of GORD symptoms on exacerbation. METHODS: 82 patients with COPD and 40 age matched controls were enrolled in this study. Symptoms were evaluated by a questionnaire using the Frequency Scale for the Symptoms of GORD (FSSG). Patients with COPD were prospectively surveyed for 6 months, and episodes of exacerbation were identified using a diary based on modified Anthonisen's criteria. Exhaled breath condensate (EBC) pH was measured in both groups, and induced sputum was evaluated in patients with COPD. RESULTS: Positive GORD symptoms were reported in 22 (26.8%) patients with COPD and in five (12.5%) controls (p = 0.10). The frequency of exacerbations was significantly associated with the FSSG score (p = 0.03, r = 0.24, 95% CI 0.02 to 0.43). Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations (p<0.01; relative risk 6.55, 95% CI 1.86 to 23.11). EBC pH was inversely correlated with FSSG score in both groups (p = 0.01, r = -0.37, 95% CI -0.55 to -0.14 in patients with COPD, and p<0.01, r = -0.45, 95% CI -0.67 to -0.16 in control subjects). CONCLUSIONS: GORD symptoms were identified as an important factor associated with COPD exacerbation.

Enhancement of superconducting transition temperature due to the strong antiferromagnetic spin fluctuations in the noncentrosymmetric heavy-fermion superconductor CeIrSi3: A 29Si NMR study under pressure.

We report a (29)Si NMR study on the pressure-induced superconductivity (SC) in an antiferromagnetic (AFM) heavy-fermion compound CeIrSi(3) without inversion symmetry. In the SC state at P = 2.7-2.8 GPa, the temperature (T) dependence of the nuclear-spin lattice relaxation rate 1/T(1) below T(c) exhibits a T(3) behavior without any coherence peak just below T(c), revealing the presence of line nodes in the SC gap. In the normal state, 1/T(1) follows a square root T-like behavior, suggesting that the SC emerges under the non-Fermi-liquid state dominated by AFM spin fluctuations enhanced around a quantum critical point. The reason why the maximum T(c) in CeIrSi(3) is relatively high among the Ce-based heavy-fermion superconductors may be the existence of the strong AFM spin fluctuations. We discuss the comparison with the other Ce-based heavy-fermion superconductors.

Eccentric stenosis of the carotid artery associated with ipsilateral cerebrovascular events.

BACKGROUND AND PURPOSE: Eccentric stenosis of the coronary artery is associated with plaque disruption and acute coronary syndrome. The purpose of the present study was to determine whether eccentric stenosis of the carotid artery contributes to cerebrovascular events. MATERIALS AND METHODS: Of 6859 patients with vascular diseases who underwent duplex carotid ultrasonography, we studied 512 internal carotid arteries in 441 patients who had a maximum area stenosis at or more than 70%, which corresponds with approximately 50% or more by the NASCET method. The maximal (A) and minimal wall thicknesses (B) were measured on cross-sectional sonography images, and an eccentricity index was calculated using the following formula: (A - B)/A. Arteries in the lowest quartile of the eccentricity index (<0.69) were defined as having a concentric stenosis, whereas the others were defined as having eccentric stenosis. The underlying clinical characteristics and plaque morphologies, as well as the occurrence of ipsilateral ischemic stroke or transient ischemic attack in the preceding year, were compared between patients with eccentric and concentric stenosis. RESULTS: Patient characteristics and plaque morphology were similar between the 2 groups. Cerebrovascular events occurred more frequently ipsilaterally to the artery with eccentric stenosis (13.5%) than to the artery with concentric stenosis (5.5%; P = .013); the difference was more evident when cerebrovascular events of presumed carotid arterial origin were assessed (P = .005). After adjusting for risk factors and plaque morphology, eccentric stenosis was independently related to the presence of recent cerebrovascular events (odds ratio = 2.76; 95% confidence interval = 1.19-6.40). CONCLUSIONS: In patients with an area carotid stenosis of 70% or more, eccentric plaque was associated with a significantly increased incidence of ipsilateral cerebrovascular events compared with patients with concentric stenosis.

First living related kidney transplantation results in excellent outcomes for small children.

OBJECTIVE: The aim of this study was to evaluated the outcomes of living related kidney transplantation in small children. MATERIALS AND METHODS: Ten pediatric patients with body weights less than 10 kg received parental kidney transplants (five mothers and five fathers). An intra-abdominal approach was used in nine children and a retroperitoneal approach in one child. Bilateral, left, or right nephrectomy was performed in seven, two, and one child, respectively. Immunosuppression consisted of either cyclosporine (n = 7) or tacrolimus (n = 3) with either mizoribine (n = 4) or mycophenolate mofetil (MMF) (n = 5) or azathioprine (n = 1), and methylprednisolone (n = 10). Antilymphocyte globulin was used in the first series of four children; basiliximab in the most recent five children. RESULTS: All renal allografts functioned immediately after transplantation despite the mismatched size of the large renal allografts. Nine of 10 children were alive with a functional allograft at 6 to 196 months posttransplantation. One child died of intra-abdominal bleeding 5 days posttransplantation. One child has suffered chronic allograft nephropathy 11 years posttransplantation (serum creatinine 3.3 mg/dL). The remaining eight children display good renal function (serum creatinine = 0.2 to 1.43 mg/dL). Steroids were withdrawn in eight of nine children; one child continues on alternative-day therapy. One child (LD55) exceeded the mean standard height. The most recent height standard deviation (SD) scores were superior (-1.75 +/- 1.39 [-3.83 to 0.54]; P < .0082) to those at transplantation (-2.91 +/- 0.79 [-2.00 to -4.14]). CONCLUSIONS: The outcomes of living related kidney transplantation in small children were excellent despite the operative risks and the difficulty of cardiovascular and fluid management. Transplantation for small children appears to result in much better quality of life and growth than dialysis.

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

Reversibility from delayed hyperacute rejection in ABO-incompatible renal transplantation: histopathological findings of renal allograft biopsy.

ABO-incompatible renal transplantation (ABOIRTx) tend to lead to blood type antibody-mediated rejection, the so-called delayed hyperacute rejection (DHAR), which results in short-term graft loss. To clarify the accurate incidence and prognostic value of DHAR among ABOIRTx, we reviewed biopsy specimens obtained from ABOKTx allografts with abrupt dysfunction during the early period after transplantation. Among 74 ABOIRTx patients, 34 patients displayed allograft dysfunction within 14 days following transplantation. The biopsy specimens were classified based on the Banff schema. The pathological diagnosis of ABO blood type antibody-mediated humoral rejection (ABO-AMHR) was made by the following 3 findings: Specimens with all of above-mentioned findings were categorized as severe ABO-AMHR; those with at least one findings, were categorized as mild ABO-AMHR. All patients were treated with steroid pulse therapy and/or modification of other immunosuppressants. Group 1 consisted of severe ABO-AMHR (n = 6); group 2 consisted of mild ABO-AMHR (n = 5); group 3 consisted of acute cellular rejection (n = 3); group 4 consisted of recovery phase of ATN (n = 11); group 5 consisted of calcineurin inhibitor toxicity (n = 2); and group 6 consisted of normal histology (n = 5). One of 6 patients (16%) in group 1 lost the graft because of DHAR irreversible by antirejection and anticoagulation therapy. However, there has been no clear definition of histpathological criteria for DHAR after ABO-incompatible kidney transplantation. The definition must prognosticate whether the rejection process is reversible.

Baseline glomerular sclerosis influences morphological changes, but not level of serum creatinine.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

The relationship between 24-hour blood pressure readings, subcortical ischemic lesions and vascular dementia.

BACKGROUND: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). METHODS: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP - nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0-0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. RESULTS: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20-9.34), advanced PVH (OR 14.42; 95% CI 5.62-36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37-115.95; reverse dipper: OR 11.95; 95% CI 1.27-112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38-11.17), high daytime (OR 2.06; 95% CI 1.03-4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13-5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03-7.05; reverse dipper: OR 3.78; 95% CI 1.38-10.34) were significantly associated with PVH. CONCLUSIONS: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

BK virus nephropathy in a patient with ABO-incompatible renal transplantation.

A 43-year-old woman with end-stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO-incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti-rejection therapy was given. At 665 days after transplantation, diagnosis of BK-virus nephropathy was made by immunohistochemical analysis and viral DNA assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the BK virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post-transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. Awareness of BKVN at the earliest opportunity is important in order to avoid over-immunosuppression.