Decreased ADAMTS13 Levels in Patients after Living Donor Liver Transplantation

Introduction

Thrombotic microangiopathy (TMA) is a complication occurring after liver transplantation (LT), and an unusually large multimer (ULM) of Von Willebrand factor (VWF) and ADAMTS13 may play an important role in the onset of TMA during LT.

Material and Methods

Eight-one patients underwent living donor LT (LDLT). Seventeen of those patients had both severe thrombocytopenia and hemolytic anemia with fragmented red cells and were diagnosed as TMA- like syndrome (TMALS).

Results and Conclusions

A significant reduction of ADAMTS13 and an increase of VWF were observed in the patients with TMALS. The ADAMTS13 activity in patients after LDLT was significantly reduced from day 1 to day 21, and it was significantly low in those with TMALS at day 14 and 28. The VWF levels in patients with LDLT were significantly high, and the VWF/ADAMTS13 ratio was significantly increased in patients at 7, 14 and 28 days after LDLT, especially in patients with TMALS at day 14 and 28 after LDLT. High molecular weight multimers of VWF were observed to have increased in patients with LDLT, and the high molecular weight multimers of VWF were further increased in those with mild TMALS but they decreased in those with severe TMA. These findings suggest that ULM- VWF and ADAMTS13 might be associated with the onset of TMA after LT.     

Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease

Objectives

Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but clinically important because they significantly impair the daily lives of patients. Causes of SAs include long-term activation of dopaminergic (especially D3) receptors. Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain.

Patients and methods

We measured levels of orexin in samples of spinal cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs, the selective dopamine D1/D2 agonist pergolide was substituted for the causative drugs with D3 stimulatory activity, and CSF-orexin levels were measured before and after switching treatment.

Results

In the 25 patients with PD, including the 4 patients with SAs, lower CSF-orexin levels were associated with a longer disease duration, which has been linked to a higher incidence of SAs. Switching treatment to pergolide significantly increased CSF-orexin levels and completely resolved SAs in the four patients with PD.

Conclusion

Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs.     

Classification of follicular cell tumors of the thyroid gland: Analysis involving Japanese patients from one institute

Prognostic analyses of thyroid carcinomas of follicular cell origin were carried out on patients treated at Kuma Hospital, Kobe, Japan. A new histopathological classification based on the prognostic evidence is proposed in this study, and it is applicable to the patients treated curatively. Major histological types of papillary carcinoma, follicular carcinoma and poorly differentiated carcinoma were combined into one single entity of follicular cell adenocarcinoma because (i) they have the same cell origin (follicular cell); (ii) clear-cut separation of papillary and follicular carcinoma is not always possible, and 10 year cause-specific survival was essentially similar when the patients were treated curatively; and (iii) poorly differentiated carcinoma usually has a background of either papillary or follicular carcinoma. This adenocarcinoma together with undifferentiated carcinoma was stratified into four prognostic groups using pure morphological criteria of the degree of cellular differentiation and histological grade. They are termed well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, poorly differentiated carcinoma and undifferentiated carcinoma of the thyroid. The 10 year disease-free survival rates were 86.3–93.1%, 65.4–78.7%, and 43.0–53.8%, and 0%, respectively. The 10 year cause-specific survival rates were 97.2–100%, 91.5–97.4%, and 71.2–80.0%, and 0%, respectively.     

Ultrasonography as a predictor of overt bleeding after renal biopsy

Background  Renal biopsy is essential for the diagnosis of kidney diseases, but complications, particularly bleeding incidents, remain problematic. Methods  To evaluate the frequency of renal biopsy complications, and to reveal clinical and laboratory factors associated with overt bleeding complications, focusing on those available at hospital ward, we conducted a retrospective observational study for the period between 2001 and 2005 at Mie University Hospital in patients who underwent percutaneous renal biopsy of a native kidney. Of a total of 323 patients, 317 met the inclusion criteria. Results  Only one patient (0.3%) required blood transfusion or intervention to stop bleeding. The mean decrease in hemoglobin (Hb) after biopsy was 0.43 ± 0.7 g/dL. Hb decreased ≥1.0 g/dL in 66 patients (20.8%) and ≥10% in 32 patients (10.1%). On ultrasonography, perirenal hematoma was detected immediately after biopsy in 273 patients (86.1%), and 41 patients (12.9%) showed hematoma ≥2 cm in width. Analgesics were required for back pain in 67 patients (21.1%). Vasovagal response developed in 31 patients (9.8%). Macrohematuria occurred in 12 patients (3.8%). Urinary catheter was used in 161 patients (50.8%). For Hb decrease ≥10% after biopsy, multivariate analysis revealed perirenal hematoma (≥2 cm) as a significant factor. Other significant factors were prolonged international normalized ratio of prothrombin time, elevated blood pressure on hospital admission, older age, increased serum creatinine level, and steroid use. Conclusion  Perirenal hematoma ≥2 cm on ultrasonography immediately after biopsy might well represent a predictive factor for bleeding complications.     

The relationship between acute phase serum amyloid A (SAA) protein concentrations and left ventricular systolic function in acute myocardial infarction patients treated with primary coronary angioplasty

BACKGROUND: Our study was planned to investigate the relationship between plasma levels of serum amyloid A protein (SAA) concentrations and the subsequent left ventricular systolic function in patients with acute myocardial infarction (AMI) treated with primary coronary angioplasty. METHODS AND RESULTS: Reperfusion by primary percutaneous coronary intervention was successful in 486 consecutive AMI patients who were admitted within 12 hours of onset. Plasma SAA concentrations were evaluated 24 hours after onset. Left ventricular (LV) function was serially determined by left ventriculography performed in the acute (soon after recanalization) and chronic phases (6 months after onset). (I) There was no significant correlation between SAA concentration and acute phase left ventricular ejection fraction (LVEF) or regional wall motion (RWM). (II) The SAA concentration was significantly correlated with both highly sensitive C-reactive protein (hs-CRP) and the peak-CK value (hs-CRP: r = 0.69, P < 0.0001, peak-CK: r = 0.21, P = 0.0003). (III) SAA was significantly negatively correlated with both LVEF and RWM in the chronic phase (LVEF: r = -0.42, P = 0.001; RWM: r = -0.41, P = 0.007). (IV) The plasma level of SAA also showed a significant negative correlation with the differences in LVEF between the 2 stages (delta-LVEF) (r = -0.43, P = 0.02). CONCLUSION: In the setting of AMI, plasma SAA concentrations may be closely related to subsequent left-ventricular systolic dysfunction.     

Left atrial volume: predictor of atrial fibrillation in patients with degenerative mitral regurgitation

BACKGROUND AND AIM OF THE STUDY: In patients with mitral regurgitation (MR) due to degenerative mitral valve prolapse (MVP), preoperative atrial fibrillation (AF) has been identified as an independent predictor of survival after surgery for MR. Thus, the determinants of preoperative AF may have critical implications to evaluate the timing of mitral valve repair. The study aim was to investigate the role of left atrial (LA) volume in predicting preoperative AF in patients with severe MR due to degenerative MVP. METHODS: Sixty-six patients with severe degenerative MR (regurgitant volume > or =60 ml, regurgitant fraction > or =50%, effective regurgitant orifice area > or =0.4 cm(2)) in sinus rhythm (SR) at diagnosis and conservatively managed were eligible for the study. Complete two-dimensional (2-D) echocardiographic and Doppler measurements, including the measurement of maximum LA volume, were performed in all patients. RESULTS: During follow up under conservative management (18.1+/-4.8 months), eight patients (12%) experienced conversion to AF, and 58 remained in SR. The mean LA dimension was 4.0+/-0.5 cm in patients with SR, and 5.1+/-0.8 cm in those who developed AF (p <0.0001). The mean LA volume and LA volume index (indexed to body surface area) were 95 +/-23 ml and 60+/-14 ml/m(2) respectively in patients with SR, and 166+/-66 ml and 104+/-42 ml/m(2) respectively in those who developed AF (both p <0.0001). The optimal cut-off value for LA volume to predict AF conversion was 117.5 ml (sensitivity 88%, specificity 83%), and for LA volume index was 75 ml/m(2) (sensitivity 88%, specificity 88%). CONCLUSION: LA volume measurement should be considered in patients with degenerative severe MR diagnosed in SR. A LA volume index > or =75 ml/m(2) reflects the risk of subsequent AF, and patients should be closely monitored.     

The evaluation of early embryonic neurogenesis after exposure to the genotoxic agent 5-bromo-2'-deoxyuridine in mice

Developmental neurotoxicity (DNT) is an important issue in children's health. Neurogenesis occurs throughout the early fetal to the postnatal period. The proliferation of embryonic stem cells can be a target for toxicants, especially genotoxic compounds. 5-Bromo-2'-deoxyuridine (BrdU), a thymidine analogue, has been used as a marker for proliferating cells. However, we reported that prenatal BrdU exposure induced behavioral abnormalities such as hyperactivity in rat and mouse offspring. In this study, to further clarify the toxic effect of BrdU on the early neurogenesis and to examine the usefulness of the evaluation of this process in DNT, C57BL/6 mice were exposed to 100 mg/kg of BrdU once on gestational day (GD) 9 or 11, and serial sections from a wide variety of areas of the embryonic brains 24 h after the exposure were examined. BrdU exposure on GD11 induced cell death in some specific areas, such as the neocortex and striatum, but not in the substantia nigra, raphe and pons, even though BrdU was incorporated into those cells. BrdU decreased the number of cells positive for phosphorylated histone 3 (phospho-histone 3), a marker for proliferating cells at metaphase of mitosis, in the cortex, mammillary body and cerebellum, suggesting that BrdU affected the proliferation of neural stem cells. Exposure on GD9 did not induce cell death in the fetal brain. These results indicate that BrdU actually impaired the early neurogenesis, supporting the postnatal results, and demonstrated that embryonic neurogenesis has heterogeneous sensitivity to the genotoxic agents BrdU that differs according to the area and developmental stage. The evaluation of events in early neurogenesis such as the proliferation of neural stem cells shortly after chemical exposure will be one of the valuable endpoints for studying postnatal neurodevelopmental disorders.     

Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity

INTRODUCTION: Generation of platelet-derived microparticle (PMP) is implicated in cardiovascular disease (CVD). However, the influence of adiposity and weight reduction on PMP generation remains to be fully elucidated. We compared PMP generation and fibrinolytic parameters between 49 non-diabetic obese (obese group) and 37 age-matched non-obese subjects (control group), and compared the effects of weight reduction on the parameters between a 12-week calorie restricted diet and diet with aerobic exercise in obese subjects. MATERIALS AND METHODS: PMP, plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) antigen were measured before and after intervention. RESULTS: Before intervention, PMP, PAI-1 activity and t-PA antigen values were elevated in the obese group compared with the control group. In all 86 subjects of both groups, these three parameters correlated with body mass index, waist circumference and fat tissue mass. There was a positive correlation between plasma levels of fibrinolytic parameters and visceral fat area (VFA). PMP values correlated with subcutaneous fat area (SFA). The intervention significantly reduced PMP, PAI-1 activity and t-PA antigen levels. There was a significant correlation between percentages of changes in PMP values and those in BMI, fat tissue mass and VFA in the obese group. No additional effect of exercise on PMP or fibrinolytic parameters was observed. CONCLUSIONS: Overproduction of PMP and fibrinolytic abnormalities may be associated with excessive adipose tissue. Weight reduction by either calorie restriction with or without exercise improves fibrinolytic abnormalities and PMP overproduction, probably through reduction of adipose tissue.