Tao-Chen Lee

Contralateral acute epidural hematoma after decompressive surgery of acute subdural hematoma: clinical features and outcome.

BACKGROUND Delayed contralateral epidural hematoma (EDH) after decompressive surgery for acute subdural hematoma (SDH) is uncommon. If unrecognized, this delayed hematoma can cause devastating consequences. We present our experience with this group of patients and discuss the diagnosis and management of this dangerous condition. METHODS This study included 12 traumatic patients with acute SDH who developed delayed contralateral EDH after acute SDH evacuation. Clinical and radiographic information was obtained through a retrospective review of the medical records and the radiographs. RESULTS There were seven males and five females. Nine patients had severe head injury (Glasgow Coma Scale {GCS} score < or = 8). Ten patients underwent acute SDH evacuation within 4 hours after the trauma. Intraoperative brain swelling during SDH evacuation was noted in 10 patients. A skull fracture at the site of the EDH on computed tomography (CT) was noted only in 10 patients. However, a skull fracture overlying the EDH was found during EDH evacuation in all patients. Only three patients with less severe head injury (GCS > 8) had good recovery. Other patients with severe head injury (GCS < or = 8) had poor outcome. CONCLUSIONS Severe head injury, a skull fracture contralateral to the original hematoma, intraoperative brain protrusion, and a poor outcome are typical clinical findings in this disorder. In patients with acute SDH and a contralateral skull fracture, immediate postoperative CT scan is indicated to evaluate this rare but potentially lethal complication. According to the findings of the postoperative CT scan, the neurosurgeon can make an appropriate strategy of treatment promptly. Early detection and prompt treatment may improve the poor outcome in this group of patients.

Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-β Receptors

TGF-beta is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize TGF-beta to ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) is a member of the TGF-beta superfamily and is highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK-49F cells (rat fibroblasts). We showed that TGF-beta1 induces an increase in fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed the TGF-beta1-induced increase in fibronectin concomitant with a significant decrease in type I TGF-beta receptors (TGF-beta RI). Moreover, BMP-2 significantly shortened the half-life of TGF-beta RI. These results are related to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2-mediated degradation of TGF-beta RI. This was confirmed because BMP-2 time course dependently enhanced the ubiquitination level of TGF-beta RI. In addition, Smads would seem to be involved in the interaction of BMP-2 and TGF-beta. We demonstrated that BMP-2 significantly reversed the TGF-beta1-induced increase in pSmad2/3 and reversed the TGF-beta1-induced decrease in inhibitory Smad7. Most importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in TGF-beta RI. We evaluated the clinical efficacy of BMP-2 using unilateral ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral ureteral obstruction kidneys, interstitial fibrosis was prominent. However, treatment with BMP-2 dramatically reduced Massons trichrome staining (collagen) in the interstitial and tubular areas of the kidneys concomitantly with a reduction in TGF-beta RI. These results suggest that BMP-2 acts as a novel fibrosis antagonizing cytokine partly by down-regulating TGF-beta RI and Smads.

Hypertensive Caudate Hemorrhage Prognostic Predictor, Outcome, and Role of External Ventricular Drainage

Background and Purpose The purpose of the present study was to analyze the outcome and outcome predictors of caudate hemorrhage and role of external ventricular drainage in acute hydrocephalus. Methods Clinical data from 36 consecutive patients with hypertensive caudate hemorrhage was used in the present study. Age, gender, volume of parenchymal hematoma, hematoma in the internal capsule, initial Glasgow Coma Scale (GCS), hydrocephalus, severity of intraventricular hemorrhage, and hemorrhagic dilatation of the fourth ventricle were analyzed for effect on outcome. Effect of external ventricle drainage for hydrocephalus was evaluated by comparing preoperative and postoperative GCS scores. Results By univariate analyses, poor outcome was associated with a poor initial GCS score (P =0.016), hydrocephalus (P <0.001), intraventricular hemorrhage severity (P <0.01), and hemorrhagic dilatation of the fourth ventricle (P =0.02). By multivariate analysis, stepwise logistic regression revealed that hydrocephalus was the only independent prognostic factor for poor outcome (P <0.001). Postoperative 48-hour GCS score was better than the preoperative score by use of paired-sample t test (P <0.001). Conclusions Hydrocephalus is the most important predictor of poor outcome. External ventricular drainage response for hydrocephalus was good in the present study, whereas an early decision should be made regarding preoperative neurological condition.

BMP-2 suppresses renal interstitial fibrosis by regulating epithelial-mesenchymal transition.

Dysregulation of epithelial‐to‐mesenchymal transition (EMT) may contribute to renal fibrogenesis. Our previous study indicated that bone morphogenetic protein‐2 (BMP‐2) significantly reversed transforming growth factor (TGF)‐β1‐induced renal interstitial fibrosis. In this study, we examined the underlying mechanism and elucidate the regulation of EMT process under BMP‐2 treatment. Cultured renal interstitial fibroblast (NRK‐49F) was treated with TGF‐β1 (10 ng/ml) with or without BMP‐2 (10–250 ng/ml) for 24 h. The expression of α‐smooth muscle actin (α‐SMA), E‐cadherin, fibronectin, or Snail transcriptional factors was analyzed by immunofluorescence staining or Western blotting. Cell migration was analyzed by wound‐healing assay. NRK‐49F treated with TGF‐β1 induced significant EMT including upregulatioin of α‐SMA, fibronectin, and snail proteins and down‐regulation of E‐cadherin. Interestingly, co‐treatment with BMP‐2 dose‐dependently reversed TGF‐β1‐induced cellular fibrosis, cell migration, and above EMT change. The above effect was closely correlated with Snail since BMP‐2 dose‐ and time‐course dependently induced a significant decrease in the level of Snail. Moreover, Snail siRNA significantly reversed TGF‐β1‐induced increases in the level of α‐SMA and fibronectin (intracellular and extracellular). We suppose that BMP‐2 have the potential to attenuate TGF‐β1‐induced renal interstitial fibrosis by attenuating Snail expression and reversing EMT process. J. Cell. Biochem. 112: 2558–2565, 2011.

Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid hemorrhage

Background and purpose:  Seizures are important neurologic complications of spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of the risk factors of seizures following aneurysmal SAH is needed to predict those who will require treatment.

Impact of body mass index on adjacent segment disease after lumbar fusion for degenerative spine disease.

BACKGROUND Adjacent segment disease is an important complication after fusion of degenerative lumbar spines. However, the role of body mass index (BMI) in adjacent segment disease has been addressed less. OBJECTIVE To examine the relationship between BMI and adjacent segment disease after lumbar fusion for degenerative spine diseases. METHODS For this retrospective study, we enrolled 190 patients undergoing lumbar fusion surgery for degeneration. BMI at admission was documented. Adjacent segment disease was defined by integration of the clinical presentations and radiographic criteria based on the morphology of the dural sac on magnetic resonance images. RESULTS Adjacent segment disease was identified in 13 of the 190 patients, accounting for 6.8%. The interval between surgery and diagnosis as adjacent segment disease ranged from 21 to 66 months. Five of the 13 patients required subsequent surgical intervention for clinically relevant adjacent segment disease. In the logistic regression model, BMI was a risk factor for adjacent segment disease after lumbar fusion for degenerative spine diseases (odds ratio, 1.68; 95% confidence interval, 1.27-2.21; P < .001). Any increase of 1 mean value in BMI would increase the adjacent segment disease rate by 67.6%. The patients were subdivided into 2 groups based on BMI, and up to 11.9% of patients with BMI ≥ 25 kg/m were diagnosed as having adjacent segment disease at the last follow-up. CONCLUSION BMI is a risk factor for adjacent segment disease in patients undergoing lumbar fusion for degenerative spine diseases. Because BMI is clinically objective and modifiable, controlling body weight before or after surgery may provide opportunities to reduce the rate of adjacent segment disease and to improve the outcome of fusion surgery.

Rotterdam computed tomography score as a prognosticator in head-injured patients undergoing decompressive craniectomy.

BACKGROUND The Rotterdam computed tomography (CT) score was developed for prognostic purposes in traumatic brain injury (TBI). OBJECTIVE To examine the prognostic discrimination and prediction of the Rotterdam CT score in the case of patients undergoing decompressive craniectomy (DC) for TBI. METHODS The CT scans with the worst findings before DC were scored according to the Rotterdam CT classification. Mortality and Glasgow Outcome Scale score at the end of follow-up were used as outcome measures. Unfavorable and favorable outcomes were defined by a Glasgow Outcome Scale score of 1 to 3 and 4 to 5, respectively. We used binary logistic and proportional odds regression for prognostic analyses. RESULTS The relationship between the Rotterdam CT score and prognosis was quantified, and higher scores indicated worse patient outcomes. Univariate analysis showed that the Rotterdam CT score was significantly associated with mortality (odds ratio: 3.117, 95% confidence interval: 1.867-5.386; P < .001) and unfavorable outcomes (odds ratio: 2.612, 95% confidence interval: 1.733-3.939; P < .001). After adjustment for published outcome predictors of TBI in multivariate regression, the Rotterdam CT score remained an independent predictor of unfavorable outcomes (odds ratio: 1.830, 95% confidence interval: 1.043-3.212; P = .035). CONCLUSION For head-injured patients undergoing DC, the Rotterdam CT score provides great prognostic discrimination and is an independent predictor of unfavorable outcomes. We suggest that the Rotterdam CT score be included as a prognosticator in the overall assessment of clinical condition of TBI patients before DC.

Multiloculated pyogenic brain abscess: experience in 25 patients.

OBJECTIVE To report our experience in treating multiloculated pyogenic brain abscess and determine whether there are differences in the bacteriology, predisposing factors, treatment choices, and outcomes between multiloculated and uniloculated brain abscesses. METHODS We studied clinical data collected during a 16-year period from 124 patients with pyogenic brain abscess, including 25 cases of multiloculated abscess. RESULTS The incidence of multiloculated brain abscess was 20%. In these 25 patients, hematogenous spread from a remote infectious focus was the most common cause of infection, as it was for the cases of uniloculated abscess. Headache and hemiparesis were the most common symptoms in patients with multiloculated abscess. In patients with uniloculated abscess, fever was the most common symptom. Viridans streptococci were the most commonly isolated pathogens. Bacteroides fragilis was the most common anaerobe in multiloculated abscess, and aerobic gram-negative bacilli were the most common pathogens in patients with uniloculated abscess. Of the patients with multiloculated abscess, 21 were treated surgically and 4 were treated with antibiotics only. Overall, eight patients (38%) needed another operation because of abscess recurrence after the initial operation. In uniloculated abscess, the rate of abscess recurrence after initial surgery was 13.1%. Mortality was 16% in multiloculated abscess and 17.1% in uniloculated abscess. CONCLUSION Multiloculated abscesses accounted for 20% of our patients with pyogenic brain abscess. Excision seems to be the more appropriate surgical choice in multiloculated abscess. Prognosis for patients with multiloculated abscess can be as good as that for patients with uniloculated abscess. However, clinicians must carefully monitor these patients because the possibility of recurrence after surgery is significantly higher in patients with multiloculated abscess than in those with uniloculated abscess.

CD36 is a novel and potential anti‐fibrogenic target in albumin‐induced renal proximal tubule fibrosis

Albumin is not only a risk factor for diabetic nephropathy (DN), but also a therapeutic target. Hence, scientists have long sought ways to elucidate the interactions between albumin and diabetic renal tubule fibrosis. CD36, a surface receptor for thrombospondin‐1, has been reported to interact with latent transforming growth factor‐beta1 (TGF‐β1) and activate its fibrogenic bioactivity. This study elucidates the interactions between CD36 and renal tubule fibrosis. LLC‐PK1 cells were applied to represent renal proximal tubule cells. The expression of CD36 was evaluated by flow cytometry. Fibronectin was assayed by Western blot and enzyme‐linked immunosorbent assay (ELISA). Bioactive TGF‐β1 was assayed by ELISA. We demonstrated that albumin was shown significantly to inhibit cell growth without affecting hypertrophy status since protein content and cell size remained unaffected under albumin treatment. Moreover, albumin dose‐dependently (0, 1, or 10 mg/ml) enhanced the secretion of bioactive TGF‐β1 and fibronectin with the upregulation of CD36. Intriguingly, CD36 siRNA, a potent silencer for CD36 effectively suppressed the albumin‐induced increase in CD36, TGF‐β1, and even fibronectin level. Accordingly, albumin is a pro‐fibrogenic factor for proximal tubule cells since albumin per se markedly upregulated the expression of TGF‐β1 and fibronectin. Most importantly, CD36 may mediate albumin‐induced cellular fibrosis since CD36 siRNA appeared to have anti‐fibrosis effects. This work suggests that CD36 is a novel and potential therapeutic target for diabetic renal tubule fibrosis. J. Cell. Biochem. 101: 735–744, 2007.

Comparison of Surface Markers between Human and Rabbit Mesenchymal Stem Cells

This study investigated whether there are marked differences in surface markers between rabbit and human mesenchymal stem cells (MSCs). Murine and rabbit MSCs have been reported to be CD90-negative. Rat MSCs have been reported to be CD71-negative. Our previous study also shows that rabbit MSCs are CD29-negative. However, human MSCs are generally considered to be CD29-, CD71-, and CD90-positive. Therefore, the surface markers of human MSCs might differ from those of other species. Rabbit bone marrow MSCs were obtained that had a multi-differentiation potential. The phenotype of these cells was studied using flow cytometry antibodies for 25 rabbit surface markers, namely, CD13, CD14, CD29, CD31, CD34, CD44, CD45, CD49d, CD49f, CD51, CD54, CD59, CD71, CD73, CD90, CD105, CD106, CD133, CD166, MHC I, MHC II, α-smooth muscle actin (α-SMA), cytokeratin, desmin, and vimentin. The phenotype of commercially available human MSCs was similarly studied using antibodies for human surface markers. CD14, CD31, CD34, CD45, CD49d, CD49f, CD51, CD54, CD71, CD106, CD133, MHC II, and cytokeratin were absent from both rabbit and human MSCs, while CD44, α-SMA, and vimentin were present on both cell lines. CD13, CD29, CD59, CD73, CD90, CD105, CD166, and MHC I were present on human MSCs, but not on rabbit MSCs. However, desmin was present on rabbit MSCs, but not on human MSCs. In total, the surface expression of nine markers differed between human and rabbit MSCs, whereas the surface expression of 16 markers was the same in the two cell lines.