Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes.

Androgen deprivation therapy is the gold standard regimen for advanced Prostate cancer (PCa) patients, nevertheless, patients eventually develop into castration-resistant prostate cancer (CRPC). Currently only a few chemotherapeutics are available for CRPC. Therefore, it is critical for identifying a new drug. In this study, we will explore a new agent, Saikosaponin-d (SSd), for CRPC therapy based on its mechanism of action. DU145 and CWR22Rv1 cells representing CRPC were employed in this study. A series of cell, biochemical, and molecular biologic assays such as Immunofluorescence, Zymography, Sphere formation, Colony formation, and MTT were used. Finally, we find SSd can significantly inhibit the growth of PCa cells in both dose- and time-dependent and suppress the colony formation during a long-term drug administration, it also can inhibit their migration and invasion abilities, which was accompanied by reverse the epithelial-mesenchymal transition (EMT) and suppress MMP2/9 expression as well as activities. Furthermore, SSd can suppress cancer stem cell (CSC) phenotypes such as self-renewal ability. Mechanistically, SSd blocks Wnt/ß-catenin signaling pathway by decreasing GSK3ß phosphorylation to affect EMT and CSC. These findings demonstrate the mechanism of anti-cancer activity of SSd in targeting EMT and CSC, suggesting SSd can be a potent agent for CRPC therapy.

Keyhole epilepsy surgery: corticoamygdalohippocampectomy for mesial temporal sclerosis.

Surgical approaches for medically refractory mesial temporal lobe epilepsy (MTLE) that previously have been reported include anterior temporal lobectomy (ATL), transcortical selective amygdalohippocampectomy, transsylvian amygdalohippocampectomy, and subtemporal amygdalohippocampectomy. Each approach has its advantages and potential pitfalls. The purpose of this report is to describe our technique of keyhole corticoamygdalohippocampectomy for patients with MTLE due to hippocampal sclerosis. Operations were performed through a 6-cm vertical linear incision and a low 2.5-cm keyhole craniotomy at the anterior squamous temporal bone. Resection of the anterior-most portions of the middle and inferior temporal gyri provided a cylinder-like corridor to the mesial temporal lobe. Identification of the temporal horn through a basal approach was followed by resection of the amygdala, uncus, and hippocampus-parahippocampal gyrus. This 9-year series included 683 patients with a minimum follow-up duration of 2 years. Surgery times were short (range, 1 h 35 min to 2 h 30 min). Only a small percentage of patients had complications (1.76%), and the rate of Engel Class I seizure-free outcome was 87%. No overt speech problems or visual field deficits were identified. Compared with the most popular conventional trans-middle temporal gyrus approach, this technique can make the operation easier, safer, and less traumatic to functional lateral neocortex.

Intractable occipital lobe epilepsy: clinical characteristics, surgical treatment, and a systematic review of the literature.

PURPOSE: We reported our experience in the surgical treatment of a relatively large cohort of patients with occipital lobe epilepsy (OLE). We also carried out a systematic review of the literature on OLE. METHODS: Thirty-five consecutive patients who underwent occipital resection for epilepsy were included. Diagnoses were made following presurgical evaluations, including magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), scalp video-electroencephalogram (EEG) monitoring, and intracranial EEG monitoring. At last follow-up, seizure outcome was classified using the Engel classification scheme. RESULTS: Twenty-five of 35 patients experienced/had experienced ≥1 type of aura before the seizure. Invasive recordings were used to define the epileptogenic area in 30 of 35 patients (85.7 %). All patients underwent occipital lesionectomies or topectomies. Histopathology revealed: cortical dysplasias, gliosis, dysembryoplastic neuroepithelial tumor, ganglioglioma, and tuberous sclerosis. After a mean follow-up of 44 months, 25 patients (71.4 %) were seizure free (Engel class I), 3 (8.6 %) rarely had seizures (Engel class II), 5 (14.3 %) improved more than 75 % (Engel class III), and 2 (5.7 %) had no significant improvement (Engel class IV). Preoperatively, 12 of 33 patients (36.4 %) had visual field deficits. Postoperatively, 25 patients (75.8 %) had new or aggravated visual field deficits. CONCLUSIONS: The management of OLE has been aided greatly by the availability of high-resolution diagnosis. Postoperative visual field deficits occur in a significant proportion of patients. Comprehensive intracranial EEG coverage of all occipital surfaces helps to define the epileptogenic area and preserve visual function, especially in cases of focal cortical dysplasia undetectable by MRI.

Outcome after anterior callosal section that spares the splenium in pediatric patients with drop attacks.

We report on the efficacy and safety of extended, one-stage anterior callosal section that spares the splenium, which is performed in a large series of pediatric patients with drop attacks. Twenty-nine pediatric patients with drop attacks were studied (19 males and 10 females; mean age: 9.9 years). As presurgical factors, the age at surgery, age at seizure onset, age at drop attack onset, sex, hemiparesis, severe mental retardation, electroencephalograph abnormalities, magnetic resonance imaging abnormalities, and (18)fluorodeoxyglucose positron emission tomography abnormalities were analyzed. All patients had multiple seizure types, including drop attacks, atypical absence seizures, complex partial seizures, tonic seizures, and generalized tonic-clonic seizures. All patients were developmentally impaired and had electroencephalograph results showing marked secondary bilateral synchrony. All patients received an extended, one-stage callosal section, leaving only the splenium intact. The mean follow-up time was 5.2 years. Seizure outcome (cessation of seizures or ≥ 90% seizure reduction) was achieved in 79.3% of patients with drop attacks. The families assessed the overall daily function as improved in 62.1% of the patients, unchanged in 24.1%, and worse in 13.8%. Family satisfaction with callosotomy was achieved in 82.8% of the patients. The majority of the patients had some degree of a transient acute postoperative disconnection syndrome that disappeared within 3 weeks. Postoperatively, patients showed a consistent increase in attention levels. We conclude that extended callosal sectioning that leaves the splenium intact should be considered a good palliative surgical option for pediatric patients with drop attacks and that diminishment of epileptic discharge synchrony is a good prognostic sign following callosotomy. We also found that the postoperative increase in attention levels was as useful as seizure control in improving the quality of life of these patients.

Long-term epilepsy surgery outcomes in patients with PET-positive, MRI-negative temporal lobe epilepsy.

This study compared the long-term efficacy of anterior temporal lobectomy (ATL) for the treatment of medically refractory temporal lobe epilepsy (TLE) in patients who presented with ipsilateral temporal PET hypometabolism and nonlesional magnetic resonance imaging (PET+/MRI-) with that in patients who had mesial temporal sclerosis (MTS) on MRI. We described the electroclinical, MRI, PET, and pathological characteristics and seizure outcome of 28 PET+/MRI--patients without discordant ictal and interictal electroencephalography (EEG) who underwent ATL (2004-2007) for medically refractory partial epilepsy while avoiding intracranial monitoring. The primary outcome was the percentages of Engel Class I outcomes at 2 and 5 years of PET+/MRI--patients compared with those of patients with MTS on MRI; neuropsychological testing was used as the secondary outcome. At 2-year follow-up, 21 (75%) patients in the PET+/MRI--group were in Engel Class I compared with 66 (75.9%) patients with MTS, and at 5-year follow-up, 20 (71.4%) patients in the PET+/MRI--group were in Engel Class I compared with 64 (73.6%) patients in the group with MTS. There were no significant differences between the groups at either time period. We concluded that normal MRI results should not preclude presurgical evaluations in patients with medically refractory TLE, as favorable long-term postoperative seizure outcomes are possible, especially in patients with unilateral anterior interictal epileptiform discharges and ipsilateral temporal PET hypometabolism.

Disconnective surgery in posterior quadrantic epilepsy: a series of 12 paediatric patients.

AIM: To assess the surgical outcomes of temporo-parieto-occipital (TPO) and parieto-occipital (PO) disconnection surgery for children with intractable posterior quadrantic epilepsy and a unilateral posterior quadrant lesion based on MRI and functional imaging abnormality in the TPO region on one side. METHODS: A retrospective review of data of 12 children who underwent TPO or PO disconnective surgery was carried out from September 2009 to September 2012. Three-dimensional surface reconstructions of MRI scans and intraoperative electrophysiological monitoring were used during surgery. Drugs were not discontinued after surgery in any patient. RESULTS: The affected hemisphere was the left in seven patients and the right in five patients. The mean ages at seizure onset and at surgery were four years and 12.3 years, respectively. At the time of surgery, 3 children had atonic seizures, 4 had symptomatic epilepsy with focal seizures and alteration of conscioussness, 4 had secondarily generalised seizures, and 1 child had spasms and tonic seizures. All patients had developmental delay. A pure TPO disconnection was performed in 11 patients and a PO disconnection was performed in the remaining patient. On pathological examination, 3 patients were shown to have focal cortical dysplasia (FCD) Ib, 2 with FCD IIa, 5 with FCD IIb, 1 with gliosis, and 1 with gliosis plus FCD IIa. Following surgery, 2 patients had oedema; 1 required another operation to resect the occipital lobe. At a mean follow-up of 34.5 months, 9 patients (75%) were classified as Engel class I, 2 as Engel Class II, and 1 as Engel class III. All 12 children had contralateral hemianopia postoperatively and improvement in median IQ (p=0.04) was reported three months postoperatively. CONCLUSIONS: With respect to the limits of a retrospective and relatively small sample size series TPO and PO disconnection are safe and effective motor-sparing epilepsy surgical procedures in selected patients with the epileptiform zone located in the posterior quadrant on one side.

[Effects of Chinese herbal medicine Dusuqing Granule on toll-like receptor 4 signaling in multiple organ injury induced by bacterial pneumonia in aged rats].

OBJECTIVE: To study the protective mechanism of Dusuqing Granule, a compound Chinese herbal medicine, on the senile multiple organ injury caused by bacterial pneumonia by observing the expression changes of molecules related to toll-like receptor 4 (TLR4) signaling. METHODS: A total of 55 male Sprague-Dawley aged rats were divided into control group, untreated group, Dusuqing group and lomefloxacin group. There were 25 rats in the untreated group and 10 rats in each of the other three groups. Multiple organ injury in a rat model of pneumonia was induced by injection of Klebsiella pneumoniae through tracheal intubation. By means of immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), examinations were made on mRNA expressions of lipopolysaccharide-binding protein (LBP), CD14, TLR4 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in the tissues of the lung, heart and small intestine, and also on the protein expressions of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor-κB (NF-κB). RESULTS: Expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the untreated group were stronger than those in the control group (P<0.01 or Plt;0.05). The protein expressions of TLR4, TRAF6 and NF-κB were increased dramatically in the untreated group as compared with the control group (Plt;0.01 or Plt;0.05). Compared with the untreated group, the expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the Dusuqing group were weakened significantly (Plt;0.01 or Plt;0.05). Meanwhile, the protein expressions of TLR4, TRAF6 and NF-κB were decreased markedly in the Dusuqing group (Plt;0.01 or Plt;0.05). CONCLUSION: Dusuqing Granule is effective in suppressing toll-like receptor signal transduction activation and reducing the secretion of cytokines and inflammatory mediators, which can further reduce the organ tissue injury. Dusuqing Granule can decrease the levels of TLR signal transduction activation including the targets LBP, CD-14, TLR4, IRAK-1, TRAF6 and NF-κB, which is different from the special inhibitor that acts only on some segments.

[A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats].

OBJECTIVE: To reproduce a model of bacterial multiple organ injury (MOI) in aged rats. METHODS: Male Sprague-Dawley (SD) rats were used. The young rats were divided into young control group (YCG, n=10) and young model group (YMG, n=15), and the elderly, aged control group (ACG, n=10) and aged model group (AMG, n=25). The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality. RESULTS: Between YMG and AMG, the mortality rates were 33.33% (5/15) and 60.00% (15/25), respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell (WBC) counts in peripheral blood increased significantly in YMG and AMG groups (all P<0.01), the rates of dysfunction of the lungs, the heart and the liver, were 60%-100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide (PaCO(2), P<0.01), and a decrease in the arterial partial pressure of oxygen (PaO(2), P<0.05 or P<0.01). Myocardial dysfunction was shown by a the sharp increase in creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH), and that of the liver by changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.05 or P<0.01). The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO(2) in AMG dropped significantly, PaCO(2) increased, CK, CK-MB, LDH, ALT and AST also increased significantly (P<0.05 or P<0.01). The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group (all P<0.05), and the same was trend in the liver and the kidney. CONCLUSION: The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome (MODS) which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.

Neuronavigation-assisted surgical treatments for medically refractory epilepsy: Single-hospital experience with 4 surgical approaches.

OBJECTIVE: Surgical treatment should be considered for patients with medically refractory epilepsy, and neuronavigation may benefit and reduce the technical difficulties during surgery. In this study, we aimed to report our single-hospital experience of incorporating neuronavigation for treating patients with medically refractory epilepsy using 4 types of surgery. PATIENTS AND METHODS: Patients who were diagnosed as medically refractory epilepsy and received neuronavigation-assisted surgery were included in this retrospective analysis. The type of surgery was decided by the surgery committee after careful evaluation and discussion, including temporo-parietal-occipital (TPO) disconnection, anterior subtotal callosal section, functional hemispherectomy and resection of the epileptogenic zone(s). Postoperative seizure outcome at the last visit was evaluated using Engel classification. RESULTS: A total of 173 patients with medically refractory epilepsy who were treated surgically under the assistance of neuronavigation were included. The majority type of surgery was resection of epileptic zone, n = 104 (60.12%). An excellent seizure outcome, Engel Class I was found in 50.86% of the patients, followed by 23.12% patients with a good outcome of Engel Class II. CONCLUSION: Overall more than half of the patients could have excellent seizure outcome of Engel Class I, the postoperative complications were manageable. These results indicated that the applicability of neuronavigation, and the use of neuronavigation provides good efficacy and safety for all kinds of surgical procedures for patients with medically refractory epilepsy.

[Effects of transurethral catheterization on uroflow rate in the pressure-flow study of patients with benign prostatic hyperplasia].

OBJECTIVE: To investigate the effects of transurethral catheterization on the uroflow rate in the pressure-flow study of patients with benign prostatic hyperplasia (BPH). METHODS: Thirty-nine men with BPH underwent free uroflowmetry and pressure-flow analysis respectively. With an 8 F urethral catheter, the standard pressure-flow variables such as the maximum flow rate, detrusor pressure at the maximum flow rate and so on were recorded. The free maximum flow rate and the maximum flow rate with transurethral catheterization were statistically analyzed. RESULTS: The maximum voided volumes of the free uroflowmetry group and the pressure-flow study group were (209.23 +/- 56. 56) ml and (210.33 +/- 62.02) ml respectively (P > 0.05). The free maximum flow rate was (8.61 +/- 2.80) ml/s, and the maximum flow rate with transurethral catheterization-was (7.39 +/- 3.01) ml/s (P < 0.05). When the patients were divided into seven grades of bladder outlet obstruction (BOO) according to the Schäfer nomogram, the free maximum flow rate and the maximum flow rate with transurethral catheterization with Grade 0-I of BOO were (12.56 +/- 1.57) ml/s and (10.95 +/- 2.51) ml/s, and those of Grade II were (9.35 +/- 0.76) ml/s and (8.41 +/- 1.23) ml/s respectively. For Grades III, IV and V-VI , the two maximum flow rates were (7.88 +/- 1.21) ml/s and (6.37 +/- 0.59) ml/s, (6.54 +/- 1.93) ml/s and (5.55 +/- 2.48) ml/s, and (6.01 +/- 2.10) ml/s and (4.84 +/- 2.89) ml/s, respectively, all with significant difference in between (P < 0.05). CONCLUSION: The 8 F urethral catheter has a significant effect on the maximum uroflow rate in the pressure-flow study and this effect is correlated with the grade of BOO.

[Delayed decompression for cauda equina syndrome secondary to lumbar disc herniation: long-term follow-up results].

OBJECTIVE: To assess the impact of delayed decompression on long-term neurological and bladder function recovery in patients with cauda equina syndrome (CES) secondary to lumbar disc herniation (LDH). METHODS: The clinical data of 35 patients receiving delayed decompression surgery for CES secondary to LDH were reviewed. The bladder empty function, bowel control, sexual ability and neurological functions of the lower limbs were evaluated after the operation, and the urodynamic changes were assessed in 6 patients with urodynamic data before and after the operation. RESULTS: Surgical decompression was performed at 4.1∓3.9 weeks in 12 patients with complete CES and at 5.5∓7.6 weeks in 23 patients with incomplete CES after the onset of symptoms. The patients were followed up for a mean of 43.0∓28.9 months (3-110 months). In the 23 patients with incomplete CES, 19 obtained full recovery, 4 had slight sensory alterations in the saddle area or the lower limbs. In the 12 patients with complete CES, 2 had full recovery, 4 reported slight sensory alterations in the saddle area or the lower limbs (including 2 with occasional constipation); 6 still had sense deficit in the saddle area and difficulties in bladder or bowl emptying, but they all reported significant improvements compared to the condition before operation. Urodynamic analysis in the 6 patients with pre- and postoperative urodynamic data showed increased abdominal pressure when voiding with significantly reduced residual urine in all the 6 patients; 4 patients with abnormal first desire volume before operation reported recovery after the operation. CONCLUSION: Patients with LDH-induced CES who missed the chance of early decompression can still expect favorable functional recovery in the long term. The improvement of bladder function following decompression is probably a result of recovery of bladder sensation and the compensation by increased intra-abdominal pressure. The key strategy to promote bladder function recovery in these patients is to promote the detrusor recovery.

[Expressions of inflammatory and fibrogenic factors in perinephric and subcutaneous adipose tissues of patients with adrenocorticotropic hormone-independent Cushing's syndrome].

OBJECTIVE: To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. METHODS: The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein ß(CEBPß), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). RESULTS: The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPß, UCP-1, and PGC1α mRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. CONCLUSION: The expression levels of the inflammation- and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.

Neuropsychological outcomes of subtemporal selective amygdalohippocampectomy via a small craniotomy.

OBJECT The objectives of this study were to describe a novel minimal-access subtemporal approach for selective resection of the amygdala and hippocampus in patients with medically refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis, and to analyze the related outcomes. METHODS The authors analyzed data from all cases involving patients with unilateral MTLE due to hippocampal sclerosis who were treated with selective amygdalohippocampectomy via the posterior subtemporal approach through a relatively small craniotomy, without a neuronavigation system, at their institution during the period from September 2010 to September 2012. Data were obtained on baseline characteristics, preoperative evaluations of unilateral mesial temporal sclerosis, surgical complications, and Engel class seizure outcomes. All patients underwent memory testing, IQ testing, and language testing. RESULTS The mean duration of follow-up was 33.6 months (range 24-48 months). There were no deaths and no cases of significant postoperative morbidity. One patient had a mild complication. At 2-year follow-up, 19 patients were seizure free (Engel Class I outcome). Verbal memory scores obtained at 3 months and at 2 years after surgery were significantly lower than preoperative scores for patients who underwent surgery on the left side of the brain (p < 0.05). Pictorial memory scores were higher following surgery compared with before surgery regardless of whether patients underwent left- or right-sided brain surgery. There was also improvement in performance IQ and total IQ following surgery in both groups. For patients who underwent right-sided brain surgery, verbal comprehension and semantic fluency testing scores were significantly higher at both 3 months and 2 years after surgery than before surgery. For patients who underwent left-sided brain surgery, scores on all language tests were significantly lower at 3 months after surgery than before surgery. Verbal comprehension testing scores returned to the preoperative level at 2 years after surgery. CONCLUSIONS The posterior subtemporal approach through a relatively small craniotomy allows adequate exposure and safe resection of mesial temporal structures and effectively reduces medically intractable MTLE. It preserves IQ but may have a detrimental effect on verbal memory and language ability.

Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.

CONTEXT: Islet allografts from 2 to 4 donors can reverse type 1 diabetes. However, for islet transplants to become a widespread clinical reality, diabetes reversal must be achieved with a single donor to reduce risks and costs and increase the availability of transplantation. OBJECTIVE: To assess the safety of a single-donor, marginal-dose islet transplant protocol using potent induction immunotherapy and less diabetogenic maintenance immunosuppression in recipients with type 1 diabetes. A secondary objective was to assess the proportion of islet transplant recipients who achieve insulin independence in the first year after single-donor islet transplantation. DESIGN, SETTING, AND PARTICIPANTS: Prospective, 1-year follow-up trial conducted July 2001 to August 2003 at a single US center and enrolling 8 women with type 1 diabetes accompanied by recurrent hypoglycemia unawareness or advanced secondary complications. INTERVENTIONS: Study participants underwent a primary islet allotransplant with 7271 (SD, 1035) islet equivalents/kg prepared from a single cadaver donor pancreas. Induction immunosuppression was with antithymocyte globulin, daclizumab, and etanercept. Maintenance immunosuppression consisted of mycophenolate mofetil, sirolimus, and no or low-dose tacrolimus. MAIN OUTCOME MEASURES: Safety (assessed by monitoring the severity and duration of adverse events) and efficacy (assessed by studying the recipients' insulin requirements, C-peptide levels, oral and intravenous glucose tolerance results, intravenous arginine stimulation responses, glycosylated hemoglobin levels, and hypoglycemic episodes) associated with the study transplant protocol. RESULTS: There were no serious, unexpected, or procedure- or immunosuppression-related adverse events. All 8 recipients achieved insulin independence and freedom from hypoglycemia. Five remained insulin-independent for longer than 1 year. Graft failure in 3 recipients was preceded by subtherapeutic sirolimus exposure in the absence of measurable tacrolimus trough levels. CONCLUSIONS: The tested transplant protocol restored insulin independence and protected against hypoglycemia after single-donor, marginal-dose islet transplantation in 8 of 8 recipients. These results may be related to improved islet engraftment secondary to peritransplant administration of antithymocyte globulin and etanercept. These findings may have implications for the ongoing transition of islet transplantation from clinical investigation to routine clinical care.

[Nephron-sparing surgery for small renal cell carcinoma: clinical analysis of 21 cases].

OBJECTIVE: To evaluate the clinical effects of nephron-sparing surgery in patients with early-stage small renal cell carcinoma. METHODS: Nephron-sparing surgery was performed in 21 patients with renal cell carcinoma including 1 with solitary kidney, 3 with unilateral tumor and contralateral renal compromise, and 17 with unilateral tumor and normal contralateral kidney. The diameter of the tumors ranged from 1.5 to 6.0 cm, with a mean of 2.8 cm. The tumor diameter in 17 patients with normal contralateral kidney was less than 4 cm (mean 2.5 cm) and the average diameter in 4 patients with contralateral renal compromise was 4.2 cm. Sixteen cases were in stage T(1), 4 in stage T(2), and 1 in stage T(3). Of the 21 patients, 4 underwent tumor enucleation, 10 polar nephrectomy and 7 wedge resection. RESULTS: All patients were followed up for an average of 40.8 months (7 to 66 months). One patient suffered a right lung and mediastinum metastasis 3 years after the surgery later and 1 with chronic glomerulonephritis required dialysis 27 months after the operation. No surgical complication or local recurrence were found in other patients. CONCLUSION: As a safe and effective therapy for early-stage small renal cell carcinoma, nephron-sparing surgery can be considered as the gold-standard therapy for patients with lesions less than 4 cm in T(1) and T(2) stages of localized unilateral tumor with normal contralateral kidney.

[Expressions of hypoxia inducible factor-1alpha and vascular endothelial growth factor in human renal cell carcinoma].

OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) and their relationship. METHODS: The expression of HIF-1alphaand VEGF was examined in 42 patients with renal cell carcinoma by SABC methods of immunohistochemistry. RESULTS: The positivity rate of HIF-1alpha was 57.1% in the RCC tissues, and there was no expression in the tissue adjacent to the tumor and normal tissues. The positivity rate of VEGF was 61.9% in the tumor tissues, with significant difference from the control tissues (P<0.05). The expression levels of HIF-1alpha and VEGF were significantly higher in metastatic RCC than in non-metastatic RCC (P<0.01) tissues, and there was a significant correlation between HIF-1alpha and VEGF expressions (Kappa=0.41, P<0.01). CONCLUSIONS: HIF-1alpha is highly expressed in renal cell carcinoma tissues in close correlation with VEGF. HIF-1alpha and VEGF may serve as important indicators to evaluate the biological behaviors of RCC such as metastasis and prognosis. HIF-1alpha is an important regulator of VEGF.

Improvement in islet yield from obese donors for human islet transplants.

BACKGROUND: The feasibility of human islet transplantations has been firmly established. To increase the number of islet transplants, the suitability of pancreases from organ donors considered inappropriate for pancreas transplantations must be evaluated. METHODS: We isolated islets from 114 human cadaver donor pancreases by the automated Ricordi method, followed by purification using continuous-density gradients. We divided the pancreases into two groups by donor body mass index (BMI)--group 1: n=51, BMI of 30 or more; group 2: n=63, BMI of less than 30. We compared the results of human islet isolation, in vitro potency assays, and a nude mouse bioassay. RESULTS: In group 1 (vs. group 2), we found a significantly higher mean pancreas weight (109.5+/-30.7 vs. 90.6+/-24.0 g; P=0.0002); higher mean islet equivalents/pancreas, after digestion (442,565+/-238,741 vs. 289,860+/-158,995; P<0.0001) and after purification (319,129+/-164,002 vs. 215,753+/-126,089; P=0.0002); and a higher islet isolation success rate--defined as isolations yielding more than 300,000 islet equivalents/pancreas, with purities of more than 50% (37.3% [19 of 51 pancreases] vs. 15.9% [10 of 63]; P=0.009). Our in vitro potency assays and bioassay uncovered no differences between the two groups. Notably, all except one of the donor BMIs for the successful isolations in group 2 exceeded 26; the mean donor BMI for the successful isolations (27.3+/-3.0, n=10) was significantly higher than for the unsuccessful isolations (24.8+/-3.3, n=53) (P=0.03). CONCLUSIONS: Pancreases from both overweight (BMI > or = 26 but <30) and obese (BMI > or = 30) cadaver donors are suitable for islet isolation and transplantations. Their use could increase the size of the islet donor pool.

Intracranial electroencephalography with subdural and/or depth electrodes in children with epilepsy: techniques, complications, and outcomes.

Intracranial electroencephalographic monitoring with subdural and/or depth electrodes is widely used for the surgical localization of epileptic foci in patients with intractable partial epilepsy; however, data on safety and surgical outcome with this technique are still inadequate. The aims of this study were to assess the morbidity of intracranial recordings and the surgical outcomes in epileptic children. We retrospectively reviewed the clinical data for 137 children with epilepsy (mean age at implantation: 12.6 ± 3.8 years) who underwent intracranial monitoring with the implantation of strip or grid subdural electrodes and/or intracerebral depth electrodes from September 2004 to September 2011 at a tertiary epilepsy center in China. Complications were classified using five grades of severity (including mortality) and were further classified as either minor or severe. Outcome was classified according to Engel's classification. Regression analysis was performed to identify risk factors for complications. The mean duration of implantation was 5.3 ± 1.3 days. Among the 133 patients who underwent resection, 65 (48.9%) were seizure free (Engel Class I) at last known follow-up, which was >2 years after surgery for all patients. Also, 31 (23.3%) patients had a significant reduction in seizures (Engel Class II). Complications of any type were documented in 29 (21.7%) patients; 15 of these patients had intracranial hematoma. The results of multivariate analysis showed that the only independent risk factor for intracranial hematoma was number of electrode contacts. The most common pathologic diagnosis was focal cortical dysplasia (n=58). Our results showed that intracranial electroencephalographic monitoring in children provides good surgical outcomes and the level of risk is acceptable. When using this technique strategies such as using as few electrode contacts as possible should be adopted to minimize the risk of intracranial hematoma.

[Detection of Skp2 and p27kip1 expression in human renal cell carcinoma using tissue chip technique].

OBJECTIVE: To detect the expression of skp2 and p27kip1 in human renal cell carcinoma (RCC) using tissue chip technique, and evaluate the relationship between the proteins and the biological behavior of RCC. METHODS: Tissue chip technique and immunohistochemical SP method was used to detect the expression of skp2 and p27kip1 in normal and tumor tissues. RESULTS: The positivity rate of Skp2 in RCC was significantly higher than that in normal renal tissues (P=0.025). The positivity rate of Skp2 expression in RCC was significantly correlated to poor differentiation of the tumor (P=0.002), and was not associated with the patients gender, age, tumor size, lymph node metastasis and stages of RCC (P>0.05). The positivity rate of p27kip1 in RCC was significantly lower than that in normal renal tissues (P=0.007). The positivity rate of p27kip1 expression was inversely correlated to the malignancy and stage of RCC (P<0.05), but not with the patients' age, gender, lymph node metastasis and tumor size (P>0.05). An inverse correlation was noted between Skp2 and p27kip1 expressions (r= -0.273, P=0.014). CONCLUSION: Overexpression of Skp2 protein may lead to decreased p27kip1 level in RCC, indicating its involvement in the carcinogenesis and development of RCC.

Caspase-3 inhibitor prevents apoptosis of human islets immediately after isolation and improves islet graft function.

OBJECTIVES: Apoptosis appears in islets after isolation, and it has a detrimental effect on the islet function. To improve the outcome of clinical islet transplantation, it is crucial to protect islets from apoptosis. The aim of this study was to determine whether a caspase-3 inhibitor (Z-DEVD-FMK) added to culture media protects islets from apoptosis and to compare the effects of fetal bovine serum (FBS) with human serum albumin (HSA) as a protein supplement in culture. METHODS: Isolated human islets were cultured under 4 different conditions: 0.5% HSA (control), 0.5% HSA + 25 micromol/L Z-DEVD-FMK, 0.5% HSA + 100 micromol/L Z-DEVD-FMK and 10% FBS for 2 days. Next, 1000 IEQ islets precultured with 0.5% HSA and with or without 100 micromol/L Z-DEVD-FMK were transplanted to diabetic nude mice. RESULTS: The islet yields were higher in Z-DEVD-FMK-treated groups, and the inhibitor prevented apoptosis dose dependently. The yield and insulin release were higher in FBS-treated group than in the control group, but FBS did not affect apoptosis. All 6 mice transplanted with islets pretreated with Z-DEVD-FMK, and 3 of 8 mice with control islets became normoglycemic posttransplantation. CONCLUSION: Z-DEVD-FMK prevented apoptosis of isolated human islets and improved its function. FBS (10%) improved the islet yield and insulin secretion more than 0.5% HSA.