High concentration sevoflurane induction of anesthesia accelerates onset of vecuronium neuromuscular blockade

PURPOSE: To investigate neuromuscular block using accelography after administration of vecuronium under sevoflurane 8% induction and maintenance with sevoflurane 2% in adults. METHODS: Patients were allocated to three groups: (1) group I: anesthesia was induced and maintained with propofol and fentanyl (n= 15), (2) group II: anesthesia was induced with propofol and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15), (3) group III: anesthesia was induced with sevoflurane 8% using a vital capacity inhalation induction and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15). 0.1 mg x kg(-1) vecuronium was used for paralysis three minutes after anesthetic induction and reversed using intravenous 0.04 mg x kg(-1) neostigmine with 0.02 mg kg atropine when the train-of-four (TOF) ratio returned to 25%. RESULTS: The onset time from initial administration of vecuronium to maximal block in the group III was shorter than that in the groups I and II (139 +/- 35, 193 +/- 35 and 188 +/- 47s, respectively: P < 0.05). The clinical duration from maximal block to 25% recovery of TOF ratio in group II and III was longer than that in the group I (47 +/- 15, 48 +/- 14 and 36 +/- 10 min, respectively: P < 0.05). The reversal times from administration of neostigmine to 75% of TOF ratio in groups II and III were longer than that in the group I (196 +/- 53, 208 +/- 64 and 136 +/- 28s, respectively: P < 0.05). CONCLUSIONS: Vital capacity inhalation induction of anesthesia with sevoflurane accelerates onset and prolongs duration of vecuronium neuromuscular block compared with propofol-fentanyl anesthesia.     

Trauma sites and clinical features associated with acute hyperextension spinal cord injury without bone damage--relationship between trauma site and severity

To elucidate whether a relationship exists between the site of trauma and severity of acute hyperextension spinal cord injury without bone damage, we examined the clinical features of 25 male and 10 female patients aged 13 to 88 years. None of the patients had vertebral damage such as fracture and dislocation. The site of impact was classified as the buccal, forehead, or mandibular region. The neurological findings were assessed according to Frankel's classification at admission and at follow up after 3 months or more to assess outcome. Eleven patients suffered trauma in the buccal region, one patient in Frankel's grade B, three in grade C, and seven in grade D at admission. All 11 of these patients showed an improvement of one grade or more to an outcome of C in one patient, D in one, and E in nine. Trauma occurred at the forehead region in 18 patients, four in grade B, 10 in grade C, and four in grade D. Improvement was seen at follow up by one grade or more to C in one patient, D in 10, and E in seven. Trauma occurred at the mandibular region in six patients, four in grade B and two in grade C. Four of these patients showed improvement of one grade or more to grade B in one, grade C in four, and grade E in one. Overall, seven patients had poor outcomes, five of whom suffered trauma to the mandibular region, indicating that impact to the mandibular region tends to have an unfavorable clinical outcome. Our findings indicate that the site of trauma greatly influences the severity of hyperextension spinal cord injury.     

Therapeutic potential of transgenic mesenchymal stem cells engineered to mediate anti–high mobility group box 1 activity: targeting of colon cancer

Background

Mesenchymal stem cells (MSCs) are being developed as a new clinically relevant stem cell type to be recruited into and to repair injured tissue. A number of studies have focused on the therapeutic potential of MSCs by virtue of their immunomodulatory properties. Systemically administered MSCs can also migrate to sites of malignancies. Because of this latter phenomenon, we transfected human MSCs to secrete anti–high mobility group box (HMGB) 1 proteins. They were then injected into mice bearing human colon cancer to evaluate their efficacy as an antineoplastic agent.

Materials and methods

The ABOX gene was used in this model, which encodes part of the HMGB1 protein and acts as an HMGB1 antagonist. It was cotransduced by electroporation with a FLAG-tag to visualize the secreted ABOX protein, levels of which in supernatants from cultured transfected MSCs were quantified by immunofluorescence imaging using an anti-FLAG antibody. Antiangiogenic effects were evaluated in vitro using a novel optical assay device for the quantitative measurement of cellular chemotaxis assessing the velocity and direction of endothelial cell movement stimulated by supernatant from tumor cells. We found that ABOX proteins released from transfected MSCs suppressed migration in this assay. Finally, MSCs were injected subcutaneously into Nonobese diabetic/severe combined immunodeficiency mice bearing human colon cancer from a cell line, which secreted large amounts of HMGB1. Ten days after MSC injection, mice were sacrificed and tumors evaluated by immunohistochemistry.

Results

From 12 ho through 7 d after gene transfection, ABOX proteins secreted from MSCs could be detected by immunofluorescence and enzyme-linked immunosorbent assay. Quantitative measurement of cellular chemotaxis demonstrated that ABOX proteins secreted from transfected MSCs decreased the velocity and interfered with the direction of movement of vascular endothelial cells. Moreover, in an in vivo human colon cancer xenograft model, injection of anti-HMGB1–transfected MSCs resulted in a decreased tumor volume due to the antiangiogenic properties of the secreted ABOX proteins.

Conclusions

MSC modified to secrete HMGB1 antagonist proteins have therapeutic antineoplastic potential. These findings may contribute to future novel targeting strategies using autologous bone marrow–derived cells as gene delivery vectors.     

Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

Background

Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.

Methods

Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.

Results

Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.

Conclusions

Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

     

Enhanced brain signal variability in children with autism spectrum disorder during early childhood

Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Surgical outcomes of laparoscopy-assisted gastrectomy versus open gastrectomy for gastric cancer: a case-control study

Background

The aim of this study was to clarify the technical feasibility and oncological efficacy of laparoscopy-assisted gastrectomy (LAG) for gastric cancer compared with open gastrectomy (OG).

Methods

Between April 2002 and March 2008, a series of 623 patients with gastric cancer underwent R0 gastrectomy (314 LAG patients and 309 OG patients). Age, gender, lymph node dissection, and pathological stage were matched by propensity scoring, and 212 patients (106 LAG and 106 OG) were selected for analysis after the exclusion of 40 patients who had proximal gastrectomy. Intraoperative factors, postoperative morbidity, long-term quality of life (QOL), and survival were evaluated. Moreover, these outcomes were also compared between the laparoscopy-assisted total gastrectomy (LATG) and the open total gastrectomy (OTG).

Results

There was no significant difference in preoperative characteristics between the two patient groups. Regarding intraoperative characteristics, blood loss was significantly lower in the LAG group (143?ml) than in the OG group (288?ml), while operation time was significantly longer in the LAG group (273?min) than the OG group (231?min). The degree of lymph node dissection and number of retrieved lymph nodes did not differ between the two groups. There were no significant differences in postoperative courses or overall and disease-specific survival (89.8% vs. 83.6%, P?=?0.0886; 100% vs. 95.2%, P?=?0.1073) except time to first flatus and time to use of nonsteroidal anti-inflammatory derivatives between the two groups. Significantly fewer patients felt wound pain in the LAG group 1?year after surgery. Analyses between the LATG and OTG groups showed similar results.

Conclusions

LAG for gastric cancer may be both feasible and safe. However, it will be necessary to conduct a well-designed randomized controlled trial comparing short-term and long-term outcomes between LAG and OG in a larger number of patients.     

Results of unilateral adrenalectomy in subclinical Cushing's syndrome due to adrenocorticotropic hormone‐independent macronodular adrenal hyperplasia

Adrenocorticotropic hormone (ACTH)‐independent bilateral adrenocortical macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome (CS). Traditionally, bilateral adrenalectomy with subsequent lifetime steroid replacement has been considered to be the treatment of choice. In the present study, we evaluated the long‐term results of unilateral adrenalectomy in subclinical CS (SCS) due to AIMAH, with regard to the main laboratory and clinical abnormalities. Two patients with confirmed SCS due to AIMAH underwent unilateral laparoscopic adrenalectomy to reduce the cortisol‐secreting tissue. These procedures were successfully conducted in both cases without open conversion, and no surgery‐related morbidity occurred. In both cases, the size of the remaining adrenal gland appeared quite stable, and neither of the patients showed a Cushingoid appearance. Unilateral adrenalectomy achieved satisfactory and prolonged control of cortisol secretion, and also reduced the risk of metabolic disorders and cardiovascular disease after surgery. It can be a safe and effective treatment for SCS due to AIMAH, while maintaining the patient's quality of life.     

An internal distraction device for Le Fort distraction osteogenesis: the NAVID system

Le Fort distraction osteogenesis is sometimes applied to improve the facial appearance in craniofacial dysostosis or cleft lip and palate. Distraction devices are generally classified into external and internal types. The movement of external distractors can be controlled easily but their large size and the need for a facial mask cause much psychological stress to the patient. Internal distractors are smaller and better tolerated, but they are not easily controllable and removal is difficult. We designed an internal distraction device to eliminate the problems of the currently available distractors -Nakajima's angle-variable internal distraction (NAVID) system - and aimed to assess its clinical applicability. Between 2000 and 2010, we treated 16 patients with the NAVID system: Le Fort I, III, III?+?I and IV distractions were performed in three, five, four and four patients, respectively. Distraction was started after a 1-week latency period. Then, the exposed rod was cut, and the distractors were left in place for 3 months or more as retention devices, and thereafter removed. All patients showed satisfactory occlusion and facial aesthetics. Open bite during the consolidation period was the main complication. In conclusion, the NAVID system is safe, effective and reliable for all types of Le Fort distraction osteogenesis.     

Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric renal diseases

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is produced mainly by tubular epithelial cells in kidney and contributes to renal interstitial inflammation and fibrosis. More recently, we have demonstrated that urinary MCP-1 excretion is increased in proportion to the degree of albuminuria (proteinuria) and positively correlated with urinary N-acetylglucosaminidase (NAG) levels in type 2 diabetic patients. Based on these findings, we have suggested that heavy proteinuria, itself, probably aggravates renal tubular damage and accelerates the disease progression in diabetic nephropathy by increasing the MCP-1 expression in renal tubuli. In the present study, to evaluate whether urinary MCP-1 excretion is increased in the proteinuric states not only in diabetic nephropathy but also in other renal diseases, we examined urinary MCP-1 levels in IgA nephropathy patients with macroalbuminuria (IgAN group; n = 6), and compared the results with the data obtained from type 2 diabetic patients with overt diabetic nephropathy (DN group; n = 23) and those without diabetic nephropathy (non-DN group; n = 27). Urinary MCP-1 excretion levels in non-DN, DN, IgAN groups were 157.2 (52.8-378.5), 346.1 (147.0-1276.7), and 274.4 (162.2-994.5) ng/g creatinine, median (range), respectively. Expectedly, urinary MCP-1 and NAG excretion levels in DN and IgAN groups were significantly elevated as compared with non-DN group. Therefore, we suggest that MCP-1 expression in renal tubuli is enhanced in proteinuric states,irrespective of the types of renal disease, and that increased MCP-1 expression probably contributes to renal tubular damage in proteinuric states.     

Difference in the Impairment of Vital Capacity and 6-Minute Walking After a Lobectomy Performed by Thoracoscopic Surgery,an Anterior Limited Thoracotomy,an Anteroaxillary Thoracotomy,and a Posterolateral Thoracotomy

Purpose: Postoperative vital capacity (VC) and the 6-min walking (6MW) test were used to compare the differences in impairment of the pulmonary function and walking capacity in patients undergoing a lobectomy by video-assisted thoracoscopic surgery (VATS), an anterior limited thoracotomy (ALT), an anteroaxillary thoracotomy (AAT), or a posterolateral thoracotomy without muscle sparing (PLT). Methods: The study was a retrospective analysis. Lung cancer patients who underwent a lobectomy by VATS, ALT, AAT, or PLT (28 in each group) were matched by sex and age (±5 years). VC was measured before surgery and at 1, 2, 4, 12, and 24 weeks after surgery. The distance covered during the 6MW test (6MWD) was measured before surgery and in a postoperative test 1 week after surgery. Results: Compared with the VATS, ALT, and AAT groups, PLT patients showed a significant impairment of VC from 1 to 24 weeks after surgery (P < 0.05–0.001) and also a significant impairment of 6MWD 1 week after surgery (P < 0.01–0.001). The AAT group showed a significant impairment of 6MWD 1 week after surgery compared with the VATS and ALT groups (P < 0.001 and P < 0.05, respectively). There was no significant difference in the impairment of either VC or 6MWD between VATS and ALT. Conclusions: The PLT without a muscle sparing procedure therefore cannot be recommended for general lung cancer surgery because of the impairment of both walking capacity and pulmonary function which continues long after surgery. VATS and ALT are better procedures than AAT regarding the recovery of walking capacity early after surgery. VATS and ALT are similar to each other regarding the impairment of pulmonary function and walking capacity after surgery. Received: October 15, 2001 / Accepted: July 2, 2002 Reprint requests to: H. Nomori