Methylthioadenosine phosphorylase (MTAP) is known as a ubiquitously expressed house keeping gene important in biochemical salvage processes. The MTAP gene is localized on the human chromosomal region 9p21, a region often deleted in cancer. Recently, several groups including our own have shown that MTAP serves as a tumour suppressor gene. The aim of this study was to analyse the role of MTAP in colon carcinoma and normal colon epithelium and the regulation of gene expression. To examine MTAP RNA and protein expression, we screened six colon carcinoma cell lines and human primary colon epithelial cells by RT-PCR and immunoblotting. MTAP expression was confirmed in vivo by immunohistochemical staining of normal colon tissue compared to adenoma and colon carcinoma. Interestingly, we found strong MTAP mRNA and protein expression by colon carcinoma cell lines but no expression by colonic epithelial cells. To analyse the regulation of MTAP expression, promoter studies were performed and revealed control of MTAP expression by LEF/TCF/bcatenin. Furthermore, we demonstrated a significant correlation between MTAP protein expression and tumour progression as the intensity of MTAP protein staining increased from normal tissue to carcinoma. In addition, the recently postulated association between MTAP activity and interferon (IFN) sensitivity was confirmed in colon epithelial cells showing only little response to IFN-gamma, in contrast to the carcinoma cell lines. In summary, these data indicate for the first time that MTAP is not expressed in normal human colonic epithelium but is strongly upregulated in colon carcinoma. This finding may be of clinical significance concerning the homeostasis of normal colon epithelium and potential treatment of colon carcinoma. Laboratory Investigation ( 2.28) plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine. MTAP catalyses the phosphorylation of methylthioadenosine (MTA), a by-product of the synthesis of polyamines, which acts as a potent inhibitor of polyamine aminopropyltransferase and methyltransferases. MTAP has been shown previously to be expressed abundantly in normal cells and tissues. 1 In contrast, many malignant cells lack MTAP activity, 2-5 and cultured MTAP-deficient cells secrete MTA instead of metabolising it. 6 The reason for the frequent loss of MTAP activity became evident after determining the chromosomal location of MTAP. Starting from the centromeric end, the gene order on human chromosome 9p21 was mapped as p15-p16-MTAP-interferon(IFN)-alpha-IFNbeta. 1 In this region, many tumours reveal selective deletions. Recently, MTAP gene deletions were described in endometrial cancer, osteosarcoma and in haematological neoplasias like lymphoblastic leukaemia or non-Hodgkin's lymphomas. [2][3][4][5] In addition to its role in polyamine metabolism, MTAP expression has recently been shown to have significant impact on signal transducer and activator of transcription (STAT) 1 activity. 7 STAT1 is
The usefulness of intraoperative neurophysiological monitoring (IONM), including somatosensory-evoked potential (SSEP) and transcranial electrical motor-evoked potentials (TcMEPs) in cervical spine surgery still needs to be evaluated. We retrospectively reviewed 200 cervical spine surgery patients from 2008 to 2009 to determine the role of IONM in cervical spine surgery. Total intravenous anesthesia was used for all patients. IONM alerts were defined as a 50% decrease in amplitude, a 10% increase in latency, or a unilateral change for SSEP and an increase in stimulation threshold of more than 100 V for TcMEP. Three patients had SSEP alerts that were related to arm malposition (2 patients) and hypotension (1 patient). Five patients had TcMEP alerts: 4 alerts were caused by hypotension and 1 by bone graft compression of the spinal cord. All alerts were resolved when causative reasons were corrected. There was no postoperative iatrogenic neurological injury. The sensitivities of SSEP and TcMEP alerts for detecting impending neurological injury were 37.5% and 62.5%, respectively. The sensitivity of both SSEP and TcMEP used in combination was 100%. No false-positive and false-negative alerts were identified in either SSEP or TcMEP (100% specificity). The total intravenous anesthesia technique optimizes the detection of SSEP and TcMEP and therefore improves the sensitivity and specificity of IONM. SSEP is sensitive in detecting alerts in possible malposition-induced ischemia or brachial plexus nerve injury. TcMEP specifically detects hypotension-induced spinal functional compromises. Combination use of TcMEP and SSEP enhances the early detection of impeding neurological damage during cervical spine surgery.
Our study suggests that intraoperative factors including prolonged surgical time, significant blood loss, larger volume of crystalloid and colloid infusion, and blood transfusion may be risk factors for delayed extubation following thoracic or lumbar spine surgery. Early blood transfusion may also increase the risk of delayed extubation. Patient factors did not affect extubation time.
While shown to be safe for administration in pediatric patients, sugammadex has recently been associated with residual weakness or recurarization. We describe 4 additional cases of pediatric patients with residual or recurrent weakness following rocuronium reversal with sugammadex. Two infant patients developed postoperative ventilatory distress, which was possibly related to recurarization after sugammadex reversal. A third patient received sugammadex with apparent waning of clinical effect and subsequently required neostigmine reversal. A fourth patient was observed to have residual weakness, which led to prolonged intubation despite appropriate train-of-four results after reversal with sugammadex.
Children with neuromuscular diseases present unique challenges to providing safe and appropriate perioperative care. Given the spectrum of disease etiologies and manifestations, this is a population that often requires specialized multidisciplinary care from pediatricians, geneticists, neurologists, dieticians, and pulmonologists which must also be coordinated with surgeons and anesthesiologists when these patients present for surgery. Several of these diseases also have specific pharmacologic implications for anesthesia, most notably mitochondrial disease and muscular dystrophies, which put them at additional risk during the perioperative period particularly in patients presenting without a formal diagnosis. Techniques and strategies to fully evaluate and optimize these patients preoperatively, manage them safely intraoperatively, and return them to their baseline status postoperative are particularly important in this vulnerable group of patients. Utilizing a review of inherited neuromuscular conditions, generalized perioperative concerns, and specific complications related to anesthesia, this article provides an overview of pertinent considerations and recommends a framework for management of these patients.
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