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61.
62.

Background

Routine preoperative laryngeal examination remains controversial. We aimed to assess the utility of preoperative routine flexible laryngoscopy (FL) by looking at the incidence, clinical significance and predictors for preoperative vocal cord paresis (VCP) and incidental laryngopharyngeal conditions (LPC) in our consecutive cohort.

Methods

A total of 302 patients underwent laryngeal examination by an independent otorhinolaryngologist and were specifically asked about voice/swallowing symptoms suggestive of VCP 1 day before surgery. As well as vocal cord (VC) mobility, the naso-pharynx and larynx were examined using FL. Any VCP and/or LPC was recorded. VCP was defined as reduced or absent movement in one or more VC. An LPC was considered clinically significant if the ensuing thyroidectomy was changed or deferred.

Results

Seven (2.3 %) patients had preoperative VCP, while an additional seven patients had an incidental LPC. Of the seven VCPs, five were caused by previous thyroidectomy, while two were caused by a benign goitre. The incidence of asymptomatic VCP in a previously non-operated cohort was 1/245 (0.41 %). Voice/swallowing symptoms (p = 0.033) and previous thyroidectomy (p < 0.001) were the two significant predictors for VCP. The seven incidental LPCs were vallecular cyst (n = 1), VC scar and polyp (n = 2), nasopharyngeal cyst and polyp (n = 3) and redundant arytenoid mucosa (n = 1); however, as they were benign, all seven patients proceeded to thyroidectomy as planned.

Conclusions

Given the low incidence (0.41 %) of asymptomatic VCP in a previously non-operated cohort and that none of the seven LPCs were considered clinically significant, routine preoperative laryngoscopic examination should be reserved for those with previous thyroidectomy and/or voice/swallowing symptoms.  相似文献   
63.
64.
65.

Objectives

The β1 integrin (CD29) is a putative marker for cancerous epithelial stem cells. Cancer stem cells are essential to drive tumor growth, recurrence, and metastasis. We investigated the role of β1-integrin expression in the development of malignant phenotypes of oral squamous cell carcinoma (OSCC).

Materials and methods

Immunostaining was used to analyze the expression levels of β1 integrins in different types of cell colonies and tumor spheres. The results of cell viability and migration assays with and without siRNA knockdown of β1-integrin expression were compared. Cells expressing β1 integrins were evaluated for their tumorigenicity in mice. The expression of β1 integrins in human specimens of oral cancers at different clinical stages was semiquantified based on immunohistochemical staining of the β1-integrin protein.

Results

The expression level of β1 integrins in Meng-1 oral epidermoid carcinoma cells (OECM-1) cells was significantly higher in holoclonal colonies and tumor spheres compared to control cells. The knockdown of β1-integrin expression in OECM-1 cells reduced cell proliferation, migration, and tumor sphere formation. Beta-1 integrin (+) cells were more tumorigenic in the mouse xenograft model than β1 integrin (?) cells. In the human specimens, the expression level of the β1-integrin protein positively correlated with the clinical stage.

Conclusion

The expression of β1 integrin in OECM-1 cells is involved in the development of malignant phenotypes of OSCC.

Clinical relevance

Inhibitors for β1-integrin signaling may be suitable to become target-specific therapies for OSCC.  相似文献   
66.
CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.The liver is acknowledged to possess unique tolerogenic properties, which have likely evolved to maintain immunological unresponsiveness toward food-derived and microbial antigens that enter the circulation via the gut (1, 2). This tolerogenic capability of the liver is demonstrated in animal models of liver transplantation, in which liver allografts are accepted across complete MHC mismatch barriers and are able to protect other donor tissues from rejection (reviewed in ref. 3). In humans, the tolerogenic hepatic environment is likely to contribute to impaired immune clearance of the hepatitis B virus (HBV) and hepatitis C virus (HCV), which result in persistent infection in a significant proportion of exposed individuals and are associated with major morbidity and mortality. In contrast, effective immune responses to hepatotropic pathogens leading to resolution of infection are observed in most hepatitis A and E virus infections, the majority of individuals infected with HBV during adulthood, and a minority of those infected by HCV (reviewed in refs. 4, 5). The liver is also susceptible to a variety of autoimmune-mediated conditions (6). Collectively, these observations indicate that effective immune responses can be initiated and/or sustained in the liver despite its apparent predisposition toward the generation of tolerance. Unfortunately, there is no small animal model in which to study the parameters that determine the balance between intrahepatic immunity and tolerance in viral hepatitis. Thus, the factors that shape immune outcome have not yet been identified.By studying the fate of antigen-specific CD8 T cells transferred into mice expressing antigen in the liver, it has been shown that, despite being a nonlymphoid organ, the liver is able to support primary CD8 T-cell activation (7). However, depending on the choice of antigen expressed and mode of delivery, the outcome of intrahepatic CD8 T-cell activation has been varied, ranging from deletion and/or functional silencing (810) to cytotoxic T lymphocyte (CTL) development (11, 12). This observed diversity of T-cell fates parallels the heterogeneous outcomes of liver-immune interactions observed during hepatotropic viral infections in humans. Thus, reconciliation of these findings holds the potential to yield critical insights into the immunopathological basis of immune-mediated liver disease as well as liver-associated tolerance.In this study, we developed an integrated system in which we manipulated parameters predicted to influence the generation of effector CD8 T cells encountering their cognate antigen on hepatocytes. By identifying three key determinants of the generation of functional effector cells in response to hepatocyte-expressed antigen, this study provides, for the first time to our knowledge, a unified model that explains and predicts the functional outcome of CD8 T-cell activation by liver-expressed antigen and reconciles findings from a number of previous studies that addressed this question.  相似文献   
67.
Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.  相似文献   
68.
We retrospectively reviewed 187 patients who presented with neurologic abnormality after total joint arthroplasty to establish the incidence of diagnosed organic brain disorders in these patients and determine the utility of advanced head imaging studies. 139 of 187 (74.3%) patients underwent imaging for altered mental status (AMS) and 48 patients for a focal neurologic deficit (FND). Acute findings on head imaging were more common in the FND group. The incidence of stroke and transient ischemic attack was significantly lower in the AMS group compared to FND group (Stroke: 0% vs 12.5%, p < 0.001; TIA: 0% vs. 16.7%, P < .001). Advanced head imaging for evaluation of TJA patients with a change in mental status is of low yield. An algorithm for evaluation of these patients is proposed.  相似文献   
69.
There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin?angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.  相似文献   
70.

Background

Mirizzi syndrome (MS) is a rare complication of gallstone disease. Despite the fact that successful laparoscopic treatments have been reported, open surgery remains the gold standard approach for this disease due to technical difficulties involved.

Methods

A minimally invasive strategy combining endoscopic retrograde cholangiopancreatography (ERCP) and robotic surgery for the management of MS was implemented in early 2012. This consisted of a preoperative ERCP for definitive diagnosis and endoscopic stent insertion. Robotic surgical approach was used during operation to facilitate gall bladder removal and suture of defect over common duct. ERCP was repeated postoperatively for stent removal. Patient demographics and treatment outcomes were collected prospectively. A historical cohort of patients with MS who underwent conventional surgery between 1999 and 2011 was identified for comparison of treatment outcomes.

Results

Five patients with MS were managed with this strategy. Robotic subtotal cholecystectomy was successfully performed in all the patients without conversion or morbidity. When compared with a historical cohort of 17 patients who underwent surgery for MS, this group of patients had significantly less conversion and shorter hospital stay though the operation time was longer. It also showed less blood loss and less postoperative complications but these were not statistically significant.

Conclusion

Mirizzi syndrome can be effectively managed with a minimally invasive approach by adopting a robot-assisted surgery together with a planned pre- and postoperative ERCP.  相似文献   
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