miRNA expression profile of mucoepidermoid carcinoma.

OBJECTIVES: MicroRNAs (miRNAs) are single-stranded RNAs that have been implicated in cancer initiation and progression and act as tumour suppressors or oncogenes. In this study, miRNA profiling was conducted on the most frequent malignancy of salivary glands, mucoepidermoid carcinoma (MEC), in comparison with normal tissues. MATERIALS AND METHODS: The TaqMan Human miRNA Cards Array was used for the miRNA profiling of MEC and normal tissues. To validate the differentially expressed miRNAs in MEC, we used real-time PCR (qRT-PCR). RESULTS: miR-302a was the most significantly increased miRNA in cancer tissues (p < .05). Here, we demonstrate that the upregulation of miR-302a expression in SGT cell lines induced cancer cell invasion in vitro. CONCLUSIONS: These promising results suggest the need for further studies to establish mir-302a as a marker of invasion and aggressiveness in MEC.

Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation-induced salivary hypofunction.

We evaluated late effects of AdhAQP1 administration in five subjects in a clinical trial for radiation-induced salivary hypofunction (http://www.clinicaltrials.gov/ct/show/NCT00372320?order=). All were identified as initially responding to human aquaporin-1 (hAQP1) gene transfer. They were followed for 3-4 years after AdhAQP1 delivery to one parotid gland. At intervals we examined salivary flow, xerostomic symptoms, saliva composition, vector presence and efficacy in the targeted gland, clinical laboratory data and adverse events. All displayed marked increases (71-500% above baseline) in parotid flow 3-4.7 years after treatment, with improved symptoms for ~2-3 years. There were some changes in [Na+] and [Cl-] consistent with elevated salivary flow, but no uniform changes in secretion of key parotid proteins. There were no clinically significant adverse events, nor consistent negative changes in laboratory parameters. One subject underwent a core needle biopsy of the targeted parotid gland 3.1 years post treatment and displayed evidence of hAQP1 protein in acinar, but not duct, cell membranes. All subjects responding to hAQP1 gene transfer initially had benefits for much longer times. First-generation adenoviral vectors typically yield transit effects, but these data show beneficial effects can continue years after parotid gland delivery.

Role of Runx2 in IGF-1Rß/Akt- and AMPK/Erk-dependent growth, survival and sensitivity towards metformin in breast cancer bone metastasis.

The mechanisms underlying reprogramming of growth factor signaling and metabolic pathways during bone metastasis of breast cancer are not clear. The Runt-related transcription factor (Runx2) regulates cell signaling during mammary epithelial morphogenesis and promotes invasion; therefore, we investigated its role in cell growth and metabolic signaling in bone-seeking breast cancer cells. We performed systemic inoculation of control or Runx2 knockdown invasive MDA-MB-231 cells in NOD/SCID mice, and compared parental and bone-derived variants for phenotypic and molecular alterations. The Runx2 knockdown showed early (0-2 weeks) inhibition of metastatic spread but late (4-6 weeks) outgrowth, suggesting Runx2-dependent bi-phasic response and reprogramming of metastatic cells. The late-stage tumor outgrowth of bone-derived Runx2 knockdown cells was associated with increased insulin-like growth factor- 1Rß (IGF-1Rß) levels. Interestingly, glucose uptake and glycolysis were reduced in the bone-derived Runx2 knockdown cells that could be further reduced by extracellular-regulated protein kinase (Erk1/2) inhibition. Furthermore, the Runx2 knockdown cells displayed activation of AMP-activated protein kinase (AMPKα), the sensor of cellular metabolism. Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKα activation by PD184161 and metformin, respectively, despite increased IGF-1Rß and AMPKα levels. Our results reveal that Runx2 promotes metastatic spread of mammary tumor cells. The growth of late-stage tumor cells can be targeted by Runx2 knockdown in combination with Mek-Erk1/2 inhibition and metformin treatment.

Postoperative coagulopathy after live related donor hepatectomy: Incidence, predictors and implications for safety of thoracic epidural catheter.

BACKGROUND: Coagulopathy after living donor hepatectomy (LDH) may endanger donor safety during removal of thoracic epidural catheter (TEC). The present study was conducted to evaluate the extent and duration of immediate postoperative coagulopathy after LDH. MATERIALS AND METHODS: A retrospective analysis of perioperative record of LDH over three years was conducted after IRB approval. Variables such as age, gender, BMI, ASA classification, liver volume on CT scan, preoperative and postoperative INR, platelet count (PC) and ALT of each donor for five days was noted. In addition, duration of surgery, remnant as percentage total liver volume (Remnant%), blood loss, day of peak in PC and INR were also noted. Coagulopathy was defined as being present if INR exceeded 1.5 or platelet count fell below 1 × 10 5 /mm 3 on any day. Data was analyzed using SPSS 20 for Windows. Between group comparison was made using the Student 't' test for continuous variables and chi square test for categorical variables. Univariate analysis was done. Multiple logistic regression analysis was used to find independent factor associated with coagulopathy. RESULTS: Eighty four (84) donors had coagulopathy on second day (mean INR 1.9 ± 0.42). Low BMI, % of remnant liver and duration of surgery were independent predictors of coagulopathy. Right lobe hepatectomy had more coagulopathy than left lobe and low BMI was the only independent predictor. There was no correlation of coagulopathy with age, gender, blood loss, presence of epidural catheter, postoperative ALT or duration of hospital stay. High INR was the main contributor for coagulopathy. CONCLUSIONS: Coagulopathy is seen after donor hepatectomy. We recommend removal of the epidural catheter after the fifth postoperative day when INR falls below 1.5.

Comparative evaluation of prophylactic use of pregabalin, gabapentin and diclofenac sodium for prevention of succinylcholine-induced myalgia: a randomized, double-blinded study.

CONTEXT: Succinylcholine a depolarizing muscle relaxant with rapid onset, predictable course and short duration of action is associated with myalgia. AIM: The aim of this study is to evaluate the efficacy of pregabalin, gabapentin and diclofenac on the incidence and severity of succinylcholine-induced myalgia. SETTINGS AND DESIGN: Tertiary Care Teaching Hospital. MATERIALS AND METHODS: A total of 120 patients undergoing laparoscopic cholecystectomy were randomly assigned into three groups: Pregabalin group received 150 mg of pregabalin, gabapentin group received 600 mg of gabapentin and diclofenac group received 100 mg of diclofenac sodium orally 2 h prior to surgery. Anesthesia was induced with fentanyl 3 µg/kg, propofol 2-2.5 mg/kg and succinylcholine 1.5 mg/kg and was maintained with oxygen with sevoflurane in the air and intermittent vecuronium bromide. A blinded observer recorded post-operative pain scores on visual analog scale at different time intervals and myalgia at 24 h. Post-operative pain relief was provided with fentanyl based patient-controlled analgesia. Fentanyl consumption in 24 h was recorded as a primary outcome. STATISTICAL ANALYSIS: Patients' characteristics and total fentanyl consumption were compared using one-way ANOVA followed by post-hoc test. Pain score was compared amongst the groups using Kruskal Wallis test. RESULTS: The myalgia occurred in 15, 14 and 13 patients in pregabalin, gabapentin and diclofenac sodium group respectively (P > 0.85). Patients in diclofenac group had significantly higher fentanyl consumption (674.85 ± 115.58 µg) compared with pregabalin group (601.87 ± 129.57 µg) (95% confidence interval [CI] = 34.8-120.7) and gabapentin group (612.29 ± 105.12 µg) (95% CI = 14.9-170.5). However, there was no significant difference in fentanyl consumption between pregabalin and gabapentin groups (95% CI = -34.8-120.7). There was a significant difference in visual analog score at time points 12, 18 and 24 h among the study groups. CONCLUSION: Pre-treatment with pregabalin, gabapentin and diclofenac had equal efficacy in reducing the incidence and severity of succinylcholine-induced myalgia. However, pre-treatment with pregabalin and gabapentin decreased post-operative pain scores and fentanyl consumption.

Quadriplegia in a child following adenotonsillectomy.

Neurological deterioration in a child following routine surgery, although rare, has potentially life threatening consequences. We report the case of a child who, following adentonsillectomy, developed quadriplegia and acute respiratory distress due to previously undetected atlanto-axial instability. Patients with atlanto-axial instability often have mild or non-specific symptoms, despite severe cervical cord compression. Subtle manifestations may be ignored or attributed to other disease processes, which render patients with undiagnosed atlanto-axial instability at risk of serious neurological injury during general anaesthesia, particularly at the time of laryngoscopy and tracheal intubation.

Use of nitinol shape memory alloy staples (NiTi clips) after cervical discoidectomy: minimally invasive instrumentation and long-term results.

BACKGROUND: Anterior cervical discoidectomy with or without fusion is a well established surgical remedy for cervical prolapsed intervertebral disc (PIVD) disease. If fusion is done by an iliac bone graft then internal fixation is commonly used to keep the graft in position. This study was conducted to determine the efficacy and tolerability of shape memory alloys, especially NiTi (nickel titanium) clips in the stabilization of grafts following anterior cervical discoidectomy. METHODS: 133 NiTi clips were applied in 119 patients between January 2002 and December 2008. The patients age ranged from 38-60 years. There were 66 male and 53 females. Various indications for fixation of the spine included degenerated cervical spondylosis with single level PIVD (105) and two level PIVD in 14 patients. The cine mode fluoroscopy confirmed the perioperative correct placement of grafts and clips in all the patients. Follow-up ranged from 2 to 8 years (mean: 4.6 years). RESULTS: Single level discoidectomy was performed in 105 patients and two level disc removal was done in 14 patients. A single NiTi clip was applied in all the cases except for 14 cases of two level PIVD. No procedural complication or adverse reaction to the clip was noted. There was no movement at the operated level in dynamic lateral view X-ray of cervical spine at the 1st postoperative day as well as on follow-up. Graft extrusion was seen in one patient on the 2nd day after surgery and was reoperated. Bony fusion occurred in all patients after 9 - 12 months of surgery. There was no incidence of breakage or dislodgement of the clip from the site where it was inserted. No artifact was noted in cervical MRI done in 33 patients. CONCLUSION: NiTi clips are a simple alternative for cervical spine stabilization after discoidectomy. Their insertion is simple, minimally invasive, does not require any special set of instruments and they are much more economical than other established methods of treatment. These clips are accepted well by human tissue and do not interfere with MRI.

Evaluation of cross-reactive cell-mediated immune responses among human, bovine and porcine adenoviruses.

The absence of preexisting immunity against porcine adenovirus (Ad) serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) in humans makes them attractive alternatives to human Ad serotype 5 (HAd5) vectors. To determine whether there is significant cross-reactivity among HAd5, BAd3 and PAd3 at the level of cell-mediated immune responses, BALB/c mice were inoculated intraperitoneally with wild-type (WT) or replication-defective (RD) HAd5, BAd3 or PAd3. After 35 days of the first inoculation, cross-reactive CD8+ cytotoxic T cells, as well as CD4+ Th1- and Th2-helper T cells, in the spleen were analyzed by enzyme-linked-immunospot, flow cytometry and cytotoxic T lymphocyte assays. Virus-neutralization assays were used to evaluate humoral cross-reactivity. CD8+ or CD4+ T cells primed with WT or RD HAd5, PAd3 or BAd3 showed significant (P<0.005) reactivity with homologous Ad antigens, whereas only minimal cross-reactivity was observed on stimulation with heterologous Ad antigens. Ad-neutralizing antibodies were found to be homologous Ad specific. Overall, these results suggest that there is no significant immunological cross-reactivity among HAd5, BAd3 and PAd3, thereby supporting the rationale for the use of BAd3 and PAd3 as alternative HAd vectors to circumvent anti-HAd immunity in humans.

Magnetic loop basket: a "two-in-one" instrument.

BACKGROUND AND STUDY AIMS: Ingested coins are the most common foreign bodies encountered in the upper gastrointestinal tract in India and if they remain in the stomach for more than 5 days they need to be removed. Ferromagnetic retrieval instruments only work if the coins are ferromagnetic; and it is difficult to maneuver a loop basket in the fundus of the stomach. A magnetic loop basket was designed in an effort to overcome these difficulties and we assessed its feasibility, safety, and effectiveness in the removal of coins from the fundus of the stomach. PATIENTS AND METHODS: Twenty patients with a history of ingested coins were scheduled for removal of the coins using the magnetic loop basket. The time taken, complications, and failure rates were recorded. RESULTS: Twelve ferromagnetic coins were removed in a mean time of 60 seconds (range 30 - 90 seconds) and eight non-ferromagnetic coins were removed in a mean time of 150 seconds (range 90 - 180 seconds) without any failures or complications. CONCLUSION: The magnetic loop basket is a safe, effective, and quick method for removing both ferromagnetic and non-ferromagnetic metallic coins.

Comparison of efficacy of oxybutynin and tolterodine for prevention of catheter related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.

BACKGROUND: Bladder discomfort related to intraoperative catheterization of urinary bladder is a distressing symptom and more so in patients awakening from anaesthesia. These symptoms are similar to symptoms of overactive bladder. Muscarinic receptor antagonists have been reported to be effective in the treatment of overactive bladder. This study was therefore undertaken to evaluate the efficacy of oxybutynin and tolterodine in preventing catheter related bladder discomfort. METHODS: Two hundred and thirty-four consecutive adult patients, ASA I and II, of either sex, undergoing elective percutaneous nephrolithotomy surgery requiring urinary bladder catheterization were randomized into three equal groups of 78 each. Group C (control) received placebo, Group O (oxybutynin) received oxybutynin 5 mg and Group T (tolterodine) received tolterodine 2 mg orally 1 h before surgery. After induction of anaesthesia patients were catheterized with a 16 Fr Foley's catheter and the balloon was inflated with 10 ml distilled water. The bladder discomfort was assessed at 0, 1, 2 and 6 h after patient's arrival in the post-anaesthesia care unit. Severity of bladder discomfort was graded as mild, moderate and severe. RESULTS: Incidence of bladder discomfort observed in the control group was higher, i.e. 58% (45/78), compared with oxybutynin and tolterodine groups where it was 35% (28/78) and 33% (26/78), respectively (P<0.05). Significant reduction in the severity of bladder discomfort was also observed after oxybutynin and tolterodine therapy compared with control (P<0.05). CONCLUSION: Pretreatment with either oxybutynin or tolterodine reduces the incidence and severity of catheter related bladder discomfort.

Evaluation of capsaicin ointment at the Korean hand acupressure point K-D2 for prevention of postoperative nausea and vomiting.

The K-D2 point is the Korean hand acupressure point in Koryo Hand Therapy for prevention of postoperative nausea and vomiting. We evaluated the efficacy of capsaicin ointment at the K-D2 point in 186 patients undergoing laparoscopic cholecystectomy in a randomised, prospective, double-blind and placebo-controlled study. Patients were randomised to have either placebo ointment or capsaicin ointment applied to the K-D2 point of both hands 1 h before surgery under standardised anaesthesia. The ointment was removed 8 h later. Postoperative nausea and vomiting was evaluated 6 and 24 h following surgery. The incidence of postoperative nausea and vomiting was lower in the capsaicin group, with an absolute risk reduction (ARR) of 21%, a relative risk reduction (RRR) of 50% and a number-needed-to-treat (NNT) of 5 at 0-6 h (p = 0.001), and an ARR of 11%, a RRR of 85% and a NNT of 9 at 6-24 h (p = 0.003). The need for rescue anti-emetic treatment was also lower at 0-6 h (3 (3%) vs 11 (12%); p = 0.04) and at 6-24 h (5 (5%) vs 0; p = 0.02).

Effect of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor agonists at LH-surge in female rats.

In a randomized, prospective, controlled and crossover study, the effects of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor directed drugs during steroid-induced preovulatory LH-surge were seen in ovariectomized female rats. Ovariectomized rats were equally distributed in two groups of 10. In group 1 rats, LH-surge was induced by sequential treatment with estradiol benzoate 7.5 micro g/rat s.c. and progesterone 5 mg/rat s.c., whereas in group 2 rats, vehicles of estradiol benzoate and progesterone were given in a sequential manner. A third group consisted of sham-operated rats, which received no treatment. Rats were exposed to insulin-induced hypoglycemic stress 1 h before the peak of LH-surge. Antinociceptive responses of morphine, buprenorphine and pentazocine were observed at peak LH-surge during hypoglycemic stress. Increased nociceptive responses to noxious stimulus and decreased percent maximal possible effect for morphine, buprenorphine and pentazocine at LH-surge were significantly (p < 0.01) reversed during insulin hypoglycemic stress. There was a significant (p < 0.01) decrease in the ED(50) values of morphine, buprenorphine and pentazocine during hypoglycemic stress. The present study indicates that insulin hypoglycemic stress is responsible for increased antinociceptive activities of morphine, buprenorphine and pentazocine and decreased sensitivity to noxious stimulus in ovariectomized rats with or without steroid-induced LH-surge.

Microwave-assisted (radio)halogenation of nitroimidazole-based hypoxia markers.

Microwave-assisted radiohalogenation for the production of short-lived radiopharmaceuticals has now been applied to the synthesis and radiolabelling of azomycin nucleosides. (Radio)halogens were incorporated either by nucleophilic substitution of a leaving group or by halogen-halogen exchange, in the synthesis of IAZA, IAZP and FAZA. A comparison of conventional labelling and microwave-assisted labelling procedures reflects a clear advantage of the microwave technique.

Endoscopic ultrasound in idiopathic acute pancreatitis.

OBJECTIVE: The aim of this study was to determine the utility of endoscopic ultrasound (EUS) in patients with unexplained acute pancreatitis, and whether endoscopic retrograde cholangiopancreatography (ERCP) is subsequently needed. METHODS: Subjects who underwent EUS for assessment of idiopathic acute pancreatitis were identified, their medical records were reviewed, and they were contacted for a follow-up telephone interview. EUS diagnosis was compared with the final diagnosis and outcome. RESULTS: EUS revealed a cause of pancreatitis in 21 of the 31 subjects (68%), including microlithiasis in five (16%), chronic pancreatitis in 14 (45%), pancreas divisum in two (6.5%), pancreatic cancer in one (3.2%), and was not diagnostic in 10 (32%). During a mean follow-up period of 16 months, diagnosis changed in four subjects (13%), and nine subjects (29%) had ERCP because of persistent symptoms or recurrent pancreatitis. CONCLUSION: EUS, a less invasive test than ERCP, demonstrated an etiology in two-thirds of patients with idiopathic acute pancreatitis. Most patients did not require ERCP during the follow-up period. EUS can be an alternative to ERCP in patients with unexplained acute pancreatitis.

Role of micro-nutrients and trace elements in carcinoma of larynx.

Cancer of the larynx is fourteenth most common cancer in the world. Evidence from case-control studies conducted in developed as well as developing countries suggest that specific micro-nutrients and trace elements have been implicated to be significantly associated with laryngeal carcinoma. The association of these micro-nutrients and trace elements with laryngeal cancer has been discussed in this review article.

Fine-needle aspiration biopsy of orbital meningioma.

Fine-needle aspiration was performed on an orbital mass in a 53-yr-old woman. The cytologic diagnosis was meningioma, which was later confirmed by histologic study of biopsy material. The cytologic features of the aspirated material (nuclear pseudoinclusions, psammoma bodies, and cells arranged in syncytial sheets and whorls) allowed a rapid, reliable, outpatient diagnosis to be formulated. The cytologic features are discussed and the literature is reviewed. Diagn. Cytopathol. 1999;21:402-404.

Focus of signet ring cell carcinoma in an adenoma of the sigmoid colon.

A case of a pedunculated adenomatous polyp of the sigmoid colon was found to have a primary focus of signet ring cell carcinoma. Histologic examination of the medium-sized polyp was consistent with an adenoma to carcinoma sequence for signet ring cell carcinoma of the colon, similar to that for the common adenocarcinomas.

Haemodynamic effects of leg raising in patients undergoing coronary artery bypass grafting.

Twenty patients undergoing elective coronary artery bypass grafting were studied prospectively to evaluate the haemodynamic effects of passive leg raising. The patients were divided into two groups: those having good left ventricular function with ejection fraction of 0.50 or more (group I, n = 10) and those having poor left ventricular function with ejection fraction of upto 0.35 (group II, n = 10). Morphine-based anaesthetic technique was used and standard haemodynamic measurements were obtained at following stages: (1) control--20 to 30 min after induction of anaesthesia; (2) one minute, and (3) five min after raising both the legs; (4) one min, and (5) five min after the legs were repositioned. In group I, heart rate decreased from 71 +/- 9 to 66 +/- 8 beats/min (p < 0.001) at stage 1 and persisted throughout the study period. This was accompanied by a decrease in cardiac index, although, the statistical significance was achieved at stage 3 and 4 only. The haemodynamic changes observed in group II were of more severe magnitude. The heart rate decreased from 90 +/- 13 to 84 +/- 13 beats/min at stage 1 (p < 0.05) and persisted throughout the study with maximum decrease of 14 percent occurring at stage 3. The cardiac index decreased significantly from 2.4 +/- 0.3 to 2.0 +/- 0.5 L/min/m2 (p < 0.05) at stage 1. This persisted throughout the study except that it recovered at stage 4. The maximum decrease in cardiac index (20%) occurred at stage 2. In addition, systemic vascular resistance increased significantly from 1458 +/- 255 to 1830 +/- 420 dyne.sec.cm-5 (p < 0.05) at stage 1 and persisted throughout the study period. We conclude that passive leg raising should be undertaken with caution in patients with coronary artery disease especially in those who have poor left ventricular function.