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IVA
Kinds of IVA Selected AbstractsEvaluation of Right Ventricular Function by Using Tissue Doppler Imaging in Patients after Repair of Tetralogy of FallotECHOCARDIOGRAPHY, Issue 8 2009lker Çetin M.D. Background: The aim of this study was to assess the relation between plasma B-type natriuretic peptide (BNP) levels and right ventricular function evaluated by tissue Doppler imaging (TDI) in patients after repair of tetralogy of Fallot (ToF). Methods: Twenty-five patients with a mean age of 14.1 ± 4.4 years who underwent repair of ToF at a mean age of 4.9 ± 5.1 years enrolled in this study. The control group consisted of 29 healthy children at a mean age of 13.1 ± 2.8 years. The right ventricle and pulmonary regurgitation (PR) were assessed by two-dimensional echocardiography and color Doppler. Blood samples for BNP levels were taken and TDI was performed at rest. Results: Plasma BNP levels were significantly higher in patients than in controls (28.3 ± 24.1 vs. 7.4 ± 2.3 pg/mL, P = 0.0001). The myocardial performance index (MPI) (1.08 ± 0.35 vs. 0.58 ± 0.11, P = 0.0001) was higher and isovolumic acceleration (IVA) (3.1 ± 0.7 vs. 5.4 ± 1.0 m/s2, P = 0.0001) was lower in patients. The correlations were also significant between the degree of PR and MPI (r = 0.7, P = 0.0001) and also IVA (r =,0.7, P = 0.0001). The correlations were also significant between the BNP level and MPI (r = 0.6, P = 0.0001), IVA (r =,0.4, P = 0.002) and the degree of PR (r = 0.6, P = 0.0001). Conclusion: As a result, plasma BNP level increases in patients with ToF and both MPI and IVA from the right ventricular basal segments might be used to assess the right ventricular function. [source] Effects of Continuous Positive Airway Pressure Therapy on Right Ventricular Function Assessment by Tissue Doppler Imaging in Patients with Obstructive Sleep Apnea SyndromeECHOCARDIOGRAPHY, Issue 10 2008Nihal Akar Bayram M.D. Objectives: The effects of continuous positive airway pressure (CPAP) therapy on right ventricular (RV) function in patients with obstructive sleep apnea syndrome (OSAS) has not been previously studied by tissue Doppler imaging (TDI). The aim of this study was to assess RV function using TDI in patients with OSAS before and after CPAP therapy. Methods: Twenty-eight patients with newly diagnosed OSAS in the absence of any confounding factors and 18 controls were included in this study. The peak systolic velocity (S,m), early (E,m) and late (A,m) diastolic myocardial peak velocities at tricuspid lateral annulus, isovolumic acceleration (IVA), myocardial precontraction time (PCT,m), myocardial contraction time (CT,m), and myocardial relaxation time (RT,m) were measured. All echocardiographic parameters were calculated 6 months after CPAP therapy. Results: The RV diastolic parameters such as E,m velocity and E,m-to-A,m ratio were significantly lower, RT,m was significantly prolonged, A,m velocity was similar in patients with OSAS compared to controls; and the RV systolic parameters such as IVA and CT,m were significantly lower and S,m was similar in patients with OSAS compared to controls. At the end of the treatment, 20 of 28 patients were compliant with CPAP therapy. E,m velocity, E,m-to-A,m ratio, IVA, and CT,m increased, PCT,m, PCT,m-to-CT,m ratio, and RT,m decreased significantly after therapy, whereas S,m velocity and A,m velocity did not change after CPAP treatment in the compliant patients. Conclusion: OSAS is associated with RV systolic and diastolic dysfunction, and 6 months of CPAP therapy improves the RV systolic and diastolic dysfunction. [source] Regional Response of Myocardial Acceleration During Isovolumic Contraction During Dobutamine Stress Echocardiography: A Color Tissue Doppler Study and Comparison with Angiocardiographic FindingsECHOCARDIOGRAPHY, Issue 10 2005Linda B. Pauliks M.D. Background: Color tissue Doppler imaging permits noninvasive quantitation of regional wall motion. In experimental studies, a new marker, the slope of the isovolumic contraction wave, isovolumic acceleration (IVA) was more insensitive to ventricular loading conditions than myocardial velocities. This study compared the regional response IVA to dobutamine stress echocardiography to angiographic findings. Methods: The Myocardial Doppler in Stress Echocardiography (MYDISE) study prospectively recruited 149 consecutive patients with chest pain for dobutamine stress tissue Doppler echocardiography prior to coronary angiography. This color tissue Doppler database was analyzed for IVA in 1192 basal and mid segments at rest and again at peak stress. Angiographic findings were compared to IVA and peak systolic velocities (PSV) in corresponding cardiac segments. The diagnostic accuracy of IVA to predict coronary artery stenosis was determined using cut-off values for three representative segments and with the MYDISE diagnostic model including eight segments. Results: Regional IVA increased in a dose-dependent manner during dobutamine infusion. The response was blunted in the supply territory of stenosed coronary artery branches. IVA performed slightly better than PSV as single marker for coronary artery stenosis. A diagnostic model incorporating IVA and PSV was 85,95% accurate (area under receiver operating characterstic curves). Conclusions: Regional changes of isovolumic acceleration during dobutamine stress echocardiography reflect regional wall motion and can be used to predict coronary artery stenosis with similar accuracy as a model based on systolic myocardial velocities. As a single marker, IVA performed better than myocardial velocities. (ECHOCARDIOGRAPHY, Volume 22, November 2005) [source] Intracellular Calcium Increase in Epileptiform Activity: Modulation by Levetiracetam and LamotrigineEPILEPSIA, Issue 7 2004Antonio Pisani Summary:,Purpose: Alterations in neuronal calcium (Ca2+) homeostasis are believed to play an essential role in the generation and propagation of epileptiform events. Levetiracetam (LEV) and lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on epileptiform events and the corresponding elevations in intracellular Ca2+ concentration ([Ca2+]i) recorded from rat neocortical slices. Methods: Electrophysiological recordings were performed from single pyramidal neurons from a slice preparation. Spontaneous epileptiform events consisting of long-lasting, repetitive paroxysmal depolarization shifts (PDSs) and interictal spike activity were induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4-aminopyridine. Simultaneously, microfluorimetric measurements of [Ca2+]i were performed. Optical imaging with Ca2+ indicators revealed a close correlation between Ca2+ transients and epileptiform events. Results: Both LEV and LTG were able to reduce both amplitude and duration of PDSs, as well as the concomitant elevation in [Ca2+]i, in a dose-dependent fashion. Whole-cell patch-clamp recordings from isolated neocortical neurons revealed that LEV significantly reduced N-, and partially P/Q-type high-voltage-activated (HVA) Ca2+ currents, whereas sodium currents were unaffected. Interestingly, the inhibitory effects of LEV were mimicked and occluded by LTG or by a combination of ,-conotoxin GVIA and ,-agatoxin IVA, selective blockers of N- and P/Q-type HVA channels, respectively, suggesting a common site of action for these AEDs. Conclusions: These results demonstrate that large, transient elevations in neuronal [Ca2+]i correlate to epileptiform discharges. The antagonistic effects of LEV and LTG on [Ca2+]i overload might represent the basis for their anticonvulsant efficacy and could preserve neuronal viability. [source] AMPA receptor-mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanismsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2004Shin'Ichiro Satake Abstract A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand-gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR-mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre-induced inhibition of GABA release from interneurons depends on AMPAR-mediated activation of GTP-binding proteins coupled with down-regulation of presynaptic voltage-dependent Ca2+ channels. A Gi/o -protein inhibitor, N-ethylmaleimide, selectively abolished the AMPAR-mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR-mediated excitatory actions on Purkinje cells. Furthermore, both Gi/o -coupled receptor agonists, baclofen and DCG-IV, and the P/Q-type calcium channel blocker ,-agatoxin IVA markedly occluded the AMPAR-mediated inhibition of GABAergic transmission. Conversely, AMPAR activation inhibited action potential-triggered Ca2+ influx into individual axonal boutons of cerebellar GABAergic interneurons. By suppressing the inhibitory inputs to Purkinje cells, the AMPAR-mediated presynaptic inhibition could thus provide a feed-forward mechanism for the information flow from the cerebellar cortex. [source] Differential Ca2+ -dependence of transmitter release mediated by P/Q- and N-type calcium channels at neonatal rat neuromuscular junctionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2002Marcelo D. Rosato-Siri Abstract N- and P/Q-type voltage dependent calcium channels (VDCCs) mediate transmitter release at neonatal rat neuromuscular junction (NMJ). Thus the neonatal NMJ allows an examination of the coupling of different subtypes of VDCCs to the release process at a single synapse. We studied calcium dependence of transmitter release mediated by each channel by blocking with ,-conotoxin GVIA the N-type channel or with ,-agatoxin IVA the P/Q-type channel while changing the extracellular calcium concentration ([Ca2+]o). Transmitter release mediated by P/Q-type VDCCs showed steeper calcium dependence than N-type mediated release (average slope 3.6 ± 0.09 vs. 2.6 ± 0.03, respectively). Loading the nerve terminals with 10 µm BAPTA-AM in the extracellular solution reduced transmitter release and occluded the blocking effect of ,-conotoxin GVIA (blockade ,2 ± 9%) without affecting the action of ,-agatoxin IVA (blockade 85 ± 4%). Both VDCC blockers were able to reduce the amount of facilitation produced by double-pulse stimulation. In these conditions facilitation was restored by increasing [Ca2+]o. The facilitation index (fi) was also reduced by loading nerve terminals with 10 µm BAPTA-AM (fi = 1.2 ± 0.1). The control fi was 2.5 ± 0.1. These results show that P/Q-type VDCCs were more efficiently coupled to neurotransmitter release than were N-type VDCCs at the neonatal neuromuscular junction. This difference could be accounted for by a differential location of these channels at the release site. In addition, our results indicate that space,time overlapping of calcium domains was required for facilitation. [source] Voltage-gated ionic currents in an identified modulatory cell type controlling molluscan feedingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Kevin Staras Abstract An important modulatory cell type, found in all molluscan feeding networks, was investigated using two-electrode voltage- and current-clamp methods. In the cerebral giant cells of Lymnaea, a transient inward Na+ current was identified with activation at ,58 ± 2 mV. It was sensitive to tetrodotoxin only in high concentrations (, 50% block at 100 µm), a characteristic of Na+ channels in many molluscan neurons. A much smaller low-threshold persistent Na+ current (activation at <,,90 mV) was also identified. Two purely voltage-sensitive outward K+ currents were also found: (i) a transient A-current type which was activated at ,59 ± 4 mV and blocked by 4-aminopyridine; (ii) a sustained tetraethylammonium-sensitive delayed rectifier current which was activated at ,47 ± 2 mV. There was also evidence that a third, Ca2+ -activated, K+ channel made a contribution to the total outward current. No inwardly rectifying currents were found. Two Ca2+ currents were characterized: (i) a transient low-voltage (,65 ± 2 mV) activated T-type current, which was blocked in NiCl2 (2 mm) and was completely inactivated at ,,,50 mV; (ii) A sustained high voltage (,40 ± 1 mV) activated current, which was blocked in CdCl2 (100 µm) but not in ,-conotoxin GVIA (10 µm), ,-agatoxin IVA (500 nm) or nifedipine (10 µm). This current was enhanced in Ba2+ saline. Current-clamp experiments revealed how these different current types could define the membrane potential and firing properties of the cerebral giant cells, which are important in shaping the wide-acting modulatory influence of this neuron on the rest of the feeding network. [source] Altered fractionation and adjuvant chemotherapy for head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2010William M. Mendenhall MD Abstract Background The aim of this review was to discuss the role of altered fractionation and adjuvant chemotherapy for patients treated with definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Methods This review explores the pertinent literature and discusses the optimal management of previously untreated patients with stage III,stage IVA and/or -B HNSCCs. Results Depending on the schedule, altered fractionation improves locoregional control and survival. Both hyperfractionation and concomitant boost RT improve locoregional control and are associated with improved overall survival (OS). Adjuvant chemotherapy improves OS; the greatest impact is observed after concomitant versus induction or maintenance chemotherapy. Monochemotherapy appears to be equivalent to polychemotherapy. Drugs associated with the greatest survival benefit include fluorouracil and cisplatin. Intraarterial chemotherapy offers no advantage over intravenous chemotherapy. Concomitant cetuximab and RT results in improved outcomes similar to those observed after concomitant cisplatin-based chemotherapy and RT. Conclusions Altered fractionation and/or concomitant chemotherapy result in improved outcomes compared with conventionally fractionated definitive RT alone for stage III,stage IV HNSCC. The optimal combination of RT fractionation and chemotherapy remains unclear. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy aloneHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2009Yih-Lin Chung MD Abstract Background. Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone. Methods. Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, real-time polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes. Results. Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPV-positive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT. Conclusions. Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before or after CCRT. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Treatment results of 1070 patients with nasopharyngeal carcinoma: An analysis of survival and failure patternsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2005To-Wai Leung FRCR Abstract Background. The aim of this analysis was to evaluate the outcomes of patients with nasopharyngeal carcinoma (NPC) treated primarily by external beam irradiation (ERT) and to explore for possible ways to improve the treatment results. Methods. One thousand seventy patients with nonmetastatic NPC treated from 1990 to 1998 were retrospectively analyzed. The distribution according to the Union Internationale Contre le Cancer (UICC) (1997 edition) staging system at initial diagnosis was as follows: stage I, n = 113; stage IIA, n = 38; stage IIB, n = 360; stage III, n = 306; stage IVA, n = 136; stage IVB, n = 117; T1, n = 284; T2a, n = 88; T2b, n = 398; T3, n = 149; T4, n = 151; N0, n = 321; N1, n = 393; N2, n = 238; N3a, n = 29; N3b, n = 89. Two hundred eight patients were given neoadjuvant chemotherapy. Ninety-seven patients were diagnosed with locally persistent disease and were salvaged with high dose rate intracavitary brachytherapy. Multivariate analysis was performed with the Cox regression proportional hazards model. Results. The 5-year actuarial local failure,free survival, regional failure,free survival, distant metastasis,free survival, progression-free survival, cancer-specific survival, and overall survival rates were 80.9%, 93.3%, 77.2%, 62.7%, 71.4%, and 66.5%, respectively. Isolated distant metastasis occurred in 191 patients (18%). The distributions were as follow: stage I, 2.1% (two of 95); stage IIA, 5.7% (two of 35); stage IIB, 14.9% (45 of 302); stage III, 26.4% (62 of 235); stage IVA, 40% (40 of 100); stage IVB, 47.1% (40 of 85). Results of the multivariate analysis of various clinical endpoints were discussed. By studying these failure patterns, it is hoped that we could refine future treatments according to the failure patterns of patients with different risks of locoregional and distant failure. Conclusions. The 18% incidence of isolated distant metastasis is too high to be ignored. Maximizing the local control and minimizing the risk of distant metastasis and late complications should be the key objectives in designing future clinical trials. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] A salvage treatment for solid liver metastasis after radical resection of Klatskin tumourHPB, Issue 4 2003Yuji Nakagawa Background Long-term survival has not been described following surgical resection for liver metastasis after radical resection of an advanced hilar bile duct carcinoma (Klatskin tumour). One such patient who developed liver metastasis after radical treatment for stage IVA (pTNM) hilar cholangiocarcinoma has survived 5.5 years after resection of the liver metastasis followed by chemotherapy. Case report A 50-year-old man developed a solid liver metastasis in segment VIII 17 months after radical resection of a stage IVA (pT3 pN1 M0) Klatskin tumour followed by postoperative radiotherapy (54 Gy) and systemic chemotherapy (oral UFT 450 mg/day plus intravenous cisplatin 20 mg on 5 consecutive days each month). The patient is alive at 7 years after the primary resection followed by resection of the liver metastasis plus further systemic chemotherapy comprising oral UFT combined with intravenous adriamycin (ADM) and mitomycin C (MMC). Conclusion Aggressive salvage resection surgery can be an effective component of a multidisciplinary treatment regimen, even for a postoperative liver metastasis that developed after radical resection of an advanced Klatskin tumour, provided that the metastasis is solid and has not failed local-regional control. [source] Individual voluntary arrangements: A ,fresh start' for salaried consumer debtors in England and Wales,INTERNATIONAL INSOLVENCY REVIEW, Issue 1 2009Adrian Walters Since the mid-1990s the number of consumer insolvencies in England and Wales has grown exponentially. The UK's Insolvency Act 1986 offers two formal responses to personal insolvency: bankruptcy and individual voluntary arrangements (,IVAs'). While consumers have used both these debt relief mechanisms in increasing numbers in recent years, IVAs,regulated agreements between debtors and creditors facilitated by a licensed insolvency practitioner, usually taking the form of a 5-year payment plan,grew faster than bankruptcies between 2003 and 2006. However, the level of new IVA approvals fell back in 2007 and the first half of 2008. This article charts the transformation of the IVA from a bankruptcy alternative originally designed for insolvent traders and professionals into a tool of consumer debt relief. It then seeks to explain both the stellar rise in IVA usage among consumer debtors and the subsequent stalling of IVA growth. The rise of consumer IVAs can be attributed largely to supply side changes in the market for debt resolution,in particular the emergence of volume providers commonly referred to as ,IVA factories',while a sustained backlash against the procedure and the providers instigated by institutional creditors demanding higher recoveries accounts for the subsequent decline in approvals. The article concludes by considering the near-term prospects for consumer IVAs within the context of the increasingly complex UK debt resolution market. Copyright © 2009 John Wiley & Sons, Ltd. [source] Infrared spectra of water molecule encapsulated inside fullerene studied by instantaneous vibrational analysis,INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 10 2009Kiyoshi Yagi Abstract Instantaneous vibrational analysis (IVA) is proposed for computing the infrared spectrum of dynamically fluctuating system, and applied to a water molecule encapsulated into fullerene (H2O@C60). A molecular dynamics simulation is first carried out to generate an ensemble of configurations averaging the rotational and translational motion of H2O inside fullerene. At each configuration, instantaneous vibrational frequencies of the water molecule are computed by the vibrational configuration interaction method, which are then employed to construct the line-shape of the spectrum. The vibrational spectrum in the OH stretching region is computed at a temperature of 10 and 100 K based on a direct potential energy surface incorporating the electronic structure theory. It is found that the vibrational frequency of the symmetric stretching mode is blue-shifted compared to that of isolated water, whereas that of the asymmetric stretching mode exhibits no shift in average. The relation between IVA and instantaneous normal mode analysis is presented, and their performances are compared. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] Calcium channel subtypes differentially regulate fusion pore stability and expansionJOURNAL OF NEUROCHEMISTRY, Issue 4 2007Alvaro O. Ardiles Abstract Various studies have focused in the relative contribution of different voltage-activated Ca2+ channels (VACC) to total transmitter release. However, how Ca2+ entry through a given VACC subtype defines the pattern of individual exocytotic events remains unknown. To address this question, we have used amperometry in bovine chromaffin cells. L, N, and P/Q channels were individually or jointly blocked with furnidipine, ,-conotoxin GVIA, ,-agatoxin IVA, or ,-conotoxin MVIIC. The three channel types contributed similarly to cytosolic Ca2+ signals induced by 70 mmol/L K+. However, they exhibited different contributions to the frequency of exocytotic events and they were shown to differently regulate the final steps of the exocytosis. When compared with the other VACC subtypes, Ca2+ entry through P/Q channels effectively induced exocytosis, it decreased fusion pore stability and accelerated its expansion. Conversely, Ca2+ entry through N channels was less efficient in inducing exocytotic events, also slowing fusion pore expansion. Finally, Ca2+ entry through L channels inefficiently induced exocytosis, and the individual blockade of this channel significantly modified fusion pore dynamics. The distance between a given VACC subtype and the release sites could account for the differential effects of the distinct VACC on the fusion pore dynamics. [source] A2A Adenosine Receptor Facilitation of Neuromuscular TransmissionJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Influence of Stimulus Paradigm on Calcium Mobilization Abstract: The influence of stimulus pulse duration on calcium mobilization triggering facilitation of evoked [3H]acetylcholine ([3H]ACh) release by the A2A adenosine receptor agonist CGS 21680C was studied in the rat phrenic nerve-hemidiaphragm. The P-type calcium channel blocker ,-agatoxin IVA (100 nM) decreased [3H]ACh release evoked with pulses of 0.04-ms duration, whereas nifedipine (1 ,M) inhibited transmitter release with pulses of 1-ms duration. Depletion of intracellular calcium stores by thapsigargin (2 ,M) decreased [3H]ACh release evoked by pulses of 1 ms, an effect observed even in the absence of extracellular calcium. With short (0.04-ms) stimulation pulses, when P-type calcium influx triggered transmitter release, facilitation of [3H]ACh release by CGS 21680C (3 nM) was attenuated by both thapsigargin (2 ,M) and nifedipine (1 ,M). With longer stimuli (1 ms), a situation in which both thapsigargin-sensitive internal stores and L-type channels are involved in ACh release, pretreatment with either ,-agatoxin IVA (100 nM) or nifedipine (1 ,M) reduced the facilitatory effect of CGS 21680C (3 nM). The results suggest that A2A receptor activation facilitates ACh release from motor nerve endings through alternatively mobilizing the available calcium pools (thapsigargin-sensitive internal stores and/or P- or L-type channels) that are not committed to the release process in each stimulation condition. [source] Melanotrope Cells of Xenopus laevis Express Multiple Types of High-Voltage-Activated Ca2+ ChannelsJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2005H.-Y. Zhang Abstract Pituitary melanotrope cells are neuroendocrine signal transducing cells that translate physiological stimuli into adaptive hormonal responses. In this translation process, Ca2+ channels play essential roles. We have characterised which types of Ca2+ current are present in melanotropes of the amphibian Xenopus laevis, using whole-cell, voltage-clamp, patch-clamp experiments and specific blockers of the various current types. Running an activation current,voltage relationship protocol from a holding potential (HP) of ,80 mV/or ,110 mV, shows that Xenopus melanotropes possess only high-voltage activated (HVA) Ca2+ currents. Steady-state inactivation protocols reveal that no inactivation occurs at ,80 mV, whereas 30% of the current is inactivated at ,30 mV. We determined the contribution of individual channel types to the total HVA Ca2+ current, examining the effect of each channel blocker at an HP of ,80 mV and ,30 mV. At ,80 mV, ,-conotoxin GVIA, ,-agatoxin IVA, nifedipine and SNX-482 inhibit Ca2+ currents by 21.8 ± 4.1%, 26.1 ± 3.1%, 24.2 ± 2.4% and 17.9 ± 4.7%, respectively. At ,30 mV, ,-conotoxin GVIA, nifedipine and ,-agatoxin IVA inhibit Ca2+ currents by 33.8 ± 3.0, 24.2 ± 2.6 and 16.0 ± 2.8%, respectively, demonstrating that these blockers substantially inhibit part of the Ca2+ current, independently from the HP. We have previously demonstrated that ,-conotoxin GVIA can block Ca2+ oscillations and steps. We now show that nifedipine and ,-agatoxin IVA do not affect the intracellular Ca2+ dynamics, whereas SNX-482 reduces the Ca2+ step amplitude. We conclude that Xenopus melanotrope cells express all four major types of HVA Ca2+ channel, as well as the resulting currents, but no low-voltage activated channels. The results provide the basis for future studies on the complex regulation of channel-mediated Ca2+ influxes into this neuroendocrine cell type as a function of its role in the animal's adaptation to external challenges. [source] A risk-based approach to establish stability testing conditions for tropical countries,,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2006Manuel Zahn Abstract The external stability risk factors heat and moisture are evaluated with respect to the development of pharmaceutical products intended to be marketed in tropical and subtropical countries. The mean daily temperatures and dewpoints measured four times per day at selected places in Southeast Asia, South America, China, Southern Africa and the Caribbean are used to calculate the daily and monthly fluctuations of temperature and partial water vapour pressure, the mean kinetic temperature and the relative humidity. Based on these data, the hottest and the most humid place in each country or region are identified to reflect the worst case for the specific region. A formula to calculate safety margins for temperature and partial vapour pressure is introduced taking into consideration the difference between measured meteorological parameters and the stability testing conditions. An appropriate long-term stability testing condition is proposed for each selected country, related to the worst case for each specific region and the safety margins, as well as its classification in either Climatic Zone IVA or IVB. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:946,965, 2006 [source] Anti-influenza virus activity of crude extract of Ribes nigrum L.PHYTOTHERAPY RESEARCH, Issue 2 2003Yoko M. Knox Abstract This experiment was designed to detect the antiviral activities of crude fruit extracts of wild Ribes nigrum L. (Kurokarin extract) against influenza virus types A and B. Kurokarin extract was prepared as follows: fruits of Ribes nigrum L. were heated at 50,°C in a heating tank, and then ground under anaerobic conditions. The extracts were centrifuged, and the supernatant fluid was filtered and sterilized by infrared rays. The crude extract was diluted with Eagle's minimum essential medium (MEM) and the solution was adjusted to a pH 7.2 with 0.1 N or 1 N NaOH. Proven anti-influenza virus effects of the extracts were shown. The concentration of extract required to inhibit the plaque formation of both IVA and IVB by 50% (IC50) was 3.2,,g/mL. Both IVA and IVB were directly inactivated up to 99% by 10,,g/mL of the extract at pH 2.8, and 95% to 98% by this dose at pH 7.2. The growth of IVA in cells treated with 10 and 100,,g/mL of the extract for 6,h after infection was completely suppressed. Virus titres in culture fluids of the cells treated with 100,,g/mL of Kurokarin extract for 1,h at 8 to 9,h after infection, were completely suppressed, indicating that the extract inhibited the virus release from the infected cells. Copyright © 2003 John Wiley & Sons, Ltd. [source] Electrophysiological and Neurochemical Evidence for Voltage-Dependent Ca2+ Channel Blockade by a Novel Neuroprotective Agent NS-7,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2001Michiko Oka In rat dorsal root ganglion neurones, NS-7 (0.3,100 ,M) inhibited the whole-cell Ba2+ currents (IBa) in a voltage-dependent manner, in which the compound more potently blocked the IBa elicited from the holding potential of ,40 mV than that induced from ,80 mV. In slices of rat cerebral cortex, KCl-evoked nitric oxide synthesis was markedly inhibited by ,-conotoxin GVIA and ,-agatoxin IVA, but only slightly attenuated by nifedipine, suggesting that the response is mediated predominantly through activation of N-type and P/Q-type Ca2+ channels. NS-7 (1,100 ,M) inhibited the KCl-stimulated nitric oxide synthesis in a manner dependent on the intensity of the depolarizing stimuli. Moreover, weak but significant inhibitory effect of NS-7 was observed even after wash-out. Similar voltage-dependent inhibition of the KCl response was observed by a limited concentration (10 ,M) of verapamil. These findings indicate that NS-7 in several concentrations blocks Ca2+ channel in a voltage-dependent manner. [source] Intravasal azoospermia: a surgical dilemmaBJU INTERNATIONAL, Issue 9 2000Y.R. Sheynkin Objectives,To determine the incidence of intravasal azoospermia (IVA) and evaluate which factors before and during surgery influence outcome, by prospectively and intentionally performing bilateral vasovasostomies (VVs) only in men with intraoperative IVA. Patients and methods,Using a multilayer technique, 472 men underwent microsurgical reconstructive procedures. Intravasal fluid was examined for sperm by the surgeon and a pathologist. Strict enrolment criteria included total absence of sperm or sperm parts and bilateral VV as a treatment procedure. Patients were followed up by semen analysis and paternity assessed only by naturally conceived pregnancies. Results,Of the 472 patients, 27 (5.7%) had bilateral IVA; 15 of these patients were available for a follow-up of 1,47 months. Eleven patients had identical gross appearance of intravasal fluid bilaterally. Of these patients, five had sperm in the ejaculate after surgery (three with clear intravasal fluid and two with no fluid). Bilaterally different vasal fluid was found in four men. Unilateral clear fluid was present in three patients, two of whom had sperm in semen analysed after VV. Overall, there was sperm in the ejaculate in seven of 15 patients with IVA; five of these seven had clear fluid in at least one vas deferens. One patient with unilaterally clear fluid achieved paternity by a naturally conceived pregnancy. The difference between the mean (sem) obstruction interval in men who had sperm in a semen sample after VV, at 16.7 (3.30) years, and in persistently azoospermic patients, at 15.5 (1.89) years, was not statistically significant (P = 0.741). Conclusion,The results of VV in patients with IVA are unsatisfactory; the patency rate is higher in men with copious clear fluid in at least one vas. The obstructive interval in patients with IVA does not appear to influence the outcome of VV. [source] A comparison of Ca2+ channel blocking mode between gabapentin and verapamil: implication for protection against hypoxic injury in rat cerebrocortical slicesBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003Michiko Oka The mode of Ca2+ channel blocking by gabapentin [1-(aminomethyl)cyclohexane acetic acid] was compared to those of other Ca2+ channel blockers, and the potential role of Ca2+ channel antagonists in providing protection against hypoxic injury was subsequently investigated in rat cerebrocortical slices. mRNA for the ,2, subunits of Ca2+ channels was found in rat cerebral cortex. Nitric oxide (NO) synthesis estimated from cGMP formation was enhanced by KCl stimulation, which was mediated primarily by the activation of N- and P/Q-type Ca2+ channels. Gabapentin blocked both types of Ca2+ channels, and preferentially reversed the response to 30 mM K+ stimulation compared with 50 mM K+ stimulation. In contrast, verapamil preferentially inhibited the response to depolarization by the higher concentration (50 mM) of K+. Gabapentin inhibited KCl-induced elevation of intracellular Ca2+ in primary neuronal culture. Hypoxic injury was induced in cerebrocortical slices by oxygen deprivation in the absence (severe injury) or presence of 3 mM glucose (mild injury). Gabapentin preferentially inhibited mild injury, while verapamil suppressed only severe injury. , -Conotoxin GVIA (, -CTX) and , -agatoxin IVA (, -Aga) were effective in both models. NO synthesis was enhanced in a manner dependent on the severity of hypoxic insults. Gabapentin reversed the NO synthesis induced by mild insults, while verapamil inhibited that elicited by severe insults. , -CTX and , -Aga were effective in both the cases. Therefore, the data suggest that gabapentin and verapamil cause activity-dependent Ca2+ channel blocking by different mechanisms, which are associated with their cerebroprotective actions and are dependent on the severity of hypoxic insults. British Journal of Pharmacology (2003) 139, 435,443. doi:10.1038/sj.bjp.0705246 [source] Central bisectionectomy for centrally located hepatocellular carcinomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2008J. G. Lee Background: Central bisectionectomy, which involves the removal of the central hepatic segments (IVA, IVB, V, VIII) for hepatocellular carcinoma (HCC), is performed to reduce the volume of resected liver and to overcome the problem of insufficient future residual volume. Methods: Twenty-seven patients with HCC underwent central bisectionectomy from January 1998 to April 2007 in one hospital. The surgical techniques, clinicopathological characteristics and outcomes were reviewed. Results: The median operating time was 330 min. Twelve patients developed postoperative complications and two died. The most common complication, occurring in five patients, was bile duct injury leading to biloma or bile leakage. Median follow-up was 19·1 (range 1·4,102·2) months and eight patients developed a recurrence. Twenty-four patients were alive at the time of writing. Conclusion: Although biliary complications occur somewhat frequently, central bisectionectomy in centrally located HCC can be performed safely to preserve liver volume. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] High-dose-rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhoodCANCER, Issue 3 2005Ricardo Akiyoshi Nakamura M.D. Abstract BACKGROUND Nasopharyngeal carcinoma in childhood is rare. Radiochemotherapy is considered the standard treatment and yields increased survival and local control rates. In this article, the authors report on the results from the multidisciplinary treatment of pediatric patients who had nasopharyngeal lymphoepithelioma with radiochemotherapy, including high-dose-rate brachytherapy of the primary tumor site. METHODS Between May 1992 and May 2000, 16 children with nasopharyngeal lymphoepithelioma received neoadjuvant chemotherapy, conventional external beam radiotherapy, high-dose-rate brachytherapy, and adjuvant chemotherapy. Patients ranged in age from 7 years to 18 years, and 9 patients were male. Patient distribution according to clinical disease stage was as follows: Stage III, 1 patient; Stage IVA, 5 patients; Stage IVB, 9 patients; and Stage IVC, 1 patient. Three cycles of neoadjuvant and adjuvant chemotherapy in 3-week intervals were administered with cyclophosphamide, vincristine, doxorubicin, and cisplatin. The median doses of external beam radiotherapy to the primary tumor, positive lymph nodes, and subclinical areas of disease were 55 grays (Gy), 55 Gy, and 45 Gy, respectively. Children received 2 insertions of high-dose-rate brachytherapy at 5 Gy per insertion: These were performed with metallic applicators inserted through the transnasal access under local anesthesia. RESULTS The median of follow-up was 54 months. At the time of last follow-up, 13 patients were alive without disease, 2 patients had died of disease, and 1 patient had died of treatment-related cardiac failure. Local control was achieved in 15 of 16 patients. Chemotherapy-related and radiotherapy-related acute toxicity was relevant but tolerable. CONCLUSIONS In the current study, it was shown that the treatment was effective in the control of both local and distant disease, although there was relevant acute and late toxicity. High-dose-rate brachytherapy was deliverable on an outpatient basis with local anesthesia. Close follow-up of these patients was necessary to evaluate the significance of treatment-related late effects and their impact on quality of life. Cancer 2005. © 2005 American Cancer Society. [source] High remnant lipoprotein levels in patients with variant anginaCLINICAL CARDIOLOGY, Issue 6 2004Kunihisa Miwa M.D. Doctor-in-Chief Abstract Background: Dyslipidemia with increased oxidative stress but without elevation of low-density lipoprotein cholesterol has been recently implicated in the pathogenesis of coronary vasospasm. Hypothesis: Disordered triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary artery spasm. Methods: Both serum remnant lipoprotein (RLP) and ,-tocopherol levels were determined in 18 patients with the active stage of variant angina (VA), in 16 patients with the inactive stage of variant angina (IVA), and in 19 control subjects (CONTROL). Results: The RLP levels were significantly (p < 0.05) higher in VA (6.4 ± 2.7 mg/dl) than in IVA (4.4 ± 1.5 mg/dl). In contrast, ,-tocopherol levels were significantly lower in VA than that in CONTROL. Serum trigyceride levels were not significantly different among the study groups, although serum high-density lipoprotein cholesterol levels were significantly lower in VA than in CONTROL. Smoking was significantly (p < 0.05) more prevalent in VA (72%) than in IVA (25%) and CONTROL (37%). Serum RLP levels correlated positively with triglyceride levels (R = 0.73) and correlated inversely with ,-tocopherol levels (R = - 0.31) significantly in all study subjects. Conclusions: Patients with active stage of variant angina had higher RLP levels than inactive patients with variant angina and lower ,-tocopherol levels than control subjects. Disordered triglyceride-rich lipoprotein metabolism with increased oxidative stress appears to be linked to the activity of coronary vasospasm, suggesting a possible role in its pathogenesis. [source] Tumoral and tissue-specific expression of the major human ,-tubulin isotypes,CYTOSKELETON, Issue 4 2010Luis J. Leandro-García Abstract The ,-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on ,-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex ,-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human ,-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total ,-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex ,-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley-Liss, Inc. [source] Habitat associations of Atlantic herring in the Shetland area: influence of spatial scale and geographic segmentationFISHERIES OCEANOGRAPHY, Issue 3 2001CHRISTOS D. Maravelias This study considers the habitat associations of a pelagic species with a range of biotic and abiotic factors at three different spatial scales. Generalized additive models (GAM) are used to analyse trends in the distributional abundance of Atlantic herring (Clupea harengus) in relation to thermocline and water depth, seabed roughness and hardness, sea surface salinity and temperature, zooplankton abundance and spatial location. Two geographical segments of the population, those east and west of the Shetland Islands (northern North Sea, ICES Div IVa), are examined. The differences in the ecological preferences of the species in these two distinct geographical areas are elucidated and the degree that these environmental relationships might be modulated by the change of support of the data is also considered. Part of the observed variability of the pre-spawning distribution of herring was explained by different parameters in these two regions. Notwithstanding this, key determinants of the species' spatial aggregation in both areas were zooplankton abundance and the nature of the seabed substrate. The relative importance of the variables examined did not change significantly at different spatial scales of the observation window. The diverse significance of various environmental factors on herring distribution was attributed mainly to the interaction of species' dynamics with the different characteristics of the ecosystem, east and west of the Shetland Islands. Results suggest that the current 2.5 nautical miles as elementary sampling distance unit (ESDU) is a reasonable sampling scheme that combines the need to reduce the data volume while maintaining spatial resolution to distinguish the species/environment relationships. [source] Effects of glycyrrhetinic acid derivatives on hepatic and renal 11,-hydroxysteroid dehydrogenase activities in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2003Yoshihito Shimoyama The purpose of this study was to examine the structure and activity relationships of glycyrrhetinic acid derivatives on the inhibition of hepatic and renal 11,-hydroxysteroid dehydrogenases (HSDs) in rats. Furthermore, we explored whether inflammatory effect of the derivatives is involved in the inhibition of 11,-HSD activity. 18,-Glycyrrhetinic acid (Ia) potently inhibited 11,-HSD activity of hepatic (IC50 (concentration giving 50% inhibition of cortisone production) = 0.09 ,m) and renal (IC50 = 0.36 ,m) homogenate. The inhibitory effect of 18,-glycyrrhetol (Id) modified at the 30-position of glycyrrhetinic acid was weaker than that of glycyrrhetinic acid itself. 18,-24-Hydroxyglycyrrhetinic acid (Ie), oxidized at the 24-position, remarkably reduced the inhibitory activity for both enzymes. 18,-11-Deoxoglycyrrhetinic acid (IIc) showed the same inhibitory effect as glycyrrhetinic acid on hepatic 11,-HSD activity, but less effect on renal 11,-HSD activity. Furthermore, the inhibitory activity of 18,-deoxoglycyrrhetol (IIa), modified at the 11- and 30-position, was markedly decreased. Dihemiphthalate derivatives (IIb, IIIb and IVb) of deoxoglycyrrhetol (IIa), 18,-olean-9(11), 12-diene-3,, 30-diol (IIIa) and olean-11, 13(18)-diene-3,, 30-diol (IVa), which are anti-inflammatory agents, also showed weak inhibition against both hepatic and renal 11,-HSDs. While glycyrrhetinic acid (200 mg kg,1, p.o.) significantly inhibited 11,-HSD activity in rat liver and kidney at 3 h after administration, compound IVb (100 mg kg,1, p.o.) had no effect on either enzyme activity. In addition, the circulating corticosterone level was slightly increased by glycyrrhetinic acid but not by compound IVb. These results suggest that the anti-inflammatory effects of compound IVb, derived from glycyrrhetinic acid, are not due to accumulation of steroids induced by the inhibition of 11,-HSD activity. Our data also showed that the 11-, 24- and 30-positions of glycyrrhetinic acid may play important roles in the differential inhibitory effects on 11,-HSD isozyme activity. [source] Prognostic influence of sub-stages according to pTNM categories in patients with stage IV gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2009Chen Li MD Abstract Background and Objectives The prognosis for patients with stage IV gastric cancer is still very poor. The purpose of this study was to evaluate the surgical outcome and prognosis, and to determine the prognostic influence of sub-stages of stage IV gastric cancer. Methods From 1992 to 2002, 287 patients histologically diagnosed with stage IV gastric cancer underwent gastrectomy at the Department of Surgery, Ruijin Hospital, China. Regarding TNM categories, we separated them into T1-3N3M0, T4N1-2M0, T4N3M0, and TanyNanyM1 groups. We compared the clinicopathological characteristics as well as the survival in these groups. Results There were largest proportions of patients who underwent extended lymphadenectomy and curative gastrectomy in T1-3N3M0 group followed by T4N1-2M0, T4N3M0, and TanyNanyM1 groups. The survival rate of patients with sub-stage IVa (T1-3N3M0 and T4N1-2M0) tumors was significant higher than that of patients with sub-stage IVb (T4N3M0 and TanyNanyM1) tumors (P,=,0.008). Multivariate analysis showed that sub-stage with the highest risk ratio (1.454), and the surgical curability were independent prognostic factors in patients with stage IV gastric cancer. Conclusions Sub-stages IVa (T1-3N3M0 and T4N1-2M0) and IVb (T4N3M0 and TanyNanyM1) may predict patients' prognosis more accurately. Curative resection should be performed whenever possible in patients with stage IV gastric cancer. J. Surg. Oncol. 2009;99:324,328. © 2009 Wiley-Liss, Inc. [source] Crystal structure and kinetic mechanism of aminoglycoside phosphotransferase-2,-IVaPROTEIN SCIENCE, Issue 8 2010Marta Toth Abstract Acquired resistance to aminoglycoside antibiotics primarily results from deactivation by three families of aminoglycoside-modifying enzymes. Here, we report the kinetic mechanism and structure of the aminoglycoside phosphotransferase 2,-IVa (APH(2,)-IVa), an enzyme responsible for resistance to aminoglycoside antibiotics in clinical enterococcal and staphylococcal isolates. The enzyme operates via a Bi-Bi sequential mechanism in which the two substrates (ATP or GTP and an aminoglycoside) bind in a random manner. The APH(2,)-IVa enzyme phosphorylates various 4,6-disubstituted aminoglycoside antibiotics with catalytic efficiencies (kcat/Km) of 1.5 × 103 to 1.2 × 106 (M,1 s,1). The enzyme uses both ATP and GTP as the phosphate source, an extremely rare occurrence in the phosphotransferase and protein kinase enzymes. Based on an analysis of the APH(2,)-IVa structure, two overlapping binding templates specifically tuned for hydrogen bonding to either ATP or GTP have been identified and described. A detailed understanding of the structure and mechanism of the GTP-utilizing phosphotransferases is crucial for the development of either novel aminoglycosides or, more importantly, GTP-based enzyme inhibitors which would not be expected to interfere with crucial ATP-dependent enzymes. [source] Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: A subset analysis of the university of pennsylvania transoral robotic surgery trial,THE LARYNGOSCOPE, Issue 9 2010Gregory S. Weinstein MD Abstract Objectives/Hypothesis: The purpose of this study was to determine the regional recurrence rate of node-positive oropharyngeal squamous cell carcinoma (OPSCC) in patients undergoing transoral robotic surgery (TORS) and selective neck dissection (SND) followed by observation, radiation, or concurrent chemoradiation. Study Design: A prospective, phase I, single-arm study was conducted. All OPSCC patients who voluntarily participated in a surgical trial with TORS and SND at an academic tertiary referral center from May 2005 to July 2007 were included. Methods: Thirty-one patients with previously untreated OPSCC undergoing TORS and SND (29 unilateral and two bilateral) were included. There were 29 males and two females, with ages ranging from 36 to 76 years (median = 55 years) with one palate, one lateral wall, 17 tonsil, 11 base of tongue, and one vallecula primary tumor classified as follows: T1 (n = 9, 29%), T2 (n = 15, 48.4%), T3 (n = 7, 22.6%), N0 (n = 6, 19.4%), N1 (n = 15, 48.4%), N2b (n = 10, 32.3%), and N2c (n = 1, 3.2%). There were three stage I (9.7%), two stage II (6.5%), 15 stage III (48.4%) and 11 stage IVa (35.5%) patients. Twenty-two patients were treated postoperatively with adjuvant therapy (12 radiation alone and 12 combined radiation and chemotherapy). Primary outcome measured was regional recurrence rate. Results: There was one regional recurrence on the contralateral, non-operated neck and one distant recurrence among the 31 patients who underwent SND. Conclusions: SND after TORS resection of primary OPSCC enables the use of selective and deintensified adjuvant therapy to reduce regional recurrence rates. Laryngoscope, 2010 [source] | ||||||||||||||||||||||||||||||||||