bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric partial cricotracheal resection: A new technique for the posterior cricoid anastomosis
Authors: Boseley Mark E. , Hartnick Christopher J. 
Published: August 2006

ObjectivePartial cricotracheal resection has become a more popular procedure in the pediatric population as a treatment for severe subglottic stenosis. We describe a new technique for the posterior cricoid anastomosis.Study Design and SettingThis is a case series of 4 pediatric patients with a Myer‐Cotton grade III or IV subglottic stensosis.SettingTertiary care hospital with a pediatric intensive care unit.ResultsAll 4 patients were decannulated and there were no observed complications to include posterior mucosal dehiscence and/or recurrent laryngeal nerve injury.ConclusionsPlacing sutures through the cricoid cartilage is technically less difficult than previously described techniques for treating subglottic stenosis near the undersurface of the true vocal folds and affords a more stable posterior mucosal suture line.SignificanceThis technique provides a surgical means to treat high subglottic stenosis that closely approximates the true vocal folds by enabling a stable posterior mucosa to mucosa apposition.EBM rating: Grade C‐4
Unique challenges of obtaining regulatory approval for a multicenter protocol to study the genetics of RRP and suggested remedies
Authors: Sherwood Mylaina L. , Buchinsky Farrel J. , Quigley Matthew R. , Donfack Joseph , Choi Sukgi S. , Conley Stephen F. , Derkay Craig S. , Myer Charles M. , Ehrlich Garth D. , Post J. Christopher 
Published: August 2006

ObjectiveInvestigations that seek to generalize findings or to understand uncommon diseases must be conducted at multiple centers. This study describes the process of obtaining regulatory approval for a minimal risk genetic study in a multi‐center setting as undertaken by the Recurrent Respiratory Papillomatosis (RRP) Task Force.Study Design and SettingSequential cohort of American children's hospitals. A single protocol was submitted to each Institutional Review Board (IRB).ResultsDocumentation was prepared for 14 IRBs over 2.5 years. The median time between enlistment and approval at the first 8 sites was 15 months. Institutions varied considerably in their requirements and in the issues that were raised. Protocols were submitted sequentially and accumulated experience was used in the preparation of applications to subsequent IRBs. Nevertheless, there was no correlation between the accumulated experience and the number of issues that were raised.ConclusionDespite uniform federal standards, all local IRBs required unique and individualized submissions. For multicenter studies, investigators should seriously consider the establishment of cooperative authorization agreements. On a simpler level, a standardized format for applications needs to be adopted nationwide.EBM rating: B‐3b
Nasal polyp diseases in allergic and nonallergic patients and steroid therapy
Authors: Alatas Necat , Baba Fusun , San Imran , Kurcer Zehra 
Published: August 2006

ObjectiveTo investigate widespread disease causes, cellular‐structural differences, and steroid response of nasal polyps (NPs).MethodStudy group consisted of NPs, allergic‐NPs, NPs with steroid therapy (ST), antrochoanal polyp (ACP), and controls. We investigated stromal eosinophil, mast cell, CD4+ and CD8+ cell counts and presence of squamous metaplasia, Ki‐67 expression, intraepithelial eosinophils‐mast cells, epithelial damage, edema, fibrosis, hyalinization, polymorphonuclear leukocyte, and glandular hyperplasia.ResultsIn allergic‐NPs, intraepithelial eosinophils and epithelial damage CD4+ were significantly higher than NPs and also, eosinophils, mast cells, intraepithelial eosinophils, and epithelial damage were significantly higher than ACP. Only stromal eosinophilic infiltration was significantly higher in NPs than ACP. There was significant increased glandular hyperplasia and decreased intraepithelial eosinophils, mast cells, CD4+ cells, squamous metaplasia, and epithelial damage with ST in allergic‐NPs. There were no significant differences with ST in NPs.ConclusionNPs in allergic and nonallergic patients may differ in their histology and in their histologic responses to ST.EBM rating: B‐3b
Frozen versus fresh reconstituted botox for laryngeal dystonia
Authors: Thomas James P. , Siupsinskiene Nora 
Published: August 2006

ObjectivesTo compare the efficacy and side effects of frozen versus fresh reconstituted botulinum toxin type A (BTX‐A) in the treatment of laryngeal dystonia.Study Design and SettingProspective open‐label crossover study; 43 adult patients with adductor spasmodic dysphonia were randomly treated with fresh or refrozen reconstituted BTX‐A at a private voice center. Treatment outcomes were assessed by duration of action and self‐rated satisfaction (7 point Likert scale). Side effects of breathiness and dysphagia for liquids were assessed as well.ResultsThere was no statistically significant difference in the duration of action (mean, 16.2 ± 8.5 vs 16.0 ± 7.6 weeks) and self‐rated satisfaction of the treatment (median, 6.0 vs 6.0 points). The side effects were similar for both BTX‐A injection types. In addition, there were no instances of infection for refrozen injections.ConclusionsBTX‐A may be safely used after being reconstituted and frozen or refrozen without a significant loss of effectiveness or additional side effects. In our experience, the period of freezing was on 2 occasions for up to 8 weeks.SignificanceRefrozen BTX‐A may be a cost‐effective use of an expensive drug.EBM rating: B‐2b
High efficiency gene delivery into laryngeal muscle with bidirectional electroporation
Authors: Saito Koichiro , Lehar Mohamed , Li Zhao Bo , Braga Natasha , King Alan D. , Samlan Robin A. , Flint Paul W. 
Published: August 2006

ObjectiveThe impact of polarity change on the efficiency of in vivo electroporative (EP) gene transfection was assessed in rat laryngeal muscle.Study Design and SettingHigh (HV) and low field voltage (LV) were combined with polarity changes to determine transfection in 5 different conditions: 1) without EP (EP[‐]), 2) HV+LV (HL), 3) HV+LV followed by HV+LV with no change in polarity (HLHL unidirectional), 4) HV+LV followed by HV+LV with opposite polarity (HLHL bidirectional), 5) HV+LV followed by LV with opposite polarity (HLL bidirectional).ResultsHLL bidirectional sequence showed the best result with less interindividual variability and extended expression period. With the exception of repeated high voltage sequences, EP parameters were not likely to induce cell injury or inflammation.ConclusionHLL bidirectional electroporative gene delivery produces high transfection rates with limited tissue trauma.SignificanceBidirectional EP provides a safe and highly efficient method for therapeutic gene delivery into skeletal muscle. © 2006 American Academy of Otolaryngology‐Head and Neck Surgery Foundation. All rights reserved.
Four suture tip rhinoplasty: A powerful tool for controlling tip dynamics
Authors: Leach Joseph L. , Athré Raghu S. 
Published: August 2006

ObjectiveTo evaluate the short‐term effectiveness of using a 4‐suture technique to control nasal tip dynamics. The 4 sutures include a medial crural suture, bilateral intradomal sutures, and an interdomal suture.Study Design and SettingRetrospective photograph analysis of preoperative and postoperative photographs of 77 patients with respect to 7 dynamic variables: supratip break, projection, rotation, tip shape, tip definition, tip symmetry, and the presence of a double columellar break.ResultsSeventy‐four patients underwent primary rhinoplasty and had an overall average score of 5.2 on a −7 to +7 scale, with a mean follow‐up period of 3.8 months. The 3 patients undergoing revision rhinoplasty had an overall average score of 5.0 and a mean follow‐up of 8.7 months.ConclusionThe 4‐suture technique worked best with respect to projection and tip symmetry, although the technique proved to be an effective tool overall in controlling all 7 variables mentioned above.EBM rating: C‐4
Gastroesophageal reflux and laryngopharyngeal reflux in patients with sleep‐disordered breathing
Authors: Wise Sarah K. , Wise Justin C. , DelGaudio John M. 
Published: August 2006

ObjectiveTo assess the relationship of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) with obstructive sleep apnea (OSA).Patients and MethodsThirty‐seven sleep‐disordered breathing (SDB) patients underwent polysomnography (PSG) and dual‐channel pH probe testing. LPR was defined as greater than 6.9 proximal reflux episodes or reflux area index (RAI) greater than 6.3. GER was defined as greater than 4% of time below pH 4.0.ResultsOSA was present in 28 patients. Twenty‐three patients had LPR (66.7% of snorers, 60.7% of OSA patients). Twenty‐one patients had GER (33.3% of snorers, 64.3% of OSA patients). Body mass index (BMI) correlated positively with respiratory disturbance index (RDI) (r = 0.67, P < 0.001). BMI did not correlate with pH probe parameters. OSA presence/severity did not correlate with LPR or GER. Supine LPR and GER events did not correlate with OSA presence/severity.ConclusionGastric acid reflux is prevalent in SDB patients. Direct correlations between reflux and PSG parameters were not identified.EBM rating: B‐2b
Optimization of Fed‐Batch Saccharomyces cerevisiae Fermentation Using Dynamic Flux Balance Models
Authors: Hjersted Jared L. , Henson Michael A. 
Published: August 2006

AbstractWe developed a dynamic flux balance model for fed‐batch Saccharomyces cerevisiae fermentation that couples a detailed steady‐state description of primary carbon metabolism with dynamic mass balances on key extracellular species. Model‐based dynamic optimization is performed to determine fed‐batch operating policies that maximize ethanol productivity and/or ethanol yield on glucose. The initial volume and glucose concentrations, the feed flow rate and dissolved oxygen concentration profiles, and the final batch time are treated as decision variables in the dynamic optimization problem. Optimal solutions are generated to analyze the tradeoff between maximal productivity and yield objectives. We find that for both cases the prediction of a microaerobic region is significant. The optimization results are sensitive to network model parameters for the growth associated maintenance and P/O ratio. The results of our computational study motivate continued development of dynamic flux balance models and further exploration of their application to productivity optimization in biochemical reactors.
The antiepileptic and anticancer agent, valproic acid, induces P‐glycoprotein in human tumour cell lines and in rat liver
Authors: Eyal S , Lamb J G , Smith‐Yockman M , Yagen B , Fibach E , Altschuler Y , White H S , Bialer M 
Published: August 2006

Background and purpose:The antiepileptic drug valproic acid, a histone deacetylase (HDAC) inhibitor, is currently being tested as an anticancer agent. However, HDAC inhibitors may interact with anticancer drugs through induction of P‐glycoprotein (P‐gp, MDR1) expression. In this study we assessed whether valproic acid induces P‐gp function in tumour cells. We also investigated effects of valproic acid on the mRNA for P‐gp and the cytochrome P450, CYP3A, in rat livers.Experimental approach:Effects of valproic acid on P‐gp were assessed in three tumour cell lines, SW620, KG1a and H4IIE. Accumulation of acetylated histone H3 in rats' livers treated for two or seven days with valproic acid was evaluated using a specific antibody. Hepatic expression of the P‐gp genes, mdr1a, mdr1b and mdr2, was determined by real‐time polymerase chain reaction. The effects of valproic acid on CYP3A were assessed by Northern blot analysis and CYP3A activity assays.Key results:Valproic acid (0.5–2.0 mM) induced P‐gp expression and function up to 4‐fold in vitro. The effect of a series of valproic acid derivatives on P‐gp expression in SW620 and KG1a cells correlated with their HDAC inhibition potencies. Treatment of rats with 1 mmol kg−1 valproic acid for two and seven days increased hepatic histone acetylation (1.3‐ and 3.5‐fold, respectively) and the expression of mdr1a and mdr2 (2.2–4.1‐fold). Valpromide (0.5–2.0 mM) did not increase histone acetylation or P‐gp expression in rat livers, but induced CYP3A expression.Conclusions:Valproic acid increased P‐gp expression and function in human tumour cell lines and in rat liver. The clinical significance of this increase merits further investigation.British Journal of Pharmacology (2006) 149, 250–260. doi:10.1038/sj.bjp.0706830
Obesity – a risk factor or a RISK factor for myocardial infarction?
Authors: Heusch G 
Published: August 2006

The detrimental actions of leptin on cardiovascular function are well established. Smith et al. report the novel finding of a reduction of infarct size by exogenous leptin when given at reperfusion. The involvement of the reperfusion injury salvage kinase (RISK) pathway in such reduction of infarct size and its relation to ischemic pre‐ and postconditioning are discussed and some methodological issues in its assessment are raised. Obesity has possibly opposite effects on the incidence and outcome of myocardial infarction.British Journal of Pharmacology (2006) 149, 1–3. doi:10.1038/sj.bjp.0706833
Kinase‐dependent, retinoic acid receptor‐independent up‐regulation of cyclooxygenase‐2 by all‐trans retinoic acid in human mesangial cells
Authors: Alique M , Moreno V , Kitamura M , Xu Q , Lucio‐Cazana F J 
Published: August 2006

Background and purpose:Preliminary results in human mesangial cells (MC) suggested that all‐trans retinoic acid (ATRA) increased the expression of COX‐2 and the production of prostaglandin E2 (PGE2), a PG with anti‐inflammatory effects in MC. The aim of this work is to confirm that ATRA increases the expression of COX‐2 in MC and to examine the mechanisms involved.Experimental approach:Cultured MC were treated with ATRA. COX expression and kinase activity were analyzed by Western blot. Transcriptional mechanisms were analyzed by Northern blot, RT‐PCR and promoter assays.Key results:COX‐2 and COX‐1 expression and PGE2 production were increased by ATRA. COX‐2 played a role in PGE2 production as production was only partially inhibited by COX‐1 inhibitor SC‐560. COX‐2 up‐regulation by ATRA was due to transcriptional mechanisms as pre‐incubation with actinomycin D abolished it and ATRA increased the expression of COX‐2 mRNA and the activity of a human COX‐2 promoter construct, whereas post‐transcriptional mechanisms were not found. Retinoic acid receptors (RAR) were not involved in the up‐regulation of COX‐2 by ATRA since it was not inhibited by RAR‐pan‐antagonists and the RAR‐pan‐agonist TTNPB did not up‐regulate COX‐2. Instead ATRA might act through a sustained activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) since up‐regulation of COX‐2 was prevented by inhibition of the activation of ERK1/2 with PD098059. Also ERK1/2, as well as downstream signalling proteins from ERK1/2, remained phosphorylated when COX‐2 increased 24 h later.Conclusions and implications:These results highlight the relevance of RAR‐independent mechanisms to the biological effects of ATRA.British Journal of Pharmacology (2006) 149, 215–225. doi:10.1038/sj.bjp.0706842
Regulation of the common carotid arterial blood flow by nicotinic receptors in the medulla of cats
Authors: Gong C‐L , Chiu Y‐T , Lin N‐N , Cheng C‐C , Lin S‐Z , Lee T J‐F , Kuo J‐S 
Published: August 2006

Background and purpose:Actions of glutamate and serotonin on their respective receptors in the dorsal facial area (DFA) of the medulla are known to regulate common carotid arterial (CCA) blood flow in cats. Less is known about acetylcholine action on its nicotinic receptor (nAChR) subtypes in the DFA for regulation of CCA blood flow and this aspect was investigated.Experimental approach:Nicotinic and muscarinic agonists and antagonists were microinjected into the DFA through a three‐barrel tubing in anesthetized cats.Results:CCA blood flow was dose‐dependently increased by nicotine (a non‐selective nAChR agonist) and choline (a selectiveα7‐nAChR agonist). These effects of nicotine were attenuated byα‐bungarotoxin (anα7‐nAChR antagonist), methyllycaconitine (anα7‐nAChR antagonist), mecamylamine (a relatively selectiveα3β4‐nAChR antagonist) and dihydro‐β‐erythroidine (a relatively selectiveα4β2‐nAChR antagonist). The choline‐induced flow increase was attenuated byα‐bungarotoxin and mecamylamine, but not by dihydro‐β‐erythroidine. Muscarinic agonists (muscarine and methacholine) and antagonist (atropine) affected neither the basal nor the nicotine‐induced increase in the CCA blood flow.Conclusions and implications:Functionalα7,α4β2, andα3β4 subunits of the nAChR appear to be present on the DFA neurons. Activations of these receptors increase the CCA blood flow. The present findings do not preclude the presence of other nAChRs subunits. Muscarinic receptors, if any, on the DFA are not involved in regulation of the CCA blood flow. Various subtypes of nAChRs in the DFA may mediate regulation of the CCA and cerebral blood flows.British Journal of Pharmacology(2006)149, 206–214; doi:10.1038/sj.bjp.0706844
Mutations within the selectivity filter of the NMDA receptor‐channel influence voltage dependent block by 5‐hydroxytryptamine
Authors: Kloda A , Adams D J 
Published: August 2006

Background and purpose:Voltage‐dependent block by Mg2+is a cardinal feature of NMDA receptors which acts as a coincidence detector to prevent the receptor from over‐activation. Inhibition of NMDA receptor currents by 5‐hydroxytryptamine (5‐HT) indicated that 5‐HT, similar to Mg2+, binds within the membrane electric field. In the present study, we assessed whether point mutations of critical asparagine residues located within the selectivity filter of NR1 and NR2A subunits of NMDA receptor‐channel affect voltage‐dependent block by 5‐HT.Experimental approach:The mode of action of 5‐HT and Mg2+on wild‐type and mutated NMDA receptor‐channels expressed inXenopusoocytes was investigated using the two‐electrode voltage clamp recording technique.Key results:The mutation within the NR1 subunit NR1(N0S or N0Q) strongly reduced the voltage dependent block by 5‐HT and increased the IC50. The corresponding mutations within the NR2 subunits NR2A(N0Q or N+1Q) reduced the block by 5‐HT to a lesser extent. This is in contrast to the block produced by external Mg2+where a substitution at the NR2A(N0) and NR2A(N+1) sites but not at the NR1(N0) site significantly reduced Mg2+block.Conclusion and implications:The block of NMDA receptor‐channels by 5‐HT depends on the NR1‐subunit asparagine residue and to a lesser extent on the NR2A‐subunit asparagine residues. These data suggest that the interaction of 5‐HT with functionally important residues in a narrow constriction of the pore of the NMDA receptor‐channel provides a significant barrier to ionic fluxes through the open channel due to energetic factors governed by chemical properties of the binding site and the electric field.British Journal of Pharmacology(2006)149, 163–169. doi:10.1038/sj.bjp.0706849
Muscarinic receptor‐activated cationic channels in murine ileal myocytes
Authors: Dresviannikov A V , Bolton T B , Zholos A V 
Published: August 2006

Background and purpose:There is little information about the excitatory cholinergic mechanisms of mouse small intestine although this model is important for gene knock‐out studies.Experimental approach:Using patch‐clamp techniques, voltage‐dependent and pharmacological properties of carbachol‐ or intracellular GTPγS‐activated cationic channels in mouse ileal myocytes were investigated.Key results:Three types of cation channels were identified in outside‐out patches (17, 70 and 140 pS). The voltage‐dependent behaviour of the 70 pS channel, which was also the most abundantly expressed channel (∼0.35 μ−2) was most consistent with the properties of the whole‐cell muscarinic current (half‐maximal activation at −72.3±9.3 mV, slope of −9.1±7.4 mV and mean open probability of 0.16±0.01 at −40 mV; at near maximal activation by 50 μMcarbachol). Both channel conductance and open probability depended on the permeant cation in the order: Cs+(70 pS) >Rb+(66pS) >Na+(47 pS) >Li+(30 pS). External application of divalent cations, quinine, SK&F 96365 or La3+strongly inhibited the whole‐cell current. At the single channel level the nature of the inhibitory effects appeared to be very different. Either reduction of the open probability (quinine and to some extent SK&F 96365 and La3+) or of unitary current amplitude (Ca2+, Mg2+, SK&F 96365, La3+) was observed implying significant differences in the dissociation rates of the blockers.Conclusions and implications:The muscarinic cation current of murine small intestine is very similar to that in guinea‐pig myocytes and murine genetic manipulation should yield important information about muscarinic receptor transduction mechanisms.British Journal of Pharmacology(2006)149, 179–187. doi:10.1038/sj.bjp.0706852
The effects of cardamonin on lipopolysaccharide‐induced inflammatory protein production and MAP kinase and NFκB signalling pathways in monocytes/macrophages
Authors: Hatziieremia S , Gray A I , Ferro V A , Paul A , Plevin R 
Published: August 2006

Background and purpose:In this study we examined the effect of the natural product cardamonin, upon lipopolysaccharide (LPS)‐induced inflammatory gene expression in order to attempt to pinpoint the mechanism of action.Experimental approaches:Cardamonin was isolated from the Greek plantA. absinthiumL. Its effects were assessed on LPS‐induced nitrite release and iNOS and COX‐2 protein expression in two macrophage cell lines. Western blotting was used to investigate its effects on phosphorylation of the mitogen activated protein (MAP) kinases, ERK, JNK and p38 MAP kinase, and activation of the NFκB pathway, at the level of IκBαdegradation and phosphorylation of NFκB. Also its effects on NFκB and GAS/GAF‐DNA binding were assessed by EMSA.Key results:Cardamonin concentration‐dependently inhibited both NO release and iNOS expression but had no effect on COX‐2 expression. It did not affect phosphorylation of the MAP kinases, degradation of IκBαor phosphorylation of NFκB. However, it inhibited NFκB DNA‐binding in both LPS‐stimulated cells and nuclear extracts of the cells (in vitro). It also inhibited IFNγ‐stimulated iNOS induction and GAS/GAF‐DNA binding.Conclusions and Implications:These results show that the inhibitory effect of cardamonin on LPS‐induced iNOS induction is not mediated via effects on the initial activation of the NFκB or MAP kinase pathways but is due to a direct effect on transcription factor binding to DNA. However, although some selectivity in cardamonin's action is implicated by its inability to affect COX‐2 expression, its exact mechanism(s) of action has yet to be identified.British Journal of Pharmacology(2006)149, 188–198. doi:10.1038/sj.bjp.0706856