Planned neck dissection before combined chemoradiation for pyriform sinus carcinoma.

CONCLUSIONS: A pretreatment neck dissection in a chemoradiation regimen for pyriform sinus carcinoma provides no delay for radiation, low complication rates, optimal radiation doses and a high nodal disease control. OBJECTIVES: The aims of this study were to evaluate the clinical feasibility, therapeutic consequences and neck nodes control of a pretreatment neck dissection in a chemoradiation regimen for organ preservation strategy for pyriform sinus carcinoma. PATIENTS AND METHODS: Seventy-six patients with untreated stage III and IV squamous cell carcinoma of the pyriform sinus were included in this study. Eighty neck dissections were performed according to the N status. Dose of radiotherapy was delivered according to the pathologic finding of neck dissections. RESULTS: The mean time between neck dissection and the chemoradiation was 24 days (+/-12 days). Only two patients (2.5%) experienced wound complications. A 'boost' radiation of 14 Gy was delivered after 49 neck dissections (61%) in patients with extracapsular spread. The rate of disease control within the regional nodes was 90%. The Kaplan-Meier 1- and 2- year overall survival rates were 78% and 43%, respectively, and specific survival rates were 88% and 67%, respectively.

Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study.

AIM: Adequate patient sedation is mandatory for most interventional endoscopic procedures. Recent anaesthesiologic studies indicates that propofol and midazolam act synergistically in combination and therefore may be superior to sedation with propofol alone in terms of sedation efficacy, recovery and costs (due to a presumed lower total dose of propofol needed). METHODS: A total of 239 consecutive patients undergoing therapeutic EGD or ERCP (EGD/ERCP-ratio, 1:1) randomly received either propofol alone (n=120, group A, loading dose 40-60 mg intravenously, followed by repeated doses of 20 mg) or propofol plus midazolam (n=119, group B, initial midazolam dose of 2. 5-3.5 mg intravenously, followed by repeated doses of 20 mg of propofol) for sedation. Vital signs (heart rate, blood pressure, oxygen saturation, electrocardiogram) were continuously monitored. Procedure-related parameters, the recovery time and quality (post-anaesthesia recovery score) as well as the patient's co-operation and tolerance to the procedure (visual analogue scale) were prospectively assessed. RESULTS: Patients of group A and B were well matched with respect to demographic and clinical data, endoscopic findings, and the type of associated procedures. In group A, a mean dose of 0.25 +/- 0.13 mg.min/kg propofol was used compared to 0.20 +/- 0.09 mg.min/kg of propofol in group B (P < 0.01, plus additional 2.9 +/- 0.5 mg of midazolam). Clinically relevant changes in vital signs were observed at comparable frequencies with a lowering of the systolic blood pressure < 90 mmHg in six out of 119 patients in group B and one out of 120 patients in group A (P=0.07). The sedation efficacy was rated similarly in both groups, whereas the mean recovery time (group A, 19 +/- 7 min vs. group B, 25 +/- 8 min, P < 0.05) as well as the recovery score (post-anaesthesia recovery score group A, 8.0 +/- 1.1 vs. post-anaesthesia recovery score group B, 7.3 +/- 1.2, P < 0.001) were significantly better with propofol alone than with propofol plus midazolam. CONCLUSION: During therapeutic endoscopy, sedation with propofol and midazolam requires a lower total dose of propofol, but otherwise has no superior sedation efficacy and is associated with a slower post-procedure recovery than sedation with propofol alone.

Endoscopic injection of botulinum toxin in patients with recurrent acute pancreatitis due to pancreatic sphincter of Oddi dysfunction.

AIM: To evaluate the technical feasibility, safety, and short-term efficacy of botulinum toxin injection for pancreatic sphincter of Oddi dysfunction and to analyse whether the symptomatic response to botulinum toxin might be a predictor of outcome for endoscopic sphincterotomy. METHODS: Fifteen consecutive patients (nine female, aged 38 +/- 12 years) with frequent attacks (median four) of acute pancreatitis within 6 months, and manometrically proven pancreatic sphincter of Oddi dysfunction underwent endoscopic injection of 100 units of botulinum toxin into the major papilla. All patients underwent prospective follow-up thereafter and in cases of recurrent pancreatitis manometry this was repeated and pancreatic sphincterotomy was performed. RESULTS: No side-effects occurred after botulinum toxin injection in any patient. Within 3 months after botulinum toxin treatment, 12 out of 15 patients remained asymptomatic (80% primary response). Only one out of three patients without symptomatic benefit showed continued elevated pancreatic sphincter pressure at manometry and only this patient benefited from pancreatic sphincterotomy later on. Eleven of the 12 patients initially responding to botulinum toxin injection developed a symptomatic relapse 6 +/- 2 months after botulinum toxin treatment. These patients then achieved long-term clinical remission from pancreatic or combined (biliary and pancreatic, n=5) sphincterotomy (median follow-up, 15 months). CONCLUSION: Endoscopic botulinum toxin injection into the papilla of Vater is a safe procedure for treatment of pancreatic sphincter of Oddi dysfunction that may provide short-term relief in about 80% of the patients. Those patients who respond to botulinum toxin may subsequently gain definitive cure from sphincterotomy.

Visible chemiluminescence associated with the reaction between methemoglobin or oxyhemoglobin with hydrogen peroxide.

Visible chemiluminescence is emitted in the irreversible deactivation of hemoglobin or methemoglobin with excess H2O2. The emission takes place in two phases. The most intense one lasts a few seconds and is followed by a second phase of lower intensity that remains for longer periods. This second phase presents chaotic or sustained oscillations. Free radicals are implicated in the luminescent process since the emission can be reduced by free radical scavengers such as 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) or ascorbic acid. These additives lead to a delay in reaching the maximum intensity, which can be related to their consumption, implying substantial recycling of the hemoprotein. Chemiluminescence is also observed in the oxidation of hemin by H2O2, suggesting a role for the heme group in the processes leading to the excited state production. The lower intensity observed in the presence of hemin can be related to the contribution of the globin chains.

Dynamics of tryptophan binding to Escherichia coli Trp repressor wild type and AV77 mutant: an NMR study.

Binding of L-tryptophan to Escherichia coli trp repressor wild type (WT) and AV77 mutant was studied by 1H NMR spectroscopy. Ligand binding to the proteins resulted in changes in line widths and chemical shifts of ligand resonances, but no changes in the coupling constant were observed. Line width and chemical shift changes of the H4 L-tryptophan proton were monitored as a function of temperature and ligand and protein concentrations. For the WT repressor, the H4 proton displays slow exchange at low temperatures (20-35 degrees C), while fast exchange occurs in the range from 45 to 65 degrees C. From 35 to 40 degrees C, the range of intermediate exchange, lines are broadened beyond detection. For the AV77 mutant, the intermediate and fast exchange regions are shifted at least 5 degrees C to higher temperatures. Line shapes of L-tryptophan H4 proton resonances were simulated using a general expression based on McConnell's modified Bloch equations for a two-site exchange. From the simulations, an exchange frequency (upsilon exch) of about 3000 Hz was obtained at 45 degrees C for WT and about 1000 Hz for AV77 mutant. The activation energy for the process is 32.7 kcal K-1 mol-1 for the WT and 29.1 kcal K-1 mol-1 for AV77. At 45 degrees C, the dissociation and association rate constants (k-1 and K+1, respectively) were calculated to be 2.0 x 10(3) s-1 and 9.9 x 10(6) M-1 s-1, for the WT.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemin-induced lipid membrane disorder and increased permeability: a molecular model for the mechanism of cell lysis.

The interaction between hemin and lipid bilayers was examined from the point of view of: (a) changes in membrane permeability, (b) changes in lipid organization, (c) catalysis of lipid peroxidation. The leakage of solutes trapped in inner aqueous compartments of vesicles and liposomes increased in a concentration-dependent manner, in the range of 100-1000 microM, saturating at ca. 400 microM hemin. Under saturating conditions, leakage was essentially complete after ca. 0.5 h. Antioxidants had practically no effect upon this behavior. Extensive leakage at 5 and 10 microM hemin was observed only in the absence of antioxidants and after ca. 10 h. Electron spin resonance spectra of a spin label incorporated in oriented lipid multibilayers indicated that hemin decreased the degree of order of the bilayer. The effect was instantaneous, time-independent, and unaffected by antioxidants, displaying a concentration dependence similar to that of the permeability studies. In contrast, hemin-catalyzed lipid peroxidation displayed a bell-shaped dependence on hemin concentration, the effect ceasing at concentrations lower than those required for instantaneous permeability and structural changes. The bell-shaped behavior was found both for the detection of thiobarbituric acid-reactive compounds (TBARS) and for oxygen consumption. The time scale of TBARS formation was much slower than that for permeability changes, significant amounts of products being detected only after leakage was essentially complete. Both permeability and lipid peroxidation occurred to a larger extent in cholesterol-containing membranes. Hemin is highly aggregated in aqueous phase. Upon binding to the membrane, the aggregates undergo dissociation in a hemin/lipid ratio-dependent manner. At low ratios, hemin is largely monomeric, while at high ratios, aggregates prevail. Monomers are more effective in promoting oxidation. Aggregates are responsible for the enhancement of permeability and membrane disorder. Oxidation of membrane components is often proposed to be involved in the mechanism of hemin-promoted cell lysis. Nevertheless, the role of oxidative processes is not clear in some hemoglobinopathies. The present results provide a molecular model for an alternative mechanism of lysis that would dominate in cases where the concentration is high enough for hemin to aggregate.