Ozonized 2-hydroxypropyl-ß-cyclodextrins as novel materials with oxidative and bactericidal properties.

Ozonized (2-Hydroxypropyl)-ß-cyclodextrins (Oz-HPbCDs) were produced by direct gas/solid reaction between gaseous ozone (O3) and solid HPbCD. The solid materials obtained were first characterized using physical and chemical methods and compared to the initial HPbCD. The main process parameters of the synthesis were studied independently to assess their effect on the oxidizing power of Oz-HPbCDs. The ability of the Oz-HPbCDs to retain their oxidative properties over time was evaluated, at different storage temperatures, for a period of at least two months. Lastly, aqueous solutions of HPbCD and Oz-HPbCD at different concentrations were contacted with bacterial strains of Escherichia coli and Streptococcus uberis to see whether these materials might have bactericidal properties. Since normal bacterial growth was noted with HPbCD, the antimicrobial efficiency of Oz-HPbCDs was clearly demonstrated on these two types of bacteria.

Novel Hydroquinone-Alumina Composites Stabilizing a Guest-Free Clathrate Structure: Applications in Gas Processing.

Organic clathrates formed by hydroquinone (HQ) and gases such as CO2 and CH4 are solid supramolecular host-guest compounds in which the gaseous guest molecules are encaged in a host framework of HQ molecules. Not only are these inclusion compounds fascinating scientific curiosities but they can also be used in practical applications such as gas separation. However, the development and future use of clathrate-based processes will largely depend on the effectiveness of the reactive materials used. These materials should enable fast and selective enclathration and have a large gas storage capacity. This article discusses the properties and performance of a new composite material able to form gas clathrates with hydroquinone (HQ) deposited on alumina particles. Apart from the general characterization of the HQ-alumina composite, one of the most remarkable observations is the unexpected formation of a guest-free clathrate structure with long-term stability (>2 years) inside the composite. Interestingly enough, in addition to a slight improvement in the enclathration kinetics of pure CO2 compared to powdered HQ, preferential capture of CO2 molecules is observed when the HQ-alumina composite is exposed to an equimolar CO2/CH4 gas mixture. In terms of gas capture selectivity toward CO2, the performance of this new composite exceeds that of pure HQ and HQ-silica composites developed in a previous study, opening up new opportunities for the design and use of these novel materials for gas separation.

New Insights on Gas Hydroquinone Clathrates Using in Situ Raman Spectroscopy: Formation/Dissociation Mechanisms, Kinetics, and Capture Selectivity.

Hydroquinone (HQ) is known to form organic clathrates with different gaseous species over a wide range of pressures and temperatures. However, the enclathration reaction involving HQ is not fully understood. This work offers new elements of understanding HQ clathrate formation and dissociation mechanisms. The kinetics and selectivity of the enclathration reaction were also investigated. The focus was placed on HQ clathrates formed with CO2 and CH4 as guest molecules for potential use in practical applications for the separation of a CO2/CH4 gas mixture. The structural transition from the native form (α-HQ) to the clathrate form (ß-HQ), as well as the reverse process, were tracked using in situ Raman spectroscopy. The clathrate formation was conducted at 323 K and 3.0 MPa, and the dissociation was conducted at 343 K and 1.0 kPa. The experiments with CH4 confirmed that a small amount of gas can fill the α-HQ before the phase transition from α- to ß-HQ begins. The dissociation of the CO2-HQ clathrates highlighted the presence of a clathrate structure with no guest molecules. We can therefore conclude that HQ clathrate formation and dissociation are two-step reactions that pass through two distinct reaction intermediates: guest-loaded α-HQ and guest-free ß-HQ. When an equimolar CO2/CH4 gas mixture is put in contact with either the α-HQ or the guest-free ß-HQ, the CO2 is preferentially captured. Moreover, the guest-free ß-HQ can retain the CO2 quicker and more selectively.

DFT calculation of the potential energy landscape topology and Raman spectra of type I CH4 and CO2 hydrates.

CO2 and CH4 clathrate hydrates of type I were studied by means of DFT and QTAIM, in order to better understand their properties at the molecular level. Sub-cells of type I hydrates were modeled as independent rigid cages, both empty and containing guest molecules. Interaction potentials of guest molecules inside each cage, and moving from a cell to the adjacent one, were calculated using the DFT approximation B3LYP/6-311+g(d,p), considering the cases with and without long range Coulombic corrections. The selected theory level was validated by comparison of the simulated Raman spectra with the experimental ones, for the case of type I lattice at full occupation of CO2 and CH4, respectively. For this comparison, Fermi resonances of CO2 were taken into account by transforming experimental bands to the corresponding theoretical non-mixed states. On the one hand, our results confirm the validity of the theory level selected for the model. We have shown the high anisotropy of the guest-cell interaction potential of the molecules analyzed, which has implications in the formulation and use of equations of state, and in the study of transport properties as well. On the other hand, our results suggest that the concentration of guest species inside type I hydrates could be computed from the comparison of experimental and predicted Raman spectra, although there are non-trivial experimental limitations to get over for that purpose.

Results and impact of routine assessment of comorbidity in elderly patients with non-small-cell lung cancer aged > 80 years.

BACKGROUND: Elderly patients now represent a bigger proportion of patients with non-small-cell lung cancer (NSCLC). However, data from clinical trials are limited for this age group, and the elderly are often excluded from optimal treatment for several reasons, including comorbidity. PATIENTS AND METHODS: We reviewed a 10-year experience on proven patients with NSCLC aged > 80 years; comorbidity was assessed using the Charlson Comorbidity index (CCI). The main objective was the impact of comorbidity on survival outcome. RESULTS: Of 109 managed patients aged > 80 years, 74 patients had a proven diagnosis of NSCLC. Performance status was < 2 in 58 patients and TNM classification of malignant tumors was I-II, IIIA-IIIB, and IV in 18, 27, and 29 patients, respectively. Comorbidity was present for 49 patients. Charlson Comorbidity Index ranged from 4 to 12 with 31 patients having a CCI >or= 6. Sixteen patients received supportive care only, whereas 23 patients were operated on, 12 received radiation therapy, and 23 had chemotherapy. Eight grade 3/4 toxicities were reported (3 patients discontinued treatment). Multivariate analysis demonstrated a significant increase in the risk of death for patients with a poor Eastern Cooperative Oncology Group performance status (hazard ratio, 2.64; 95% confidence interval, 1.3-5.36; P = 0.007) and an advanced TNM stage (hazard ratio, 3.31; 95% confidence interval, 1.99-5.5; P < 0.00001). Although statistic significance was not reached, a difference in overall survival was shown between patients with a CCI < 6 and CCI >or= 6 (12.2 months vs. 8.2 months; P = 0.08). CONCLUSION: These results support a role for the CCI as a routine means to assess comorbidity, because patients with fewer comorbidities tolerate and derive survival benefit of optimal NSCLC management. These findings must be confirmed in prospective studies.

Comparative prognostic features of stage IIIAN2 and IIIB non-small-cell lung cancer patients treated with surgery after induction therapy.

OBJECTIVE: Induction Therapy (IT) before surgery emerged as a widely used strategy for IIIAN2 and selected IIIB NSCLC patients. However, IT is associated with a possible increase in postoperative complications. Consequently, selection of patients with the best chances to benefit from combined treatment is mandatory. METHODS: Study recorded demographics, treatment and outcome of consecutive patients treated with IT plus surgery for IIIAN2 or IIIB NSCLC. Survival was analysed by Kaplan-Meier and prognostic factors were analysed by log-rank and Cox regression. RESULTS: From 1993 to 2003, 155 patients (IIIAN2=95/IIIB=60) were treated. Complete resection was associated with a significant prolonged median survival both for IIIAN2 (20 vs 16 months, P=0.05) and IIIB (20 vs 15 months, P=0.02) patients. A lower risk of death for IIIAN2 patients was independently associated with postoperative mediastinal lymph node clearance (HR=0.45, 95%CI [0.25-0.81], P=0.009) and absence of postoperative complication (HR=0.54, 95%CI [0.31-0.93], P=0.02). Absence of blood vessel invasion only was identified as an independent predictor of a lower risk of death (HR=0.27, 95%CI [0.12-0.59], P=0.01) for stage IIIB patients. CONCLUSIONS: Besides similarities as the role of a complete R0 resection, treatment-related factors influence outcome of IIIAN2 patients while disease-related factors prevail on survival of IIIB patients, in whom the benefit of IT is unclear.

Efficiency of hepatitis C virus screening strategies in general practice.

UNLABELLED: Hepatitis C viral infection (HCV) is a frequent and severe disease; screening strategies to-date remain insufficient. OBJECTIVE: To assess the efficiency of HCV screening of high-risk groups among patients consulting general practitioners. METHODS: A cost-effectiveness analysis was performed involving general medicine screening practices recorded during a survey of 127 practitioners (10,041 patients) conducted in 1997. A reference strategy, defined as HCV screening for illicit drug users and transfused patients, and five extended strategies, where the screening population was broadened to include other risk groups as well, were considered. Average cost and marginal cost-effectiveness ratios were determined for each extended strategy and compared with those observed for the reference strategy. The sensitivity of HCV screening to funding modalities, HCV seroprevalence and proportion of HCV high-risk groups among patients attending general practitioners was studied. RESULTS: The reference strategy was the most cost-effective method irrespective of the funding modality considered. Fixed practitioner payment was the least efficient funding modality. The average cost of one positive test was sensitive to variations of HCV seroprevalence in the high-risk group as well as the proportion of high-risk patients among the general practitioners' patients. CONCLUSION: Extension of hepatitis C screening to risk groups other than transfused patients and illicit drug users implies a substantial increase in healthcare costs as well as social consensus for such expenditures.

Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer.

OBJECTIVE: To assess the value of Cyfra 21-1, carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) combined, all three together as prognostic factors in advanced stage non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Serum samples from untreated NSCLC patients were prospectively collected. All assays were performed using commercial kits blind to clinical information. Serum levels of CEA, NSE and Cyfra 21-1 higher than 10, 13 and 3.5 ng/ml, respectively, were considered as elevated. RESULTS: 264 patients (men, 87%), with Performans Status (PS) of 0/1 in 80% and stage IV disease in 65% were studied. Cyfra 21-1, CEA and NSE were elevated in 52.5%, 41.8% and 33.2% of patients, respectively. Median survival was 9 months (range, 1-77). Cyfra 21-1, age, PS, stage as well as the combination of the three markers together correlated with prognosis in univariate analysis. Multivariate analysis demonstrated that age > or = 65 years (HR = 1.3 [1.02-1.70], p = 0.03), PS 2 (HR = 4.3 [3.13-6.11], p < 0.0001), Cyfra 21-1 > or = 3.5 ng/ml (HR = 1.3 [1.06-1.78], p = 0.01) and the combination of the three markers (HR = 1.06 [1.009-1.13], p = 0.02) remained prognostic determinants. CONCLUSION: Combining Cyfra 21-1, NSE and CEA correlated with prognosis in a significant and independent manner.

Vascular stenting for palliation of superior vena cava obstruction in non-small-cell lung cancer patients: a future 'standard' procedure?

BACKGROUND: Stenting is a relatively new option in the management of superior vena cava obstruction (SVCO), but available data often concern non-malignant and/or various malignant diseases. OBJECTIVE: The aim of this study was to assess the efficacy of vascular stenting as a first-choice treatment in SVCO in the exclusive setting of NSCLC. PATIENTS AND METHODS: Retrospective study of NSCLC patients with SVCO treated in the past year. Demographic data, disease characteristics, etiologic and palliative treatment (use of vascular stenting) were recorded as well as treatment outcome and survival. RESULTS: 17 patients were recruited. Eight had vascular stenting while 9 did not. Except for stenting, there was no difference between the two groups (median age 54 years; 80% men; 53% stage IIIB and 47% stage IV). Stenting (median length 60 mm) achieved complete resolution of SVCO more frequently (75 vs. 25%, p = 0.05) and faster (2 vs. 21 days, p = 0.002) without immediate or delayed complication. All patients with stents received anticoagulation therapy. Relapse rate after complete response (33 g, 50%, p = 0.6) was lower and time to relapse (6.5 g, 2 months) was longer for patients undergoing stenting, without reaching statistical significance. Median overall survival was not statistically different (8 and 5 months, p = 0.06). CONCLUSIONS: This study demonstrated the effectiveness of vascular stenting for SVCO in NSCLC patients. The high response rate, quick effect and safety of vascular stenting make this palliative treatment a candidate as a potential standard procedure. The results, however, must be confirmed in a prospective randomized trial including quality of life assessment.

Survival and postoperative complication in daily practice after neoadjuvant therapy in resectable stage IIIA-N2 non-small cell lung cancer.

Regarding persisting controversies about neoadjuvant treatment (NT), we studied the impact of neoadjuvant therapy in daily practice. Patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) resected after NT were eligible. Data on preoperative treatments, surgical procedure, postoperative complications and survival were collected. Overall, 71 (60 men, median age of 60 years) patients met inclusion criteria. All patients received a two-drug platinum-based regimen (median of 2.5 cycles [2-4 cycles]) and 15 (21%) had an associated radiotherapy (20-40 Gy). Nine complete and 27 partial responses were achieved. Surgical procedure principally was a lobectomy (44%), a left (15.5%) or a right (27%) pneumonectomy. Operative mortality was 4.2% while 21 patients (29%) experienced postoperative complications. Median survival was 17 months (95% CI, 13-21 months) with 3- and 5-year survival rates of 24 and 13%, respectively. Five-year survival was worse if postoperative complication occurred (18 versus 0%, p=0.09). Multivariate analysis showed male gender (RR=0.37, 95% CI, 0.16-0.81, p=0.013) and postoperative positive lymph node (RR=2.7, 95% CI, 1.4-5.2, p=0.002) to influence survival. In conclusion, achievement of a clinical and pathological response after NT for stage IIIA-N2 NSCLC patients enables a better survival. More efficient but also less toxic regimens of chemotherapy should be developed regarding its impact on long-term survival.