Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07.

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR+PR+SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

The development of a stable oral solution of captopril for paediatric patients

Study objectives: Many major drugs are not available in paediatric form. The aim of this study was to develop a stable liquid solution of captopril for oral paediatric use allowing individualised dosage and easy administration to newborn and young patients. Methods: A specific HPLC-UV method was developed. In a pilot study, a number of formulations described in the literature as affording one-month stability were examined. In the proper long-term study, the formulation that gave the best results was then prepared in large batches and its stability monitored for two years at 5°C and room temperature, and for one year at 40°C. Results: Most formulations described in the literature were found wanting in our pilot study. A simple solution of the drug (1 mg/mL) in purified water (European Pharmacopeia) containing 0.1% disodium edetate (EDTA-Na) as preservative proved chemically and microbiologically stable at 5°C and room temperature for two years. Conclusion: The proposed in-house formulation fulfils stringent criteria of purity and stability and is fully acceptable for oral administration to newborn and young patients.

Characterization of CD4+ CD25+ T cells in solid organ transplant recipients

Although important progresses have been achieved in the therapeutic management of transplant recipients, acute and chronic rejections remain the leading causes of premature graft loss after solid organ transplantation. This, together with the undesirable side effects of immunosuppressive drugs, has significant implications for the long-term outcome of transplant recipients. Thus, a better understanding of the immunological events occurring after transplantation is essential. The immune system plays an ambivalent role in the outcome of a graft. On one hand, some T lymphocytes with effector functions (called alloreactive) can mediate a cascade of events eventually resulting in the rejection, either acute or chronic, of the grafted organ ; on the other hand, a small subset of T lymphocytes, called regulatory T cells, has been shown to be implicated in the control of these harmful rejection responses, among other things. Thus, we focused our interest on the study of the balance between circulating effectors (alloreactive) and regulatory T lymphocytes, which seems to play an important role in the outcome of allografts, in the context of kidney transplantation. The results were correlated with various variables such as the clinical status of the patients, the immunosuppressive drugs used as induction or maintenance agents, and past or current episodes of rejection. We observed that the percentage of the alloreactive T lymphocyte population was correlated with the clinical status of the kidney transplant recipients. Indeed, the highest percentage was found in patients suffering from chronic humoral rejection, whilst patients on no or only minimal immunosuppressive treatment or on sirolimus-based immunosuppression displayed a percentage comparable to healthy non-transplanted individuals. During the first year after renal transplantation, the balance between effectors and regulatory T lymphocytes was tipped towards the detrimental effector immune response, with the two induction agents studied (thymoglobulin and basiliximab). Overall, these results indicate that monitoring these immunological parameters may be very useful for the clinical follow-up of transplant recipients ; these tests may contribute to identify patients who are more likely to develop rejection or, on the contrary, who tolerate well their graft, in order to adapt the immunosuppressive treatment on an individual basis.

Use of NIR spectroscopy and multivariate process spectra calibration methodology for pharmaceutical solid samples analysis

Accomplish high quality of final products in pharmaceutical industry is a challenge that requires the control and supervision of all the manufacturing steps. This request created the necessity of developing fast and accurate analytical methods. Near infrared spectroscopy together with chemometrics, fulfill this growing demand. The high speed providing relevant information and the versatility of its application to different types of samples lead these combined techniques as one of the most appropriated. This study is focused on the development of a calibration model able to determine amounts of API from industrial granulates using NIR, chemometrics and process spectra methodology.

Simple and fast methods based on solid-phase extraction coupled to liquid chromatography with UV detection for the monitoring of caffeine in natural and waste waters as marker of anthropogenic impact

Two concentration methods for fast and routine determination of caffeine (using HPLC-UV detection) in surface, and wastewater are evaluated. Both methods are based on solid-phase extraction (SPE) concentration with octadecyl silica sorbents. A common “offline” SPE procedure shows that quantitative recovery of caffeine is obtained with 2 mL of an elution mixture solvent methanol-water containing at least 60% methanol. The method detection limit is 0.1 μg L−1 when percolating 1 L samples through the cartridge. The development of an “online” SPE method based on a mini-SPE column, containing 100 mg of the same sorbent, directly connected to the HPLC system allows the method detection limit to be decreased to 10 ng L−1 with a sample volume of 100 mL. The “offline” SPE method is applied to the analysis of caffeine in wastewater samples, whereas the “on-line” method is used for analysis in natural waters from streams receiving significant water intakes from local wastewater treatment plants

Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.

OBJECTIVE: To validate a revision of the Mini Nutritional Assessment short-form (MNA(R)-SF) against the full MNA, a standard tool for nutritional evaluation. METHODS: A literature search identified studies that used the MNA for nutritional screening in geriatric patients. The contacted authors submitted original datasets that were merged into a single database. Various combinations of the questions on the current MNA-SF were tested using this database through combination analysis and ROC based derivation of classification thresholds. RESULTS: Twenty-seven datasets (n=6257 participants) were initially processed from which twelve were used in the current analysis on a sample of 2032 study participants (mean age 82.3y) with complete information on all MNA items. The original MNA-SF was a combination of six questions from the full MNA. A revised MNA-SF included calf circumference (CC) substituted for BMI performed equally well. A revised three-category scoring classification for this revised MNA-SF, using BMI and/or CC, had good sensitivity compared to the full MNA. CONCLUSION: The newly revised MNA-SF is a valid nutritional screening tool applicable to geriatric health care professionals with the option of using CC when BMI cannot be calculated. This revised MNA-SF increases the applicability of this rapid screening tool in clinical practice through the inclusion of a "malnourished" category.

Slip-Form Paving as Developed and Pioneered in Iowa,1961.

Summarizes Iowa's 14 years of experience in pioneering and developing slip-form paving methods

Recueil de pièces relatives au prieuré de Dhuisy, diocèse de Meaux, formé par Charles de Chantecler, prieur et seigneur de Dhnisy, pour les besoins de son procès contre Henri de Bourbon, prince de Condé, en 1573.

L'acte de fondation de ce prieuré (fol. 17) porte la date de 1170. — Ce ms. a appartenu à « l'abbé de Sencour, chanoine de Rouen. »

Recueil de pièces, manuscrites et imprimées, formé par le président Achille III DE HARLAY, relatives principalement à l'histoire religieuse, politique, administrative, diplomatique et littéraire des XVIe et XVIIe siècles. VIII.

Contient : Lettre d'Innocent XI ; « Observations sur l'Histoire du luthérianisme du P. Maimbourg » ; Extraits des Registres capitulaires de l'Église de Paris, 1654 ; Copies de pièces du XIIIe et du XIVe siècles relatives à différentes affaires ecclésiastiques ; Copie d'une lettre à Baluze sur un manuscrit chaldéen reçu du Levant par Colbert ; Sur la « Conférence de Cartage » ; Fragment orig . d'Ismaël Boulliau sur l'échéance du jour de Pâques ; « Observations sur un Traité de l'Usure fait par M. Poncet » ; « Oraison funèbre de M. de Candale par M. l'abbé Roquette, depuis évêque d'Autun » ; « Éclaircissement par M. Bernier sur le livre de Monsr de La Ville » pour la défense d'opinions de Descartes ; Mémoire pour la liberté de la Faculté de théologie de Paris ; Extraits impr. des Registres capitulaires de l'Église de Paris ; Sur la Visitation d'Angers ; Mémoires de procédure impr. relatifs à la Sainte-Chapelle ; Recueil de pièces mss et impr., bulles pontificales, lettres royales, etc., relatives à la Régale, 1198-1681 ; Établissement d'une Chambre royale à Metz, et extraits des Registres de cette Chambre royale, impr ; Lettre orig. de D. Godefroy, 1680 ; Pièces relatives à la principauté de Charleville ; Entrée de la reine de Suède Ulrique-Éléonore à Stockholm, 1680 ; Pièces impr. relatives à l'Hôpital général de Paris ; Ordonnances impr. du magistrat d'Amsterdam portant interdiction des carrosses dans ladite ville, en hollandais

Recueil de pièces, manuscrites et imprimées, formé par le président Achille III DE HARLAY, relatives principalement à l'histoire religieuse, politique, administrative, diplomatique et littéraire des XVIe et XVIIe siècles. XXXI.

Contient : Pièces sur les Jésuites (f. 1), — sur les Frères Prêcheurs, impr. (f. 34), — sur la Sorbonne (f. 48) ; Pièces sur Descartes ; Extrait des Registres du Conseil d'État relatif à l'acquisition, pour la Bibliothèque du roi, d'une partie de la bibliothèque de Mazarin, 1668 ; « Epistola » R. Rapini, S. J., « ad... Cl. Pelterium », impr., 1684, in-8° ; Extraits de Registres du Parlement ; « Procédures faites... contre Antoine, comte de Shaftsbury », 1681 ; Sur la « Prévention » en Anjou ; Factums divers impr., affaire Bruant des Carrières ; Pièces relatives à la Compagnie des Indes orientales ; Factums impr., affaire Marcara Avachins ; Pièces relatives au commerce : « Avis sur le fait des ardoises », impr., 1683, in-4° ; Notes sur « Les édits et règlements des libraires, imprimeurs, relieurs et doreurs » ; Note sur le commerce des harengs

Can smaller-scale comprehensive cancer centers provide outstanding care in abdominal and thoracic pediatric solid tumor surgery? Results of a 14-year retrospective single-center analysis.

PURPOSE: Quality of care and its measurement represent a considerable challenge for pediatric smaller-scale comprehensive cancer centers (pSSCC) providing surgical oncology services. It remains unclear whether center size and/or yearly case-flow numbers influence the quality of care, and therefore impact outcomes for this population of patients. PATIENTS AND METHODS: We performed a 14-year, retrospective, single-center analysis, assessing adherence to treatment protocols and surgical adverse events as quality indicators in abdominal and thoracic pediatric solid tumor surgery. RESULTS: Forty-eight patients, enrolled in a research-associated treatment protocol, underwent 51 cancer-oriented surgical procedures. All the protocols contain precise technical criteria, indications, and instructions for tumor surgery. Overall, compliance with such items was very high, with 997/1,035 items (95 %) meeting protocol requirements. There was no surgical mortality. Twenty-one patients (43 %) had one or more complications, for a total of 34 complications (66 % of procedures). Overall, 85 % of complications were grade 1 or 2 according to Clavien-Dindo classification requiring observation or minor medical treatment. Case-sample and outcome/effectiveness data were comparable to published series. Overall, our data suggest that even with the modest caseload of a pSSCC within a Swiss tertiary academic hospital, compliance with international standards can be very high, and the incidence of adverse events can be kept minimal. CONCLUSION: Open and objective data sharing, and discussion between pSSCCs, will ultimately benefit our patient populations. Our study is an initial step towards the enhancement of critical self-review and quality-of-care measurements in this setting.

Recueil, formé de 1573 à 1578, d'extraits (généalogies, chartes, épitaphes, etc.) concernant l'histoire des familles de Lorraine, attribué à Nicolas Bousmard, chanoine de l'église de Verdun (d'après D. Calmet, Bibl. lorr., 165).

Contient : Épitaphes des Cordeliers de Neufchâteau ; Épitaphes de Bayon ; Épitaphes de l'abbaye de Beaupré ; Épitaphes de Magnières ; Épitaphes des Cordeliers de Mirecourt ; Épitaphes des Carmes de Besançon ; Épitaphes des Cordeliers de Besançon ; Épitaphes de Bourbonne ; Épitaphes de l'abbaye de Morimond ; Épitaphes de Beaufrémont ; Épitaphes de Remennecourt ; Copie abrégée de l'épitomé de Jean Daucy ; Extrait du Trésor de l'évêché de Verdun