Influence of the drying processes of yeasts on their volatile phenol sorption capacity in model wine.

Volatile phenols, such as 4-ethylphenol, are responsible for a "horsey" smell in wine. Thus, the study of volatile phenol sorption in yeasts, and their subsequent elimination from wine, helps to optimize eco-friendly wine curative processes. Here, we compared the influences of spray drying, lyophilization and evaporative drying at low water activity on yeast, for improving the 4-ethylphenol sorption capacity in a synthetic model wine. The changes that occur in the physico-chemical characteristics of the yeast surface (surface hydrophobicity, electron-donor character and zeta potential) during these drying processes were determined to assess if any correlation exists between these factors and the 4-ethylphenol sorption capacities of the cells. Evaporative drying at low water activity, spray drying and lyophilization induced, respectively, 61.5%, 169% and 192% greater 4-ethylphenol sorption than biomass without drying treatment. Surface hydrophobicity of yeasts was also significantly greater, but the zeta potential of yeast cells was significantly lower after the drying processes. This is the first report investigating changes to the physico-chemical variables affected during yeast drying. These cell surface modifications were correlated with the 4-ethyphenol sorption value measured.

Yeast adapted to wine: nitrogen compounds released during induced autolysis in a model wine.

As important as the blend of base wines before bottling, one of the most important steps in the champagne-making process is the long ageing on lees. Two yeast strains of Saccharomyces cerevisiae MC001 and MC002, used in champagne wine production, were allowed to autolyse. After 8 days of autolysis, active dry yeasts adapted to wine released 1.7- to 1.8-fold more nitrogen compounds than nonadapted active dry yeast. The nitrogen content (total, proteins, peptides and amino) present in autolysates was measured for yeasts adapted to wine. The composition of free amino acids and amino acids constituting peptides showed no difference between the two strains of yeast used. Studies of intracellular proteolytic activity and release of peptides showed no correlation between these two phenomena. These results indicate that yeasts adapted to wine give results similar to those that occur in wine during ageing.

Aroma compound sorption by oak wood in a model wine.

Oak wood used for wine barrels was immersed into a model wine containing eight aroma compounds (e.g., aromatic and terpene alcohols, ethyl esters, and aldehyde), for which activity coefficients in water and model wine were determined using the mutual solubility measurement. A mass balance of these volatiles considering their reactivity in model wine was established. For most of the studied aroma compounds, and mainly for linalool and ethyl octanoate, a sorption behavior into wood was reported for the first time. This phenomenon was selective and could not be related to the solubilities in model wine and hydrophobicities of the studied aroma compounds, suggesting that acid-base and polar characteristics of wood were more involved in this sorption mechanism. This study has also shown that the level of sorption is a function of the ratio of wood surface area/solution volume.

Protease A activity and nitrogen fractions released during alcoholic fermentation and autolysis in enological conditions.

Determination of protease A activity during alcoholic fermentation of a synthetic must (pH 3.5 at 25 degrees C) and during autolysis showed that a sixfold induction of protease A activity occurred after sugar exhaustion, well before 100% cell death occurred. A decrease in protease A activity was observed when yeast cell autolysis started. Extracellular protease A activity was detected late in the autolysis process, which suggests that protease A is not easily released. Evolution of amino acids and peptides was determined during alcoholic fermentation and during autolysis. Amino acids were released in early stationary phase. These amino acids were subsequently assimilated during the fermentation. The same pattern was observed for peptides; this has never been reported previously. During autolysis, the concentration of amino acids and peptides increased to reach a maximum of 20 and 40 mg N l(-1), respectively. This study supports the idea that although protease A activity seemed to be responsible for peptides release, there is no clear correlation among protease A activity, cell death, and autolysis. The amino acid composition of the peptides showed some variations between peptides released during alcoholic fermentation and during autolysis. Depending on aging time on yeast lees, the nature of the peptides present in the medium changed, which could lead to different organoleptic properties.

Evaluation of cosmetic results of a randomized trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face.

Basal cell carcinoma is the most frequent cutaneous carcinoma, and it is characterized by its local spreading and an exceptional tendency to metastasize. Radical excision or destruction ensures the highest chance of cure. The most frequent site of this tumor is the face, where radical excision is limited by the proximity of essential anatomic structures. The main difficulty is to avoid mutilation and to provide good cosmetic results despite the vicinity of the eyes, the nose, and the mouth. Surgery and radiotherapy are known to provide similar chances of cure, but results concerning cosmetic sequelae are controversial, depending sometimes on the specialty of the physician in charge of the treatment. A randomized trial was performed at the Gustave-Roussy Institute to compare basal cell carcinomas of the face treated either by surgery or by radiotherapy. In summary, a significant advantage was observed in favor of surgery, as has been published elsewhere. Looking at the details of the cosmetic results, we analyzed the specific methodology of the cosmetic evaluation set up to eradicate the usual bias owing to subjective judgments. We looked also to the evolution of the cosmetic results with time. A panel of five judges performed repeated evaluations during the follow-up, and standardized photographs were taken at each visit and rated later by three nonmedical judges. In total, 174 patients were treated by surgery and 173 by radiotherapy; the choice of the treatment was allocated by randomization. Postoperative complications were higher in the radiotherapy group. The final cosmetic results after 4 years of follow-up were rated significantly better with surgery than with radiotherapy (good in 87 percent versus 69 percent according to the patient, 79 percent versus 40 percent according to the dermatologist, and respectively for each of the observers). Evolution of the ratings during the follow-up demonstrated an improvement of the cosmesis after surgery and stable or deteriorated results after radiotherapy. The same trend was observed regardless of the site of the tumor on the face, except for the nose, where the difference--still in favor of the surgery--was not significant. Concordance of all assessments in our study was the main guarantee of reliability of our methodology for cosmetic evaluation.

Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas.

PURPOSE: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. RESULTS: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). CONCLUSION: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).

Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

Quality assurance in brachytherapy: the role of the ICRU in achieving uniformity in dose and volume specification for reporting.

A quality assurance programme in brachytherapy implies a general consensus on the method of dose and volume specification for reporting. This in turn implies a consensus on certain definitions of terms and concepts. For several decades, the ICRU (International Commission on Radiation Units and Measurements) has been actively involved in an effort to reach a consensus between different brachytherapy centres worldwide, and to improve uniformity in reporting. The ICRU has prepared two reports containing recommendations for reporting brachytherapy treatments. The first, report #38 published in 1985, deals with intracavitary therapy in gynecology. The second deals with interstitial therapy, and is now in press. A summary of these two ICRU reports is presented here. Some definitions of terms and concepts are first recalled and discussed: Total Reference Air Kerma (TRAK), gross tumor volume (GTV), clinical target volume (CTV), treated volume, mean central dose, dose uniformity parameters, etc. Specific recommendations for reporting interstitial and intracavitary brachytherapy are then presented.

6-O-alpha-L-Arabinopyranosyl-beta-D-glucopyranosides as aroma precursors from passion fruit.

The 6-O-alpha-L-Arabinopyranosyl-beta-D-glucopyranosides of linalool, benzyl alcohol and 3-methyl-but-2-en-1-ol were isolated from passion fruit (Passiflora edulis) by adsorption chromatography on XAD-2 resin, then further extracted on the same resin after partial enzymic hydrolysis and semi-preparative chromatography on RP-18 phase by HPLC. Their structures were identified by 1H NMR spectroscopy and mass spectral analysis and by methylation analysis of the carbohydrate moieties.

[Evaluation of individual dosimetric data on patients in an international radiotherapy trial]. / Evaluation des données dosimétriques individuelles des patients d'un essai thérapeutique international en radiothérapie.

A quality control programme has been developed in the radiotherapy department of the Institut Gustave-Roussy for an international clinical trial on the use of Etanidazole as a radiosensitizer in association with radiotherapy for head and neck tumors. Twenty-nine european centers belonging to Germany, United Kingdom, Austria, France and Italy contributed to this trial during 374 patients has been included from 1987 to 1988. This programme concerned the control of the external radiotherapy equipment available in the participating centers and the examination of the patient treatment data. The authors present, in this paper, the methods applied and the main results obtained during the analysis of the individual patient treatment data. This analysis shows that 83% of the evaluable treatments were done in compliance with the protocol recommendations and 17% contained a major deviation and among them only 3% were judged unacceptable.

A comparison of early effects with two dose rates in brachytherapy of cervix carcinoma in a prospective randomised trial.

This phase III randomised trial examined the early effects of two low dose rates (0.38 and 0.73 Gy/h) in brachytherapy of stage I and IIp cervical cancer patients. A total of 204 patients were included between January 1985 and September 1988. Since the main analysis of this paper concerned surgical difficulties, only the 155 patients (76%) on whom surgery was performed at the Institut Gustave-Roussy were retained in this analysis. Treatment consisted of uterovaginal 137Cs irradiation followed by immediate or deferred surgery. The two groups were similar for pretreatment characteristics except for endocervix involvement. Their brachytherapy parameters were also similar (60 Gy pear dimensions, doses to critical organs, total kerma, etc.). The factors with a poor prognosis were, for surgical difficulties, older age, stage II and a small irradiated pear volume; for difficulties with haemostasis, immediate surgery, stage II and previous surgery; and for difficulties in dissection, lymph node involvement. The dose rate significantly influenced surgical difficulties for the stage IIp patients operated on by deferred surgery. Those treated with the higher dose rate showed a 2-fold increase in surgical difficulties compared to those irradiated at the lower dose rate (P = 0.03). The independent prognostic factors for sterilisation of the surgical specimen were small tumour size and absence of lymph node involvement. An inverse dose rate effect was observed for medium size tumours, with significantly more sterilisations observed in stage IIp patients in the lower dose rate group (P < 0.01).

Overall treatment time in advanced cervical carcinomas: a critical parameter in treatment outcome.

PURPOSE: To search for possible influence of overall treatment time on the clinical outcome of advanced cervical carcinomas treated with radiation alone. METHODS AND MATERIALS: Three hundred and eighty-six patients with Stage IIB and III cervical carcinomas treated with external radiation and intracavitary curietherapy between 1973 and 1983 were entered in the study. A multivariate analysis was carried out on data concerning these patients to determine whether overall treatment time was a prognostic factor. RESULTS: Overall treatment time and blood transfusions during treatment were the two most highly significant factors in the multivariate analysis. Loss of local control and overall survival, when treatment exceeded 52 days, was approximately 1% per day in both cases. CONCLUSION: These results suggest that overall treatment time might be a highly significant prognostic factor in the treatment outcome of advanced cervical carcinomas. Prospective randomized studies are strongly warranted to confirm this hypothesis.

A glossary for reporting complications of treatment in gynecological cancers.

Reporting and scoring treatment complications in gynecological cancers is difficult because of the variety of normal tissues, anatomical structures and treatment disciplines involved, making it impossible to compare series of patients treated in different institutions even with the same strategy. An international group of experts (gynecologists, radiotherapists and surgeons) developed a multidisciplinary database to identify, score and report early and late normal tissue damage regardless of treatment strategy. The principles involve: (1) The identification of relevant organs and tissues; (2) An accurate definition of the type and score of each complication; (3) Reporting combinations of complications of various degrees; (4) A computerized format for data acquisition, update and retrieval. In the present version, the "Glossary" describes five degrees of increasing severity (0 to 4) in 14 organs and/or normal tissues. The rationale of the glossary leaves it open for as yet undescribed types of complications. This paper contains the definition and scoring for each type of complication, general guidelines for their use.

Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: report at two years.

This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy.h-1) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal 137Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....) There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group.

First analysis of tumor regression for the European randomized trial of etanidazole combined with radiotherapy in head and neck carcinomas.

From July 1987 to July 1990, 374 patients were randomized in a multicenter trial coordinated by the Gustave-Roussy Institute. Patients were treated either by radiotherapy alone (RT) or by combined etanidazole with radiotherapy (ETA). The same radiotherapy protocol was used in both arms. Major deviations from the protocol occurred in 16% of the patients. Etanidazole was given at a dose of 2 g/m2, 3 times per week, for a total of 30-34 g/m2. Seventeen percent of the patients received less than 14 injections (4% refused, 12% presented a toxicity, 1% died before beginning). The rate of neuropathy was 28% in the ETA arm and 3% in the RT arm. Acute radiotherapy reactions occurred in similar proportions in both arms. The 3-month rates of complete regression are presently 75.3% in the RT alone group and 77.6% in the ETA group; this difference is not significant. No definitive results are presently available and we must wait for the two-year survival results. In addition, if a meta-analysis could be performed with the parallel RTOG study, the results would be more valid.

Combined radio-surgical treatment in early invasive cervix carcinoma according to prognostic factors. Experience of the Gustave-Roussy Institute.

In the Gustave-Roussy Institute the standard protocol of limited stages (IB, proximal II) of cervix carcinoma, combines endocavitary brachytherapy (low dose rate) and surgery (BSOH + lymphadenectomy) are eventually followed by external beam irradiation. According to age of patients and to prognostic factors adaptations of this combined treatment are discussed: young patient (40 years) with small tumor, large volume of primary tumor (4 cm), lymphatic node involvement. Analysis of the results in 2 series of patients entirely treated at the Gustave-Roussy Institute: survival, local control, metastases, complications.

Progress report of a phase II and a phase III trial with etanidazole (SR-2508): a multicentre European study.

A group of 6 European cancer centers, coordinated by the Institut Gustave-Roussy, began a phase II trial of the radiosensitizing drug, etanidazole, in November 1986. The trial was designed to study the toxicity of the drug and the feasibility of a phase III trial on the combination of etanidazole with radiotherapy for treating head and neck squamous cell carcinomas. Thirty-one patients were included in the phase II trial between November 1986 and June 1987; 25 completed the whole course of treatment. Most of the neuropathies occurred during the two weeks following radiotherapy, but had no major effect on radiotherapy itself. The area under the curve (AUC) was measured in 22 patients; there was no correlation between total AUC and the incidence of neuropathy, although there was a trend towards more neuropathies at high total AUC. The toxicity of Eta did not appear excessive. A phase III trial was therefore begun in July 1987. Twenty-nine centers in 5 European countries (France, Italy, Germany, Austria and the UK) took part. A total of 330 patients had been enrolled by the end of November 1989. This report presents the results available to date. 15% of the patients treated with Eta plus radiotherapy have received less than 15 Eta injections, mainly because of skin rashes (5%), peripheral neuropathies (3%) or patient refusal (3%). The overall frequency of neuropathies was 27%, but most were grade I and occur mainly after treatment. There were similar percentages of radiotherapy-related toxicities, mainly acute reactions in irradiated normal tissues, in both Eta and control arms.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix.

The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases.