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Biomedical subjects

D Chevalier

Publications and source records attributed to D Chevalier.

At least 37 records · Page 2Linked to original sources

Composite reconstruction of hypopharynx and esophagus.

Extended surgical resection of the whole esophagus and associated hypopharynx may require composite reconstructions using a combination of pediculated and free tissue units. Twelve patients were assigned to composite reconstructions of the hypopharynx and esophagus for either metachronous carcinoma of the esophagus and head and neck (group I, n = 4), cervical anastomotic recurrence of esophageal carcinoma (group II, n = 3), or secondary reconstruction after the failure of a previous reconstruction of hypopharynx or esophagus (group III, n = 5). Pediculated tissues were the stomach (n = 10), colon (n = 1), or jejunum (n = 1). A free jejunal graft was constantly interposed between the pharynx and the mobilized organ. There were no hospital deaths. Swallowing function was restored in all patients except one who had cervical leakage as a result of partial necrosis of the free jejunal graft. Composite reconstruction permitted, even in groups I and II in which prognosis was extremely poor, prolonged survival and oral feeding, which proved beneficial in terms of the patients' quality of life.

Adult↗

Molecular analysis of the N-acetyltransferase 1 gene (NAT1*) using polymerase chain reaction-restriction fragment-single strand conformation polymorphism assay.

One major interest to analyse the extent of N-acetyltransferase 1 (NAT1*) allelic variation in the human population stems to a great extent from the possible association of interindividual differences in the metabolism of aromatic amines with certain chemically induced diseases, including cancer. Considering the increasing number of mutations in the NAT1 gene that are detected, NAT1* genotyping using conventional polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) or allele-specific amplification assays has become complicated. We developed a rapid and powerful strategy allowing the full characterization of NAT1* alleles. This method, based on single-strand conformation polymorphism analysis of a unique PCR product encompassing the entire intronless NAT1*-coding region along with additional flanking segments in the 5' and 3' untranslated regions, was then applied to DNA samples from 270 individuals. Nine NAT1* allelic variants, including two novel (NAT1*28 and NAT1*29), and 15 different genotypes were identified. This approach could be advantageously used in epidemiological studies to provide more definite data on suspected associations between NAT1* genotype and certain pathological processes.

Alleles↗

Molecular analysis of NOZZLE, a gene involved in pattern formation and early sporogenesis during sex organ development in Arabidopsis thaliana.

Sexual reproduction is a salient aspect of plants, and elaborate structures, such as the flowers of angiosperms, have evolved that aid in this process. Within the flower the corresponding sex organs, the anther and the ovule, form the male and female sporangia, the pollen sac and the nucellus, respectively. However, despite their central role for sexual reproduction little is known about the mechanisms that control the establishment of these important structures. Here we present the identification and molecular characterization of the NOZZLE (NZZ) gene in the flowering plant Arabidopsis thaliana. In several nzz mutants the nucellus and the pollen sac fail to form. It indicates that NZZ plays an early and central role in the development of both types of sporangia and that the mechanisms controlling these processes share a crucial factor. In addition, NZZ may have an early function during male and female sporogenesis as well. The evolutionary aspects of these findings are discussed. NZZ encodes a putative protein of unknown function. However, based on sequence analysis we speculate that NZZ is a nuclear protein and possibly a transcription factor.

Amino Acid Sequence↗

Surgical treatment of T1-T2 glottic carcinomas.

Transoral laser surgery (TLS) is a safe, time and cost-effective method of treatment for early stage glottic squamous cell carcinoma. This technique is more controversial in case of local extension to other subsite or in case of limited mobility.

Carcinoma, Squamous Cell↗

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

Alleles↗

Supraglottic hemilaryngopharyngectomy plus radiation for the treatment of early lateral margin and pyriform sinus carcinoma.

BACKGROUND: Supraglottic hemilaryngopharyngectomy is a functional procedure suitable for the treatment of carcinoma of the upper part of the pyriform sinus and carcinoma of the lateral laryngeal margin. It consists of resection of the supraglottic hemilarynx and ipsilateral pyriform sinus. METHODS: Forty-nine patients underwent this procedure from 1979 through 1994. The median age was 51 (40-72). The data were collected by a review of patients' records. RESULTS: Two patients died in the postoperative period. The average time of removal of the nasogastric tube was 14 days. The survival rate at 3 years was 52% and at 5 years, 47%. The local recurrence rate was 2%, the overall neck recurrence was 15%, metastasis occurred in 15% of cases. CONCLUSIONS: Indications for this procedure are carcinoma of the upper part of the pyriform sinus and carcinoma of the laryngeal margin with normal vocal cord mobility.

Adult↗

Free jejunal graft reconstruction after total pharyngolaryngeal resection for hypopharyngeal cancer.

The free jejunal graft is a very useful procedure for hypopharyngeal reconstruction after total pharyngolaryngectomy. Between 1985 and 1994 56 patients with squamous cell carcinoma of the hypopharynx were treated by this method. The median age was 54 (range 35-76). There were 54 men and 2 women. The mortality rate was 4% (2/56). The graft failure was 4% (2/56). Good swallowing function was achieved in 91% (49/54 assessable patients). Nine patients developed local recurrences, four patients had local and neck recurrences. Distant metastases occurred in six patients and five developed metachronous cancers. Follow-up analysis showed a 5-yr survival rate of 33%. After 10 yr, the free jejunal graft has become, for us, the method of choice for hypopharyngeal reconstruction after total pharyngolaryngectomy.

Adult↗

Glutamate transport and not cellular content modulates paracellular permeability in LLC-PK1-F+ cells.

Uptake of glutamate modulates two cellular processes: 1) glutamine flux through the cellular glutaminase (GA) and 2) paracellular permeability (PP). Because both responses are the result of a decreased glutamate uptake, the present study was designed to determine whether the transport step or resulting fall in cellular glutamate modulates PP. To do so, advantage was taken of the ability of D-glutamate to competitively displace the natural L-isomer yet maintain transporter activity at or even above that normally occurring with L-glutamate. As a consequence cellular L-glutamate would fall while transporter fluxes remained. Accordingly, LLC-PK1-F+ cells were grown to confluent monolayers on porous supports in Dulbecco's modified Eagle's medium containing 50 microM L-glutamate and 1.8 mM L-glutamine with and without 1 mM D-glutamate. After a 90-min exposure to D-glutamate monolayer, L-glutamate content had fallen 38%. D-Glutamate was transported in place of the L-isomer as evidenced by the accumulation of L-glutamate in the media and uptake of the D-isomer. Although GA activation occurs as the result of the fall in cellular L-glutamate, PP did not increase; in fact, it slightly decreased as evidenced by an increased electrical resistance (from 180 +/- 12 to 210 +/- 10 omega x cm2, P < 0.02) and reduction in L-[(14)C]glucose permeability (2.72 +/- 0.75 to 2.28 +/- 0.37%, P = 0.10). Thus glutamate transporter activity and associated ionic fluxes rather than the fall in cellular glutamate and GA activation appear to play the critical role in modulating PP.

ATP-Binding Cassette Transporters↗

Sequential evaluation of pulmonary function and bronchial hyperresponsiveness in patients with nasal polyposis: a prospective study.

Nasal polyposis (NP) is commonly associated with nonspecific bronchial hyperresponsiveness (BHR) and/or asthma. The aim of this prospective study was to investigate the changes of pulmonary function and BHR in patients with nasal polyposis. Forty-four consecutive patients with NP were included in the study and were followed for 12 mo. Nonspecific BHR was assessed by a carbachol challenge test to determine the provocating dose (PD20) necessary to decrease FEV1 by 20% from baseline values; 17 of 22 patients who demonstrated BHR also exhibited asthma. Spirometric measurements and carbachol challenge were performed before initiating any treatment and 12 mo later. All patients were treated first with beclomethasone (600 microg/d). Intranasal ethmoidectomy was performed in 23 patients who did not improve when treated with topical steroids alone (nonresponders); in contrast, 21 patients were successfully treated with beclomethasone alone (responders). PD20 significantly decreased in the group of nonresponders (p = 0.018), whereas it remained unchanged in responders (p = 0.95). FEV1 (% pred) and FEF25-75 (% pred) significantly decreased in nonresponders (p < 0.001), whether BHR existed or not, whereas no significant change was observed in responders. Our results demonstrate that nonresponders who required nasal surgery exhibited an enhancement of BHR and a slight but significant decrease of FEV1 and FEF25-75 values. However, no change in pulmonary symptoms and/or asthma severity occurred. Clinical and functional follow-up of these patients should assess the long-term evolution of these parameters and their clinical relevance.

Adolescent↗

Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion of the true vocal cord: 5-year oncologic results with 112 patients.

The medical charts and operative files of 112 patients (combined inception cohort) with well to moderately differentiated invasive glottic squamous cell carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and 10.8%, respectively. The 5-year absolute and cause-specific survival rates were 85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for patients with impaired motion of the TVC. The 5-year actuarial local control rates for patients with fixation or impaired motion of the TVC were 95.4% and 94.4%, respectively. Local recurrence was statistically more likely in patients with positive margins (p = .007). Nodal recurrence was statistically more likely in patients with local recurrence (p = .005). Permanent tracheostomy related to postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related completion total laryngectomy and/or permanent gastrostomy were never requested. Overall, local control and laryngeal preservation were achieved in 97.3%, and 95.5% of patients, respectively. At our institutions, the change from the conservative treatment modalities of radiotherapy and vertical partial laryngectomy to CHEP has brought about an increase in long-term survival, local control, and laryngeal preservation rates when compared to historical controls using vertical partial laryngectomy or radiotherapy.

Adult↗

[Thyroplasty by external approach with silastic prosthesis in the treatment of laryngeal paralysis].

From August 1995 to January 1997 8 phonosurgical procedures were performed to correct glottal incompetence. There were 4 men and 4 women, the median age was 42 years. The most common indication for thyroplasty was recurrent or vagal nerve injury (6/8 cases). In 7 cases the paralyzed vocal cord was unilateral and in 1 case bilateral after oesophagectomy. Two patients were previously treated by endoscopic injection without success. The procedure was conducted under general anaesthesia. A window in the thyroid ala was created and silastic implant inserted. This technique was indicated to correct large glottal incompetence or in case of failure after endoscopic treatment. There have been no complications. Improvement of post operative voice was noted. The maximum phonation duration, intensity and objective voice measurements were improved in all cases.

Adult↗

Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group.

BACKGROUND: As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. PURPOSE: A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. METHODS: Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance. RESULTS: Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively. CONCLUSIONS AND IMPLICATIONS: Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.

Adult↗

Helical CT of the larynx: a comparative study with conventional CT scan.

AIM: To compare helical and conventional CT scans of the larynx. PATIENTS AND METHODS: Thirty-three patients underwent helical and conventional CT studies of the neck and the larynx using 3 mm section collimation for both studies and a table feed of 4 mm/sec for helical CT. Helical scans were reconstructed at 2 mm increments. Two independent observers rated the visibility of the laryngeal structures from 1 (poor and non diagnostic) to 5 (excellent and diagnostic), and motion artifacts from 1 (> or = 10 degraded scans) to 5 (no motion artifacts). RESULTS: The motion artifacts score was significantly better for helical CT. No significant difference was observed for the laryngeal structures score between helical and conventional CT studies. The interobserver kappa mean value was 0.756 and 0.68 for helical and conventional CT, respectively. CONCLUSION: Helical CT can be routinely performed and replace conventional CT study for the evaluation of laryngeal diseases.

Adult↗

[Iatrogenic laryngotracheal stenosis. A follow-up of 20 recent cases].

The aim of this study was to analyse the follow-up of patients with a history of endotracheal intubation and/or tracheotomy because of respiratory distress, surgical necessity or long-term resuscitation. Twenty adults were followed up in a ENT facility for laryngeal or tracheal stenosis, of which 7 cases were diagnosed during 1994. This study shows that, in patients with a history of intubation, or intubation followed by tracheotomy, the stenosis developed within two months after resuscitation with a favourable outcome. After tracheotomy only, the stenosis developed later (2 months or more) with more recurrences. The diagnosis of stenosis was made on gradual or acute dyspnea. While respiratory resuscitation methods are essential and often life-saving, they are not without complications. Laryngeal and tracheal stenosis could be largely prevented by more careful techniques of endotracheal intubation and tracheotomy. Periodic endoscopic airway surveillance is useful to detect stenosis even when there is no clinical symptom.

Adolescent↗