PubMed Health⌕ Search

Biomedical subjects

M Ménard

Publications and source records attributed to M Ménard.

At least 37 records · Page 2Linked to original sources

Cisplatin-fluorouracil exclusive chemotherapy for T1-T3N0 glottic squamous cell carcinoma complete clinical responders: five-year results.

PURPOSE: To evaluate cisplatin-fluorouracil exclusive chemotherapy (EC) for T1-T3N0 glottic squamous cell carcinoma complete clinical responders (CCR) after cisplatin-fluorouracil induction chemotherapy (IC). PATIENTS AND METHODS: A retrospective analysis was performed of 58 patients with T1-T3N0 glottic squamous cell carcinoma CCR after IC consecutively managed at our department between 1985 and 1992. Twenty-one CCR were managed with EC. Thirty-seven CCR were managed with IC and a conventional laryngeal-preservation modality. Analyses of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor were performed using the Kaplan-Meier actuarial life-table method. In CCR managed with EC, the independent factors of age, tumor classification, exact tumor location, true vocal cord motion, arytenoid cartilage motion, total dosage of drugs delivered, and number of courses received were tested for potential correlation with survival, local recurrence, nodal recurence, and distant metastasis. RESULTS: The 5-year survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor rates in CCR managed with EC were 95.2%, 70.7%, 0%, 0%, and 14.3%, respectively. The 5-year rates of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor in CCR managed with IC and a conventional laryngeal-preservation modality were 86.1%, 97%, 2.7%, 6%, and 14.5%, respectively. Local recurrence was statistically more likely in CCR managed with EC (P = .002). Local recurrence in CCR managed with EC was always salvaged with partial laryngectomy or radiation therapy, which resulted in an overall 100% local control and laryngeal-preservation rate within this group. In CCR managed with EC, none of the variables analyzed was statistically related to survival, local recurrence, nodal recurrence, or distant metastasis. CONCLUSION: The present retrospective studies demonstrated that within T1-T3N0 glottic squamous cell carcinoma CCR, there is clearly a significant subset of patients with chemocurable tumors who achieved both perfect preservation of structure-supporting voice and long-term survival after EC. Careful monthly follow-up evaluation allowed for timely successful salvage of local recurrence after EC without the need for total laryngectomy. Such management did not appear to increase the risk for subsequent nodal failure, subsequent distant metastasis, or reduced survival.

Adult↗

[Exclusive chemotherapy in T1-T3N0 cancers of the vocal cord with complete clinical response after neoadjuvant treatment with a cisplatin-fluorouracil combination].

OBJECTIVES: Evaluation of cisplatin-fluorouracil exclusive chemotherapy for invasive squamous cell carcinoma of the glottis staged as T1-T3N0 with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy. METHODS: A retrospective analysis of the files of 69 patients with a well-differentiated untreated invasive squamous cell carcinoma, staged as T1-T3N0 with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy is presented. Actuarial analysis (Kaplan Meier method) of survival and local failure is presented among the group of 25 patients treated with exclusive chemotherapy and the group of 44 patients in whom the local treatment (partial laryngeal surgery or radiation therapy) initially planned was maintained. RESULTS: Three-year survival and local control estimate was 91.8% and 69.3%, respectively after exclusive chemotherapy and 92.5% and 97.2% if the local treatment was performed as initially planned. Patients with local recurrence after exclusive chemotherapy were always salvaged with partial laryngeal surgery or radiation therapy resulting in an overall 100% local control and laryngeal preservation rate. CONCLUSION: Exclusive chemotherapy for T1-T3N0 glottic carcinomas with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy should be considered especially in patients in whom preservation of voice is of utmost importance.

Adult↗

Structure-activity relationships of carbapenems that determine their dependence on porin protein D2 for activity against Pseudomonas aeruginosa.

A number of carbapenem derivatives were examined to determine the structure-activity relationships required for dependence on porin protein D2 for activity against Pseudomonas aeruginosa. As suggested by J. Trias and H. Nikaido (Antimicrob. Agents Chemother. 34:52-57, 1990), carbapenem derivatives, such as imipenem and meropenem, containing a sole basic group at position 2 of the molecule utilize the D2 channel for permeation through the outer membrane of pseudomonads; they are more active against D2-sufficient strains of P. aeruginosa. Our results indicated that carbapenems with a basic group at position 1 or 6 of the molecule did not depend on the D2 channel for activity; i.e. they were equally active against D2-sufficient and D2-deficient pseudomonal strains. However, addition of a basic group at position 1 or 6 of a carbapenem derivative already containing a basic group at position 2 resulted in its lack of dependency on the D2 pathway. Comparison between meropenem and its 1-guanidinoethyl derivative, BMY 45047, indicated that they differed in their dependence on D2; while meropenem required the D2 channel for uptake, BMY 45047 activity was independent of D2. Meropenem and BMY 45047 had similar affinities for the penicillin-binding proteins of P. aeruginosa. However, BMY 45047 and meropenem differed in the morphological changes that they induced in pseudomonal cells. While meropenem induced filamentation, BMY 45047 induced filaments only in BMS-181139-resistant mutants and not in imipenem-resistant mutants or in carbapenem-susceptible P. aeruginosa strains. These results suggested that in Mueller-Hinton medium the uptake of BMY 45047 through the non-D2 pathway is more rapid than that of meropenem through the D2 porin. In summary, the presence of a basic group at position 2 of a carbapenem is important for its preferential uptake by the D2 channel. However the addition of a basic group at position 1 or 6 of a carbapenem already containing a basic group at position 2 dissociates its necessity for porin protein D2 for activity.

Bacterial Proteins↗

Rapid neutrophil accumulation and protein oxidation in irradiated rat lungs.

Exposure of lungs to high doses of ionizing radiation can initiate an injurious acute inflammatory response. We show that neutrophil content in the lungs of rats exposed to 10 Gy whole body gamma radiation increased threefold 4.5 h after irradiation and returned to normal by 24 h. Oxidized methionine in the proteins of the lungs, heart, liver, kidney, and jejunum increased significantly in 2 h. Treatment with the antioxidant dithiothreitol immediately after irradiation prevented methionine oxidation. Methionine oxidation was also observed after intrabronchial instillation of phorbol myristate acetate, a model of neutrophil oxidant-mediated pulmonary injury, as well as in isolated lungs perfused with hypochlorous acid, confirming the ability of neutrophil oxidants to cause protein oxidation in lungs. No change in glutathione or protein sulfhydryl content was detected in irradiated lungs 4.5 h after irradiation, possibly as a result of protection by the observed increase in pulmonary glutathione reductase. We therefore show that the acute pulmonary inflammatory response to radiation involves rapid neutrophil accumulation, oxidant production, and protein oxidation.

Animals↗

Total conservative parotidectomy for primary benign pleomorphic adenoma of the parotid gland: a 25-year experience with 229 patients.

A 25-year experience with total conservative parotidectomy for primary benign pleomorphic adenoma (PBPA) of the parotid gland in a consecutive series of 229 patients has been reviewed. This study focuses on survival, morbidity, PBPA recurrence, postoperative facial nerve dysfunction, and Frey's syndrome. Surgical death was never encountered in this study. The overall incidence for postoperative hemorrhage, hematoma, seroma, skin necrosis, great auricular nerve schwannoma, and keloid scar was 1.7%, 6.1%, 4.8%, 0.9%, 15.7%, and 8.3%, respectively. Five-, 10-, 15-, and 20-year PBPA control actuarial rate was 99.6%. The overall incidence for temporary facial paresis and paralysis was 64.6% and 5.6%, respectively. Kaplan-Meier actuarial analysis demonstrated that paresis recovery was noted until the eighteenth postoperative month. The overall incidence for permanent facial paresis and paralysis was 3.9% and 0%, respectively. None of the following variables--sex, age, PBPA size, PBPA location, PBPA contact with the facial nerve, inadvertent PBPA spillage, or surgeon's experience--was statistically related to PBPA recurrence and facial nerve dysfunction. The overall incidence for Frey's syndrome was 65.9%. Kaplan-Meier actuarial analysis demonstrated the need for a minimal 5-year follow-up to assess Frey's syndrome incidence. The mean age was statistically lower in patients presenting with Frey's syndrome.

Adenoma, Pleomorphic↗

Cricohyoidopexy in selected infrahyoid epiglottic carcinomas presenting with pathological preepiglottic space invasion.

Nineteen patients who presented with infrahyoid epiglottic squamous cell carcinoma with gross pathological preepiglottic space invasion, not amenable to a partial horizontal supraglottic laryngectomy, were offered a supracricoid partial laryngectomy with a cricohyoidopexy technique; this was an attempt to preserve physiological phonation, respiration, and deglutition while achieving the same local control rate as with a total laryngectomy. Preoperative chemotherapy and bilateral jugulocarotid lymph node dissection were performed in all cases. Patients were monitored for at least 5 years or until death. No patients were unavailable for follow-up. The 5-year actuarial survival (Kaplan-Meier method) was 84.2%. Local recurrence, nodal recurrence, and distant metastasis occurred once in our series, while six patients presented with a second primary tumor. We present, analyze, and compare functional results with those of the previously reported series. Our experience with the supracricoid partial laryngectomy with a cricohyoidopexy, in the face of selected infrahyoid epiglottic squamous cell carcinoma invading the preepiglottic space, not amenable to a partial horizontal supraglottic laryngectomy, suggested that a total laryngectomy might be avoided without decreasing the cure rate.

Adult↗

Supracricoid hemilaryngopharyngectomy in selected pyriform sinus carcinoma staged as T2.

From 1964 to 1985 supracricoid hemilaryngopharyngectomy (SCHLP) was performed at the authors' institution for 34 selected pyriform sinus carcinomas staged as T2. Tumors involved the anterior part of the pyriform sinus, the lateral wall, the medial wall, and the whole aryepiglottic fold in all cases. Tumors with invasion of the apex of the pyriform sinus, of the retrocricoid region, of the posterior pharyngeal wall, or with fixation of the true vocal cord were excluded from the study. Such a technique was aimed at preserving physiologic phonation, respiration, and swallowing while achieving the same local control rate as pharyngolaryngectomy. Patients were monitored for at least 6 years or until death. No patients were lost to follow-up. The 5-year cause-specific survival rate was 55.8%. The main cause of death was second primary tumor. The 5-year actuarial local recurrence rate was 3.4%. The authors' experience with the SCHLP technique challenges the traditional teaching of pharyngolaryngectomy and establishes this technique as a safe method of voice preservation in selected cases of pyriform sinus carcinomas.

Adult↗

[Conservative surgery of the larynx as an alternative to total laryngectomy after neoadjuvant chemotherapy. Initial results].

A retrospective study of 149 squamous cell carcinomas of the larynx and epilarynx in whom a total laryngectomy was initially planned is reported. All the patients were treated by neoadjuvant chemotherapy. After completion of chemotherapy, the initially planned therapeutic protocol was modified in 56 patients (37.6%) in order to preserve the laryngeal physiologic functions. A total laryngectomy was performed in 23 patients (41%), radiation therapy was administered to 14 (25%) patients chemotherapy was prolonged in 15 patients (26.8%) and four deaths were related to chemotherapy toxicity (7.2%). Actuarial survival of patients treated by partial laryngectomy was statistically higher than survivals of patients treated either by radiation therapy or prolonged chemotherapy. After completion of neoadjuvant therapy patients who refused a total laryngectomy had the worst survival of the series. These results suggest that surgery of the residual tumor (partial laryngectomy) after neoadjuvant chemotherapy could be indicated for selected laryngeal carcinoma in whom a total laryngectomy was initially planned.

Actuarial Analysis↗

Oxidant-induced mobilization of zinc from metallothionein.

Neutrophils which accumulate at sites of inflammation secrete a number of injurious oxidants which are highly reactive with protein sulfhydryls. The present study examined the possibility that this reactivity with thiols may cause protein damage by mobilizing zinc from cellular metalloproteins in which the metal is bound to cysteine. The ability of the three principal neutrophil oxidants, hypochlorous acid (HOCl), superoxide (.O2-), and hydrogen peroxide (H2O2), to cleave thiolate bonds and mobilize complexed zinc was compared using two model compounds (2,3-dimercaptopropanol and metallothionein peptide fragment 56-61), as well as metallothionein. With all compounds, 50 microM HOCl caused high rates of Zn2+ mobilization as measured spectrophotometrically with the metallochromic indicator 4-(2-pyridylazo)resorcinol. Xanthine (500 microM) plus xanthine oxidase (30 mU), which produced a similar concentration of .O2-, also effected a rapid rate of Zn2+ mobilization which was inhibited by superoxide dismutase but not catalase, indicating that .O2- is also highly reactive with thiolate bonds. In contrast, H2O2 alone was much less reactive at comparable concentrations. These data suggest that HOCl and .O2- can cause damage to cellular metalloproteins through the mobilization of complexed zinc. In view of the essential role played by zinc in numerous cellular processes, Zn2+ mobilization by neutrophil oxidants may cause significant cellular injury at sites of inflammation.

Amino Acid Sequence↗

Hypochlorous acid-induced mobilization of zinc from metalloproteins.

Hypochlorous acid (HOCl), a neutrophil oxidant, can contribute to tissue injury at sites of inflammation by its reactivity with protein sulfhydryls. The present study shows that physiological concentrations (50-200 microM) of HOCl can displace Zn2+ from metalloproteins, such as metallothionein and alcohol dehydrogenase, in which the metal is bound to sulfhydryls by means of thiolate (S-Zn) bonds. No mobilization of Zn2+ was observed from superoxide dismutase in which the metal is not bound to cysteine, suggesting that HOCl reacts selectively with thiolate bonds. Zn2+ mobilization, measured spectrophotometrically with the metallochromic indicator 4-(2-pyridylazo)resorcinol, was also observed from complexes of this metal with other thiol-containing compounds such as 2,3-dimercaptopropanol and metallothionein fragment 56-61. HOCl cleavage of the thiolate bonds was confirmed by the decrease in absorbance at 250 nm. This study shows for the first time that HOCl can mobilize protein-bound Zn2+ and suggests that neutrophil oxidant injury may be partially mediated by the mobilization of cellular Zn2+.

Amino Acid Sequence↗

Hypochlorous acid mobilizes cellular zinc.

Neutrophil oxidants, in particular hypochlorous acid (HOCl), can cause injury to healthy tissues at sites of inflammation. Some of this injury may be caused by oxidant-induced mobilization of metals. We examined the ability of HOCl to mobilize Zn2+ in target tissues. Arterial endothelial cell cultures and heart tissue sections were incubated for 90 s in buffered saline, pH 7.3, containing a suspension of N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (100 nmol/mL), a Zn(2+)-specific fluorescent chelator, and were subsequently exposed to 200 microM HOCl for 5 min. The cellular fluorescence was analyzed histologically and showed a marked increase in intensity after HOCl treatment, which was indicative of an increase in cellular free Zn2+ concentration. Incubation of HOCl-treated tissues with dithiothreitol, a membrane-permeable metal chelator, caused a sharp decline in cellular fluorescence. This study shows for the first time that HOCl can mobilize cellular Zn2+. In view of the multiple cellular roles played by Zn2+, its mobilization by oxidants at sites of inflammation may contribute to the observed injury. The ability of dithiothreitol to chelate the mobilized Zn2+ suggests that it may be able to reverse Zn(2+)-mediated injury.

Aminoquinolines↗

Primary and secondary lysosomes in megakaryocytes and platelets from cattle with the Chediak-Higashi syndrome.

The ultrastructure of lysosomes from megakaryocytes (MK) and platelets of cattle with the Chediak-Higashi syndrome (CHS) was characterized using acid phosphatase histochemistry with beta-glycerophosphate as substrate and cerium as a capturing agent. Acid phosphatase was localized in the trans aspect of the Golgi complex and/or granules in MK at all stages of maturation. Morphometric analysis of the diameter of each lysosome was performed on MK from CHS cattle and compared to MK from normal cattle. Lysosomes in CHS MK were neither enlarged nor different with respect to classification as secondary lysosomes, which composed 35% of the lysosomes in CHS MK. Lysosomes were demonstrated in 22% of the CHS platelet sections and appeared similar to those from normal cattle, 56% of them being classified as secondary lysosomes. Why lysosomes are not enlarged in bovine CHS MK and platelets, whereas they are enlarged in most other cell types, remains unknown.

Acid Phosphatase↗

Demonstration of secondary lysosomes in bovine megakaryocytes and platelets using acid phosphatase cytochemistry with cerium as a trapping agent.

The ultrastructure of lysosomes from bovine megakaryocytes (MK) and platelets was characterized using acid phosphatase cytochemistry with beta-glycerophosphate as substrate and cerium as a trapping agent. The technique was easily reproducible; cerium-phosphate precipitates were uniform, readily visualized, and there was a virtual absence of nonspecific reaction product. Acid phosphatase was localized in the trans aspect of the Golgi complex and/or granules of less than 50 nm to 650 nm diameters in MK at all stages of maturation. Forty percent of the MK lysosomes contained inclusions of variable shapes, sizes and electron-density and were classified as secondary lysosomes. Twenty-four percent of the platelet sections contained acid phosphatase-positive granules. Fifty-four percent of these were secondary lysosomes. This is the initial report demonstrating secondary lysosomes in either resting MK or platelets using acid phosphatase cytochemistry. These findings suggest that MK and platelet lysosomes have an intracellular function in resting MK and platelets.

Acid Phosphatase↗

Myomucosal shunt following total laryngectomy: a report of 31 cases.

An original technique of voice rehabilitation following total laryngectomy based on the concept of a myomuscosal unit was originally described by Strome. Thirty-one cases of myomucosal shunts (MMS) are analyzed in the present report. The 14 initial cases failed because of a lack clinical and surgical experience and insufficient selection of the patients. Among the last 17 cases, 1 was lost to follow-up, 1 had an insufficient follow-up, and 2 patients refused to speak with the MMS instead of a patent shunt; 5 of the remaining patients had voices evaluated as excellent, 7 had voices interpreted as good and only 1 patient had a voice evaluated as poor. Aspiration was not a problem. Eleven patients were found to stenose their shunt, but fistula were recalibrated successfully. The MMs can be used safely in oncological surgery and only 1 of 31 deaths in our total experience was due to a local recurrence. These findings show that the MMS is a reliable procedure for voice restoration following total laryngectomy; a prosthesis is not required and there are currently no oncological limits to the procedure. However, a very close follow-up of the patients is required after surgery.

Adult↗

[Tumors of the nasal fossa. Retrospective study of a series of 67 cases].

This retrospective study reviews 67 tumors of the nasal fossa treated at hospital Laënnec (Paris). The clinical significance of histology and the therapeutic results for each pathological tumor (mainly, carcinoma, melanoma, lymphosarcoma, neuroma, malignant plasmocytoma, inverted papilloma, vascular tumors) are described. Treatment and surgical procedure will be analyzed.

Adult↗

[Inoperable cancers of the upper respiratory and digestive tracts. Value of chemotherapy: 185 cases].

A series of 185 squamous cell carcinomas of the head and neck was retrospectively analyzed. Induction chemotherapy was systematically administered. The overall tumour response rate was 38 per cent, and 39 tumours (22.4 per cent) became resectable after chemotherapy. The survival of complete responders was statistically higher than that of non or partial responders. Complete responders treated either by radiation therapy or surgery had similar survivals. Surgery improved the prognosis and reduced the rate of local and regional failures in non responders, including poor responders (less than 50 per cent).

Carcinoma, Squamous Cell↗