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Biomedical subjects

E Dulmet

Publications and source records attributed to E Dulmet.

At least 37 records · Page 2Linked to original sources

Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases.

The medical records and histologic documents of 14 patients treated at our institution for a thymic carcinoid tumor were reviewed. There were 3 women and 11 men with an age range from 35 to 71 years. One patient had a multiple endocrine neoplasia syndrome; another had a neurofibromatosis. Twelve tumors were revealed by local symptoms and two were asymptomatic. One patient had Cushing's syndrome that appeared secondarily and was related to metastases. Tumors ranged from 6 to 20 cm and had the characteristic histologic appearance of atypical carcinoid tumor. Immunohistochemical evaluations were done. Tumors were positive for cytokeratin (92%), neuroendocrine markers (100%), and p53 oncoprotein (29%). S-100 protein antibody revealed numerous sustentacular cells in one case. Overall survival was 46% and 31% at 3 and 5 years, respectively. However, all patients died of the disease within 109 months as a result of local progression (n = 5), local relapse (n = 3), distant metastases (n = 8), or a combination of these reasons. Median survival was 71, 30, and 5 months for patients who had total resection (n = 4), partial resection (n = 5), or simple biopsy (n = 4), respectively (p = 0.023). In conclusion, thymic carcinoid tumors can be considered thymic neuroendocrine carcinomas because of their malignant behavior and histologic appearance of atypical carcinoid tumors. Complete surgical resection offers the best hope for long-term survival.

Adult↗

M1 and M3 muscarinic receptors in human pulmonary arteries.

1. Acetylcholine (ACh) and the M1 agonists (McN-A-343 or PD142505) relaxed human isolated pulmonary arteries which were pre-contracted with noradrenaline (10 microM). In preparations where the endothelium had been removed ACh induced a contractile response whereas the M1 agonists (McN-A-343 or PD142505) had no effect. 2. ACh- and McN-A-343-induced relaxations were abolished after treatment of endothelium-intact preparations with the drug combination NG-nitro-L-arginine (L-NOARG: 0.1 mM) and indomethacin (1.7 microM). 3. The affinity (pKB value) for pirenzepine was higher in human pulmonary arteries when tissues were relaxed with McN-A-343 as compared with ACh (pKB values, 7.71 +/- 0.30 (n = 4) and 6.68 +/- 0.15 (n = 8), respectively). In addition, the affinity for pFHHSiD against McN-A-343- and ACh-induced relaxations was 6.86 +/- 0.13 (n = 3) and 7.35 +/- 0.11 (n = 9) respectively. 4. The low affinities for methoctramine in human isolated pulmonary arteries with the endothelium either intact or removed, suggested the lack of involvement of M2 and M4 receptors in the Ach responses. 5. Phenoxybenzamine (3 microM: 30 min) abolished both ACh contraction and relaxation in human pulmonary artery. The ACh contraction was present when the phenoxybenzamine treatment was preceded by incubation with pFHHSiD (2 microM) but not with pirenzepine (1 microM). In addition, the ACh relaxation was present when preparations were treated with either pFHHSiD (2 microM) or pirenzepine (1 microM), before exposure to phenoxybenzamine. 6. These results in human isolated pulmonary arteries support the notion that only M3 receptors, on smooth muscle, mediate the ACh-induced contraction whereas M3 and M1 receptors are involved in the endothelium-dependent ACh-induced relaxation.

Acetylcholine↗

Experimental tracheal and tracheoesophageal allotransplantation. Paris-Sud University Lung Transplantation Group.

We investigated the effects of allograft perfusion with a preservative technique and of combined thyrotracheoesophageal implantation on airway epithelium of long segments of thyrotracheal grafts allotransplanted on their own vascular pedicles into immunosuppressed pigs. Four groups of five animals each underwent heterotopic (into the neck) thyrotracheal (group 1) and thyrotracheoesophageal (group 2) and orthotopic thyrotracheal (group 3) and thyrotracheoesophageal (group 4) allotransplantation. Allograft revascularization included (1) interposition of donor right subclavian artery--incorporating the inferior thyroid artery--to recipient right carotid artery (end-to-end fashion) and (2) end-to-side anastomosis of donor anterior vena cava to recipient right external jugular vein. All thyrotracheoesophageal blocks were harvested after inferior thyroid artery perfusion with 4 degrees C Euro-Collins solution. The overall lengths of tracheal and esophageal grafts were 10.7 +/- 2.7 cm and 13.4 +/- 3.6 cm, respectively. In the heterotopic groups, all allografts were viable and histologically normal at postmortem examination and the incidence and severity of airway ischemia and rejections (at equal residual levels of cyclosporine) were not different between groups 1 and 2. In the orthotopic groups, the first two pigs died of airway collapse with histologically normal grafts. In the remaining pigs, temporary airway stenting was inserted and allografts remained viable and histologically intact for their entire length 30 days after transplantation. Transplanted tracheal smooth muscles had concentration-dependent contractions and relaxations similar to those of nontransplanted (native) tracheas. This study documents the feasibility of allotransplanting long tracheal and esophageal segments on their own vascular pedicles and demonstrates that allograft preservation and thyrotracheoesophageal transplantation are equally effective in minimizing airway ischemia. Thyrotracheoesophageal transplantation does not enhance recipient alloimmune response compared with thyrotracheal transplantation alone.

Animals↗

Prognostic significance of peritumoural blood and lymphatic vessel invasion by tumour cells in T4 non-small cell lung cancer following induction therapy.

We investigated the impact of new biological prognostic factors is in 28 patients receiving a median of two courses of cisplatin-based chemotherapy with (n = 14) or without (n = 14) radiation and operation for stage IIIB (T4) non-small cell lung cancer (NSCLC). After induction therapy, 5 patients had a complete and 21 a partial response; 2 had a stable disease. A complete resection was made in 26 patients (93%). Five patients (18%) had their primary tumour and involved vestiges completely sterilized. In the remaining 23, the majority of the tumours showed abnormalities in the p53 gene expression (56%), harboured proliferating cells (91%) and induced angiogenesis (91%). Peritumoural blood and lymphatic vessel invasion (PBLVI) by tumour emboli was observed in 6 tumours. With a median follow-up of 25 months, overall 3-year survival was 48%; disease-free survival (DFS) has not been reached yet. The only significant factor influencing DFS in multivariate analysis was PBLVI by tumour cells; PBLVI-positive patients had a significantly higher likelihood ratio (P = 0.000001) of developing metastasis than their PBLVI-negative counterparts. This study documents the prognostic implication of PBLVI by tumour cells in T4 NSCLC.

Adult↗

Giant bilateral fibrous dysplasia of first ribs: compression of mediastinum and thoracic outlet.

A 43 year old woman presented with two large bilateral tumours of the first ribs that compressed the right subclavian vessels, trachea and oesophagus and led to right arm oedema, severe dyspnoea and dysphagia. The resected tumours showed typical histological features of fibrous dysplasia without malignant transformation. The right tumour weighed 1.5 kg and measured 17 x 13 x 10 cm. This report demonstrates that major surgery is still possible for resection of such exceptional giant compressive lesions, since fibrous dysplasia is a benign and non-infiltrative tumour.

Adult↗

Endothelin-1 modulates cyclic GMP production and relaxation in human pulmonary vessels.

The aim of this study was to examine the effects of endothelin-1 (ET-1) on sodium nitroprusside (SNP) induced relaxation and cyclic 3',5'-guanosine monophosphate (cGMP) accumulation in human pulmonary vessels. The basal levels of cGMP were similar in arteries (2.48 +/- 0.24 pmol/mg protein; n = 7) and veins (3.25 +/- 0.24 pmol/mg protein; n = 7). In tissues (n = 7) treated with N omega-nitro-L-arginine and indomethacin, cGMP values were significantly reduced (arteries, 1.30 +/- 0.24 pmol/mg protein and veins, 1.95 +/- 0.28 pmol/mg protein). In treated tissues, SNP (10 microM) increased the cGMP level by 10-fold in arteries and veins. ET-1 (0.02 and 0.2 microM) reduced significantly the cGMP increase in SNP-stimulated vessels. This inhibition was greater in veins (76%) when compared with arteries (34%). Norepinephrine (10 microM) did not affect the cGMP levels. The sensitivity and the maximal relaxation induced by SNP in veins contracted with ET-1 (0.2 microM) was significantly diminished (in comparison with norepinephrine; 10 microM). In arteries, SNP relaxations were not altered by ET-1 contraction. Inasmuch as 8-bromo-cyclic 3',5' guanosine monophosphate curves were not altered by ET-1 treatment in either arteries or veins, the relaxant mechanisms that are downstream of guanylate cyclase activation apparently are not affected. These results suggest that ET-1 may play a role in the control of muscle tone in the human pulmonary vascular bed by modifying cGMP levels associated with vasorelaxant agonist stimulation.

Cyclic GMP↗

[Endo- and exo-bronchial schwannoma treated by resection-anastomosis of the left bronchial stump].

Bronchial schwannomas are rare tumours. We report a case of an endo and exobronchial schwannoma which presented with dyspnoea and left pulmonary atelectasis. This was treated by complete resection of the tumour with a resection and anastomosis of the left bronchial stump flush with the lobar bifurcation. This tumour is most often benign and a conservative approach should be taken each time that this is permissible anatomically.

Adult↗

Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading the thoracic inlet.

We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene p53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed p53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29% and the median disease-free interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and significant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly (p = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels.

Adenocarcinoma↗

Cholinesterase inhibition by vecuronium and pancuronium in human airways.

Vecuronium (100 microM) but not pancuronium (100 microM) increased the sensitivity of human isolated bronchial preparations (HBP) to exogenous acetylcholine (ACh). The pD2 values obtained from concentration-dependent contractions were: control, 4.59 +/- 0.29 vecuronium, 5.86 +/- 0.31. Vecuronium or pancuronium (100 microM) significantly decreased (50%) the neostigmine contractions in HBP. In addition, vecuronium was more potent than pancuronium in preventing exogenous ACh degradation. These results suggest that vecuronium and pancuronium may have physiological effects in human airways by inhibiting both the tissue cholinesterases and muscarinic (M3) receptors.

Bronchi↗

Heterotopic pig model for direct revascularization and venous drainage of tracheal allografts. Paris-Sud University Lung Transplantation Group.

A macrosurgical technique of thyrotracheal harvesting and direct revascularization with and without venous drainage in a heterotopic thyrotracheal and immunosuppressed allograft in the pig model is described. Harvesting included en bloc cervicothoracic exenteration of the aortic arch and its supraortic trunks, anterior vena cava, jugular veins, subclavian vessels, thyroid gland, cervicothoracic trachea, and esophagus. This technique conserves the tracheal arterial supply provided by either the right or left subclavian artery, directly or indirectly via the inferior thyroid artery, and venous return provided by the anterior vena cava, directly or indirectly via the descending cervical vein. In recipients, implantation included (1) arterial end-to-end anastomoses of the proximal and postscalenic stumps of donor's subclavian artery to the proximal and prescalenic stumps of recipient's subclavian artery; (2) end-to-side venous anastomosis of the donor's anterior vena cava to the recipient's brachiocephalic venous trunk; and (3) heterotopic implantation of the proximal and distal orifices of the grafted trachea into the neck. Ten adult Large White pigs underwent direct revascularization of a thyrotracheal allograft with (n = 6, group 1) and without (n = 4, group 2) venous drainage. All grafts of group 2 exhibited a venous infarction, extensive inferior thyroid artery thrombosis, and ischemic and suppurative thyrotracheal necrosis 1 to 2 days after transplantation. In group 1, the length of the grafted trachea and number of rings were 9.75 +/- 1.5 cm and 22.1 +/- 3.3, respectively; ischemic time was 236.3 +/- 338.3 minutes. Group 1 pigs were put to death 4 (n = 4) and 3 (n =2) weeks after transplantation. All tracheal grafts had histologically normal airway epithelium; isolated areas of necrotic ischemia of the chorion and submucosa lasted for the first 7 days after transplantation but disappeared after epithelial regeneration. Premortem angiograms showed that all vascular anastomoses were patent. Grafts were histologically normal at postmortem examinations and all but one had no rejection. This large animal model demonstrates that long tracheal allografts might be transplanted by means of this direct revascularization and venous drainage technique.

Animals↗

Tracheoesophageal fistula caused by mycobacterial tuberculosis adenopathy.

Tracheoesophageal fistulas resulting from a Mycobacterium tuberculosis infection are uncommon. We describe a patient with such a lesion that had the radiologic and clinic appearance of a malignant tracheoesophageal fistula. Use of an anterior cervical approach with one-stage esophageal repair along with tracheal resection and anastomosis allowed definitive diagnosis and treatment of this life-threatening complication.

Aged↗

Tracheal allograft replacement. An unsuccessful method.

Replacement of the tracheal conduit remains a difficult and unresolved surgical problem. We present an experimental study of 20 pigs undergoing replacement of the cervical trachea using glutaraldehyde (n = 5), glycerol (n = 5), lyophilized (n = 5) and cryopreserved (n = 5) pretreated allogenic grafts (AGs). In the lyophilized group, a stainless steel spiral endoprosthesis was used as stent. A segment of native trachea measuring 3.2 +/- 0.3 cm (range: 1-5 cm) in length and 1.4 +/- 0.02 cm in diameter was resected and replaced with AGs measuring 3.8 +/- 0.2 cm in length and 1.4 +/- 0.2 cm in diameter. Neither immunosuppressive agents nor steroids were given. Animals were followed up with weekly bronchoscopy, and trachea and chest roentgenography. Those receiving glutaraldehyde AG (21.6 +/- 6.4 days) and lyophilized AG (19.5 +/- 7.8 days) had a longer survival than those receiving glycerol AG (6.8 +/- 0.3 days) and cryopreserved AG (5 +/- 0.5 days). At postmortem, grafts were examined grossly and with light microscopy. The cause of death was always airway obstruction, and the underlying processes were: 1) collapse due to cartilaginous microscopic necrosis in cryopreserved and glycerol AGs; 2) necrosis of allograft which crossed the spiral stent for lyophilized AGs; 3) granulation formation, tissue necrosis and anastomosis leakage in glutaraldehyde AGs. Results demonstrate that passage of necrotic tissue across the grafts represent the common failure denominator, making the different AGs studied unsuitable for long-segment tracheal replacement.

Animals↗

Degradation of acetylcholine in human airways: role of butyrylcholinesterase.

1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso-OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso-OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue.

Acetylcholine↗

[Parathyroid cyst of the anterior mediastinum].

A mediastinal cyst measuring 6 cm was removed by manubriotomy in a 66-year-old woman. This patient had no clinical or biological evidence of hyperparathyroidism. The cyst was close to the thymus and compressed the innominate venous trunk. It contained a clear fluid. Normal parathyroid tissue was present in the capsular wall that was fibrous and partially calcified. This cysts are rare and their mediastinal localization is exceptional.

Aged↗

[Solitary plasmacytoma of the trachea. Apropos of a case].

A case of solitary plasmacytoma of the trachea is reported. Immunohistochemical study is mandatory to prove a monoclonal immunophenotyping. Research for signs of systemic disease and follow up over a long period of time are indicated. Surgery alone, sometimes followed by irradiation, seem to be the treatment of choice. In most cases, complete resolution is observed.

Aged↗