[Chronic lymphoid B-cell leukemia].
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Female↗
Biomedical subjects
J P Marie
Publications and source records attributed to J P Marie.
Malignant hematopoietic cells induce an increased expression of VEGFR-1 and VEGFR-3 on bone marrow endothelial cells via AKT and mTOR signalling pathways.
Angiogenesis plays a significant role in a variety of malignant hematologic diseases, and it is recognized that it has prognostic value. However, the cellular mechanisms by which malignant hematologic cells induce angiogenesis are not well understood. In order to investigate the role of cells from B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on matrigel. It was found that, in addition to the secretion of angiogenic factors VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. In response to MM cells-increased VEGF receptors on HBMEC, endothelial cell migration was enhanced in a wound artificially produced in a semi-confluent HBMEC culture, a phenomenon which was also down-regulated by the same inhibitors that reversed the increase in VEGF receptors. The present study suggests that, in addition to the classic angiogenic pathway, another mechanism related to an increased expression of VEGFRs on HBMEC might exist in malignant hematopoietic angiogenesis.
Bone Marrow Cells↗
A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia.
To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).
Acute Disease↗
Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?
We determined bone marrow karyotype at diagnosis in four female acute myeloid leukemia (AML) or myelodysplasia patients, aged between 52 and 56 years. In each case, we observed chromosome rearrangement involving the same 4q24 band. Three patients had a balanced reciprocal translocation as the sole abnormality - t(3;4)(q26;q24), t(4;5)(q24;p16) and t(4;7)(q24;q21) - and the fourth had del(4)(q23q24), +4. We used a set of 4q BAC probes for fluorescent in situ hybridization (FISH) in these four cases. We found a 4q24 submicroscopic deletion in all three translocations, with a common deletion of approximately 0.5 Mb. In three cases, we concluded that rearrangement occurred in an early hematopoietic stem cell, as it was detected, in mosaic with a normal karyotype, in a fraction of remission bone marrow cells, peripheral T and B lymphocytes, malignant lymph node T-lymphoma cells in one case and B-lymphoblastoid cell lines established in two cases. Moreover, one of 10 additional AML patients tested by FISH had a normal karyotype and deletion of one of the commonly deleted probe sequences. A tumor suppressor gene may therefore be involved, especially as two patients developed malignant lymphoma at the same time as myeloid proliferation.
Acute Disease↗
Hamartoma of the middle ear: a case study.
Hamartomas and teratomas are rare tumors in children. Its location in head and neck is quite exceptional. An unusual case of hamartoma in the middle ear is reported in a 5-month-old child. The tumor was isolated without associated malformation. Definitive diagnosis was made after surgery and based on histological results. At 2 years follow-up, no recurrence was observed. CT-scan is useful in order to reach a final diagnosis. Although rare, this type of tumor should be considered in the differential diagnosis of a middle ear mass during childhood.
Ear Diseases↗
Implementation of the European Laryngological Society (ELS) basic protocol for assessing voice treatment effect.
OBJECTIVES: 93 patients with various kinds of organic benign voice pathology (vocal fold nodules, polyp, Reinke's oedema, unilateral paralysis, sulcus/scar) and/or with muscle tension dysphonia, were evaluated before and after their voice treatment (phonosurgery with voice therapy, antireflux medication, or voice therapy alone) in order to check the clinical relevance of a basic multidimensional protocol for assessing functional results of voice treatments, as developed by the Committee on Phoniatrics of the ELS. MATERIAL AND METHOD: The protocol has been used in different university voice clinics. It comprises 5 dimensions: Perception: Grade, Breathiness and Roughness from the GRBAS-scale, rated by two experienced judges: a phoniatrician/laryngologist and a speech therapist. Acoustics: Jitter % and Shimmer % computed on a /a:/, at comfortable loudness and pitch. Also Fo-range and softest possible intensity. Videostroboscopy: Glottal closure, regularity, mucosal wave and symmetry, rated separately. Phonation quotient: computed by dividing the vital capacity (ml) by the maximum phonation time (s) (best value of 2x3 trials). Self rating by the patient: voice quality in itself and general social/occupational handicap due to the voice problem rated separately. RESULTS: Results show that, at group level, the overall effects for each parameter indicate a significant improvement after treatment. However, the correlations between the pre/post changes for the different parameters are weak (low redundancy). CONCLUSION: The assessment of voice pathology needs to be multidimensional, as these multidimensional informations about voice changes lead to a better understanding of the actual way in which a treatment works.
Acoustics↗
Comparison between anatomy and resistance of upper airway in normal subjects, snorers and OSAS patients.
Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty-five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone.
Adult↗
[Therapeutic impact of streptococcal and enterococcal bacteremia in hematology patients].
From January 1999 to May 2000 (17 months), 21 strains of streptococci and four strains of enterococci have been isolated from 74 blood cultures in 25 infectious episodes in hematologic patients. They concerned 21 patients, of 21 to 77 years old. These patients suffered from acute leukaemia (14 cases), chronic lymphoid leukaemia (two cases), non-Hodgkin's lymphoma (two cases) or myeloma (three cases). Seventeen patients displayed a single streptococcal or enterococcal episode, two had two episodes in the course of a single stay in the hospital, two others in the course of two different stays. During 16 episodes (64%), the bacteremia occurred within 15 days after the onset of neutropenia consecutive to antimitotic chemotherapy, and in nine episodes (36%) it has occurred after a period exceeding 15 days. In six cases the patients had already received antibiotics with a large antibacterial activity (beta-lactam, fluoroquinolone and/or glycopeptide +/- aminoside) and in four cases a single antibiotic (synergistine or cotrimoxazole). Most streptococci (20/21) were oral streptococci (ten Streptococcus mitis, five S. oralis, two S. sanguis, three S. pneumoniae). A single strain of beta-hemolytic streptococci has been identified as S. dysgalactiae subsp. equisimilis. The enterococci were one strain of Enterococcus faecalis and three E. faecium. Ten streptococci were susceptible to 0.25 mg/L of penicillin G, ten were less susceptible (0.5 < or = MIC < 32 mg/L), and a strain was resistant (MIC = 32 mg/L). Eighteen strains were susceptible to amoxicillin and cefotaxime. For three strains, the MICs of amoxicillin and cefotaxime (8-16 mg/L and 8-32 mg/L, respectively) were higher. Levels of resistance of the enterococci to the beta-lactam (penicillin, amoxicillin, and piperacillin) were variable. All species were susceptible to glycopeptides. Three patients were transferred in intensive care unit for respiratory distress or shock syndrome. Their evolution has remained severe under antibiotherapy comprising beta-lactam or vancomycin associated with an aminoside. This results demonstrate the interest of species identification to adapt the antibiotic treatment and confirms the frequency of oral streptococci in severe bacteremia in neutropenic patients.
Adult↗
[Ewing's sarcoma of the head and neck: a case report].
We report a case of Ewing's sarcoma located in the ethmoid sinus. The patient complained of facial pain, anosmia and visual defect. Diagnosis was established at microscopic examination with histoimmunochemistry and molecular biology. Treatment combined chemotherapy and surgical resection with skull base reconstruction and post-operative ratio and chemotherapy.
12E7 Antigen↗
JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia.
One of the best-characterized resistance mechanisms in acute myeloid leukemia (AML) is the drug extrusion mediated by P-glycoprotein (Pgp). Recently the results of workshops organized by several groups concluded that accurate measurement of low activity of Pgp is a difficult goal in clinical samples. Therefore, highly sensitive and specific assays were developed to assess the functionality of Pgp using JC-1, a fluorescent molecule with the different emission wavelength (green and red fluorescence) according to its concentration in 129 AML samples. It was shown that JC-1 (green and red bands) may define 3 groups of patients: resistant (R) (29% of patients), intermediate (I) (36%), and sensitive (S) (35%). In contrast, rhodamine 123 assay detected only the R group defined by JC-1. Nevertheless, the I group has an intermediate expression of Pgp (0.39, 0.29, and 0.19 for the R, I, and S groups, respectively, P =.002), an intermediate biologic profile (percentage of CD34, 95%, 67%, and 44%, respectively, P <.0001; in vitro resistance to daunorubicin, 94 microM, 20 microM, and 12 microM, respectively, P =. 02), and an intermediate prognosis (achievement of complete remission, 55%, 65%, and 87%, P =.006; 3-year disease-free survival, 11%, 16%, and 36%, respectively, P =.005; and 3-year overall survival, 0%, 20%, and 51%, respectively, P <.0001). Therefore, JC-1 appeared to be a more convenient and simple way to detect a functional Pgp in clinical AML samples than rhodamine 123. (Blood. 2001;97:502-508)
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Post-intubation vocal cord paralysis: the viral hypothesis. A case report.
After digestive surgery, a 20-year-old man presented dysphonia and fever. Indirect laryngoscopy revealed a left vocal cord paralysis with no structural lesion. IgM and IgG were positive for cytomegalovirus and negative for human immunodeficiency virus, herpes simplex virus, varicella zoster virus and Epstein-Barr virus. The patient recovered spontaneously with a normal voice, and the mobility of vocal cord recovered within 3 months. The aetiology of post-intubation vocal cord paralysis (VCP) remains controversial. Vocal cord paralysis with cytomegalovirus has been reported in two cases associated with acquired immunodeficiency syndrome. Vocal cord paralysis secondary to viral disease has also been described in other circumstances. panied by polyneuritis, especially in immunocompromised patients. We report the case of a patient with transitory unilateral post-intubation vocal cord paralysis which could have been related to a virus infection.
Adult↗
Dysphonia and dysphagia as primary manifestations of invasive aspergillosis.
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Aspergillosis↗
A case of disseminated aspergillosis with thyroid involvement.
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Aged↗
Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects.
Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.
Adult↗
Cell cycle regulatory protein expression in fresh acute myeloid leukemia cells and after drug exposure.
Characteristics of treatment-induced cell cycle arrest are important for in vitro and in vivo sensitivity of acute myeloid leukemia (AML) cells to cytotoxic drugs. We analyzed the expression of the major G1 cell cycle regulators (p21Cip1, p27Kip1, cyclins D, cyclin E and pRb) in 41 fresh AML cell samples. The level of p27 expression was the only factor correlated with the response to chemotherapy, a high level of p27 expression being predictive of complete remission. There was a close relation between expression of pRb, cyclin D2 and FAB subtype, illustrated by the absence of both proteins in most samples having a monocytic component (M4, M5). We also assessed the expressions of pRb, cyclin E, p21 and p27 and the activity of cdk2, the major regulator of S-phase entry, after exposure to cytosine-arabinoside (AraC) and daunorubicin (DNR), and found these proteins could characterize time- and dose-dependent cellular response to each drug. We observed hyperphosphorylated pRb, increased levels of cyclin E and a high cdk2 activity, but no p21 induction, in AML cells exposed to 10(-6) M AraC. After exposure to 10(-5) M AraC, corresponding to the serum concentration reached in high-dose AraC regimens (HDAraC), a strong p21 induction was observed, associated with similarly overexpressed cyclin E and even higher cdk2 activity than after 10(-6) M AraC, while apoptosis was significantly increased. These data suggest that cdk2 activity is likely to play a role in AraC-induced apoptosis in AML cells. This mechanism may account for high efficacy of HDAraC in cells showing little sensitivity to conventional AraC doses.
Apoptosis↗
Drug resistance in hematologic malignancies.
Drug resistance eventually occurs in most hematologic malignancies treated with chemotherapy. The mechanisms responsible for drug resistance include expression of transporters of xenobiotics of the adenosine triphosphate-binding cassette protein superfamily (P-glycoprotein, multidrug resistance associated proteins, breast cancer resistance protein), modifications of enzymes like deoxycytidine kinase, and defects in chemotherapy-induced apoptosis. The efforts to overcome this drug resistance have been focused, thus far, on modulation of P-glycoprotein. Several compounds were manufactured for this purpose, and phase III trials of PSC833, one of the most potent P-glycoprotein inhibitors, are completed. The emergence of modulators with several adenosine triphosphate-binding cassette protein targets, like GG120918 (inhibiting P-glycoprotein and breast cancer resistance protein) and VX710 (inhibiting P-glycoprotein and multidrug resistance associated protein 1), are of clinical interest in malignancies often expressing several efflux pumps simultaneously. Another approach is the use of "furtive" drugs like liposomal or nanoparticular anthracyclines.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Adenocarcinoma of the ethmoid sinuses: results of a retrospective study in Rouen].
Ethmoid adenocarcinoma is a rare tumour of the ethmoidal sinuses. The authors report on the clinical features, treatment and follow-up results in 19 cases. Risk factors were those regularly encountered. Delay to diagnosis was long due to the nonspecific clinical features and course. Nasal endoscopy was essential for follow-up. Computed tomography and magnetic resonance imaging were also required to assess tumour spread. Our results suggest that radiotherapy following surgery should be preferred. Survival rate is generally low for this type of tumor. We had 77% survival at 5 years.
Adenocarcinoma↗
[Cutaneous manifestations of B-CLL masked by florid epithelioid granulomatous response].
We report an unusual case of iterative cutaneous manifestations of B-cell chronic lymphocytic leukaemia, masked by a florid epithelioid granulomatous response. These cutaneous lesions appeared without blood hyperlymphocytosis or lymph node enlargement. The diagnosis of cutaneous tumorous infiltrates was morphologically very difficult and required immunohistochemistry as well as PCR. This observation stresses the diagnostic difficulties encountered in lymphoma, with intense stroma reaction and the need for complementary techniques to reach the right diagnosis and thus deliver appropriate therapy.
Aged↗