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2.
Expert Rev Vaccines ; 19(4): 305-311, 2020 04.
Article in English | MEDLINE | ID: mdl-32163307

ABSTRACT

INTRODUCTION: Decision-making for patients and their families in the field of vaccination is difficult, involving many multidimensional factors. The complexity of this process is directly responsible for the phenomenon of vaccine hesitancy. Decision aids are instruments that provide information on a specific subject, explaining the advantages and disadvantages of a decision in a personalized way, thus clarifying the patient's values. AREAS COVERED: A systematic review using PRISMA guidelines was conducted to carry out an inventory of decision aids in the field of vaccination and assess their impact on vaccine coverage and decisional conflict. EXPERT OPINION: Decision aids reduce decision-making conflict and could be good tools to address the phenomenon of vaccine hesitancy. It seems essential to integrate health professionals and patients into the design of future decision aids. This would simplify the use of these tools during the consultation. However, their effect on vaccine coverage remains uncertain. Further studies seem necessary in order to conclude that vaccination coverage is effective.


Subject(s)
Decision Support Techniques , Vaccination Refusal/psychology , Vaccination/psychology , Decision Making , Humans , Patient Participation , Vaccination Coverage , Vaccines/administration & dosage
3.
Proc Math Phys Eng Sci ; 474(2209): 20170678, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29434516

ABSTRACT

The static reconfiguration of flexible beams exposed to transverse flows is classically known to reduce the drag these structures have to withstand. But the more a structure bends, the more parallel to the flow it becomes, and flexible beams in axial flows are prone to a flutter instability that is responsible for large inertial forces that drastically increase their drag. It is, therefore, unclear whether flexibility would still alleviate, or on the contrary enhance, the drag when flapping occurs on a reconfiguring structure. In this article, we perform numerical simulations based on reduced-order models to demonstrate that the additional drag induced by the flapping motion is almost never significant enough to offset the drag reduction due to reconfiguration. Isolated and brief snapping events may transiently raise the drag above that of a rigid structure in the particular case of heavy, moderately slender beams. But apart from these short peak events, the drag force remains otherwise always significantly reduced in comparison with a rigid structure.

5.
Leukemia ; 29(1): 76-85, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24813920

ABSTRACT

Kinase inhibitors block proliferative signals in BCR-ABL1+ leukemic cells, but their capacity to induce apoptosis is poorly understood. Initial studies suggested that very brief exposure to kinase inhibitors was sufficient to induce apoptosis in chronic myeloid leukemia (CML) cells. However, flaws in this experimental model have subsequently been identified, leading to the conclusion that apoptosis only occurs with sustained low-level kinase inhibition. Thus, the minimum duration of complete kinase inhibition required to commit CML cells to death is unknown. Here we confirm that <1 h is insufficient to induce significant commitment to death in BCR-ABL1+ cell lines and in primary CD34+ progenitor cells, and establish that commitment to cell death only occurs if kinase inhibition is maintained for 4 h or more. Remarkably, signal transducer and activator of transcription 5 (STAT5) inhibition in combination with transient (<1 h) tyrosine kinase inhibitor (TKI) exposure proved lethal for CML progenitors, despite the reactivation of Bcr-Abl after 1 h. JAK kinase inhibition did not induce cell death in combination with transient TKI exposure. Thus, STAT5 appears to be a critical determinant of the time-dependent sensitivity of CML progenitor cells to TKI treatment in a Bcr-Abl-dependent, but JAK-independent, manner. We conclude that combining kinase inhibition with STAT5 inhibition represents a promising therapeutic approach in BCR-ABL1+ leukemias.


Subject(s)
Apoptosis/drug effects , Janus Kinase 2/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Protein Kinase Inhibitors/pharmacology , STAT5 Transcription Factor/antagonists & inhibitors , Antigens, CD34/immunology , Blotting, Western , Genes, abl , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology
6.
Ann Fr Anesth Reanim ; 33(6): 421-6, 2014 Jun.
Article in French | MEDLINE | ID: mdl-24880555

ABSTRACT

A 30-year-old woman, with no medical history, is operated on for breast implants. In recovery room, an episode of torsade de pointes occurs, progressing to ventricular fibrillation. The ECG after cardiopulmonary resuscitation and conversion to a normal sinus rhythm shows a corrected QT interval prolongation, whereas it is normalized after 48hours. We hypothesize that a ventricular fibrillation occurred after a torsade de pointes, due to drug-induced long QT syndrome during general anesthesia, with probably drug interaction.


Subject(s)
Anesthesia, General/adverse effects , Heart Arrest/chemically induced , Long QT Syndrome/chemically induced , Adrenergic beta-Antagonists/therapeutic use , Adult , Breast Implantation/methods , Cardiopulmonary Resuscitation , Electrocardiography , Female , Heart Arrest/physiopathology , Heart Arrest/therapy , Humans , Long QT Syndrome/physiopathology , Long QT Syndrome/therapy , Torsades de Pointes/chemically induced , Torsades de Pointes/therapy , Ventricular Fibrillation/therapy
9.
Oncogene ; 30(3): 372-8, 2011 Jan 20.
Article in English | MEDLINE | ID: mdl-20838377

ABSTRACT

Sphingosine kinase 1 (SK1) catalyses the formation of bioactive phospholipid sphingosine 1-phosphate (S1P). Elevated cellular SK1 activity and S1P levels enhance cell proliferation and survival, and are strongly implicated in tumourigenesis. Regulation of SK1 activity can occur through various mechanisms, including phosphorylation and protein-protein interactions. We have previously shown that eukaryotic elongation factor 1A (eEF1A) interacts with and directly activates SK1, but the mechanisms regulating this were undefined. Notably, eEF1A has GTPase activity and can exist in GTP- or GDP-bound forms, which are associated with distinct structural conformations of the protein. Here, we show that the guanine nucleotide-bound state of eEF1A regulates its ability to activate SK1, with eEF1A.GDP, but not eEF1A.GTP, enhancing SK1 activity in vitro. Furthermore, we show that enhancing cellular eEF1A.GDP levels through expression of a guanine nucleotide dissociation inhibitor of eEF1A, translationally controlled tumour protein (TCTP), increased SK1 activity in cells. We also examined a truncated isoform of eEF1A1, termed prostate tumour inducer-1 (PTI-1), which can induce neoplastic cell transformation through undefined mechanisms. PTI-1 lacks the G protein domain of eEF1A1 and is therefore unable to undergo the GTP-binding-induced conformational change. Notably, we found that PTI-1 can directly activate SK1 and that this seems to be essential for neoplastic transformation induced by PTI-1, as chemical SK1 inhibitors or overexpression of a dominant-negative SK1 blocked this process. Thus, this study defines the mechanism regulating eEF1A-mediated SK1 activation, and also establishes SK1 as being integral for PTI-1-induced oncogenesis.


Subject(s)
Cell Transformation, Neoplastic , Guanine Nucleotides/physiology , Peptide Elongation Factor 1/physiology , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Animals , Base Sequence , CHO Cells , Cricetinae , Cricetulus , DNA Primers , Enzyme Activation , Humans , Tumor Protein, Translationally-Controlled 1
11.
Neurochirurgie ; 47(1): 25-33, 2001 Feb.
Article in French | MEDLINE | ID: mdl-11283452

ABSTRACT

Retrospective analysis of 222 cases of degenerative disc disease treated by threaded cage fusion. The objective was to determine the safety and efficiency of lumbar interbody fusions using screwed titanium cages and autogenous bone. Two hundred twenty-two patients had lumbar fusion at 243 levels between L2 and S1, at one or two disc spaces. Main indication was discogenic back pain with radicular leg radiation in degenerative discopathy complicated by disc protusion, segmental canal stenosis with chronic instability or spondylolysthesis of the first degree. Previous failed surgery after discectomy, nonunion or biologically cured discitis were other indications in selected cases. Results were classified as good to excellent in 80%, 15% improved but remained disabled, 5% had minimal or no improvement. Fusion rate was 91% at one year and 96% at 2 years. Peroperative dural tears occurred in 10 patients and transient neurological deficits in 9. A superficial infection occurred in one patient. Reoperation in the first three months included a cage revision in one patient and a foraminotomy in another. Two osteoporotic women needed an additional posterior fixation for kyphotic deformity. In conclusion, lumbar interbody fusion with threaded titanium cages appears to be efficacious with an acceptable rate of complications. Experience up to 7 years confirms that impression. Long term observation is needed before recommending this new method.


Subject(s)
Bone Screws , Spinal Diseases/surgery , Spinal Fusion/methods , Adult , Aged , Female , Humans , Low Back Pain/etiology , Male , Middle Aged , Postoperative Complications , Radiography , Reoperation , Retrospective Studies , Spinal Diseases/complications , Spinal Diseases/diagnostic imaging , Titanium , Treatment Outcome
12.
Acta Neurochir (Wien) ; 142(4): 425-33; discussion 434, 2000.
Article in English | MEDLINE | ID: mdl-10883340

ABSTRACT

STUDY DESIGN: Retrospective analysis of 357 cases of degenerative disc disease treated by interbody fusion with threaded titanium cages. OBJECTIVE: To determine the safety and efficiency of cervical and lumbar interbody fusions using threaded titanium cages and autogenous bone. SUMMARY OF BACKGROUND DATA: Stabilizing the anterior column by interbody fusion, though reported over 50 years ago, is less commonly done than posterior fusions. The recent development of rigid cages housing autogenous bone simplifies the technique of interbody fusion. This report shows our combined results using this technique. MATERIALS AND METHODS: One hundred thirty-five patients had cervical fusions at 175 levels between C3 and C7. Two hundred twenty-two patients had lumbar fusion at 243 levels between L2 and S1. All surgeries involved one or two disc spaces except for one three level cervical fusion. We implanted all disc spaces with threaded cages containing autogenous bone. RESULTS: In the cervical area, 95% of the radiculopathic patients had a good to excellent result, but only 50% of the myelopathic patients did so. At lumbar level, 80% of the patients were classified as good to excellent, 15% improved but remained disabled, 5% had minimal or no improvement. The cervical fusion rate was 90% at 6 months and 100% at one year. Lumbar fusion rate was 91% at one year and 96% at 2 years. No late breakage or cage displacement occurred. CONCLUSIONS: Cervical and lumbar interbody fusions with threaded titanium cages appear to be efficacious with few complications. Long term follow-up (4 years cervical, 7 years lumbar) confirms that impression.


Subject(s)
Cervical Vertebrae/surgery , Internal Fixators , Lumbar Vertebrae/surgery , Spinal Fusion/instrumentation , Titanium , Adult , Aged , Cervical Vertebrae/diagnostic imaging , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Radiography , Reoperation , Spinal Fusion/adverse effects , Spinal Fusion/methods , Treatment Outcome
14.
J Clin Neurosci ; 2(2): 129-31, 1995 Apr.
Article in English | MEDLINE | ID: mdl-18638797

ABSTRACT

Though recommended some years ago by Cloward, PLIF (posterior lumbar interbody fusion) was not widely used for many years. Recently many authors have recognised PLIF as a preferred technique for lumbar stabilisation. Preservation or re-establishment of disc height is associated with an improved patency of the intervertebral foramen. The use of the threaded fusion cage (TFC) provides immediate stabilisation, preservation of disc height due to highly resistant material, and long term fusion with autogenous bone. The instrumentation, designed in association with the cage, provides a safe environment for the neural structures during the procedure. It also makes the procedure more reproducible and less dependent on the operator. The learning curve for doing the operation is rapid. Using the Prolo scale, on the economic and functional scales, 83% of cases were rated good to excellent. The fusion rate was 94% at one year.

15.
Prostaglandins ; 44(6): 543-54, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1335586

ABSTRACT

The 5-lipoxygenase (5-LO) inhibitors BI-L-239 and A-64077 were compared with the 5-LO translocation inhibitor MK-886 for the ability to inhibit leukotriene B4 (LTB4) biosynthesis by chopped (1 mm3) guinea pig lung. LTB4 synthesis by ovalbumin-sensitized chopped lung tissue was determined after stimulation with either calcium ionophore (A23187) or antigen. With A23187 stimulation, MK-886 was more potent (IC50 = 0.39 +/- 0.23 microM, mean +/- SEM, p < 0.01) than BI-L-239 (IC50 = 2.48 +/- 0.46 microM) or A-64077 (IC50 = 4.68 +/- 0.70 microM) and BI-L-239 was more potent than A64077 (p < 0.02). Thus, the order of potency was MK-886 > BI-L-239 > A-64077 for inhibition of calcium ionophore-induced LTB4 generation. There was no significant differences in potency of the compounds in chopped lung stimulated with antigen: IC50 for LTB4 synthesis by A-64077 = 3.31 +/- 1.70 microM, for BI-L-239 = 9.06 +/- 4.94 microM, and for MK-886 = 13.33 +/- 7.91 microM. The ability of these compounds to inhibit contraction of tracheal tissue from actively sensitized guinea pigs in response to antigen was also determined in the presence of indomethacin (15 micrograms/ml), mepyramine, and atropine (5 micrograms each/ml). Both 5-LO inhibitors inhibited antigen-induced contraction, with IC50 values for BI-L-239 and A-64077 of 1.58 and 4.35 microM respectively. MK-886 was ineffective at inhibiting antigen-induced tracheal contraction in vitro at concentrations up to 30 microM. In summary, these compounds inhibit antigen-induced and A23187-induced leukotriene biosynthesis in guinea pig tissue. These 5-LO inhibitors were similarly effective at inhibiting antigen-induced tracheal contraction where MK-886 was ineffective.


Subject(s)
Indoles/pharmacology , Leukotriene B4/antagonists & inhibitors , Leukotriene B4/biosynthesis , Lipoxygenase Inhibitors/pharmacology , Lung/drug effects , Muscle, Smooth/drug effects , Animals , Guinea Pigs , Hydroxyurea/analogs & derivatives , Hydroxyurea/pharmacology , In Vitro Techniques , Lung/metabolism , Male , Muscle Contraction/drug effects , Muscle Contraction/immunology , Muscle, Smooth/immunology , Ovalbumin/immunology , Phenols/pharmacology , Trachea/drug effects
16.
J La State Med Soc ; 143(7): 25-9, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1919286

ABSTRACT

A series of 60 cases of percutaneous disc excisions is presented. There were 43 males and 17 females with an average age of 36 years. All cases were failures of conservative treatment and were disabled for their usual occupation. Results were excellent or good in 44 cases, satisfactory in four and failures in eight. There was no postoperative complication. The importance of a complete radiologic workup is emphasized. The cost/benefit and risk/benefit ratios of this operation compare favorably with conventional open laminectomy. The procedure is best indicated in younger patients with good distal water content and contained herniated lumbar disc. It is contraindicated in patients with a free fragment and in patients with previous surgery at the same level.


Subject(s)
Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Adult , Aged , Female , Humans , Length of Stay , Male , Methods , Middle Aged , Prognosis
18.
J Neurosurg ; 65(6): 856-9, 1986 Dec.
Article in English | MEDLINE | ID: mdl-3021933

ABSTRACT

Cylindromas are rarely encountered in the neurosurgical field. Four cases of this rare tumor are presented. Conventional and computerized tomography scanning were most useful in establishing the diagnosis; angiography did not provide any further information. Because these tumors are well demarcated from surrounding structures, even in cases of recurrence, surgery is the treatment of choice. Radiation therapy is useful in the postoperative management. Long survival times with multiple recurrences are the rule.


Subject(s)
Carcinoma, Adenoid Cystic/surgery , Skull Neoplasms/surgery , Adult , Carcinoma, Adenoid Cystic/pathology , Female , Humans , Male , Middle Aged , Skull Neoplasms/pathology
19.
Surg Neurol ; 26(1): 37-44, 1986 Jul.
Article in English | MEDLINE | ID: mdl-3715698

ABSTRACT

A series of 28 cases of meningioma of the tuberculum sellae is reviewed. This tumor was most frequent in the fifth decade, with a clear predominance in women. Neurological and endocrine deficits were minimal, whereas ophthalmologic signs were always present. Visual deficits were bilateral in cases with more than a 1-year history. Osteoma of the tuberculum sellae was rare and had no correlation with tumor size. Angiography of the internal carotid artery was found useful in demonstrating vascular displacements and tumor blush. Computed tomography was the most reliable diagnostic tool. All patients underwent a unilateral pterional craniotomy using the operating Outside of patients with total blindness, improvement of visual acuity was the rule, even in cases of long-term duration. Best results were obtained in patients operated upon within 1 year of the onset of visual symptoms.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Aged , Female , Humans , Male , Meningeal Neoplasms/diagnostic imaging , Meningioma/diagnostic imaging , Middle Aged , Radiography , Sella Turcica/diagnostic imaging , Sella Turcica/surgery
20.
Surg Neurol ; 25(4): 361-8, 1986 Apr.
Article in English | MEDLINE | ID: mdl-3952630

ABSTRACT

Six cases of hyperthyroidism secondary to thyroid-stimulating hormone (TSH)-hypersecreting pituitary adenomas are presented (five females and one male). Hyperthyroidism presenting with diffuse goiter was associated with hyperprolactinemia in three cases. Elevation of triiodothyronine (T3) and thyroxine (T4) plasma levels was associated with TSH levels ranging between 2 and 2,000 microU/mL. Polytomography and computed tomography scanning with coronal views revealed four invasive and two enclosed tumors. Two patients underwent transfrontal operations, four underwent transsphenoidal operations, and one underwent both. Two cases of enclosed adenoma were cured primarily by a transsphenoidal approach without additional pituitary deficit. In four cases of invasive adenomas, operations and radiation therapy resulted in three failures and one cure. In cases presenting with hyperthyroidism and detectable TSH, early neuroradiological studies are indicated, as biological cure can be achieved by the transsphenoidal approach. Early treatment is also advocated because of the tendency for these tumors to become invasive (four out of six tumors).


Subject(s)
Adenoma/metabolism , Hyperthyroidism/etiology , Pituitary Neoplasms/metabolism , Thyrotropin/metabolism , Adenoma/diagnosis , Adenoma/therapy , Adult , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/therapy , Time Factors
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