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1.
Orthop Traumatol Surg Res ; 102(2): 255-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26947733

ABSTRACT

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was recently licensed for local administration during posterior lumbar fusion. In this indication, considerable uncertainty remains about the nature and mechanisms of the many adverse effects of rhBMP-2, such as ectopic bone formation. We report a case of ectopic bone formation with impingement on a facet joint and incapacitating low back pain after minimally invasive transforaminal L5-S1 interbody fusion with local application of rhBMP-2 (InductOs(®)). Revision surgery was eventually performed to alleviate the symptoms by removing the ectopic bone. Caution is in order regarding the use of rhBMP-2 during posterior lumbar fusion. Every effort should be made to minimise the risk of complications.


Subject(s)
Bone Morphogenetic Protein 2/adverse effects , Ossification, Heterotopic/chemically induced , Spinal Fusion/adverse effects , Transforming Growth Factor beta/adverse effects , Adult , Female , Humans , Low Back Pain/etiology , Lumbar Vertebrae , Ossification, Heterotopic/complications , Ossification, Heterotopic/surgery , Recombinant Proteins/adverse effects , Reoperation , Spinal Fusion/methods
2.
Neurochirurgie ; 61(6): 398-400, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26597606

ABSTRACT

Epidural angiolipomas are uncommon benign tumors of the spine. Their clinical presentation is usually a progressive spinal cord compression. We report the case of a 22-year-old patient who presented with an acute paraparesis and a spontaneous epidural hematoma, which revealed a epidural angiolipoma which extended from C7 to T3. The patient underwent a C7-T3 laminectomy, in emergency, with evacuation of the hematoma and extradural complete resection of a fibrous epidural tumor bleeding. The postoperative course was favorable with regression of neurological symptoms. Epidural angiolipomas can be revealed by spontaneous intratumoral hemorrhage without traumatism. The standard treatment is total removal by surgery.


Subject(s)
Angiolipoma/complications , Hematoma, Epidural, Spinal/etiology , Spinal Cord Neoplasms/complications , Cervical Vertebrae , Humans , Male , Thoracic Vertebrae , Young Adult
3.
Orthop Traumatol Surg Res ; 100(7): 775-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25281548

ABSTRACT

INTRODUCTION: Transoral odontoidectomy is the treatment of choice in cases of anterior bulbo-medullary compression. The development of endoscopic procedures has made it possible to perform odontoidectomy via a minimally invasive endoscopic endonasal approach. We discuss the feasibility, advantages, and limitations of this surgical approach. MATERIALS AND METHODS: We report a two-center retrospective series of patients who underwent endoscopic endonasal odontoidectomy between September 2011 and February 2013. Preoperative characteristics, intraoperative data, clinical course, and postoperative complications were studied. The patients were followed for a minimum of 6 months. Cervico-occipital posterior fusion was performed during the same hospital stay in cases of preoperative instability. RESULTS: Nine patients underwent decompressive odontoidectomy, for rheumatoid pannus in five cases and basilar impression in four cases. All had progressive neurological symptoms. Seven patients also underwent posterior fusion. In six patients, the C1 anterior arch was preserved. Decompression was achieved satisfactorily in all nine cases. The patients were able to resume oral feeding the day after the intervention. No patient required tracheostomy. We observed no dural fistulae or infectious complications. One patient died 2 months after the intervention of a pulmonary embolism. All patients improved in terms of their preoperative neurological status. CONCLUSION: This short series shows the feasibility of the endoscopic endonasal approach for resection of the dens. This approach allows optimal viewing when using angulated instrumentation and seems to result in low morbidity. In some cases, this approach makes it possible to preserve the C1 anterior arch, thus limiting the risk of cranial settling. LEVEL: IV retrospective study.


Subject(s)
Arthritis, Rheumatoid/complications , Decompression, Surgical/methods , Natural Orifice Endoscopic Surgery/methods , Odontoid Process/surgery , Spinal Cord Compression/surgery , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nose , Retrospective Studies , Spinal Cord Compression/etiology , Treatment Outcome
5.
Orthop Traumatol Surg Res ; 99(1): 94-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23246007

ABSTRACT

BACKGROUND: The anterior approach to the thoraco-lumbar junction of the spine allows therapeutic interventions on post-traumatic, infectious, and neoplastic vertebral lesions from T11 to L2 combining spinal cord decompression, corporectomy, and vertebral body fusion. However, this approach also has a reputation for damaging the intervening anatomic structures (lungs, peritoneum, and diaphragm). The objective of this study was to show that both nervous structure decompression and anterior vertebral reconstruction can be achieved via an anterior minimally invasive extrapleural retroperitoneal (AMIER) approach. MATERIAL: We describe each of the steps of the AMIER approach to the thoraco-lumbar junction of the spine. RESULTS: The AMIER approach ensures excellent exposure that allows full decompression and satisfactory anterior anatomic reconstruction. The main difficulties and complications relate to the lungs, and a painstaking and rigorous technique limits the complications compared to conventional thoraco-phreno-lumbotomy.


Subject(s)
Orthopedic Procedures/methods , Spinal Diseases/diagnosis , Decompression, Surgical/methods , Humans , Lumbar Vertebrae , Minimally Invasive Surgical Procedures , Plastic Surgery Procedures/methods , Retroperitoneal Space , Spinal Fractures/surgery , Spinal Neoplasms/surgery , Thoracic Vertebrae
6.
Neurochirurgie ; 58(6): 369-71, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22727337

ABSTRACT

OBJECTIVE: This case reports atlantoaxial stabilization in case of V3 segment anomaly. PATIENT: We report the case of a patient who was victim of a complex C2 fracture requiring atlantoaxial stabilization whereas the initial cervical 3D CT angiography showed a persistent first intersegmental artery consisting in a V3 segment of the vertebral artery penetrating dura-mater in the spinal canal below the C1 posterior arch without passing through the C1 foramen transversarium. RESULTS: This rare vascular anomaly described in 2 to 5% of the patients led us to modify the screw entrance over the C1 posterior arch in order to obtain a satisfactory stabilization and to limit the risk of vertebral artery injury.


Subject(s)
Axis, Cervical Vertebra/injuries , Bone Screws , Fracture Fixation, Internal/methods , Internal Fixators , Spinal Fractures/surgery , Spinal Fusion/methods , Vertebral Artery/abnormalities , Accidental Falls , Accidents, Home , Aged , Angiography/methods , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/surgery , Axis, Cervical Vertebra/surgery , Dura Mater/blood supply , Fracture Fixation, Internal/instrumentation , Humans , Intraoperative Complications/prevention & control , Male , Neck Pain/etiology , Spinal Fusion/instrumentation , Tomography, X-Ray Computed , Vertebral Artery/diagnostic imaging
7.
Neurochirurgie ; 58(4): 241-5, 2012 Aug.
Article in French | MEDLINE | ID: mdl-22464602

ABSTRACT

INTRODUCTION: Cerebrospinal fluid (CSF) leak is a frequent complication after trans-sphenoidal pituitary surgery. We try to determine the incidence, risk factors, diagnostic procedures, and management of CSF leaks following trans-sphenoidal pituitary macroadenoma surgery. METHODS: A retrospective analysis of 337 patients data. RESULTS: Postoperative CSF leaks occurred in 11 patients (3,1%). Ten patients had to be reoperated. Three patients had meningitis. Intraoperative CSF leak is the only significant predictive factor of postoperative CSF leak. Revision surgery, wide opening of the sella turcica and insufficient reconstruction of the sellar floor also seem to play a role (for six cases of postoperative CSF leak, the closure material had been excluded). CONCLUSION: Prevention of the postoperative CSF leak needs screening of intra-operative CSF leak. The strength of the sellar floor is essential in order to avoid the ejection of the closure material, related to the intracranial pression.


Subject(s)
Cerebrospinal Fluid Rhinorrhea/etiology , Endoscopy/methods , Pituitary Gland/surgery , Postoperative Complications/etiology , Sphenoid Bone/surgery , Cerebrospinal Fluid Rhinorrhea/prevention & control , Humans , Intraoperative Period , Meningitis/complications , Pituitary Neoplasms/surgery , Postoperative Complications/prevention & control , Predictive Value of Tests , Recurrence , Retrospective Studies , Sella Turcica/surgery , Tomography, X-Ray Computed
8.
Neurochirurgie ; 58(5): 275-81, 2012 Oct.
Article in French | MEDLINE | ID: mdl-22425580

ABSTRACT

INTRODUCTION: Atypical and malignant meningiomas are a rare disease whose histological definition is still recent. Their management is not consensual. The aim of this study was to review the outcome, prognostic factors and the role of complementary therapies. PATIENTS AND METHODS: Between 1999 and 2007, 36 patients with atypical or malignant meningiomas were managed in our hospital. All surgical specimens were reviewed according to the 2007 WHO classification system. The sex ratio was 1.25 male, the median age was 59 years. The median follow-up was 55 months. Thirty meningiomas were atypical and six were malignant. RESULTS: Five and 10 years overall survival rate are respectively 72 and 41%, whereas 5 and 10 years progression free survival rate are 61 and 23%. We only identify female sex, age over 70 years and Karnofsky status under 70% as negative prognostic factors. CONCLUSION: Atypical and malignant meningiomas are difficult to manage and have high recurrence and poor survival rates. The prognostic of OMS II meningiomas is heterogeneous. Adjuvant radiation therapy is recommended in case of malignant menigioma or in case of atypical meningioma if incomplete surgical excision is performed.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Adult , Aged , Aged, 80 and over , Disease Progression , Disease-Free Survival , Female , Humans , Karnofsky Performance Status/statistics & numerical data , Male , Meningeal Neoplasms/mortality , Meningeal Neoplasms/radiotherapy , Meningioma/mortality , Meningioma/radiotherapy , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Survival Rate , Treatment Outcome , World Health Organization
9.
Neurochirurgie ; 57(2): 68-72, 2011 Apr.
Article in French | MEDLINE | ID: mdl-21530987

ABSTRACT

Microvascular decompression is an important procedure for the management of microvascular compression syndromes in the cerebellopontine angle (CPA) like trigeminal neuralgia or hemifacial spasm. The ability to identify the offending vessel is the key to success. Can the endoscope help surgeons to identify and understand the responsible conflict in order to treat them? Our series concerns 27 consecutive patients who underwent microvascular decompression systematically using an endoscope with an angulation of 30° at the beginning and the end of the intervention. The decompression procedure was done under microscope. Endoscopic exploration was successful for all patients. Endoscopy improved visualization of the cranial nerves and allowed to see and understand the neurovascular conflicts, which were not able to be observed using the microscope alone for two of the 27 patients. The endoscope is a useful adjunct to microscopic exploration of the cranial nerves in the CPA avoiding significant cerebellar or brainstem retraction.


Subject(s)
Cerebellopontine Angle/blood supply , Cerebrovascular Disorders/surgery , Decompression, Surgical/methods , Endoscopy , Adult , Aged , Combined Modality Therapy , Endovascular Procedures , Humans , Microsurgery , Middle Aged , Retrospective Studies , Vascular Surgical Procedures/methods , Young Adult
10.
Neurochirurgie ; 57(1): 42-5, 2011 Feb.
Article in French | MEDLINE | ID: mdl-20870256

ABSTRACT

We report the case of a 31-year-old patient who had had frontal cephalalgias for several years. CT and MRI anatomical imaging objectified a frontal osteolytic tumor respecting the osseous external table but compressing the superior sagittal sinus. Total en bloc resection of the tumor associated with titan cranioplasty was performed. The postoperative course was uneventful. Three months after surgery the patient no longer reported headache. The anatomical and pathological results concluded in intradiploic cavernous hemangioma. We discuss this case and others described in the literature.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/surgery , Neurosurgical Procedures/methods , Skull Neoplasms/surgery , Skull/surgery , Adult , Craniotomy , Endothelium/pathology , Headache/etiology , Hemangioma, Cavernous, Central Nervous System/pathology , Humans , Magnetic Resonance Imaging , Male , Skull/pathology , Skull Neoplasms/pathology , Superior Sagittal Sinus/pathology , Tomography, X-Ray Computed
11.
Orthop Traumatol Surg Res ; 97(1): 94-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21094109

ABSTRACT

Osteochondromas are usually benign bone tumors found on the metaphysis of long bones. These tumors are rarely located on the spine especially at cervical level. This report presents the case of a 23-year-old man who had previously developed tetraparesis at the age of 13 after infectious myelitis. Recent severe clinical neurological deterioration revealed the diagnosis of osteochondroma arising in the C4 vertebral arch compressing the spinal cord and associated with syringomyelia. Of note in his past history was a treated hip localization. The patient underwent complete surgical excision of the osteochondroma. Postoperative outcome was good with slow clinical recovery from the spinal cord compression. We report this rare cause of spinal cord compression and other cases reported in the literature.


Subject(s)
Cervical Vertebrae , Osteochondroma/complications , Spinal Cord Compression/etiology , Spinal Neoplasms/complications , Diagnosis, Differential , Humans , Laminectomy/methods , Magnetic Resonance Imaging , Male , Osteochondroma/diagnosis , Osteochondroma/surgery , Spinal Cord Compression/diagnosis , Spinal Cord Compression/surgery , Spinal Neoplasms/diagnosis , Spinal Neoplasms/surgery , Young Adult
12.
Neurochirurgie ; 56(5): 404-7, 2010 Oct.
Article in French | MEDLINE | ID: mdl-20594960

ABSTRACT

Primitive malignant rhabdoid tumors of the central nervous system are rare and have a poor prognosis. Adult and adolescent cases are exceptional. We report the case of a 16-year-old girl who presented an intratumoral hemorrhage in a rhabdoid tumor. She was treated with surgery, followed by intravenous and intrathecal chemotherapy. Despite intensive treatment, she died 5 months after diagnosis. We discuss the different therapeutic options for this patient and review the literature on this kind of tumor.


Subject(s)
Brain Neoplasms , Rhabdoid Tumor , Adolescent , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Fatal Outcome , Female , Humans , Rhabdoid Tumor/diagnosis , Rhabdoid Tumor/therapy
13.
Neurochirurgie ; 56(1): 55-8, 2010 Feb.
Article in French | MEDLINE | ID: mdl-20074758

ABSTRACT

We report the case of a patient with spinal cord compression evolving over 36 months with spastic paraparesis. Anatomic imagery showed epidural lipomatosis. No predisposing factors were found. Surgical treatment was decided. A T1-T10 laminectomy with excision of the surplus epidural fat was performed. Immediate and medium-term postsurgical follow-up was favorable with the disappearance of the pyramidal syndrome. Other cases found in literature and the principal predisposing factors are discussed.


Subject(s)
Epidural Space/pathology , Lipomatosis/complications , Lipomatosis/pathology , Spinal Cord Compression/etiology , Epidural Space/surgery , Humans , Laminectomy/methods , Lipomatosis/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Spinal Cord Compression/surgery
14.
Acta Neurochir (Wien) ; 152(3): 481-3, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19652905

ABSTRACT

Spinal neurenteric cyst is a rare congenital lesion that may occur either alone or in the context of a complex malformative disorder. Our case is unusual because of its rare intramedullary location, the association with an important intrathoracic development, and the age of the child at presentation (1 month). An anterior approach through a right-sided lateral thoracotomy was performed for a total resection of the intrathoracic part and a subtotal resection for the intramedullar portion. During 2 years of follow-up, the child presented no neurological deficit and post-operative magnetic resonance imaging found a small residue fixed on the anterior spinal cord without progression.


Subject(s)
Neural Tube Defects/pathology , Neural Tube Defects/surgery , Spinal Cord/abnormalities , Spinal Cord/surgery , Spinal Dysraphism/pathology , Spinal Dysraphism/surgery , Cervical Vertebrae/abnormalities , Cervical Vertebrae/surgery , Humans , Infant, Newborn , Magnetic Resonance Imaging , Male , Neural Tube Defects/complications , Neurosurgical Procedures/methods , Spinal Canal/pathology , Spinal Canal/surgery , Thoracotomy/methods , Thorax/abnormalities , Thorax/pathology , Treatment Outcome
15.
Ann Fr Anesth Reanim ; 28(10): 885-8, 2009 Oct.
Article in French | MEDLINE | ID: mdl-19837548

ABSTRACT

We present the case of a 73-year-old man, operated on for paralyzing sciatica, who displayed acute postoperative respiratory distress and intra-alveolar haemorrhage following the administration of dabigatran etexilate, a new oral antithrombin used in the prevention of venous thromboembolism. This serious incident occurred in a patient who had a 20-year history of chronic thrombocytopenia (platelet level at 100G/l) and a heparin-induced thrombocytopenia and in whom no other aetiology was found (tuberculosis, pneumo-renal syndrome, etc.). The postoperative prevention of thromboembolic events in a patient with high risk bleeding requires intensive monitoring, notably, when prescribing new drugs such as new anticoagulant agents.


Subject(s)
Anticoagulants/adverse effects , Antithrombins/adverse effects , Benzimidazoles/adverse effects , Postoperative Complications/chemically induced , Pyridines/adverse effects , Respiratory Distress Syndrome/chemically induced , Acute Disease , Aged , Dabigatran , Humans , Male , Severity of Illness Index
16.
Acta Neurochir (Wien) ; 151(8): 935-44; discussion 944-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19415173

ABSTRACT

PURPOSE: Therapeutic options for vestibular schwannomas (VS) include microsurgery, stereotactic radiosurgery and conservative management. Early treatment of intracanalicular vestibular schwannomas (IVS) may be advisable because their spontaneous course will show hearing loss in most cases. Advanced microsurgical techniques and continuous intraoperative monitoring of cranial nerves may allow hearing preservation (HP) without facial nerve damage. However, there are still controversies about the definition of hearing preservation, and the best surgical approach that should be used. METHODS: In this study, we reviewed the main data from the recent literature on IVS surgery and compared hearing, facial function and complication rates after the retrosigmoid (RS) and middle fossa (MF) approaches, respectively. RESULTS: The results showed that the average HP rate after IVS surgery ranged from 58% (RS) to 62% (MF). HP varied widely depending on the audiometric criteria that were used for definition of serviceable hearing. There was a trend to show that the MF approach offered a better quality of postoperative hearing (not statistically significant), whereas the RS approach offered a better facial nerve preservation and fewer complications (not statistically significant). CONCLUSIONS: We believe that the timing of treatment in the course of the disease and selection between radiosurgical versus microsurgical procedure are key issues in the management of IVS. Preservation of hearing and good facial nerve function in surgery for VS is a reasonable goal for many patients with intracanalicular tumors and serviceable hearing. Once open surgery has been decided, selection of the approach mainly depends on individual anatomical considerations and experience of the surgeon.


Subject(s)
Craniotomy/methods , Microsurgery/methods , Neuroma, Acoustic/pathology , Neuroma, Acoustic/surgery , Neurosurgical Procedures/methods , Postoperative Complications/prevention & control , Cranial Fossa, Middle/anatomy & histology , Cranial Fossa, Middle/surgery , Cranial Fossa, Posterior/anatomy & histology , Cranial Fossa, Posterior/surgery , Facial Nerve/anatomy & histology , Facial Nerve/surgery , Facial Nerve Injuries/etiology , Facial Nerve Injuries/physiopathology , Facial Nerve Injuries/prevention & control , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sensorineural/prevention & control , Humans , Microsurgery/adverse effects , Neuroma, Acoustic/diagnostic imaging , Neurosurgical Procedures/adverse effects , Occipital Bone/anatomy & histology , Occipital Bone/surgery , Petrous Bone/anatomy & histology , Petrous Bone/surgery , Radiography , Vestibulocochlear Nerve/anatomy & histology , Vestibulocochlear Nerve/pathology , Vestibulocochlear Nerve/surgery
17.
Neurochirurgie ; 55(6): 569-72, 2009 Dec.
Article in French | MEDLINE | ID: mdl-19095271

ABSTRACT

Clostridium perfringens is rare in neurosurgery. The source of clostridial brain abscess is usually a penetrating head injury. We report the case of a 57-year-old man who had parietal glioblastoma resection with local carmustine chemotherapy and who presented a clostridial brain abscess three weeks later. Progression was especially brutal, leading to patient's death in few hours. We discuss the etiology and progression of this case compared to the data reported in the literature.


Subject(s)
Brain Abscess/etiology , Brain Abscess/microbiology , Brain Neoplasms/surgery , Clostridium Infections/etiology , Clostridium Infections/microbiology , Glioblastoma/surgery , Postoperative Complications/microbiology , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/complications , Brain Neoplasms/therapy , Carmustine/adverse effects , Carmustine/therapeutic use , Combined Modality Therapy , Fatal Outcome , Glioblastoma/complications , Glioblastoma/therapy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Complications/etiology , Tomography, X-Ray Computed
18.
J Virol ; 74(19): 9306-12, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10982378

ABSTRACT

The impact of drug resistance mutations induced by nucleoside reverse transcriptase (RT) inhibitors (NRTI) on cytotoxic T-lymphocyte (CTL) recognition of human immunodeficiency virus type 1 strain LAI (HIV-1(LAI)) RT was addressed in 35 treated or untreated patients. Two HIV-1(LAI) RT regions encompassing mutation M41L, L74V, M184V, and T215Y/F were recognized in 75 and 83% mutated and in 33 and 42% unmutated samples, respectively. A total of 41 new CTL epitopes overlapping these mutations were predicted. Mutations enhanced HLA-binding scores of 17 epitopes, decreased scores of 5, and had no effect in 19. Four predicted epitopes containing mutations 41, 74, and 184 were tested and recognized by CD8 cells from mutated or unmutated samples, with frequencies up to 270 gamma interferon spot-forming cells per 10(6) peripheral blood mononuclear cells. Therefore, RT mutations induced by NRTI can increase the immunogenicity of RT for CTL and might allow a better immune control of resistant viruses in vivo, suggesting that specific immune therapy might help prevent these mutations.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cytotoxicity, Immunologic , HIV Infections/immunology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/immunology , Reverse Transcriptase Inhibitors/immunology , Anti-HIV Agents/immunology , Anti-HIV Agents/therapeutic use , Epitopes, T-Lymphocyte/immunology , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Humans , Mutation , Reverse Transcriptase Inhibitors/therapeutic use
19.
AIDS ; 12(12): 1427-36, 1998 Aug 20.
Article in English | MEDLINE | ID: mdl-9727563

ABSTRACT

OBJECTIVES: To determine immunodominant regions and new epitopes for cytotoxic T cells (CTL) directed against the HIV-1 pol products reverse transcriptase (RT), integrase and protease in a large cohort of patients at different stages of disease. DESIGN AND METHODS: Cross-sectional analysis of 98 patients from the French IMMUNOCO cohort (CD4 counts: 125-1050 x 10(6) cells/l), monitored for CTL recognition of HIV-1 pol products using recombinant vaccinia virus constructs and synthetic peptides. RESULTS: Memory CTL responses against HIV-1 pol products were detected in 78% of all patients whatever the stage of disease. RT was more immunogenic (81%, 30 out of 37 patients) than integrase and protease (51% and 24%, respectively). CTL recognition of RT was more frequent against Pol amino acids 310-460 (61%, 11 out of 18 patients) than against the other three portions (Pol 168-310, Pol 450-600, Pol 590-728) in patients with CD4 counts > 400 x 10(6)/l, whereas in patients at advanced stages no prominent differences were observed. Two new clusters of antigenic regions were found in the NH2 segment: three epitopes between amino-acids Pol 200 and 217 and four epitopes between amino-acids Pol 346 and 387, using five different HLA-restricting elements. A new cluster of three conserved epitopes was found in the COOH segment of RT. CONCLUSIONS: This study shows that memory CTL responses against HIV-1 RT, integrase and protease are detectable in most patients at different stages of disease. The capacity of CTL to recognize simultaneously clusters of epitopes may become important for the immune control to reinforce antiretroviral drug efficiency.


Subject(s)
HIV Integrase/immunology , HIV Protease/immunology , HIV Reverse Transcriptase/immunology , T-Lymphocytes, Cytotoxic/immunology , Cohort Studies , Epitopes , Gene Products, pol/immunology , Humans , Immunodominant Epitopes , Immunologic Memory , Peptides/chemical synthesis , Peptides/immunology , Vaccines, Synthetic/immunology , Vaccinia virus/genetics
20.
Int Immunol ; 10(3): 311-23, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9576619

ABSTRACT

Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+ isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8+CD57+ cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-alpha. Altogether these data suggest that CD8hi+CD57+ cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.


Subject(s)
CD57 Antigens/analysis , CD8 Antigens/analysis , Cytotoxicity, Immunologic , T-Lymphocytes/immunology , Cell Differentiation , Down-Regulation , Humans , Lymphocyte Activation , T-Lymphocytes, Cytotoxic/immunology
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