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1.
Eur Ann Otorhinolaryngol Head Neck Dis ; 139(1): 13-16, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34083168

ABSTRACT

OBJECTIVES: The main objective of this study was to determine the rate of outpatient management in a population of patients undergoing bilateral ethmoidectomy. The secondary objectives were to evaluate the quality of outpatient management (rate of unscheduled overnight admission, readmission rate, complications) and to compare inpatient and outpatient groups to determine which elements of the phenotype and care pathway favored outpatient management. MATERIALS AND METHODS: A single-center observational study included 204 patients operated on for bilateral ethmoidectomy. Study variables comprised: type of care pathway (outpatient/inpatient), outpatient quality indicators (unscheduled admission, readmission, complications), care pathway, and population characteristics. RESULTS: One hundred and twenty (58.8%) outpatients were operated on. No deaths occurred. The unscheduled admission rate was 7.5%, and the readmission rate 4.1%; at the P<0.005 threshold, there were no significant differences between in- and out-patient groups. Outpatients had earlier surgery (P<0.005), and nasal packing rates and pain on VAS were lower (P<0.005). CONCLUSION: Ethmoidectomy could be carried out as an outpatient procedure in 58.8% of cases, with acceptable quality of care. Selection of patients and the organization of a dedicated care pathway seem to be elements favoring this management.


Subject(s)
Ambulatory Surgical Procedures , Outpatients , Ethmoid Sinus/surgery , Humans , Patient Readmission , Postoperative Complications , Retrospective Studies
2.
Eur Ann Otorhinolaryngol Head Neck Dis ; 138(4): 241-245, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33309220

ABSTRACT

OBJECTIVES: Vocal morbidity resulting from damage to the motor branch of the superior laryngeal nerve (SLN) after endocrine surgery is well known, but diagnosis is often delayed. The present study aimed to quantify these vocal changes acoustically (main objective), and correlate this with the vocal complaints of patients with suspected SLN motor impairment (secondary objective). MATERIAL AND METHODS: Thirty females patients with suspected injury of the SLN cricothyroid branch (CT-) were compared to 30 patients without postoperative vocal impairment (CT+) and to 30 control subjects. Mean, minimal and maximal fundamental frequencies (F0mean, F0min and F0max) and vocal range were measured on /e/ at high frequency, sirens (glissandi), a reading text, and minimal intonation pairs. Subjective vocal impairment was evaluated on the Voice Handicap Index (VHI). RESULTS: A lowering of F0mean associated with vocal range reduction by one fifth (in the reading text) seemed to be specific to CT- patients. Production of questions was affected, with differences in melodic curve and attack. Thyroidectomy within 2 months in itself (without suspected SLN cricothyroid branch injury) also affected these parameters, but to a lesser degree. CT- patients reported greater voice impairment than CT+ patients or controls (P=0.0004). CONCLUSION: Alterations in speech intonation, quantified on minimal pair test, and self-assessed vocal handicap (VHI) are tools that can easily be used in daily practice to screen for SLN motor branch lesion.


Subject(s)
Voice Disorders , Voice , Female , Humans , Laryngeal Nerves , Self Concept , Thyroidectomy , Voice Disorders/etiology
3.
Eur Ann Otorhinolaryngol Head Neck Dis ; 137(5): 387-391, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32057698

ABSTRACT

AIM: To assess the CT scan aspect of cement bridges used to repair incudostapedial joint discontinuity (ISD) and correlate these observations to audiometric data over time. MATERIAL AND METHODS: A retrospective study in 12 patients with cement rebridging for ISD compared pre- and post-operative pure-tone average thresholds, Hounsfield units (HU), and bridge size and position on postoperative CT scans. RESULTS: Mean pre- and post-operative air-bone gap (ABG) was 24.5 and 16dB, respectively. HU did not vary over time post-surgery, with no significant correlation between HU and time to postoperative CTnscan up to 24months (p=0.219). However, a "suggestive" correlation was found between postoperative ABG and HU (p=0.004, r=-0.7). High cement density correlated with good functional outcome: HU <500 indicating functional failure and >1000 indicating ABG closure. CONCLUSION: Immediate cement polymerization quality (high HU) was stable over time and a marker of ossiculoplasty success, correlating with good functional outcome. Particular care should be taken in preparing the cement, and solidification needs to be on dry mucosa-free ossicles.


Subject(s)
Ossicular Prosthesis , Ossicular Replacement , Glass Ionomer Cements , Hearing Loss, Conductive , Humans , Incus/diagnostic imaging , Incus/surgery , Retrospective Studies , Treatment Outcome , Tympanoplasty
4.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(6): 465-468, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31548133

ABSTRACT

AIM: Day surgery (DS) in otology in France is insufficiently implemented compared to other countries of comparable socio-economic level. The aim of the present study was to evaluate changes in surgical practice in "major otology" cases in a hospital center after launching a dedicated ENT DS unit. MATERIAL AND METHODS: This new unit, designed in collaboration with the surgeons, was inaugurated in 2014. Number of procedures, patient demographics, surgery durations, and rates of crossover from DS to conventional management were recorded prospectively for the year before and the year after the launch. All otologic surgery procedures with at least tympanomeatal flap elevation were included; minor surgeries such as grommet insertion were excluded. RESULTS: Between the two time periods, major otology day cases increased from 106 to 153 procedures (+43%). In 2013, the DS rate was 27%, versus 56% in 2015. Otosclerosis surgeries represented 7% in 2013 and 15% in 2015, and type II and III tympanoplasties 3% and 24% respectively. Difference in patient age between DS and conventional surgery was lower in 2015. Crossover rates were 10% in 2013 and 21% in 2015, mainly due to nausea/vertigo (56%) and surgery ending too late in the day (33%). CONCLUSION: Major otologic cases are suitable for DS. Launching this dedicated unit with its specific organization enabled a very significant increase in DS rates, probably due to greater patient satisfaction and surgeons' growing confidence. The main pitfall was in scheduling, with surgery ending too late in the day for discharge home; this has since been corrected.


Subject(s)
Ambulatory Surgical Procedures , Models, Organizational , Otologic Surgical Procedures/methods , Adolescent , Adult , Aged , Ambulatory Surgical Procedures/statistics & numerical data , Ambulatory Surgical Procedures/trends , Appointments and Schedules , Child , Female , Forecasting , France , Health Impact Assessment/methods , Health Impact Assessment/statistics & numerical data , Health Impact Assessment/trends , Humans , Interdisciplinary Communication , Intersectoral Collaboration , Male , Middle Aged , Operative Time , Otologic Surgical Procedures/statistics & numerical data , Otologic Surgical Procedures/trends , Otosclerosis/surgery , Patient Discharge , Patient Selection , Tympanoplasty/methods , Tympanoplasty/statistics & numerical data , Tympanoplasty/trends , Young Adult
5.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(5): 385-391, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31221590

ABSTRACT

OBJECTIVES: The authors present the guidelines of the French Society of Otorhinolaryngology - Head and Neck Surgery (Société française d'oto-rhino-laryngologie et de chirurgie de la face et du cou - SFORL) on the indications for cochlear implantation in children. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: The SFORL recommends that children with bilateral severe/profound hearing loss be offered bilateral cochlear implantation, with surgery before 12months of age. In sequential bilateral cochlear implantation in children with severe/profound hearing loss, it is recommended to reduce the interval between the two implants, preferably to less than 18months. The SFORL recommends encouraging children with unilateral cochlear implants to wear contralateral hearing aids when residual hearing is present, and recommends assessing perception with hearing-in-noise tests. It is recommended that the surgical technique should try to preserve the residual functional structures of the inner ear as much as possible.


Subject(s)
Cochlear Implants , Age Factors , Auditory Perception , Autism Spectrum Disorder , Brain/diagnostic imaging , Deafness/surgery , France , Glucocorticoids/therapeutic use , Hearing Aids , Humans , Infant , Magnetic Resonance Imaging , Quality of Life , Societies, Medical , Vestibular Function Tests
6.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(3): 193-197, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31005457

ABSTRACT

The authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding indications for cochlear implantation in adults. After a literature review by a multidisciplinary workgroup, guidelines were drawn up based on retrieved articles and group-members' experience, then read over by an independent reading group to edit the final version. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence. There is no upper age limit to cochlear implantation in the absence of proven dementia and if autonomy is at least partial. Bilateral implantation may be proposed if unilateral implantation fails to provide sufficiently good spatial localization, speech perception in noise and quality of life, and should be preceded by binaural hearing assessment. Rehabilitation by acoustic and electrical stimulation may be proposed when low-frequency hearing persists. Quality of life should be assessed before and after implantation.


Subject(s)
Cochlear Implantation/standards , Otolaryngology/standards , Aged , Cochlear Implantation/methods , Cognitive Dysfunction/etiology , Cognitive Dysfunction/rehabilitation , France , Hearing Loss/complications , Hearing Loss/rehabilitation , Humans , Middle Aged , Quality of Life , Societies, Medical
7.
Rev Laryngol Otol Rhinol (Bord) ; 135(4-5): 197-200, 2014.
Article in English | MEDLINE | ID: mdl-26521368

ABSTRACT

OBJECTIVES: The "silent sinus syndrome" (SSS) also known as imploding antrum syndrome or chronic maxillary sinus atelectasis consists of painless enophthalmos and inward retraction of the ipsilateral maxillary sinus walls. The aims of the present study were: i) to look for a correlation between the level of volume asymmetry of the maxillary sinuses and the presence of ophthalmological and rhinosinusitis signs, ii) to determine the benefits of a middle meatal antrostomy in SSS cases, and iii) to evaluate the preventive role of neuronavigation surgery in the morbidity of this specific surgery. MATERIALS AND METHODS: We retrospectively analyzed the data of 13 patients operated on for a SSS by middle meatal antrostomy, with the aid of neuronavigation in 7 cases. The median follow up was 30 months. No reconstruction of the orbital floor was performed. Morphometric analysis and modeling of the sinus volume from the preoperative CT scanners were performed to assess the impact of the loss of sinus volume on the symptoms. RESULTS: all patients displayed a retraction of the orbital floor. There was a significant correlation between the magnitude of the decrease in sinus volume and clinical manifestations. Surgical treatment allowed rhinosinusitis symptom disappearance in 53% of patients. Ophthalmological symptoms did not decrease, but stayed stable after the surgical treatment. When neuronavigation surgery was performed, no complications were observed. CONCLUSION: SSS symptoms correlated with the reduction of volume of the maxillary sinuses. This measure may be related to the severity of the disease. The middle meatal antrostomy seemed sufficient to stop the evolution of the SSS, avoiding the occurrence of severe enophthalmos. Neuronavigation surgery helped preventing serious eye complications.


Subject(s)
Enophthalmos/diagnosis , Facial Asymmetry/diagnosis , Maxillary Sinusitis/diagnosis , Maxillary Sinusitis/surgery , Adolescent , Adult , Enophthalmos/etiology , Enophthalmos/surgery , Female , Follow-Up Studies , Humans , Male , Maxillary Sinus/pathology , Maxillary Sinus/surgery , Middle Aged , Ophthalmologic Surgical Procedures/methods , Otorhinolaryngologic Surgical Procedures/methods , Retrospective Studies , Severity of Illness Index , Syndrome , Treatment Outcome
8.
Eur Ann Otorhinolaryngol Head Neck Dis ; 129(2): 98-103, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22104578

ABSTRACT

The cochlear implant (CI), by enabling oral communication in severely to profoundly deaf subjects, is one of the major medical advances over the last fifty years. Despite the globally very satisfactory results, individual outcomes vary considerably. The objective of this review is to describe the various factors influencing the results of CI rehabilitation with particular emphasis on the better understanding of neurocognitive mechanisms provided by functional brain imaging. The following aspects will be discussed: 1. Peripheral predictors such as the degree of preservation of nerve structures and the positioning of the electrode array. 2. The duration of auditory deprivation whose influence on brain reorganization is now becoming more clearly understood. 3. The age of initiation of hearing rehabilitation in subjects with pre-lingual deafness influencing the possibility of physiological maturation of nerve structures. 4. The concepts of sensitive period, decoupling and cross-modality. 5. In post-lingually deaf adults, brain plasticity can allow adaptation to the disability induced by deafness, subsequently potentiating CI rehabilitation, particularly as a result of audiovisual interactions. 6. Several studies provide concordant evidence that implanted patients present different phonological analysis and primary linguistic capacities. The results of CI rehabilitation are dependent on factors situated between the cochlea and cortical associative areas. The importance of higher cognitive influences on the functional results of cochlear implantation justify adaptation of coding strategies, as well as global cognitive management of deaf patients by utilising brain plasticity capacities.


Subject(s)
Cochlear Implantation/rehabilitation , Deafness/rehabilitation , Deafness/surgery , Adult , Auditory Cortex/physiopathology , Child , Deafness/physiopathology , Humans
9.
Neuropsychologia ; 49(9): 2475-82, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21557954

ABSTRACT

Neurofunctional patterns assessed before or after cochlear implantation (CI) are informative markers of implantation outcome. Because phonological memory reorganization in post-lingual deafness is predictive of the outcome, we investigated, using a cross-sectional approach, whether memory of non-speech sounds (NSS) produced by animals or objects (i.e. non-human sounds) is also reorganized, and how this relates to speech perception after CI. We used an fMRI auditory imagery task in which sounds were evoked by pictures of noisy items for post-lingual deaf candidates for CI and for normal-hearing subjects. When deaf subjects imagined sounds, the left inferior frontal gyrus, the right posterior temporal gyrus and the right amygdala were less activated compared to controls. Activity levels in these regions decreased with duration of auditory deprivation, indicating declining NSS representations. Whole brain correlations with duration of auditory deprivation and with speech scores after CI showed an activity decline in dorsal, fronto-parietal, cortical regions, and an activity increase in ventral cortical regions, the right anterior temporal pole and the hippocampal gyrus. Both dorsal and ventral reorganizations predicted poor speech perception outcome after CI. These results suggest that post-CI speech perception relies, at least partially, on the integrity of a neural system used for processing NSS that is based on audio-visual and articulatory mapping processes. When this neural system is reorganized, post-lingual deaf subjects resort to inefficient semantic- and memory-based strategies. These results complement those of other studies on speech processing, suggesting that both speech and NSS representations need to be maintained during deafness to ensure the success of CI.


Subject(s)
Auditory Pathways/physiology , Cochlear Implants , Deafness/rehabilitation , Memory/physiology , Neuronal Plasticity/physiology , Speech Perception/physiology , Adaptation, Physiological , Adult , Association Learning/physiology , Auditory Perception/physiology , Brain Mapping , Case-Control Studies , Cerebral Cortex/physiology , Cross-Sectional Studies , Deafness/physiopathology , Discrimination, Psychological/physiology , Female , Humans , Language Development , Magnetic Resonance Imaging , Male , Matched-Pair Analysis , Middle Aged , Photic Stimulation , Reference Values , Speech , Statistics, Nonparametric , Treatment Outcome
10.
Eur Ann Otorhinolaryngol Head Neck Dis ; 127(5): 189-92, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20934935

ABSTRACT

INTRODUCTION: Salivary duct carcinoma (SDC) is an uncommon entity of salivary gland cancers with a poor prognosis due to local aggressiveness or distant recurrences involving lymph nodes, lung, and long bones, in which secondary lesions are usually osteolytic. The authors report the first case of mandibular SDC, atypical due to its osteosclerotic presentation and its site, attributed to aggressive neural spread of the tumor along the trigeminal nerve. CASE STUDY: This asymptomatic osteosclerotic bone involvement was diagnosed based on pathological enhancement of the trigeminal nerve demonstrated on MRI and was accompanied by facial nerve involvement up to its third intracranial portion. Radical surgery ensured disease control with continued good quality of life at the 4-year follow-up visit. CONCLUSION: Nerve enhancement on MRI and determination of specific tumor markers (HER-2/neu and p53) should be taken into account to evaluate the prognosis of SDC and to propose appropriate surgical treatment.


Subject(s)
Carcinoma/complications , Carcinoma/pathology , Cranial Nerve Neoplasms/complications , Facial Nerve Diseases/complications , Mandibular Diseases/etiology , Osteosclerosis/etiology , Parotid Neoplasms/complications , Parotid Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Invasiveness , Tropism
11.
Neuroimage ; 49(4): 3443-51, 2010 Feb 15.
Article in English | MEDLINE | ID: mdl-19931402

ABSTRACT

Cochlear implants work well, yet the outcome is not fully accounted by the data routinely available to the clinician, and remains unpredictable. A more in-depth understanding of the neural mechanisms that determine the clinical recovery after cochlear implantation is warranted, as they may provide the background for an accurate individual prognosis. In this study in post-lingually deaf adults, we show that while clinical data offer only prognosis trends, fMRI data can prospectively distinguish good from poor implant performers. We show that those deaf cochlear implant (CI) candidates who will become good performers rely on a dorsal phonological route when performing a rhyming task on written regular words. In contrast, those who will become poor performers involve a ventral temporo-frontal route to perform the same task, and abnormally recruit the right supramarginal gyrus, a region that is contralateral to classical phonological regions. These functional patterns reveal that deafness either enhances "normal" phonological processing, or prompts a substitution of phonological processing by lexico-semantic processing. These findings thus suggest that a simple behavioral pre-operative exploration of phonological strategies during reading, to determine which route is predominantly used by CI candidates, might fruitfully inform the outcome.


Subject(s)
Cerebral Cortex/physiopathology , Cochlear Implants , Deafness/physiopathology , Deafness/rehabilitation , Magnetic Resonance Imaging/methods , Recovery of Function , Speech Perception , Adult , Aged , Deafness/diagnosis , Female , Humans , Male , Middle Aged , Treatment Outcome
12.
Allergy ; 64(8): 1136-43, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19245428

ABSTRACT

BACKGROUND: Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1. METHODS: Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated. RESULTS: In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts. CONCLUSION: After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.


Subject(s)
Cell Differentiation , Nasal Mucosa/cytology , Wound Healing , Axonemal Dyneins , Cell Differentiation/drug effects , Cells, Cultured , Cilia/metabolism , Down-Regulation , Dyneins/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Humans , Keratin-14/metabolism , Mucin 5AC/genetics , Mucin 5AC/metabolism , Mucins/metabolism , Nasal Mucosa/metabolism , Nasal Polyps/metabolism , Nasal Polyps/pathology , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Tubulin/metabolism
13.
Ann Otolaryngol Chir Cervicofac ; 121(3): 156-60, 2004 Jun.
Article in French | MEDLINE | ID: mdl-15224001

ABSTRACT

OBJECTIVES: When tracheal stenosis is symptomatic, the treatment may consist of surgical resection and anastomosis. A multifilament absorbable suture is usually used. The aim of this experimental work on rats was to study the benefits of using a monofilament absorbable suture with high initial resistance. MATERIAL AND METHODS: We compared Ethilon, a nylon monofilament non-absorbable suture (MNA), with Monocryl, a polyglecaprone 25 (P25) monofilament absorbable suture (MA). The sutures were used for tracheal anastomosis on 16 rats. P25 has a high initial strength but its intra-tissular disappearance is fast. Animals were killed at 1, 2 and 3 months. Anastomoses were studied by optical microscopy and histological analysis. RESULTS: At 3 months no disunity or stenosis was seen with the MA. With the MNA, a modification of the tracheal transverse section and a stenosis were observed. The histological examination showed an initial important inflammatory cell reaction with the MA and at 3 months, a surgery-free like tracheal aspect. At 3 months the rats with MNA had a persistent foreign body cell reaction. CONCLUSION: Good results obtained by using P25 could be due to high initial resistance of the suture protecting the anastomosis. The semi-fast absorption of the suture avoided persistent inflammatory cell reaction. Confirmation of these results by working on larger animals and tracheal anastomosis under tension could allow the use of this suture on human beings, in this instance.


Subject(s)
Sutures/classification , Tracheal Stenosis/surgery , Adsorption , Anastomosis, Surgical/methods , Animals , Dioxanes/therapeutic use , Female , Polyesters/therapeutic use , Rats , Rats, Wistar , Tracheal Stenosis/pathology
14.
Rev Laryngol Otol Rhinol (Bord) ; 124(4): 207-10, 2003.
Article in French | MEDLINE | ID: mdl-15038561

ABSTRACT

OBJECTIVE: Positron emission tomography (PET) is becoming more and more useful in head and neck tumour detection, guiding diagnostic and therapeutic decision. However, techniques, similar to PET, but using modified conventional tomography equipment, are used. The most commonly used is the dual-head positron emission tomography using coincidence detection (CDET). This study was aimed at searching if CDET could be as reliable as PET in some of its indications. PATIENTS AND METHODS: Between 1997 and 2001, 19 patients, with head and neck cancer, had a CDET, for 3 indications. We studied retrospectively sensitivity (Se) and specificity (Sp) rates for these 3 indications. RESULTS: 1 degree) Detection of unknown primary head and neck cancers with lymph node manifestation: Se = 100%, Sp = 66,7%. 2 degrees) Detection of body metastasis: Se = 50%, Sp = 33%. 3 degrees) Detection of local recurrent cancer: Se = 100%, Sp = 25%. CONCLUSION: CDET seems to be useful in finding unknown primary cancers with lymph node manifestation but is not reliable to look for metastasis and local recurrences. It cannot be used in all indications for PET. If no other tool is available, this investigation can be used, keeping in mind its limitations.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Tomography, Emission-Computed/statistics & numerical data , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis/diagnostic imaging , Male , Neoplasms, Unknown Primary/diagnostic imaging , Radiography , Radiopharmaceuticals , Retrospective Studies , Sensitivity and Specificity
15.
Transplantation ; 67(5): 748-52, 1999 Mar 15.
Article in English | MEDLINE | ID: mdl-10096533

ABSTRACT

BACKGROUND: Pancreatic pig islets may provide a substitute in the future for difficult to obtain human islets for transplantation in insulin-dependent diabetes millitus (IDDM) patients. However, the immune response to xenografts may significantly hamper this approach. Because neonatal tissue is believed to be less immunogenic, we examined whether the T-cell response to neonatal pig islets differs from the response to adult islets. METHODS: The T-cell proliferative response to different concentrations of sonicated neonatal and adult pig islets, as well as to insulin and mitogens, was tested in 21 recent onset IDDM patients and 21 healthy controls. We determined the presence of various circulating islet autoantibodies and their association with the T-cell response in IDDM patients. RESULTS: In the IDDM patients, sonicated adult pig islets (at 1 microg protein/ml) induced a significantly higher frequency (12 of 21 vs. 1 of 21, p<0.001) and magnitude (2.58+/-0.44 vs. 1.38+/-0.13, p<0.02) of positive T-cell responses than neonatal islets at the same concentration. Similar results were obtained with a 10-fold higher concentration of islet sonicate. There was no significant association between the individual T-cell responses and the presence of circulating autoantibodies in IDDM patients. CONCLUSION: These results indicate that neonatal pig islets induce a lower T-cell reactivity than adult islets, suggesting that the neonatal tissue may be immunologically more suitable for future islet xenotransplantation.


Subject(s)
Animals, Newborn , Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation/immunology , Islets of Langerhans/immunology , T-Lymphocytes/immunology , Adolescent , Animals , Autoantibodies/analysis , Child , Child, Preschool , Diabetes Mellitus, Type 1/immunology , Female , Humans , Infant , Insulin/immunology , Male , Swine
16.
Clin Immunol Immunopathol ; 89(3): 279-83, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9837698

ABSTRACT

D-penicillamine (d-PA) was reported to induce various immunological abnormalities including production of autoantibodies to insulin. These abnormalities were mainly described in patients with primary immunological disorders such as rheumatoid arthritis. In order to clarify whether d-PA-induced immune disorders are restricted to patients genetically prone to develop autoimmune diseases or to a direct drug effect, we tested for the presence of various autoantibodies and for molecular HLA typing in 17 patients with Wilson's disease treated with this drug. In 2/17 patients, low-titer (10 JDFU) circulating islet cell autoantibodies (ICA) were detected, while another patient was positive for the presence of insulin autoantibodies. None of the sera tested showed reactivity for glutamic acid decarboxylase or ICA512. Five of twelve patients were positive for anti-single-stranded DNA autoantibody. Molecular HLA typing of the autoantibody-positive subjects showed that they carry HLA haplotypes not associated with insulin-dependent diabetes. The insulin response to intravenous glucose tolerance test in two patients with autoantibodies was found to be normal. A second blood testing of the autoantibody-positive patients 5 months following initial evaluation revealed conversion to negativity in all three. Our results suggest that d-PA-induced autoantibodies in patients with Wilson's disease are independent of the immunogenetic background characteristics of diabetes.


Subject(s)
Autoantibodies/biosynthesis , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/immunology , Islets of Langerhans/immunology , Penicillamine/adverse effects , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Female , HLA Antigens/genetics , Haplotypes , Hepatolenticular Degeneration/genetics , Humans , Immunogenetics , Male
17.
J Clin Endocrinol Metab ; 83(1): 88-92, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9435421

ABSTRACT

Insulin-induced hypoglycemia (IIH) is the gold standard test for assessment of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, but it may be hazardous. We sought to determine whether the standard (250 micrograms) or low-dose (1 microgram/1.73 m2) short ACTH test can replace IIH in patients with idiopathic multiple pituitary hormone deficiencies (MPHD). Three groups of subjects were studied: 1) control group, children with early or accelerated puberty and no other evidence of adrenal or pituitary pathology (n = 13, age 10.1 +/- 2.2 yr, 3 males); 2) patients with idiopathic hypothalamic pituitary insufficiency and either isolated GH deficiency or MPHD and preserved HPA function (n = 20, age 13.7 +/- 4.4 yr, 13 males); and 3) MPHD patients with impaired HPA axis function (n = 10, age 16.8 +/- 4.8 yr, 9 males). IIH and the 250 micrograms and 1 microgram/1.73 m2 ACTH tests were performed in groups 2 and 3; group 1 underwent only the ACTH tests. Pass peak cortisol level was defined as 520 nmol/L. No significant difference was noted between the standard and low-dose tests in the 30-min cortisol response to ACTH. Basal and peak cortisol levels attained on both ACTH tests were similar in groups 1 and 2 and significantly lower in group 3 (P < 0.0001). Both the 250 and 1 microgram ACTH tests were highly correlated with IIH (r = 0.71, P < 0.0001 for the 250 micrograms, r = 0.7, P < 0.0001 for the 1 microgram, n = 30), and both demonstrated high sensitivity (90% each) and specificity (100% and 90%, respectively) compared with IIH. We conclude that in idiopathic MPHD patients, both the standard and low-dose ACTH tests are equivalent to IIH in detecting HPA insufficiency. We suggest that they can replace IIH as a screening test for the integrity of the HPA axis in children with suspected MPHD.


Subject(s)
Adrenocorticotropic Hormone/deficiency , Human Growth Hormone/deficiency , Hydrocortisone/blood , Hypopituitarism/diagnosis , Hypothalamo-Hypophyseal System , Insulin , Pituitary Hormones/deficiency , Pituitary-Adrenal System , Adolescent , Age of Onset , Analysis of Variance , Child , Female , Humans , Hypoglycemia/blood , Hypoglycemia/chemically induced , Hypopituitarism/blood , Male
19.
Biochem J ; 306 ( Pt 1): 87-92, 1995 Feb 15.
Article in English | MEDLINE | ID: mdl-7532401

ABSTRACT

Murine N1E-115 neuroblastoma cells are shown to express a single class of angiotensin II (Ang II) receptors that display all the pharmacological properties defining the Ang II receptor subtype 2 (AT2): high affinity for 125I-labelled AT2-selective agonist CGP 42112 (Kd 91 +/- 19 pM); expected rank order of potency (CGP 42112 = (Sar1,Ile8)Ang II > or = Ang II > PD 123319 >> DUP 753) for several Ang II analogues; increased binding in the presence of the reducing reagent dithiothreitol (DTT); and insensitivity to analogues of GTP. Molecular cloning of cDNA encoding AT2 receptors from N1E-115 cells reveals nucleotide sequence identity with the AT2 subtype expressed in fetal tissue. Murine AT2 receptors transiently expressed in COS cells display the same pharmacological profile as endogenous Ang II receptors of N1E-115 cells. Taken together, these data reveal the exclusive presence of the AT2 receptor subtype in N1E-115 cells. Incubation of N1E-115 cells with Ang II leads to a marked decrease in the level of tyrosine phosphorylation of several proteins with apparent molecular masses of 80, 97, 120, 150 and 180 kDa respectively. Tyrosine dephosphorylation of the same set of proteins is observed after treatment with the AT2-specific agonist CGP 42112. The response to both effectors is rapid and transient, showing a maximum between 5 and 10 min, and returning to basal levels after 20-30 min. In both cases, tyrosine dephosphorylation can be prevented by co-incubation with an excess of the antagonist Sarile. These data thus establish that AT2 receptor activation leads to protein tyrosine dephosphorylation in N1E-115 cells, and support a possible role for AT2 receptors in the negative regulation of cell proliferation.


Subject(s)
Neuroblastoma/metabolism , Protein-Tyrosine Kinases/metabolism , Receptors, Angiotensin/physiology , Tyrosine/analogs & derivatives , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary/genetics , Dithiothreitol/pharmacology , Gene Expression , Guanosine Triphosphate/analogs & derivatives , Guanosine Triphosphate/pharmacology , Mice , Molecular Sequence Data , Oligopeptides/metabolism , Phosphorylation , Phosphotyrosine , Receptors, Angiotensin/genetics , Transfection , Tumor Cells, Cultured , Tyrosine/metabolism
20.
Eur J Biochem ; 220(3): 919-26, 1994 Mar 15.
Article in English | MEDLINE | ID: mdl-8143746

ABSTRACT

The angiotensin II receptors of human myometrial tissue were characterized using ligand binding, cross-linking with radioactive label, detergent solubilization and partial purification by lectin-affinity chromatography. Human myometrial membrane preparations contained variable amount (5-650 fmol/mg protein) of high affinity (Kd = 44-65 pM) binding sites for 125I-CGP42112, a ligand specific for the AT2 subtype of angiotensin II receptors. Competition studies with AT1-specific and AT2-specific compounds indicated that angiotensin II receptors on these membranes were exclusively of the AT2 subtype. The binding sites for 125I-CGP42112 were efficiently solubilized by the detergent Chaps, albeit with a marked decrease in affinity (Kd = 1.2 nM). The proteins in the myometrial membrane preparation were cross-linked to 125I-[Sar1, Ile8]angiotensin II (Sarile) with disuccinimidyl suberate. When low concentrations of cross-linker were used, a single radiolabelled band of about 66-70 kDa was revealed on SDS/PAGE. At higher concentrations additional bands of about 105-120 kDa and 200 kDa were labelled. The 66-70-kDa and 105-120-kDa bands were separated by electroelution of SDS/PAGE gel slices and submitted to trypsin cleavage. The tryptic-peptide maps were identical for both products, suggesting that the additional bands are homodimers and trimers of the labelled polypeptide. The Chaps-solubilized receptor was retained on wheat-germ-agglutinin-Sepharose and specifically eluted by the competing sugar triacetylchitotriose, leading to a fivefold purification factor. Treatment of the 125I-Sarile-labelled protein with N-glycanase caused a shift in its apparent molecular mass on SDS/PAGE from 66-70 kDa to 33 kDa.


Subject(s)
Myometrium/chemistry , Receptors, Angiotensin/chemistry , 1-Sarcosine-8-Isoleucine Angiotensin II/metabolism , Cell Membrane/metabolism , Cross-Linking Reagents , Female , Humans , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/metabolism , Molecular Weight , Oligopeptides/metabolism , Receptors, Angiotensin/metabolism , Solubility
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