[Show abstract][Hide abstract] ABSTRACT: This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIbalpha, the -5T/C polymorphism in the Kozak sequence of GPIbalpha, the 807C/T polymorphism of GPIa, and the PI(A1)/PI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 x s(-1). At 2600 x s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 x s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the PI(A1)/PI(A2) polymorphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIbalpha and GPIa receptors. The effect of these polymorphisms was dependent on the blood flow rate.
[Show abstract][Hide abstract] ABSTRACT: Otosclerosis is a heritable disease affecting the otic capsule. Its genetics have been studied since the 19th century, but several issues remain controversial.
The goals of this study were to assess the prevalence of sporadic and familial forms of otosclerosis in a population of otosclerotic patients and to compare the radiologic findings between both groups.
This retrospective study was conducted in a single institution.
This study included 211 patients operated on for otosclerosis.
Clinical data, including pure tone audiograms, were available from patients' charts. A questionnaire assessing family history of otosclerosis and deafness was mailed to the otosclerotic patients. A relative was considered otosclerotic if surgery confirmed the disease. The family history was correlated with the computed tomography results. This examination was performed before surgery in all patients.
A family history of otosclerosis was found in 24.2% of the patients. The radiologic findings differed between patients with a sporadic form of otosclerosis and those with a familial form. The lesions were more often detectable, bilateral, and severe in the familial forms (p < 0.05).
These findings lead to the assumption that fenestral radiologic otosclerosis occurs more in sporadic forms, whereas more extensive lesions on computed tomography seem to indicate the familial forms. Hereditary forms demonstrated to be familial seem to lead to more severe disease. The search for a genome locus of otosclerosis may be enlightened by these findings.
[Show abstract][Hide abstract] ABSTRACT: A retrospective study of 102 selected patients operated for otosclerosis (34 outpatient surgery, 68 hospitalised), having all of them the inclusion criteria of the ambulatory surgery, treated as outpatient in a traditional health sector or hospitalised, depending on their own choice, has been lead. We analysed the results of the pure tone audiometric tests two to six months after surgery. No significative difference was found between the two groups on audiometric results as for the postoperative complications. On the other side, it seems that young patients are more interested by the one-day surgery. The failure of the ambulatory surgery could be explained by the vertigo or dizziness per- or postoperatively. Finally, the evaluation of the cost-benefit shows that the ambulatory surgery in a traditional health sector could lead a budgetary saving policy. A saving way that will grow in a specialized sector devoted to the ambulatory practice.
Revue de laryngologie - otologie - rhinologie 02/2001; 122(4):273-7.
[Show abstract][Hide abstract] ABSTRACT: The indication for surgery of vestibular schwannomas (VS) remains controversial and depends on several factors. The ability to predict their patterns of growth would allow better surgical planning. This growth may depend on tumoral proliferation but also depends on dystrophic changes.
The aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in predicting the evolution of VS. For this purpose, the authors attempted (1) to compare the MRI appearance of VS with its histopathologic features, (2) to correlate the MRI appearance of VS and its histopathologic features with its size, and (3) to evaluate the index of proliferation (IP) of each VS.
Thirty VS were studied with MRI before surgery. The VS were measured and classified as homogeneous, heterogeneous, and cystic. After surgery, IP was evaluated with immunohistochemical study using MIB-1 monoclonal antibody, and compared with tumor size. Pathologic studies evaluated the prevalence of Antoni type A and type B tissue, the amount of fibrosis, and the presence of siderin-loaded macrophages, xanthomatous cells, and cysts.
The IP was low (0.2%-2.2%) and was not correlated with VS size. On MRI, 13 VS were homogeneous, 12 heterogeneous, and 5 cystic. The 13 homogeneous VS were smaller and were predominantly made of Antoni type A tissue. The 12 heterogeneous and 5 cystic VS were larger and were predominantly made of Antoni type B/mixed tissue. Heterogeneous and cystic VS showed significantly more hemosiderin deposits. There was a significant relation between the amount of hemosiderin deposits and the mean size of VS. Microscopic cysts were observed only in VS with cystic MRI appearance. Fibrosis was present in all tumors regardless of their size and MRI appearance.
A heterogeneous MRI aspect (correlated with larger mean size) not only is related to the ratio of type A to type B tissue but also is caused by other pathologic changes, mainly hemosiderin deposits and cystic formation. Increasing tumor size probably depends less on IP than on dystrophic changes (hemosiderin, cysts) and/or on the presence of type B tissue.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine if a relationship exists between bone level thresholds and the extension of otosclerotic foci within the otic capsule. The study consisted of a retrospective case review in a university hospital. We included patients who underwent surgery for otosclerosis in our department and who had a CT scan prior to surgery. We analyzed the data charts and CT scans of 437 cases (386 patients). On CT scan, we distinguished patients with fenestral otosclerosis and/or with a pericochlear focus. A pericochlear focus could be extended (Group 2) or not (Group 1) to the cochlear endosteum. Data for Groups 1 and 2 were compared with those for the control group of all patients for whom CT scan showed no cochlear focus (Group 3). Of the 437 CT scans, 399 were positive (91.3%). An anterior focus was reported in 305 cases (69.8%), a footplate thickening in 21 cases (4.8%) and both anomalies were encountered in 60 cases (13.7%). A pericochlear focus was reported in 53 examinations. This focus was extended to the endosteum in 14 cases (26.4% of the pericochlear foci). In Group 1, preoperative air conduction (AC) thresholds were significantly lower than in the control group (p < 0.05). The air--bone gap was also significantly larger in Group 1 (p < 0.05). Bone conduction (BC) thresholds were lower in Group 1 than in the control group but the difference was not significant. In Group 2, preoperative AC thresholds were significantly lower than in the control group (p < 0.05). BC thresholds were also lower in Group 2 than in the control group and the difference was significant (p < 0.05). As a result of this study, we assume that there may be a relationship between bone level thresholds and the radiological extension of otosclerosis within the otic capsule.
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to assess the effectiveness of the conservative management in patients with acoustic neuroma (vestibular schwannoma).
This retrospective study was performed in a university hospital.
Patients were selected for this wait-and-see policy on the basis of age, general condition, audiometric results, tumor size, and patient preference. The study group included 97 patients, 87 of whom had at least two neuroradiologic examinations. The mean age of this population was 63 years (29 to 89 years). The mean length of follow-up of this population was 31 months. Eighty-seven of these patients had at least two radiologic examinations (magnetic resonance imaging or computed tomography). The mean interval between the initial and follow-up radiologic examinations was 15 months.
Tumor size was measured by use of two-dimensional data in all patients. The mean tumor size was 12 mm. The growth rate of the tumor was estimated by comparison of the results of the measurements from the initial and follow-up neuroradiologic examinations.
Of the 97 patients studied, 6 patients required surgery and 6 required radiotherapy. Sixty patients (62%) were still being treated conservatively at the end of the study period. Three patients of 28 who were classified as candidates for hearing preservation surgery lost their candidacy during the observation period. The mean annual tumor growth rate was 1.52 mm/year. The tumor was stable in size in 36% of patients, regressed in 11% of patients, or grew in 53% of patients. The growth patterns of the acoustic neuroma fell into five categories: continuous growth in 15% of patients, negative growth in 5%, growth followed by negative growth in 40%, negative growth followed by growth in 20%, and no variation of tumor size in 20%.
Conservative management of acoustic neuromas carries difficulties: long-term follow-up of the patients and unpredictability of the tumor growth pattern. A reliable and reproducible radiologic method for evaluating tumor size is of great importance.
The American journal of otology 12/2000; 21(6):857-62.
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic parameters, virologic characteristics and frequency of HLA class II DR and DQ antigens were compared between 63 subjects with spontaneous hepatitis C virus clearance (group 1) and 282 patients with chronic active hepatitis C virus infection (group 2). DRB1*1101 and moreover DQB1*0301 alleles were more frequent in group 1 than in group 2 (33.8% vs. 14.7% and 64.4% vs. 28.6%; P=0.012 and P=0.003, respectively). The frequency of DQB1*02 was lower in group 1 than in group 2 (25.4% vs. 49%; P=0.04). No difference was observed in viral genotype distribution between group 1 and group 2. Univariate analysis showed that female sex and contamination by intravenous drug use were associated with self limited infection. However, by multivariate analysis, the only independent factor associated with hepatitis C virus RNA clearance was female sex (P=0.004). In conclusion, spontaneous hepatitis C virus RNA clearance is determined by class II antigens (mainly DQB1*0301) and female sex, while viral genotype plays no role.
[Show abstract][Hide abstract] ABSTRACT: Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.
[Show abstract][Hide abstract] ABSTRACT: To determine the intracytoplasmic expression of TNF-alpha, IL-2, IL-6 and IFN-gamma, ex vivo and in vitro, in both monocytes and T lymphocytes by flow cytometry after appropriate stimulation using phorbol myristate acetate (PMA)/ionomycin or lipopolysaccharides (LPS) in the presence of monensin, in order to assess the bio(in)compatibility of different dialysis membranes.
We examined monocytes and T lymphocytes taken from chronic hemodialysis patients (using either cuprophane (CUP), n = 6; polyacrylonitrile (AN 69), n = 6; or polysulfone (PS), n = 6 membranes), before and after a dialysis session. We compared the results with those obtained from end-stage chronic renal failure patients (n = 3) and healthy volunteers (n = 11).
Before any stimulation there was a statistically significant difference in the percentages of TNF-alpha, IL-6, and IFN-gamma- expressing monocytes with respect to the dialysis membrane used. The highest percentages were observed for CUP and AN69 patients with figures of around 30% for each cytokine; the lowest percentages were found in PS patients and healthy volunteers. One hour after LPS stimulation the patterns remained unchanged for TNF-alpha and IFN-gamma, whereas the percentages of IL-6-expressing cells in PS patients and in healthy volunteers reached the figures obtained in the other groups. When we examined the percentage of IFN-gamma-, TNF-alpha- and IL-6-expressing monocytes in patients before and after a dialysis session, before any stimulation, we found that the results were significantly different for the three membranes (p = 0.01). Thus, a dialysis session with polysulfone membranes had no significant effect on the precentages of IFN-gamma-, TNF-alpha-, and IL-6-expressing monocytes, whereas percentages were significantly lower after the dialysis session when using cuprophane or AN69 membranes, suggesting a release of these cytokines by the monocytes during dialysis. A significant number of IFN-gamma- and IL-2-expressing T lymphocytes were only detected after 18 hours of PMA/ionomycin stimulation. The percentages of IFN-gamma-expressing T cells recorded for the different membranes were not statistically different from those recorded for healthy subjects or pre-dialysis patients, i.e., they were between 11.5 and 20%. However, the percentages of IL-2-expressing T lymphocytes were significantly different between the 5 groups, i.e., 31.3, 30.5, 18.6, 13.9 and 7. 6%, respectively, for CUP patients, pre-dialysis patients, healthy volunteers, PS and AN69 patients. This suggests that pre-dialysis and CUP patients have, at baseline, a stimulation of their T lymphocytes. Finally, a 4-hour dialysis session had no impact on the percentages of IL-2-expressing T lymphocytes, whereas it was associated with a significant decrease in the percentage of IFN-gamma-expressing cells, but only when cuprophane membranes were used.
Cytokine flow cytometry enables one to study, ex vivo, i.e., without any stimulation of the cells, and in vitro after appropriate stimulation, the bio(in)compatibility of dialysis membranes assessed by the intracytoplasmic cytokine profiles of TNF-alpha, IFN-gamma, IL-6 and IL-2, evaluated at the single cell level.
American Journal of Nephrology 01/2000; 20(1):18-26. DOI:10.1159/000013550 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between serum hepatitis C virus (HCV) RNA and the outcome of alpha-interferon (alpha-IFN) therapy in patients with chronic hepatitis C has important implications for therapeutic research and clinical care. Serum HCV RNA was tested for HCV genotype and quantified by a standardized reverse transcriptase-polymerase chain reaction assay as a measure of viral load in a cohort of 130 patients with chronic hepatitis C treated with alpha-IFN at a standard dose of 3 million units three times a week scheduled for 6 (n = 50) or 12 months (n = 76). Twenty-one of 126 evaluable patients (16.7%) developed a sustained complete response to alpha-IFN according to biochemical and virological criteria. The 3 pretreatment independent factors associated with a sustained complete response were a low baseline serum HCV RNA concentration, non-1 HCV genotype, and female sex. A multivariate logistic regression model, with pretreatment and month 1 variables, showed that a lower baseline serum HCV RNA concentration, female sex, and a greater suppression of RNA were the significant predictors of sustained complete response. The lowest baseline serum HCV RNA concentration was observed in patients with genotype 2 infection and the greatest decrease in HCV RNA from baseline to month 1 in those with genotype 3. The findings suggest that measuring HCV RNA in serum before and soon after beginning treatment can be helpful for selecting patients who are most likely to have a sustained complete response to standard schedule of alpha-IFN and for identifying patients in whom alternative strategies should be examined.
Journal of Medical Virology 03/1998; 54(2):86-91. DOI:10.1002/(SICI)1096-9071(199802)54:23.0.CO;2-K · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain.
Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus. In this series of patients (n = 159), the daily doses of intrathecal morphine were determined as a function of duration of follow-up.
The mean follow-up period was 95 days (range, 5-909 d), the mean starting daily dose of intrathecal morphine was 2.69 mg (range, 1-7.5 mg), and the mean terminal dose was 7.82 mg (range, 1-80 mg). The results demonstrated that only a moderate increase in daily dose of intrathecal morphine was required during the course of treatment (a two- to threefold increase for a 3-mo period). Furthermore, the dose increment was similar for patients followed up for more or less than 60 days. This increase did not result in any central opioid-related side effects, and the pain was managed satisfactorily.
The requirement for a moderate increase in intrathecal opioid doses reflects the development of tolerance but did not limit the patients' ability to obtain adequate analgesia during the course of their painful disease.
[Show abstract][Hide abstract] ABSTRACT: The host's immune response may influence the course of hepatitis C virus (HCV) infection. The aim of this study was to investigate the distribution of HLA class II alleles in white subjects who spontaneously recovered from HCV infection compared with that in patients with persistent infection.
HLA-DRB1 and -DQB1 typing were performed in 103 consecutive patients with persistent HCV infection (HCV antibody positive, HCV RNA positive) and in 25 subjects with transient HCV infection (HCV antibody positive, persistently negative HCV RNA).
No significant differences between subjects with transient or persistent infection were observed for age, sex, source of infection, or HCV serotype. The frequency of DQB1*0301 and DRB1*1101 alleles was higher in patients with transient infection than in those with persistent infection (84% vs. 30.8%, 40% vs. 9.8%; P < 0.01 and P < 0.02, respectively [Bonferroni correction]). DRB1 and DQB1 alleles did not influence viral load as an independent factor. Mean Knodell's scores were lower in patients with DQB1*0301 allele (6.12 +/- 0.4) than in those negative for DQB1*0301 (7.37 +/- 0.3; P < 0.05).
Our results suggest that host- rather than virus-related factors are probably involved in the spontaneous clearance of HCV.
[Show abstract][Hide abstract] ABSTRACT: Fifteen kidney transplant recipients with chronic hepatitis C were given 3 million units recombinant alpha2b-interferon for 142+/-35 days. There were significant decreases in hepatitis C virus (HCV) RNA 1 month after the initiation of treatment (p < 0.01), and at the end of treatment (p < 0.05). HCV RNA was undetectable by PCR analysis during treatment in 5 patients. But HCV RNA reappeared in all patients 1 month after the cessation of therapy, and the level of viremia returned to baseline. While all patients had normalized alanine aminotransferase (ALT) activities at the end of therapy, 11 experienced a relapse during the follow-up period (1 year). There was a correlation between the amount of HCV RNA at the end of treatment and the time of relapse. Serum IgM against core protein of HCV were detected in 7/15 patients. Anti-core IgM remained detectable during treatment and afterwards. There was no correlation between IgM status and other virological parameters, or ALT activity.
American Journal of Nephrology 01/1997; 17(5):417-20. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.
[Show abstract][Hide abstract] ABSTRACT: Risk factors for developing cytomegalovirus (CMV) infection and pneumonitis were analysed in 100 unselected consecutive patients undergoing allogenic BMT. This series is homogeneous because of the same diagnostic procedures, BMT technique and supportive care (exclusive seronegative blood products, no CMV immunoglobulin, no prophylactic antiviral). The incidence of CMV infection and CMV interstitial pneumonitis (CMV-IP) were 44% and 13% respectively, of whom five patients died. Variables such as age, sex, underlying disease, conditioning regimen and occurrence of GVHD were not found as significant risk factors. We confirm that the only major factor was recipient's serology as CMV infection and IP occurred in 4% and 0% respectively among negative recipients (R-) compared with 79% and 25% among positive R. In contrast to some studies among R+, neither donor's immunity nor recipient's CMV humoral response improved the clinical outcome. This study validates the good predictive value of viremia and urinary virus excretion for the occurrence of CMV-IP (respectively positive in 11 and 13 patients out of 13 with IP), always preceding IP by a median of 37 and 27 days. The highest risk patients for lethal CMV-IP were older recipients (> 30 years). Thus, prospective prophylactic trials with antiviral agents are suggested in such viremic or viruric patients. Furthermore, the use of seronegative blood products is highly effective and sufficient to prevent CMV infection in R-patients.
Bone Marrow Transplantation 03/1993; 11(3):209-14. · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.
[Show abstract][Hide abstract] ABSTRACT: Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.
Journal of Clinical Oncology 06/1991; 9(5):865-70. · 18.43 Impact Factor