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1.
Br J Haematol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747092

RESUMO

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

2.
Prog Urol ; 30(3): 162-171, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32127312

RESUMO

INTRODUCTION: Nowadays, diagnostic biomarker research is oriented on a genomic characterisation of prostate cancer (PCa). This study evaluated diagnostic values of TMPRSS2-Erg fusion transcripts expression (TE) and androgen receptor variant 7 (AR-V7) on urine (tU) and biopsic rince material (tLRB) samples. MATERIALS AND METHODS: TE and AR-V7 have been tested by RT-PCR and RT-qPCR on urine and biopsies' rince liquid on 372 patients referred for prostate biopsies. RESULTS: Two hundred thirty-three patients (62%) were diagnosed with PCa. tU.AR-V7 was positive for 15 healthy patients (28%) and 30 patients diagnosed with PCa (37%). tLRB.AR-V7 was positive for 66 patients (42%) diagnosed with PCa. Concerning TE for patients diagnosed with PCa, tU was positive for 59 patients (54%) and tLRB for 132 (55%). TE and TE/AR-V7 combination were significantly associated with PCa (P<0.001), as tLRB.AR-V7 (P<0.001). Sensitivity and specificity for TE/AR-V7 combination for PCa were respectively: tU.TE/AR-V7 67% and 70%, tLRB.TE/AR-V7 68.8% and 71%, and, tUtLRB.TE/AR-V7 83% and 60%. There was no benefit for AR-V7 and TE association versus TE alone when comparing AUC. CONCLUSION: AR-V7 is not specific of PCa because of detection on healthy patients. This study did not managed to show a sufficient diagnostic value for TE/AR-V7 combination on urine and biospic rince material tests. LEVEL OF EVIDENCE: 3.


Assuntos
Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/diagnóstico , Receptores Androgênicos/genética , Idoso , Biomarcadores Tumorais , Biópsia , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
3.
Leukemia ; 31(3): 565-572, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27694926

RESUMO

Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Translocação Genética , Alelos , Biomarcadores Tumorais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Criança , Pré-Escolar , Epigênese Genética , Exoma , Feminino , Regulação Leucêmica da Expressão Gênica , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Mutação , Proteínas de Fusão Oncogênica/genética , Prognóstico , Transdução de Sinais , Proteínas WT1/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
4.
J Viral Hepat ; 24(1): 80-85, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27699936

RESUMO

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP), in comparison with alpha-fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty-two patients with virus-related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof-of-concept study. DCP was measured on new Lumipulse® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow-up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20 µg/L, sensitivity and specificity for AFP were 63% and 82%. NRI>0 for the association of "AFP+DCP" were 101%, P<.0001, and 23%, P=.03, compared to "AFP" or "DCP" alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Precursores de Proteínas/sangue , Idoso , Carcinoma Hepatocelular/sangue , Feminino , França , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Protrombina , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Soro/química , alfa-Fetoproteínas/análise
6.
Leukemia ; 27(7): 1479-86, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23321953

RESUMO

The mTORC1 signaling pathway is constitutively activated in almost all acute myelogenous leukemia (AML) patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10-70 mg were administrated orally on days 1 and 7 (d1 and d7) of a 3+7 daunorubicin+cytarabine conventional induction chemotherapy regimen. Twenty-eight patients were enrolled in this trial. The treatment was well tolerated with <10% toxicity, mainly involving the gastrointestinal tract and lungs. In this phase Ib trial, the RAD001 maximum tolerated dose was not reached at 70 mg. Sixty-eight percent of patients achieved CR, of which 14 received a double induction. Eight subsequently were intensified with allogeneic-stem cell transplant. Strong plasma inhibition of P-p70S6K was observed after RAD001 administration, still detectable at d7 (d7)at the 70 mg dosage. CR rates in patients with RAD001 areas under or above the curve median were 53% versus 85%. A 70 mg dose of RAD001 at d1 and d7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Transdução de Sinais/efeitos dos fármacos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
8.
J Nutr Health Aging ; 10(2): 91-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16554939

RESUMO

Malnutrition is common in patients with advanced cancer and is associated with worse prognosis. The aim of this study was to follow-up the nutritional status of elderly patients with advanced cancer in comparison with that of younger ones, in the course of hospitalization. Eighty-eight (44 males and 44 females) patients with advanced cancer entered the study. Two groups were defined according to age : superior 70 y (n = 45) and < 70 y (n = 43). Nutritional status by means of anthropometric variables and daily intake were assessed on Day 0, Day 30 and Day 60. A blood sample was collected on Day 0 for determination of serum proteins. The two groups of patients did not differ in terms of anthropometry and biological variables on admission to our department ; only bicipital skinfold thickness and energy intake were lower in the elderly patients. After one month hospitalization, tricipital skinfold thickness and fat mass decreased in these patients. After two months, mid-arm circumference also decreased. Unlike the older group, the younger patients increased their daily energy and protein intakes. During hospitalization, older persons with advanced cancer cannot improve their energy intake and therefore, are at particular risk of aggravating their nutritional status.


Assuntos
Envelhecimento/patologia , Desnutrição/epidemiologia , Neoplasias/complicações , Estado Nutricional , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anorexia/complicações , Antropometria , Caquexia/complicações , Ingestão de Energia , Feminino , Hospitalização , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Náusea/complicações , Prognóstico , Fatores de Risco , Dobras Cutâneas , Inquéritos e Questionários , Redução de Peso
9.
Clin Nutr ; 23(4): 551-9, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15297091

RESUMO

BACKGROUND & AIMS: We have estimated the prevalence of severe malnutrition in groups of patients hospitalized for different medical causes and assessed the sensitivity of BMI in the diagnosis of severe malnutrition. DESIGN: A prospective study enrolled 1052 patients: 396 patients with liver cirrhosis including 165 non-ascitic patients (NAP), 124 patients with mild ascites (MAP), 107 patients with tense ascites (TAP), 251 patients after cardiac surgery (SCP), 81 patients with cardiac diseases (MCP), 85 patients with stroke (SP), 36 patients with degenerative neurological diseases (DNP), 68 patients after surgery of a hip fracture (HFP), 91 patients with palliative care for cancer (CP) and 44 elderly patients with medical affections (EP). BMI, mid-arm muscular circumference (MAMC) and triceps skinfold thickness (TST) were measured within 48 h after admission. Patients with MAMC and TST below the 5th percentile of a reference population when aged < or = 74 or the 10th percentile when aged > or = 75 were defined as severely malnourished. Sensitivity of BMI < 20 to detect malnutrition was assessed. RESULTS: The prevalence of severe malnutrition was the highest in TAP (39.1%) HFP (25.6%) and MAP (24.3%) and the lowest in SCP (4%), SP (4.8%), DNP (5.7%) and MCP (7.4%) (P < 10(-4)). In multivariate analysis, low TST was associated with female gender (P < 10(-4)) mild and tense ascites (P = 0.038, P = 0.0004), low MAMC with male gender (P < 10(-4)), low BMI with female gender (P = 0.0082), hip fracture (P = 0.0407) and cancer (P = 0.0059). The sensitivity of BMI to detect severe malnutrition was the highest in HFP, CP and EP (100%, 80% and 100% respectively) and the lowest in TAP, MCP and SP (40%, 33.3% and 50% respectively). After exclusion of TAP, sensitivity of BMI to detect malnutrition correlated significantly with the coefficient of correlation between MAMC and TST observed in each group (r = 0.821, P = 0.0066). CONCLUSION: Ascitic cirrhotic patients and elderly patients after surgery of hip fracture had the highest prevalence of severe malnutrition. BMI had the highest sensitivity when both TST and MAMC were damaged to the same extent. BMI < 20 has a high sensitivity in the diagnosis of severe malnutrition in elderly and cancer patients but not in cirrhotic patients with tense ascites, cardiovascular and neurological patients.


Assuntos
Antropometria , Ascite/complicações , Índice de Massa Corporal , Fraturas do Quadril/complicações , Desnutrição/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Cirrose Hepática/complicações , Masculino , Desnutrição/epidemiologia , Desnutrição/etiologia , Desnutrição/patologia , Análise Multivariada , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Dobras Cutâneas
10.
Rev Med Interne ; 22(3): 238-44, 2001 Mar.
Artigo em Francês | MEDLINE | ID: mdl-11270266

RESUMO

PURPOSE: To study the nutritional status in elderly patients hospitalized for rehabilitation and to compare it among patients with hip fracture and those with medical care. METHODS: Patients were nutritionally assessed upon admission (d0) to our unit by measurement of anthropometric, biological parameters and dietary intake. Thirty-seven patients were operated for hip fracture (group I) and 21 were hospitalised for medical disease (group II). Nutritional status was compared in the two groups on d0 and was evaluated after one month (d30) in the operated group. RESULTS: No significant difference could be observed for any anthropometric or biologic (albumin, transthyretin and transferrin) in the two groups. Daily food intake related to body weight was much the same in both groups (31 kcal/kg). C-reactive protein and orosomucoid levels were above the reference range in both groups. Hip fracture operated patients had higher orosomucoid than non-operated ones (1.50 +/- 0.4 versus 1.14 +/- 0.4 g/L; P = 0.002). One-month follow-up of nutritional status performed in 31 operated patients showed a significant decrease in TST and MAC (respectively p = 0.02 and p = 0.007) and in orosomucoid (p = 0.003) although daily food intake increased. CONCLUSION: Twenty-eight percent of patients were undernourished upon admission in the unit. A moderate inflammatory state still remained in all our patients, particularly in those who had undergone surgery. This inflammatory state persisted two months after surgery.


Assuntos
Estado Nutricional , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino
11.
J Hepatol ; 33(3): 376-81, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11019992

RESUMO

BACKGROUND/AIMS: Septic shock results in high mortality in patients with cirrhosis. Nitric oxide synthase 2 (NOS2) is induced by bacterial lipopolysaccharides (LPS) and plays a major role in the inflammatory response to bacterial infections. Little is known about the regulation of NOS2 in cirrhosis under septic conditions. Thus, the aim of this study was to determine tissue NOS2 activity, serum nitrate and tumor necrosis factor (TNF-alpha) levels and hepatic toxicity in cirrhotic rats after LPS administration. METHODS: Serum nitrates, TNF-alpha and transaminases were determined after LPS-administration in rats with secondary biliary cirrhosis and in sham-operated rats. Liver, lung, aortic and peritoneal macrophage NOS2 activities were determined by converting L[14C] arginine into L[14C] citrulline in a calcium free medium. Nitrate and TNF-alpha production were determined in a culture medium of peritoneal macrophages after in vivo LPS administration. RESULTS: LPS (1.5 mg/kg) induced 50% mortality in cirrhotic rats and no mortality in sham-operated rats. After LPS, TNF-alpha, nitrate and transaminase levels were significantly higher in cirrhotic rats compared to sham-operated rats. After LPS administration, there were no differences in NOS2 activity in the aorta, lungs, or peritoneal macrophages of the two groups, whereas NOS2 activity was significantly higher in the cirrhotic liver compared to the normal liver. CONCLUSIONS: In rats with cirrhosis, LPS administration induces higher mortality, hepatic toxicity, hepatic NOS2 activation and TNF-alpha release than in sham-operated rats. These results confirm the harmful role of septic shock in liver disease.


Assuntos
Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/intoxicação , Cirrose Hepática/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Óxido Nítrico Sintase/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Sprague-Dawley , Transaminases/sangue , Fator de Necrose Tumoral alfa/análise
12.
Clin Nutr ; 19(5): 349-54, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11031074

RESUMO

BACKGROUND AND AIMS: Serum IGF-1 level declines with advancing age and is a reliable index of protein-energy undernutrition in elderly patients in a metabolically stable condition. We have examined the value of IGF-1 as an indicator of malnutrition in elderly patients during recovery within 1 month after surgery for a hip fracture and we have studied the relationship between changes in IGF-1 levels, nutritional status and inflammatory reaction during 2 month follow up. STUDY DESIGN: Forty elderly patients (mean age 84.0+/-1.9) were nutritionally assessed upon admission to our rehabilitation unit (D0) then monthly (D30-D60) by measurement of anthropometric and biological parameters. Two groups of patients were defined on the basis of mid-arm circumference (MAC) and tricipital skinfold thickness (TST) measurement at D0: group 1, undernourished (n=13) and group 2, normally nourished (n=27). Changes in anthropometric and biological parameters during the study were compared between these two groups of patients. RESULTS: IGF-1 level was significantly lower in group 1 (79.5+/-9.1 vs 108+/-8.6 ng/ml, P<0.05) while usual serum protein levels were in the same range in the two groups. Orosomucoid level significantly decreased during 2 month follow-up in group 2 (P<0.01), CRP level decreased but not significantly. TST and MAC decreased in group 2 (respectively P<0.02 and P<0.05) while anthropometric parameters tended to slightly increase in group 1 in relation with an increase in caloric intake (P<0.05). IGF-1 level increased significantly during the study in group 2 (P<0.05) and was significantly lower in patients with complications occurring between D0 and D30 in comparison with patients without complications (respectively P<0.05 at D0, P<0.02 at D30). IGF-1 level correlated with body mass index, MAC, TST, muscle midarm circumference, albumin and transthyretin levels. Changes in IGF-1 levels positively correlated with those in transthyretin levels and negatively with those in orosomucoid levels. CONCLUSION: IGF-1 level seems a reliable index of protein-energy under-nutrition in elderly patients in the recovery period after surgery for a hip fracture. This marker is influenced by the inflammatory reaction. Decline of inflammatory reaction, rather than change in nutritional status, is responsible for the variation in IGF-1 level during a 2 month follow-up.


Assuntos
Fraturas do Quadril/cirurgia , Inflamação/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Antropometria , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Desnutrição Proteico-Calórica
13.
Br J Nutr ; 83(2): 97-103, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10743488

RESUMO

A 2-month follow-up of nutritional status was performed in forty elderly patients with recent hip fracture. Patients were nutritionally assessed on admission to our rehabilitation unit (day 0), then monthly (day 30, day 60) by measurement of resting energy expenditure (REE), anthropometric, impedance and biological variables. Patients were defined as undernourished (n 13) or normally nourished (n 27) on the basis of mid-arm circumference (MAC) and triceps skinfold thickness (TST) measurements. Seven patients recovered a walking autonomy and were discharged from the hospital before day 30 (group I) whereas thirteen patients were discharged after day 30 (group II); twenty patients remained in the study at day 60 (group III). MAC and TST decreased in normally nourished patients from group III throughout the study whereas they did not change in group II or in undernourished patients from group III. REE values in relation to fat-free mass were increased compared with normal values and were similar in the three groups on day 0; they did not change during the study. Daily energy intake in relation to body weight was higher in group I and increased in group II and in undernourished patients from group III throughout the study. In contrast, it was below the recommended value at day 0 and it did not significantly improve in normally nourished patients from group III. Serum albumin, transthyretin and transferrin levels on day 0 were below reference intervals in the three groups. Albumin levels increased in group III throughout the study. Inflammatory proteins decreased in groups II and III, with C-reactive protein levels returning to normal values in group II by day 30 and in group III at day 60, while orosomucoid levels did not become completely normal over this period. Our findings indicate no improvement in nutritional status in undernourished patients after surgery for recent hip fracture, despite an adequate energy intake. An insufficient spontaneous energy intake for normally nourished patients was associated with a delayed favourable outcome resulting in a prolonged duration of hospitalization. A hypermetabolic state persisted during the 3 months after surgery.


Assuntos
Metabolismo Energético , Fraturas do Quadril/metabolismo , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Feminino , Seguimentos , Fraturas do Quadril/sangue , Humanos , Tempo de Internação , Masculino , Pré-Albumina/análise , Albumina Sérica/análise , Dobras Cutâneas , Transferrina/metabolismo
14.
Am J Nephrol ; 20(1): 18-26, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10644863

RESUMO

AIMS: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.


Assuntos
Materiais Biocompatíveis , Citocinas/metabolismo , Leucócitos Mononucleares/metabolismo , Membranas Artificiais , Diálise Renal , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
15.
J Hepatol ; 30(5): 896-903, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10365818

RESUMO

BACKGROUND/AIMS: The aim of this study was to determine the relative roles of constitutive NOS (NOS3) and inducible NOS (NOS2) isoforms during the development of two models of portal hypertension in rats. METHODS: Vascular reactivity of aortic rings for norepinephrine was performed in control, sham-operated, portal-vein-stenosed and secondary biliary cirrhotic rats 1, 4, 7, 14 and 28 days after surgery. NOS activity and nitrate plasma levels were also measured. RESULTS: An impaired response to norepinephrine observed in sham-operated, portal-vein-stenosed and cirrhotic rats at days 1 and 4 compared with controls was reversed after L-NNA and aminoguanidine. Portal hypertensive rats remained hyporeactive at days 7, 14 and 28 compared with sham-operated rats. At days 7 and 14 in portal-vein-stenosed rats, vascular hyporeactivity was reversed by L-NNA and W7. At days 14 and 28 in cirrhotic rats, vascular hyporeactivity was reversed by L-NNA and W7. Nitrate levels increased at day 1 in the 3 groups, and increased at days 14 and 28 in portal hypertensive rats. Total NOS-activity increased in cirrhotic rats at day 28, in portal-vein-stenosed rats at day 14, and in sham-operated rats at day 1 compared to controls. NOS2 activity increased only in sham-operated rats at day 1. CONCLUSIONS: This study shows that for two models of portal hypertension, increased NO production in the first days is related to NOS2 induction secondary to surgery. On the other hand, when portal hypertension has fully developed, the NOS3 isoform appears to play the major role.


Assuntos
Aorta Torácica/fisiopatologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática Biliar/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Óxido Nítrico Sintase/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Modelos Animais de Doenças , Guanidinas/farmacologia , Hipertensão Portal/enzimologia , Técnicas In Vitro , Cirrose Hepática Biliar/enzimologia , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Nitratos/sangue , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Norepinefrina/farmacologia , Veia Porta , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Trombose/enzimologia , Trombose/fisiopatologia , ômega-N-Metilarginina/farmacologia
17.
Transplantation ; 61(5): 745-9, 1996 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-8607178

RESUMO

The purpose of the present study was to investigate whether nitrate serum level, reflecting total body production of nitric oxide in vivo, could serve as a noninvasive marker for acute human cardiac rejection. Serum nitrate concentration was determined by an enzymatic method. During routine right ventricular endomyocardial biopsies in 59 recipients, 145 tissue samples were obtained. Two groups of biopsy specimen were considered on the basis of posttransplant delay: group 1, < or = 90 days (n=47; 12-90 days); and group 2, >90 days (n=98; 3-81 months). All patients had normal ventricular systolic function on the day of biopsy and none had evidence of infection. Rejection grade correlated closely with serum nitrate concentration (P<0.001). In both groups, nitrate serum concentrations differed significantly (P<0.001) among cases without rejection, those with mild ongoing rejection (grade 1A/1B), and those with focal or diffuse aggressive infiltrates (grade 2 or higher). A cutoff value of 20 micromol/L, was determined that was positively predictive for grade 2 or higher rejection in 62% cases of early episodes of rejection and in 68% cases of late rejection. Conversely, a serum nitrate level below 20 micromol/L was negatively predictive in 97% and 94% of early and late cases, respectively. We conclude that the acute rejection process of the human transplanted heart is accompanied by a significant increase in serum nitrate level, reflecting increased nitric oxide production during the immune response. Because of its high negative predictive value, irrespective of the posttransplantation delay, nitrate serum determination may have clinical utility in the noninvasive monitoring of the cardiac transplant patient and could also add important information to endomyocardial biopsy analysis for treatment decision making.


Assuntos
Rejeição de Enxerto , Transplante de Coração , Nitratos/sangue , Óxido Nítrico/biossíntese , Transplante de Coração/imunologia , Humanos , Óxido Nítrico Sintase/metabolismo
19.
Am J Nephrol ; 15(6): 524-7, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8546177

RESUMO

Vascular calcifications are common in uremic patients whereas calciphylaxis is rare. We report the case of a 45-year-old woman on chronic hemodialysis since 1977. She had a subtotal parathyroidectomy in 1985, aortic and mitral valve replacement in 1986, and has been treated since then with nicoumalone. In June 1991, she presented with repeated, painful cutaneous necrosis suggesting panniculitis. A skin biopsy showed lobular panniculitis and evidence of calciphylaxis. There was an obvious biological hyperparathyroidism. Protein C functional level was in the normal range whereas protein S functional level was low, i.e. 42%. The patient underwent cervical surgery to remove two parathyroid glands, and daily hemodialysis sessions. Despite this treatment, cutaneous necrosis progressed with superinfection. A few weeks later, the patient died from a septic shock after a myocardic infarction. Necropsy was not performed.


Assuntos
Calciofilaxia/etiologia , Deficiência de Proteína S/complicações , Diálise Renal , Feminino , Humanos , Hiperparatireoidismo/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Pessoa de Meia-Idade
20.
Rev Prat ; 44(3): 319-23, 1994 Feb 01.
Artigo em Francês | MEDLINE | ID: mdl-8178096

RESUMO

A disorder of the internal ear of unknown origin, Menière's disease is not characterised by vertigo but rather by the associated auditory symptoms and a chronic course. The first differential diagnosis is the acoustic neurinoma. Study of auditory evoked potentials, which is reliable and inexpensive, can preclude the use of more expensive imaging techniques. Menière's disease can be invalidating in patients who are often young and active. Treatment remains symptomatic and empiric. Destructive surgery can be a solution if it respects audition. Overall management remains the basis of treatment.


Assuntos
Doença de Meniere , Adulto , Criança , Doença Crônica , Feminino , Humanos , Masculino , Doença de Meniere/diagnóstico , Doença de Meniere/etiologia , Doença de Meniere/terapia , Fatores de Tempo
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