Biomedical subjects

J Bienvenu

Publications and source records attributed to J Bienvenu.

At least 19 recordsLinked to original sources

PubMed1997

Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial.

Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.

Adenoviridae↗

PubMed1997

LPS increases biomaterial degradation by human monocytes in vitro.

Different cell lines are involved during an immunological reaction, principally lymphocytes and monocytes. Monocyte/macrophage cells, which are among the first to appear in wound-healing and infection sites, are largely implicated in phagocytosis and could be involved in calcium-phosphate degradation. Their role in these processes may relate to cytokine secretions and/or their sensitivity to certain cytokines. We tested the behavior of human monocytes placed on the surface of biphasic calcium-phosphate (BCP) tablets in the presence of two lipopolysaccharide (LPS) concentrations. After short-term culture (48 h), cytokine release (IL-1beta, IL-6) was measured by ELISA, and morphological cell events and biomaterial degradation were observed in scanning electron microscopy. BCP surface pits were noted near cells stimulated by 0.5 microg/mL LPS but were not apparent with 10 microg/mL LPS. The number of lacunae on BCP was increased after LPS treatment of human monocytes. An upmodulation of IL-1beta and IL-6 (in culture medium) released by LPS-activated human monocytes was observed, indicating good cell stimulation. This study demonstrates that LPS-activated human monocytes can degrade the surface of calcium-phosphate ceramic and confirms the role of human monocytes in biomaterial degradation.

Biocompatible Materials↗

PubMed1997

CD4 monoclonal antibody administration in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory dermatosis that probably involves a dysregulated activation of helper T cells, type 2 (Th2 cells). Severe refractory AD can be controlled by cyclosporine treatment. OBJECTIVE: We attempted to determine whether short-term CD4 monoclonal antibody (mAb) therapy could improve severe AD in adults. METHODS: The CD4 mAb, B-F5, was infused over 2 days in three patients with severe refractory AD and, for control purposes, in two patients with severe psoriasis. RESULTS: Administration of B-F5 was well tolerated, despite moderate first dose side effects. Clinical improvement was observed in two patients. In the third patient, a dramatic worsening occurred between 8 and 30 days after treatment, associated with an increased percentage of activated CD4+, CD25+, HLA-DR+, and CD45RO+ cells and peripheral blood eosinophilia. The same CD4 mAb administered to two patients with severe psoriasis induced marked clinical improvement of the lesions. CONCLUSION: Although CD4 mAb infusion may be potentially useful in the treatment of AD, the risk of aggravating the Th1/Th2 imbalance in AD should be considered in the design of future protocols.

Adult↗

PubMed1997

Procalcitonin and C-reactive protein levels in neonatal infections.

In order to assess the potential fo procalcitonin measurement in the management of neonatal sepsis, daily variations in serum procalcitonin (measured by an immunoluminometric assay) were evaluated in 94 control and infected newborn infants in comparison to C-reactive protein (measured by an immunonephelometric method). High levels of procalcitonin correlated with bacterial invasion and showed no discrepancies with C-reactive protein. procalcitonin increased (up to 400 micrograms l-1 and returned to the normal range (< 0.1 microgram l-1) more quickly than C-reactive protein, suggesting that procalcitonin may be an early marker of favourable outcome. Another finding is a significant procalcitonin peak on the first day of life in the control group, independent of any infectious stimulus. In conclusion, procalcitonin seems to be an interesting marker of neonatal sepsis but additional investigations are needed to understand better its mechanism of synthesis in order to determine its clinical usefulness.

Bacterial Infections↗

PubMed1997

Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.

PURPOSE: A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS: One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION: TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.

Antigens, CD↗

PubMed1996

[Do corticotherapy and hemodilution decrease postoperative inflammation after maxillofacial surgery?].

OBJECTIVE: To assess the efficiency of corticosteroids and preoperative acute normovolaemic haemodilution (PANHD) in reducing postoperative inflammation after maxillofacial surgery. STUDY DESIGN: Randomized clinical trial. PATIENTS: Thirty-two patients scheduled to undergo maxillary osteotomy for facial dysmorphia were randomized into four groups of eight (PANHD or not; corticosteroids or not). METHODS: PANHD decreased haematocrit to 30%. In the corticosteroid groups, methylprednisolone 1.5 mg.kg-1 was given intravenously at the beginning of surgery (after PANHD in haemodiluted group), and after surgery, 1.5 mg.kg-1 iv daily for three days. Postoperative inflammation was assessed with an X-Ray technique (radiotelemetry) providing data on tissue thickness (extent of facial oedema), and by measurement of plasma concentrations of four acute phase proteins during the first postoperative week. RESULTS: No change in facial oedema and in acute phase proteins occurred with PANHD. Corticosteroids decreased postoperative oedema and acute phase proteins. CONCLUSION: Corticosteroids decrease postoperative inflammation after maxillofacial surgery but not PANHD.

Acute-Phase Proteins↗

PubMed1996

Elevated circulating levels of TNFalpha and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients.

In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFalpha) and soluble TNF type I receptor (p55-R-TNF) were prospectively determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto-centroblastic lymphoma, 13 patients with other low-grade lymphoma, and 56 with high-grade lymphoma. Median TNFalpha plasma values were 20 pg/ml (range 5-380 pg/ml) in patients versus 7 pg/ml (range 4-9 pg/ml) in 20 healthy control subjects. Presence of TNFalpha level > or = 20 pg/ml was significantly associated with elevated LDH level (P<0.0001), serum beta2-microglobulin level > or = 3 mg/l (P<0.0001), haemoglobin < or = 12 g/dl (P=0.0001), Ann Arbor stage III or IV disease (P<0.005), and with bulky tumour (P=0.01). High level of TNFalpha was also associated with B symptoms (P<0.005), poor performance status (P<0.05), and serum albumin < or = 35 g/l (P<0.05). Levels of p55-R-TNF were also markedly elevated in these lymphoma patients (median of 3.5 ng/ml, range 0.8-18.8 ng/ml) versus 1.45 ng/ml in control subjects (range 1.1-2.3 ng/ml). Level of p55-R-TNF > or = 3.5 ng/ml was significantly associated with poor performance status (P<0.0001), B symptoms (P<0.0001), beta2-microglobulin levels > or = 3 mg/l (P<0.0001), serum albumin < or = 35 g/l (P=0.0001), C-reactive protein > 6 mg/l (P=0.0003), elevated (>20 pg/ml) IL-6 level (P<0.005), haemoglobin < or = 12 g/dl (P<0.005), and bulky tumour (P<0.001). In the whole group of 88 patients, both high TNFalpha and p55-R-TNF levels strongly predicted short progression-free survival (P<0.005 for both variables) and overall survival (P<0.001 and P<0.001 respectively). In multivariate analyses the elevation of p55-R-TNF retained a higher significance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNF gamma and p55-R-TNF levels have high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.

Aged↗

PubMed1996

Cytokine and hormonal changes after cholecystectomy. Effect of ibuprofen pretreatment.

OBJECTIVE: Surgical stress induces hormonal and cytokine responses proportional to the extent of the injury. Therefore, the authors assessed the effect of ibuprofen pretreatment on metabolic and hormonal changes after surgery. SUMMARY BACKGROUND DATA: Postoperative administration of cyclo-oxygenase inhibitor reduces cytokine production and nitrogen losses. METHODS: The authors studied the plasma hormones and metabolic and cytokines changes after perioperative ibuprofen administration in 22 patients undergoing cholecystectomy under inhalational anesthesia. Suppositories containing ibuprofen (500 mg) or placebo were administered 12 and 2 hours before surgery, and every 8 hours until the third postoperative day. Blood samples were collected 24 and 2 hours before surgery and 2, 4, 6, 24, 48, and 72 hours after surgery for glucose, C-reactive protein, leukocytes, adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor, and interleukin-1 and interleukin-6 determinations. RESULTS: In both groups, plasma cortisol levels remained elevated for 3 days, whereas plasma ACTH levels returned to the basal level at day 1. The ACTH (p < 0.01), cortisol (p < 0.01), and glucose changes (p < 0.001) were smaller in the ibuprofen group and their duration was shorter. The interleukin-6 levels increased gradually after skin incision until the sixth hour and were significantly lower (p < 0.05) in the ibuprofen group. CONCLUSION: Ibuprofen pretreatment in perioperative course is able to reduce the endocrine response and cytokine release. Therefore, ibuprofen may be useful in decreasing the stress response in severely surgical patients.

Adult↗

PubMed1996

Evaluation of the fully automated Cobas Core enzyme immunoassay for the quantitation of antibodies against hepatitis B virus surface antigen.

The Roche Cobas Core automated enzyme immunoassay of antibodies against hepatitis B virus surface antigen (anti-HBs) was evaluated using a protocol complying with the Société Française de Biologie Clinique guidelines. Results showed good precision (CV below 6 and 9% for intra- and inter-assay precision) and accuracy (according to the Paul-Ehrlich-Institute standard); the detection limit of the test was 2 IU/l. The manufacturer's specifications were confirmed and a satisfactory correlation (r = 0.901) was found with an automated method (IMx, Abbott) used for comparison.

Evaluation Studies as Topic↗

PubMed1996

Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists.

The release in 1993 of a new reference material for serum proteins, CRM 470/RPPHS 5 has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. Conversion to the new reference material results in significant changes in reference values for some proteins. The establishment of new reference ranges will take a considerable time, and in the interim several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies already undertaken.

Blood Proteins↗

PubMed1996

[Aerosol administration of a replication defective recombinant adenovirus expressing normal human cDNA-CFTR in the respiratory tractus in patients with cystic fibrosis].

At present it is conceivable to think that gene therapy represents a way to treat or even prevent the respiratory manifestations of cystic fibrosis. Consistent to such a concept, there is sufficient evidence that Ad-CFTR, a recombinant replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator cDNA, can vectorize the expression of a functional CFTR (cystic fibrosis transmembrane conductance regulator) to the nasal and airway epithelia. The clinical protocol was designed to assess the safety of single escalating doses of a replication defective adenovirus expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR) when administered to the tracheobronchial portion of the airways and whether biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis patients received nasal instillation and subsequent aerosol (Optineb, Air Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu) applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP) and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG), respectively. No acute toxic effects, no increase in the titer of anti-adenovirus antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad-CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and bronchial cells) were detected up to 14 days following Ad-CFTR administration. These results show that the nebulisation of Ad-CFTR is a possible approach for treating the respiratory manifestation of cystic fibrosis.

Adenoviridae↗

PubMed1995

Acute normovolaemic haemodilution does not reduce the inflammatory process induced by facial surgery.

The place of preoperative acute normovolaemic haemodilution (haematocrit = 28%-32%) in reducing postoperative inflammation was evaluated after facial surgery. Thirty-two patients scheduled for mandibular osteotomy were randomized to a nonhaemodiluted group or to a haemodiluted group. The degree of postoperative inflammation was evaluated: first by an x-ray technique (radiotelemetry) providing measurements of the tissue thickness (quantitation of facial oedema), and second by the measurement of four acute phase protein plasma concentrations during the first postoperative week. Throughout the study, no changes in facial oedema or in variation of acute phase proteins were detected after haemodilution. It is concluded that acute normovolaemic haemodilution has no effect on the intensity of facial oedema and the biological inflammation process after facial surgery.

Acute-Phase Proteins↗

PubMed1995

Implication of cytokines in the aggravation of malnutrition and hypercatabolism in elderly patients with severe pressure sores.

The objectives of this work were to study the production of the cytokines Interleukin 1 (IL-1), Interleukin 6 (IL-6), and tumour necrosis factor (TNF) in elderly patients with severe pressure sores and to assess their potential contribution to the aggravation of malnutrition. Nineteen bedridden patients with stage III or IV pressure sores, 12 bedridden patients free from pressure sores, but at risk of them, and 12 control patients without risk of pressure sores were studied. Nutritional status was evaluated using anthropometry, serum albumin, prealbumin, retinol-binding protein analyses, and delayed hypersensitivity skin tests. Acute-phase proteins (APP), cortisol, and cytokines blood levels together with cytokine production were measured. Nutritional status was poor in patients with sores and their APP, and IL-6 blood levels were significantly increased; IL-1 and TNF serum concentrations were not elevated in these patients. A significant difference in cortisol levels was observed between patients with stage III and IV sores. A local cytokine origin (especially IL-6, and also IL-1) was demonstrated. Thus cytokines, mainly IL-6, produced by tissue cells in damaged areas together with cortisol may aggravate malnutrition and hypercatabolism in patients with sores.

Acute-Phase Proteins↗

PubMed1995

sIL-2R levels in rheumatoid arthritis: poor correlation with clinical activity is due in part to disease duration.

The serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in an attempt to determine whether they correlated with 'disease activity' in 59 patients suffering from rheumatoid arthritis. Our results indicate that serum levels of sIL-2R do not permit patients to be classified as having active or inactive disease according to standard clinical indices. A correlation between sIL-2R and disease duration could offer one explanation for the current discrepancies found in the literature.

Aged↗

PubMed1995

Production of proinflammatory cytokines and cytokines involved in the TH1/TH2 balance is modulated by pentoxifylline.

The modulation of cytokine release induced by pentoxifylline (PTX) has recently been demonstrated not to be restricted solely to tumor necrosis factor (TNF)-alpha. This prompted us to study the influence of PTX on a larger spectrum of cytokines with proinflammatory actions [TNF-alpha, interleukin-6, (IL)-6, IL-1 beta, IL-8] or with implied actions in the TH1 (IL-2, IFN-gamma)/TH2 (IL-10) balance. The IL-1RA was also explored. This work was performed using a whole-blood model in which cytokine production is measured after stimulation by lipopolysaccharide (LPS) (25 micrograms/ml) and phytohemagglutinin (PHA) (5 micrograms/ml) in 1:10 diluted whole blood. The stimulation test was performed in blood from healthy controls and from septic patients (without septic shock) in the presence or absence of PTX at 10(-6), 10(-5), 10(-4), or 10(-3) M. In controls and septic patients, at a 10(-4) M PTX concentration the production of IL-2 is strongly diminished (26-32% of the basal level), followed by diminution of IFN-gamma (30-40%). As expected, of the proinflammatory cytokines TNF was the most strongly suppressed (50% of baseline) followed by IL-1 (about 80% of basal production). Finally, IL-10 was also influenced by PTX (65% of baseline). At 10(-4) M, IL-1RA and IL-6 were unaffected by PTX. Taken altogether, our data demonstrate that PTX possesses a much broader spectrum of activity on cytokine production than was initially described, and it appears to be a potential and promising immunotherapeutic agent.

Adult↗

PubMed1995

Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion.

Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.

Aged↗

PubMed1995

IL-3 increases marrow and peripheral erythroid precursors in chronic pure red cell aplasia presenting in childhood.

In most patients with Diamond-Blackfan anaemia (DBA) the addition of IL-3 to in vitro cultures increases the number of erythroid progenitors. However, a small proportion of patients show an erythroid response to in vivo administration of IL-3. We treated two adult patients with corticosteroid-refractory DBA, who had shown a clear in vitro erythroid response to IL-3, with increasing doses of IL-3 (from 2.5 to 10 micrograms/kg/d) by subcutaneous injections for 7 and 9 weeks. Monitoring of marrow and circulating progenitors showed a sustained elevation of BFU-E and CFU-E as well as an increase of other progenitors and CD34+ cells during therapy. However, this effect did not translate into a clear clinical response, although transfusion requirements decreased transiently in one patient. This report shows that a sustained elevation of erythroid progenitors induced by in vivo IL-3 administration may not translate into an increase of mature red cells production in DBA patients.

Adult↗

PubMed1995

[Methods for studying cytokines in biological media].

Accurate and sensitive methods for the measurement of cytokines in biological fluids are an absolute prerequisite for a proper use of these mediators in clinical practice. The authors describe the numerous molecular forms under which cytokines can possibly circulate. The potential influence of inhibitors (autoantibodies, soluble receptors) on cytokine assays is discussed. Blood collection for cytokines needs a particular attention to prevent a possible contamination by endotoxins which can trigger cytokines cellular production after sampling. If bioassays historically preceded immunoassays, these last techniques are now very popular, but there is an urgent need for standardisation between the different kits commercially available. In addition, in situ detection of cytokines using molecular biology is an helpful complementary technique to the measurement of circulating cytokines.

Artifacts↗