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Biomedical subjects

B Royer

Publications and source records attributed to B Royer.

At least 19 recordsLinked to original sources
PubMed2006

High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia.

Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Hepatic markers and development of type 2 diabetes in middle aged men and women: a three-year follow-up study. The D.E.S.I.R. Study (Data from an Epidemiological Study on the Insulin Resistance syndrome).

AIM: It has been shown, mainly in men, that gamma-glutamyltransferase (gammaGT) and alanine-aminotransferase (ALT) predict the development of type 2 diabetes. This study investigates the association between hepatic markers and the 3-year risk of diabetes. METHODS: Incident diabetes was studied in 2071 men and 2130 women without diabetes at baseline from the D.E.S.I.R. cohort. RESULTS: Adjusting on age, only gammaGT was predictive of diabetes in both sexes, whereas ALT and aspartate-aminotransferase (AST) were only predictive in men, and bilirubin was not predictive. After adjustment on classical confounding factors and on ALT activity, the odds ratios (OR) for incident diabetes increased across baseline gammaGT quartiles: 1, 3.1, 2.6, 5.0 in men (P<0.0003) and 1, 0.9, 3.2, 3.5 in women (P<0.01). The relations with ALT and AST were not significant after adjusting on gammaGT. Additional adjustment on markers of insulin resistance, BMI or fasting plasma glucose attenuated the risk associated with gammaGT in both sexes, and it remained significantly predictive only in the men. Pooling men and women, those with gammaGT above the median had adjusted ORs of developing diabetes of 13.7 (1.8-99.8) if WHR > =0.85 and 1.7 (0.6-4.8) if WHR<0.85 (interaction P<0.007). CONCLUSION: gammaGT was the main hepatic risk marker for type-2 diabetes in both sexes, especially in subjects with central adiposity.

Biomarkers↗
PubMed2005

First-line autologous stem cell transplantation in primary CNS lymphoma.

The treatment of primary central nervous system lymphoma (PCNSL) has been considerably improved over recent years. In this article, we report six cases of PCNSL treated by first-line induction chemotherapy followed by intensive chemotherapy and autologous stem cell transplantation (ASCT). Six immunocompetent patients presenting with a PCNSL, confirmed by thoraco-abdomino-pelvic computer tomography scan and bone marrow biopsy, were treated with induction chemotherapy followed by BEAM intensive chemotherapy and ASCT and radiotherapy. At the end of the treatment, all the patients were in complete remission. After a median follow-up of 41.5 months (17-70 months), four patients were alive without signs of relapse (median survival: 35.5 months). Two patients died from relapse at 19 and 23 months. The neurotoxicity was low with epilepsy in one patient and persistent left side dysesthesia in another one. These results are fairly encouraging. Other studies with greater numbers of patients and longer follow-up are needed to confirm this study.

Adult↗
PubMed2004

A clinical and pharmacological study of arsenic trioxide in advanced multiple myeloma patients.

We previously showed that arsenic trioxide (ATO) and melarsoprol may inhibit the growth of multiple myeloma (MM) cells in vitro and in vivo. We report here the administration of arsenic derivatives in 12 relapsing or refractory secretory MM patients. A total of 10 patients received ATO (eight in a continuous schedule, two discontinuously) and two received melarsoprol. The melarsoprol arm was prematurely closed due to toxicity. In the ATO arm, median duration of treatment was 38 days (9-54). Hepatic toxicity was grade 3 and 2 in one and eight patients, respectively. Other toxicities included neuropathy (n=2, grade 2), encephalitis (n=1, grade 3) and leuconeutropenia (n=4, grade 3). At 2 weeks after treatment initiation, mean serum concentration of arsenic was 1.11+/-0.16 micromol/l. No complete or partial remission was observed. A minor response (25-49% reduction of M protein in serum) and a stabilization of the M-protein level were observed in three and four patients, respectively. After ATO discontinuation, these responses were of short duration in all cases. ATO as a single agent did not produce any significant response in advanced MM patients despite sufficient arsenic exposure. Strategies to improve biodistribution, pharmacokinetic and efficacy of the drug as well as treatment combinations are needed.

Aged↗
PubMed2002

[Study of the motivation of physicians participating in public health research].

In order to explore practitioners' motivations to participate in epidemiological research, a study was conducted among doctors who had been requested to provide clinical information on their patients included in the group study DESIR in the Inde and Loire regions of France. Six semi-structured individual interviews were carried out by two sociologists, and were then followed-up by 216 questionnaires, 80 of which were completed and analysed. Finally, 18 telephone interviews were conducted to complete the data collected. Reasons given for participating in epidemiological studies are mainly the perceived scientific interest, relevance for public health and the feeling of being a partner in the research. The obstacles seem to be the vague image of the promoter, ignorance of the DESIR study's objectives, lack of direct contact for communicating information, and the mixture and confusion between filling out the study's questionnaire and handling administrative constraints in general. Therefore, better communication, centred on the concept of partnership between research and practical medicine, informing on the usefulness of knowledge from epidemiological studies for the practice of medicine, and clarifying the promoter's role, could improve the level of participation from general practitioners.

Communication↗
PubMed2001

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

Adult↗
PubMed2001

Inhibition of IgE-induced activation of human mast cells by IL-10.

BACKGROUND: IL-10 exhibits anti-inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen-induced airway inflammation in vivo in murine models. The effects of IL-10 on the allergic activation of human MC are presently unknown. OBJECTIVE: In light of the well-known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL-10. Moreover, the impact of IL-10 on MC-derived proinflammatory mediators is still unknown. Thus, the objective of this study was to investigate the effects of IL-10 on the release of inflammatory mediators by IgE/anti-IgE-challenged human cord blood-derived mast cells (CBMC), used as an in vitro model of MC phenotypically similar to human lung MC. MATERIALS AND METHODS: Highly purified human MC were obtained by a first step of long-term culture of cord blood mononuclear cells in the presence of human recombinant stem cell factor (rhSCF) and of human recombinant IL-6 (rhIL-6), followed by a second step of purification by depletion of contaminating cells with an immunomagnetic METHOD: The cells were treated with human IgE, then challenged with anti-human IgE, in the presence or the absence of recombinant rhIL-10 used at various concentrations. Histamine, tumour necrosis factor-alpha (TNF-alpha), IL-5 and IL-8 were measured in the various supernatants collected at different times after the beginning of the challenge. RESULTS: IL-10 inhibited the release of TNF-alpha and of IL-8, but not of IL-5, by activated CBMC. Interestingly, IL-10 also inhibited the release of histamine by activated CBMC, contrasting with data reported for rodent MC. CONCLUSIONS: These findings suggest that IL-10 might have anti-inflammatory effects on IgE/anti-IgE-challenged human MC by inhibiting their release of TNF-alpha, IL-8 and histamine. These data provide new insights into the control of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.

Cell Culture Techniques↗
PubMed2001

Autocrine regulation of cord blood-derived human mast cell activation by IL-10.

BACKGROUND: Ligation of the high-affinity receptor for IgE on human mast cells (MCs) induces the release of proinflammatory mediators, including vasoactive amines and cytokines (TNF-alpha, IL-5, and IL-8). Moreover, we have recently shown that IL-10 inhibits the release of proinflammatory mediators by activated MCs. OBJECTIVE: We investigated whether human cord blood-derived MCs (CBMCs) could produce IL-10 and whether this production could inhibit their activation in an autocrine fashion. METHODS: IL-10 synthesis by resting or activated human MCs derived from cord blood progenitors was investigated in cell supernatants or by using immunostaining and RT-PCR methods. In addition, the effect of IL-4 on such synthesis was also studied. Anti-IL-10-neutralizing antibodies were used to investigate the validity of the hypothesis of an autocrine regulation of MCs by IL-10. Finally, the presence of specific receptors for IL-10 was searched on human CBMCs by using flow cytometric analysis. RESULTS: Human CBMCs spontaneously synthesize and release IL-10, and this synthesis is increased after IgE/anti-IgE stimulation. In addition, the presence of IL-10 in resting or in activated MCs was proved by immunostaining. Interestingly, the release of IL-10 was also increased after incubation of the cells with IL-4. Besides, the use of neutralizing antibodies against IL-10 confirmed that IL-10 released inhibited MC activation in an autocrine fashion. Finally, the presence of specific receptors for this cytokine was observed on the membranes of our population of human CBMCs. CONCLUSION: Taken together, our data are in favor of an autocrine regulation pathway through synthesis and release of IL-10 by human MCs. Such an autoregulatory mechanism is, to our knowledge, the first described for these elements.

Antibodies↗
PubMed2000

Study of the B cell memory compartment in common variable immunodeficiency.

We evaluated the B cell memory pool among blood B cells from 20 patients with common variable immunodeficiency (CVID). CD27+ B cell number was normal or increased in 6 patients (with 95% CD27+ B cells in 1 patient) and decreased in 14 patients. In 13 or 15 patients studied, the CD27 molecule was detectable on less than 50% IgG or IgA B cells, indicating a defect in the maturation of these memory cells. Within the group of patients with a low number of CD27+ B cells, no up-regulation of this molecule was observed after in vitro stimulation of purified B cells from 3 of 5 patients studied, suggesting an intrinsic B cell defect. In addition, ligation of the CD27 molecule was unable to trigger terminal differentiation of purified B cells in 1 of 2 cases with a large number of CD27+ B cells. Finally, the CD27 ligand was normally expressed on activated T cells in only 5 of 14 patients studied. These data confirm the heterogeneity of immunological defects in patients with CVID. Abnormal expression and/or function of the CD27-CD70 members of the TNF/TNF receptor family contribute to the immunological defect.

Antigens, CD↗
PubMed2000

Extensive biopsy protocol improves the detection rate of prostate cancer.

PURPOSE: We evaluated improvement in the rate of prostate cancer detection when using an extensive biopsy protocol involving peripheral cores. MATERIALS AND METHODS: We prospectively evaluated 303 consecutive men who underwent transrectal ultrasound guided biopsy due to elevated prostate specific antigen (PSA) and/or abnormal digital rectal examination. Ten biopsies were performed, including at least 5 at the base and middle of each lobe. In addition to standard biopsy at a 45-degree angle, a more peripheral 30-degree angle biopsy was obtained. At the apex only 1 standard biopsy was done. However, when prostate volume was greater than 50 cm.3, an additional peripheral biopsy was obtained at the apex. RESULTS: The complication rate in this biopsy protocol was 1% (3 patients). Prostate cancer was detected in 118 of the 303 men (38. 9%). Overall this extensive protocol resulted in 6.6% improvement in the detection rate. Improvement was 6.5% in men with PSA 10 ng./ml. or less and 7% in those with PSA greater than 10 (not significant). CONCLUSIONS: Increasing the number of biopsy cores and improving prostate peripheral zone sampling resulted in a significant improvement in the detection of prostate cancer.

Adult↗
PubMed1999

Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines.

Mast cell (MC) activation may occur in vitro and in vivo following stimulation with various immunologic or nonimmunologic agents. Such activation leads to the release of several biological mediators, including vasoactive amines, nitric oxide and cytokines, which account for the adverse effects observed during allergic reactions. While high affinity binding sites for benzodiazepines (BZDs) have been reported on MC, the effects of the ligation of these receptors on the proliferation of, and the mediator release from, these cells are poorly documented. In the present work, we have examined the effects of midazolam and of diazepam on the proliferation of mucosal (MMC)-like and of serosal (CTMC)-like mouse MC. In addition, we have studied the effects of these BZDs on beta-hexosaminidase, TNF-alpha and nitrite release induced from mouse mast cells through IgE receptor activation. We demonstrated that each of the two BZDs studied inhibited the proliferation of MMC- and CTMC-like elements in a dose-dependent fashion (10 to 100 microM). Furthermore, the BZDs inhibited the IgE-mediated release of beta-hexosaminidase, TNF-alpha and nitrites from MMC- or CTMC-like cells. Altogether, these data provide new insights into the pharmacological regulation of MC activation and may lead to the discovery of new and potent antiallergic compounds.

Animals↗
PubMed1999

[Histamine-producing neuroendocrine tumor of the ampulla of Vater].

Neuroendocrine tumors of the ampulla of Vater are rare (less than 100 cases reported). We report here a new case characterized by histamine secretion, a hitherto unreported feature. Clinical presentation is similar to that of other tumors of the ampulla of Vater. In our observation, the patient had noticed urticaria on the right forearm for several months. Tumor of the ampulla was confirmed by endoscopic ultrasonography, while neuroendocrine characterization was assessed on biopsies after endoscopic sphincterotomy. Histamine concentration in blood was the only elevated neuroendocrine marker and returned to normal after surgical resection. Histology showed a neuroendocrine tumor with extension to lymph nodes. On immunohistochemical analysis, production of histamine was confirmed, and the diagnosis of mastocytoma was eliminated. In view of the literature, neuroendocrine tumors of the ampulla of Vater are associated with a good prognosis (5 year-survival rate: 90%) despite early lymph node involvement.

Aged↗
PubMed1997

Lymphomas in patients with Sjogren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses.

The occurrence of non-Hodgkin's lymphoma (NHL) is the most serious complication of Sjogren's syndrome (SS). We performed a study of 16 NHLs occurring in patients with an underlying SS. These lymphomas arose not only in salivary glands (7 cases) but also in other mucosal extranodal sites (the stomach [4 cases], the lung [3 cases], the skin [3 cases], the buccal mucosa [1 case], the thymus [1 case]) and in nodal sites (8 cases). Low-grade marginal zone lymphomas (MZL) were diagnosed in 12 of the 16 patients, 9 of mucosa-associated lymphoid tissues (MALT) type in mucosal sites and 3 exclusively nodal. The 4 other patients presented with a high-grade B-cell lymphoma that was probably a histological transformation of an underlying low-grade MZL at least in 3 of the cases involving skin, stomach, and parotid, respectively. A t(14;18) translocation was detected in 1 of 8 lymphomas tested. We detected serum anti-p53 antibodies in 2 of the 14 studied patients. p53 protein was detected in 1 of 11 lymphomas tested. LMP protein and Eber RNAs of Epstein-Barr virus (EBV) were not detected in the 16 NHL biopsies. Using polymerase chain reaction, EBV was never detected except in 1 of 4 parotid lymphomas. No human T-lymphotropic virus 1 or human herpes virus 8 DNAs were detected in NHL biopsies. None of the patients had hepatitis C virus infection found using serological methods. Chemotherapy was usually efficient. In conclusion, lymphomas occurring in patients with an underlying SS are in most cases MZL. These lymphomas are not associated with viruses known to be present in other types of lymphomas. Some of the translocations or mutations of oncogenes or antioncogenes described in other lymphomas are detected in SS-associated lymphomas.

Adolescent↗
PubMed1995

[Primary non-Hodgkin lymphomas of the breast. Focus].

Although very rare (0.12 to 1.1% of all breast tumours), primary non-Hodgkin's lymphomas of the breast need to be distinguished from the group of malignant epithelial tumours, as the staging and therapeutic modalities are different, corresponding to those applied to lymphomas in general. In the majority of cases, the current techniques of aspiration cytology, needle or surgical biopsy, immunohistochemistry allow the diagnosis and typing according to the usual histological classifications.

Adult↗
PubMedDate not supplied

[Interest in therapeutic drug monitoring of the main antibiotics].

The therapeutic drug monitoring aims at optimising the prescribed dosages to improve efficacy and prevent toxicity. The aim of this study were to review the main pharmacodynamic and pharmacokinetic properties of aminoglycosides, glycopeptides and ceftazidime. Then, the therapeutic drug monitoring of these antibiotics and their methods of analysis is reviewed.

Aminoglycosides↗