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Biomedical subjects

C Blanc

Publications and source records attributed to C Blanc.

At least 19 recordsLinked to original sources
PubMed2003

Nutritional effects of carnitine supplementation in hemodialysis patients.

AIMS: Carnitine is involved in fatty acid metabolism and it is cleared by dialysis. As it plays a role in energy utilization and because malnutrition is a frequent complication of HD treatment, we studied the effects of carnitine supplementation on several nutritional parameters in HD patients. MATERIAL AND METHODS: The main selection criterion was a body mass index (BMI; body weight/(height)2) < 22 kg/m2. Fifty-three patients were enrolled to participate in this open and randomized study. For 6 months, 28 patients received 15 mg/kg of intravenous L-carnitine at the end of each hemodialysis (HD) treatment (Group A), the remaining 25 patients were controls (Group B). The measured parameters were the post-dialysis body weight, serum albumin concentration (nephelemetry), food intake assessed by a 3-day food questionnaire, nPNA (normalized protein equivalent of nitrogen appearance), creatinine generation, and anthropometry. RESULTS: Forty-five patients completed the study (Group A: 14 F/9 M, 66.7 years old; Group B: 11 F/11 M, 65.2 years old). At the beginning of the study, there were no differences between the groups for age, gender, HD duration, BMI, diabetes prevalence, plasma carnitine levels and measured nutritional parameters. 65.2% and 77.3% in each group were carnitine-deficient (plasma total carnitine level < 35 micromol/l). After 6 months of L-carnitine supplementation, none of the nutritional parameters had changed in either group, except that serum albumin concentration decreased in both groups. Dividing each group according to their respective median serum albumin concentrations, daily energy and protein intakes, creatinine generation or triceps skinfold thickness did not show any difference in the various nutritional parameters with or without carnitine supplementation. CONCLUSION: Carnitine supplementation, despite normalization of plasma carnitine levels, has no effect on the nutritional status of HD patients.

Adult↗
PubMed2003

[Cohorts and bio-libraries for studying malaria in tropical areas].

The relationship between Plasmodii transmission, infection, morbidity, genetic susceptibility and acquisition of natural immunity is studied among two cohorts in the Senegalese villages of Dielmo (300 inhabitants) and Ndiop (350 inhabitants) where malaria is holoendemic (about 200 P. falciparum infective bites/person/year) and mesoendemic (about 20 P. falciparum infective bites/person/year), respectively. The populations are under a daily active clinical survey. Blood samples are collected at least once per month. Plasma and red blood cells are stored in bio-libraries that allow longitudinal studies of the immune responses against plasmodial antigens and the investigation of the natural history of P. falciparum infections by molecular genotyping methods.

Animals↗
PubMed2001

Measurement of the anisotropy of the energy of an isotropic-smectic interface in a smectic cylinder: application to the L3-L alpha interface.

In order to measure the relative anisotropy of a smectic-isotropic interfacial energy, we propose an alternative to the classic Wulff construction. We derive the Gibbs-Thomson equation that describes the equilibrium of a droplet of isotropic phase in a smectic sample confined within a cylindrical capillary. We then discuss the influence of the curvature energy term and show that the profile of the droplet gives the variation of the surface energy, either analytically or by means of a modified Wulff construction. From this approach, we measure the relative anisotropy of the sponge-lamellar interfacial energy in the dilute Cetylpyridinium Chloride/hexanol/brine surfactant system. We quantitatively confirm and complete previous observations of this interface, which displays strong crystalline features, such as cusps and forbidden orientations.

Journal Article↗
PubMed2001

Malnutrition in long-term haemodialysis survivors.

BACKGROUND: Long survival is now common in patients with end-stage renal disease owing to improvement in dialysis techniques and kidney transplantation. As malnutrition is commonly reported in dialysis patients, we evaluated the nutritional status of patients treated with haemodialysis (HD) for more than 20 years. METHODS: Ten patients (59.5 years old; 4F/6M; HD treatment for 304 months; group A) underwent an extensive nutritional examination and were compared to a control group of 10 patients treated with HD for an average of 51 months and strictly matched for age (58.6 years old), gender, and height (group B). The patients were treated on a similar basis (long-duration HD, cellulosic membranes, Daugirdas index >2). RESULTS: The body weight (BW) in group A had decreased gradually from the 11th year of HD treatment, whereas it had increased by an average of 1.9+/-4.4% since the beginning of the HD treatment in group B. The body mass index (BMI) was lower in group A (19.3 +/- 2.3 vs 21.4 +/- 2.8 kg/m(2); P = 0.05). The arm-muscle circumference (AMC), the arm-muscle area (AMA), and triceps skinfold (TSF) were lower in group A than in group B. The fat mass assessed with anthropometry (10.8 +/- 4.0 vs 14.8 +/- 4.2 kg) was significantly lower in group A. The deviation of actual BW from ideal BW (IBW) was significantly lower in group A than in group B (80.6 +/- 10.7% vs 89.6 +/- 9.0%; P = 0.028); The deviations of actual BW, TSF, and AMA from standard values of the NHANES II study were more marked in group A than in group B. On the other hand, daily energy and protein intakes (DEI and DPI) were identical in both groups and met the recommendations for dialysis patients when normalized to the actual BW. When normalized to the IBW, the DEI appeared low. Energy expenditure was not different between groups, and not different from the resting metabolism calculated from the Harris and Benedict formula. Average albumin, prealbumin, and IgF-1 were normal and not different between groups. Branched-chain amino acids (BCAA), and especially leucine, were correlated with BMI in group A but not in group B. Serum total and free carnitine were low in both groups. Three patients had ascorbic acid deficiency in group A but none in group B. CONCLUSIONS: Hence, despite adequate dialysis dose and protein intake, patients treated with HD for a long period of time became malnourished, whereas the classical nutritional markers remained in normal ranges. Among the potential causes leading to malnutrition, inadequate energy intake and micronutrient deficiencies were found in these patients.

Aged↗
PubMed2001

Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance.

BACKGROUND: Rectal sensory thresholds are lowered in patients with irritable bowel syndrome (IBS), reflecting visceral hyperlagesia, which might be related to subclinical inflammation. AIM: To evaluate the effects of an intraluminal injection of glycerol, a mucosal irritant, on rectal tone and perception of distension in 12 healthy subjects. METHODS: Rectal tone was evaluated with a barostat. First sensation, need to defecate and pain thresholds were evaluated during isobaric phasic distensions, before and 20 and 120 min after injection of 10 ml glycerol in the rectum. RESULTS: Baseline bag volume (97.9 +/- 56.2 ml) significantly decreased 20 min (49.7 +/- 42.2 ml; P= 0.026) and 120 min (66.5 +/- 38.3 ml; P= 0.050) after injection of glycerol, indicating its hypertonic effect. The pressure defining sensory thresholds was decreased significantly 20 min after glycerol injection: first sensation, 14.6 +/- 2.9 versus 18.3 +/- 7.2 mm Hg (P = 0.01); need to defecate, 19.6 +/- 3.7 versus 26.0 +/- 6.9 mm Hg; pain, 23.8 +/- 4.5 versus 35.6 +/- 9.5 mm Hg (P = 0.001). This effect was maintained for 120 min after injection of glycerol. Slopes of the compliance curves did not differ before and after injection of glycerol. CONCLUSIONS: Intraluminal injection of glycerol significantly increases rectal tone and sensitizes healthy volunteers to rectal distension, since they show significantly lower thresholds after glycerol. This could constitute a model of visceral hypersensitivity in healthy volunteers.

Administration, Rectal↗
PubMed2000

Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells.

In this study, we sought to investigate in more detail the role of caspase-3 in apoptotic processes in cultured cells and in cell-free extracts of breast cancer cells. We present evidence that apoptosis of caspase-3-deficient MCF-7 breast cancer cells is defective in response to cisplatin treatment, as determined by chromatin condensation, nuclear fragmentation, DNA fragmentation, and release of cytochrome c from the mitochondria. Reconstitution of MCF-7 cells by stable transfection of CASP-3 cDNA restores all these defects and results in an extensive apoptosis after cisplatin treatment. We further show that in extracts from caspase-3-deficient MCF-7 cells, procaspase-9 processing is strongly impaired after stimulation with either cytochrome c or recombinant caspase-8. Reconstitution of MCF-7 cell extracts with procaspase-3 corrects this defect, resulting in an efficient and complete processing of procaspase-9. Together, our data define caspase-3 as an important integrator of the apoptotic process in MCF-7 breast cancer cells and reveal an essential function of caspase-3 for procaspase-9 processing.

Antineoplastic Agents↗
PubMed2000

Monoclonal antibodies against the human interleukin-11 receptor alpha-chain (IL-11Ralpha) and their use in studies of human mononuclear cells.

A panel of 14 hybridoma cell lines secreting monoclonal antibodies against the human interleukin-11 receptor alpha chain (hIL-11Ralpha) was obtained using two different approaches. Two antibodies were raised against peptides of the N- and C-terminal sequences, respectively, of the extracellular part of the hIL-11Ralpha. Another group of 12 antibodies was generated against a hybrid protein consisting of the extracellular part of the hIL-11Ralpha fused to mature full-length human IL-2. All these antibodies recognized native hIL-11Ralpha and most also recognized the denatured receptor on immunoblots after SDS-PAGE. Four different epitopes were identified on the extracellular part of the hIL-11Ralpha. One epitope, defined by the E27 antibody, is located at the N-terminus and the other three epitopes are clustered in the membrane-proximal, C-terminal region. The antibodies defining epitopes I and II recognized membrane-bound hIL-11Ralpha expressed in gp130/hIL-11Ralpha-co-transfected Ba/F3 cells. The E27 antibody cross-reacted with murine IL-11Ralpha, in agreement with the fact that the N-terminal region is highly conserved between species. The other 13 antibodies all recognized a region between amino acids 319 and 363, which is the membrane-proximal part of the hIL-11Ralpha. This region, which is less conserved between mouse and human, is shown here to be an immunodominant region. Anti-IL-11Ralpha monoclonal antibodies, which have not been described previously enabled us to explore the expression and tissue distribution of IL-11Ralpha on human peripheral blood mononuclear cells and cell lines. The antibodies provide powerful tools for the study of the regulation and function of the receptor.

Amino Acid Sequence↗
PubMed2000

CD4+Ki67+ lymphocytes in HIV-infected patients are effector T cells accumulated in the G1 phase of the cell cycle.

Entry into the cell cycle represents a fundamental step before generating an effector immune response. The relationship between the cell cycle and antigen-driven T cell response remains, however, poorly understood in virus infection, including HIV. We have identified a critical fraction of CD4+CD45RO+ memory T lymphocytes that express the Ki67 antigen in chronically HIV-infected patients. A high accumulation of Ki67 protein is detected in CD4+CD45RO+Ki67+ cells that are in the G1 phase of the cell cycle (92 ¿ 5 %) but not in S and G2 + M phases, in contrast to normal individuals. Of these cells, 20 - 60 % are spontaneously producing IL-2 and IFN-, unlike CD4+CD45RO+ that do not express Ki67. In addition, HIV-p24 antigen is detectable only in a small fraction CD4+Ki67+ cells. In conclusion, CD4+Ki67+ lymphocytes are circulating effector cells accumulated in the G1 phase of the cell cycle and may be involved in the immune surveillance during HIV infection.

Antiretroviral Therapy, Highly Active↗
PubMed2000

A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma.

The aim of this study was to evaluate the efficacy of docetaxel as first-line chemotherapy in patients with unresectable metastatic or locally advanced pancreatic adenocarcinoma and to further characterise the safety and pharmacokinetic profiles of docetaxel. 43 patients were enrolled into this phase II study. Treatment consisted of a 1-h infusion of docetaxel 100 mg/m2 every 3 weeks without premedication with corticosteroids until progression or unacceptable toxicity occurred. Dose modifications were planned for adverse events. Patients were observed for 1 month after the last docetaxel infusion, to document any late adverse events, with a follow-up every 3 months until death. Response rate and duration were the major efficacy endpoints. Response status was reviewed by an external independent panel. Pharmacokinetic analysis was performed during the first treatment cycle. 40 patients were evaluable for response, and all were evaluable for safety. After independent review, partial response was recorded in 6 patients (overall response rate, 15%; 95% confidence limit (CI), 7.7-29.8%) and stable disease was recorded in 15 patients (38%). The median duration of response was 5.1 months (range: 3.1-7.2). The median pain control time was 4.5 months (range: 0-8) and the median time to performance status worsening was 2.3 months (range: 0-4.5). Most patients 40 (93.0%) received a relative dose intensity of more than 70% of the planned dose. The incidence and severity of adverse events reflected the known safety profile for docetaxel. Docetaxel clearance was reduced in patients with elevated concentrations of hepatic enzymes or bilirubin. Docetaxel is an active agent for unresectable metastatic or locally advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Nuclear localization of procaspase-9 and processing by a caspase-3-like activity in mammary epithelial cells.

Caspases are aspartate-specific proteases that are specifically activated by numerous death stimuli. Caspase activation is thought to play a major role for the execution of apoptosis. Inactive caspase-9 zymogen is known to be localized within the mitochondrial intermembrane space where it is involved in monitoring mitochondrial damage-associated cytochrome c release and subsequent activation of procaspase-3. Here we show that in mammary epithelial cell lines a significant fraction of caspase-9 proform is associated with discrete structures in the nucleus. Stimulation of cells with chemotherapeutic agents leads to the processing of nuclear procaspase-9 and to the accumulation of nuclear and cytoplasmic caspase activity. Using cell-free extracts from caspase-3-deficient MCF-7 cells we show that caspase-8-mediated processing of nuclear procaspase-9 requires caspase-3. In caspase-3-expressing breast cancer cells, cytochrome c-induced processing of nuclear procaspase-9 is blocked by the caspase inhibitors z-VAD and DEVD but not by YVAD. Purified active caspase-3 is sufficient to cleave nuclear caspase-9 zymogen. These results suggest that, in addition to the mitochondrial localization, caspase-9 proform is found within the nucleus and its processing can be regulated by caspase-3.

Animals↗
PubMed2000

Tiling the plane with noncongruent toric focal conic domains

This paper deals with regular arrays of macroscopic defects (focal conic domains) observed when a slab of lamellar phase is sandwiched between two substrates imposing different orientational anchorings. We report, in particular, detailed observations of the texture of a lyotropic lamellar phase in contact with a glass substrate and a lyotropic sponge phase. We consider several models for the defects depending on the material and the substrate parameters. Their energy has a common form, and the main features of the textures are explained in the framework of a simple model where disks of different sizes tile a plane in order to minimize a particular interface energy.

Journal Article↗
PubMed2000

[Pituitary gland MRI and Cushing disease: report of 14 operated patients].

PURPOSE: Evaluate the MR sensibility for detection and localisation of ACTH-secreting microadenomas of the pituitary gland. PATIENTS: and method. The MRI studies of the pituitary gland, performed before transsphenoidal surgical exploration, about 14 patients who present clinical and biological signs of Cushing disease, were reviewed retrospectively. We have always used unenhanced sagittal and coronal spin-echo T1 sequences, and coronal T1 after injection of gadolinium (1 Tesla). RESULTS: The global sensibility for detection of an adenoma was 100% (84 to 92% when the lesional localisation was considered). The injection of gadolinium increased the sensibility of 38 to 42% according the readers. 7 to 14% of the lesions were isointense after injection. The estimation of lesional size after injection was the nearer to the surgical results. The indirect sign most frequently seen (35.7 to 64.3%) was focal bulging of the sellar diaphragm. The only differences between the different radiologists, statistically significant, concerned the lesional size before injection and location of the lesion in the sagittal plane. CONCLUSION: This study confirmed the good sensibility of contrast-enhanced MRI in detection of ACTH-secreting microadenomas. The anatomo-radiological correlations are nevertheless incomplete.

Adult↗
PubMed1999

T cell changes after combined nucleoside analogue therapy in HIV primary infection.

OBJECTIVE: To characterize the immune changes after treatment of acute HIV-1 infection with triple nucleoside analogue therapy. DESIGN: Immunological and virological parameters were monitored from day 0 to weeks 36-44 in eight patients [median CD4 cells = 451 cells/microl (range: 149-624), viral load = 4.8 log10 copies/ml (range: 6.5-3.3)] who started at time of primary HIV infection (PHI) a therapy including zidovudine (ZDV), didanosine (ddl), and lamivudine (3TC). METHODS: Lymphoid subsets were evaluated on peripheral blood lymphocytes by four-colour flow cytometry using a panel of mAbs directed against differentiation and activation markers. RESULTS: We observed a median -2.1 (range: -1; -3.3) log10 copies/ml viral load decrease and a median +158 cells/microl (range: +7 to +316) CD4 cell count increase at week 4 reaching normal CD4 cell count values of 761 CD4 cells/microl (range: 389-1153) at weeks 36-44. Virus undetectability was obtained at week 24 for all subjects. A rapid CD4 T cell amplification involved both memory and naive CD4 T cells. This was associated with a very rapid and significant decrease in activation markers [human leukocyte antigen-DR (HLA-DR), CD38] on both CD4 and CD8 T cell subsets together with a CD8+CD28+ cell increase as early as week 4. CONCLUSIONS: These results show that early therapy with nucleoside analogues can correct the immunological abnormalities observed in CD4 and CD8 T cell subsets at the time of PHI. This early kinetics in T cell recovery appears to be faster than in established disease.

Adult↗
PubMed1999

[Immunologic reconstruction after antiretroviral treatment].

DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection.

Antiviral Agents↗
PubMed1999

Restoration of the immune system with anti-retroviral therapy.

Clinical benefits of highly active anti-retroviral treatments (HAART) are increasingly evidenced by resolving opportunistic infections and malignancies, as well as declining hospitalization and mortality rates [1]. This suggests that potent and sustained suppression of viral replication, at least to some extent, is associated with reconstitution of the immune system even in adult patients treated at advanced stages of the disease. Increased susceptibility to opportunistic infections and tumors mainly results from the loss of memory CD4+ T cell reactivity against recall antigens which is an early event in HIV disease progression. Primary responses of naive CD4+ T cells against new pathogens are suppressed even earlier in the course of HIV disease, and the progressive depletion in naive CD4+ T cells reflects profound alterations in T cell regeneration capacities. Previous studies revealed that monotherapy with ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+ T cell responses to recall Ags only when detectable prior to onset of therapy, suggesting that the loss of CD4+ T cell reactivity might be irreversible at advanced stages of the disease [2]. In contrast our group demonstrated more recently that restoration in CD4+ T cell reactivity to specific antigens was feasible when HAART was administered in progressors [3]. Here we address some of the questions raised by immune restoration with HAART when administered at advanced stages of the disease.

Adult↗
PubMed1999

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).

The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.

Adult↗
PubMed1999

Has the prognosis of adult patients with acute myeloid leukemia improved over years? A single institution experience of 784 consecutive patients over a 16-year period.

We reviewed the reports of 784 consecutive patients admitted to our department for newly diagnosed acute myeloid leukemia (AML) over a 16-year period. Median, 5-year and 10-year overall survivals were 9. 5 months, 17.3% and 11.7% respectively. Induction treatment (698 patients) resulted in 50% complete remissions (CR) (from 26.5% in secondary AML to 81.2% in patients <60 years with de novo AML). Period of diagnosis (1980-84/85-89/90-95) demonstrated a major significance for CR achievement and OS in multivariate analysis. In patients >/=60 years (372), CR rate increased (25% to 36.8%, P = 0. 03), and 5-year OS (3.7% to 10.6%, P = 0.022) improved, probably due to an increase in the proportion of patients administered conventional combined chemotherapy (54.5% to 83.8%, P < 0.0001). In younger patients CR rate continuously increased (61.5% to 74.8%, P = 0.028) with an associated improvement of 5-year OS (19.2% to 35.4%). No significant change in DFS and CR durations was observed. This large single center study on a large cohort of unselected AML patients reflects the improvement achieved in the management of AML patients, likely due to improvement of supportive care practices, administration of conventional induction to more elderly patients, and intensification of induction and post-remission treatments in patients <60 years.

Acute Disease↗