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Biomedical subjects

L Lafleur

Publications and source records attributed to L Lafleur.

At least 19 recordsLinked to original sources
PubMed1997

Nosocomial pneumonia and tracheitis in a pediatric intensive care unit: a prospective study.

We conducted a prospective study in the multidisciplinary pediatric intensive care unit (pediatric ICU) of a tertiary-care university hospital in order to determine the incidence, risk markers, risk factors, and complications related to bacterial nosocomial pneumonia (BNP) and tracheitis (BNT) in children. A cohort of 1,114 consecutive admissions to the pediatric ICU was enrolled over a 56-wk period; 154 cases were excluded mostly (75%) because they already had a respiratory infection at entry. The final sample included 960 admissions (831 patients). Diagnosis of BNP or BNT was based on Centers for Disease Control of Atlanta criteria using a consensus method involving three experts, who also attributed complications to BNP and BNT. A total of 29 BNP and BNT (3.0%; 95% CI: 1.1 to 4.1%) were diagnosed (BNP: 1.2%, 95% CI: 0.7 to 1.9%; BNT: 1.8%, 95% CI: 0.8 to 2.6%). Three factors were retained by multivariate analysis as independent risk factors or markers for BNP (immunodeficiency, immunosuppression, and neuromuscular blockade), and two for BNT (head trauma and respiratory failure). Gram-negative bacteria and Staphylococcus aureus were the microorganisms most frequently found in the tracheal aspirates. Prescription of antibiotics was commonly attributable to BNP (75%) and BNT (59%). Death, as well as multiple organ system failure, resulted from BNP in 8% of cases, but never from BNT. In BNT, the reintubation rate was 24%. Nosocomial bacterial respiratory infections are rare in critically ill children. However, BNP causes significant complications, and more attention should be focused on BNT in the critically ill child.

Child, Preschool↗
PubMed1996

Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line.

Immunotoxins were prepared by linking the type 1 ribosome-inactivating proteins (RIP) momordin I, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6 to the 48-127 monoclonal antibody (MAb) recognising a glycoprotein (gp54) expressed on all human bladder tumours tested and on human bladder carcinoma cell lines, in particular on the T24 cell line. T24 cells required a 2 hr contact with immunotoxins to ensure binding and endocytosis. A time course of exposure, followed by further incubation without the immunotoxins, showed that maximum inhibition of protein synthesis by T24 cells was reached after 2 hr of contact followed by 3 days without the immunotoxins. Under optimal conditions, 48-127/RIP immunotoxins at nanomolar concentrations inhibited by 50% protein synthesis of target T24 cells. No toxicity was observed if (i) target cells were treated with non-conjugated RIP, (ii) target cells were treated with momordin I- or PAP-S-containing immunotoxins made with an irrelevant antibody and (iii) a non-target cell line was treated with the same 2 RIP conjugated to 48-127 antibody. The in vitro selective toxicity of these immunotoxins encourages further studies in view of a possible use in clinical trials for the local therapy of human bladder carcinomas.

Humans↗
PubMed1996

[Clinical value of the study of proliferation and cell activation antigens with flow cytometry in bladder cancer].

The proliferative rate of tumor cells is frequently proportional to their degree of aggressiveness. The objective of the present study was to determine the correlation between the expression of three antigens associated with proliferation and the stage and ploidy of bladder cancers. The reactivity of antibodies against the nuclear antigen Ki-67 and membrane antigens T43 and the epidermal growth factor receptor (EGFR) was studied by flow cytometry on a series of 35 clinical samples of superficial and infiltrating bladder cancer and as well as on 5 specimens of normal urothelial cells. A preferential expression of the T43 antigen was observed on invasive cancer. EGFR was less frequently expressed; however, seven of the nine positive samples were from invasive cancers. Ki67 on the other hand did not show any selective expression according to tumor stage. When comparing Ki-67 and T43 expression on individual tumor samples, a negative correlation was found in that no tumor strongly expressed both markers simultaneously. These results suggest that markers of proliferation and activation do not all measure the same tumor parameters. Together, they may provide prognostic information that may be useful in the follow-up of patients with bladder cancer.

Antigens, Surface↗
PubMed1992

Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder.

Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events.

Antigens, Neoplasm↗
PubMed1992

Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis.

We undertook a prospective, controlled study to evaluate the effect of trimethoprim-sulfamethoxazole in children with proven Escherichia coli O157:H7 enteritis on the duration fo symptoms, on fecal excretion of pathogen, and on the risk of progression to hemolytic-uremic syndrome. There was no statistically significant effect of treatment on progression of symptoms, fecal pathogen excretion, or the incidence of HUS (2/22 vs 4/25; p = 0.67). Our results suggest that a multicentric trial using rapid diagnostic methods to permit early randomization should be carried out.

Child↗
PubMed1992

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients.

We report the clinical, electrophysiologic, ophthalmologic, and neuropsychologic features of six patients with hyperammonemia-hyperornithinemia-homocitrullinuria syndrome, an inborn error of ornithine metabolism. Pyramidal signs, decreased vibration sense, bucco-facio-lingual dyspraxia, and learning difficulties or subnormal intelligence were found in the majority. Anomalies of peripheral nerve conduction velocity and of evoked potentials were common, and one patient had markedly abnormal white matter images on cranial magnetic resonance imaging. One patient had retinal depigmentation and chorioretinal thinning. The clinical severity varied greatly among patients; in general, the three younger patients had less neurologic and intellectual impairment than did the three older patients. Only two of our patients have had episodes of symptomatic hyperammonemia. We conclude that hyperammonemia-hyperornithinemia-homocitrullinuria syndrome can be associated with widespread manifestations in the central and peripheral nervous systems. Although the control of hyperammonemia is an essential element in the treatment of these patients, the relationship of hyperammonemia to the chronic neuropsychologic problems of these patients is unclear.

Adolescent↗
PubMed1991

Arterial catheter-related infections in children. A 1-year cohort analysis.

To determine the incidence of infection secondary to arterial catheterization in children as well as the risk markers, we prospectively evaluated, during a 1-year period, all arterial catheters installed in children admitted to the pediatric intensive care unit. A total of 340 cannulas were placed in 310 children aged 80 +/- 4 months (mean +/- SEM) for a period of 64 +/- 4 hours. Most catheters were inserted percutaneously (99%) in the radial artery (86.5%). Ninety-two percent (313/340) of the catheters were sterile (group 1), 5% (17/340) were contaminated (less than 10 colony-forming units on semiquantitative culture) (group 2), and 3% (10/340) were considered either locally infected (ie, greater than or equal to 10 colony-forming units) (eight of 10) or associated with a possible catheter-related sepsis (two of 10) (group 3, or infected group). The incidence of local inflammation at the insertion site was higher in group 2 than in group 1 (18% vs 2.9%) but not statistically different between groups 3 and 1 (10% vs 2.9%). The duration of arterial catheterization was longer in group 3 than in group 1 (125 +/- 31 vs 61 +/- 4 hours). The risk of infection was nonexistent in the first 48 hours of catheterization. Thereafter it was calculated as being 6.2% (10/161), but it correlated poorly with the duration of arterial catheterization. These results confirm the very low incidence of infection related to arterial catheterization in children. Thus, routine catheter reinsertion is, in our opinion, unjustified.

Adolescent↗
PubMed1989

[Sterilization and quality control].

The dental profession has always considered the sterilization of surgical instruments as an important element in the prevention of infection. During the last decade the concern with blood and to a lesser degree with saliva in the transmission of infection, due primarily to the hepatitis and HIV viruses, has resulted in many corporate organizations releasing recommendations to reinforce the use of sterilization techniques and disinfection techniques when sterilization is not applicable or justifiable. As a result of the fact that the two terms are often intermingled, the authors review the fact that each one pursues different objectives and put the emphasis on sterilization by briefly reviewing the principal advantages and disadvantages of each method of sterilization presently available for use in dental offices. Subsequently, they stress the importance of introducing quality control in any infection prevention program, in order to assure that the sterilization process is not at the mercy of human error or mechanical failure. The pharmaceutical industry, food chains and hospital centres have for more than 40 years realized the importance of using chemical indicators and especially biological testing. Only biological testing can put one's mind at ease, for the professional in a dental office and the patient receiving care, that the instruments or objects that one comes in contact with are truly sterile. The dental profession did not wait for the discovery of the hepatitis B and HIV viruses to become preoccupied with the spread of disease and have sterilized their surgical instruments for many years.(ABSTRACT TRUNCATED AT 250 WORDS)

Communicable Disease Control↗
PubMed1988

Incidence of infection related to arterial catheterization in children: a prospective study.

The incidence of infection related to arterial catheterization has not been studied in critically ill children, using systematic catheter cultures. We studied prospectively 68 children in whom 70 arterial catheters were inserted. After the aseptic catheterization procedure, no component of the system was changed. The insertion site was inspected daily for signs of inflammation. Upon removal, catheters were cultured using a semiquantitative method. Blood and infusion fluid specimens were also cultured if septicemia was clinically suspected. Mean duration of catheterization was 59 +/- 6 (SE) h. In our series, all catheter and infusion fluid cultures were negative. Local inflammation was not predictive of catheter tip infection and correlated poorly with duration of catheterization (r = 0.2). In our experience, the incidence of infection related to arterial catheterization is low. Routine change of infusion fluid, tubing, dressing and insertion site as well as systematic catheter culture in the absence of fever appears unwarranted.

Adolescent↗
PubMed1988

A novel lymphocyte activation antigen present on allospecific primed lymphocytes and defined by the monoclonal antibody VG01.

This study describes VG01, a monoclonal antibody to a novel lymphocyte activation antigen. The cells reacting with VG01 were first characterized by indirect immunofluorescence and fluorescence-activated cell sorter analysis. The antigen defined by VG01 was expressed on circulating T lymphocytes (23.8 +/- 9.0) and on the majority of large granular lymphocytes and monocytes (greater than 90%), while granulocytes stained weakly. All other cells tested so far--thymocytes, hematological malignancies and several cell lines--were negative. Upon activation with mitogens or allogeneic cells more than 90% of the transformed lymphocytes became VG01-positive. The kinetic studies demonstrated that the antigen defined by VG01 lags the expression of the IL-2 receptor by 48 hr and remains present for up to 18 days after stimulation in culture. Thus, this antigen does not seem to be involved in the initial steps of T cell activation and its expression continues after cell division has stopped. Assays with purified sorted populations showed that lymphocyte proliferation to mitogens and in mixed lymphocyte culture came primarily from the VG01- population. The responding cells became VG01+ during activation--and when alloantigen-primed lymphocytes were sorted and restimulated with the original stimulators, all the in vitro memory response came from the VG01+ population. Thus, VG01 antibody is efficient in selecting for alloreactive T lymphocytes in vitro and has potential for selective modulation of immune responses. Its reactivity with activated T cells and NK cells may also help define a common functional program for these two cell types, adding to the understanding of their mechanism of action and/or their origin.

Antibodies, Monoclonal↗
PubMed1988

Mucoid and pigmentation characters can be suppressed by non-anti-Pseudomonas aeruginosa antibiotics in cystic fibrosis: a report of promising preliminary results.

In an effort to develop new strategies, the authors are exploring the hypothesis that non-anti-Pseudomonas aeruginosa antibiotics can affect some major virulence factors in cystic fibrosis P. aeruginosa. Recent samples (127) of P. aeruginosa isolated from the sputum of cystic fibrosis patients and manifesting a mucoid growth were stored at -70 degrees C until experimentation. The mucoid character was retested after thawing and one 24-h in-vitro passage at 37 degrees C onto 100-mm blood agar plates to prepare a bacterial suspension for inoculation (Steers or MIC-2000 plus replicator) and cultivation (48 h, 37 degrees C) onto different 100-mm or 150-mm Mueller-Hinton agar plates containing either no antibiotics or antibiotics alone, and antibiotic combinations without presumed anti-P. aeruginosa activity. Some isolates (49, 38.6%) of P. aeruginosa expressed again the mucoid character on antibiotic-free Mueller-Hinton agar and growth was prevented by antibiotics in a number of them: 7 with doxycycline (16.0 micrograms/ml), 2 with rifampicin (16.0 micrograms/ml), 6 with roxithromycin-sulfamethoxazole (16.0-304.0 micrograms/ml) and 23 with trimethoprim-sulfamethoxazole. In the remaining evaluable isolates, the mucoid was modified towards the rough character in 36 out of 42 with doxycyline, 36 out of 47 with rifampicin, 31 out of 43 with roxithromycin-sulfamethoxazole and 20 out of 26 with trimethoprim-sulfamethoxazole. In parallel, the pigmentation was lost in the presence of antibiotics in those P. aeruginosa isolates having manifested this character on Mueller-Hinton agar. These results suggest that non-anti-P. aeruginosa antibiotics can modify the in vitro markers of virulence in cystic fibrosis P. aeruginosa and that they merit further investigation.

Anti-Bacterial Agents↗
PubMed1985

Monoclonal antibodies against histone H5. Epitope mapping and binding to chromatin.

Monoclonal antibodies against chicken erythrocyte histone H5 were produced. Nine hybridomas of different clonal origin were selected, and the antibodies were purified by affinity chromatography. Typing of the antibodies indicated that all but one (IgM) belong to the IgG1 class and contain kappa light chains. Indirect immunoprecipitation, solid-phase radioimmunoassay, and competitive inhibition assays using various H5 fragments revealed that the antigen-binding sites were localized on the central region of H5 (GH5, residues 22-100). Results of immunoblots from gels containing different denaturing agents indicate that some of the antibodies recognize related continuous epitopes localized at the junction of the GH5 with the rest of the molecule. Competition experiments between pairs of the eight different IgGs suggest that they recognize at least seven distinct sites on GH5. The epitopes appear to represent different regions of GH5 although some of them overlap. In general, the antibodies recognize epitopes which are not too accessible to the environment in the native conformation of the histone. All of the antibodies examined, except one of them (5H10), react with nuclei and chromatin from the erythroid cells but not from other cell lines. The site recognized by 5H10 is likely to be one of the regions where GH5 interacts with the nucleosome. No cross-reactivity of the antibodies with other histones including H1, H2A, H2B, H3, H4, and rat liver histone H1(0) was observed.

Amino Acid Sequence↗
PubMed1984

Heterogeneity of endothelial cells of adult rat liver as resolved by sedimentation velocity and flow cytometry.

Sinusoidal cells isolated from adult rat liver were fractionated by velocity sedimentation at 1 X g ( primarily on the basis of size) and the various cell fractions were further analysed by flow cytometry on the basis of forward and perpendicular light scattering and autofluorescence. Cell volume was also measured electronically using a Coulter counter. At least four enriched cell populations were resolved after velocity sedimentation. They corresponded to cells having a modal diameter of 6.5, 7.5, 9, and 11 microns, respectively. Transmission electron microscopy (TEM) analysis of the various cell populations revealed that the 7.5- and 9-microns cell fractions represented two distinct classes of endothelial cells while the 11-microns cells corresponded to Kupffer cells. The 6.5-microns cells were identified as lymphocytes. Fat-storing cells, identified by their autofluorescence and lipid content, were included in the Kupffer population. Further information about the nature of the two physically distinct endothelial cell populations was obtained by TEM. It demonstrated that the smaller endothelial cells possessed quantitatively and relatively less retracted sieve plates than the larger ones. This ultrastructural feature can be possibly correlated to a differential localization of the two classes of endothelial cells within the liver acinus.

Animals↗
PubMed1982

The nylon wool adherence marker of the B cell lineage appears at the resting pre-B cell stage.

The proliferative state of functionally defined populations of size-separated pre-B cells was investigated. The results presented here support the hypothesis that pre-B cells are in the G2 phase when stable membrane IgM is first expressed. Small resting precursor cells significantly adhere to nylon wool columns, unlike larger cycling cells which can be enriched in the nonadherent fraction. These results suggest that the nylon wool "receptor' is a useful early B cell marker. Since the in vitro recruitment of both cycling and resting precursors was shown to be essentially dependent on agar mitogen(s), cumulative data suggest that the receptors for agar mitogen(s) appear shortly before surface IgM on proliferating pre-B cells. Nylon wool adherence potential develops next on their resting progeny, followed by full lipopolysaccharide reactivity as cells further mature.

Animals↗
PubMed1982

Pre-B cell differentiation in the bone marrow: a proliferative pathway parallels the post-mitotic maturation of early B cells.

Considerable heterogeneity was found in bone marrow B cell progenitors as functionally defined, size-separated populations were analyzed for their density of membrane IgM receptors, their adherence potential to nylon wool fibers and their susceptibility to lipopolysaccharide-induced differentiation to IgM secretion. The investigation of their cycling status with tritiated thymidine further permitted definition of resting and actively proliferating populations. Heterogeneity was found in the fraction of resting small cells as expected for early B cells progressing through postmitotic maturation. However, the data suggest that part of the pre-B cell progeny can also mature during a proliferative phase.

Animals↗
PubMed1982

Light-chain diversification during pre-B cell differentiation.

The possibility that a committed normal pre-B cell can generate progeny expressing more than one light chain was studied by isoelectric focusing of supernatants from pre-B cells cultured at limiting dilution. Supernatants from mitogen-stimulated mature spleen B-cells analysed on day 6 have shown the presence of a rather homogeneous IgM spectrotype profile. Supernatants from the 8-10-day cultures were usually negative. Isoelectric focusing profiles of supernatants from cultures of bone marrow pre-B cells were different from those of mature spleen cells. Many IgM spectrotypes appeared in the culture supernatants of bone marrow pre-B cells between days 6 and 13, whether the cultures were negative or restricted in their IgM profiles on day 6. These results support the idea that normal pre-B cells, during differentiation, can associate a variety of light chains with an already chosen mu heavy chain.

Animals↗
PubMed1982

In vivo enhancement of mitogen-induced lymphocyte DNA synthesis by sodium diethyl-dithiocarbamate (DTC).

Sodium diethyl dithiocarbamate (DTC), a low molecular weight sulphur compound, has been previously shown to be endowed of immunomodulatory properties. To get a better understanding of the mechanisms whereby DTC regulates the immune response, mitogen-induced lymphoproliferation was studied in spleen from guinea pigs treated with a single i.v. injection of DTC. The results clearly show that DTC enhances, after a lag period, DNA synthesis in T and B lymphocytes. DTC which appears not to act at the level of immuno-competent cells seems to modulate the immune responses through indirect pathways.

Animals↗