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Biomedical subjects

D Pierard

Publications and source records attributed to D Pierard.

47 records · Page 3Linked to original sources

Efficacy and safety of pefloxacin in the treatment of severe infections in patients hospitalized in intensive care units.

Sixteen patients, 14 with an infection of the lower respiratory tract and two with cholangitis, were treated with pefloxacin 400 mg bid or tid. The original pathogens were eradicated in all but one patient. Pefloxacin therapy resulted in clinical cure in 11 patients, three patients were improved clinically and in two patients a clinical failure was observed. No adverse effects were noticed during or after pefloxacin administration.

Adolescent↗

Aztreonam treatment of gram-negative septicemia.

Seventy-five aztreonam treatment courses in 74 patients with gram-negative septicemia resulted in 56 clinical cures (75%), 12 partial clinical cures (16%), and 7 clinical failures (9%). Eradication of the original pathogen from the blood was obtained in all patients but two, who had relapses 1 and 4 days, respectively, after treatment. In nine patients (12%) a superinfection was reported. Significant adverse reactions were limited to one transient urticarial rash. Aztreonam may prove to be an effective alternative for the treatment of gram-negative septicemia, but superinfections should be carefully monitored.

Adolescent↗

Characterization of a spontaneously transformed pulmonary embryonic rat (PER) epithelial cell line.

A spontaneously transformed pulmonary embryonic rat epithelial cell line (PER) is described in terms of growth, tumorigenicity, growth factor responsiveness and biosynthetic capacity. At low-passage subcultures, PER cells grew as a monolayer and did not form colonies in soft agar. After long-term subcultivation, they lost contact inhibition, became anchorage-independent and formed tumours in nude mice. Low concentrations of foetal calf serum permit the maximum growth rate. The multiplication and metabolic activity, assessed by 2-deoxy-D-glucose uptake, was significantly stimulated by growth factors. PER cells synthesized collagen types I, III, IV and V, laminin and fibronectin, and organized a pericellular matrix made up of only basement membrane components (type IV collagen and laminin) and fibronectin. These data enabled us to define PER cells as a transformed epithelial cell line evolving towards malignancy with long-term subcultivation. These cells appeared to be a valuable tool in studies of tumour cell-matrix interactions and regulation of growth factor receptors in tumorigenesis.

Animals↗

Radioimmunoassay for the amino-terminal sequences of type III procollagen in human body fluids measuring fragmented precursor sequences.

Antisera specifically directed against the amino-terminal precursor sequence of bovine p-N-collagen type III (Col 1-3 III) have been raised in rabbit. When tested in a radioimmunoassay, parallel displacement curves and complete cross-reactivity were observed between bovine and human purified Col 1-3 III. However, these displacement curves were not parallel to that obtained with serially diluted human sera which presented a smoother slope. Cleavage of the Col 1-3 III peptide by collagenase at high temperature yielded an immunoreactive preparation containing two smaller peptides (Col 1 plus Col 2) III. The displacement curves obtained with human or bovine (Col 1 plus Col 2) preparations were parallel to those obtained with serially diluted human sera or other human body fluids (amniotic and ascitic fluids). Quantitative measurements of the circulating antigen in normal and pathological conditions are possible only when the (Col 1 plus Col 2) is used as standard antigen. This radioimmunoassay represents an original and simple technique offering good accuracy. The amount of (Col 1 plus Col 2) III in human adults is 69.1 +/- 27.7 ng/ml, with a distribution of frequency close to the normal. It is increased in liver cirrhosis and other conditions characterized by an active neoformation of connective tissue.

Adult↗

[Changes in antibiotic resistance of organisms isolated from blood cultures in a recently built hospital].

The change in antimicrobial resistance of organisms isolated from blood cultures was studied in a university hospital that opened in July 1977 and had 550 beds by December 1982. Minimal inhibitory concentrations (MIC) were studied by an automatic microdilution technique. Analysis of MICs in the different groups of organisms in relation with time demonstrated no enhancement of resistance during these first 5 1/2 years, except for Pseudomonas aeruginosa that became significantly more resistant (p less than 0.05) to five of the seven antibiotics tested. However, comparison of the two periods July 1977-December 1980 and january 1981-December 1982 evidenced a trend towards a decrease in Enterobacteriaceae (p. less than 0.001) and increase in P. aeruginosa (p less than 0.01) and S. aureus (p less than 0.001). This suggests that the selective pressure from hospital use of antibiotics caused no increase in resistance of different organisms but rather a modification of their relative frequency.

Anti-Bacterial Agents↗

Polyclonal and monoclonal antibodies as reagents in biochemical and in clinical-chemical analysis.

Conventionally prepared polyclonal antibodies have been used for a long time in biomedical research and in clinical-chemical diagnosis. The hybridoma technology introduced by Köhler & Milstein [1975) Nature 256, 495-497), has opened the way to a new dimension in serology. It is now possible to prepare monoclonal antibodies to any determinant on any component of biological matter. Such monoclonal and thus specific antibodies can be obtained even against previously unknown antigens which had not been available in purified or enriched form. Thus the dreams of immunologists and clinical scientists who were searching for new disease-related markers, have become a reality. The present impact and the predictable future influence of these new developments on biomedical research and especially on clinical-chemical diagnosis, as well as their potential, limitations and problems, will be critically reviewed in this paper. As an example of the potential of the new technology, recent results of tests on the quantitation of urinary kidney-derived antigens with the help of monoclonal antibodies are presented. With these monoclonal antibodies, which are specific for antigens in defined regions of the nephron of the human kidney, recognition of the location and extent of primary damage at the cellular level will be possible without invasive techniques.

Animals↗

Developmental aspects of immunologically characterized proteins.

The spectrum of clinical tests for proteins characterized by their antigenic rather than by their enzymatic properties has been very limited, and still is today. This is mainly due to technical problems in the development of tests for such "antigens". The recently developed hybridoma technology has supplied us with the urgently needed new approach to overcome these problems. It is now possible to develop specific monoclonal antibodies against any determinant on antigens in any tissue, membrane or extract without the need to prepare antigens of high purity. Diagnostically valuable tissue marker molecules without known biological activity have become accessible, and can be detected and quantitated in tissues and body fluids with the new reagents. In most of the tests that will become available now or in the near future, polyclonal antisera will be substituted by monoclonal antibodies. Future developments, however, will exploit the advantages of the new technology to their full extent. In this paper, the advantages and disadvantages of monoclonal antibodies are evaluated and illustrated by the example of monoclonal antibodies to human kidney tissue antigens. Future developments comprising all fields of clinical diagnosis as well as applications in therapy are discussed.

Animals↗

Group JK corynebacterium peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis.

We describe a case of peritonitis with isolation of a group JK corynebacterium from the peritoneal effluent in a patient undergoing continuous ambulatory peritoneal dialysis and treated with corticosteroids. Therapy with intraperitoneal vancomycin resulted in a rapid eradication of the organism. However, only 1 month after discontinuation of the 26-day therapy, a second episode of peritonitis with JK corynebacterium occurred. After vancomycin was restarted, the organism disappeared again from the peritoneal fluid, but the patient died a few days later from heart failure apparently unrelated to the infection. Some authors have mentioned the isolation of diphtheroids (without further identification) from peritoneal effluent of continuous ambulatory peritoneal dialysis patients, but to our knowledge, this is the first report of peritonitis associated with JK corynebacterium, an opportunistic organism that must be differentiated from other corynebacteria.

Aged↗

[Evaluation of ceftriaxone (R013-9904) in the treatment of septicemia caused by gram-negative bacilli].

Thirty-four patients admitted for a suspicion of septicaemia were treated with ceftriaxone, a third generation cephalosporin. Ceftriaxone was administered IV at a dose of 2 grams daily, either as a single injection of 2 g or as two injections of 1 g each. 43 organisms were isolated from the blood of the 34 patients: 20 E.coli; 5 Klebsiella; 2 Salmonella; 2 indole positives Proteus; 1 indole negative Proteus; 1 Enterobacter; 2 Acinetobacter; 3 Staphylococcus aureus; 2 Streptococcus; 1 Enterococcus; 1 Meningococcus and 3 anaerobes. The MIC of the enterobacteria for ceftriaxone ranged from less than or equal to 0.097 microgram/ml to 1.56 microgram/ml. Only two staphylococci, one Acinetobacter and the enterococcus were resistant to the drug. Serum assays of ceftriaxone were performed on the second day of treatment for 15 patients. Within the group treated with a single dosis of 2 g per day, the blood levels were: maximal level (10 min, after the injection): 175 to 460 micrograms/ml (average: 315), minimal level (before injection) 12 to 100 micrograms/ml (average 53). Among the patients treated with two doses of 1 g per day, we obtained: maximal levels 121 to 260 micrograms/ml (average 178), minimal levels 31 to 70 micrograms/ml (average 52). A clinically favorable evolution was obtained for 29 patients (85%). In the cases of 4 patients, the antibiotherapy had to be adapted in view of the susceptibility of the organisms isolated. Ceftriaxone was very well tolerated. The only observed secondary effect was a drug fever occurring in 3 patients who remained febrile in spite of a general improvement.

Bacteria↗

Secretory proteins induced in human fibroblasts under conditions used for the production of interferon beta.

Human fibroblast cells treated with a combination of inhibitors of protein and RNA synthesis [cycloheximide and actinomycin D as used to superinduce interferon beta (IFN-beta)] secrete two proteins with molecular masses of 22000 and 27000 kilodaltons (called 22-kDal and 27-kDal) that are precipitable with an antiserum raised against impure IFN-beta but are antigenically distinct from IFN-beta 1. Translation in vitro of mRNA extracted from human fibroblast cells induced for the production of IFN-beta leads to the synthesis of a 26-kDal protein that is structurally closely related to the 22- and 27-kDal proteins. This 26-kDal protein mRNA is relatively abundant and also appears in human fibroblasts induced only with cycloheximide. It has been partially purified by sucrose gradient centrifugation and more extensively by diazobenzyloxymethyl-cellulose hybridization to plasmid DNA from a bacterial cDNA clone. When translated in an in vitro reticulocyte system supplemented with dog pancreas microsomes, the 26-kDal protein and two other intermediates corresponding presumably to its signal-cleaved (19-kDal) and partially glycosylated (24-kDal) forms were observed. Crude, partially purified, and highly purified 26-kDal mRNA failed to program the synthesis of antiviral or ppp(A2'p5')nA synthetase-inducing activity when translated in Xenopus laevis oocytes. Moreover, partially purified 22-kDal and 27-kDal (i.e., the in vivo equivalents of the 26-kDal protein) are also devoid of antiviral or ppp(A2'p5')nA synthetase-inducing activity. Hence, this 26-kDal mRNA, although presumably identical to the human IFN-beta 2 mRNA described by Weissenbach et al. [Weissenbach, J., Chernajovsky, Y., Zeevi, M., Shulman, K., Soreq, H., Nir. U., Wallach, D., Perricaudet, M., Tiollais, P. & Revel, M. (1980) Proc. Natl. Acad. Sci. USA 77, 7152-7156], cannot be considered to be a fibroblast interferon mRNA.

Cells, Cultured↗