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Biomedical subjects

E Masson

Publications and source records attributed to E Masson.

At least 37 records · Page 2Linked to original sources

[Automation of the cytometric analysis of the DNA content of solid tumors].

An automatic machine, dedicated to solid tumor DNA ploidy quantitation has been built in order to provide pathologists with a tool usable in clinical practice. Main efforts were focused on an automation of each step of the analysis and on an elimination of any subjective choice, while preserving the quality of measurement. As the software is independent of the machine architecture, it offers performances which increase in parallel with the rapid evolution of the computers. An illustration of the various functionalities of the automaton is proposed through the study of deparaffined breast cancer samples.

Breast Neoplasms↗

[Human contamination by baits for vaccinating foxes against rabies in France].

During 1992 and 1993, 4.4 million of baits have been distributed in France over 121,381 km2 for vaccinating foxes against rabies. Phone calls and visits addressed to the local veterinary authorities and to the centres for human antirabies treatment have been recorded according to an appropriate questionnaire. 70 persons declared to have found and sometimes to have touch a bait, 38 of them received a antirabies treatment. Only 9 children (less than 10 year old) handled a bait. Activities that led to find a bait have been: walking in the countryside or hunting (50% of cases), gardening or playing in the garden or near home (35%) and farming (13%). Often dogs were the first to discover the baits and led to a contact of humans with the vaccine in 54% of cases. No casualty occurred. The frequency of these reports decrease by 80% during the period which is considered to be the result of a better information and awareness of the public.

Adult↗

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Methotrexate (MTX) is one of the most widely used drugs for the treatment of childhood acute lymphoblastic leukemia (ALL) and is commonly given in high doses. However, the rationale for high-dose MTX (HDMTX) has been challenged recently. To determine whether higher MTX polyglutamate (MTXPG) concentrations in ALL blasts translate into greater antileukemic effects, 150 children with newly diagnosed ALL were randomized to initial treatment with either HDMTX (1,000 mg/m2 intravenously over 24 h) or lower-dose MTX (30 mg/m2 by mouth every 6 h x 6). ALL blasts accumulated higher concentrations of MTXPG and long-chain MTXPG (MTXPGLC) after HDMTX (P < 0.00001). Of 101 patients evaluable for peripheral blast cytoreduction, MTXPG concentrations were higher in patients whose blast count decreased within 24 h (P = 0.005) and in those who had no detectable circulating blasts within 4 days (P = 0.004). The extent of inhibition of de novo purine synthesis in ALL blasts was significantly related to the blast concentration of MTXPGLC (IC95% = 483 pmol/10(9) blasts). The percentage of patients with 44-h MTXPGLC exceeding the IC95% was greater after HDMTX (81%) than LDMTX (46%, P < 0.0001). These data indicate that higher blast concentrations of MTXPG are associated with greater antileukemic effects, establishing a strong rationale for HD-MTX in the treatment of childhood ALL.

Adolescent↗

Safety study of the SAG2 rabies virus mutant in several non-target species with a view to its future use for the immunization of foxes in Europe.

The safety of the SAG2 virus, a low virulence mutant of the SAD strain, was investigated in ten species of mammals and seven species of birds liable to consume vaccine baits. These species are the western hedgehog (Erinaceus europaeus), the meadow vole (Microtus arvalis), the bank vole (Clethrionomys glareolus), the water vole (Arvicola terrestris), the field mouse (Apodemus flavicollis or A. sylvaticus), the Norway rat (Rattus norvegicus), the european badger (Meles meles), the domestic ferret (Mustela putorius furo), the wild boar (Sus scrofa), the domestic goat (Capra hircus), the carrion crow (Corvus corone), the rook (Corvus frugilegus), the buzzard (Buteo buteo), the red kite (Milvus milvus), the tawny owl (Strix aluco), the long-eared owl (Asio otus) and the barn owl (Tyto alba). The vaccine was administered orally to each species, by an intramuscular (i.m.) route to the rodents and ferret, and by an intracerebral route to the field mouse. No pathogenicity was observed in the 169 animals vaccinated throughout an observation period of over 30 days. After euthanasia, no rabies virus could be detected either in the brain or in the salivary glands of any of the animals. The SAG2 virus administered orally, triggered a specific seroconversion in the field mouse, wild boar, ferret and most of the raptors. Following administration by the i.m. route, specific antibody titres were observed in most of the rodents, as well as in the ferrets.

Animals↗

Field use of a vaccinia-rabies recombinant vaccine for the control of sylvatic rabies in Europe and North America.

During recent years, most research on the control of sylvatic rabies has concentrated on developing methods of oral vaccination of wild rabies vectors. To improve both the safety and the stability of the vaccine used, a recombinant vaccinia virus, which expresses the immunising glycoprotein of rabies virus (VRG), has been developed and tested extensively in the laboratory as well as in the field. From 1989 to 1995, approximately 8.5 million VRG vaccine doses were dispersed in Western Europe to vaccinate red foxes (Vulpes vulpes), and in the United States of America (USA) to vaccinate raccoons (Procyon lotor) and coyotes (Canis latrans). In Europe, the use of VRG has led to the elimination of sylvatic rabies from large areas of land, which have consequently been freed from the need for vaccination. Nevertheless, despite very good examples of cross-border cooperation, reinfections have occurred in some regions, due to the difficulty of co-ordinating vaccination plans among neighbouring countries. In the USA, preliminary data from field trails indicate a significant reduction in the incidence of rabies in vaccinated areas.

Animals↗

Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with acute lymphoblastic leukemia.

Allopurinol is used to prevent hyperuricemia in newly diagnosed patients with acute lymphoblastic leukemia (ALL). Although allopurinol has been shown to inhibit de novo purine synthesis (DNPS) in fibroblasts in vitro, this effect has not been assessed in ALL lymphoblasts. We assessed DNPS in ALL lymphoblasts in 46 consecutive patients with ALL. DNPS was determined by 14C-formate incorporation in purine bases both at diagnosis (n = 46) and 44h after MTX therapy +/- allopurinol (n = 31). The 27 patients who had received no allopurinol prior to the diagnostic bone marrow aspirate had significantly higher rates of DNPS (median, 102 fmol new purines/nmol total purines/h) compared to the 12 patients who had received more than one dose of allopurinol (100 mg/m2 orally) (median, 2.3 fmol/nmol/h; P < 0.001); the seven patients who received one dose of allopurinol had intermediate rates of DNPS (median, 58.5 fmol/nmol/h). Among patients who were evaluable for MTX effects at 44h (n = 31), the percent inhibition of DNPS was greater in the eight patients who received concomitant allopurinol (median, 100% inhibition) compared to the 23 patients who received only methotrexate therapy (median, 89% inhibition, P = 0.03). These data indicate that allopurinol suppresses may contribute to the decrease in circulating blasts in patients with newly diagnosed acute leukemias.

Adolescent↗

Comparison of the efficacy of the antirabies vaccines used for foxes in France.

Three manufactured antirabies vaccine baits made with the SAD B19, SAG 1 or VRG viruses have been used in a large scale programme in France since 1986. All three baits were found to be effective in achieving a significant decrease in the incidence of rabies, or even its local eradication. The VRG vaccine bait was found to be the most efficient, and resulted in rabies elimination in a non-alpine region after only two campaigns. The fact that the VRG-vaccinated bait was significantly better than the others was probably due to the better conservation of this vaccine and the bait casing in the environment even under summer conditions. The stability of the SAG 1 vaccine bait was improved in 1992, and it has since been giving good results. The choice of the pattern of the vaccination periods appeared to be a determining factor: distribution during spring, then autumn, then spring was found to be more efficient than a distribution during autumn, then spring, then autumn. A distribution of VRG bait during the summer of 1992 was far less efficient due to the lower percentage of foxes that take the baits during this period, despite the proven stability of the baits in such conditions.

Animal Feed↗

Favorable pharmacodynamic features and superior anti-leukemic activity of B43 (anti-CD19) immunotoxins containing two pokeweed antiviral protein molecules covalently linked to each monoclonal antibody molecule.

Standard immunotoxin production procedures using whole IgG as the MoAb moiety yield a heterogeneous mixture of 180 kDa, 210 kDa, and 240 kDa immunotoxin species with 1 to 1, 1 to 2, and 1 to 3 MoAb to toxin ratios. This heterogeneity makes it impossible to precisely deliver a predetermined immunotoxin dose to target cells and impairs the accuracy of pharmacologic studies. In this report, we describe the preparation and characterization of B43(anti-CD19)-pokeweed antiviral protein (PAP) immunotoxins containing either one or two 30 kDa PAP toxin molecules covalently linked to each 150 kDa B43 monoclonal antibody molecule. Compared to the 180 kDa immunotoxin, the 210 kDa immunotoxin displayed greater in vitro chemical stability, resulted in higher systemic exposure levels in vivo, and was a more effective anti-leukemic agent in a SCID mouse model of human B-lineage acute lymphoblastic leukemia. Taken together, the results of this study recommend the clinical evaluation of 210 kDa B43-PAP as a potentially more effective immunotoxin against relapsed B-lineage ALL.

Animals↗

DNA cytometric abnormalities in human esophageal squamous intraepithelial and invasive carcinomas.

DNA ploidy abnormalities of 21 archival human esophageal intraepithelial neoplasia samples were assessed, using image cytometry of deparaffinized samples, with reference to invasive squamous cell carcinoma and corresponding uninvolved squamous epithelium. Cytometric parameters investigated were proportion of G0G1 aneuploid cell population, histogram typing, proportion of G0G1 diploid nuclei, coefficient of variation, mean DNA content, crude 5c exceeding proportion, 2c deviation index, malignancy index and grade, and entropy. The distributions of the above parameters were compared using the paired t test and Fisher's exact test. Among 10 parameters used, Auer typing of DNA histograms, crude 5c exceeding rate, 2c deviation index and malignancy grade according to Böcking allowed discrimination between uninvolved epithelium and invasive squamous cell carcinoma as well as intraepithelial neoplasia. In particular, the distribution of 2c deviation index in the uninvolved epithelium did not overlap that of intraepithelial and invasive carcinomas. The above four parameters, however, were unable to discriminate intraepithelial neoplasia from invasive carcinoma.

Aneuploidy↗

Efficacy of three oral rabies vaccine-baits in the red fox: a comparison.

The three commercial vaccine-baits currently available in western Europe were fed to caged red foxes. The vaccines were: SADB19, Bundesforschunganstalt für Viruskrankheiten der Tiere-Tübingen, Germany: a live attenuated rabies strain; SAG1 VIRBAC, France: low pathogenicity mutant of the SAD strain and "Raboral", Rhône-Mérieux, France: a vaccinia rabies glycoprotein recombinant (V-RG). Protection rates conferred by the vaccine-baits were respectively 7 of 15 (SADB19), 5 of 9 (SAG1) and 6 of 12 (V-RG) when the vaccinated foxes were challenged intramuscularly with 10(4.7) Mice Intra-Cerebral Lethal Doses 50% (MICLD50) of rabies virus which killed all of 6 unvaccinated control foxes.

Administration, Oral↗

Diabetes in prison: can good diabetic care be achieved?

OBJECTIVE: To investigate the clinical characteristics and metabolic control of diabetic patients given structured diabetic care in prison. DESIGN: Survey of diabetic men serving prison sentences during a 22 month period in a large British prison. SETTING: HM Prison, Walton, Liverpool. SUBJECTS: 42 male diabetic prisoners, of whom 23 had insulin dependent and 19 non-insulin dependent diabetes. MAIN OUTCOME MEASURES: Episodes of diabetic instability, glycated haemoglobin concentrations, body mass index. RESULTS: No serious diabetic instability occurred. Between the initial assessment by the visiting consultant diabetologist and a second assessment 10 weeks later glycated haemoglobin concentrations had fallen from 10.8 (SD 2.9)% to 9.8 (2.4)% (p less than 0.05) in prisoners with insulin dependent diabetes and from 8.7 (1.9)% to 7.6 (1.2)% (p less than 0.05) in those with non-insulin dependent diabetes. Good glycaemic control continued, a mean glycated haemoglobin concentration of 7.6 (1.5)% being recorded in seven men remaining in prison for six to 18 months. Mean body mass index (weight (kg)/(height(m))2) did not change during the study (insulin dependent prisoners 23.3 (SD 2.1), non-insulin dependent prisoners 27.9 (3.8)). CONCLUSIONS: Good diabetic metabolic control is usual in prison, probably due to the rigid dietary regimen, no alcohol, and compliance with treatment. Many younger men had defaulted from their home diabetic clinics, and imprisonment allowed screening for diabetic complications and reassessment of treatment. Structured diabetic care should be offered in all prisons.

Adult↗

Symptoms, anxiety and handicap in dizzy patients: development of the vertigo symptom scale.

Questionnaires assessing symptoms, anxiety and handicap were completed by 127 vertiginous patients. Factor analysis identified four distinct symptom clusters which formed the basis for the construction of scales quantifying the number and frequency of symptoms of: (a) vertigo (of long and short duration); (b) autonomic sensations and anxiety arousal; and (c) somatization. Scores on the vertigo severity scale were significantly related to clinical diagnosis and had near-zero correlations with measures of anxiety. Vertigo severity, autonomic signs and depressed mood each independently contributed to variance in handicap, taking precedence over the relationship between handicap and trait and state anxiety. Our findings suggest that the familiar association between anxiety and vertigo may be mediated principally by autonomic symptomatology arising as a result of somatopsychic and psychosomatic processes.

Adolescent↗

Development of an automatic program for the stereological estimation of the volume weighted mean volume of cell nuclei.

A stereological method was recently developed for the estimation of the volume weighted mean volume of particles from 2D sections. Several authors successfully applied this manual method to paraffin sections of bladder cancers and malignant melanomas and found a good correlation between the mean nuclear volume and the histological grading and prognosis of these tumors. The implementation of this measuring method on an automatic image analyser, devoted to routine work in tumor pathology, is presented. The accuracy of the automatic measurement has been evaluated together with the first results obtained from human esophageal cancers.

Cell Nucleus↗

Apical root canal anatomy in the dog.

240 permanent teeth from 8 different dogs aged 1, 3, 8, 10, 15 years, were used for an anatomic study. The teeth were cleaned, their root canal system was stained with dye, then the teeth were decalcified and cleared to determine the root canal anatomy. The apical root canal anatomy in dogs can be described as a "sprinkler-rose" anatomy: at the tip of the pulpal canal, the canal is divided in numerous narrow channels radiating peripherally through the dentin and the cementum and ending in numerous apical foramina on the cementum surface. This architecture constitutes a very complex apical delta.

Animals↗

Somatic and psychological factors contributing to handicap in people with vertigo.

Questionnaires assessing symptoms, disability and handicap, predisposition to anxiety, and current anxiety and depression were completed by 127 people attending neuro-otology clinics with a major complaint of vertigo or dysequilibrium. Definite signs of vestibular dysfunction (spontaneous or positional nystagmus, or canal paresis) were found in 56% of the sample, but the presence or absence of abnormal vestibular test results was unrelated to diagnosis, reported symptoms, handicap and psychological status. Two-thirds of employed respondents admitted to occupational difficulties, and more than one in seven had left work because of vertigo. Although the number of people in the sample with a predisposition to anxiety was not unusually high, over a third of the sample had abnormally elevated levels of current anxiety. Multiple regression analyses indicated that disability was determined mainly by physical factors (vertigo severity and duration, age and sex). Handicap was influenced by a mixture of somatic and psychological variables, including the severity of autonomic symptoms. Anxiety and depression were only indirectly related to the severity and duration of the vertigo, insofar as this contributed to handicap. The partial dissociation between these different aspects of patient well-being suggests a need for separate evaluation and differing management of problems at each level of functioning.

Adaptation, Psychological↗

Three-dimensional DNA image cytometry by confocal scanning laser microscopy in thick tissue blocks.

A method for the quantification of nuclear DNA in thick tissue blocks by confocal scanning laser microscopy is presented. Tissues were stained en bloc for DNA by chromomycin A3. Three-dimensional images, 60 microns deep, were obtained by stacking up confocal fluorescent images obtained with an MRC-500 (Bio-Rad, Richmond, CA). The effects due to bleaching and attenuation by depth of fluorescence emission were corrected mathematically. The DNA contents were estimated by summing up the detected emission intensities (discretized into pixel gray levels) from each segmented nucleus. Applications to an adult rat liver and to a human in situ carcinoma of theesophagus are shown to demonstrate, respectively, the precision of the method and its potential usefulness in histopathology. Comparisons are made with DNA histograms obtained on the same materials by image cytometry on smears and by flow cytometry. Ploidy peaks obtained with the confocal method, although wider than with other methods, are well separated. Confocal image cytometry offers the invaluable advantage of preserving the tissue architecture and therefore allowing, for instance, the selection of histological regions and the evaluation of the degree of heterogeneity of a tumor.

Animals↗