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Biomedical subjects

M Guiguet

Publications and source records attributed to M Guiguet.

At least 73 records · Page 4Linked to original sources

Epidemiology of aplastic anemia in France: a prospective multicentric study. The French Cooperative Group for Epidemiological Study of Aplastic Anemia.

Incidence rates of aplastic anemia (AA) are rare among defined populations. Since June, 1984, a cooperative group, including 83 University medical centers throughout metropolitan France, prospectively recorded new cases of AA and followed them up. Inclusion criteria were: at least two depressed blood cell lineages (hemoglobin less than or equal to 10 g/100 mL and reticulocytes less than or equal to 50 x 10(9)/L, granulocytes less than or equal to 1.5 x 10(9)/L, platelets less than or equal to 100 x 10(9)/L) and a bone marrow biopsy compatible with the disease. Between May, 1984, and April, 1987, 292 cases were recorded. After exclusion of constitutional disease, 27 patients did not satisfy the inclusion criteria with relation to either bone marrow or blood evaluations and seven patients were initially misdiagnosed (shown in the follow-up), leaving 250 confirmed AA cases in the register. The annual incidence in France appeared to be about 1.5 per million inhabitants. The sex ratio of AA cases was similar to that of the population. In men, two peaks of incidence were observed: one between 15 and 30 years and one after 60 years. In women, the only peak was observed after 60 years. An excess of cases was observed in small towns but not in rural areas. About two of every three cases had severe AA, with a possible excess in younger cases. Based on a minimum follow-up of 1 year for 238 patients, the fatality rate was estimated at 17% at 3 months after diagnosis and at 34% at 1 year. Among 243 suspected etiologies reported by the physicians, 74% were declared idiopathic, 13% presumably associated to drug toxicity, and 5% related to hepatitis. AA appears to be a rare and severe disease in metropolitan France, often of unknown origin, a fact that emphasizes the necessity of controlled etiologic studies.

Adolescent↗

Effectiveness of simple measures to control an outbreak of nosocomial methicillin-resistant Staphylococcus aureus infections in an intensive care unit.

Between June 1985 and March 1986, 14 cases of severe nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection, including septicemia, were observed in the intensive care unit (ICU) of a 400-bed cancer reference center. Simple control measures including contact isolation of colonized patients and reinforcement of handwashing practices among personnel were followed by a sharp decrease in the rate of infection and colonization. An epidemiological investigation showed that a single serophage variant MRSA strain was involved; peak incidence of infection was 17 per 100 ICU patient discharges; the index case was identified as a patient admitted from another hospital and the epidemic strain was then transmitted from patient-to-patient in the ICU; risk factors for acquiring infection were length of prior hospitalization, invasive procedures and number of antibiotic treatments; dissemination of the strain to other wards was only anecdotal. These results stress the effectiveness of simple measures to control outbreaks of MRSA nosocomial infections even in immunocompromised cancer patients.

Cancer Care Facilities↗

Fiberoptic bronchoscopy in ventilated patients. Evaluation of cardiopulmonary risk under midazolam sedation.

One hundred seven acutely ill ventilated patients were prospectively studied to ascertain the severity and frequency of alterations in gas exchange and hemodynamic parameters during brief bronchoscopy. Sedation was performed using midazolam (0.1 mg/kg IV) without topical anesthesia. An average decline in PaO2 of 26 percent was observed at the end of the procedure, compared to the baseline value, and this was associated with a mild increase in PaCO2 in spite of the use of a special adapter. Alterations in mean systolic blood pressure appeared to be modest, consisting of a 10 percent decrease from the control level, related to sedation, and a 10 percent rise from baseline during the procedure, associated with a concomitant mild tachycardia. At that time, central hemodynamic measurements performed in a subset of 31 patients showed a significant increase in cardiac output associated with higher pulmonary wedge pressure. Fourteen patients developed hypoxemia of less than 60 mm Hg on FIO2 adjusted to 0.8. Of the ten risk factors univariately associated with hypoxemia, only the presence of ARDS (p less than 0.001) and "fighting" the ventilator during the procedure (p less than 0.05) remained significant after stepwise logistic regression. Attempts to prevent hypoxemia in critically ill patients should focus on inducing complete sedation, with careful attention to hemodynamic status, or providing maximal levels of oxygen to the ventilator (or both).

Adult↗

Detection of nosocomial lung infection in ventilated patients. Use of a protected specimen brush and quantitative culture techniques in 147 patients.

To determine the usefulness of samples obtained by bronchoscopy using a protected specimen brush and evaluated by quantitative culture techniques in establishing the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation, we prospectively studied 147 ventilated patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. Positive cultures of protected brush specimens (greater than 10(3) cfu/ml) were found in only 45 patients (31%). Subsequent follow-up confirmed the diagnosis of pneumonia in 34 of 45 patients, and in only 4 of 45 patients was a positive culture firmly established to be a false positive result. No patient with less than 10(3) cfu/ml was subsequently shown to have had pneumonia, and the diagnosis was definitely excluded in 72 of 102 patients by the absence of pneumonia at autopsy or recovery without antibiotic therapy. In contrast, when 16 clinical variables were evaluated by stepwise logistic regression analysis, no combination could be identified that was useful in distinguishing patients with bacterial pneumonia. Furthermore, when the actual costs of evaluation and therapy of our patients were compared with the projected costs entailed in treating all patients suspected of having pneumonia with antibiotics, evaluation using the protected specimen brush and quantitative cultures was less expensive after only 6 days of treatment. These results suggest that the appearance of pulmonary infiltrates and purulent tracheal secretions does not result from bacterial pneumonia in a majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Third component of rat complement. Purification from plasma and radioimmunoassay in culture media from cell lines.

A double antibody radioimmunoassay for rat C3 has been developed. The assay required the preparation of C3 from plasma. A new purification procedure using ion exchange high performance liquid chromatography is described. The final product was homogeneous on SDS-PAGE analysis. Rat C3 has an apparent molecular weight of 187,000 and is composed of two polypeptide chains with molecular weights of 125,000 and 73,000, respectively. The purified C3 antigen with high hemolytic reactivity, as assessed by its specific functional activity, was used in preparing anti-C3 sera to perform a specific radioimmunoassay for quantifying C3 in the presence of heterologous sera contained in the cell culture media. All the validating criteria, such as precision, recovery and dilution studies, were investigated. The high sensitivity of the method allowed replicate determination of C3 in small aliquots of the cell culture medium.

Animals↗

Biosynthesis of the third component of complement in rat liver epithelial cell lines and its stimulation by effector molecules from cultured human mononuclear cells.

Rat liver epithelial cell lines, growing in a serum-supplemented medium, synthesize and secrete into the culture medium the third component of complement (C3). We studied the regulation of C3 production in this system. We found that human peripheral blood mononuclear leukocytes in culture released one or more soluble factors which stimulated rat liver epithelial cells to produce increased quantities of C3. This stimulating effect was strongly enhanced when the mononuclear cell cultures were treated with phytohemagglutinin, a T-lymphocyte mitogen. The factor(s) failed to enhance C3 biosynthesis by rat dermal fibroblasts, which are known to produce this protein. This reveals a tissue-specific differential response between the fibroblasts and the liver epithelial cells. The physical and chemical characteristics, such as heat sensitivity, 2.8 M ammonium sulphate precipitation, and lower activity after digestion by proteases unambiguously indicate that the effector molecules are proteins. When the crude supernatant of mononuclear leukocytes was fractionated by gel filtration, the stimulating factor(s) eluted as two peaks with apparent molecular weight of 25 to 60 and 15 to 20 kdalton, respectively. As to the cellular origin of the C3-stimulating factor(s), several observations were made: (a) in separate cultures containing either T-cells or monocyte-enriched populations from the same sample of blood mononuclear cells, no activity was detected in the presence or absence of phytohemagglutinin, (b) conditioned media from each of these cultures could not substitute for the corresponding intact cell populations, and (c) the addition of purified T-cells to the monocyte-enriched population in the presence of phytohemagglutinin restored the production of the stimulating activity by the mixed culture. Finally, experiments were carried out to verify whether monokine interleukin 1 affects the hepatic C3 biosynthesis. It was demonstrated that interleukin 1 enhanced this biosynthesis, but could not completely substitute for conditioned medium from stimulated mononuclear cells.

Animals↗

Epidemiological survey of a major outbreak of nosocomial legionellosis.

Forty-seven nosocomial cases of legionellosis due to Legionella pneumophila serogroup 1 were diagnosed in one major outbreak from November 1982 to March 1983 in a 960-bed teaching hospital. Contaminated water was considered to be a possible source of infection because, during that period, monthly samples were found to be positive with averages of 10(4) CFU/l. After chlorination of hot water associated with flushing of outlets, nearly all samples taken in the next two years were found to be negative. A case-control study was performed to examine potential risk factors. Three groups of controls were randomly selected among eligible patients. In a multivariate analysis, only three clinical factors were found to be associated with legionellosis patients: malignant illness (relative risk, RR = 3.5), presence of an ultimately fatal disease (RR = 2.6), and exposure to corticosteroids prior to admission (RR = 7.9). Investigations of in-hospital exposures suggest that during this nosocomial outbreak diagnostic or therapeutic respiratory procedures had not increased the risk of illness. Although the epidemiological association between water contamination and disease remains unclear, the eradication of L. pneumophila from the identified supply seems to have been effective in preventing disease in this hospital.

Adolescent↗

Pseudoepidemic of aspergillosis after development of pulmonary infiltrates in a group of bone marrow transplant patients.

During February and March 1985, seven patients in the pediatric bone marrow transplant unit (PBMTU) of a 350-bed cancer hospital developed pulmonary infiltrates. Five of the patients had Aspergillus spp. isolated from the respiratory tract, and two of these patients had histologic evidence of aspergillosis. Between 26 February and 22 April, Aspergillus spp. were isolated in a total of 70 cultures from 39 hospitalized patients. Of the 70 cultures, 14 (group 1) were from respiratory specimens of PBMTU patients with pulmonary infiltrates and were submitted to the laboratory intermittently over the 56-day period. However, of the other 56 Aspergillus-positive cultures (group 2), 41 (73%) were submitted on six days during this period (P less than 0.001, chi-square goodness of fit), including 8 blood cultures submitted on one day. When Aspergillus sp. was recovered from group 1 cultures early during this period, the isolates were stored in the culture-processing room. Aspergillus isolates were not handled in a biological safety cabinet, and blood cultures were done by using a system which requires opening of an evacuated bottle to room air. The presence of stored Aspergillus isolates was associated with a markedly elevated concentration of airborne fungi in the culture-processing room. After removal of the stored Aspergillus isolates from the culture-processing room, the concentration of airborne fungi returned to background level and there were no further Aspergillus-positive cultures. These findings suggested that group 2 cultures had been contaminated by stored Aspergillus isolates. No evidence for a common source of infection was found in the PBMTU patients with pulmonary infiltrates.

Air Microbiology↗

Radiation carcinogenesis: cumulative empirical distribution functions and risk projection models.

The use of cumulative empirical distribution functions (CEDF) in connection with the prediction of radio-induced cancer risk is discussed. Two models are generally used for risk prediction: the relative risk and the absolute risk models. It can be easily demonstrated that if the relative projection model is valid, then the CEDFs of the cohort exposed to radiation and of the non-exposed cohort are the same. Land and Tokunaga have shown that for several sets of data the CEDF of exposed and non-exposed cohorts are indistinguishable. They used this result to recommend the use of the relative risk projection model and the rejection of the absolute projection model. This report discusses their argument and shows that when the absolute projection model is valid, the non-exposed and exposed CEDFs are also indistinguishable.

Humans↗

Additive models for dependent cell populations.

We propose an additive model for cell population growth which allows for positive correlation between sister cell lifetimes but arbitrary correlations between mother and daughter cell lifetimes. In the model each cell lifetime is the sum of two independent components, one of which is shared with its sister cell and which is also a function of the components of the lifetime of their mother. Assuming that the components follow a gamma distribution, the model is fitted to cell lifetime data of EMT6 cells obtained by the method of time-lapse cinematography.

Animals↗

Oxidoreductive and hydroxylating metabolism of progesterone in rat liver epithelial cell lines.

Mechanisms and sequences of reduction and hydroxylation of progesterone into 6-hydroxypregnanolones were studied in proliferating rat liver epithelial cell cultures. These cell lines had an intense metabolic activity and all the metabolites were unconjugated. The formation of 3 alpha,6 alpha- and 3 beta,6 alpha-dihydroxy-5 alpha-pregnan-20-one was observed when the cells were incubated with progesterone, 5 alpha-pregnane-3,20-dione, 3 alpha- or 3 beta-hydroxy-5 alpha-pregnan-20-one and 6 alpha-hydroxy-5 alpha-pregnane-3,20-dione but not with 6 alpha- or 6 beta-hydroxyprogesterone, 5 beta-pregnane-3,20-dione, 3 alpha- or 3 beta-hydroxy-5 beta-pregnan-20-one. These findings indicate that the potential precursors of the 6 alpha-hydroxypregnanolones have a 5 alpha-configuration. The reduction of 5 alpha-pregnane-3,20-dione at C-3 followed by a 6 alpha-hydroxylation can be postulated as the major, if not the only, metabolic pathway. However, the possibility that 6 alpha-hydroxylation may occur prior to reduction of the C-3 oxo group cannot be entirely ruled out. The stereospecificity of reduction at C-5 and hydroxylation at C-6 are discussed and compared with 6-hydroxylated progesterone metabolites found in man and some other mammals during pregnancy and the neonatal period.

Aging↗

Laser nephelometric measurement of seven serum proteins compared with radial immunodiffusion.

Quantification of immunoglobulins IgG, IgA, IgM, C3 complement, siderophilin, alpha 2-macroglobulin and haptoglobin in serum by a Behring laser nephelometer coupled with a date processing apparatus was compared with values obtained by the radial immunodiffusion method of Mancini. The precision was not improved by the use of the laser nephelometer as compared to Mancini radial immunodiffusion, but within run precision was better than that among runs for both methods. The analytical recovery studies for laser nephelometry showed a close concordance between the theoretical and measured values for all proteins. The two techniques were also compared by means of correlation studies.

Blood Proteins↗

Statistical analysis of splenic colony histology: an attempt to confirm that external factors could affect the channelling of CFUS differentiation.

The aim of this work was to analyze quantitatively experimental data, which suggest that CFUS determination can be manipulated by external fibers. This hypothesis was based on the comparison of the ratio of erythroid to granulocytic spleen colonies generated by normal bone marrow exposed to factors released by either untreated or arabinoside cytosine treated mouse bone marrow. To investigate mechanisms able to produce this modification of spleen colony histology, statistical analysis was performed by testing three different schemes of evolution of the number of splenic colonies according to this histology from normal to treated groups. The total number of colonies per spleen is similar in both groups, but a significant increase of the number of erythroid colonies per spleen and a significant decrease of the number of granulocytic colonies are observed in the treated group as compared to control. Bias due to the used experimental technique are investigated but could not explain the observed differences. A unique mechanism acting on only one committed stem cell population does not fit the experimental data. Although other possible mechanisms are suggested, the experimental observations can be interpreted as the consequence of a shift of CFUS differentiation toward the erythroid pathway at the expense of at least the granulocytic lineage due to some humoral factors, secreted by treated mouse bone marrow.

Animals↗

[Production of complement C 3 fraction by rat liver epithelial cells in culture. Stimulating effect of monocyte supernatants from human circulating blood].

A noticeable increase has been observed in the production of the C 3 component of the complement by Rat liver epithelial cells cultured in vitro in the presence of small quantities of supernatant of human blood mononuclear cells cultured for 72 hrs. with phytohemagglutinin. The physicochemical properties suggest that the stimulating factor(s) is(are) protein(s).

Animals↗

Proliferation kinetics of rabbit articular chondrocytes in primary culture and at the first passage.

The in-vitro proliferation kinetics of young rabbit articular chondrocytes were compared in primary culture and at the first passage. The growth curves labelling and mitotic indices, percentage labelled mitosis (PLM) curves and DNA content distributions by flow-microfluorometric analysis during a 7-day growth period were determined in both cases. The length of the cell cycle and the doubling time calculated from the exponential part of the growth curve were quite similar: Tc = 19 hr and Td = 20 hr for the primary culture, Tc = 17 X 3 hr and Td = 20 hr for the first passage. However, the growth curve and the DNA distribution during the 7-day period showed some differences. The duration of the lag period studied by the growth curve was longer in the primary culture than at the first passage. This phenomenon was also observed using the FCM analysis. The growth fraction determination on the second day of culture was in accordance with the lower proliferation capacity of the cells in primary culture. These data suggest that it would be better to study growth kinetics and drug modifications in articular chondrocytes at the first passage than in primary culture.

Animals↗