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M Druguet

Publications and source records attributed to M Druguet.

At least 19 recordsLinked to original sources
PubMed2004

Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.

OBJECTIVE: To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients. METHODS: Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach. RESULTS: Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data. CONCLUSION: Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.

Aged↗
PubMed2002

[Efficacy and toxicity of aminoglycoside therapy in the elderly: combined effect of both once-daily regimen and therapeutic drug monitoring].

UNLABELLED: This study was aimed to compare with previous results (Grillot et al., 1994), the efficacy of amikacin adaptive optimal control in a geriatric hospital. PATIENTS: During six months, 32 patients (aged of 82 +/- 8 years) were included versus 51 during two years (aged of 80 +/- 5). The mean age was not different between the two populations (NS, Student test). They received amikacin initial dosage of 17.7 +/- 5.1 mg/kg/d (vs 13.3 +/- 3.5 for the reference study) and maintenance dosage of 15.1 +/- 4.8 mg/kg/d (vs 11.8 +/- 5.1 for the reference study). METHOD: Two efficacy outcomes (E1 and E2) and 1 toxicity outcome (T) were taken into account: E1 estimated the effect of adaptive control on maximal drug level, E2: overall recovery. Toxicity outcome was used: T the nephrotoxicity (increasing creatininémia over 44 mumol/l). RESULTS: All the results are given versus the reference study. 57.6% versus 29.4% of adaptive strategy were once-a-day. E1: Chi square test show that initial dosage and maintenance dosage are greater our study than the previous one (p < 0.05: 78.8% versus 5.9% for initial dosage, 84.4% versus 13.8% for maintenance dosage). E2: 73.6% overall of recovery versus 77% (NS, Chi square test). T: 94% versus 85% (p < 0.05, Chi square test) of creatininemia variation are lower than 44 mumol/l. Duration of treatment is 9.8 +/- 4.8 versus 15 +/- 9 days (p < 0.5, Student test). CONCLUSIONS: Once-a-day strategy in amikacin therapeutic regimen is no more efficient but decreases toxicity and duration treatment.

Aged↗
PubMed1994

[Adaptive control of therapeutics using amikacin in very old patients: retrospective analysis of efficacy and toxicity].

UNLABELLED: The authors previously showed the precision of adaptive control of amikacin therapy in elderly patients. The present retrospective study evaluated the effects of such therapy on outcomes. 48 patients, aged 80 +/- 5 years, with estimated creatinine clearance (eCCR) of 48 +/- 15 ml/mn, received amikacin initial dosage of 13.3 +/- 3.5 mg/kg/d, alone or with other drugs. Efficacy outcomes were: E1 = changes in dosage during therapy; E2 = fever reduction within 3 days after therapy; E3 = eradication of infection by culture data; E4 = reduction of white blood cell count (WCB) to normal; E5 = overall recovery. Toxicity outcomes were: T1 = subjective ototoxicity; T2 = nephrotoxicity, variation of serum creatinine low (between 18 et 44 mumol/l) or high (over 0.5 mg/dl). RESULTS: E1: final dose = 11.8 +/- 5.1 mg/kg/d (NS), 57% reduced, 33% increased, during 15.1 +/- 9.3 days in therapy, with 88% having effective peaks over 15 micrograms/ml. E2: fever reduced within 3 days 16/37; after 12/37; no change, 9/37. E3: cultures became negative, 13/28. E4: WBC fell early, 10/21; late, 7/21; no change, 2/21. E5: recovery 36; death, 8; change in therapy, 3. T1: no clinical signs of ototoxicity. T2: low(+), 9/51; low(-), 11/51; high(-), 7/51. final eCCR: 48 +/- 14 ml/mn (NS); no nephrotoxicity. These results suggest that adaptive control of amikacin regimens yields good efficacy and avoid toxicity in the Elderly. However, prospective controlled clinical trials should be done for confirmation.

Aged↗
PubMed1988

Immunohistochemical micromethods for the measurement of specific collagen types in human liver biopsies.

Micromethods are needed for measuring the amount of collagen and other matricial proteins in human liver biopsies. Recently, a colorimetric method for the quantitative estimation of total collagen and protein has been developed. This method is sensitive, can be applied to fresh and fixed tissues and provides the absolute value of total collagen per section. Results are expressed as microgram of collagen per mg of proteins or per section. We now report two micromethods for the determination of specific collagen types in fresh frozen liver sections. The first method is a direct method utilizing the tissue section as an ELISA plate. Results are expressed as the amount of color reaction read at 450 nm per slide. After cleaving the antigen antibody complex with dilute acetic acid, the amount of total collagen can be measured by the colorimetric microchemical method and the amount of specific collagen type is expressed as the amount of color reaction per microgram of total collagen. The second method is an indirect method: the floating tissue section is incubated with an optimal amount of specific anti-collagen antibody and the residual amount of antibody present in the supernatant is measured in an ELISA plate coated with the specific collagen type. The amount of specific collagen type present in the tissue section is determined by comparing the optical deviation obtained with a standard curve prepared with known amounts of specific collagen, and values are expressed as microgram of collagen per tissue sections. As with the direct method, the amount of total collagen per section can be measured by the colorimetric method and then, the amount of specific collagen type can be expressed as microgram of specific collagen type per microgram of total collagen.

Biopsy, Needle↗
PubMed1987

Sequential connective matrix changes in experimental acute pancreatitis. An immunohistochemical and biochemical assessment in the rat.

The effects of acute pancreatitis on the rat pancreatic connective tissue matrix were studied following intraductal pancreatic injection of trypsin solution and serial killing of the animals. Pancreatic tissue was examined using light microscopy, hydroxyproline measurement and indirect immunofluorescence, using antibodies against collagen types I, III, IV, procollagen III, fibronectin and laminin. Light microscopy revealed that acute pancreatitis was present for up to four days after injection and that perilobular and intralobular fibrosis appeared at four days and subsequently regressed. Immunofluorescence studies demonstrated an abnormal fibronectin deposit at one day in acute pancreatitis. At four days this deposit was co-located with fibrosis which was composed of collagen and procollagen type III. By eight days the immunofluorescence and light microscopic changes were minimal. Biochemical analysis confirmed a significant rise in hydroxyproline concentration at four days, which was maximal at eight days, subsequently decreasing. This peak at eight days probably reflects collagen breakdown products.

Acute Disease↗
PubMed1982

[Distribution of collagen, fibronectin, and laminin during morphogenesis of skin and cutaneous appendages in the chick embryo (author's transl)].

In the dermis of inter-appendage and glabrous skin, interstitial collagen types I, III, and V are abundant, while fibronectin is scarce. Conversely, in the morphogenetically active foci of cutaneous appendages, interstitial collagen is scarce or absent, whereas fibronectin is abundant. Type IV collagen and laminin are localized at the dermal-epidermal junction and distributed evenly.

Animals↗
PubMed1980

Radioimmunoassay for immunoconglutinins.

A competitive radioimmunoassay for immunoconglutinin (IK) was developed using isolated antostimulated rabbit IK labelled with 125I and glutaraldehyde-fixed sheep erythrocytes coated with fixed complement (EAC). IKs in test sera of human or animal origin produced specific inhibition of uptake of [125I]IK onto EAC and this was quantitated by reference to a calibration curve established with pure rabbit IK. Among 20 normal human sera the IK levels were: median 62 microgram/ml, range 41-170 microgram/ml and in 7 rat sera the levels were: median 71 microgram/ml, range 58-80 microgram/ml. Preliminary studies showed raised IK levels in the sera of patients with rheumatoid arthritis and with Crohn's disease.

Animals↗
PubMed1980

Collagen immunotyping in human liver: light and electron microscope study.

Types I, III, IV, and AB collagens have been extracted from human cirrhotic livers and specific antibodies have been raised in rabbits and purified. Histological immunofluorescent staining of collagen types in normal and fibrotic human livers reveals the respective distribution of the various collagens among the hepatic connective matrix and the modification of the normal pattern in fibrosis: types I and III appear to be the main components of the fibrotic connective matrix in enlarged portal spaces and of the Dissian reticulin framework; type IV collagen deposits are thickened around portal vessels and ducts and outline lobular capillarized sinusoids; type AB collagen appears as thin punctual deposits in portal and Dissian fibrotic connective matrix. Ultrastructural immunoperoxidase labeling of type I and III collagen makes it possible to identify the typical collagen fibers, using 65 nm periodicity, as type I collagen and the fibrillar associated network as type III collagen. Fibers of type I collagen are preferentially organized in large dense bundles in Dense Connective Matrix Organization (DCMO), since fibrillar type III collagen network is predominant in Loose Connective Matrix Organization (LCMO) surrounding vascular and biliary tracts.

Collagen↗
PubMed1980

[Corneoscleral trabecular collagen. Ultrastructural changes and immunotyping in chronic and cortisone-induced glaucoma].

Ultrastructural changes in connective matrix of corneoscleral trabeculum in primary open-angle glaucoma and corticosteroid-induced glaucoma are described. Four forms of collagen fibers were observed: typical, hyper-, segmented fibers and cross-banded collagen. Light and electron microscopy, using antibodies against collagen types, demonstrates the presence of type I collagen widely distributed in trabecular connective matrix and type III collagen in perivascular zones. Type IV collagen is located on basal membranes on endothelial lamina. In glaucomatous disease, the ultrastructural aspect of connective matrix reflects a continuous remodelling process associating fibrolysis and fibrogenesis.

Adolescent↗
PubMed1978

Response of anamnestic IgA-producing cells in the mouse gut after repeated intragastric immunization.

1) Repeated intragastric immunization after a 90-day interval results in a local immunologic memory. 2) Repeated intragastric immunization does not induce the same circulation of gut lymphocytes as does the initial oral immunization. 3) Measurement of circulating antibodies is a poor criterion for gauging the local immune status. 4) A gastric intubation dose of 4 X 10(9) SRBC given daily for 4 days appears to be suboptimal for the induction of a local immune response.

Animals↗