Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 163 records · Page 9Linked to original sources

PubMed1996

[Testicular biopsy at the stopping of the treatment in acute lymphoblastic leukemia: value of the immunohistochemical detection of residual blasts].

BACKGROUND: The prognostic value of clinical and histological detection of testicular leukemia after completion of therapy is still debated. Immunohistochemical study could improve the results of this detection. PATIENTS AND METHODS: Between 1982 and 1992, 70 consecutive boys with acute lymphoblastic leukemia (ALL) and treated with the same therapeutic regimen were included in the study. Testicular biopsy (TB) was surgical and bilateral. One piece of tissue was fixed and analysed by conventional microscopy. An immunohistochemical study was performed on the other sample with a panel of anti-T and anti-B Mc Ab, including JCB 117 (anti-CD79a) which stains early pre B lymphoblasts. RESULTS: Twenty-five children relapsed while on treatment and did not undergo TB. Among the 45 boys who underwent routine TB, one had a diffuse infiltration seen in conventional histology. Thirty-nine had normal morphological and immunohistochemical study: among them, six relapsed subsequently in bone marrow; in this group, event free survival (EFS) was 85 +/- 10% with a median follow-up of 80 months after the biopsy. In the five remaining boys, anti-CD79a was found positive on blasts in four cases and anti-CD3 in one case; four of those relapsed, including two in the testes during the year following the biopsy; EFS was 20 +/- 36% (P = 0.001). CONCLUSIONS: New Mc Ab such as JCB 117 (anti-CD79a) might detect a minimal residual disease in the testes of children treated for ALL, particularly on routine histological material. These results, if confirmed in larger series, might influence further therapeutic strategy.

Adolescent↗

PubMed1996

Population pharmacokinetics of carboplatin in children.

OBJECTIVES: In pediatric patients, administration of carboplatin according to body surface area results in a large variation in the area under the plasma ultrafilterable carboplatin concentration versus time curve. A population pharmacokinetic study using the NONMEM program was undertaken to determine the effects of a variety of covariates on the clearance of ultrafilterable carboplatin. PATIENTS: Plasma carboplatin pharmacokinetics were determined in 57 children (2 months to 18 years old, with serum creatinine levels ranging from 27 to 268 mumol/L) treated for various tumor types. RESULTS: The best fit corresponded to the formula: clearance (ml/min) = 2.85.weight.(1-0.00357.serum creatinine).(1-0.372.Np) + 8.7 (with serum creatinine in micromoles per liter, weight in kilograms, and Np = 1 or 0 for unilateral nephrectomy or not, respectively). The interindividual variability in clearance, as expressed by the coefficient of variation, decreased from 74% (no covariates) to 49% by taking account of weight, and to 29% under the final regression formula. CONCLUSION: The ability of this formula to predict carboplatin clearance in children should be evaluated prospectively and compared to a method based on the determination of the glomerular filtration rate.

Adolescent↗

PubMed1996

Dispersion of ventricular repolarization in hypertrophic cardiomyopathy.

On an averaged QRS-T cycle from a 15-lead record (12-lead electrocardiogram + XYZ leads) and through interactive editing, four electrocardiographic indices of the dispersion of ventricular repolarization (DVR) are automatically computed and represent the maximal interlead difference of QT and JTend and QT and JTapex. The values of these indices were then examined in three clinical groups matched for age and sex: normal subjects (control), patients with left ventricular hypertrophy (LVH group), and patients with hypertrophic cardiomyopathy (HCM group) without ventricular arrhythmias and without interacting drugs. The mean values of all four DVR indices were significantly increased in the HCM group compared with the control group and the LVH group of another origin (ie, for the QTe dispersion index, the mean values and the 97.5th percentiles were, respectively, 65 +/- 18 ms and 97 ms in the HCM group, 41 +/- 25 ms and 79 ms in the LVH group, and 31 +/- 15 ms and 58 ms in the control group). The maximal QT interval was also significantly longer in the HCM group (464 +/- 30 ms) than in the LVH group (436 +/- 32 ms) and the control group (428 +/- 25 ms).

Adult↗

PubMed1996

Tagging a Vibrio cholerae El Tor candidate vaccine strain by disruption of its hemagglutinin/protease gene using a novel reporter enzyme: Clostridium thermocellum endoglucanase A.

The celA gene encoding Clostridium thermocellum endoglucanase A was expressed in Vibrio cholerae on its own promoter and used to tag a candidate El Tor biotype cholera vaccine strain. Colonies of the tagged strain could be unequivocally distinguished by overlaying them with CM-cellulose indicator agar and Congo Red staining. Expression of celA did not affect growth of V. cholerae in vitro and in vivo. The celA gene was inserted in the chromosomal hap locus encoding V. cholerae hemagglutinin/protease, a putative "detachase", to create a hap- mutant that could be identified and scored by its halo of cellulolytic activity. The inactivation of hap had a positive effect on colonization in the infant mice model. The above results indicate that celA is a suitable marker gene for V. cholerae and hap is an appropriate locus for insertion of foreign DNA in vaccine development. Inactivation of hap, by increasing the duration of adherence, might decrease excretion of the resulting vaccine vector strain and thus increase its immunogenicity.

Animals↗

PubMed1996

Prothrombin time in liver failure: time, ratio, activity percentage, or international normalized ratio?

Prothrombin time (PT) is a universal indicator of liver disease severity. However, variability in thromboplastin reagents leads to large interlaboratory differences in PT results. The aim of this study was to determine whether the use of the international normalized ratio (INR) or other modes of expression might achieve PT standardization in patients with liver failure. PT was measured with seven thromboplastin reagents with different sensitivities in plasmas from 27 patients with miscellaneous chronic and acute liver failure and, as a control population, 29 patients on oral anticoagulation therapy. PT was expressed in seconds, ratio, activity percentage, and INR. In patients with liver failure, only activity percentage expression eliminated variability in PT results obtained with the seven thromboplastins while INR, seconds, and ratio values remained significantly different (P < .01). In patients on oral anticoagulant therapy, only INR normalized PT results. We conclude that, in patients with liver failure, INR fails to yield a PT expression independent of the thromboplastin used and only activity percentage expression may provide a common international scale of PT reporting.

Analysis of Variance↗

PubMed1996

Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats.

Dietary supplementation with oligofructose (OFS; 100 g/kg), a non-digestible oligomer of beta-D-fructose, decreases serum triacylglycerols in serum and VLDL of rats. In order to investigate the role of hepatic metabolism in the hypolipidaemic effect of OFS, male Wistar rats were fed on a standard diet with or without 100 g Raftilose P95/kg as OFS source for 30 d. OFS feeding (1) significantly decreased triacylglycerol and phospholipid concentrations in both blood and liver, (2) increased the glycerol-3-phosphate liver content but decreased the hepatic activity of glycerol-3-phosphate acyltransferase (EC 2.3.1.15), suggesting a decrease in acylglycerol synthesis, (3) did not affect the blood non-esterified fatty acid concentrations, but (4) reduced by 54% the capacity of isolated hepatocytes to synthesize and secrete triacylglycerols from labelled acetate; the activity of fatty acid synthase, a key lipogenic enzyme was also significantly decreased. These findings suggest that OFS decreases serum triacylglycerols by reducing de novo fatty acid synthesis in the liver; the lower insulin level in the serum of OFS-fed rats could explain, at least partly, the metabolic effect induced by such non-digestible carbohydrates.

Animals↗

PubMed1996

Functional N-methyl-D-aspartate receptors in O-2A glial precursor cells: a critical role in regulating polysialic acid-neural cell adhesion molecule expression and cell migration.

The capacity for long-distance migration of the oligodendrocyte precursor cell, oligodendrocyte-type 2 astrocyte (O-2A), is essential for myelin formation. To study the molecular mechanisms that control this process, we used an in vitro migration assay that uses neurohypophysial explants. We provide evidence that O-2A cells in these preparations express functional N-methyl-D-aspartate (NMDA) receptors, most likely as homomeric complexes of the NR1 subunit. We show that NMDA evokes an increase in cytosolic Ca2+ that can be blocked by the NMDA receptor antagonist AP-5 and by Mg2+. Blocking the activity of these receptors dramatically diminished O-2A cell migration from explants. We also show that NMDA receptor activity is necessary for the expression by O-2A cells of the highly sialylated polysialic acid-neural cell adhesion molecule (PSA-NCAM) that is required for their migration. Thus, glutamate or glutamate receptor ligands may regulate O-2A cell migration by modulating expression of PSA-NCAM. These studies demonstrate how interactions between ionotropic receptors, intracellular signaling, and cell adhesion molecule expression influence cell surface properties, which in turn are critical determinants of cell migration.

Calcium↗

PubMed1996

A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block.

This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.

Adrenergic alpha-Agonists↗

PubMed1996

Serum levels of endothelial injury markers creatine kinase-BB and soluble thrombomodulin during human liver transplantation.

Endothelial damage within the sinusoids of the liver probably plays a key role in primary liver dysfunction following transplantation. The aim of this work was to study the serum levels of two potential markers of endothelial damage, creatine kinase-BB and soluble thrombomodulin, during human graft revascularization. Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h). Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels were measured: 1) in effluent and 2) in serum samples sequentially collected before revascularization, then during the first 120 min of revascularization and first post-operative week. No correlation was observed between serum values (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities were correlated with soluble thrombomodulin levels (p = 0.01). Both increased significantly during the first minutes of the revascularization, then decreased markedly. In contrast, AST activity was maximal at day 1. This detectable and early release of creatine kinase-BB and soluble thrombomodulin in blood is in keeping with the early occurence of endothelial damage. Together with previous data, these findings suggest that serum determination of these two markers may be a useful tool in the assessment of endothelial injury in liver transplantation.

Alanine Transaminase↗

PubMed1996

Anticoagulant response to Agkistrodon contortrix venom (ACV test): a new global test to screen for defects in the anticoagulant protein C pathway.

As specific assays used to identify defects in the protein C (PC) anticoagulant pathway are laborious and expensive, we describe here a global test to screen for these defects. This assay is expressed as the ratio of two activated partial thromboplastin times, one in the absence and one in the presence of 0,125 U/ml of the PC activator of Agkistrodon contortrix venom (ACV). Eight of the 168 healthy volunteers of the control group exhibited an ACV ratio below the lower normal limit of 3.37 [6 subjects with the mutation Arg 506 to Gln in their factor V gene (FV R506Q) and one with PS deficiency]. 128 patients who have had at least one episode of deep-vein thrombosis were retrospectively studied. All patients carrying FV Q506R (n = 48), PC deficiency (n = 14) or combined defects, i.e. FV Q506R and PC deficiency (n = 4) or FV Q506R and PS deficiency (n = 3), had ACV ratios < 3.37. PS deficient plasmas (n = 20) exhibited ACV ratios which overlapped normal range. ACV ratios of one out of seven patients with antithrombin deficiency, and 10% of patients without identified defect in the PC anticoagulant pathway (n = 30) were < 3.37. An ACV ratio raised to 3.70 could lead to a test identifying all patients with a defect in the PC anticoagulant pathway.

Adolescent↗

PubMed1996

The tissue thromboplastin inhibition test in the detection of lupus anticoagulants: importance of a correction factor eliminating the influence of fibrinogen level.

Tissue thromboplastin inhibition test (TTI) is a highly sensitive but poorly specific test used in the diagnosis of lupus anticoagulant (LA) which is usually requested for patient with inflammatory status. Therefore, we investigated the influence of fibrinogen level on TTI using Recombiplastin (Ortho), Neoplastine (Diagnostica Stago) and Thromborel S (Behring), in a group of 84 patients with fibrinogen levels ranging from 1.6 to 11.8 g/l. The highly significant (p < 0.0001) positive correlation observed between fibrinogen level and TTI with the 3 thromboplastins allowed the calculation of a new TTI value corrected for fibrinogen level named TTIfg. TTIfg was defined as TTI - ("S" x fibrinogen level) where "S" was the slope of the regression line defining TTI as a function of fibrinogen values. In the group studied, the low TTI specificity, respectively 64%, 67% and 75% with Recombiplastin, Neoplastine and Thromborel S, was greatly improved to respectively 95%, 93% and 95% when results were expressed as TTIfg. TTIfg remained as sensitive as TTI when evaluated in a group of 38 patients with previously diagnosed LA.

Fibrinogen↗

PubMed1996

Genetic manipulation of Vibrio cholerae for vaccine development: construction of live attenuated El Tor candidate vaccine strains.

The recent spread of El Tor cholera to America augments the need for an effective, safe and economical vaccine. In the present paper we describe the construction of live attenuated V. Cholerae strains by specifically deleting the genes encoding cholera toxin and other putative toxins from the bacterial chromosome. To maximize the likelihood of exposing protective antigens relevant to currently circulating vibrios we selected for genetic manipulation recent epidemic V. cholerae isolates from Peru. The mutant strains did not produce cholera toxin in vitro and in vivo. Deletion of the virulence cassette was accompanied by marked attenuation in the infant mouse cholera model. A selected El Tor Ogawa candidate vaccine strain was refractory to acquisition of foreign genes by conjugation with toxigenic vibrios.

Animals↗

PubMed1996

[A good model of acute hepatic failure: 95% hepatectomy. Treatment by transplantation of hepatocytes].

The aim of this study was to develop in rats, a model of acute hepatic failure that mimics human fulminant hepatitis and to study the effect on survival of transplantation of isolated hepatocytes. This study showed that the mortality after 90% hepatectomy was reduced by the sole correction of hypoglycemia. On the other hand, 95% hepatectomy appeared as a reliable and reproductable model, associated with a period of hepatic coma, a deep disorder of coagulation, and a high mortality rate (> 80%) despite correction of hypoglycemia. In this model of acute hepatic failure, intraperitoneal transplantation of encapsulated isolated hepatocytes significantly reduced the mortality rate from 80% in the control groups to 31% in the transplanted group. A complete regeneration of the native liver was observed in all rats surviving. All animals survived after explantation of the hollow fibers. Well preserved hepatocytes were observed in hollow fibers two months after transplantation.

Animals↗

PubMed1995

Hydrophobicity engineering to facilitate surface display of heterologous gene products on Staphylococcus xylosus.

Protein engineering has been employed to investigate the effect of specific amino acid changes on the targeting of heterologous proteins to the outer cell surface of the Gram-positive bacterium Staphylococcus xylosus. Three different variants, corresponding to a 101 amino acid region of the major glycoprotein (G protein) of human respiratory syncytial virus (RSV), were generated in which multiple hydrophobic phenylalanine residues were either substituted or deleted. The different G protein fragments were expressed as one part of recombinant receptors designed for surface display on S. xylosus cells. The engineered variants of the RSV G protein hybrid receptors were, in contrast to a non-engineered fragment, efficiently targeted to the outer cell surface of recombinant S. xylosus cells as determined by different methods, including fluorescence-activated cell sorting. In addition, immunization of mice with live recombinant S. xylosus demonstrated that surface exposure was required to generate receptor-specific antibodies. The present strategy of hydrophobic engineering should be of general interest in surface-display applications and for secretion of proteins otherwise difficult to translocate through host cell membranes.

Amino Acid Sequence↗

PubMed1995

Determination of urinary 4,4'-methylenedianiline and its acetylated metabolites by solid-phase extraction and HPLC analysis with UV and electrochemical detection.

An analytical procedure based on solid-phase extraction and high-performance liquid chromatography using both ultraviolet and electrochemical detection was developed to determine, without derivatization, stable urinary forms of 4,4'-methylenedianiline (MDA) and of its acetylated metabolites at the micrograms/l level, in post-shift urine from 63 exposed workers. The determination of MDA, N-acetyl MDA (MAMDA) and N,N'-diacetyl MDA (DAMDA) was achieved on the non-hydrolysed urine samples, and that of total MDA on urine samples after alkaline hydrolysis. It was necessary to protect urine samples with sulfamic acid in order to stabilize amines and to improve the precision and accuracy of the analyses. Under these conditions, unstable labile conjugates were determined as their parent stable amine. The distribution of total MDA, MDA, MAMDA and DAMDA was assessed in 116 urine samples. Their relative concentrations (arithmetic means) were found to be in the following order: total MDA > MAMDA > MDA > DAMDA. While MAMDA represented more than 50% of total MDA, MDA and DAMDA were lower than 15% and 3% respectively. Acetylation of MDA, described as a possible pathway of detoxication, is confirmed to be an important metabolization route in humans, essentially through the monoacetylated metabolite. However, the individual ratio MAMDA/total MDA was found to vary widely (roughly from 0% to 100%).

Acetylation↗

PubMed1995

Aortic valve replacement with allograft/autograft: subcoronary versus intraluminal cylinder or root.

From April 1990 to May 1994, 89 patients (median age, 42 years; range, 10 days to 66 years) underwent aortic valve or root replacement with allografts or autografts. Thirteen patients were less than 18 years old at the time of operation. Indication for aortic valve replacement was aortic stenosis (50 patients, 56%), small stenotic prosthesis (2 patients, 2%), aortic valve endocarditis (19 patients, 21%), isolated aortic regurgitation (17 patients, 19%), and type II truncus arteriosus (1 patient, 1%). The subcoronary implantation was used in 45 patients (group A), and implantation of an intraluminal cylinder (16 patients) or complete root replacement (28 patients) was performed in the remaining 44 patients (group B). The Ross procedure was performed in 22 patients. Intraoperative transesophageal echocardiography was used routinely. Five patients died in the early postoperative period (6%), 2 in group A and 3 in group B. Three other patients required immediate replacement of a failing graft by a mechanical prosthesis (1 in group A and 2 in group B). There has been no late death. All survivors remained in New York Heart Association functional class I and were free of thromboembolic complications. Endocarditis occurred in 2 patients, 1 year after operation. Both were successfully treated medically. Echocardiographic studies were obtained serially in every patient. Four patients, 2 in group A and 2 in group B underwent reoperation because of mild-to-moderate aortic regurgitation (rate of reoperation, 5%). Two valves were repaired and two were replaced by an allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1995

Intracellular concentrations of fura-2 and fura-2/am in vascular smooth muscle cells following perfusion loading of fura-2/am in arterial segments.

A new method for the determination of tissue concentrations of Fura-2 and Fura-2/AM was developed based upon acetonitrile extraction followed by RP-HPLC separation (using tetrahexylammonium as counter-ion), post-column alkaline hydrolysis of Fura-2/AM, and fluorimetric detection. The detection limit was 1.2 nM and 1 nM for Fura-2 and Fura-2/AM, respectively. When this technique was applied to perfusion-loaded segments of the rat tail artery, intracellular concentrations of Fura-2 determined by tissue disruption were 10 times those obtained by comparing the increase in fluorescence at the isoemissive point (following loading), with a calibration curve for Fura-2. Loading conditions of 90 min at [Fura-2/AM]e = 5 microM were optimal in terms of [Fura-2]i which attained a concentration not significantly different from [Fura-2/AM]e. Under such conditions, however, Fura-2/AM also accumulated in the arterial wall. Although incompletely de-esterified, Fura-2/AM metabolites produced by in vitro incubation of Fura-2/AM with pig liver esterases could be easily detected, fluorescent forms of Fura-2 with a different sensitivity for calcium were not detected in arterial extracts.

Animals↗

PubMed1995

[Disseminated intravascular coagulation associated with prostatic cancer].

Disseminated intravascular coagulation (DIC) associated with prostate adenocarcinoma is a bad prognostic sign. Most of the cases are limited to biological abnormalities. Some, however, come to medical attention due to thromboembolic or hemorrhagic complications. We report 4 such cases and review the pertinent literature. The characteristic features are low platelets and coagulation factors in an elderly man. In two out of the four cases, bleeding due to the DIC revealed the cancer. All patients received hormonotherapy and heparin. The worst fate (case 3) was a subacute one with no effect of the drugs and death in a short time. The other cases went into a five- to seven months remission before uncontrollable bleeding led to death. No favorable effect of the chemotherapy was observed. Thus, new treatments are sought for this rare but ominous complication of prostate cancer.

Aged↗