Hepatitis virus infections in heart transplant recipients.
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Heart Transplantation↗
Biomedical subjects
C Robert
Publications and source records attributed to C Robert.
Phase I/II study of 3TC (lamivudine) in HIV-positive, asymptomatic or mild AIDS-related complex patients: sustained reduction in viral markers. The Lamivudine European HIV Working Group.
OBJECTIVE: To evaluate the efficacy of 3TC (lamivudine), a synthetic nucleoside analogue that inhibits HIV reverse transcriptase in vitro, as treatment for HIV-positive, asymptomatic or mild AIDS-related complex patients. DESIGN: Open-label, multinational and multicentre, non-comparative, escalating dose study. METHODS: Patients who meet the selection criteria (n = 104) were enrolled in three European countries. Ten to 15 patients were included at each of the six dose levels of 3TC (0.5, 1.0, 2.0, 4.0, 8.0, 12.0 and 20.0 mg/kg daily in two divided doses every 12 h). Virological parameters--immune-complex dissociation (ICD) assay for HIV p24 antigenaemia, plasma HIV RNA load, whole blood assay and cellular viraemia--were evaluated at weeks 0, 4, 12 and 24. RESULTS: Sustained reductions in HIV RNA load and in ICD p24 antigen levels were observed and maintained over the 12-week assessment period. Greater reductions were noted at higher doses but this trend did not reach statistical significance. In 38 patients, reductions of cell viraemia were significantly greater at 4 weeks for patients treated at higher doses of 3TC. CONCLUSION: These virological data show that 3TC is a potent inhibitor of HIV replication in HIV-positive, asymptomatic or mild ARC patients as assessed by ICD p24 antigenaemia, plasma HIV RNA load and cell viraemia.
AIDS-Related Complex↗
Reduction of intimal hyperplasia by naroparcil, a 4-methylumbelliferyl beta-D-xyloside analogue, after arterial injury in the hypercholesterolemic rabbit.
4-Methylumbelliferyl beta-D-xylosides (beta-D-xylosides) inhibit proteoglycan synthesis, and this is associated with reduced proliferation and extracellular matrix production by vascular smooth muscle cells. This study evaluated whether treatment with naroparcil, a beta-D-xyloside analogue, reduced intimal hyperplasia after arterial injury in the hypercholesterolemic rabbit. Forty-two rabbits were assigned to three groups that received either a 1% cholesterol-enriched diet (group 1, n = 15) or the same diet with added 100 mg.kg-1 naroparcil (group 2, n = 15) or 300 mg.kg-1 naroparcil (group 3, n = 12). All animals underwent iliac artery endothelial abrasion at day 14 and were killed at day 56. At the time of death, the angiographic minimal luminal diameter was significantly larger in both treated groups. Morphometric analysis showed a larger luminal area in treated rabbits (groups 2 and 3) compared with control rabbits (group 1) (0.75 +/- 0.54 and 0.85 +/- 0.61 mm2 versus 0.32 +/- 0.25 mm2, respectively; P < .05), with a decreased intimal thickness in groups 2 and 3 (average reduction of 37% and 39%, respectively, compared with group 1; P < .05) but without changes in medial area. Total vessel area was comparable among all groups. In the media, immunohistochemistry suggested reduced infiltration by macrophages and a larger fractional area of smooth muscle cells. There were no differences in plasma or arterial wall cholesterol content between groups. Plasma levels of glycosaminoglycans and dermatan sulfate content were increased only in group 3. In this model, oral treatment with naroparcil appears to preserve the arterial lumen and reduce intimal thickness after arterial injury.
Administration, Oral↗
Is it clinically possible to distinguish nonhemorrhagic infarct from hemorrhagic stroke?
BACKGROUND AND PURPOSE: Diagnosis of the nonhemorrhagic ischemic type of stroke by analysis of patients' clinical features is considered unreliable because no clinical feature is specific. The diagnosis is so difficult to establish that we cannot hope to use the same method to make a reliable diagnosis in all stroke cases. In this study, we propose a simple scoring system with a positive predictive value of close to 100% to distinguish nonhemorrhagic infarct from hemorrhagic stroke. This scoring is available for all physicians in bedside diagnosis even if this score can be applied to a subgroup of patients. METHODS: Twenty-six clinical variables that might potentially distinguish cerebral hemorrhage from infarction were recorded in patients consecutively admitted to our stroke unit for stroke lasting more than 24 hours with at least unilateral motor weakness affecting face and/or arm and/or leg (internal validity study). Patients previously receiving anticoagulant therapy were excluded. We used CT scan as the gold standard. We used multivariate logistic regression to establish a clinical score from which we derived the classification rule. This rule was validated with data from the next 200 consecutive patients hospitalized in the stroke unit (external validity study). RESULTS: Three hundred sixty-eight patients were enrolled in the internal study. The obtained score was (2 x alcohol consumption) + (1.5 x plantar response) + (3 x headache) + (3 x history of hypertension)--(5 x history of transient neurological deficit)--(2 x peripheral arterial disease)--(1.5 x history of hyperlipidemia)--(2.5 x atrial fibrillation on admission). All patients with a score less than 1 (n = 123) had a nonhemorrhagic infarct (ie, 40% of the 305 patients with a nonhemorrhagic infarct). No threshold was found to diagnose cerebral hemorrhage with a sufficiently high positive predictive value. Among the 200 patients enrolled in the external validity study, 72 patients with a score below 1 had a nonhemorrhagic infarct (ie, 43% of patients with a nonhemorrhagic infarct). CONCLUSIONS: Diagnosis of nonhemorrhagic infarct can be made in 36% (95% confidence interval [CI], 29 to 43) of patients with a high level of accuracy (100% in the external validity study, which gives a 95% CI of 93 to 100). Thus, 43% (95% CI, 36 to 50) of patients with a nonhemorrhagic infarct could receive a bedside diagnosis. The score is simple and can be calculated from information available to all physicians.
Adult↗
Informations on the active site of palmito polyphenol oxidase.
pH studies of palmito polyphenol oxidase are carried out with either 4-methylcatechol or pyrogallol as substrates. The pH profile is independent of the nature of the substrates tested. The symmetrical behaviour and the very slight differences between the values obtained suggest the existence of only one site on the molecule for o-diphenol substrates.
Antioxidants↗
[Hypopigmented mycosis fungoides].
INTRODUCTION: Isolated areas of hypopigmented skin can be a manifestation of mycosis fungoides. This is a rare clinical form with a particular clinical course and histology which has been described only in black subjects. CASE REPORT: Over a 10-year period, a 28-year-old woman from Mali developed non-infiltrated hypopigmented and discretely squamous macules involving the entire body. The diagnosis of mycosis fungoides was made on pathology evidence of epidermotropic lymphocyte infiltration with a few small nests. PUVA led to rapid regression of the lesions. DISCUSSION: Hypopigmented mycosis fungoides has been described in young black subjects (mean age 19 years). The diagnosis is usually made late because benign skin affection is usually the first diagnosis (pityriasis alba, pityriasis versicolor). The pathogenesis of these hypopigmented lesions is not known. PUVA appears to be effective in most cases.
Adult↗
Quantitative image analysis of cell proliferation after balloon catheter injury in the rabbit carotid artery.
OBJECTIVE: To perform color image analysis to assess the course of morphometric and proliferative changes in the intima and media of rabbit carotid arteries following balloon injury. STUDY DESIGN: Proliferating smooth muscle cells were labeled with proliferating cell nuclear antigen and vizualized by immunohistochemical staining of histologic sections. Morphometry was performed on histologic cross-sections of injured arteries stained with hematoxylin. RESULTS: The development of intimal hyperplasia following an acute mechanical injury was detectable early on and was accompanied by a burst of cell proliferation. Medial cell proliferation peaked on day 3 after balloon injury, and the maximum of intimal cell proliferation was noted on day 7. CONCLUSION: The color image analysis method described here could be a useful tool in evaluating drugs for their ability to prevent restenosis.
Animals↗
Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy.
Unfixed chicken erythrocyte chromatin fibers in very low salt have been imaged with a scanning force microscope operating in the tapping mode in air at ambient humidity. These images reveal a three-dimensional organization of the fibers. The planar "zig-zag" conformation is rare, and extended "beads-on-a-string" fibers are seen only in chromatin depleted of histones H1 and H5. Glutaraldehyde fixation reveals very similar structures. Fibers fixed in 10 mM salt appear somewhat more compacted. These results, when compared with modeling studies, suggest that chromatin fibers may exist as irregular three-dimensional arrays of nucleosomes even at low ionic strength.
Animals↗
Real-time sleep-wake scoring in the rat using a single EEG channel.
A new method of analysis of sleep in the rat based on the electrocorticogram (ECoG) is described. Three states, awake (W), nonrapid eye movement (NREM) and rapid eye movement (REM) sleep are automatically classified by the system. After amplification of the ECoG over a restricted bandwidth (3.18-25 Hz) and sampling at 512 Hz, the data are processed in 8-second epochs by a microcomputer, which generates three statistical and two harmonic variables. Each 8-second epoch is thus compressed into five numerical values occupying 10 bytes of memory. Epochs for each state of vigilance are identified by an expert observer to produce three reference models. The program classifies each epoch into the appropriate state by the least quadratic distance. The system was validated by comparing the results with a visual analysis of polygraph recordings. The agreement between the program and the two independent scorers for 24-hour tracings of six rats was 83% for REM sleep, 96% for W and 97% for NREM sleep.
Animals↗
Induction of kinin B1 receptor-dependent vasoconstriction following balloon catheter injury to the rabbit carotid artery.
1. Balloon catheter injury to the rabbit carotid artery damaged the endothelium and induced neointima formation over 7 days. The area of intima, expressed as a percentage of the media, was 16.2 +/- 4.2% and 8.2 +/- 0.1% in balloon catheter-injured and sham-operated arteries. 2. Seven days after arterial injury, carotid arteries were isolated and set up as ring preparations in organ baths for isometric tension measurements. Balloon catheter-injured arteries first contracted with noradrenaline (0.01-0.1 microM), contracted further in a concentration-dependent manner to bradykinin (BK; pD2, 5.98 +/- 0.22; Emax, 41.3 +/- 5.2% of KCl) and to des-Arg9-BK (pD2, 7.12 +/- 0.36; Emax, 46.0 +/- 9.9% of KCl). In contrast, vessel segments with endothelium either intact or acutely removed were unresponsive to both BK receptor agonists. 3. The concentration-contraction curves for BK and for des-Arg9-BK were shifted to the right by the B1 receptor antagonist, [Leu8]des-Arg9-BK (3 microM), but not by the selective B2 receptor antagonist, Hoe 140 (1 microM). 4. Thus, BK and its metabolite, des-Arg9-BK act as vasoconstrictor agents following balloon catheter injury. These effects appear to be mediated by activation of B1 receptors.
Angioplasty, Balloon↗
Identification of human herpesvirus 6 variants A and B by amplimer hybridization with variant-specific oligonucleotides and amplification with variant-specific primers.
Two distinct PCR-based procedures were evaluated for the detection and identification of human herpesvirus 6 (HHV-6) variants A and B in uncultured human samples. Variant-specific oligonucleotide hybridization (VSOH) is based on the amplification of two distinct regions of the HHV-6 genome, followed by hybridization of amplimers with variant-specific oligonucleotide probes. Variant-specific primer PCR (VSPP) is based on the amplification of each variant by using variant-specific primers. The study of 10 well-characterized HHV-6 strains allowed us to demonstrate the high sensitivity and specificity of both methods. With variant mixtures, however, some limitations of VSOH were evidenced and VSPP was required to obtain unambiguous results. The combination of VSOH and VSPP was applied to the direct study of 300 peripheral blood mononuclear cell samples from French subjects. HHV-6 was detected in 15 samples: 11 corresponded to variant B, 3 corresponded to variant A, and 1 corresponded to a mixture of both variants.
Adolescent↗
[Xeroderma pigmentosum. What may be expected from biological studies?].
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Cockayne Syndrome↗
[Enzymatic kinetics and mid-infrared spectroscopy combined with multidimensional data analysis].
An alternate method for enzyme study is proposed. This technique allows enzymatic reactions by a one step assay, and visualisation of variations in FTIR spectral data of substrate during the reaction. Hydrolysis of sucrose by beta-fructosidase is carried out as an example.
Data Interpretation, Statistical↗
High mutation frequency in ras genes of skin tumors isolated from DNA repair deficient xeroderma pigmentosum patients.
Xeroderma pigmentosum (XP) patients are clinically characterized by a very high incidence of skin cancers on exposed skin, at an early age. XP cells in vitro are strongly deficient in excision-repair and highly mutagenized by UV light. We were, therefore, interested in measuring mutation frequency and in determining mutation spectra in patients' tumors exposed to UV lesions. We chose to look at oncogene activation in skin tumors with the idea that more mutations, particularly of the ras gene family, would be found in XP tumors where lesions remain unrepaired compared to normal individuals. Our results clearly show that more than a 2-fold significantly higher mutation frequency (50%) of the ras genes was found in XP in contrast to control tumors (22%). The majority of the mutations were found at codon 12 of all three ras genes with a preponderance for N-ras in XP samples. The mutation spectra indicate that all mutations found were located opposite pyrimidine-pyrimidine sequences which represent a hot spot for UV-induced DNA lesions. Most of the mutations were of the type expected from studies performed in vitro with model systems. This high mutation frequency in XP was accompanied by a very high level of Ha-ras and c-myc gene amplification and rearrangement. All these data are consistent with a fundamental role of unrepaired UV-induced DNA lesions as an initiating event in human skin tumors on exposed parts of the body.
Base Sequence↗
[Blackwater fever after ingestion of mefloquine. Three cases].
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Adult↗
Comparative study of human expertise and an expert system: application to the diagnosis of child's meningitis.
We present a general method of statistical evaluation for expert systems, applied to a system for the diagnosis of child's meningitis. Fifty difficult clinical cases of child's meningitis were submitted to the system, to seven senior specialists and to seven young physicians. Multidimensional analysis of the diagnosis of the infection category reveals that the two groups of physicians separate naturally and that the system is located among the group of experts. The study of the agreement of the microbiological diagnosis and therapeutic advice shows that the advice of the two groups of physicians is significantly different and that the advice of the system is significantly closer to that of the experts. This result is confirmed by the study of therapeutic errors. This type of study allows one to classify the performance of the system among physicians having different levels of expertise without referring to an objective solution.
Child↗
Conditional suicide system of Escherichia coli released into soil that uses the Bacillus subtilis sacB gene.
The sacB gene from Bacillus subtilis confers sucrose sensitivity upon gram-negative bacteria. The gene was investigated for use as a potential conditional suicide system for Escherichia coli released into soil. To ensure against the loss of the cell death function encoded under nonselective conditions, the nptI-sacR-B suicide cassette was inserted into the E. coli chromosome by using a circular nonreplicative integration vector. Stability studies yielded no loss of the suicide cassette in the integrated E. coli EL1026 strain. sacB induction in the absence of a selective pressure resulted in a lysis efficiency of up to 99.9%. The microcosm experiments confirmed the ability of the suicide cassette to limit the growth and reduce the survival of E. coli strains released into soil. Sucrose addition to sterile soil resulted in a 10(-3)-fold reduction of the final E. coli population density. sacB induction prevented the proliferation and triggered the rapid disappearance of E. coli from natural soil. Mutation to sucrose tolerance occurred at a frequency of 10(-5), making E. coli EL1026 a potential counterselectable donor strain for gene transfer studies. Specificity and potential adaptability to a wide range of gram-negative bacteria are additional conveniences of this conditional suicide system for the containment and counterselection of engineered microorganisms.
Bacillus subtilis↗
Bullous amyloidosis. Report of 3 cases and review of the literature.
We report 3 cases of bullous immunoglobulinic amyloidosis and review 25 published cases. In 2 of our patients, amyloid deposits were not detected with special staining, but by means of ultrastructural methods. Investigations of the skin lesions permitted the diagnosis of associated plasma cell dyscrasia in 2 patients. Unexplained bullous lesions should be investigated for amyloid deposits and the presence of monoclonal gammopathy by methods including electron microscopy and immunochemical analysis of serum and urine.
Aged↗