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Biomedical subjects

M Giraud

Publications and source records attributed to M Giraud.

At least 37 records · Page 2Linked to original sources

N-conjugates of 2,5-disubstituted pyrrole and glutathione. Evaluation of their potency as antioxidants against photosensitization of NCTC 2544 keratinocytes by excess endogenous protoporphyrin IX.

A novel glutathione compound in which the amino group has been derivatized by a 2,5-dimethyl pyrrole is shown to be very effective against cell photosensitization in vitro. Protoporphyrin IX either added to the medium or produced endogenously by incubation of NCTC 2544 keratinocytes with 5-aminolevulinic acid has been chosen as the photosensitizer. The antioxidant effectiveness of glutathione-pyrrole derivatives against protoporphyrin photosensitization depends critically on the type of 2,5 substitution on the pyrrole ring. This structure-function relationship may be attributed to the difference in compartmentation and/or uptake of the various glutathione-pyrrole derivatives under study. The 2,5-dimethyl pyrrole derivative is much more effective than glutathione as a protective agent against phototoxic reactions induced by protoporphyrin IX.

Aminolevulinic Acid↗

In vivo functional investigations of lactic acid in patients with respiratory chain disorders.

OBJECTIVE: To assess the prevalence of in vivo detectable abnormalities of lactate metabolism in mitochondrial disorders. DESIGN: Retrospective study in a metabolic investigation unit. PATIENTS: 28 patients with a respiratory chain disorder identified from biochemical or genetic analyses, or both, and 133 age matched controls. Controls were children in whom causes of secondary hyperlactataemia and/or disorders, affecting the energy pathways could be excluded. METHODS: Lactate and pyruvate were measured in blood, together with other intermediary metabolism indices, before and one hour after four meals each day. Lactate and creatinine in a 24 hour urine sample collected at the same time were analysed. When basal hyperlactataemia was not evident, an intravenous glucose or pyruvate loading test was performed as a provocative test. RESULTS: Abnormal lactate metabolism was found in 25 of 28 patients thus demonstrating the potential usefulness of these investigations in the diagnosis of mitochondrial disease. Moderate lactate accumulation was present in relatively mild disease, associated with a mitochondrial DNA mutation and combined respiratory complexes deficiency. By contrast, high lactate concentrations were observed in very young children, with severe disease, isolated complex deficiency, and no apparent mitochondrial DNA defect.

Adolescent↗

[Criteria for quantification and characterization of aneurysms of the abdominal aorta using ultrasonography. The AFFCA study. French Association of Continuous Education in Angiology].

OBJECTIVE: To validate ultrasonographic quantification and characterization criteria for aneurysms of the abdominal aorta (AAA) by comparing computed tomography data and surgical findings in order to standardize diagnosis and follow-up of AAA. PATIENTS AND METHODS: A multicentric prospective study included 80 patients with AAA (January to August 1996). Standardized data on quantitative (diameter, surface area) and qualitative (topography, form, wall, thrombus) data were obtained at each ultrasound examination and at surgery. Ultrasound (US) and computed tomography (CT) explorations were performed and interpreted without prior knowledge by independent operators. US findings versus CT reference were compared in 77 cases, US findings versus surgical reference in 31, and CT findings versus surgery reference in 28. RESULTS: Compared with CT-scan, B mode ultrasound (n = 77) underestimated the anteroposterior diameter of the aneurysm (mean difference -2.16 mm; p < 0.001), the anteroposterior diameters of the flow channel lumen (-5.54 mm; p < 0.001) and upper neck of the aneurysm (-2.74 mm; p < 0.001). Surface area measurements were not significantly different both the aneurysmal sac (p = 0.3) and the flow channel lumen (p = 1). Compared with surgical findings, US (n = 30) underestimated the transverse diameter (mean difference (-4.29 mm; p = 0.0037). Compared with surgery, US findings (n = 28) were not significantly different for the anteroposterior ans transverse diameters. Analyzing the form and wall of the AAA, US/CT-scan performance was good for symmetrical fusiform aneurysms (sensitivity 77%, specificity 67%). US and CT-scan were reliable for detecting wall bugles (same sensitivity, 29%). The angle formed by the thrombus with the wall (expressed in degrees) was not significantly different (p = 0.9). When the lower pole of the aneurysm was situated above the aortic bifurcation, US (sensitivity 75%) was more reliable than the CT-scan (sensitivity 50%) compared with surgical findings. CONCLUSION: Ultrasonography should not be limited to the simple positive diagnosis of AAA. A precise analysis of the diameters and surface areas of the aneurysm should be performed.

Aged↗

Morphological studies of skeletal muscle in lactic acidosis.

This paper underscores the contribution of routine morphological examination of skeletal muscle in patients with lactic acidosis. Mitochondrial disorders are by far the most common causes of primary lactic acidosis, in which muscle biopsy analysis helps in diagnosis and in the search for the molecular anomalies. Thus, we focus our attention on one particular point: the contribution of the morphological study of muscle biopsy in primary lactic acidosis due to mitochondrial disorders, especially mitochondrial respiratory-chain diseases.

Acidosis, Lactic↗

Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochrome c oxidase deficiency. Among the patients, the enzymatic defect differed in the level of residual activity, expression in different tissues and subunit composition in muscle (as analysed by immunohistochemistry). Southern blot analysis of the mitochondrial DNA was normal in 7 patients. The heterogeneity of cytochrome c oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutations.

Cytochrome-c Oxidase Deficiency↗

Laryngotracheal stenosis after intubation or tracheostomy in patients with neurological disease.

OBJECTIVE: This retrospective study evaluated the incidence of airway complications in neurological patients following translaryngeal intubation, tracheostomy, or both. DESIGN: The medical records of 315 consecutive patients (200 with traumatic brain injuries, 31 traumatic tetraplegics, and 84 with other neurological disorders) were reviewed. The type of artificial airway, duration of intubation, and use of nocturnal ventilation were recorded. Eighty-six percent of the patients underwent some combination of tracheal tomograms, flow-volume loop analysis, and fiberoptic tracheolaryngoscopy. Stenosis was classified as severe if it required surgery, if it required maintaining the tracheostomy, or was lethal. It was classified as benign if it was successfully treated by medical or local means. RESULTS: Fifty-five percent of the patients were intubated translaryngeally only (mean = 17 days). Three percent underwent tracheostomy only, and 42% underwent tracheostomy after intubation for a mean of 13 days. The overall incidence of airway stenosis was 20%, 1/4 of which was severe. Fifteen percent of these patients died as a result of tracheal complications. The incidence of stenosis was higher following tracheostomy than following intubation only (29% vs 13%, p < .01). The incidence of severe stenosis in intubated-only patients was low (1%) compared with that following tracheostomy (10%, p < .01). No significant relationship was found between the length of intubation or the timing of tracheostomy. CONCLUSION: Fewer complications are associated with transtracheal intubation than with tracheostomy. The data suggest that longer periods of intubation be used when attempting ventilator weaning before restoring to tracheostomy if weaning fails.

Adolescent↗

Cytotoxic T cell response to Mengo virus in mice: effector cell phenotype and target proteins.

The Mengo virus specific cytotoxic T lymphocyte (CTL) response was investigated after intraperitoneal infection of mice with the attenuated Mengo virus strain vMC24. A high level of CTL activity was detected in spleen cell cultures obtained from infected C3H/HeJ (H-2k) or C57BL/6 (H-2b) mice after a secondary in vitro stimulation with Mengo virus-infected cells. The CTL activity, which was MHC class I-restricted, was shown to be mediated by CD8+ T cells. Recombinant vaccinia viruses that expressed capsid proteins VP0, VP1 or VP3 were produced and used to identify the protein(s) recognized by the Mengo virus-specific CTLs. In both C3H/HeJ and C57BL/6 mice, analysis of CTL activity against target cells expressing each capsid protein showed that VP0 was the only capsid protein recognized by the CD8+ CTLs. The CTL epitope(s) could be further located in the C-terminal half of VP0, i.e. in capsid protein VP2. Moreover, using unlabelled target cells expressing VP0 as cold competitors, we were able to almost completely inhibit recognition and lysis of Mengo virus-infected cells by specific CD8+ CTLs. Thus, the CTL response directed against VP2 was immunodominant in both C3H/HeJ- and C57BL/6-infected mice.

Animals↗

Glutathione peroxidase and glutathione reductase activities towards glutathione-derived antioxidants.

A new class of glutathione derivatives with antioxidant properties has been prepared by transformation of the NH2 group into a pyrrole ring with various substitutions at the 2 and 5 positions. Due to steric hindrance and/or hydrophobicity of the 2-5-disubstituted pyrrole ring, the reduced glutathione derivatives are poor substrates of the glutathione peroxidase and do not effectively compete with GSH. The oxidized glutathione derivatives are, in turn, relatively good substrates (Km = 1.5 mM) of the glutathione reductase as compared to natural oxidized glutathione (Km = 0.51 mM) but are not effective competitors of the enzyme. It can be considered that the new glutathione derivatives do not strongly interfere with the natural enzymatic defence against fatty acid hydroperoxides formed during an oxidative stress.

Animals↗

A pulse radiolysis study of one-electron oxidation and .OH radical reaction of a new class of antioxidants: 2,5 dimethylpyrrole--amino acid N-conjugates.

A new class of 2,5 dimethylpyrrole functionalized amino acid and peptide antioxidants has been synthesized. Pulse radiolysis studies have been carried out on these compounds to determine their reactivity in one-electron oxidation reactions with Br2- and (SCN)2-, as well as their reactivity toward the water radicals .OH and eaq-. When compared to similar reactions with parent amino acids and peptides, both rate constants and transient spectra indicate considerable interaction between the electronic states of the pyrrole moiety and amino acid or peptide. Where comparison data is available, radical reactions are significantly more rapid with these derivatives than with the parent compounds. Exceptions occur in some cases of .OH attack where steric hindrance may be evoked to explain a lower rate constant in the derivative compounds. Electron attachment rates are also found to be enhanced by the presence of the pyrrole ring.

Amino Acids↗

[Descriptive modeling of the chemical structure-biological activity relations of a group of malonic polyethylenic acids as shown by different pharmacotoxicologic tests].

48 new polyethylenic-malonic acids have been submitted to an antimicrobial and antifungal screening. After a suitable recording, the experimental results were analyzed according to two mathematical multivariate analysis using a computer process i.e. Correspondence Factorial Analysis and Cluster Analysis. These methods allowed an accurate study of the structure of the system and a thorough investigation of the structure-activity-specificity relationships. On the other side, magnitude and/or specificity of the observed biological effects were related to structural features. These results should be useful in order to elaborate synthetic strategies.

Anti-Bacterial Agents↗

[Epidemiologic aspects of polyarterial pathology].

UNLABELLED: With the considerable technical progress in vascular investigations made in the last decade, evaluation of multifocal ischemic pathology (MIP) has become easier and allows better assessment of strategy for reperfusion. In vascular surgery, 50% of post-operative mortality and morbidity are related to coronary heart disease (CHD). Epidemiologic data, not biased by specific recruitment of medical and surgical departments, are needed to assessing the real incidence of MIP. Different clinical date have already shown the problem of MIP: the post-operative cardiac mortality rate in vascular surgery has been evaluated at between 0.9% and 3.5% for abdominal aortic aneurysms and 0.3% and 3.2% for peripheral vascular disease (PVD) according to recent statistics (2, 7, 10, 12, 21) (Table I). The total cardiac mortality rate is between 1% and 2% for vascular surgery and is 0.2% for general surgery (8). Thus, though early post-operative over-risk in vascular surgery is not very high, the long term-prognosis is far more impaired: 25% to 55% of patients will die within 10 years after vascular surgery (4, 10, 13, 20). Hertzer, using systematic pre-operative coronary angiograms, found significant coronary stenosis in 57% of patients referred for vascular surgery (11). POPULATION AND METHODS: This study was performed in a representative sample taken from an ongoing prospective survey of 10,446 council employees in Marseille (5,177 men (M.), 5,269 women (W.)). This sample of 1,883 M. and 1,212 W. (mean age: 42.3 +/- 9 for M., 44.9 +/- 11 for W., range 25-65 years) was submitted to a detailed questionnaire on personal and family history of CHD, risk factors and symptoms of CHD (22), and to a physical examination including height, weight and blood pressure measurements. Every subject underwent an ECG recording and a dietetic (5) and psychologic (1) interview, and a blood sample was taken for plasma glucose, total cholesterol and lipoprotein assay. According to epidemiologic data, the prevalence of MIP appears to be lower as compared to clinical data. Undoubtedly, clinical data from surgical departments overestimate the true prevalence of MIP since patients referred for surgical therapy are usually suffering from more advanced pathology. Epidemiology, mainly based on non invasive data probably underestimates the prevalence of MIP but confirms the highest prevalence of CHD as compared to prevalence of other localisations of atherosclerosis and shows CHD as being the earliest localisation of vascular ischemic lesions in most cases. When unifocal ischemic pathology (UIP) and MIP are compared, risk factors are the same, although different proportions of patients are concerned with some of them: in MIP, age is still the major risk factor, whereas smoking in M. and overweight in W. seem to be more frequent than in UIP. RESULTS: Sixty-eight cases (5%) of ischemic pathology were found in men and 47 cases (4%) in women, with 4.1% cases of unifocal ischemic pathology (UIP) in M. and 3.3% in W...

Adult↗

[Polyarterial pathology. Epidemiological aspects].

Polyarterial arteriosclerosis is a problem facing more and more clinicians because of the technical advances in exploration and revascularization methods. Epidemiologic data are rare in this field except for Framingham's study. We are reporting here the results of a French epidemiologic study regarding a representative sample of a group of 11,000 active men and women, with age ranging between 25 and 65 years. Methodologic difficulties cannot be avoided, but a minimal estimation may be expressed: polyarterial pathology represents approximately 15 p. cent of the pathology in each case. Polyarterial pathology is as prevalent as monoarterial pathology with a 10 years delay between the two sexes. Coronary diseases are the most frequent and represent the initial location in two-thirds of the cases. The same risk factors are found, but their chronology is different: more than ever, age is an essential factor since there is a ten years difference. Hyperglycaemia in men, overweight in women are major factors as important as tobacco abuse in men, arterial hypertension and dyslipidemia in both sexes. Finally the type A behavior seems to occupy an even larger role in polyarterial patients of both sexes.

Adult↗

Macromolecular transport in jejunal mucosa of children with severe malnutrition: a quantitative study.

Small intestinal permeability to horseradish peroxidase (HRP) was assessed in jejunal biopsies of malnourished children. Clinical examination, intestinal function (D-Xylose test), and the histological appearance of the mucosa were assessed in 14 children during the malnutrition phase and in eight children after 3 months of nutritional rehabilitation. Macromolecular permeability was evaluated by measuring transepithelial HRP fluxes from mucosa to serosa (JHRPms) using Ussing chambers. Intact HRP transport, i.e., nondegraded protein transport, was measured by enzyme assay, and tritiated HRP was concomitantly used to measure intact and degraded HRP fluxes (J[3H]HRPms). Electrical parameters (short-circuit current, potential difference, and ionic conductance) were also recorded. Transepithelial HRP fluxes were significantly higher during malnutrition (JHRPms = 8.85 +/- 1.44; J[3H]HRPms = 77.11 +/- 10.66 pmol X h-1 X cm-2) than in the same children after 3 months of nutritional rehabilitation (JHRPms = 2.94 +/- 1.10; J[3H]HRPms = 22.93 +/- 8.15 pmol X h-1 X cm-2). The total ionic conductance, which is an index of paracellular permeability, did not change significantly. Calculated intratissue degradation of the protein did not appear to alter during malnutrition. These results point to a clinical situation in which malnutrition with diarrhea in children is associated with increased intestinal permeability to macromolecules by a mechanism not related to any paracellular leak of the protein, but rather to increased transcellular absorption.

Acute Disease↗

[Evaluation of the performance of the Coagulyzer II (Lancer)].

The automation of equipment is essential in laboratories performing a large number of procedures with high precision. An evaluation of performance characteristics of a photoelectric automated coagulation instrument, the Coagulyzer II (Lancer) is reported and compared with performances of the Coag-a-pet 200.

Autoanalysis↗

[Measurement of insulin sensitivity in obese or diabetic children in vivo. A comparison of three methods (author's transl)].

Three groups of ten similar obese children were infused with one of three protocols. Protocol I glucose only (1.15 mM/min/m2). protocol II, glucose, insulin (42 mM/min/m2). Protocol III, glucose insulin, propanolol (0.04 mg/min/m2) adrenalin (3 micrograms/min/m2). Eighteen newly diagnosed diabetic children without acidosis received glucose according to protocol II. Thirteen normal adults (controls) received glucose infusion according to protocol I. Protocols I and II were well tolerated and gave consistent results but Protocol III was not well tolerated and did not give interpretable results. In obese children steady state blood glucose levels are significantly higher than in controls but this difference was only moderate (8.8 + 0.7 mM, against 6.6 +/- 0.4 mM for protocol I). There was no difference in insulin levels. In diabetic children the steady state was more rarely obtained after a 120 min infusion and blood glucose levels were higher than in the controls or in obese children.

Adolescent↗