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C Charpentier

Publications and source records attributed to C Charpentier.

At least 19 recordsLinked to original sources
PubMed1995

[Sleep and COPD].

In COPD patients hypoxaemia does worsen during sleep and particularly during REM sleep. However, severe sleep-related O2 desaturation is only observed in patients who exhibit a marked daytime hypoxaemia. Nocturnal desaturation is due to the combination of alveolar hypoventilation and ventilation-perfusion mismatch; alveolar hypoventilation is the predominant mechanism, at least during REM sleep. Sleep-related hypoxaemia leads to peaks of pulmonary hypertension but also to cardiac arrhythmias. Hypoxaemia can be particularly severe when COPD is associated with a sleep apnoea syndrome (this association is rather frequent). A severe nocturnal desaturation needs a treatment with prolonged oxygen therapy, especially if daytime hypoxaemia (PaO2 < 55-60 mmHg) is present. The real benefit from oxygen therapy limited to sleep time in nocturnal desaturators who have not a significant daytime hypoxaemia, has not been yet demonstrated.

Humans↗
PubMed1995

Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure.

Prognostic factors in COPD patients receiving long-term oxygen (LTO) therapy were recently analyzed, but very few studies considered the prognostic value of pulmonary artery pressure (PAP) in these patients. We investigated 84 patients who had undergone a right heart catheterization just before the onset of LTO. There were 75 men and 9 women, with a mean age of 63.0 +/- 9.9 (SD) years, at the onset of LTO. When PaO2 was persistently less than 55 mm Hg, LTO was initiated. This therapy was started in some patients with PaO2 in the range of 55 to 60 mm Hg if they had signs of cor pulmonale or a resting PAP of 25 mm Hg or greater at right heart catheterization. The daily duration of LTO was 16 h/d or more. Oxygen flow was adapted to achieve a PaO2 of 65 mm Hg or more. The patients were subdivided into subgroups according to the median value of age (cutoff value = 63 years); vital capacity (2,250 mL); FEV1 (800 mL); residual volume-total lung capacity ratio (58%); PaO2 value (52 mm Hg), PaCO2 level (45 mm Hg); and PAP (25 mm Hg). The cumulative 5-year survival rate was 48% for the group as a whole. Actuarial survival curves were plotted for the two subgroups of patients subdivided according to the initial median value of the variables just listed. There was no significant difference in survival rate between subgroups except when taking into account the level of PAP and age. In patients with an initial PAP of 25 mm Hg or less (n = 44), the 5-year survival was of 62.2 vs 36.3% in the remainder (n = 40) [p < 0.001]. We performed a multivariate analysis of survival using Cox's model of the proportional hazards regression including sex and the variables with the same categorization in the stepwise procedure: PAP and age were the only variables included in the final model. We conclude that the best prognostic factor in COPD patients receiving LTO is not the FEV1, nor the degree of hypoxemia or hypercapnia, but the level of PAP.

Actuarial Analysis↗
PubMed1994

Relationship between ethanol tolerance, lipid composition and plasma membrane fluidity in Saccharomyces cerevisiae and Kloeckera apiculata.

The lipid composition of a strain of each of two yeasts, Saccharomyces cerevisiae and Kloeckera apiculata, with different ethanol tolerances, was determined for cells grown with or without added ethanol. An increase in the proportion of ergosterol, unsaturated fatty acid levels and the maintenance of phospholipid biosynthesis seemed to be responsible for ethanol tolerance. The association of ethanol tolerance of yeast cells with plasma membrane fluidity, measured by fluorescence anisotropy, is discussed. We propose that an increase in plasma membrane fluidity may be correlated with a decrease in the sterol:phospholipid and sterol:protein ratios and an increase in unsaturation index.

Bacterial Proteins↗
PubMed1994

Clinical outcome of long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia.

We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.

Age Factors↗
PubMed1994

[Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study].

Changes in transfusion behaviour induce a widespread use of colloid plasma substitutes, the range of which has recently been enlarged by the marketing of starch derivatives. The product chosen depends, at least in part, on its adverse effects, anaphylactoid reactions being a part of these. This study aimed to discover the frequency and severity of these reactions according to the type of substitute available in France, to look for possible risk factors, and determine the mechanisms involved. A prospective inquiry was carried out in 49 public and private hospitals spread throughout France. It lasted for 15 months, between June 1991 and October 1992. A data sheet was filled in for each patient who was given a plasma substitute, whether or not there was an incident. When a reaction did occur, an assessment was carried out in two stages: straightaway, with the measurement of the concentrations of serum tryptase, antigelatin antibodies, urinary methylhistamine; and four to six weeks later, with skin tests. A series of 19.593 patients was thus collected: 48.1% were given gelatins, 26.7% starches, 15.7% albumin, and 9.5% dextrans. 43 anaphylactoid reactions were recorded, giving an overall frequency of 0.219%, or 1 reaction for 456 patients. The frequency differed according to the substitute considered: 0.345% for gelatins, 0.273% for dextrans, 0.099% for albumin, and 0.058% for starches. These reactions (grades III and IV) were serious in 20% of cases. Multivariate analysis revealed four independent risk factors: giving gelatins (odds ratio: 4.81), giving dextrans (odds ratio: 3.83), a history of drug allergy (odds ratio: 3.16), and being male (odds ratio: 1.98). The relative risks of anaphylactoid reactions due to one type of substitute with respect to another were estimated to be 6 times less for starches with respect to gelatins, and 4.7 times less than with dextrans. The relative risk of albumin is 3.4 times less than that of gelatins, and almost identical to that of the starches. An immuno-allergological assessment was only carried out in 15 patients who had been given a gelatin (Plasmion). IgE-dependent anaphylaxis was proven in 7 of these. To conclude, it was shown that gelatins and dextrans should be avoided in patients with a known history of drug allergy. When a reaction does occur, an allergological assessment must be carried out, as this may be due to specific antibodies. Should this prove to be the case, that particular substitute would be contraindicated for the rest of the patient's life.

Anaphylaxis↗
PubMed1994

[Angioplasties: is anesthesia necessary?].

Percutaneous transluminal angioplasty of lower limbs, renal, mesenteric, coronary or supra-aortic arteries is a technique in progress. Nevertheless patients concerned are high-risk patients who are always anxious about the angioplasty result. Ambulatory anaesthesia is required. Local anaesthesia of artery puncture site is effective. Low-osmolality contrast media should be chosen to reduce injection pain. Calcium blockers and molsidomine could prevent "arterial vasospasme". Finally, the major aim of anaesthesia is to limit patient's anxiety. In most cases orally premedication is enough. The presence of the anaesthesiologist during the procedure is not required but resuscitation devices must be available.

Adolescent↗
PubMed1994

[Diagnosis of metabolic coma in children].

This article describes the metabolic investigations to be applied in any clinical situation consistent with a late acute form of inborn error of metabolism: unexplained coma with or without focal neurological manifestations, recurrent vomiting with lethargy, episodes of ataxia with or without behaviour disorder, fits of psychiatric troubles. In each of these situations, careful medical history is of major importance searching for previous clinical manifestations such as episodes of coma, ataxia or vomiting, anorexia, failure to thrive, developmental delay, all very suggestive of metabolic disorder. The association of neurological symptoms and abnormal hepatic tests is also of great value and must not lead to the diagnosis of Reye's syndrome without considering a metabolic defect of fatty acid oxidation, urea cycle, respiratory chain, or Wilson's disease. When looking for an etiological origin, it is mandatory to collect all the biological information at the same time, also knowing that metabolic abnormalities may be mild and transitory, and that many of them are non specific (metabolic acidosis, hyperlactacidemia, hyperammonemia, hepatic tests disturbances) being encountered in collapsus, shock and multiple organ failure syndrome.

Acute Disease↗
PubMed1994

Ethanol adaptation mechanisms in Saccharomyces cerevisiae.

Determination of the membrane lipid composition of Saccharomyces cerevisiae revealed an increase in the unsaturation index, qualitative and quantitative changes in sterol content and an alteration of the activity of the plasma membrane ATPase when cells were pre-adapted to ethanol. All these changes may constitute different adaptation mechanisms which allow the cell to cope with ethanol stress. The importance of the lipid environment on the plasma membrane ATPase activity is also discussed.

Adaptation, Physiological↗
PubMed1994

[Protocol of metabolic investigations in hereditary metabolic diseases].

The authors describe a laboratory investigations protocol to be used by pediatricians facing conditions suggestive of inherited metabolic disorders. This protocol includes: 1) an emergency screening to be systematically performed during the acute clinical phase; 2) samplings to be kept frozen for possible secondary specific investigations according to the results of the emergency screening. In addition a perimortem protocol is also presented, to be applied in every lethal situations in which an inherited metabolic disorder is suspected. The equipment required in order for the clinician to properly perform the different investigations is also described.

Clinical Laboratory Techniques↗
PubMed1993

Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency.

Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity.

Cells, Cultured↗
PubMed1993

Clinical and biochemical phenotype in 11 patients with mevalonic aciduria.

OBJECTIVE: Mevalonic aciduria is a consequence of the deficiency of mevalonate kinase, the first enzyme after 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the biosynthesis of cholesterol and nonsterol isoprenes. To establish the clinical and biochemical phenotype of mevalonic aciduria, the authors assembled their experience with 11 patients including attempts at therapeutic interventions. METHODS: Mevalonic acid in body fluids was determined by stable isotope dilution gas chromatography/mass spectroscopy with selected ion monitoring, ubiquinone-10 concentrations by reversed-phase high-pressure liquid chromatography. RESULTS: Varying degrees of severity of clinical illness were observed despite uniform, virtual absence of residual activity of the enzyme. The most severely affected patients have had profound developmental delay, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, and anemia, as well as diarrhea and malabsorption, and have died in infancy. Less severely affected patients have had psychomotor retardation, hypotonia, myopathy, and ataxia. All patients have had recurrent crises in which there was fever, lymphadenopathy, increase in size of liver and spleen, arthralgia, edema, and a morbilliform rash. Neuroimaging studies revealed selective and progressive atrophy of the cerebellum. Mevalonic acid concentrations were found to be grossly elevated in body fluids of all patients. Concentrations of plasma cholesterol were normal or only slightly reduced. Concentrations of ubiquinone-10 in plasma were found to be decreased in most patients. Abnormalities such as hypoglycemia, metabolic acidosis, or lactic acidemia, the usual concomitants of disorders of organic acid metabolism, were conspicuously absent. CONCLUSIONS: These observations establish the broad range of clinical symptoms and biochemical findings in mevalonic aciduria. It is concluded that although patients with mevalonic aciduria have a recognizable phenotype of serious clinical manifestations, some patients are likely to remain undiagnosed and may be found in a variety of subspecialty clinics, including neurology, gastroenterology, cardiology, and genetics.

Abnormalities, Multiple↗
PubMed1992

Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.

We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle.

Acidosis, Lactic↗
PubMed1992

Medium chain acyl-CoA dehydrogenase deficiency.

From 65 reported cases of medium chain acyl-CoA dehydrogenase deficiency, we found an average presenting age of 13.5 months and a mean age at death of 18.5 months. One quarter of patients died of a Reye-like syndrome and/or sudden infant death. In half the cases there had been at least one sibling death. Asymptomatic cases were not uncommon (12% of cases). The crises were generally induced by a prolonged fast and after a viral prodromal phase in three quarters of cases. The crises consisted of somnolence progressing to lethargy which could lead to coma. Vomiting was frequent (60% of cases). Seizures, which were found in 29% of cases, represented a bad prognosis. The physical examinations revealed frequently a variable and regressive anicteric hepatomegaly. Blood and urine analysis revealed in most instances hypoglycaemia (96% of cases) with hypoketonuria and sometimes metabolic acidosis. Hepatic and muscular cytolytic enzymes were frequently raised, as were plasma ammonia, urea, and uric acid. Plasma total or free carnitine concentrations, especially non-fasting, were diminished in most cases. Plasma saturated medium chain fatty acids and particularly unsaturated cis-4-decenoate were on the other hand raised during the crises or during fasting. Urinary organic acid analysis revealed a characteristic profile of medium chain aciduria: C6-C10 dicarboxylic acids, hydroxy acids, glycine conjugates, and carnitine conjugates. Oral loading tests with carnitine or phenylpropionate allow a precise diagnosis. The diagnosis is confirmed by specific assays in various tissues. Avoidance of prolonged fasting seems to be the mainstay of treatment.

Acyl-CoA Dehydrogenases↗
PubMed1991

Organic acids in aqueous humour and plasma: post mortem study in infants and diagnosis of enzymopathies.

Organic acids have been determined in aqueous humour and plasma by gas chromatography-mass spectrometry in 38 cases of infant death and 4 cases of inherited metabolic disease: one had a complex fatty-acid oxidation disorder with a large urinary excretion of adipic acid, the others had a disorder of propionate catabolism with a large urinary excretion of methylmalonic acid. In each case we found in aqueous humour the abnormal metabolite present in urine. Thus aqueous humour could be a suitable material for retrospective diagnosis of inherited metabolic diseases at autopsy in sudden infant death syndrome.

Adipates↗