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Biomedical subjects

P Allain

Publications and source records attributed to P Allain.

At least 19 recordsLinked to original sources

[Increase of sialic acid concentration in the plasma of patients with coronary disease].

OBJECTIVES: Plasma levels of sialic acid are elevated in patients with coronary heart disease. We evaluated the specificity of this increase and attempted to correlate it with the severity of coronary lesions. METHODS: Total plasma sialic acid levels measured in 60 control subjects were compared with that in 135 patients with heart disease requiring coronarography. RESULTS: Plasma levels of sialic acid were significantly higher in patients (664 +/- 146 mg/l) than in controls (584 +/- 100 mg/l). In the group of patients, sialic acid level was only increased in those with coronary lesions - infarcts (738 +/- 166 mg/l) and angina (664 +/- 121 mg/l) - but was not raised above normal levels in those with other heart diseases (cardiomyopathy, valve failure, etc.). There was a positive correlation (p < 0.001) between raised sialic acid level and the severity of the coronary lesions as measured on coronarography. CONCLUSIONS: The elevated level of sialic acid in patients with coronary heart disease could be related to disorders in cell adhesion.

Adult

Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration.

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent containing Sr (S 12911) has shown positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13-week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day orally). The distribution of Sr was determined and quantified by X-ray microanalysis. Changes at the crystal level were evaluated by X-ray diffraction and Raman microspectrometry. In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tissue. In the treated monkeys, Sr could only be detected in calcified matrix. In monkeys sacrificed at the end of the treatment, Sr was found to be dose-dependently incorporated into the mineral substance of the compact and cancellous bone. Sr was heterogeneously distributed with three to four times more Sr in new than in old compact bone, and approximately two and a half times more Sr in new than in old cancellous bone. The bone Sr content dramatically decreased in the animals sacrificed 6 weeks after the end of the treatment. Diffraction showed no significant changes in the characteristics of the crystal lattice. Sr appeared to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions. Even at the highest dose level tested, less than 1 calcium ion out of 10 was substituted by 1 Sr ion in each crystal. In conclusion, taken up by bone, Sr was heterogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystallinity, crystal structure) at the crystal level. As a result, a treatment with S 12911 Sr salt should not induce any alteration of bone mineral.

Administration, Oral

4-Methylpyrazole and hemodialysis in ethylene glycol poisoning.

CASE REPORTS: Two patients severely intoxicated with ethylene glycol became anuric and were treated by hemodialysis and the antidote, 4-methylpyrazole. On admission, their plasma ethylene glycol concentrations were 0.42 and 3 g/L respectively and no alcohol was detected. The elimination of 4-methylpyrazole in the dialysate represented 45% of the total body elimination. Clearances of 4-methylpyrazole by hemodialysis were 80 mL/min and 52 mL/min respectively. RESULTS: In such cases, the authors propose infusion of a 4-methylpyrazole loading dose of 10-20 mg/kg before dialysis and intravenous infusion of 1-1.5 mg/kg/h during the 8-12 hours of hemodialysis to compensate the loss in dialysate.

Adult

Enhancement of aluminum digestive absorption by fluoride in rats.

Aluminum, responsible of dialysis encephalopathy, is suspected to be involved in other neurological disorders such as Alzheimer disease. Absorption of aluminum from the digestive tract can be enhanced by the concommittant intake of substances such as citrate. We studied in rats and mice the interactions between fluoride and aluminum for their digestive absorption and showed that fluoride increased the levels of aluminum in plasma as much as citrate whereas aluminum decreased the absorption of fluoride. This result could be the consequence of the high affinity between aluminum and fluoride which form complexes able to increase the absorption of aluminum and to decrease the absorption of fluoride.

Aluminum

[Study of blood lead levels in a population of 616 subjects from the regions: Centre and Pays de Loire].

OBJECTIVES: Low-lead level exposure has been associated with harmful health effects. Blood lead is the most widely used marker of exposure. In this work, our purpose was to evaluate the present level of blood lead in a group of 616 subjects from the general population living in two regions of France: Centre and Pays de Loire. METHODS: Subjects were randomly included in the study. Blood lead was measured by inductively coupled plasma mass spectrometry which is the most sensitive and specific method. RESULTS: The mean blood lead concentration of the population studied ranged from 46.7 +/- 20.5 micrograms/l in the 6-10 year old to 86.6 +/- 42.4 micrograms/l in the 50-66 year old subjects. From 385 children under 13 years old, 5 had blood lead higher than 100 micrograms/l, the maximum acceptable level recommended by the American Centers for Disease Control. Women had lower blood lead values than men and their levels remained unchanged until 50 years but increased beyond this age. CONCLUSION: Mean lead levels were low in this French population. There is however risk of higher levels in persons living in old housing.

Adolescent

Long-term pharmacokinetic behavior of platinum after cisplatin administration.

PURPOSE: The platinum concentration in plasma was studied in 19 patients treated by 3 or 4 successive courses of chemotherapy including cisplatin for head and neck cancers. METHODS: Cisplatin was given i.v. daily at 25 mg/m2 by 1-h infusions for 4 days every 3 weeks. Total and ultrafiltrable platinum were measured in plasma using an inductively coupled plasma mass spectrometry (ICPMS) technique. RESULTS: A progressive accumulation of total platinum in plasma was observed with consecutive infusions. The mean (+/- SD) total plasma platinum level detected at the end of cisplatin infusion was 1134 +/- 234, 1407 +/- 268, and 1618 +/- 282 micrograms/l at the end of the first, second, and third courses, respectively. The minimal platinum concentration measured before the second and third courses also increased to 221 +/- 59 and 309 +/- 76 micrograms/l, respectively. The steady state was not reached before the third course. However, differences in the evolution of platinum plasma levels were found among the 19 patients. In 14 patients the pharmacokinetics of platinum was characterized by low initial levels, a progressive accumulation, and a long terminal half-life with a very late steady state. In 5 patients, the pharmacokinetic behavior of platinum was different: platinum levels were directly high, without progressive accumulation, the steady state being reached as early as the first course. Significant levels of ultrafiltrable platinum were found throughout the treatment, even during the intervals between courses with this very sensitive analytical method. A close equilibrium between ultrafiltrable and total platinum (ratio, 6%) persisted for as long as 3 weeks after cisplatin administration. DISCUSSION: These results underline the importance of individual differences in platinum metabolism. The relationship between total and ultrafiltrable platinum are discussed.

Aged

PET imaging of neocortical monoaminergic terminals in Parkinson's disease.

Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11C-S-Nomifensine (11C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11C-NMF asymmetries, suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss, and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism.

Aged

Unaltered thyroid function in mice responding to a highly immunogenic thyrotropin receptor: implications for the establishment of a mouse model for Graves' disease.

Grave's disease (GD) is a common disorder characterized by the presence of autoantibodies to the thyrotropin receptor. In the past, the exceedingly low expression of the thyrotropin receptor on thyrocytes has not allowed its purification in quantities sufficient to investigate the establishment of an animal model for this disease. In this study, we have purified the 398-amino acid, extracellular region of the human thyrotropin receptor (TSH-R.E) from insect cells using recombinant baculovirus, and explored its immunopathogenic properties in H-2b,d,q,k,s strains of mice. The receptor preparation was highly immunogenic since it elicited strong specific proliferative T cell responses as well as IgG responses in all strains tested. In addition, hyperimmunization with TSH-R.E induced (i) serum antibodies that blocked the binding of 125I-TSH to its receptor, a common feature of GD autoantibodies; and (ii) IgG that reacted with a synthetic peptide (residues 32-54) from the N-terminus of the receptor, a region implicated in the binding of thyroid stimulating antibodies. In SJL animals only, a weak antibody response to two other thyroid antigens, thyroglobulin and thyroid peroxidase, was also observed. The presence of these antibodies, however, was not accompanied by a detectable alteration in thyroid function as assessed by the measurement of serum TSH, T4 and iodine levels. Also mononuclear infiltration of the thyroid gland or morphological changes compatible with an activation state of thyrocytes were not apparent in TSH-R-challenged mice. In contrast, mice treated with the anti-oxidant aminotriazole showed a dramatic increase in serum TSH levels and an activated follicular epithelium. These data demonstrate that a highly immunogenic TSH-R.E in mice does not necessarily provide a proper stimulus for the induction of a hyper- or hypothyroid status as defined by hormonal or histological criteria. Main reasons for the inability to induce receptor-specific antibodies that affect thyroid function such as those generated in GD are likely to be the inappropriate folding of the recombinant extracellular domain of the receptor, or the xenogeneic nature of the autoantigen.

Animals

[Uncontrolled retrospective study of 75 pregnancies in women treated for epilepsy].

OBJECTIVE: Our purpose was to study pregnancies and birth outcomes in a population of women treated for epilepsy. STUDY DESIGN: A retrospective uncontrolled study of 75 pregnancies in 55 epileptic women under treatment was conducted in the nursery of CHU Angers. The course of pregnancies and deliveries, the frequency of congenital malformations and the clinical state of the neonates during the first 6 days of life were recorded. RESULTS: There was a high rate of prematurity (15%) especially in patients treated by phenobarbital, a 10.5% rate of intra-utero growth retardation, a 11% rate of major congenital malformations and a 9% rate of isolated minor congenital malformations. Congenital malformations were mainly facial dysmorphia, cardiopahties, urogenital tract abnormalities. The neonatal symptomatology was associated with a high level of antiepileptic drugs in neonates or to a withdrawal syndrome or to hypovitaminosis. CONCLUSION: Overall results justify implementing prevention and detection measures.

Abnormalities, Drug-Induced

Sulfate and cysteine levels in the plasma of patients with Parkinson's disease.

The study of Heafield et al. (1990) has prompted us to compare the levels of sulfate cysteine and homocysteine in the plasma of healthy subjects and of patients with Parkinson's disease treated by L-Dopa and dopa decarboxylase inhibitors. The levels of sulfate and cysteine in the plasma of controls and patients with Parkinson's disease were not statistically different but the level of homocysteine was higher in patients.

Aged

Efficacy of 4-methylpyrazole in ethylene glycol poisoning: clinical and toxicokinetic aspects.

Potentially fatal ethylene glycol intoxication in an adult with normal renal function was treated with 4-methylpyrazole administered three hours after the incident occurred. The plasma ethylene glycol concentration was 3.5 g l-1 on admission. The metabolic acidosis present on admission resolved within four hours, and the subsequent clinical course was uneventful. The apparent plasma half-life of ethylene glycol was 16 h and the mean renal and plasma clearances of ethylene glycol were 24 and 25 ml min-1, respectively. These results support the hypothesis that complete blockade of hepatic metabolism of ethylene glycol is achieved by 4-methylpyrazole. The only side-effect observed as a result of treatment was a transient slight increase in serum transaminase activity.

Adult

Decrease of isoprene concentrations in blood during general anesthesia.

Isoprene is present in human breath and in human blood. The fact that isoprene concentrations in breath are linked to states of sleep and wakefulness led us to study its concentration in blood of 12 patients before, during, and after general anesthesia. Isoprene concentrations in blood of patients before anesthesia were 3.3 +/- 1.6 micrograms/liter. During anesthesia, isoprene concentrations decreased to 0.9 +/- 0.5 micrograms/liter. One hour after the end of anesthesia isoprene increased to levels similar to or higher than the preanesthetic ones.

Adult

Use of plasma iodine assay for diagnosing thyroid disorders.

AIMS: To examine the advantage of systematic plasma iodine assays in establishing the thyroid function of patients with thyroid disorders. METHODS: Iodine was determined by inductively coupled plasma mass spectrometry (ICPMS) in the plasma of 799 patients consulting for possible thyroid disorders, indicated by FT4 and TSH assays. RESULTS: Plasma iodine was below 40 micrograms/l in 57 (7%) patients, most of whom had hypothyroidism; 40-80 micrograms/l in 439 (55%) patients, most of whom had normal thyroid hormone function; 80-250 micrograms/l in 240 (30%) patients, most of whom had hyperthyroidism; and above 250 micrograms/l in 63 (8%) patients, almost all of whom had iodine overload caused by iodinated drugs, particularly amiodarone, resulting in euthyroidism (24%), hyperthyroidism (36%), and hypothyroidism (16%). Sixty five (7%) had been treated with amiodarone and 27 (3%) with other iodinated drugs. More than 10% of patients with thyroid disorders therefore had an iodine overload. CONCLUSIONS: The determination of total plasma iodine using the simple, accurate ICPMS technique, should be carried out in patients consulting for thyroid disorders, particularly for the detection of an iodine overload.

Adult

Bromine and thyroid hormone activity.

AIMS: To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS: Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS: The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION: An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.

Bromine

Is pentane a normal constituent of human breath?

Breath analysis is a non-invasive method for investigation of the volatile compounds produced by humans. Pentane has often been taken as an indicator of lipid peroxidation. Our purpose in this study was to determine its normal concentration in the breath of healthy humans. Using a specific and sensitive gas chromatography-mass spectrometry technique pentane concentrations in breath were lower than 10 pmoles/l. The high levels of pentane found by some authors in healthy humans were probably due to the coelution of pentane with isoprene, a volatile hydrocarbon present in human breath.

Adult