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Biomedical subjects

P Allain

Publications and source records attributed to P Allain.

At least 73 records · Page 4Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Inhibition of cholinesterases by histamine 2 receptor antagonist drugs.

Many studies have demonstrated that histamine 2 receptor antagonists (H2RA) have in vitro anticholinesterase effects, but discrepancies about type and potency of this inhibitory effect exist among published results. Moreover, cholinesterase inhibition has not been shown in patients receiving H2RA. These discrepancies led us to study the in vitro antibutyryl- and in vitro antiacetylcholinesterase activities of ranitidine, cimetidine, nizatidine comparatively to pyridostigmines. Plasma cholinesterase activity (PCEA), erythrocyte cholinesterase activity (ECEA) and plasma ranitidine levels were measured in six patients before and during continuous IV infusion (150 or 200 mg/d) of ranitidine. Our in vitro results confirm the weak anticholinesterase activity of H2RA. Ranitidine is the most potent inhibitor of butyrylcholinesterase (Ki = 61 microM). Ranitidine and nizatidine are the most potent inhibitors of acetylcholinesterase (Ki' = 2.1 microM, Ki' = 5.1 microM, respectively) but one thousand times less effective than pyridostigmine (Ki = 0.003 microM). The results in patients show no statistically significant difference between PCEA and ECEA measured before and during ranitidine infusion (plasma ranitidine levels between 0.31 and 1.25 microM).

Acetylcholinesterase↗
PubMed1993

Diethyldithiocarbamate and brain copper.

To test the hypothesis that the increase of copper concentration in brain after diethyldithiocarbamate (DEDTC) administration was due to the formation of a DEDTC-copper complex, able to cross the blood-brain barrier, we compared in rats the effects on brain copper of DEDTC given alone, in combination with copper or as a copper-DEDTC complex. The daily administration for three weeks of DEDTC alone, of DEDTC with copper and DEDTC-copper complex gave the same increase of the level of copper in brain. The time course effects of a single administration of DEDTC and of the DEDTC-copper complex were approximately the same: after a delay of about 24 h, there was an increase in brain copper concentrations which persisted for at least three days. This delayed effect explains discrepancies found in the literature concerning changes of copper in brain after a single administration of DEDTC according to the time interval between administration and tissue sampling. The results show that the additional copper does not increase the effect of DEDTC and that the formation of a DEDTC-copper lipophilic complex which could cross the blood-brain barrier is probably not the mechanism responsible for the increase of brain copper induced by DEDTC. Mechanisms other than direct copper chelation may be involved.

Administration, Oral↗
PubMed1992

[Chronic lead nephropathy. Epidemiology and diagnosis].

Chronic lead nephropathy has recently been rediscovered. Its usual manifestations are hypertension, gout and renal impairment. Retrospective epidemiological data suggest that prolonged exposure to lead increases the risk of hypertension and nephropathy. An increase in EDTA-induced urinary lead concentration (above 600 micrograms/72 hours), perfectly representative of lead concentration in bone, has been found with a 5 to 12 percent prevalence in chronic renal impairment irrespective of its cause. The origin of lead impregnation and its influence on the course of the renal disease have not yet been elucidated.

Chronic Disease↗
PubMed1992

Evaluation of inductively coupled mass spectrometry for the determination of platinum in plasma.

Among the different analytical methods used for the determination of platinum in blood plasma from patients treated by platinum derivatives, inductively coupled plasma mass spectrometry appears to be the most sensitive (detection limit 0.05 microgram l-1) and the best adapted for measuring low concentrations. The preparation of the samples consisted only of a dilution. The recoveries were close to 100% and both within-run and between-days reproducibility were very good. The determination of free platinum which was only about 5% of total plasma platinum was chosen to illustrate the inductively coupled mass spectrometric method.

Cisplatin↗
PubMed1992

Blood isoprene concentrations in humans and in some animal species.

The concentrations of isoprene, the main hydrocarbon of human breath, were measured in the blood of humans and of different animal species (rat, rabbit, dog, ewe, cow). In human blood, the concentrations of isoprene were between 15 and 70 nmol/liter (mean value of 37 +/- 25 (SD) nmol/liter). In the blood of the different animal species tested, traces of isoprene were unambiguously detected by mass spectrometry, but the levels were always lower than 1 nmol/liter.

Adult↗