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Biomedical subjects

P Loiseau

Publications and source records attributed to P Loiseau.

At least 145 records · Page 8Linked to original sources

Exercise tolerance in chronic obstructive pulmonary disease: importance of active and passive components of the ventilatory system.

We investigated which components of ventilatory function are related to exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Physical characteristics, usual lung function, timing and neuromuscular components of ventilation were measured in 113 outpatients in whom FEV1/VC was less than 75% of the predicted value and exercise was limited by breathlessness. These variables were used to predict the maximum work load during progressive bicycle exercise. The prediction was obtained using a stepwise procedure in men and women separately. Among the variables selected, age, body weight, FEV1/VC, PImax, and P0.1/VT/TI accounted for 79% of the variability in maximum performance in men. The predictive model was statistically verified and was stable. The mean prediction error was 12 Watts. Among these variables, P0.1/VT/TI, PImax, and FEV1/VC were the main determinants of maximum work load (MWL). These results show that exercise limitation in COPD is related to impairment of both the active (inspiratory muscles) and passive (respiratory impedance) components of the ventilatory system. The same conclusions concerning passive components are proposed for women, despite a smaller population which prevented verification of the prediction.

Adult↗

Macrofilaricidal activity of metabolites of diethylcarbamazine.

The antifilarial compound diethylcarbamazine (N,N-diethyl-4-methyl-2-piperazine, DEC) is known rather for its micro- than macrofilaricidal activity. But in some human filariasis i.e. loaiasis, lymphatic filariasis, the spectrum of DEC activities extends to adult filaria. The potential role of the metabolites of DEC in the action of the parent drug once it had been metabolized in the body of infected animals was investigated. The metabolites were evaluated in a new experimental model on which DEC is active: Molinema dessetae in its natural host, the rodent Proechimys oris. Experimental studies were carried out in vivo and in vitro, on microfilariae, infective larvae and adult filaria. Several other nematodes were also used. The metabolites were DEC itself, N-ethyl-4-methyl-1-piperazine-carboxamide (MEC) and their N-oxides, 4-methyl-piperazine-carboxamide and N,N-diethyl-1-piperazine-carboxamide. In vivo most of the metabolites were found active on microfilariae and both N-oxides active on adults and infective larvae. In vitro, the activity of the metabolites was observed only with high concentrations; the in vitro test could not be used as a screening method for antifilarial chemotherapy with piperazine derivatives. Infective larvae were the most sensitive stage. In the rodent and in man, the antifilarial action of DEC is swift and of short duration. This action is prolonged by the activity of metabolites, especially the N-oxides.

Animals↗

[After ivermectin, is it necessary to look again for a macrofilaricide?].

The use of ivermectin for mass treatment in human onchocerciasis is justified, because no other drug was available. But, as this compound is ineffective on adult filariae and as the emergence of drug resistance is quite possible, the evaluation of new chemical compounds for their macrofilaricidal activity should be continued. Several new compounds of interest are presented.

Animals↗

Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3' end of the BCR gene first intron.

About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M-BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8-kb region of the first intron of the BCR gene (called bcr2 or m-BCR-1). In this report we examined two cases of Ph1 acute lymphoblastic leukemia in adult patients that exhibited breakpoints in a 5-kb segment of the BCR gene first intron, 16 kb upstream of the previously described cluster, suggesting the possibility of a second minor breakpoint cluster. In addition, the breakpoints on chromosome 9 were located in a region just 5' of the c-abl exon la.

Chromosomes, Human, Pair 22↗

The V gamma locus of the human T cell receptor gamma gene. Repertoire polymorphism of the first variable gene segment subgroup.

Southern blot analysis using a genomic probe of the human TCR-gamma chain first variable gene subgroup (V gamma I) was performed on DNA samples from both parents of 36 healthy Caucasian families. Two types of polymorphisms were found in these 72 unrelated DNA samples: three repertoire polymorphisms and two restriction fragment length polymorphisms (RFLP). In all cases, Mendelian inheritance of these polymorphisms was demonstrated. The most frequent repertoire polymorphism consists in the lack of the V gamma 4 and V gamma 5 segments. In 16% of chromosomes, the Eco RI and Taq I restriction fragments corresponding to V gamma 4 and V gamma 5 were lacking, with no additional bands. In these cases, a decrease of 10 kb was observed in the Bam HI fragment containing all V gamma I segments as compared with samples containing V gamma 4-V gamma 5 segments. To better understand this polymorphism, which takes place in a previously incompletely defined region, the central part of the V gamma I region, including the polymorphic V gamma 4-V gamma 5 segments, was cloned. This allowed us to localize precisely the V gamma 5 segment and thus complete the description of the V gamma I region. A striking homology of DNA and deduced amino acid sequences is present between V gamma 2 and V gamma 4 and between V gamma 3 and V gamma 5, much higher than that observed between V gamma 2 and V gamma 3 and between V gamma 4 and V gamma 5. The differences in nucleotide sequence occur mainly in the intron and three hypervariable regions. These results strongly suggest a gene duplication relationship between the segments V gamma 2-V gamma 3 and the segments V gamma 4-V gamma 5. The most frequent RFLP documented in this study is due to the combined absence of the Eco RI and the Taq I sites located in the noncoding region between V gamma 3 and V gamma 4. The haplotypic frequence of this RFLP is 6.9% of the general population. As the gamma/delta receptor may play an important role in immunological response, the biological relevance of the high degree of polymorphism occurring in the V gamma I region, as well as its possible association with some immune disturbances, should be further explored.

Amino Acid Sequence↗

[Peripheral neuropathies disclosing sarcoidosis].

A 54 year-old woman presented with an asymmetrical polyneuropathy, with in addition signs of hepatitis and hypercalcemia. The diagnosis of sarcoidosis was made by hepatic and neuromuscular biopsies. Electrophysiological studies showed an asymmetrical clear neurogenic involvement with an axonal pattern. Ultrastructural study of the nerve showed sarcoid granulomas in epineurium, perineurium and endoneurium, with images of Wallerian degeneration. No features of primary demyelination were found. Granulomas were also present in muscle and liver. Possible etiological mechanisms are discussed: compression of nerve or vessels, or immune angiitis.

Electrophysiology↗

The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells.

The authors have analyzed the involvement of V gamma and J gamma segments in TRG gamma rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG gamma are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V gamma 11 and psi V gamma 12, which rearrange in T- and B-neoplastic cells. To date three subgroups of translatable V gamma segments have been described. The authors show that V gamma 11 is the unique member of a new fourth V gamma subgroup that also rearranges in normal polyclonal T cells and that psi V gamma 12 is located at 5-kilobase (kb) downstream to V gamma 11. As shown by DNA sequence analysis, V gamma 11 shares a 60% homology with V gamma 10 (third subgroup) and a 50% homology with V gamma 9 (second subgroup) but no appreciable homology with the V gamma segments from the first family. In contrast to psi V gamma 12, V gamma 11 is translatable. In this paper the authors have also attempted to determine which V gamma segments were rearranged in the ALL cases by hybridization with a J gamma probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J gamma 1 or J gamma 2 involvement, the authors have identified the corresponding V gamma segments and have not found any other rearrangements suggestive of the existence of further V regions. The V gamma segments, belonging to the first subgroup, were the most frequently used (41 alleles). V gamma 9, V gamma 10, V gamma 11, and psi V gamma 12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo psi V gamma 1, psi V gamma 5, and psi V gamma 6 segments were found. Pseudo V gamma segments were not found rearranged in T cells, while V gamma 2 and V gamma 4, segments are frequently used. In contrast to the V gamma I gene rearrangement, the involvement of the V gamma II, V gamma III, and V gamma IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+).(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Differentiation, T-Lymphocyte↗

[An adult case of Leigh's subacute necrotizing encephalomyelopathy].

Leigh's encephalomyelopathy has been mainly observed in infancy and childhood. A later onset, during adolescence or adulthood has been rarely reported. Our patient was a 35 year-old man who died after 10 months of evolution of a subacute neurological syndrome, beginning with behavioural changes then a confusional state, epileptic fits, ataxia, autonomic disorders, abnormal alimentary behaviour and dementia. Diagnosis was only obtained by neuropathology, as in most of the published reports. However this diagnosis is suggested when exists an acute or subacute neurological pattern, beginning with visual defects and alimentary and social impairment, followed by a brain-stem syndrome. CT and M.R.I. will make it more easy. An earlier diagnosis could perhaps allow to discover the suspected enzymopathy responsible for Leigh's encephalomyelopathy and make clearer the relationship between Leigh's disease and encephalopathies with abnormal mitochondria.

Adult↗

[MRI and surgery of epilepsy].

The evaluation of M.R.I. in the presurgical management of epilepsies requires establishing the significance of the abnormal signals. In 15 cases, correlations among M.R.I., electrophysiological data obtained by chronic intracerebral recordings and histological examination were studied. Abnormalities were detected by M.R.I. in 12 cases (80%). An accurate epileptic-focus topographical orientation was obtained by M.R.I. in 10 cases. But M.R.I. findings did not coincide with functional data obtained by S.E.E.G. recordings. Abnormalities detected by M.R.I. led to rectify the previous hypothesis about the epileptic focus localization in two cases. One false positive and one case of incomplete data would have been misleading if S.E.E.G. had not been performed. M.R.I. abnormalities included two morphological changes and ten high intensity T2 signals. The increased T2 intensity was more often focal (9) than diffuse (1). Among the 8 cases of increased T2 intensity correlated to the epileptic focus, 1 was histologically normal, 3 corresponded to specific lesions (astrocytoma: 1, hamartoma: 2) and 4 corresponded to non specific lesions (gliosis: 2, spongiosis: 2). When M.R.I. was normal at the site of the epileptic focus, either no alteration (2) or non specific lesions (2) were found. Uncus herniation could not be identified with M.R.I. M.R.I. has proven sensitive, detecting small epileptogenic lesions missed by C.T. Moreover in some cases, high T2 signals have been correlated topographically with the epileptic focus and histologically with non specific lesions. These signals are more likely related to a functional phenomenon such as an increase in water content than to the histopathological findings themselves.

Adolescent↗

[Cerebrovascular complications of sickle-cell anemia].

Cerebrovascular disorders are frequent in sickle-cell anemia. They occur mainly in homozygous children. Traditionally, they were believed to result from an arteriolar sickle-cell thrombosis, the "sludge" phenomenon, which is generally responsible for sickle cell anemia disorders. It is now well known that several other kinds of cerebral damages are involved such as moya-moya syndrome, cerebral hemorrhage, subdural hematoma, extra-dural hematoma and cerebral thrombophlebitis. In this disease, the identification of these different processes cannot be always made by a simple clinical examination. However, specific therapies are sometimes necessary, such as neurosurgical intervention in the case of aneurysm or hematoma, and, according to some authors, the necessity of repeated appropriate transfusions, in the case of moya-moya. So it is imperative to carry out without delay a complete neuroradiological assessment of the lesions. At present, the most widely accepted theory to explain the arteriolar lesions, is that they result from a sickle-cell thrombosis of the vasa-vasorum, but, we think it is not the only valid hypothesis and we think that other phenomena may be involved with a genetic factor (patients with connective tissue disorders may have a particular genotype), and with infectious or autoimmune or coagulation disorders, the latter being frequently observed in this disease.

Adolescent↗

[A new series of antiparasitic organic arsenicals: the spiroarsoranes. Experimental trypanocidal activity].

Arsenical compounds are the main therapeutic way, effective in the neurological phase of trypanosomiasis. Unfortunately, their important toxicity prevents their easy administration. Structural cyclization of arsonic acid derivatives has led to a class of non-toxic compounds: spiroarsoranes. A 47 compound primary screening on an in vivo murine model of Trypanosoma brucei brucei resulted in the isolation of a very effective derivative after a single subcutaneous injection of 30 mg.kg-1 body weight (Chemotherapeutic Index = 21). In this study, trypanocidal activity of this compound was evaluated on an in vivo sheep model of trypanosomiasis by T. brucei brucei, according to experimental model of the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France). A single subcutaneous injection of 30 and 100 mg.kg-1 b.w., and 30 and 60 mg.kg-1 b.w. was given respectively during first and second phase of trypanosomiasis. Ovine pharmacokinetics of this compound will be evaluated in a further study.

Animals↗

Determinants of compliance in epileptic patients.

A questionnaire was filled out by 270 epileptic outpatients responsible for taking their own medication to assess the extent of drug compliance-adherence and look for factors associated with poor compliance. Eighty-six patients (31.8%) were considered non-compliers. Significant factors for non-compliance were a duration of disease from 10 to 20 years, a low frequency of seizures and a drug intake considered as very bothersome. Neither sex nor age at onset, nor age at survey, nor type of epilepsy were different in compliers and non-compliers. Stopping medication to see if one is cured was more frequent in women than in men and a fear of drug toxicity was more frequent in patients over 30 years old.

Adolescent↗

[Neurophysiological and therapeutic evaluation of stiripentol in epilepsy. Preliminary results].

The main objective of this study was to determine whether stripentol (STP) alleviates side-effects commonly observed in treated epileptic patients, since preliminary data suggested a positive psychotropic effect. A secondary objective was an evaluation of drug efficacy. Eleven patients with either a drug-resistant epilepsy or toxic effects of AEDs completed the study. Ten had symptomatic partial epilepsies and one an idiopathic generalized epilepsy. STP was added to the baseline therapy (1 or 2 AEDs) and the dose of the baseline AEDs was reduced to maintain plasma levels unchanged (mean reduction: PB 26%, PHT: 49%, CBZ: 38%). Several motor, perceptual and attention tasks and the Washington Psychosocial Seizure Inventory were performed before and after STP administration. Seizure frequency and clinical side-effects were evaluated during a baseline period and after two months of constant therapy. Effects of repeated administration of the neuropsychological battery were assessed by administration of the battery on two occasions at 12-week interval to a randomized subgroup of patients. No practice effect was observed. A trend of improvement (p less than 0.05) in the performance of two tasks requiring sustained attention was noted. Previous side-effects (mainly drowsiness) decreased or disappeared in 7 of 9 patients who became more alert. Six of the nine uncontrolled patients experienced a decrease in seizure frequency equal to or larger than 50 per cent.

Adult↗

[Wilson's disease: demonstration of lesions of the cortex and white matter by MRI].

Lesions of cortex and white matter are present in Wilson's disease in approximately 10 p. cent of cases. Before Magnetic Resonance Imaging (MRI) only post-mortem examination evidenced them. We report the case of a 15 year-old girl in whom Wilson's disease was diagnosed after partial motor epileptic seizures. She later presented with progressive extrapyramidal and pyramidal signs, severe cognitive weakening and disorder of behaviour. MRI clearly showed cortical and subcortical lesions by an enhanced signal (T2 values). It showed as well the classical picture of lesion in the lenticular nuclei. With T1 values it showed an extensive cortical atrophy and a widening of the ventricules.

Adolescent↗