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Biomedical subjects

A Perrin

Publications and source records attributed to A Perrin.

At least 55 records · Page 3Linked to original sources

[Indications for botulinum toxin in laryngectomy].

The botulinum toxin is a highly potent neurotoxin, used since several years in the treatment of the focal musculary dystonias. We define the laryngeal dystonia as a clinical entity, which is represented by a spasmodic dysphonia or an inspiratory dyspnea without dysphonia, related to a specific dystonia of the thyroarytenoid muscles. The laryngeal functional exploration (i.e. fibroscopy, videostroboscopy, acoustic analysis, computerized voice analysis), the neurological and electrophysiological assessment allow to make diagnosis and evaluation of the therapeutical results of this rare laryngeal neurologic disease which was relatively misunderstood until now. There are several clinical types of spasmodic dysphonia: adductor form (with a jerky voice, pitch beaks, vocal arrests and pneumophonatory incoordination); abductor form (with a breathy voice of very low intensity) and mixed types which can be difficult to identify. Since 1989, we have treated 55 laryngeal dystonias with local intra-muscular botulinum toxin injection: 48 spasmodic dysphonia and 7 inspiratory dyspnea without dysphonia, with hyperactivity of the thyroaryténoïd muscles. We present our therapeutical protocol and results which are good in 87% of cases.

Aged↗

Stridor and focal laryngeal dystonia.

Fibreoptic laryngoscopy in 6 patients with laryngeal stridor showed immobile vocal cords in a paramedian position but no other local cause. Thus a diagnosis of Gerhardt's syndrome, usually ascribed to paralysis of vocal-cord abductor muscles, was made in 3 patients who had no other signs or symptoms of dystonia, and in 3 patients who had multifocal dystonia. Electromyography (EMG) showed evidence of overactivity of vocal-cord adductors, with no evidence of denervation in the abductor muscles. Botulinum toxin injection of the overactive thyroarytenoid muscles abolished stridor. These clinical and EMG findings indicate that Gerhardt's syndrome is not caused by paralysis of vocal-cord abductors, but represents a focal laryngeal dystonia which may be treatable by botulinum toxin injections of vocal-cord adductor muscles rather than by arytenoidopexy or tracheostomy.

Aged↗

Site-specific recombination determined by I-SceI, a mitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus.

The Saccharomyces cerevisiae mitochondrial endonuclease I-SceI creates a double-strand break as the initiating step in the gene conversional transfer of the omega+ intron to omega- DNA. We have expressed a galactose-inducible synthetic I-SceI gene in the nucleus of yeast that also carries the I-SceI recognition site on a plasmid substrate. We find that the galactose-induced I-SceI protein can be active in the nucleus and efficiently catalyze recombination. With a target plasmid containing direct repeats of the Escherichia coli lacZ gene, one copy of which is interrupted by a 24-bp cutting site, galactose induction produces both deletions and gene conversions. Both the kinetics and the proportion of deletions and gene conversions are very similar to analogous events initiated by a galactose-inducible HO endonuclease gene. We also find that, in a rad52 mutant strain, the repair of double-strand breaks initiated by I-SceI and by HO are similarly affected: the formation of deletions is reduced, but not eliminated. Altogether, these results suggest either that the two endonucleases act in the same way after double-strand break formation or that the two endonucleases are not involved in subsequent steps.

Base Sequence↗

[Spasmodic dysphonia. Investigation and therapeutic methods].

We report the successful treatment of three patients with adduction spasmodic dysphonia by direct injection of botulinum toxin into the vocal cord(s). This was achieved under electromyographic control, and this and other otolaryngeal techniques were used to monitor treatment and study this often puzzling condition.

Adult↗

Purification and properties of steroid 17 alpha-hydroxylase from calf testis.

Steroid 17 alpha-hydroxylase has emerged as a key enzyme in steroidogenic cells: (i) it represents the branch point between the 17-deoxy (mineralo) and the 17-hydroxy (gluco) corticosteroid pathways in the adrenal cortex; (ii) the corresponding specific cytochrome (P-450(17 alpha] is highly dependent upon hormonal regulation; and (iii) the enzyme also catalyzes the steroid 17-20 lyase reaction, leading to the major androgens in the testis. As a prerequisite to the study of its regulation in intact cell, 17 alpha-hydroxylase was purified from calf testis microsomal preparations. Following five chromatographic steps, the enzyme was obtained as an apparently homogeneous protein of Mr = 57 kDa upon gel electrophoresis. The procedure yielded a recovery of about 10% as judged by cytochrome P-450 assay. Whereas 17 alpha-hydroxylase specific activity was about 30-fold enriched during the purification, that of the C17-20 lyase was increased by about 6-fold, strongly suggesting that its organelle environment may modulate the enzymatic activity. The purified enzyme yielded a 20 N-terminal amino-acid sequence showing a complete homology with that of its adrenal counterpart and a polyclonal antibody raised against our preparation revealed a 57 kDa protein band in bovine adrenocortical microsomal extracts, upon immunoblotting experiments. It was thus concluded that bovine 17 alpha-hydroxylase activity is supported by highly similar if not identical enzymatic proteins in both testis and adrenal cortex tissues. The purified P-450(17 alpha) preparation is now being used in reconstitution experiments which suggest that microsomal components may contribute to a different expression of the enzyme specificity in its native testis or adrenocortical intracellular environment, respectively.

Amino Acid Sequence↗

Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha-hydroxylase expression in bovine adrenocortical cells.

Transforming growth factor beta 1 (TGF-beta 1) has been shown previously to induce striking alterations of bovine adrenocortical cell steroidogenic functions. One of the major lesions was characterized as a loss of steroid-17 alpha-hydroxylase activity, a key step in the biosynthetic pathway leading to active corticosteroid hormones. The mechanism of this negative effect of TGF-beta 1 on adrenocortical differentiated functions was investigated. It was observed that: 1) bovine adrenocortical 17 alpha-hydroxylase activity rapidly decreased in cells exposed to TGF-beta 1, in a time (10-20 h)-dependent manner; 2) immunoblotting of the corresponding cytochrome P-450(17) alpha showed that the loss of activity was superimposable to the decrease of the cellular protein content; 3) the cell content in 17 alpha-hydroxylase messenger RNA sharply dropped under TGF-beta 1 treatment (70-75% loss within 3-4 h) as determined by Northern blot analysis; 4) TGF-beta 1 inhibited as well the induction of P-450(17) alpha normally observed under adrenocorticotropin treatment; and 5) these TGF-beta 1 effects were selectively directed toward P-450(17) alpha expression, whereas another major steroidogenic cytochrome, i.e. P-450scc, was not affected. These observations showed that TGF-beta 1 is a potent negative modulator of 17 alpha-hydroxylase expression in bovine adrenocortical cells, very possibly at the transcriptional level. TGF-beta 1 (whose gene is expressed in these cells) may thus be examined as a possible autocrine inhibitory factor implied in the regulation of adrenocortical differentiated functions, in balance with ACTH, which represents the major positive signal in this system.

Adrenal Cortex↗

[Treatment of spasmodic dysphonia with botulinum toxin].

Spasmodic dysphonia is a focal laryngeal dystonia, a rare form of dystonia. Videostroboscopy, acoustic analysis, computerized voice analysis and over all electrophysiological analysis allow for the study of the different muscles involved in this dysphonia. There are two types of spasmodic dysphonia: adductor spasmodic dysphonia and abductor spasmodic dysphonia. The most efficient therapy nowadays is the injection of botulinum toxin into the thyroarytenoid muscle under fiberoptic visualization. We report 6 patient's cases of spasmodic dysphonia that we have been treating for about 2 years by direct injection of botulinum toxin in the vocal cords.

Adult↗

A 31P-NMR study of bovine adrenocortical mitochondrial metabolic activities.

High-field 31P-NMR spectroscopy has been used to study the metabolic activities of coupled bovine adrenocortical mitochondria in vitro. These differentiated organelles use oxygen as a substrate to support both oxidative phosphorylation and specific steroid hydroxylation reactions. The NMR technique allowed the resolution of two inorganic phosphate signals, attributed to the matrix and external medium phosphate pools, at low and high field, respectively. These signals were used to calculate the respective Pi concentrations and to obtain the pH of the two corresponding compartments. In addition, the NMR spectra displayed resonance signals corresponding to ADP added to the medium and to ATP synthesized during oxidative phosphorylation. NMR analysis of the mitochondrial perchloric acid extracts identified the major phosphate-containing metabolites, namely NADP+, NAD+, phosphocholine, phosphoethanolamine, sn-glycero-(3)phosphocholine, AMP, ADP, ATP and Pi. Upon addition of ADP and malate to the oxygenated suspension, the kinetics of mitochondrial external Pi consumption and of ATP synthesis, along with the intra- and extraorganelle pH variations could be monitored over time periods of approximately 30 min, in the absence and presence of different steroid hydroxylation substrates. A major observation was that oxidative phosphorylation, which takes place in the absence of steroid, was markedly inhibited as soon as steroid hydroxylation was operating. These observations show the potential of 31P-NMR spectroscopy in the study of metabolic activities of isolated intact mitochondrial organelles. Such an approach appears promising for further determination of the underlying mechanisms in the balance between vital oxidative phosphorylation and differentiated steroid hydroxylation which are under hormonal control in adrenocortical mitochondria as well as in other steroidogenic cell systems.

Adenosine Triphosphate↗

Purification and characterization of the in vitro activity of I-Sce I, a novel and highly specific endonuclease encoded by a group I intron.

Group I intron encoded proteins represent a novel class of site specific double strand endonucleases. The endonuclease activity of this class of proteins has been first demonstrated in vivo for I-Sce I which is encoded by a mitochondrial intron of Saccharomyces cerevisiae. Assays using crude cell extracts have shown that I-Sce I can be used in vitro as a restriction endonuclease potentially useful for recombinant DNA technology owing to its large recognition sequence (18 nucleotides). We report here the purification and the first detailed analysis of the in vitro activity and properties of I-Sce I.

Base Sequence↗

Biochemical and pharmacological consequences of the interaction between methotrexate and ketoprofen in the rabbit.

Severe methotrexate (MTX) toxicity is a proven complication of associations of MTX and non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated the interaction between MTX (50 or 100 mg kg-1) and ketoprofen (KP) (3 mg kg-1 day-1, pretreatment for 8 days) in the rabbit. The drug association induced a reversible increase in blood urea and creatinine. The severity degree of renal dysfunction was significantly related to the MTX dose; it was not modified by prolonged exposure to KP after MTX administration. The biological markers of haematopoietic and hepatic functions were unchanged. Pretreatment by KP induced a marked reduction (70%) in the urinary excretion of the prostaglandin 6-keto-PGF1 alpha. MTX dose-related alterations in MTX pharmacokinetics were also observed with the drug association: at a MTX dose of 100 mg kg-1, the presence of KP significantly reduced the total body clearance, the renal clearance and the fraction of MTX eliminated in urine as compared to controls. An appreciable reduction in the plasma binding of MTX was also noted in vivo when KP was associated. This experimental study confirms the existence of an interaction between MTX and KP and demonstrates its renal origin.

6-Ketoprostaglandin F1 alpha↗

When crisis intervention gets physical.

The only way to control violence may be by using physical intervention techniques. The time to learn these techniques is now--before you need them.

Crisis Intervention↗

[The base of the piriform sinus in the surgical treatment of fistula of the 4th endobranchial pouch. Apropos of 8 cases].

Fistula of the fourth endobrachial pouch, a congenital malformation, can be defined as an abnormal persistence of the canal joining the base of the piriform sinus and the deep surface of the lateral lobe of the thyroid. These fistulae, which have been more clearly understood over the last ten years, still constitute a delicate surgical problem, which is rarely discussed in the literature, based on the detection of their tract at their origin, the piriform sinus. The 8 cases operated at Hôpital Necker since 1981 reveal the variability of their tract, which, according to the authors, warrants an anatomosurgical analysis.

Adolescent↗

[Functional results of ossiculoplasty. Apropos of 216 cases].

Results of 219 ossiculoplasties performed during closed technic tympanoplasties over a 7-year period are reviewed. Ossiculoplasty involved the implantation of ossiculo-tympanic plate homografts, ossicular auto- or homo-grafts or Klein type prostheses. Results are analyzed as a function of disease causing the ossicular lysis, types of mounting and number of operations required. From these are determined etiopathogenic factors and technics providing improved results. Absence of residual inflammation, stability of mounting and use of remaining ossicles are conditions that ensure best results. Contact between columella and tympanic membrane should be as wide as possible, with greater preference therefore for stapes-malleus or foot of stapes-malleus than stapes-tympanic plate or foot of stapes-tympanic plate mountings. These former mountings improve functional gain in a homogeneous manner throughout the frequency range.

Cholesteatoma↗

[D-penicillamine in the treatment of recurrent laryngeal stenosis in children].

Five children with recurrent tracheal stenosis after use of an endolaryngeal calibrator and/or a laryngoplasty were treated with D-penicillamine and chloroquine. The relevant literature relating to biological processes of normal and pathologic healing is reviewed, particularly with respect to the effect of D-penicillamine on collagen synthesis. Decannulation was possible in 4 of the children reported presently, including three in whom medical treatment was combined with use of an endolaryngeal calibrator.

Child↗

[Long-term anatomic results of tympanic homografts. Apropos of 170 cases].

Long-term anatomic results of 170 tympanic homografts performed in the Necker-Enfants-Malades hospital, France between 1977 and 1983 showed high frequency of complications: early perforation (17.7%); late perforation (14%); myringitis (8.5%); recurrence of retraction (7.31%); lateralization (9.4%). These complications are of much higher frequency than after tympanoplasty with autograft, and indications for tympano-ossicular homografts are now limited to total tympanic destruction with absence of handle of malleus.

Adolescent↗

[ORL localizations of Rosai-Dorfman disease. Apropos of 4 cases].

Four cases of Rosai and Dorfman's disease are presented. This adenomegalic sinusal histiocytosis is usually a benign affection even though the appearance and degree of glandular enlargement can suggest malignant disease. A literature review showed 215 cases reported up to the present.

Adolescent↗