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Biomedical subjects

A M Heudes

Publications and source records attributed to A M Heudes.

7 recordsLinked to original sources

[Muscular damage during isotretinoin treatment].

BACKGROUND: The effect of isotretinoin on muscle is considered to be uncommon and benign. We analyzed the files of all our patients given isotretinoin over a 5-year period and determined the incidence and gravity of its effect on muscles. MATERIALS AND METHODS: Sixty treatments with isotretinoin were studied. Myalgia and elevated CPK observed at the pretherapeutic consultation and each month or 2 months thereafter were recorded. RESULTS: Muscle symptoms were noted in 60 p. 100 of the cases: myalgia in 51 p. 100 and elevated CPK in 41 p. 100. In this group, male sex (H/F = 2.6) and sports activities (70 p. 100) were found more often. In 5 patients, CPK level was 5 times the normal, defining rhabdomyolysis. One patient interrupted treatment because of persistently high CPK levels. DISCUSSION: Myalgia and elevated CPK signal skeletal muscle involvement. These signs were more frequent in our series than in reports in the literature, probably because we systematically looked for them. Besides use of isotretinoin, one case of viral infection and sports activities, no other explanatory cause could be found. Isotretinoin could have a potentializing effect on other myotoxicity inducers (drugs, infection, fever, muscular exertion...). The benign nature of the muscle effect appears to be validated although there were some patients who had persistent and/or severe signs.

Acne Vulgaris↗

Monitoring of 8-methoxypsoralen during extracorporeal photochemotherapy: evidence for a "first-dose" effect.

Therapeutic monitoring of 8-methoxypsoralen (8-MOP) was studied in 12 patients (age range 43-85 years, weight range 48-76 kg) treated for Sezary's syndrome by extracorporeal photochemotherapy (ECP) for 14-41 months. Before the beginning of each ECP cycle (2 sessions on consecutive days at about 4-week intervals), a blood sample was drawn to determine the 8-MOP plasma concentration 2 h after drug ingestion. Plasma 8-MOP levels were measured using a high-performance liquid chromatography method with spectrophotometric detection. Monitoring parameters (dose, 2-h plasma 8-MOP concentration) showed important interindividual and intraindividual variations. The 8-MOP dose ranged from 0.57 to 1.04 mg/kg. Intraindividual variations of 2-h 8-MOP levels ranged from 21% to 75%. Of the 652 measurements, 13% were < 100 ng/ml, the therapeutic threshold for effective ECP; in three of the seven patients, increasing the dose obtained levels exceeding the therapeutic threshold, i.e, the absorption was not saturable. Orthogonal regression analysis between plasma 8-MOP concentrations measured in two consecutive ECP sessions showed a first-dose effect: the 2-h plasma 8-MOP concentration was significantly lower after the first administration than after the second (approximately 1.26-fold). Because 8-MOP has been proven to be a potent suicide inhibitor of drug metabolism in rats and humans, it is possible that 8-MOP had an inhibitory effect on its own metabolism within the therapeutic dose range for ECP, which would explain in part the inter- and intraindividual variability in 8-MOP kinetics and first-dose effect.

Adult↗

In vitro kinetics of 8-methoxypsoralen penetration into human lymphoid cells.

Extracorporeal photochemotherapy (ECPC) requires ex vivo UVA irradiation of blood lymphocytes during the time of the theoretical peak 8-methoxsalen (8-MOP) concentration. The aims of this study were to determine the mechanism of cellular uptake of 8-MOP, its possible saturation and the time needed to reach maximal concentration (Tmax) in lymphoid cells. 8-MOP was measured by liquid chromatography in the supernatant of lymphoid cell suspensions incubated with a known amount of 8-MOP. The kinetics of cellular uptake were determined and showed that equilibrium had already been reached after 2 min and remained constant for at least 60 min. The uptake was independent of temperature (4, 25 and 37 degrees C) and was proportional to the 8-MOP concentration in the supernatant. This indicated that 8-MOP penetrated into lymphoid cells by passive diffusion, rather than by active transport or facilitated diffusion, and was thus a non-saturable process. In addition, intracellular metabolism was negligible. These findings demonstrated that the plasma and lymphocytic Tmax were reached simultaneously and statistical analysis showed them to be significantly correlated, thereby validating the standard ECPC protocol for drug ingestion and lymphocyte irradiation.

Humans↗

[Acquired disseminated elastolysis of the mid-dermis].

A young woman in a good health noticed the occurrence of inelegant wrinkled plaques on her trunk and limbs. The histological aspect was particular in so far as there were no layers of elastic fibres left in the middermis. None of the classical diagnoses could be accepted. Five similar cases have been reported in the literature and make it possible to discuss a new entity among cutaneous elastolysis.

Adult↗

[Neurotrophic ulcerations in the area of the trigeminal nerve in Wallenberg's syndrome].

We report two new cases of neurotrophic ulceration of the trigeminal nerve associated with Wallenberg syndrome, and we present the six cases published since the first description of the neurologic syndrome, in 1895. This peculiar etiology supports the argument for the dominant physiopathologic hypothesis: ulcerations due to multiple microtraumatisms caused by the thermoalgic anesthesia.

Aged↗