[Diplopia and hypersomnia caused by flunitrazepam].
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Biomedical subjects
Publications and source records attributed to P Netter.
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Serum and cerebrospinal fluid (CSF) concentrations of ketoprofen have been measured in 36 patients hospitalised for sciatica. Diagnostic lumbar puncture was done 15 min to 13 h after a single 100 mg intramuscular dose of ketoprofen. Serum and CSF were sampled at the same time. Free serum concentrations were determined by equilibrium dialysis. Total and free concentrations were assayed by a highly sensitive and specific HPLC method. Ketoprofen rapidly crossed the blood-brain barrier and was detected in CSF 15 min after its administration. The rapid diffusion can be explained by the high lipid solubility of the drug. The CSF level was in equilibrium with the free serum concentration from the second to the 13th hours.
Salicylate kinetics were determined in 28 subjects 25 to 92 years old who received single, oral doses of sodium salicylate (1 gm/1.73 m2). The serum AUCinfinity of total salicylate did not correlate with age. There was a weak positive correlation between the AUCinfinity of free (unbound) drug and age, but there was no apparent difference between the AUCinfinity values of the 15 women and 13 men. Seven of the 16 subjects greater than 70 years of age cleared salicylate at about the same rate as the younger subjects. A comparison of these seven subjects with the nine greater than 70 years old who were slow eliminators of salicylate revealed that the latter group consisted of more bedridden patients and that these patients had somewhat lower serum albumin concentrations, but they did not differ from the more rapid eliminators with respect to serum creatinine or urea nitrogen levels, SGOT, average age, female/male ratio, and average body weight. The serum protein binding of salicylate decreased with increasing age, apparently due mainly to decreasing serum albumin concentrations.
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The effect of D-penicillamine on human bone marrow granulocyte-monocyte precursor cells (CFU-C) is studied in vitro. Bone marrow samples were obtained from 47 donors (40 patients and 7 healthy volunteers) and cultured in semisolid agar in the presence of various concentrations of the drug. We found an inhibitory, possibly dose-dependent, effect of D-penicillamine on colony formation. The pathophysiological mechanism and the clinical relevance of this effect remain poorly understood. These findings, however, emphasize the need for careful monitoring of the granulocyte counts during D-penicillamine therapy.
Silicon-containing particles were observed by scanning electron microscopy (SEM) in synovial fluid samples from patients with crystal-induced or inflammatory synovitis, or both. This material was an artefact produced by the technical procedures, but these particles could be easily differentiated from naturally occurring compounds by their morphology and their composition determined by analytical spectrometry.
In a study using metamizole and placebo as equivalents of a strong and a weak stimulus in a signal detection device female headaches patients show better ability to discriminate the two drug stimuli than males, whereas there is no significant effect with respect to response bias.
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The paper entitled "Configural Frequency Analysis, XXI b. Type analysis of bivariate response curves in hypertensive and normotensive subjects" is concerned with plasma levels of epinephrine and norepinephrine recorded in the course of a mental strain experiment. Plasma level response curves allow to identify univariate and bivariate types of response patterns. "Discriminant" and "association" types of hyper- and normotensives are demonstrated as two alternative ways of interpretation. The types are seen as psycho-endocrinological correlates of psychosomatic induced hypertension.
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In the mitochondrial DNA of Saccharomyces cerevisiae, the genes cob-box and oxi3, coding for apocytochrome b and cytochrome oxidase subunit I respectively, are split. Several mutations located in the introns of the cob-box gene prevent the synthesis of cytochrome b and cytochrome oxidase subunit I (this is known as the 'box effect').-We have elucidated the molecular basis of this phenomenon: these mutants are unable to excise the fourth intron of oxi3 from the cytochrome oxidase subunit I pre-mRNA; the absence of a functional bI4 mRNA maturase, a trans-acting factor encoded by the fourth intron of the cob-box gene explains this phenomenon. This maturase was already known to control the excision of the bI4 intron; consequently we have demonstrated that it is necessary for the processing of two introns located in two different genes. Mutations altering this maturase can be corrected, but only partially, by extragenic suppressors located in the mitochondrial (mim2) or in the nuclear (NAM2) genome. The gene product of these two suppressors should, therefore, control (directly or indirectly) the excision of the two introns as the bI4 mRNA maturase normally does.
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High-angle x-ray diffraction was applied to the study of four meniscal fibrocartilages and 11 articular cartilages from patients suffering from various articular disorders. In eight samples microcrystals were seen, apatite most frequently, CaHPO4 in two instances, calcium pyrophosphate dihydrate (CPPD) in one. These results confirm the association of various crystals in a single joint, and favour their heterogenous partition on collagen fibres.
The goal of this experimental study was to examine the effect on articular tissue of tribasic aluminium phosphate (crystalline and amorphous forms) after intraarticular injection in rabbit and to compare it with that of various phlogistic compounds such as carrageenin, calcium hydrogen phosphate dihydrate and diamond powder, as a control. Synovium and cartilage were studied with light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive micro-analysis (EDM). Crystalline and amorphous aluminium phosphate could induce a synovitis with articular effusion in rabbits. With TEM, lysosomal inclusions of phagocytosed material were observed. Through SEM coupled with EDM, aluminium associated with phosphate was found in cellular elements.
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We studied the concentrations of aluminum in the articular tissues of 5 hemodialysed patients treated with aluminum compounds. Aluminum crosses the synovial barrier, is found in synovial fluid (SF) and accumulates in the joint structures (synovial membrane and joint cartilage). The concentrations found in synovial tissue were 2.7 to 10 times control values, in SF 2.5 to 8 times the control concentrations and in cartilage 2.6 times the control concentrations. Transmission electron microscopy showed localization of aluminum in the lysosomal structures and wavelength dispersive microprobe analysis showed aluminum in cellular components associated with phosphate. The possible toxicity of aluminum to joints merits further investigations.