Destructive beta 2-microglobulin amyloid arthropathy of the cervico-occipital hinge in a hemodialyzed patient.
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Biomedical subjects
Publications and source records attributed to P Netter.
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Ketoprofen was assayed in tissues of surgical patients after mechanical grinding of the tissue in liquid nitrogen; the fine powder obtained allowed the drug to be determined by HPLC in the same way as for liquid samples. The method was applied to the study of ketoprofen diffusion into the tonsillar tissue of 15 patients after a single intramuscular injection of ketoprofen (100 mg). A correction was made for blood contamination after hemoglobin determination.
Plasma and cerebrospinal fluid (CSF) concentrations of indomethacin have been determined in 52 patients hospitalized for nerve-root compression pain. Samples of blood and CSF were collected at the same time in each subject, 0.5 to 12 h after a single intramuscular injection of 50 mg indomethacin. Analgesic effect was assessed by the absolute and percentage variation in Huskisson's visual analogue scale between dosing and sampling. According to its high lipid solubility, indomethacin rapidly crossed the blood-brain barrier, being detected in CSF 0.5 h after administration. After attainment of equilibrium within 2 h, the CSF level exceeded the free plasma level. Since the drug was extensively bound to serum albumin (99.7 +/- 0.1%), this phenomenon may represent a slight degree of binding of indomethacin in CSF. The analgesic activity was not related to either the plasma or CSF concentration of indomethacin.
The catalytic core of the sunY intron of bacteriophage T4 is separated from its 3' exon by 837 nucleotides, most of which are part of an open reading frame (ORF). Here, we report that transcripts truncated within the sunY ORF self-splice in vitro to a variety of sites in the segment immediately 3' of the core. Recognition of these proximal splice sites is shown to depend on (1) the presence on the intron side of a terminal G, which must not be part of a secondary structure; and (2) the ability of the penultimate intron nucleotide to base-pair with a 3' splice site-binding sequence (3'SSBS) located within the core. The counterpart of the 3'SSBS can be identified in most group I introns. The possible significance of such alternative splicing events for in vivo expression of intron-encoded proteins is discussed.
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Most NSAIDs are chiral molecules: they exist under 2 configurations of non-superimposable mirror images which are termed enantiomers or optical isomers or optical antipodes. Direct or indirect (resolution) methods are used to separate this equal mixture of compounds. Some of the enantiomers of the NSAIDs are able to undergo chiral inversion from the inactive R(-) to the active S(+) form. The pharmacokinetics in terms of absorption, distribution, metabolism, protein binding and elimination may be different for the 2 enantiomers, leading to interindividual variability in clinical response and drug toxicity.
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Conflicting results on clinical effects of serotonergic drugs gave rise to this investigation on the relationship between depression-related personality factors and effects of the 5-HT uptake inhibitor fluoxetine on psychomotor functions and emotional states. In a double-blind, balanced, crossover design, 24 healthy male subjects divided according to scales of "Experiencing of Stress" and "Neuroticism," were tested with a single dose of 60 mg fluoxetine or placebo. Reaction time and feelings of activation and energy of highly neurotic or stressed subjects were deteriorated by fluoxetine while emotionally stable subjects were improved by the drug. The findings were interpreted in terms of personality related differences in 5-HT neurotransmission and receptor sensitivity.
A clinical, biological and radiological prospective study was carried out in 21 patients over 70 years of age and treated by hemodialysis or chronic ambulatory peritoneal dialysis (CAPD) to evaluate the frequency and specificity of rheumatic diseases observed in aged chronic renal failure patients. Some are caused or favored by old age and are not in any way related to renal failure and its replacement therapy. Such was the case with arthrosis which was present in 85% of patients, ankylosing vertebral hyperostosis (14%), Paget's disease (5%) and gouty arthritis (10%). Elsewhere there is an implication between abnormalities due to aging and those linked to renal failure and/or dialysis, some of which can worsen or accelerate others. Secondary hyperparathyroidism seems less frequent in the elderly than in the young patients. Common vitamin dependent osteomalacia should not be neglected because it can be either prevented or efficiently treated. Osteoporosis is another important factor in osteopenia. Extra-skeletal calcifications are frequent: periarticular calcifications (38%), chondrocalcinosis (14%) and disc calcifications (24%). Dialysis arthropathy comprising: carpal tunnel syndrome, erosive lesions of large and intermediate limb joint articulations and destructive spondylarthropathy is observed in 43% of patients after an average dialysis period of 44 months. The advent of this complication seems to be quite early in the elderly, as compared to the young population, which confirms the role played by age as a favoring factor.
A study was designed to answer the questions if low doses of ethanol would reduce stress induced increases in heart rates, if covariations would be observed between ethanol induced changes in heart rates and changes in emotional states and mental performance and if tolerance to ethanol or other personality factors would influence the ethanol induced cardiac effects. Forty-four male students with a history of high and low alcohol consumption according to questionnaire scores were matched for extraversion and neuroticism and then assigned to a group receiving either 0.8 g/kg of ethanol or a placebo drink. A stress condition of mental arithmetic was applied prior to and 45 minutes after ingestion of the drink. Heart rates and ratings of emotional states by adjective check lists were recorded before and after each stress session. A significant reduction of stress induced heart rate increases in both high and low drinking groups but no ethanol dependent change of resting heart rates were observed. Reductions of autonomic stress response by ethanol were weakly but positively correlated to respective reductions of affective stress responses and impairment of the quality of mental performance. High trait anxiety subjects seemed to benefit more from ethanol with respect to reductions of cardiac and emotional arousal than low anxious subjects.
Protein binding of sodium salicylate in synovial fluid and in serum from 23 inpatients with rheumatic diseases were studied, ex vivo, by equilibrium dialysis. Scatchard model with two classes of sites was used as a mathematical tool. At therapeutic concentrations, protein binding of sodium salicylate was significantly higher in serum than in synovial fluid. The ratio of areas under the curves for bound concentrations for synovial fluid to that for serum was 0.867. This difference was attributed to the hypoalbuminemia observed in the synovial fluid; for a given molar ratio of drug to albumin, or in other words, for the same amount of available drug per mole of albumin. The number of sites occupied was the same in the two biological media.
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An isocratic high-performance liquid chromatographic procedure is presented for the screening of plasma samples for the presence of sixteen non-steroidal anti-inflammatory drugs. Detection was achieved simultaneously at two wavelengths (254 and 370 nm) and the purity of the eluted peaks was tested using absorbance ratios at the two wavelengths; identification could thus be effective without interferences from substances of other pharmacological classes. The drugs were extracted simultaneously with diethyl ether after acidification and separated from each other on an octadecyl reversed-phase column using only one eluent, acetonitrile-0.3% acetic acid-tetrahydrofuran (36:63.1:0.9, v/v). The recovery, precision and reproducibility of the method were satisfactory as it allowed the determination of the drugs from infra- to supratherapeutic concentrations.
It is well known that the yeast Saccharomyces cerevisiae can be affected by mutations, called 'petite colonie', which correspond to the loss of the major part of the mitochondrial DNA and the concomitant amplification of the remaining sequence, the basic repeat unit (BRU). We describe here a new phenomenon, the internal overamplification (IOA), due to the differential amplification (up to 20-fold) of short sequences within the BRU. These IOAs are very stable and stimulate the recombination. We discuss here the possible mechanisms giving rise to the appearance and maintenance of the IOAs within the BRU and their effect on the recombination process.
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The pharmacokinetics of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cerebrospinal fluid (CSF) is of clinical interest as it may be related to some of their properties and side-effects. Two types of NSAIDs can be described with respect to their concentration and time course in CSF: in the first type, the transfer across the blood-brain barrier seems to be controlled by simple physico-chemical factors. These drugs (oxyphenbutazone, indomethacin, ketoprofen) are characterized by a high lipophilicity. At steady state, their free plasma concentrations correspond to their CSF concentrations. The second group consists of more hydrophilic compounds (salicylates); there is no correlation between plasma concentrations and CSF concentration. Further investigation needs to be carried out on CNS side-effects and the antialgesic activity of salicylates in relation on their CSF distribution.
The "tension reduction hypothesis" of ethanol was investigated with respect to stress- and ethanol-induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty-two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress-related emotional arousal, it did not affect stress-induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. "Biochemical tension reduction" (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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