The Clinical investigator
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The Clinical investigator · Oct 1994
Multicenter Study Clinical TrialLow-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group.
There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines, thus protecting the host from its own defence reactions. In severe sepsis and septic shock cortisol levels are usually elevated, but some patients may have relative adrenal insufficiency. This may contribute to the overwhelming systemic inflammatory response syndrome. ⋯ The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock. From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases. A randomized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients.
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The Clinical investigator · May 1994
Case ReportsMyotonic dystrophy and limb girdle muscular dystrophy in one family.
A family is reported in which a 29-year-old woman showed the clinical features of myotonic dystrophy while her 26-year-old brother presented with the clinical picture of limb girdle syndrome. In the affected female, direct genetic testing for the specific myotonic dystrophy mutation on chromosome 19 revealed abnormal expansion of a repeat unit containing the three nucleotides cytosine, thymine, and guanine (CTG)-typical for myotonic dystrophy-while her diseased brother displayed two normal alleles. ⋯ The number of CTG repeats in the diseased women was approximately tenfold higher than in her asymptomatic relatives who revealed an abnormal allelic pattern. The increase in CTG repeats with transmission to a subsequent generation in this family was paralleled by a dramatic increase in the severity of myotonic dystrophy.
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The Clinical investigator · Dec 1993
ReviewThe pharmacogenetics of the selective serotonin reuptake inhibitors.
Citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are selective serotonin reuptake inhibitors (SSRIs), which are thought to act as antidepressants through their ability to inhibit presynaptic serotonin reuptake in the brain. The elimination of the SSRIs proceeds predominantly via oxidation catalyzed by cytochrome P450 in the liver. Paroxetine and fluoxetine are potent inhibitors of cytochrome P4502D6 and hence may cause serious interactions with drugs metabolized by this isozyme, notably tricyclic antidepressants, some neuroleptics, and some antiarrhythmics. ⋯ Citalopram and fluoxetine are administered as racemates, but practically nothing is known about the stereoselective metabolism of the two drugs. Citalopram is partially metabolized via the mephenytoin oxidation polymorphism, and paroxetine is partially metabolized via the sparteine/debrisoquine oxidation polymorphism. The pharmacogenetic differences in the oxidation of the SSRIs themselves are probably of no clinical relevance.
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The Clinical investigator · Nov 1993
Comparative StudyDifferent inhibitory effect of etomidate and ketoconazole on the human adrenal steroid biosynthesis.
The narcotic agent etomidate and the antimycotic drug ketoconazole are known to block steroid biosynthesis in man. To study the different effects of these imidazole derivatives on human adrenal steroid biosynthesis we incubated slices of human adrenal glands with 3H-labeled precursors and increasing concentrations of etomidate or ketoconazole (0-2000 microM). After extraction the labeled metabolites were separated by thin-layer chromatography and quantified by scintillation counting. ⋯ Both imidazole drugs showed a similar strong inhibitory effect on the activity of 17 alpha-hydroxylase (IC50 6-18 microM) and 16 alpha-hydroxylase (IC50 4-8 microM) and did not affect 21-hydroxylase. These in vitro data indicate a predominant inhibitory effect of etomidate on corticosteroid biosynthesis by relative selective inhibition of 11 beta-hydroxylase and of ketoconazole on the adrenal androgen biosynthesis by a predominant inhibition of C17,20-desmolase. This differential inhibitory effect of etomidate and ketoconazole on human steroid biosynthesis may be of clinical importance for a possible therapeutic use of these imidazole derivatives in endocrine disorders.