Background: Serum free light chain analysis is now well established in the investigation of monoclonal gammopathies. In the UK there has, until recently, been a single supplier of kits for such analysis. Recently, a second method using monoclonal antisera was introduced. We have compared the performance of these two kits in four routine laboratories. Method: Samples submitted for routine analysis (327 samples, 258 [79%] from patients with B-cell lymphoproliferative disease) for serum free light chains were tested by both technologies (Freelite, Binding Site and N Latex FLC, Siemens), according to the manufacturers' instructions. Results: Qualitative data were available by both methods on 313 samples for serum free kappa chains and 324 samples for lambda free light chains. We found poor correspondence of 81% for kappa and 74% for lambda. Five percent of samples were significantly discordant in these assays. Conclusions: These assays perform very differently in clinical practice. They cannot be used interchangeably, especially if monitoring patient responses to therapy.
In human subjects, the acute tryptophan (TRP) depletion (ATD) paradigm has been shown to have effects on mood and cognition. It is assumed that these effects are mediated through the serotonin system. In this study, we have examined the effects of ATD on the central concentrations of the monoamine transmitters, noradrenaline (NA) and dopamine (DA) as well as on serotonin (5-HT). Effects on NA and DA could also affect mood and cognition. Following oral administration of TRP-containing (TRP+) and TRP-free (TRP-) amino acid mixtures, neurotransmitter concentrations and free plasma TRP concentrations were determined by High Performance Liquid Chromatography (HPLC) with electrochemical detection. Free plasma TRP was significantly and substantially reduced (79%) in rats given a TRP- amino acid mixture when compared with those given a TRP+ mixture. ATD also significantly decreased 5-HT and 5-hydroxyindolacetic acid in the frontal cortex, remaining cortex and hippocampus, but did not significantly reduce these in the striatum. Furthermore, ATD did not significantly alter the concentration of NA and DA in any brain region examined. This study demonstrates that the administration of a TRP- amino acid mixture in rats can reduce free plasma TRP to levels comparable to those reported in human studies. These results indicate that behavioural and cognitive changes produced by ATD in preclinical or clinical studies are likely to be due to specific effects on the serotonergic system.
The effects of a series of six ECT treatments were observed on the CSF concentrations of HVA, MHPG, and 5-HIAA in 12 patients suffering from schizophrenia. Four patients were previously neuroleptic drug-free, and eight had received only oral neuroleptic drugs at the same dose for more than 4 weeks. A significant increase in the concentration of HVA was observed after the first ECT treatment but not after the final treatment. No significant changes were observed in the concentrations of MHPG and 5-HIAA. The patients improved clinically, and the results suggest that ECT has important effects on dopaminergic systems.
Previous biochemical and clinical data suggest there may be an interaction between digoxin and lithium. The pharmacodynamics and pharmacokinetics of an intravenous infusion of digoxin were studied in six male subjects before and after 2 weeks treatment with lithium carbonate. The effects of lithium on sodium pump activity, intracellular electrolytes and extracellular electrolytes were studied. No significant interaction between digoxin and lithium was found. No significant effects of lithium on sodium pump activity or electrolyte concentrations were found.
Eleven chronic treatment-resistant schizophrenic in-patients were treated with haloperidol (HPL) or placebo with a fixed ascending dose schedule for 20 weeks. Seven patients relapsed and were withdrawn and five of these re-entered, single-blind, on known active treatment. Two weekly clinical ratings and weekly serum HPL levels were carried out throughout the study. More patients on placebo dropped out and at an earlier stage than those on active treatment but the difference was not statistically significant. Despite wide individual variations in both serum HPL levels and clinical response, these were positively correlated. HPL appeared to be of more value in the prevention of relapse than in symptom reduction. Overall, the clinical response was poor and a 'therapeutic window' could not be demonstrated either for the group as a whole or in any individual patient. There was no additional therapeutic benefit in exceeding serum HPL levels of 20 ng/ml in any of our patients. Since this serum level was achieved by daily doses of 10-40 mg HPL and the relationship between dose and serum level is linear, the use of serum HPL estimations is not likely to be of value in the routine clinical management of treatment-resistant patients.
Fifty-three hospitalized chronic schizophrenic patients were treated with either propranolol, chlorpromazine or placebo in a double-blind randomized trials for up to three months. Propranolol in a usual dose of 640 mg/day, produced marked cardiovascular effects but no improvement in schizophrenic symptomatology relative to placebo. The effects of chlorpromazine were small and inconsistent.
In view of the central side effects of beta‐adrenoceptor blocking agents and their alleged antipsychotic action in the absence of DA receptor blockade, it is important to establish which neurotransmitters are likely to be involved. Previous animal and patient studies have, however, produced conflicting data on this point. The changes in CSF HVA, 5HIAA and MHPG during treatment with propranolol (960 mg/day) in chronic schizophrenic patients were monitored on four occasions over 30 days. Clinical changes were monitored by the Wing and Krawiecka Scales and motor activity was assessed by pedometer. CSF HVA levels were significantly increased by propranolol and the rise continued throughout the 30 day period. There were no significant changes in the other metabolites. There was no evidence of any therapeutic benefit from propranolol treatment in these patients. These findings may explain the central side‐effects and occasional reports of schizophreniform psychosis after propranolol, since an increase in DA turnover occurs without DA receptor blockade.
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