Pharmacoclinical value of the study of lithium cycles during 24 hours]

One cannot base a posology only upon morning lithiemy which turns out to be an unreliable criterion. It is useful to appreciate therapy equilibration through lithiemic cycle i.e. and every two hours dosage among patients on lithium carbonate or gluconate. Certain patients with quite an insufficient lithiemic morning level may be well equilibrated during day time. Lithiemy variations during the day are constantly reliable with the same patient. The study of nycthemeral variations among lithium salts treated patients allows us to understand some pathological subphenomena : intermittent tremor, subconfusional transitory onsets. Lastly lithiemic cycles allow comparison between lithiemy variations in manic or depressive relapses.     

Norepinephrine metabolism in mouse heart after lithium and rubidium treatment.

This report describes the effects of treatment with lithium (Li), rubidium (Rb) and sodium (Na; 1 mEq/kg/day) for 7 days on norepinephrine (NE) turnover in mouse heart. The effects of several drugs which modify the uptake and storage of NE were also studied in similarly pretreated mice. A method based on the combustion of tissue tritium to tritiated water was used to assay tritiated l-norepinephrine (l-NE-3H) concentrations in individual hearts. The rate of decline of tissue tritium concentrations in groups of pretreated mice maintained at ambient temperature (23--24 degrees C) or in the cold (4--5 degrees C) was determined. The results indicate that, compared to Na, Li and Rb did not modify the tritium turnover rate in mouse heart. Pretreatment with Li or Rb did not modify the uptake of tritiated NE in the heart. The effects of desipramine. cocaine, bretylium and chlorpromazine on NE uptake were not altered by the alkali ions. Further, pretreatment did not modify NE release by tyramine, metaraminol and guanethidine. These studies suggest that Li and Rb do not modify NE uptake, release and storage in mouse heart.     

24 hours plasma tryptophan levels in patients with endogenous depression (author's transl)

The variations of total and free tryptophan during 24 hours were measured in patients with endogenous depression. In depressive patients, plasma tryptophan levels are significantly lower than in control subjects. Plasma tryptophan levels in depressive patients are low during the night (when high at the same hours in normal subjects). The physiopathological mechanisms of such alterations and their possible influence on symptomathology are described.     

Response of a brain protein fraction 24 hours after training in rats.

The aim of the study was to follow the amount and incorporation of 14C-valine into separate, soluble protein fractions of the hippocampus, thalamus, and visual cortex of rats from 0 to 72 hr after training. The behavioral test consisted of reversal of handedness with training twice daily for 25 min for 2 days, followed by a 5-day intermission without training, and a final session of 24 min. The animals were injected intraperitoneally with 14C-valine 30 min before sacrifice and taken 0, 24, 48, and 72 hr after last training. After 24 hr, and only at that time, double incorporation values and increased amounts were observed in a protein fraction, No. 6 from the front, in all three brain areas of the trained rats compared to active controls. At 48 hr this protein fraction was at control level.     

Concurrent lithium administration results in higher haloperidol levels in brain and plasma of guinea pigs

The effects of lithium (Li) on brain and plasma levels of concurrently administered haloperidol (HAL) were investigated. One group of guinea pigs (n=12) was also treated with HAL for 11 days, but Li was added during the last 5 days of treatment. At the end of treatment, the HAL + Li group had significantly higher brain and plasma levels of HAL than the group treated with HAL alone. The correlation coefficient between plasma and brain HAL (0.97) indicated that plasma levels of HAL determine brain levels of this drug.     

Labeling of rabbit cerebral cortex poly(A) RNA 24 hours after a single electroconvulsive shock

The labeling of poly(A)-associated RNA in the cerebral cortex of rabbits was studies 24 h after a single electroconvulsive shock. At this time, the animals received an injection of [³H]uridine subarachnoidally and were killed 1 h later. The data indicate that in this phase of the postconvulsive period the fractionation patterns of newly synthesized nuclear and microsomal poly(A)⁺ RNA had returned to the control distribution. However, the labeling of microsomal poly(A)⁺ RNA increased compared with the control.     

Plasma lithium levels and side effects during administration of a slow release lithium sulphate preparation (Lithium lipett C) and lithium carbonate tablets

Lithium lipett C (ACO Läkemedel, Sweden), a new lithium sulphate preparation with slow release achieved by dissolution in fat which releases 90% of its lithium content within less than 4 hours when treated with intestinal juice was compared with lithium carbonate tablets. In spite of a fairly swift release, there was a smoother plasma lithium curve with the lipett C than with the carbonate tablets. The frequency of the side effect diarrhoea with the lipett C administered twice a day (7 out of 19) was higher than with carbonate tablets administered three or four times a day and similar to that with a previously studied, slower releasing lithium sulphate lipett (7 out of 20). The diarrhoea is probably caused both by the effect of the lithium ion on distal parts of the intestinal canal and by the sulphate ion. The frequency of other side effects was similar with the lipett C and the carbonate tablets. The advantages of the lipett C in the form of dosing twice a day are counteracted by the drawbacks of the rather frequent side effect diarrhoea.     

The effect of lithium administration on LH response in healthy volunteers

1. As part of a systematic investigation of the effects of lithium administration on neuroendocrine function we investigated the luteinizing hormone (LH) response to luteinizing hormone releasing hormone (LHRH) of healthy males. 2. In healthy volunteers after 3 weeks of therapeutic doses of lithium the LH response to LHRH was significantly increased in comparison with the responses prior to lithium administration. 3. An attempt is made to explain these findings by underlying neurotransmitter changes.     

Cortisol levels in plasma after dexamethasone administration and the nosology of depression

The authors have studied 89 depressed patients diagnosed according to three different systems: DSM-III, Kiloh and Garside, Winokur. They administered 1 mg of Dexamethasone at 11 pm; blood samples were taken at 8 am and 8 pm the next day. They find the most significant differences in cortisol levels according to the DSM classification whereas there are no significant differences according to the Winokur classification. They refer the great variance obtained in the endogenous groups to a high incidence of suppressors in these non-suppressor groups. In 26 non-depressed patients, they found 10 non-suppressors. According to the authors, these results demonstrate the importance of DST and other biological tests in the reformation of nosology in psychiatry.     

Assessment of suicide risk 24 hours after psychiatric hospital admission.

Of 69 patients admitted to a hospital because of suicide risk, 30 (44 percent) were completely free of suicidal ideation 24 hours after admission. Scores on the Scale for Suicide Ideation at the time of admission distinguished patients who continued to have suicidal ideation 24 hours later (the sustained-ideation group) from those who did not (the transient-ideation group). Patients in the transient group were more likely than those in the sustained group to have made a suicide attempt during the week before admission. At admission patients in the sustained group were more likely to have psychotic symptoms and to report a family history of psychiatric illness.     

EEG during combined administration of lithium and neuroleptics

Some investigators have indicated the clinical usefulness of EEG monitoring during treatment with lithium-neuroleptic combination. Nine patients who were maintained on this combined therapy, were investigated with EEG. The authors report their negative findings.     

Changes in cerebral calcium, sodium and potassium after single or repeated administration of lithium in the rat

A single administration (IP) of lithium chloride in the rat induces a decrease in erythrocyte calcium, proportional to the lithium level (p less than 0.01) and a diminution in cerebral calcium (p less than 0.001) which is accompanied by decrease in cerebral sodium and potassium levels (p less than 0.001). Repeated administration (IP + VO) has the same cerebral effects. The authors report that the reversible decrease in calcium, sodium and potassium, resulting from an increase in cerebral lithium levels, can be demonstrated on sampling at 1.30 and 3 hours (IP), or at 12 hours (VO). These results are relevant to the treatment of manic illnesses using calcium antagonists.     

Circadian analysis of plasma cortisol levels before and after dexamethasone administration in depressed patients

Pituitary-adrenal regulation in healthy subjects and in depressed patients is very dynamic. Interpretation of results of the 1-mg dexamethasone suppression test has usually depended on the result of a single blood cortisol level measurement obtained in the morning or afternoon. We analyzed circulating cortisol concentrations by obtaining blood samples at 20-minute intervals for 24 hours before and after dexamethasone administration in depressed patients. The results illustrate the variability in patterns of escape from the effects of dexamethasone among depressed patients; they also indicate the influence of the sampling time on the test results and thus on the relationship of the test result to various clinical classifications. Finally, these results provide the basis for understanding the consequences of alternative sampling strategies.     

Indications of lithium plasma levels in professional practice. Average of a 7-year follow-up]

With a mean follow-up duration of 7 years, the retrospective analysis of 57 charts of lithiotherapy shows that: Better results are observed when the lithium blood level reactus 0.87 mmoles/l. In that case, the best lithiotherapy indication is the major recurrent long cycles depression. We also propose as lithiotherapy indication in order of efficacy: 1--The maniac-depressive psychosis (P.M.D.) in its mixed form. 2--The schizo-affective troubles. The curative and preventive lithium efficacy is on favour of the diagnosis of recurrent endogenous psychiatric disease.     

Transient hyperkinesia after a single intravenous perfusion of diphenylhydantoin. Report of a case associated with nontoxic plasma levels of diphenylhydantoin.

Transient hyperkinesia was observed in a 16-year-old epileptic and mentally retarded patient after a single intravenous perfusion of diphenylhydantoin (DPH). No clinical signs of DPH intoxication were associated with the movement disorder. Repeated plasma anticonvulsant level determinations never showed toxic concentrations of DPH. Since a few spontaneous episodes of hyperkinesia had been observed before, the DPH intravenous perfusion could have unmasked a preexisting latent movement disorder in our patient. However, neuroradiological investigations failed to demonstrate the existence of any anatomical damage of the basal ganglia, and HVA as well as 5-HIAA levels measured in the CSF with the probenecid technique were within the normal range 2 months after cessation of hyperkinesia. HVA and 5-HIAA levels have also been measured in the CSF during the period with hyperkinesia; the results are discussed with reference to previously published data concerning cerebral monoamine metabolism in drug-treated epileptic patients.