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18 subjects, affected by manic-depressive psychosis, have been studied during lithium therapy, in order to control EEG. changes in relation to erythrocyte lithium concentration. According to data obtained, significant relation subsistes between EEG. changes and erythrocyte lithium concentration.
The distribution of lithium in the rat brain following chronic i.p. injections of lithium chloride has been determined by a radiographic dielectric track registration technique. The study indicated significant differences in lithium distribution in various areas of the brain. Consistently high levels were observed in the neocortex and putamen, and low concentrations in the cerebellum and white matter structures such as the corpus callosum and basis pedunculi. Intermediate levels were found in the thalamus, hypothalamus, septal nuclei, dentate gyrus, hippocampus and substantia grisea centralis.
We recently reported the synthesis of a new quaternary hydride in the lithium-boron-nitrogen-hydrogen quaternary phase diagram with the approximate composition LiB0.33N0.67H2.67 having a theoretical hydrogen content of 11.9 wt %. This new compound forms by the reaction of appropriate amounts of lithium amide (LiNH2) and lithium borohydride (LiBH4) and releases greater than 10 wt % hydrogen when heated. A small amount of ammonia, 2-3 mol % of the generated gas, is also released. We now report a study of hydrogen and ammonia release from the series of reactant mixtures (LiNH2)x(LiBH4)1-x, where x=0.667 corresponds to the composition LiB0.33N0.67H2.67. We measured hydrogen and ammonia release amounts as a function of composition and found that maximum hydrogen and minimum ammonia release do occur for x=0.667. We also present evidence for an additional new quaternary phase and for two possibly metastable phases in this system.
We present accurate ionization potentials (IPs) for small lithium clusters and hydrogenated lithium clusters (n=1-4), computed using coupled-cluster singles and doubles theory augmented with a perturbative correction for connected triple excitations [CCSD(T)] with the correlation-consistent weighted core-valence quadruple-zeta basis set (cc-pwCVQZ). In some cases the full CCSDT method has been used. Comparison of computed binding energies with experiment for the pure cationic lithium clusters reveals excellent agreement, demonstrating that previous discrepancies between computed and experimentally derived atomization energies for the corresponding neutral clusters are due to the use of an inaccurate experimental IP for Li(4). The experimental IP for Li(4) falls 0.43 eV below our theoretical adiabatic value of 4.74 eV, which should be a lower bound to the measured IP. Our recommended zero-point corrected adiabatic IPs for Li, Li(2), Li(3), Li(4), LiH, Li(2)H, Li(3)H, and Li(4)H are 5.39, 5.14, 4.11, 4.74, 7.69, 3.98, 4.69, and 4.05 eV, respectively. Zero-point vibrationally corrected CCSD(T) atomization energies per atom for Li(2) (+), Li(3) (+), Li(4) (+), LiH(+), Li(2)H(+), Li(3)H(+), and Li(4)H(+) are 0.64, 0.96, 0.90, 0.056, 1.62, 1.40, and 1.40 eV, respectively.
Lithium intoxication is a frequent condition with sometimes severe symptoms. Despite repeated plasma measurements, it is not always possible to prevent serious side effects because they can occur at therapeutic plasma levels. Several aspects of the lithium metabolism are reviewed and illustrated by two case reports.
Eighteen patients were studied with behavioral ratings and the somatosensory (SER), auditory (AER), and visual (VER) cerebral-evoked response and quantified EEG before and during lithium carbonate treatment. The amplitude of early positive SER components and most AER components increased during treatment, but VER did not change. The intensity of EEG delta and theta frequencies increased, and the dominant alpha frequency slowed. Before treatment, there were few significant correlations to symptom intensity. Patients with an increase in symptoms on treatment had the greatest increase in EEG delta intensity and the dominant alpha frequency slowed in patients who became more depressed. The EEG slowing in patients with a normal sensorium and the change in cerebral cortical activity after transmission in the somatosensory pathway over just three synapses demonstrate a unique and specific effect of lithium carbonate on brain function.
Five healthy volunteers were treated orally with lithium carbonate, sulphate, or chloride. There were no significant differences in area under time-concentration curves, half-lives, total body clearance or apparent distribution volumes between the various salts, either in plasma or in the RBC compartment. The carbonate salt did show a higher RBC/plasma distribution ratio than the other salts, which might possibly imply greater therapeutic effectiveness of this salt. Some considerations on the tolerability of various lithium salts are discussed.
Patients treated with a combination of lithium (Li) and neuroleptics are reported to be at greater risk for toxicity. Previous findings suggested that treatment with a combination of Li and neuroleptics would increase the lithium ratio (LR) and intraerythrocyte Li levels. We studied 67 bipolar patients who were treated with Li alone (20 patients) or Li combined with haloperidol (17 patients), or Li combined with chlorpromazine (30 patients). Results revealed that the neuroleptic groups showed significantly lower LR and intracellular Li concentration as compared with those on Li alone. There was no significant difference in Li dosage among these three groups. No difference was found among these three groups with respect to mean blood pressure and weight. The number of hypertensive patients in the Li only group was twice as high as that in either of the two other groups, and the LR of the former was significantly higher than those of the latter groups.
Forty-six lithium (Li) patients who had been on Li for about 1-11 years were studied while on Li and after about 3 months (7 weeks-26 months) off Li. Kidney function was compared between patients on Li and the same patients off Li, and, in 32 matched pairs, between patients on and off Li and psychiatric controls. Urine osmolality (U-osmol) was significantly lower, urine volume higher in patients on Li than in controls. Measures of both glomerular and tubular function improved when Li-patients discontinued medication. U-osmol remained somewhat lower than in controls and was negatively correlated with time-on-Li. Although serum creatinine was somewhat higher in Li-patients off Li than in controls, clearance values were not different between the two groups. Long-term lithium treatment causes a permanent reduction of tubular function. Time-on-Li is a risk factor. In this population the reduction was clinically insignificant. In addition, Li treatment causes a reversible reduction of both tubular and glomerular function. The results can probably be generalized to other outpatient Li populations with the same time-on-Li and with U-osmol below 800 mOsm/kg during ongoing treatment.
The value of lithium carbonate as an adjunctive treatment of resistant schizophrenia was tested in a 4-week clinical trial using a single-blind, randomized, consent design. Treatment and control groups were drawn from a population of detained patients in an English special (maximum security) hospital. The 2 groups were comparable in terms of age, sex, severity of symptoms, length of hospitalization and concurrent neuroleptic dosage. The addition of lithium carbonate to the treatment regimen did not result in symptomatic improvement in patients completing the treatment protocol. The ethical and practical difficulties raised by the trial are discussed.
We have collected information about 118 children born to mothers who were given lithium treatment during the first trimester of pregnancy. The data show that the risk of teratogenic effects is lower than one might have expected from some of the studies carried out on rats and mice; they do not answer the question of whether or not lithium is teratogenic in man. The data were collected retrospectively and therefore overestimate rather than underestimate the risk of teratogenicity.
Accidental ingestion of electrical batteries occurs commonly in children. This rarely is associated with severe morbidity and mortality. Significant symptoms can arise due to leakage of alkali or heavy metals from the battery after degradation in the gastrointestinal tract. The main heavy metal of concern in electrical batteries is mercury; this is the first report of ingestion of a lithium battery in a child associated with systemic absorption of lithium.
Lithium was given to eight aggressive, non-manic-depressive female defectives in a doubleblind placebo-controlled study. The group as a whole showed a reduction in aggression scores while on lithium (p greater than 0.01): three patients became less aggressive,one became worse and two were unchanged. Both affective and predatory aggression seemed to be reduced. Two patients had to be withdrawn from the trial at an early stage because of the development of neurotoxicity.
Correlations between the ratio of erythrocyte to plasma lithium (Le/Lp) and clinical status have been reported by some authors and disputed by others. Examination of the literature on Le/Lp and erythrocyte physiology suggests that Le/Lp is determined by peripheral pharmacokinetic parameters and has no direct relationship to central pathophysiology. Because of this, and because of inconsistencies between studies reporting correlations of the ratio with clinical status, such correlations probably cannot illuminate either the pathophysiology of affective illness or the mode of action of lithium.
The incidence of anogenital warts (condyloma acuminatum) is rapidly increasing while there is still no totally satisfactory treatment available. In light of the emphasis of experimental approaches toward the prevention of viral replication and evidence of the antiviral action of lithium salts it was proposed to investigate the efficacy of Topical Lithium Succinate cream (LSC) in the treatment of anogenital warts. A total of 101 patients (42 women, 59 men) were randomized to receive either active or placebo treatment for a period of 4 weeks. Assessment of the number, location, size and area of coverage of the warts was made by the clinician at baseline, weeks 2, 4, 6 and 12. Compliance to the study protocol following cessation of treatment at week 4 was extremely poor. The high drop-out rate after this was felt to invalidate data collected after that point. It was therefore decided that the analysis should concentrate on the treatment period. Of 101 patients entering the trial 51 received active (30 male and 21 female) and 50 received placebo (29 male, 21 female). The primary efficacy variable was percentage change from baseline in the overall coverage of lesions. Over all patients LSC treatment resulted in a reduction of 42% (P<0.02) in the overall coverage of lesions. Separate analyses for male and female patients showed that for males there was a highly significant reduction in the coverage of lesions of 65% (P<0.02). However for females the reduction of 11% was not significant. A possible explanation for this difference between the sexes is that as many of the lesions in the female patients were internal therefore this could lead to difficulty in both application of the cream, and subsequent lesion assessment.
This paper suggests some of the possible advantages of a liquid lithium preparation and describes an open, cross-over, pilot study comparing solid (capsule or tablet) with liquid lithium salt preparations in terms of obtained blood levels and side-effects for a nonmanic-depressive prison population.
The method of obtaining the multi-unit gastrointestinal diffusion system (m-GDS), containing lithium acetate, consists in encapsulating the lithium acetate in a form of microballs and thereafter coating the resulting microballs with a porous membrane which controls the diffusion rats of the drug. For the coating, a water-insoluble polymer (cellulose acetate) and two types of polymer-modifying agents (cetyl alcohol and shellac) were used. In this paper in vitro studies of drug release from the unit in relation to the microballs' coating and mass, and exposed surface area of the capsules are presented. Most in vitro systems provide zero-order dry delivery by appropriate selection of manufacturing parameters.
In 2 patients receiving a long-term lithium carbonate therapy, persistent cerebellar, pyramidal, and extrapyramidal signs were observed, following a febrile pulmonary event. The mechanism of these disturbances is discussed, emphasizing the lithium-neuroleptics interaction as well as the possible role of hyperthermia.