Lithium Group Research Articles

Lithium compliance in alcoholic males: A six month followup study

One hundred alcoholic patients were followed at monthly outpatient clinics for 6 months. Half were assigned low to moderate doses of lithium carbonate and half to chlordiazepoxide (10 mg tid) (active placebo). Drinking behavior and medication compliance were monitored at monthly clinics. After 6 months 52% of the lithium and 44% of the chlordiazepoxide patients were medication compliant. Of the 48% remaining in the lithium group, 14% did not return for a single visit while 14% came only once. Twenty percent came to clinic regularly; however they had never taken the medication as assigned. Of the 56% non-compliant chlordiazepoxide patients, 16% did not attend a single clinic; 24% came only once or twice and the remaining 16% attended clinics regularly although they were never medication-compliant. Drinking days and the percentage of patients reporting abstinence for one or more months were determined for medication compliant patients and for patients who attended clinic regularly but who did not take medication. Data were analyzed by Kruskal-Wallis one way analysis of variance tests. While lithium and chlordiazepoxide compliant patients tended to report fewer mean drinking days per month (4.6 and 4.8 respectively) than the non-medication group (6.9) these differences were not significant; however, compared to 44% in the non-medication group, 60% of the lithium patients and 58% of the chlordiazepoxide patients reported having significantly more months of abstinence ( p < .05). These results do not show that lithium is differentially efficacious in reducing alcohol consumption.

Diurnal variations in serum lithium and renal lithium clearance in rats given lithium as a single small dose or as multiple high doses.

Clearance determinations were carried out in three groups of rats: A high lithium group given food to which 70 mmol/kg of lithium were added for 4-6 weeks leading to a mean serum lithium concentration of 0.85 mmol/l, a low lithium group given food to which 15 mmol/kg of lithium were added for two days before the clearance period leading to a mean serum lithium concentration of 0.22 mmol/l, and a group given the same food without lithium. The sodium and potassium contents of the food were kept high in order to avoid lithium-induced development of negative sodium balance and excessive polyuria. The rats were housed in four rooms with 6-hour displaced 24-hour light-dark cycles. The results showed that high doses of lithium led to a significant increase of the lithium clearance and the urine flow. Small amounts of lithium influenced neither the clearance values nor the urine flow. All renal variables were increased by about 50-100% during the dark period. The serum lithium concentration was least influenced by the diurnal rhythm. It is concluded that serum lithium concentrations measured at any time of the day are fairly representative of the 24 hours. A lithium clearance measured during daytime is valid for this period only. Long-term lithium treatment leads to an increase of the renal lithium clearance but does not diminish the normal diurnal rhythm of the kidney function.

An ultrahigh vacuum reaction chamber/transfer mechanism attached to an Auger electron spectrometer for the study of the reactions of clean lithium surfaces

An ultrahigh vacuum reaction chamber/transfer system is described which is used for the production of clean lithium and other soft group I metals. The system is used to study the reactions of clean lithium surfaces with small molecules of interest in electrochemical applications. Auger electron spectroscopy, in a spectrometer coupled to this chamber, shows that the product of the reaction of SO2 with the clean Li surface is a combination of Li2S and Li2O in a 1 : 2 ratio. The transfer system/reaction chamber also allows for the study of the rates of reaction of small molecules with the clean surface. Mechanical scraping of the metal transforms the passive surface into the active, clean state. Study of the SO2/Li reactions at a variety of temperatures (made possible by the special temperature control in the reaction chamber) shows a low activation energy for the dissociation reaction (2–5 kcal/mol).

No change in rat cerebral cortex calmodulin content following chronic treatment with lithium, reserpine, imipramine, and lithium combined with reserpine or imipramine.

Rats were treated 2-3 weeks with lithium, reserpine, imipramine, and combinations of lithium with reserpine or imipramine. Lithium was given in the diet, while the other drugs were dissolved in 0.9% saline and given intraperitoneally twice daily. The control and lithium groups received only vehicle injections. Twenty-four hours after the last injection the rats were decapitated and the cerebral cortex dissected. The tissue was sliced and the noradrenaline-stimulated cyclic AMP accumulation determined or the tissue was homogenized and centrifuged at 10,000 X g for 30 min. and the calmodulin content determined in the pellet and the supernatant. Reserpine treatment was found to cause an 50% increase in the noradrenaline-stimulated cyclic AMP accumulation, while treatment with imipramine and the combination lithium-imipramine decreased the noradrenaline-stimulated cyclic AMP accumulation by 40%. The tissue content of calmodulin was, however, found unaltered by all treatments.

The responses to water deprivation in lithium-treated patients with and without polyuria.

1. Urine osmolality and plasma and urine arginine vasopressin (AVP) were measured before, during and at the end of 23 h of water deprivation in four groups of subjects. There were eight non-polyuric manic-depressive patients taking lithium (the lithium group), seven manic-depressive patients taking other psychotropic drugs but not lithium (the other drug group), seven healthy subjects (the control group) and three lithium-treated patients with polyuria (the polyuric lithium group). 2. The lithium group had a resistance to the effect of AVP on the renal tubule with a fivefold increase in AVP excretion at a given urine osmolality. However, their water homoeostasis was intact as they lost no more weight during water deprivation than did the control group. 3. The relationship beween urine osmolality and AVP excretion has been defined from these results and the effect of lithium treatment on it has been characterized. The results suggest that lithium competitively inhibits the effect of AVP on the renal concentrating mechanism but does not decrease the ‘theoretical’ maximum urine osmolality. 4. The other drug group had a high basal urine flow which was due to a primary increase in water intake. The responsiveness of the renal concentrating mechanism to AVP was the same in this group as in the control group. 5. The polyuric lithium group had the highest basal urine flow and lost the greatest amount of weight during water deprivation. Neither urine osmolality nor AVP excretion was at a maximum in the basal state, as both increased during water deprivation. These relationships between urine osmolality and AVP excretion indicated a much greater resistance to AVP than in the other lithium-treated patients. 6. We suggest that these patients are polyuric as they become thirsty and drink before their AVP secretion increases to levels high enough to overcome the resistance to AVP. The results suggest, however, that in the basal state their water intake may be more than the minimum determined by the resistance to AVP.

Humoral autoimmune phenomena during long-term lithium treatment with special reference to thyroid autoantibodies

In a retrospective study, 58 outpatients under long-term therapy with lithium were examined with regard to humoral autoantibodies. Fifty-five schizophrenic outpatients under neuroleptic treatment served as controls. We examined antithyroidal antibodies (TAK, MAK), smooth muscle antibodies (SMA), antimitochondrial antibodies (AMA), and antinuclear antibodies (ANA). In the lithium group there was a significant higher prevalence of antithyroidal antibodies (33%) as compared to the control group (9%). Ten patients out of 19 patients with antithyroidal antibodies showed MAK as well as TAK; moreover we found a characteristic pattern: MAK greater than or equal to TAK. All lithium-treated patients were euthyroid. Five patients out of the group with antithyroidal antibodies had goiter, three showed temporarily elevated serum concentrations of basal thyroid-stimulating hormone (TSH). We did not find such elevated levels of TSH in the group of eight patients with goiter but without antithyroidal antibodies. There was neither a correlation between the examined parameters and the lithium serum concentration nor the additional psychotropic medication. Our results indicate a significant higher prevalence of antithyroidal antibodies under long-term therapy with lithium as compared to a psychiatric control group. We do not consider these autoimmune phenomena as relevant pathogenetic factors.

Lithium and Granulocytopenia during Induction Treatment of Adult Acute Lymphoblastic Leukemia

Twelve adult patients with acute lymphoblastic leukemia (ALL) received lithium carbonate, 300 mg, three times a day during induction treatment. They were compared to 12 similar patients consecutively treated with the same induction regimen; patients and controls were comparable for age, degree and presence of splenomegaly, hemoglobin level, blast cell count, polymorphonuclear (PMN) cell count and platelet count at diagnosis. All patients developed a severe neutropenia. PMN count at nadir was slightly higher in the lithium group, but not at a level of statistical significance (p = 0.100). The median number of days with PMN less than 1 x 10(9)/liter was 4 in the lithium group and 14.5 in the non-lithium group (p = 0.014), while the median number of days with PMN less than 0.5 x 10(9)/liter was 0 and 2 days, respectively (p = 0.004). Duration of thrombocytopenia was similar in the 2 groups and so was the remission rate; 2 infective episodes occurred, one in the lithium group and one in the controls.

Effect of chronic lithium treatment on twenty four hour variation in plasma and red blood cell lithium and sodium concentrations, drinking behavior, body weight, kidney weight, and corticosterone levels

This study tested the hypothesis that lithium alters the phase relationships of various 24-hour rhythms. Six point 24-hour patterns were measured throughout a 12 hour light/12 hour dark cycle from separate groups of individually housed adult male wistar rats maintained for six weeks on ad lib water and either 1) Normal lab chow, 2) Lab chow supplemented with 50mM/KG of lithium chloride, or 3) Lab chow supplemented with 50mM/KG of sodium chloride. Plasma lithium levels were 0.7–1.0 mEq/1. The sodium diet had no effect on any of the variables measured relative to normal controls. Plasma but not red blood cell lithium levels demonstrated a 24-hour rhythm with higher levels during darkness. Serum and red blood cell sodium levels did not differ among the diets and showed no 24-hour variation. Lithium treated rats weighed signficantly less than controls and had significantly heavier kidneys per 100 grams of body weight than controls. Resting plasma corticosterone levels demonstrated the expected 24-hour pattern in all groups, however, the lithium group evidenced higher levels during the middle of the dark hours than either control group. Water consumption also demonstrated a 24-hour rhythm. Lithium animals consumed far greater quantities of water than controls and this behaviour became increasingly exaggerated over the duration of the study. The data are interpreted as suggesting that lithium broadens the peak of twenty four hour rhythms such that normal elevation in these measures appear earlier and last longer.

Structural principles of lithium group III compounds

Structural principles of lithium group III compounds

CHROMOSOME STUDIES OF PATIENTS ON LONG‐TERM LITHIUM THERAPY FOR PSYCHIATRIC DISORDERS

Chromosome studies, including sister chromatid exchange techniques, were performed on blood samples from 23 patients receiving long-term, continuous lithium therapy for psychiatric disorders. Nineteen healthy, age-matched individuals were used as controls. No increase in chromosome damage was detected, when samples from the lithium group were compared with the control group samples.

Lithium carbonate in patients with small cell lung cancer receiving combination chemotherapy

Lithium administration has been shown to attenuate the leukopenia associated with systemic chemotherapy. The results of a randomized trial of lithium in 45 patients with small cell lung cancer who received combination chemotherapy and radiation therapy are reported. Patients randomized to receive lithium were started on 300 mg three times daily for 18 days of every 21 day chemotherapy cycle. Patients who received lithium experienced significantly less mid-cycle leukocyte and neutrophil count depression and spent fewer days with leukopenia and neutropenia than control patients regardless of age or extent of disease. Patients who received lithium spent fewer days hospitalized and fewer days with fever in the presence of severe neutropenia than control patients. The cumulative risk of fever with signs of infection was greater in control patients regardless of age, disease extent or the presence of marrow involvement. Patients who were given lithium received significantly more chemotherapy than control patients. Patient survival was greatest in those with limited disease, in complete responders and in those who received more than 75 percent of their induction chemotherapy although it did not differ between the two study groups. The majority of patients required either reduction or discontinuation of lithium. Those who received lithium continuously demonstrated a higher objective response rate and longer survival than either patients in whom the lithium had to be discontinued or those randomized to the control group. Infection was an important cause of death in the control group and cardiovascular events occurred frequently in the lithium group, but the major cause of death in this patient population remains progressive malignant disease.

Control of seawater composition

We have previously discussed1 the correlations between the seawater/rock partition function KY(sw) (mean concentration of Y in seawater/mean concentration of Y in crustal rock) and the electronegativity function QYO[=(xY–xO)2 where x is the electronegativity of the subscripted element]2. The parameter QYO, which is a measure of the ionic interaction between the element Y and oxygen, was used to extimate the tendency of Y to become incorporated in the oxide-based mineral lattices which constitute most marine particulate matter. The nature of the correlations between KY(sw) and QYO (Fig. 2, ref. 1) led us to suggest that the partitioning of an element between seawater and crustal rock is controlled predominantly by its solid state chemistry with solution chemistry playing a secondary part. More recent estimates of the composition of mean world river water and mean crustal rock3 significantly improve the correlations described earlier and provide fresh data on the concentrations of the lanthanides in these reservoirs. Here we compare the chemistry of the lanthanides with that of alkali and alkaline earth metals with a similar electronegativity (the ‘lithium group’ Li, Mg, Ca, Sr, Table 1) to confirm that solid state chemistry plays a major part in controlling the composition of seawater.

Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia

Twenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.

Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia

AbstractTwenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.

Changes in learning, memory, and mood during lithium treatment

In a double-blind study the effects of a 14-day lithium medication (dosage: 24 mval/day to 36 mval/day) were investigated. The subjects were 24 healthy male volunteers. The effect of lithium on their mood, ability to learn nouns, and memory of the words learnt was measured after 2 hours and 14 days. In spite of a relatively low mean plasma lithium level on the 14th day (0.54 +/- 0.15 mmol/l), the lithium volunteers assessed themselves after 2 weeks of treatment as significantly less relaxed, less active, less socially involved, more bored, and more tired than the placebo group. As to learning, the lithium group showed only a slight impairment of performance compared with the placebo groups. As to memory, there was a significant difference in free recall over 2 weeks: the lithium group remembered fewer words than the placebo group. Additional motivation of free recall over 2 hours was ineffective. It is discussed whether lithium changes spontaneous initial action and thereby the will to act. This could be interpreted as a change in the production of the characteristics of experience and behaviour.

Mianserin and Lithium in the Prophylaxis of Depression

Forty-one out-patients with a history of at least three attacks of depressive illness were randomly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets, or to lithium tablets once daily plus placebo mianserin tablets. After one year, the dosage of mianserin was increased to 30 mg t.d.s. for a further six months. All but three of the patients had previously been stabilized on prophylactic lithium therapy. Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT. The overall affective morbidity index, calculated from global rating, showed no significant difference between drugs, but the index of the mianserin group was higher in the second six months than in the first. The lithium group showed no such change. Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness.

Studies of silyl and germyl Group VI species. Part II. Bis(methylgermyl) and bis(dimethylgermyl) chalcogenides and related species

Comparative reactions of some halogenogermanes with lithium(I), lead(II), and organosilicon Group VI species have been investigated, leading to the efficient syntheses of the chalcogermanes of the formula (MenH3−nGe)2E, where E = O, S, Se, Te; n = 0 → 3. The spectroscopic properties of the new bis(methylgermyl) and bis(dimethylgermyl) chalcogenides are discussed. Germanethiols and germaneselenols, viz. MenH3−nGeEH (E = S, Se; n = 0, 3) are isolated as intermediates in the reaction of digermoxanes with H2E and from equilibrium mixtures of (MenH3−nGe)2E with excess H2E. Evidence is presented for the condensation of the chalcogermanes to species of the type MenH3−nGe(EGeH3−nMen)2 (n = 1, 2) and for the elimination of metallic selenium or tellurium giving digermanes of the type (MenH3−nGe)2 (n = 1, 2).

Effects of lithium salts on memory.

Thirteen patients diagnosed as having affective disorders, and who were taking lithium, were compared with drug-free controls on short-term and long-term memory tasks. There was some indication that patients on lithium may show an impairment of short-term memory at fifteen-second delay intervals, and possibly enhanced long-term recall of difficult material. Further comparison with results obtained from six patients on tricyclic antidepressants seemed to reduce the possibility that the lithium group's scores were a function of their psychiatric status. As the group sizes were small, all the findings need to be replicated.

Pharmacological Aftercare for Homogeneous Groups of Patients

In a study to evaluate the effectiveness of specific pharmacological treatment groups, former VA inpatients who have similar diagnoses and respond satisfatorily to drug treatment join a Prolixin group, a lithium group, or an affective disorder group. In monthly meetings patients learn about their illness, the importance of the taking medication as prescribed, and possible side-effects; they also receive psychological support. The 85 patients who joined the groups during the first 12 months attended 87.3 per cent of the sessions. Twenty per cent of them were rehospitalized, about half of them because they did not take medication as prescribed. The authors believe the groups are an economical and effective way to provide aftercare.

Effects of alpha methyltyrosine and parachlorophenylalanine on open field behavior in rats given tranylcypromine stereoisomers and lithium carbonate

Parachlorophenylalanine (PCPA) and alpha methyltyrosine (AMT) were used to study the roles of serotonin and catecholamines in hyperactivity produced by the stereoisomers of Tranylcypromine (d-Tc and l-Tc) in male Wistar rats fed a normal diet (control groups)or a diet containing lithium carbonate (lithium groups). Components of locomotor activity were measured in an open field. Lithium decreased ambulation. d-Tc increased ambulation and caused jerky side-to-side movements. PCPA and AMT prevented the effect of d-Tc on ambulation while only PCPA prevented the effects of d-Tc on movement. l-Tc increased ambulation. The effects of l-Tc on ambulation were potentiated by PCPA and prevented by AMT. Rearing was increased by l-Tc and d-Tc in rats given lithium. PCPA and AMT prevented the effects of l-Tc and d-Tc on rearing in lithium groups. The findings suggest that the roles of serotonergic and catecholaminergic mechanisms differ for components of open field behavior in control rats and rats given lithium.