Effects Of Lithium Research Articles

The Management of Chronic Behavior Disorders in Mentally Retarded Adults with Lithium Carbonate

The authors review the medical literature and present two case histories regarding the efficacy of lithium carbonate in the treatment of chronic behavior disorders in mentally retarded adults. They conclude that the available data lend tentative support for the use of lithium to manage behavior disorders in retarded individuals which are characterized by lifelong hyperactivity, aggressiveness, and/or self-mutilation. They recommend that, when lithium is used for this indication, a blood level of approximately 1.0 mEq/1 is necessary, and that all patients be given a drug-free trial once a therapeutic effect has been achieved in order to assess the continued need for treatment. Etiological issues, a possible mechanism of action involving lithium's effect on CNS serotonergic activity, and areas for future research are discussed.

Pharmacokinetics of gentamicin during exchange transfusions in neonates

6. Steinherz P, Rosen G, Ghavimi F, Wollner N, Wang Y, and Miller D: Improved leukocyte counts after chemotherapy with lithium carbonate, Proc Am Soc Clin Onc 20:439, 1979. 7. Ghavimi F, Exelby P, Jereb B, Scott BF, Lieberman PH, and Kosloff C: The multidisciplinary treatment for advanced stages of embryonal rhabdomyosarcoma in children, JNCI (in press). 8. Snedecor GW, and Cochran WG: Statistical methods, Ames, Iowa, 1976, Iowa State University Press, p 128. 9. Tisman, G, Herbert V, and Rosenblatt S: Evidence that lithium induces human granulocyte proliferation: Elevated Serum vitamin BI~ binding capacity in vivo and granulocyte colony proliferation in vitro, Br J Haematol 24:767, 1973. 10. MaUoy NL, Zauber NP, and Chervenick PA: The effect of lithium on blood and marrow neutrophils, Blood 52:228, 1978. 11. Rothstein G, Clarkson DR, Larsen W, Grosset BI, and Athens JW: Effect of lithium on neutrophil mass and production, N Engl J Med 298:178, 1978. 12. Rossof AH, and Coltman CA: The effect of lithium carbonate on the granulocyte phagocytic index, Experimentia 32:238, 1976. 13. Shenkman L, Borkowsky W, Holzman RS, and Shopsin B: Enhancement of lymphocyte and macrophage function in vitro by lithium carbonate, Clin Immunol Immunopathol 10:187, 1978. 14. Cohen MS, Zakhireh G, Metcalf JA, and Root RK: Granulocyte function during lithium treatment, Blood 53:913, 1979. 15. Harker WG, Rothstein G, Clarkson D, Athens JW, and Macfarlane JL: Enhancement of colony-stimulating activity production by lithium, Blood 49:263, 1977. 16. Morley DC, and Galbraith PR: Effect of lithium on granulopoiesis in culture, Can Med Assoc J 118:288, 1978. 17. Tisman G: Lithium carbonate protection against druginduced leukopenia in lymphosarcoma patients, J Int Res Commun 2:1509, 1974. 18. Catone R, Kaufman J, Mittelman A, and Murphy GP: Attenuation of myelosuppression with lithium, N Engl J Med 297:452, I977. 19. Charron D, Barrett AJ, Faille A, Alby N, Schmitt T, and Degos L: Lithium in myeloid leukemia, Lancet 1:1307, 1977. 20. Greco FA, and Brereton HD: Effect of lithium carbonate on the neutropenia caused by chemothearpy: A preliminary clinical trial, Oncology 34:153, 1977. 21. Lyman GH, Williams CG, and Preston D: A prospective randomized study of the effect of lithium carbonate on the granulocytopenia and incidence of infection associated with intensive chemotherapy and radiation therapy for undifferentiated small cell bronchogenic carcinoma, Blood 52:228, 1978. 22. Stein RS, Hanson G, Koethe S, and Hanson R: Lithiuminduced granulotosis, Ann Intern Meal 88:809, 1978. 23. Stein RS, Flexner JM, and Graber S: Lithium and granulocytopenia during induction therapy for acute myelogenous leukemia, Blood 52:277, 1978. 24. Tiefenbach A, Konja J, Potkonjak-Sesko M, and Mestrovic B: Effect of Li~CO3 on leukopenia in children during treatment of acute leukemia, Lijec Vjesm 99:163, 1977.

The effect of lithium carbonate on leukopenia after chemotherapy

To evaluate the efficacy of lithium carbonate in ameliorating leukopenia, 37 patients (3 to 26 years old, mea (less than or equal to 1,000/mm3) over 40% of the time were designated at random on the last day of 82 separate chemotherapy courses to receive lithium or no treatment. Four could not take the drug because of the size of the capsules. There were 39 controls and 39 patients given lithium. Blood levels were maintained at 0.2 to 1.2 mEq/1 (median 0.7). The median drop of WBC in the treated group was 3,400/mm3 with a nadir of 1,800/mm3 vs 5,000 and 1,400, respectively, for the untreated patients (P LESS THAN 0.01). Eight patients (21%) in the lithium-treated group became severly leukopenic (less than or equal to 1,000/mm3) while 14 (36%) in the control group became leukopenic to that extent. Twenty-four patient days were spent with the WBC less than or equal to 1,000/mm3 after lithium and 57 days in the control group. Three patients required admission for 24 hospital days for fever while leukopenic after lithium, whereas seven patients spent 62 days in the hospital in the control group. Lithium reduces the period of leukopenia after chemotherapy during which time the patients may acquire infections.

The biological effects of lithium

Lithium is a simple metallic ion yet it has a dramatically beneficial effect on a major form of serious mental illness, manic-depressive psychosis. It is this unique combination which stimulates great interest as well as research activity into lithium's biological effects, which Michael Sheard describes here.

The effect of lithium carbonate on lymphocyte, granulocyte, and platelet function

The effect of lithium carbonate on lymphocyte, granulocyte, and platelet function

Lithium's effect on depression clarified

Manic-depressive illness may have 20 different causes, says Barbara Ehrlich of the University of California's medical school in Los Angeles. lithium makes a thousand things change in the body. So which of these things causes the difference? Ehrlich isn't the only one who wonders. It's been 30 years since the Australian physician John Cade discovered that lithium salts could control the violent mood swings of his manic-depressive patients. Lithium carbonate now has become the drug of choice for a large fraction of manic-depressives. Yet scientists still don't know exactly what lithium is doing. During the past six or seven years, however, they've started to find out. For instance, they think that manic-depressive illness almost certainly is a hereditary disease that produces some kind of biochemical defect. And lithium probably interacts with the transport system in cellular membranes, the same system that controls the body's natural levels of sodium, potassium, calcium, and magnesium ions. ...

Possible Mechanism of Lithium's Effect in Bronchial Asthma

Possible Mechanism of Lithium's Effect in Bronchial Asthma

Conformational influences on brain tryptophan hydroxylase by submicromolar calcium: opposite effects of equimolar lithium.

Tryptophan hydroxylase from rat midbrain, EGTA-pretreated and dialyzed, manifested allosteric properties with respect to its substrate tryptophan, cofactor tetrahydrobiopterin, and the calcium ion. Kinetic studies suggest two preferred enzyme conformations in the presence of low concentrations of the cosubstrates: a higher affinity form manifesting hyperbolic substrate kinetics, induced by submicromolar (0.4--0.8 microM) calcium in vitro and cocaine in vivo, and a lower affinity form exaggerating cooperativity with respect to substrate, induced by submicromolar (0.4 to 0.8 microM) lithium in vitro and lithium in vivo. Lithium's effect on serotonin biosynthesis may be due to its antagonism of the positive effector influence of calcium on tryptophan hydroxylase, either as a negative effector or by blocking the calcium site.

Electron microscopic observations of renal lesions caused by lithium carbonate: Hypertrophy of endothelial and epithelial cells

The effects of lithium carbonate on the ultrastructure of the rat kidney were studied. Fifteen male rats of the Sprague-Dawley strain were given aqueous lithium carbonate by mouth, 74mg/kg/day. These rats were killed on days 5, 10 and 15. Six control rats were given NaCl solution equivalent in volume and tonicity to the lithium dosage. Blood analyses were performed on both experimental and control animals. Test animals with a serum level of 0.5mEq/L showed marked hypertrophy of endothelial and epithelial cells in the glomeruli. The capillary lumens and urinary spaces were almost completely occluded by these enlarged cells. Among the prominent features of these cells were the hypertrophy of the Golgi apparatus and an increase in the rough endoplasmic reticulum. Similar proliferation of the Golgi apparatus was also observed in the epithelial cells of the proximal, distal and collecting tubules.

Effect of lithium carbonate on memory processes of bipolar affectively ill patients.

The effect of long-term lithium carbonate treatment on parameters of immediate, short-, and long-term memory was examined in a group of bipolar affectively ill patients. The lithium treatment group recalled significantly fewer words across trials on a verbal learning task than a group of bipolar affectively ill patients receiving no medication. The ability to consistently recall material for which prior learning had been demonstrated was also decreased and accounted for most of the variance in total number of words recalled. Possible mechanisms of effect are discussed.

Morbidity suppressive effect of lithium carbonate in cycloid psychosis.

The possible morbidity suppressive effect of lithium carbonate on cycloid psychosis has been investigated in 30 patients who had suffered from recurrent episodes. The patients were followed up from 1 to 8.5 years after starting lithium treatment. In the analysis, patients were divided into those who took lithium regularly and those who took it irregularly, the division being based on the lithium plasma levels at the periodic control examinations. The study, which is of the so-called mirror tye, supports the hypothesis that well-conducted lithium maintenance treatment has a favorable morbidity suppressive effect in patients suffering from cycloid psychosis.

LITHIUM CARBONATE AND NEUROMUSCULAR BLOCKING AGENTS

The effects of lithium carbonate on the responses to five neuromuscular blocking agents were evaluated in dogs anesthetized with halothane (1 per cent) and N2O (60 per cent) in O2. Latency (time from first twitch-height depression to maximal blockade), maximal twitch-height depression, and times to return to 50 per cent and 100 per cent control twitch tension were measured before and after intravenous infusion of lithium carbonate (1 mg/kg/min for one hour) during neuromuscular blockades produced by succinylcholine, decamethonium, gallamine, d-tubocurarine, or pancuronium. Lithium prolonged the latencies of neuromuscular blockades produced by 0.1 mg/kg succinylcholine and 0.1 mg/kg decamethonium by 248.1 per cent and 49.0 per cent, respectively, but had no effect on latency produced by 0.02 mg/kg pancuronium. The times for return to 50 per cent of control twitch height were prolonged by 69.5, 40.0, and 120.1 per cent, respectively. Lithium had no effect on latency or duration of blockades produced by 0.15 mg/kg d-tubocurarine and 0.6 mg/kg gallamine, but enhanced maximal twitch-height depressions produced by 0.9 mg/kg gallamine and 0.02 mg/kg pancuronium by 22.9 and 9.9 per cent, respectively. Twitch tensions decreased 5-10 per cent over three hours in three dogs receiving lithium infusion without relaxants. Twitch tension was depressed 0-2 per cent in three dogs after five hours of anesthesia in the absence of lithium or relaxants. Lithium prolonged the time required for neostigmine to reverse neuromuscular blockade produced by pancuronium in two of three dogs from a mean of 60 seconds to 135 seconds.

The action of lithium carbonate on the sleep-waking cycle in the cat

The therapeutic effect of lithium carbonate on manic-depressive psychosis is now universally recognized. In view of this positive action on the cyclic endogenous manifestations, it was interesting to investigate the possible effects of lithium on the sleep-waking cycle in the cat. Polygraphic recording from three adults cats was carried out during 24 h periods before, and on different days after, beginning treatment with lithium carbonate. With low doses (30 and 50 mg/kg/day), important morphological changes were observed 5 days later while a new balance of the sleep-waking stages occurred. The EEG of each stage was characterized by slowing and amplitude increase of the different frequencies. The rhythms which appeared in long runs during quiet wakefulness and paradoxical sleep (PS) in the somaethetic cortex (mu rhythm) and the visual areas (alpha rhythm) were increased, slowed and almost continuously present. From the quantitative point of view, the percentage of time of deep slow wave sleep (DSWS) was increased from 38% to 55%. Conversely, the waking and PS times were both reduced, the latter from 18% to 10%. In contrast with human data, the mean duration of PS episodes was unchanged. Furthermore, lithium induced a slight dissociation between EEG activity and waking behaviour. With toxic dose (90 mg/kg/day) all the above changes were again observed, but more conspicuously. During wakefulness and SWS, bursts of generalized paroxysmal events appeared, in frequent association with a myoclonic jerk. SP became atypical and its percentage of time was drastically reduced.

The Effect of Lithium Carbonate on the Cognitive Functions of Normal Subjects

The responses of 24 normal male subjects were compared after weeks of placebo administration and two weeks of lithium carbonate administration (mean serum lithium level, 0.9 mEq/liter) on a series of tasks of intellectual function, aesthetic judgement, and semantic creativity. This was a placebo-controlled, split-half crossover, double-blind design. There were no significant changes on semantic creativity or aesthetic perception measures following lithium carbonate maintenance. There were lithium carbonate-related performance deficits on three of five performance tasks concerned with cognitive and/or motor functions. The deficit is probably due to a lithium carbonate-induced slowing of performance, consistent with our previous report of subjective effects in normal subjects. The implications of slowing on possible behavioral mediating mechanisms by which lithium carbonate exerts its clinical effects are discussed.

The Effect of Lithium Carbonate on Affect, Mood, and Personality of Normal Subjects

Data reflecting affect, mood, and personality attributes of 23 normal men were compared after two weeks of placebo administration and two weeks of therapeutic serum lithium levels (mean, 0.91 mEq/liter). The study was a placebo-controlled, split-half crossover, double-blind design. Affect and mood were measured by three self-rating instruments, independent rater observation, and by the subjects' "significant others." Two personality inventories were administered. Substantial affect and mood changes are induced by lithium carbonate. Lethargy, dysphoria, a loss of interest in interacting with others and the environment, and a state of increased mental confusion were reported. No generalized effects were found in the responses to ther personality inventories.

Lithium carbonate and neuromuscular blocking agents.

The effects of lithium carbonate on the responses to five neuromuscular blocking agents were evaluated in dogs anesthetized with halothane (1 per cent) and N2O (60 per cent) in O2. Latency (time from first twitch-height depression to maximal blockade), maximal twitch-height depression, and times to return to 50 per cent and 100 per cent control twitch tension were measured before and after intravenous infusion of lithium carbonate (1 mg/kg/min for one hour) during neuromuscular blockades produced by succinylcholine, decamethonium, gallamine, d-tubocurarine, or pancuronium. Lithium prolonged the latencies of neuromuscular blockades produced by 0.1 mg/kg succinylcholine and 0.1 mg/kg decamethonium by 248.1 per cent and 49.0 per cent, respectively, but had no effect on latency produced by 0.02 mg/kg pancuronium. The times for return to 50 per cent of control twitch height were prolonged by 69.5, 40.0, and 120.1 per cent, respectively. Lithium had no effect on latency or duration of blockades produced by 0.15 mg/kg d-tubocurarine and 0.6 mg/kg gallamine, but enhanced maximal twitch-height depressions produced by 0.9 mg/kg gallamine and 0.02 mg/kg pancuronium by 22.9 and 9.9 per cent, respectively. Twitch tensions decreased 5-10 per cent over three hours in three dogs receiving lithium infusion without relaxants. Twitch tension was depressed 0-2 per cent in three dogs after five hours of anesthesia in the absence of lithium or relaxants. Lithium prolonged the time required for neostigmine to reverse neuromuscular blockade produced by pancuronium in two of three dogs from a mean of 60 seconds to 135 seconds.

Effect of lithium carbonate on the neutropenia caused by chemotherapy: a preliminary clinical trial.

Lithium carbonate (Li2CO3) increases circulating polymorphonuclear leukocytes (PMN) and perhaps granulopoiesis in man. 25 patients with advanced malignancies ingested Li2CO3 during a cycle of intermittent combination chemotherapy. Weekly hemoglobin, platelet, total white blood cell (WBC) and lymphocyte counts in the evaluable patients were not significantly different from cycles before and after the Li2CO3 cycles. However, the mean absolute PMN nadir while on Li2CO3 was 26% and 40% higher than the control cycles before and after Li2CO3 respectively. When compared individually, the PMN nadirs were significantly higher during the cycle with Li2CO3, than before (p = .05) or after (p = .05). The clinical and biological significance of this observation is presently unclear.

Felty's syndrome: Effect of lithium on granulopoiesis

The effect of lithium carbonate upon granulopoiesis was studied in eight patients with Felty's syndrome. Absolute granulocyte counts increased in all patients receiving 900 mg lithium carbonate daily for six weeks. Increased urinary and serum granulocyte colony-stimulating activity was observed in all patients during lithium therapy. A causal relationship between increases in colony-stimulating activity and increased granulocytes is postulated.

Clinical effects of lithium carbonate on depression.

Summary1. Therapeutic effects of lithium carbon ate were studied on a total of 55 cases comprising 15 cases of involutional melancholia, 23 cases of monopolar depression and 17 of bipolar depression.2. Lithium carbonate was found to be effective to seven cases (47%) of involutional melancholia, 14 cases (61%) of monopolar depression, and nine cases (53%) of bipolar depression, indicating no significant difference among these three groups.3. There was observed no correlation between the characteristics of symptoms and the therapeutic effect in depressive states.4. The serum lithium concetration in the lithium responder was 0.47±0.13 mEq/1 and that in non‐responder 0.55 ±0.14 mEq/1, showing no significant difference between the two groups.5. Lithium carbonate has been found to be effective in the treatment of depressive states. Therefore, it requires further studies using the double‐blind controlled method for clarification of its therapeutic effects.

The effect of lithium carbonate on the ultrastructural transformation of kidney mitochondria

Lithium carbonate has been shown to cause swelling of mitochondria in the distal portion of the nephron of rat kidneys. The present study determined the ADP:O and respiratory control ratios of isolated kidney mitochondria from lithium-treated rats and their ability to undergo ultrastructural transformation while in state IV respiration (absence of phosphate acceptor, ADP). The kidney mitochondria isolated from the animals treated with the 10 or 30 mg/kg/day lithium carbonate dosage showed no changes in the ADP:O ratio at day 12 when compared to control values. However, by day 60 both dosages caused a decrease in ADP:O ratio. The kidney mitochondria isolated from the animals that received the 100 mg/kg/day lithium carbonate dosage showed a decrease in ADP:O ratio by day 12 and a further decrease by day 40. Control kidney mitochondria respiring in state IV underwent ultrastructural transformation from a condensed to orthodox configuration. Some kidney mitochondria from the lithiumtreated rats transformed from the condensed to orthodox configuration while respiring in state IV but they continued to swell. Other mitochondria stayed in the condensed configuration. More mitochondria seemed to swell and undergo degeneration at the higher lithium dosage and the longer time periods of the experiment.