Calcium Concentrations In Patients Research Articles

Requesting patterns for serum calcium concentration in patients on long-term lithium therapy

Long-term lithium therapy is associated with hypercalcaemia in 10-60% of patients, but unlike creatinine and thyroid stimulating hormone (TSH), monitoring by general practitioners of serum calcium for patients on lithium is not a requirement of the Qualities and Outcomes Framework (QOF) of 2004. We aimed to assess requesting patterns for serum calcium in patients on long-term lithium therapy and subsequent diagnosis of hypercalcaemia. We identified 100 patients on long-term lithium therapy, as indicated by regular monitoring of lithium levels in our laboratory for at least 1 year. We determined how many of these patients had had serum calcium analysed, noting the assay date, concentration, source of request and clinical details stated. Forty-three out of hundred patients had serum calcium analysed during the course of their treatment including 28 in the previous 15 months. Twenty-one patients had serum calcium analysed by their GP, including 12 in the previous 15 months. Hypercalcaemia was diagnosed in five patients (11.6%). A significant proportion of patients in whom calcium was checked developed hypercalcaemia on lithium therapy. However, only 12% of the patients had serum calcium requested by their GP in the previous 15 months, which compares unfavourably with TSH and creatinine, for which monitoring approaches 100%. We recommend that serum calcium be checked every 15 months along with creatinine and TSH. This might be achieved by incorporating appropriate targets into the QOF, or by reflective or reflex adding-on of calcium to lithium specimens from patients who have not had calcium analysed in the previous 15 months.

Synthesis of Conjugatable Bisphosphonates for Molecular Imaging of Large Animals

Synthesis of Conjugatable Bisphosphonates for Molecular Imaging of Large Animals

Cinacalcet hydrochloride: calcimimetic for the treatment of hyperparathyroidism

Mineral metabolism disorders, including those related to secondary hyperparathyroidism, affect a large number of patients with chronic kidney disease and are associated with increased relative risk of morbidity and mortality in hemodialysis patients. The traditional therapy of secondary hyperparathyroidism based on vitamin D compounds and calcium-based phosphate binders is often limited by the increase of serum calcium and phosphorus levels limiting the dose that can be given safely, and thus, preventing the attainment of treatment targets. Cinacalcet hydrochloride (Sensipar®, Mimpara®, Parareg®) is the first in a new class of therapeutic agents, the calcimimetics, that increase the sensitivity of calcium-sensing receptors to the extracellular calcium ions, thus lowering parathyroid hormone production and release, decreasing serum calcium and phosphorous concentrations simultaneously. Different randomized, double-blind, placebo-controlled trials evaluated the safety and ability of cinacalcet hydrochloride treatment to improve achievement of target levels of parathyroid hormone, calcium, phosphorus and calcium phosphorus product in dialysis patients. Cinacalcet hydrochloride has also demonstrated to be effective in reducing parathyroid hormone and serum calcium concentrations in patients with primary hyperparathyroidism. On the basis of available data, calcimimetics represent an important innovation and will change the management of mineral metabolism disorders in patients with chronic kidney disease and primary hyperparathyroidism.

Salivary calcium concentration in patients with high incidence of calculus formation

Salivary calcium level was determined in this study in individuals with good oral hygiene who have no repetitive history of calculus accumulation, and in individuals with a history of repetitive calculus formation whether subgingival or supragingival in spite of their attempts in controlling their oral hygiene. Salivary calcium concentration was significantly higher in the second group. Moreover, salivary calcium concentration in this study varied according to age. It is advisable to use alkaline mouthwashes and intensive good oral hygiene to control their calculus formation

Uses and Effectiveness of Pamidronate Disodium for Treatment of Dogs and Cats with Hypercalcemia

Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia, vomiting, diarrhea, lethargy, and depression and contributes to the development of primary renal failure and soft tissue mineralization. Treatment of hypercalcemia includes diagnosis and treatment of the underlying disease process and some combination of extracellular fluid volume expansion by administration of fluids intravenously and administration of glucocorticosteroids, salmon calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may be safe and effective in the treatment of hypercalcemia. The purpose of our study was to characterize the efficacy and safety of pamidronate in the treatment of hypercalcemia attributable to several different disease processes in the dog and cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05‐2.0 mg/kg IV for a variety of disease processes, including neoplasia (n = 4), calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia with chronic renal failure (n = 1). In all the animals, IV pamidronate administration rapidly decreased serum calcium concentrations without evident toxicosis. Two animals received pamidronate several times without obvious toxicosis. On the basis of the findings in our retrospective study, pamidronate may be a safe and effective drug with which to lower both serum total and ionized calcium concentrations in patients with hypercalcemia arising from a wide variety of underlying disease processes.

Uses and Effectiveness of Pamidronate Disodium for Treatment of Dogs and Cats with Hypercalcemia

Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia, vomiting, diarrhea, lethargy, and depression and contributes to the development of primary renal failure and soft tissue mineralization. Treatment of hypercalcemia includes diagnosis and treatment of the underlying disease process and some combination of excracellular fluid volume expansion by administration of fluids intravenously and administration of glococorticosteroids, salmon calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may be safe and effective in the treatment of hypercalcemia. The purpose of our study was to characterize the efficacy and safety of pamidronate in the treatment of hypercalcemia attritutable to several different disease processes in the dog and cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05-2.0 mg/kg IV for a variety of disease processes, including neoplasia (n = 4), calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia with chronic renal failure (n = 1). In all the animals, IV pamidronate administration rapidly decreased serum calcium concentrations without evident toxicosis. Two animals received pamidronate several times without obvious toxicosis. On the basis of the findings in our retrospective study, pamidronate may be a safe and effective drug with which to lower both serum total and ionized calcium concentrations in patients with hypercalcemia arising from a wide variety of underlying disease processes.

The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without haemodialysis.

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in patients with secondary hyperparathyroidism; however, hypercalcaemia, hyperphosphataemia, or both, often develop. Calcimimetic agents, employed in alternative therapeutic approaches, directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands. In this study, patients were given orally 25, 50, and 100 mg doses of the calcimimetic agent KRN 1493 each on two occasions, on the day of haemodialysis and on the day without haemodialysis. In the pharmacokinetic results, because the clearance of KRN 1493 by haemodialysis was much smaller than the systemic clearance, the influence of haemodialysis was not remarkable. In the pharmacodynamic study, on both the days with or without haemodialysis, plasma PTH concentrations decreased in a dose-dependent manner. Serum calcium concentrations decreased in association with the decrease in plasma PTH concentrations. Mild dose-dependent adverse effects (mainly nausea) were seen after the administration of KRN 1493 on both the day of haemodialysis and the day without haemodialysis. We conclude that the pharmacokinetics of KRN 1493 after a single administration were similar on the day of haemodialysis and the day without haemodialysis. KRN 1493 is safe and effective in suppressing PTH secretion and serum calcium concentrations on the day of haemodialysis and on the day without haemodialysis in patients with secondary hyperparathyroidism.

Sodium/lithium countertransport and intracellular calcium concentration in patients with essential hypertension and coronary heart disease

The present study was designed to test the hypothesis that enhanced intracellular calcium signalling and increased sodium/lithium countertransport (Na+/Li+ CT) activity may be associated with coronary heart disease (CHD) in non-diabetic patients with essential hypertension. Platelet-activating factor (PAF)-evoked rises in the intracellular calcium concentration ([Ca2+]i) were measured in Epstein–Barr-virus-immortalized lymphoblasts from 62 hypertensive patients with CHD and 34 patients without CHD. Na+/Li+ CT activity was assessed in erythrocytes from 80 hypertensive patients with CHD and 46 patients without CHD. Baseline values of unstimulated and PAF-stimulated [Ca2+]i were not significantly different between hypertensive subjects with (baseline, 126±5nmol/l; stimulated, 550±43nmol/l) and without (baseline, 125±5nmol/l; stimulated, 654±105nmol/l) CHD. Similarly, Na+/Li+ CT activity was not significantly different between the two groups (patients with CHD, 219±8µmol·l-1·h-1; patients without CHD, 234±10µmol·l-1·h-1). We conclude that intracellular signal transduction, as indicated by PAF-induced rises in [Ca2+]i and Na+/Li+ CT activity, is not associated with an increased risk of CHD in non-diabetic patients with essential hypertension.

Sodium/lithium countertransport and intracellular calcium concentration in patients with essential hypertension and coronary heart disease.

The present study was designed to test the hypothesis that enhanced intracellular calcium signalling and increased sodium/lithium countertransport (Na(+)/Li(+) CT) activity may be associated with coronary heart disease (CHD) in non-diabetic patients with essential hypertension. Platelet-activating factor (PAF)-evoked rises in the intracellular calcium concentration ([Ca(2+)](i)) were measured in Epstein-Barr-virus-immortalized lymphoblasts from 62 hypertensive patients with CHD and 34 patients without CHD. Na(+)/Li(+) CT activity was assessed in erythrocytes from 80 hypertensive patients with CHD and 46 patients without CHD. Baseline values of unstimulated and PAF-stimulated [Ca(2+)](i) were not significantly different between hypertensive subjects with (baseline, 126+/-5 nmol/l; stimulated, 550+/-43 nmol/l) and without (baseline, 125+/-5 nmol/l; stimulated, 654+/-105 nmol/l) CHD. Similarly, Na(+)/Li(+) CT activity was not significantly different between the two groups (patients with CHD, 219+/-8 micromol x l(-1) x h(-1); patients without CHD, 234+/-10 micromol x l(-1) x h(-1)). We conclude that intracellular signal transduction, as indicated by PAF-induced rises in [Ca(2+)](i) and Na(+)/Li(+) CT activity, is not associated with an increased risk of CHD in non-diabetic patients with essential hypertension.

Lamotrigine and the treatment of mania in bipolar disorder

Anticonvulsants, including valproate and carbamazepine, have established efficacy in the treatment of mania. The anticonvulsant, lamotrigine, has been reported to have antimanic and antidepressant efficacy, and mood-stabilising effects in case reports and preliminary open trials. The efficacy and tolerability of lamotrigine has been compared with olanzapine and lithium in a randomised, prospective, controlled fashion over a period of 4 weeks’ treatment in a total of 45 hospitalised patients with DSM-IV-defined mania. Significant improvements of a similar magnitude were observed for all treatment groups and lamotrigine was well tolerated. Mechanisms of action proposed to explain the antimanic activity of lamotrigine include inhibition of voltage-sensitive and use-dependent sodium channels, inhibition of glutamate release and calcium channel blockade. Platelet studies have indicated supersensitivity of glutamate receptors and increased intracellular calcium concentrations in patients with mania. Further clinical and mechanistic studies of lamotrigine use in mania are warranted.

Influence of twenty-five per cent human serum albumin on total and ionized calcium concentrations in vivo.

BACKGROUND: A inverse correlation has been found between changes in ionized calcium concentrations and the addition of albumin in vitro, which may explain adverse cardiovascular effects attributed to exogenous albumin in vivo. The purpose of this investigation was to determine the interaction (if any) between exogenous 25% albumin administration (100 ml given over < 30 min) and calcium concentrations in patients, all but one of whom were in an intensive care unit. RESULTS: There were no significant differences in the ionized calcium concentrations obtained before, at the end and 6 h after the administration of albumin (1.09 +/- 0.23, 1.06 +/- 0.22, 1.06 +/- 0.21 mmol/l, respectively). Similarly, there were no significant differences in the total calcium concentrations between these same time periods (2.03 +/- 0.18, 2.05 +/- 0.20, 2.08 +/- 0.23 mmol/l, respectively). CONCLUSIONS: In patients receiving infusions of 25% albumin, it appears that circulating calcium concentrations are well regulated by homeostatic mechanisms. Albumin infusions had no effect on calcium concentrations, although it is possible that temporary changes of questionable clinical importance may have occurred between measurement periods.

Effects of parathyroid hormone and serum calcium on the phenotype and function of mononuclear cells in patients with primary hyperparathyroidism.

Several studies have demonstrated specific influence of parathyroid hormone (PTH) on immune parameters, especially on T- and B-cell function, migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in patients with secondary hyperparathyroidism and chronic renal failure and recently also in patients with primary hyperparathyroidism (pHPT). We therefore examined 12 patients with pHPT before and 6 months after parathyroidectomy (PTX) and nine sex- and age-matched control subjects to determine the impact of PTH and serum calcium concentrations on several immune parameters, including (a) serum concentrations of immunoglobulins, (b) immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)-induced lymphocyte proliferation and (d) monocytic surface marker expression. Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes (CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution and were not different before and after PTX in patients with pHPT when compared with the control group. CD4+ T-helper lymphocytes were significantly elevated pre- and post-operatively in patients with pHPT. The lymphocyte proliferation response to PHA in the highest concentration (12.5 micrograms L-1) tested was significantly suppressed in patients with pHPT preoperatively when compared with the patients post-operatively and the control group. In addition, both CD4+ and CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2 (IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially restored 6 months after PTX, but did not reach normal values. In summary, in contrast to the findings in patients with secondary HPT, pHPT appears to be associated with less alterations of immune functions. Chronically elevated serum PTH and calcium concentrations in patients with pHPT induce a higher percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to PHA as well as a reduced expression of activation markers on peripheral blood lymphocytes.

Short-Term Inhibition of Parathyroid Hormone Secretion by a Calcium-Receptor Agonist in Patients with Primary Hyperparathyroidism

Surgery is the usual therapy for patients with primary hyperparathyroidism. We investigated the ability of a calcimimetic drug that inhibits parathyroid hormone secretion in vitro to decrease serum parathyroid hormone and calcium concentrations in patients with this disorder. We performed a randomized, placebo-controlled study of single oral doses of 4 to 160 mg of the calcium-receptor agonist drug R-568 in 20 postmenopausal women with mild primary hyperparathyroidism. At base line, the mean (+/-SE) serum calcium concentration was 10.7+/-0.2 mg per deciliter (2.67+/-0.05 mmol per liter). Serum parathyroid hormone and calcium were measured repeatedly after each dose, and safety was assessed. Administration of R-568 resulted in a dose-dependent inhibition of parathyroid hormone secretion. The mean serum parathyroid hormone concentration, which was 77+/-11 pg per milliliter (18.8+/-2.7 pmol per liter; normal range, 16 to 65 pg per milliliter [3.9 to 15.9 pmol per liter) at base line, fell by 26+/-8 percent after 20 mg of R-568 (P=0.03), by 42+/-7 percent after 80 mg (P = 0.01), and by 51+/-5 percent after 160 mg (P=0.005). Serum ionized calcium concentrations fell only after the 160-mg dose, with the decrease closely following the decrease in the serum parathyroid hormone concentration. The calcimimetic drug R-568 reduces serum parathyroid hormone and ionized calcium concentrations in postmenopausal women with primary hyperparathyroidism.

Platelet cytosolic calcium concentration in patients with liver cirrhosis: Relationship with hepatic and systemic hemodynamics

Backgrouond/Aims: Due to structural and functional similarities between platelets and vascular smooth muscle cells, platelet cytosolic calcium concentration ([Ca 2+] 1) has been suggested to be a useful tool to study regulatory mechanisms of peripheral vascular tone. The aim of the present study was to investigate platelet [Ca 2+] i in patients with cirrhosis and whether this parameter is related with the systemic and splanchnic vasodilation found in these patients. Methods: Seventeen patients with cirrhosis and eight age- and sex-matched controls were studied. Mean arterial pressure, cardiac output, femoral blood flow and basal and thrombin-stimulated platelet [Ca 2+] i were measured. Cardiac output (thermal dilution), azygos blood flow, hepatic venous pressure gradient and hepatic blood flow were also measured in patients with cirrhosis. Results: Patients with cirrhosis had severe portal hypertension and a significantly higher cardiac output and femoral blood flow and a significantly lower systemic and femoral vascular resistance than controls. Patients with cirrhosis had a lower basal platelet [Ca 2+] i than normal subjects. However, there was no relationship between platelet [Ca 2+] i and any of the hemodynamic parameters that evaluate systemic or splanchnic vasodilatation. Conclusions: This study shows that cirrhotic patients with portal hypertension have a significant reduction in platelet basal [Ca 2+] i. The lack of correlation between platelet [Ca 2+] i and hepatic and systemic hemodynamics does not support the use of platelet [Ca 2+] i as a model to study mechanisms involved in the pathophysiology of the hyperdynamic circulation associated to portal hypertension.

Treatment of Cancer-Associated Hypercalcemia

<h3>Background:</h3> We assessed the effects of 60-mg single doses of pamidronate disodium compared with saline alone in the treatment of cancer-associated hypercalcemia. <h3>Methods:</h3> After pretreatment hydration, patients with corrected serum calcium concentrations of 3.0 mmol/L (12 mg/dL) or greater secondary to cancer were randomized to double-blind treatment with a single infusion of pamidronate disodium, 60 mg, over either 4 or 24 hours or continued infusions of 0.9% saline alone (n=23 per group). Corrected serum calcium levels were measured daily for 7 days of inpatient evaluation. <h3>Results:</h3> Response rates for both of the pamidronate regimens were significantly (<i>P</i>&lt;.05) higher than that for saline alone. A complete response to treatment (corrected serum calcium concentration normalized) was observed for five (22%), 18 (78%), and 14 (61%) patients, respectively, who received saline alone, 4-hour infusion of pamidronate, and 24-hour infusion of pamidronate. There were no significant differences between the two pamidronate regimens. Median durations of complete response were 6, 6, and 11 days, respectively, and median times to relapse (includes complete plus partial responders and nonresponders) were 0, 7, and 7 days, respectively. Pamidronate was well tolerated as assessed by all clinical and laboratory measures, regardless of the time of infusion. <h3>Conclusions:</h3> A 4-hour infusion of pamidronate disodium, 60 mg, was as safe and effective as a 24-hour infusion, and both were superior to saline alone in lowering corrected serum calcium concentrations in patients with cancer-associated hypercalcemia. (Arch Intern Med. 1994;154:1935-1944)

Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate.

To investigate the prognostic importance in neurologic recovery of the lumbar cerebrospinal fluid (CSF) variables creatine kinase (CK) and brain-type creatine kinase isoenzyme (CK-BB), lactate dehydrogenase (LDH) and its isoenzymes (LDH 1-5), CSF acid phosphatase, beta-D-N-acetylglucosaminidase activity, and CSF lactate, pyruvate, sodium, potassium, and calcium concentrations in patients who experienced cardiac arrest. Prospective clinical study with blood and CSF samples collected 4, 28, 76, and 172 hrs after resuscitation. Medical ICU in a university hospital. Twenty consecutive victims of out-of-hospital cardiac arrest. Eight patients recovered neurologically and 12 patients remained comatose or neurologically disabled until death. CSF CK, CK-BB, LDH, and LDH isoenzyme 1-3 concentrations in all disabled patients were markedly increased at 76 hrs after the resuscitation. However, these variables were not changed in the recovered subjects. Patients (n = 7) with a mean CSF CK level of 25 +/- 33 (SD) U/L, CK-BB 23 +/- 33 U/L, and CSF lactate 3.8 +/- 0.9 mmol/L at 28 hrs after cardiac arrest remained unconscious and died. In the recovered patients, the mean CSF CK concentration was 2.0 +/- 1.5 U/L (p less than .001) and CSF lactate concentration 2.5 +/- 0.5 mmol/L (p less than .002). The lactate concentration was highest at 4 hrs after resuscitation, declining thereafter. Patients with a mean CSF total LDH level of 609 +/- 515 U/L and acid phosphatase 2.4 +/- 1.2 U/L 76 hrs after resuscitation died without regaining consciousness. In the recovered patients, the mean total CSF LDH activity was 82 +/- 58 U/L (p = .003) and CSF acid phosphatase was 0.8 +/- 0.5 U/L (p = .01) 76 hrs after resuscitation. CSF CK, CK-BB, and CSF lactate concentrations reflect a patient's outcome most reliably when measured within 28 to 76 hrs of the cardiac arrest. Similarly, CSF LDH, its isoenzymes 1-3, and CSF acid phosphatase concentrations, when measured at 76 hrs, can be used to monitor the patient's outcome after cardiac arrest. When correlated with Glasgow Coma Scale scores, the closest negative correlation was again seen in CSF CK and CK-BB at 28 and 76 hrs, as well as in LDH, LDH1-3, and acid phosphatase values at 76 hrs. The negative correlation between CSF lactate and Glasgow Coma Scale scores was most distinct at 28 hrs.

Effect of salmon calcitonin and etidronate on hypercalcemia of malignancy.

Hypercalcemia of malignancy is a commonly encountered serious clinical problem that often requires aggressive therapy. In order to combine the rapid hypocalcemic effects of calcitonin with the more delayed effect of a bisphosphonate, we administered etidronate, 7.5 mg/kg/day intravenously and salmon calcitonin, 100 IU subcutaneously, every 12 hours for 3 days in 9 patients with hypercalcemia associated with malignancy. The mean serum calcium concentration fell from 3.33 +/- 0.1 mmol/liter (mean +/- SEM) to 2.88 +/- 0.1 mmol/liter within 24 hours (P less than 0.001). All patients had a fall in the serum calcium concentration of greater than 0.5 mmol/liter and it returned to normal in 7 of the 9 patients. We conclude that the combination of salmon calcitonin with etidronate more effectively lowers the serum calcium concentration in patients with hypercalcemia of malignancy then the use of either agent alone.

Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85±0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21±0.08 mmol/l, p<0.01, and 1.09±0.05 mol/ll, p< 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration ( p< 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group ( p< 0.05), and serum and CSF PTH were positively correlated ( p< 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium ( r = −0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.

Effects of lithium on platelet ionic intracellular calcium concentration in patients with bipolar (manic-depressive) disorder and healthy controls

Lithium is an effective drug in the treatment of both manic and depressive episodes of bipolar disorder. Lithium has been shown to block the metabolism of the intracellular second messenger inositol-1,4,5-trisphosphate which is involved in the rise in ionic intracellular calcium ([Ca ++] i) which triggers neurotransmitter release and other cellular changes in secretory cells. We have measured the effect of lithium on [Ca ++] i dynamics in platelets from bipolar patients stabilized with lithium treatment, and from healthy controls. Both resting [Ca ++] i and the thrombin stimulated increase in [Ca ++] i were higher in bipolar patients than in controls. Lithium added in vitro tended to increase the thrombin-stimulated rise in [Ca ++] i. The use of the fluorescent Ca ++ probe fura-2 in human platelets provides a useful method to investigate the mechanism of lithium's action in bipolar disorder and to study Ca ++ related systems which may be abnormal in bipolar disorders.

The Effects of Zero Magnesium Dialysate and Magnesium Supplements on Ionised Calcium Concentration in Patients on Regular Dialysis Treatment

The effect of oral magnesium carbonate or aluminium hydroxide on serum ionised calcium, total calcium, aluminium and magnesium, was assessed in 31 patients with chronic renal failure, during and after one haemodialysis. The behaviour of ionised calcium and total calcium was the same in both groups. Each showed a slight fall during dialysis, which was not significant. Serum total calcium was 0.2-0.3 mmol/l (0.8-1.2 mg/dl) greater throughout the period of dialysis in the group taking aluminium hydroxide. Serum magnesium and aluminium were both lower in the group treated with magnesium carbonate. In the group taking magnesium carbonate, serum magnesium concentrations fell markedly during dialysis, but otherwise were maintained within the reference range by the use of a magnesium-free dialysate. These results show the effectiveness of magnesium carbonate oral phosphate-binding agents and zero magnesium dialysate in reducing serum aluminium without affecting the behaviour of serum calcium fractions during dialysis.