Biomedical subjects

R K Rude

Publications and source records attributed to R K Rude.

At least 37 records · Page 2Linked to original sources

PubMed1995

Vitamin D3 analogs: effect on leukemic clonal growth and differentiation, and on serum calcium levels.

In vitro, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) induces differentiation of HL-60 cells and inhibits their proliferation as well as the proliferation of leukemic cells from patients. In vivo, the survival of mice challenged with syngeneic leukemic cells is enhanced by treatment with 1,25(OH)2D3. Patients treated with 1,25(OH)2D3 develop hypercalcemia at a serum level of 2 x 10(-10) mol/l which is a concentration too low to achieve an antileukemic effect in vitro. Several interesting vitamin D3 analogs have recently been developed. We initially examined the effect of 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3 and 24a,26a,27a-tri-homo-22,24-diene-1-alpha,25-(OH)2-D3 on clonal growth and differentiation of HL-60 cells. Each of the analogs had comparable effects on clonal growth with 50% inhibition (ED50) at concentrations of 0.2-0.5 x 10(-9) M; 1,25(OH)2D3 was about 20- to 50-fold less active in inhibiting growth. Differentiation was determined by induction of superoxide production, as measured by nitroblue tetrazolium (NBT) reduction and by expression of a macrophage-specific enzyme (alpha napthyl acetate esterase (ANAE)). The 24a,26a,27a-tri-homo-22,24-diene-1-alpha,25-(OH)2-D3 and 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3 were about 5- to 14-fold more potent than 1,25(OH)2D3. The hypercalcemia inducing side-effects of these analogs and three other previously identified, extremely potent vitamin D3 compounds, as well as 1,25(OH)2D3, were studied. The analogs were administered intraperitoneally every other day (qod) for 5 weeks; serum was collected weekly and Ca2+ measured by atomic absorption spectrophotometry. The highest tolerated dose of each analog leaving all mice alive was for 1,25(OH)2D3: 0.25 micrograms; 1,25(OH)2-24a,26a,27a-tri-homo-22,24-diene-D3: 0.25 micrograms; and 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3: 0.0625 micrograms. Another hexafluoro compound with potent abilities to induce differentiation (1,25(OH)2-16ene-23yne-26,27-F6-D3) was very toxic, all mice died in the second week while receiving 0.0625 micrograms qod. Prior studies showed that the most potent compound in inducing differentiation of HL-60 was 1,25(OH)2-20-epi-D3; but it is very toxic as only one mouse survived a dose of > or = 0.0125 micrograms qod for 5 weeks. 1,25(OH)2-16ene-23yne-D3 is an extremely active inducer of differentiation but, on the other hand, it has low potential to produce hypercalcemia; mice maintained normal serum calcium levels even while receiving 2 micrograms qod for 5 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect.

To examine potential mechanisms for the blood pressure-lowering action of the thiazolidinedione compound, pioglitazone (PIO), we studied the effects of the drug on blood pressure and insulin action in vivo and on vascular tissue in vitro. In vivo, PIO lowered blood pressure in fructose-fed and chow-fed rats to an extent that could not be explained by alterations in fasting plasma insulin or free magnesium concentrations or by alterations in whole-body insulin sensitivity. In vitro, PIO caused significant blunting of the contractile responses of aortic rings to NE, arginine vasopressin (AVP), and potassium chloride; the blunting of responses to NE was maintained after removal of the endothelium. To assess the potential importance of extracellular calcium to the vasodepressor effect of PIO, we measured contractile responses to NE in the absence of calcium, and then after acute restoration of calcium in the presence of NE. PIO had no effect on the contractile response in the absence of calcium. By contrast, PIO blunted by 42% the contractile response that occurred when the extracellular calcium supply was acutely restored in the presence of NE, suggesting that the blunting was mediated by blockade of calcium uptake by vascular smooth muscle. Such an effect was confirmed in cultured a7r5 vascular smooth muscle cells, which exhibited a brisk increase in intracellular calcium in response to AVP that was blocked by PIO in a dose-dependent fashion. Our data indicate that PIO has a direct vascular effect that appears to be mediated at least in part by inhibition of agonist-mediated calcium uptake by vascular smooth muscle. The direct vascular effect may contribute to the blood pressure-lowering actions of PIO in vivo, because that effect could not be explained by alterations in whole-body insulin sensitivity.

Animals↗

PubMed1995

Disorders of magnesium metabolism.

Magnesium depletion is more common than previously thought. It seems to be especially prevalent in patients with diabetes mellitus. It is usually caused by losses from the kidney or gastrointestinal tract. A patient with magnesium depletion may present with neuromuscular symptoms, hypokalemia, hypocalcemia, or cardiovascular complication. Physicians should maintain a high index of suspicion for magnesium depletion in patients at high risk and should implement therapy early.

Bone and Bones↗

PubMed1995

Magnesium transport induced ex vivo by a pharmacological dose of insulin is impaired in non-insulin-dependent diabetes mellitus.

Diabetes mellitus may be associated with magnesium depletion, which in turn may contribute to metabolic complications of diabetes including vascular disease and osteoporosis. Intracellular depletion is thought to be due to osmotically induced renal magnesium loss; however, impaired ability of insulin to increase intracellular magnesium during insulin deficiency or insulin resistance could also play a role. Magnesium deficiency per se has also been reported to result in insulin resistance. In order to determine if magnesium transport is altered in non-insulin-dependent diabetes mellitus (NIDDM), we measured intracellular Mg(2+) in circulating lymphocytes obtained from nine normal subjects and seven patients with NIDDM. Ionized intracellular Mg(2+) was determined by fluorescent spectroscopy using Mg-fura-2. A 30 min incubation of insulin with lymphocytes obtained from normal subjects resulted in an increase in Mg(2+) of 8.6 +/- 3.6 percent (mean +/- SEM) at 100 mu U/ml which reached a plateau at approximately 250 mu U/ml (11.0 +/- 1.7 percent). The mean lymphocyte Mg(2+) in the patients (0.198 +/- 0.011 mM) was not significantly lower than normal (0.218 +/- 0.017). Insulin (500 mU/ml) added acutely during the fluorescence reading caused a rapid 31 +/- 3.9 percent rise in intracellular Mg(2+) in the normal subjects, which was significantly greater than the 18 +/- 1.6 percent rise observed in the NIDDM subjects (P < 0.01). The effect of magnesium deficiency was also studied in 3 normal subjects experimentally Mg deficient for 3 weeks. The mean lymphocyte Mg(2+) fell from 0.198 +/- 0.009 mM pre-diet to 0.153 +/- 0.006 mM post-diet. and the insulin-induced rise in Mg(2+) fell from 27.2 percent pre-magnesium depletion to 12.7 percent post-magnesium depletion. These data suggest that insulin resistance and magnesium depletion may result in a vicious cycle of worsening insulin resistance and decrease in intracellular Mg(2+) which may limit the role of magnesium in vital cellular processes.

Adult↗

PubMed1994

Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy.

BACKGROUND: Hypercalcemia is a serious and common complication of malignancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24-hour infusion of etidronate disodium in patients with HCM. METHODS: Selected patients with HCM had disease refractory to at least 24-hours of intravenous fluid (more than 3 l/day) with two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underdose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 53 years (range, 20-75 years). Twelve patients (6 in each treatment group) had confirmed skeletal metastases. RESULTS: During the week after treatment, the 25 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 +/- 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 +/- 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.8 +/- 0.4 mg/dl to a mean nadir of 10.5 +/- 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived from the patients' nadirs in the 25 mg/kg dose group was 2.5 +/- 0.4 mg/dl and 3.3 +/- 0.3 mg/dl for the 30 mg/kg dose. Time to effect (either a partial response defined as a 15% or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3.7 in the 30 mg/kg group. Nine of the 13 (69%) patients in the 25 mg/kg treatment group had either partial or complete response to the 24-hour infusion. Five of these patients (38% of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucalcemic range before day 7 (a complete response), 4 (31%) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92%) patients had at least partial responses. Eight of the 12 (67%) patients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25%) had a partial response, and 1 had no response. Reported adverse experiences generally were attributable to the underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P < 0.0001). CONCLUSIONS: Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.

Adult↗

PubMed1994

Magnesium deficiency in alcoholism: possible contribution to osteoporosis and cardiovascular disease in alcoholics.

Magnesium (Mg) deficiency occurs frequently in chronic alcoholism and may contribute to the increased incidence of osteoporosis and cardiovascular disease seen in this population. Mg deficiency is primarily due to renal Mg-wasting and is exacerbated by dietary Mg deprivation, gastrointestinal losses with diarrhea or vomiting, as well as concomitant use of drugs such as diuretics and aminoglycosides. Osteoporosis is prevalent in the alcoholic population. Mg deficiency may contribute to increased bone loss by its effects on mineral homeostasis. In Mg depletion, there is often hypocalcemia due to impaired parathyroid hormone (PTH) secretion, as well as renal and skeletal resistance to PTH action. Serum concentrations of 1,25-vitamin D are also low. These changes are seen with even mild degrees of Mg deficiency and may contribute to the metabolic bone disease seen in chronic alcoholics. Hypomagnesemia in alcoholics may also contribute to increased cardiovascular disease by altering platelet function. Mg deficiency has been demonstrated to enhance platelet reactivity. In these studies, Mg was shown to inhibit platelet aggregation against various aggregation agents. Patients with Mg deficiency were shown to have increased platelet aggregation that was normalized with Mg therapy. The antiplatelet effect of Mg may be related to the finding that Mg inhibits the synthesis of thromboxane A2 and 12-hydroxyeicosatetraenoic acid, eicosanoids thought to be involved in platelet aggregation. Mg also inhibits the thrombin-induced Ca2+ influx in platelets, as well as stimulates synthesis of prostaglandin I2, the potent antiaggregatory eicosanoid. Therefore, Mg deficiency may increase platelet aggregation and cause increased hypertension and atherosclerotic cardiovascular disease in alcoholics.

Alcoholism↗

PubMed1994

Dietary magnesium prevents fructose-induced insulin insensitivity in rats.

Increased dietary fructose may produce insulin insensitivity and elevate blood pressure in rats. It is possible that the reduced magnesium content of the high-fructose commercial diet used in some studies may play a role in these abnormalities because it is known that magnesium deficiency can produce insulin insensitivity and increased angiotensin II action in humans. To study this, we maintained rats for 9 weeks on either a normal control diet, a standard high-fructose diet, or the same high-fructose diet supplemented with magnesium. Glucose uptake was assessed using a perfused rat hindquarter preparation sequentially with 0, 900, and 120,000 pmol/L of added insulin. Basal serum glucose, plasma insulin, and basal glucose uptake in the absence of insulin were similar among all three groups. However, insulin sensitivity, defined as glucose uptake in the presence of 900 pmol/L insulin minus basal, was depressed in the high-fructose compared with the control group (1.02 +/- 0.38 to 1.77 +/- 0.57 mumol/g per hour, P < .05). In contrast, the high-fructose group supplemented with normal magnesium had similar insulin sensitivity as the control group (2.09 +/- 0.69 mumol/g per hour). Total serum magnesium was reduced in the high-fructose group compared with control or high-fructose plus magnesium-supplemented groups. Blood pressure and fasting insulin levels were also lower in the magnesium-supplemented group. These results suggest that magnesium deficiency and not fructose ingestion per se leads to insulin insensitivity in skeletal muscle and changes in blood pressure.

Animals↗

PubMed1994

Should we supplement magnesium in critically ill patients?

Magnesium (Mg) deficiency is a common yet underdiagnosed problem in the ICU. Since only 1% of total body Mg is in the extracellular fluid, serum Mg concentrations may not adequately reflect Mg status. Utilizing techniques to measure intracellular Mg concentrations, Mg depletion has been shown to be present in about one half of all ICU patients. These patients have significantly higher morbidity and mortality rates than Mg-replete patients. Accurate identification of patients with Mg depletion requires a knowledge of the risk factors associated with Mg deficiency. These factors include poorly controlled diabetes mellitus, alcohol ingestion, severe diarrhea and steatorrhea, and the use of a number of pharmacologic agents that induce renal Mg wasting. Manifestations of Mg deficiency include hypokalemia, hypocalcemia, neuromuscular hyperexcitability, respiratory muscle weakness, and intractable arrhythmias. Mg deficiency may also play a role in the genesis of myocardial ischemia. In this article, we review the assessment, causes, and manifestations of Mg deficiency and suggest guidelines for adequate treatment.

Clinical Protocols↗

PubMed1993

Clinical manifestations of magnesium deficiency.

Magnesium (Mg) is critical for the function of numerous enzyme systems. Mg deficiency thereby may result in many and varied clinical manifestations. Mg deficiency is common as approximately 10% of patients admitted to city hospitals are hypomagnesemic. Mg deficiency is usually due to losses from the gastrointestinal tract or from the kidney. A serum Mg concentration of < 1.5 mEq/l usually indicates Mg deficiency, however, intracellular Mg deletion may be present despite a normal serum Mg concentration. Acute clinical manifestations of Mg deficiency include neuromuscular hyperexcitability, cardiac arrhythmias, and biochemical abnormalities of hypokalemia and hypocalcemia. Chronic Mg depletion may contribute to hypertension, atherosclerotic vascular disease, altered glucose homeostasis, and metabolic bone disease. Therapy of the acute manifestations usually requires parenteral Mg administration of 24-48 mEq Mg/day for 3-5 days. Long-term Mg repletion may be accomplished by the administration of 300-600 mg of Mg orally/day.

Humans↗

PubMed1993

Magnesium metabolism and deficiency.

Magnesium is a prominent intracellular cation required for the function of hundreds of enzyme systems. Magnesium depletion is observed frequently in hospitalized patients and is usually secondary to renal or intestinal magnesium loss. Clinically, magnesium deficiency may present with neuromuscular hyperexcitability, hypocalcemia, hypokalemia, and cardiac arrhythmias. Magnesium therapy appears to improve survival in patients with myocardial infarction. The diagnosis of magnesium deficiency is usually made by a low-serum magnesium concentration, although the magnesium tolerance test may be more indicative of low magnesium states. In acutely ill patients, magnesium is usually give parenterally; oral magnesium may be given for long-term repletion.

Diagnosis, Differential↗

PubMed1993

Cortisone-induced osteoporosis: effects on bone adenylate cyclase.

Glucocorticoid excess results in osteoporosis by inhibiting bone formation as well as by increasing bone resorption. The cellular mechanism for the glucocorticoid effect is unknown but has been postulated to be due to enhancement of the cyclic AMP response to PTH. This study examined the effect of in vivo administration of a glucocorticoid on adenylate cyclase activity in plasma membranes isolated from mineralized bone. Glucocorticoid excess was induced by implanting cortisone subcutaneously in adult female guinea pigs. At the end of 3 weeks skeletal plasma membranes were obtained, and adenylate cyclase activity was compared with that of normal age-matched guinea pigs. The specific activity of basal adenylate cyclase activity was significantly greater in the cortisone-treated animals (77.7 +/- 10 vs. 41.9 +/- 4.4 pmol cAMP/mg protein/15 min, p < 0.005), but PTH stimulated both to an equal degree. In contrast to the increased specific activity of intact adenylate cyclase, the specific activity of the catalytic unit was lower in the membranes from cortisone-treated animals. We also examined the effect of cortisone treatment on the modulation of adenylate cyclase by divalent cations. Neither the KaMg or the ability of Ca2+ to inhibit enzyme activity was found to differ between normal and cortisone-treated animals. In addition, PTH caused an increase in Mg2+ affinity in both sets of membranes to a comparable degree. The effect of cortisone could not be attributed to altered amounts of Ni present in these membranes; we were unable to satisfactorily quantitate the amounts of Ns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1992

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.

Animals↗

PubMed1992

Lack of effect of ovariectomy on divalent cation regulation of skeletal adenylate cyclase.

Both estrogen and androgen have been reported to attenuate cyclic AMP responses to parathyroid hormone stimulation in cultured bone cells. The present study examines the effect of in vivo estrogen deficiency on skeletal adenylate cyclase (AC) activity. The AC activity was compared in bone membranes prepared from normal female guinea pigs and from age-matched guinea pigs 3 weeks after ovariectomy. Histomorphometric analysis of femoral specimens from the ovariectomized guinea pigs demonstrated significant decreases in percentage bone volume, the percentage eroded surfaces and osteoclast numbers, and increased osteoid thickness, compared with the normal controls. No differences were found in basal AC activity, the ability of bone AC to be stimulated by parathyroid hormone (bPTH(1-34)) or isoproterenol, or in the regulation of AC activity by calcium and magnesium. We conclude that bone AC is not a direct target for estrogen effects on bone cells and that the reported effects of sex steroids on cAMP levels in bone cells probably act via an indirect mechanism.

Adenylyl Cyclase Inhibitors↗

PubMed1992

Magnesium deficiency and diabetes mellitus. Causes and effects.

A large body of evidence demonstrates the prevalence and adverse clinical consequences of magnesium deficiency in patients with diabetes mellitus. It would be prudent for physicians who treat these patients to consider magnesium deficiency as a contributing factor in many diabetic complications and in exacerbation of the disease itself. Repletion of the deficiency or prophylactic supplementation with oral magnesium may help avoid or ameliorate such complications as arrhythmias, hypertension, and sudden cardiac death and may even improve the course of the diabetic condition.

Arrhythmias, Cardiac↗

PubMed1992

Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus.

OBJECTIVE: Mg deficiency may be an important factor leading to cardiovascular disease. Diabetic subjects show an increase in platelet reactivity that can enhance the risks of vascular disease. In addition, diabetic patients have been reported to be at risk of developing extracellular Mg deficiency. However, the intracellular free Mg concentration and its role in the enhanced platelet reactivity in diabetes is not known. RESEARCH DESIGN AND METHODS: We evaluated the intracellular erythrocyte (RBC) Mg2+ concentration in 20 non-insulin-dependent (type II) diabetics. In addition, the effects of intravenous 3-h drip or 8 wk of oral Mg supplementation on intracellular RBC Mg2+ levels and platelet reactivity was studied. To more clearly evaluate the direct role of Mg in these effects, we induced isolated Mg deficiency in 16 nondiabetic control subjects with an Mg-free liquid diet for 3 wk. RESULTS: The intracellular RBC Mg2+ concentration of diabetic patients was significantly reduced compared with values in nondiabetic control subjects (166 +/- 7 vs. 204 +/- 7 microM, P less than 0.01). Serum Mg levels were also reduced in the diabetic patients compared with the control subjects (1.59 +/- 0.04 vs. 1.9 +/- 0.1 mEq/L, P less than 0.05). Oral Mg supplementation for 8 wk (400 mg/day) restored RBC Mg2+ concentration to normal without significantly changing serum Mg concentration. Both intravenous and oral Mg supplementation markedly reduced platelet reactivity in response to the thromboxane A2 analog, U46619. The Mg-free diet resulted in a significant reduction in RBC Mg2+ concentration and markedly enhanced the sensitivity of platelet aggregation to U46619 and ADP. CONCLUSIONS: These results suggest that type II diabetic patients have intracellular Mg2+ deficiency and that Mg deficiency may be a key factor in leading to enhanced platelet reactivity in type II diabetes. Therefore, Mg supplementation may provide a new therapeutic approach to reducing vascular disease in patients with diabetes.

Adult↗

PubMed1991

Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism.

Magnesium (Mg) deficiency in man may result in hypocalcemia, impaired PTH secretion, and low serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D]. To determine whether these changes are due to selective Mg depletion, we studied 26 normal subjects before and after a 3-week low Mg (less than 1 meq/day) diet. This diet induced Mg deficiency, as demonstrated by a fall in pre- to postdiet serum Mg levels from 0.80 +/- 0.01 to 0.61 +/- 0.02 mmol/L (P less than 0.001), an increase in Mg retention from 11 +/- 4% to 62 +/- 4% (P less than 0.001), and a fall in red blood cell free Mg2+ from 205 +/- 10 to 162 +/- 7 microM (P less than 0.001). Serum calcium (Ca) fell significantly from 2.36 +/- 0.02 to 2.31 +/- 0.03 mmol/L (P less than 0.05), and serum 1,25-(OH)2D fell from 55 +/- 4 to 43 +/- 3 pmol/L (P less than 0.05). PTH secretion was impaired, as demonstrated by a fall or no change in serum PTH in 20 of 26 subjects despite a fall in the serum Ca and Mg. In addition, an iv injection of Mg in eight subjects after the diet resulted in a significant rise in PTH from 15 +/- 2 to 19 +/- 2 ng/L (P less than 0.01), whereas a similar injection given to six of the subjects before the diet resulted in a significant fall from 28 +/- 5 to 13 +/- 3 ng/L (P less than 0.001). The fall in serum 1,25-(OH)2D may be due to both the decrease in PTH secretion and a renal resistance to PTH. PTH resistance was suggested, as no increase in serum 1,25-(OH)2D was observed in the six subjects in which the PTH concentration rose by mean of 68% after the diet. Also, the rise in serum 1,25-(OH)2D after a 6-h human PTH-(1-34) infusion was significantly less after Mg deprivation. The results demonstrate that mild Mg depletion can impair mineral homeostasis and may be implicated as risk factor for osteoporosis in disorders such as chronic alcoholism and diabetes mellitus, in which Mg deficiency and osteoporosis are both common.

Adult↗

PubMed1991

Effectiveness of a 24-hour infusion of etidronate disodium in the treatment of hypercalcemia of malignant disease. A dose-ranging pilot study.

A dose-ranging, baseline-controlled study was undertaken to assess the safety and effectiveness of a 24-hour infusion of etidronate disodium in treating patients with hypercalcemia of malignant disease. Patients with hypercalcemia refractory to at least 48 h of saline loading (greater than 3 1/day) with two albumin-adjusted serum calcium values between 11.1 and 12.0 mg/dl or one albumin-adjusted serum calcium greater than 12.0 mg/dl within 48 h of therapy were admitted to the study. A total of 26 patients were treated in a dose-escalating fashion with 5, 10, 15, 20 or 25 mg/kg of intravenous etidronate disodium over 24 h. Patients treated with 5, 10 or 15 mg/kg did not have significant reductions in albumin-adjusted serum calcium during the first 7 days. In the 6 patients who made up the 20 mg/kg group, adjusted serum calcium levels fell from an average of 13.8 +/- 0.5 mg/dl on day 1 before infusion to 11.7 +/- 0.3 mg/dl (p less than 0.05) by day 7. In the 8 patients in the 25 mg/kg group, adjusted serum calcium levels decreased from an average of 12.9 +/- 0.5 mg/dl on day 1 before infusion to 10.9 +/- 0.4 mg/dl (p less than 0.05) by day 7. All 8 patients in the 25 mg/kg group achieved a fall in albumin-adjusted serum calcium to less than 11.1 mg/dl within the 1 week with a minimum decrement of 0.6 mg/dl and a maximum of 5.5 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Etidronic Acid↗

PubMed1990

Effect of intravenous epinephrine on serum magnesium and free intracellular red blood cell magnesium concentrations measured by nuclear magnetic resonance.

Hypomagnesemia is a common clinical finding in hospitalized patients and can cause hypocalcemia, cardiac arrhythmias, muscular weakness, and hypokalemia. Hypomagnesemia usually implies cellular magnesium (Mg) depletion, but stress and some clinical conditions which raise serum catecholamine concentrations may lower serum Mg (sMg) concentrations. To help investigate the mechanism and degree of the effect of catecholamines on sMg concentration, we gave intravenous epinephrine (0.1 microgram/kg/min) to 12 normal volunteers for 2 hours. The sMg concentration fell from 1.86 +/- 0.04 mg/dl to 1.63 +/- 0.05 mg/dl (mean +/- SEM, p less than 0.01). Pre-infusion intracellular free Mg (Mg++) in red blood cells (RBC) as measured by nuclear magnetic resonance spectrophotometry (NMR) was 171 +/- 7.6 microM and did not differ significantly from post-infusion RBC Mg++, 186 +/- 12.6 microM. Total blood mononuclear cell Mg content and urine Mg excretion also did not change. These data suggest that epinephrine has a small but significant effect on the lowering of sMg concentrations. Endogenous catecholamine release during stress or acute illness may therefore contribute to the hypomagnesemia seen in acutely ill patients. Our data also suggest that hypomagnesemia seen under conditions of acute stress may not always imply depleted tissue Mg stores. As no absolute change in cellular Mg or in urinary Mg excretion was demonstrated, acute intracellular shifts of Mg into blood cells and/or urinary Mg losses may not account for the hypomagnesemia. The prevalence and clinical consequences of stress hypomagnesemia require further investigation.

Adolescent↗