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Factors influencing the ionization of calcium during major surgical procedures.

The existence of a clinically feasible calcium electrode makes it possible to obtain rapid, accurate levels of ionized calcium. It is now possible to study the actual ionization of calcium under normal and abnormal physiologic conditions. The present investigation was directed at changes in ionized calcium during major surgical procedures. The total series of 125 patients was divided into three groups according to the type of plasma volume expander: group 1, whole blood alone; group 2, whole blood plus exogenous albumin, and group 3, albumin alone. Ionized calcium levels dropped significantly, p less than 0.001, in all three groups. Although albumin alone produced a decrease in ionized calcium, the addition of albumin to whole blood did not result in a greater decline than that experienced with whole blood alone. Chelation with the citrate ion of bank blood preservative was the major factor responsible for the decrease in ionized calcium. There was no statistically significant relationship between the extent of the decrease, the total volume of blood, the volume of blood per kilogram of the rate of transfusion in milliliters per kilogram per minute. Although the ionized calcium level fell initially, it increased while blood administration continued. In view of these facts, it is difficult to estimate the acutal level of ionized calcium at any point during the operation. Twenty patients in the series had ionized calcium levels below 1.25 milliequivalents per liter, range of 0.51 to 1.24 milliequivalents per liter. With the possible exception of one patient, no adverse cardiovascular effects could be attributed to the low levels of ionized calcium. The results in this series confirm our previous conclusion that the administration of exogenous calcium is not necessary during massive transfusion, with the possible exception of bypass open heart procedures and exchange transfusions in children.

Adolescent↗

Ionized calcium concentration in horses with surgically managed gastrointestinal disease: 147 cases (1988-1990).

Packed cell volume, total plasma protein, serum sodium, potassium, and ionized Ca2+ concentrations, and blood pH were determined at the time of admission and following surgery in 147 horses with acute abdominal crisis. Horses were allotted to 3 categories on the basis of the surgical lesion: (1) nonstrangulating obstruction of the ascending or descending colon (category A, n = 76), (2) strangulating and nonstrangulating infarction of the cecum or ascending colon (category B, n = 37), and (3) strangulating and nonstrangulating infarction of the small intestine (category C, n = 25). Horses with low serum ionized Ca2+ concentration following surgery were given 23% calcium gluconate (100 to 300 ml) IV to effect, and ionized Ca2+ concentration was determined following treatment. The serum ionized Ca2+ concentrations of horses in categories A, B, and C before and after surgery were lower than our normal laboratory reference range. Prior to surgery, serum ionized Ca2+ concentration measured from horses in category B and C was lower than that in horses in category A. There was no difference in ionized Ca2+ concentration in serum samples obtained before surgery in horses from category B and C, and in serum samples obtained following surgery. There was a decrease in ionized Ca2+ concentration during surgery in horses in category A. There was no change between preoperative and postoperative ionized Ca2+ concentration in the samples obtained from horses in category B and C. After calcium gluconate administration, all horses with low serum ionized Ca2+ after surgery had concentrations within our normal range. Measurement of serum ionized Ca2+ in horses with an acute abdominal crisis is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen, Acute↗

[Absorbed dose measurement of photon beam with Farmer-type ionization chambers in Japanese dosimetry protocols].

The Japan Society of Medical Physics (JSMP) has published a new dosimetry protocol "JSMP-01" (standard dosimetry of absorbed dose in external beam radiotherapy) which conforms to the recommendations of the International Atomic Energy Agency (IAEA TRS-398) and the American Association of Physicists in Medicine (AAPM TG-51) protocols for the calibration of radiotherapy beams. Since the new protocol offers the physical data for the Famer-type ionization chambers of the various wall materials, the user can measure the absorbed dose at reference point (D(r)) using most of the commercially available Famer-type ionization chambers. In this paper, the six Famer-type ionization chambers of the various wall materials are examined for photon beam by two ways. To verify the JSMP-01 protocol as the first way, D(r) was cross-measured based on the JSMP-01 protocol using a Farmer-type ionization chamber of the acrylic wall material which is called "JARP-chamber" and the Farmer-type ionization chambers of the various wall materials, and compared. To compare the basic data in previous and new protocols as the second way, D(r) was measured based on the previous protocol (JSMP-86) and the JSMP-01 protocol using the Farmer-type ionization chambers of the various wall materials. Dose calculation was made using common exposure calibration factor for (60)Co gamma-rays (Nc) for each of the Farmer-type ionization chambers. Measurement was made with each ionization chamber for 6 and 10 MV photon beams in two facilities. D(r) were found to agree to that of JARP-chamber within about +/- 1% despite significant differences of ratio of calibration factor (k(D,X)) and beam quality conversion factor (k(Q)) for photon beams. The ratios JSMP-01/JSMP-86 of the reference dose were found to lie on between 0.999 and 1.004 for 6 MV and on between 0.999 and 1.005 for 10 MV depending upon the Farmer-type ionization chambers used. The largest discrepancies between the previous and new protocols arise from the use of different data of k(D,x) x k(Q) and C(lambda) for the absorbed dose conversion factors of each ionization chamber.

Calibration↗

A comparative study of serum ultrafiltrable, ionized, and total calcium in the diagnosis of primary hyperparathyroidism in patients with intermittent or no elevation in total calcium.

Measurement of serum ionized calcium has been shown to be more sensitive a method of diagnosing primary hyperparathyroidism than total calcium in patients with subtle or intermittent elevations of total calcium. The measurement of ionized calcium, however, is technically difficult. The measurement of serum ultrafiltrable calcium would circumvent technical difficulties because atomic absorption spectroscopy would be used to measure the calcium of a filtrate produced by passing serum through a filter which excludes protein-complexed calcium (Worthington ultrafree filter). The normal range for ultrafiltrable calcium (4.7 to 6.8 mg/dl) was determined in 138 patients by nonlinear least-squares analysis and chart review. The serum concentration of ultrafiltrable calcium correlated well with ionized calcium (r = 0.91). Previous studies have demonstrated no benefit in measuring ionized calcium, as opposed to total calcium, in the diagnosis of primary hyperparathyroidism unless there was subtle, intermittent, or no elevation of the total calcium. This comparative study of ultrafiltrable, ionized, and total calcium was, therefore, done in six patients with primary hyperparathyroidism who exhibited intermittent, minimal, or no elevations in serum total calcium. All six patients had symptoms referrable to hyperparathyroidism. All six underwent parathyroid surgery, and a parathyroid adenoma was found in each case. These six patients had a total of 24 concurrent preoperative determinations of ionized, ultrafiltrable, and total calcium levels. The total calcium value was elevated in only 9 of these 24 determinations (38%), ultrafiltrable calcium was elevated in 15 (63%), and ionized calcium was elevated in 23 (96%). The values of ionized calcium were elevated more frequently than both total calcium (p less than 0.0005) and ultrafiltrable calcium (p less than 0.025). The values for ultrafiltrable calcium were more frequently elevated than those for total calcium; this difference, however, was not significant. This study confirms our previous reports showing that ionized calcium is a more sensitive indicator of primary hyperparathyroidism in patients with intermittent or borderline elevation of the total calcium and extends those observations to show that ionized calcium is also a more sensitive indicator of primary hyperparathyroidism than ultrafiltrable calcium in this group of patients.

Calcium↗

Variations in total and ionized calcium during cardiac surgery.

Twenty patients undergoing cardiac surgery were studied to examine variations in total and ionized serum calcium and urine calcium during cardiopulmonary bypass. Serial samples of blood and urine were analyzed during bypass using a highly specific calcium electrode to determine the effects of hemodilution, various pharmacologic agents, and transfusions of citrated blood. Calcium chloride was routinely added to the crystalloid pump prime (400 mgs/L) and also administered when additional blood or crystalloid were infused. An average of 4.8 +/- .50 grams of calcium chloride was given per procedure. After induction of general anesthesia with nitrous oxide and Halothane, total serum calcium decreased from 10.0 +/- 0.3 to 8.5 +/- 0.8 mg% (p less than 0.05). Following heparinization, ionized calcium decreased from 4.2 +/- .08 to 3.9 +/- 12 mg% (p less than 0.05). Ionized calcium was not affected by reversal of heparin with Protamine. Following institution of cardiopulmonary bypass the ratio of ionized to total calcium declined about 13.4% (0.49 vs. 0.43). This ratio did not change during bypass but returned to normal immediately post-perfusion. Urinary calcium excretion averaged 1.9 +/- 0.6 mg/min and could not be implicated as a cause of hypocalcemia during bypass. Post-perfusion, ionized serum calcium rose 1.3 +/- .01 mg% for each gram of exogenously administered calcium chloride (p less than 0.05). From these observations, we conclude: (1) ionized and total serum calcium levels decreased significantly following institution of cardiopulmonary bypass alone, presumably as a result of hemodilution from the crystalloid pump prime and addition of citrated blood products; (2) induction of general anesthesia alone with nitrous oxide and Halothane is associated with a significant decrease in total serum calcium; (3) ionized calcium declined following heparinization but is unchanged by Protamine administration; (4) changes in total and ionized serum calcium are unaffected by urinary excretion during bypass; (5) exogenously administered calcium chloride significantly increases serum ionized calcium and these changes are inversely related to the circulating pool of calcium; (6) current protocols for administration of exogenous calcium chloride during bypass may result in insufficient levels of ionized calcium and we have adopted measures to correct these deficiencies, when indicated.

Calcium↗

Measurement of serum ionized versus total levels of magnesium and calcium in hemodialysis patients.

Until recently, only techniques for measuring total magnesium have been available. Now commercially available instruments using new ion-selective electrodes (ISE) for Mg+2 have made possible reliable measurement of ionized magnesium also in clinical practice. We measured changes induced by a hemodialysis session in serum ionized and total pools of magnesium and calcium using ISE methods. When compared with levels in age- and sex-matched control subjects, both serum ionized magnesium (0.68 +/- 0.11 vs. 0.56 +/- 0.06 mmol/l, p < 0.001) and total magnesium (1.00 +/- 0.19 vs. 0.82 +/- 0.08 mmol/l, p < 0.001) were higher in hemodialysis patients. The fraction of ionized Mg was 68.6 +/- 2.9% in hemodialysis patients, and did not differ significantly from that in controls (68.7 +/- 5.3%). The postdialysis value was 68.1 +/- 7.7%. The corresponding ratios of calcium (ionized/total) were 51.0 +/- 2.8% pre- and 50.9 +/- 4.6% postdialysis. Both prior to and after dialysis the correlation between ionized and total magnesium was high (r = 0.976, p < 0.001, and r = 0.925, p < 0.001, respectively). The corresponding ionized versus total calcium correlations were r = 0.724 (p < 0.001) before and 0.423 (p = 0.003) after dialysis. The changes induced by a hemodialysis session in serum concentration of ionized magnesium and calcium were dependent on the concentration of the cation in the dialysate. The change in PTH (suppression or stimulation) was very closely related to the changes in the serum concentration of ionized calcium. We concluded that measurement of ionized magnesium using ion-selective electrodes for Mg++ is an interesting new method in evaluating body magnesium status. Its definitive role in clinical practice cannot be judged on the basis of the results of the present study, but it will probably not achieve the same importance as the measurement of ionized calcium in clinical nephrology.

Calcium↗

Multiple-site titration and molecular modeling: two rapid methods for computing energies and forces for ionizable groups in proteins.

Computer models of proteins frequently treat the energies and forces associated with ionizable groups as if they were purely electrostatic. This paper examines the validity of the purely electrostatic approach, and concludes that significant errors in energies can result from the neglect of ionization changes. However, a complete treatment of ionizable groups presents substantial computational obstacles, because of the large number of ionization states which must be examined in systems having multiple interacting titratable groups. In order to address this problem, two novel methods for treating the energetics and forces associated with ionizable groups with a minimum of computer time have been developed. The most rapid method yields approximate energies by computing the free energy of a single highly occupied ionization state. The second method separates ionizable groups into clusters, and treats intracluster interactions exactly, but intercluster interactions approximately. This method yields both accurate energies and fractional charges. Good results are obtained in tests of both methods on proteins having has many as 123 ionizable groups. The more rapid method requires computer times of 0.01 to 0.34 sec, while the more accurate method requires 0.7 to 15 sec. These methods may be fast enough to permit the incorporation of ionization effects in iterative computations, such as energy minimizations and conformational searches.

Animals↗

Ionization behavior of native and mutant insulins: pK perturbation of B13-Glu in aggregated species.

Upscale titration from pH 2.5 to 11.2 is used as a means for probing solvent accessibility of ionizing groups in zinc-free preparations of native and mutant insulins. Stoichiometry and pK alpha values of ionizing groups in the titration curves are determined by iterative curve fitting. Under denaturing conditions, the titration curve of human insulin is in good agreement with that predicted from the sum of unperturbed titrations of the constituent ionizing groups and yields an apparent isoionic point of 5.3. Under nondenaturing conditions where aggregation and precipitation occur, titrations show that only five out of six carboxylate residues of human insulin ionize in the expected region. Consequently, one carboxylate ionization is masked and the apparent isoionic point located at pH 6.4. Correlation between ionization behavior and patterns of aggregation and solubility is established by titrations of mutant insulins and of dilute native insulin. Titration of an unusually soluble species, B25-Phe----His, shows that precipitation is not responsible for the masked carboxylate ionization of native insulin. Titrations of mutants B13-Glu----Gln and B9-Ser----Asp show that the masked ionization probably originates from monomer-monomer interactions in the insulin dimer. We conclude that the B13-Glu side chain is responsible for the masked carboxylate ionization in aggregated forms of human insulin.

Humans↗

Brain ionized magnesium and calcium levels during magnesium supplementation and deficiency in female Long-Evans rats.

OBJECTIVE: To examine the effect of changes in the state of magnesium balance on ionized magnesium and ionized calcium in serum and brain tissue of female rats. METHODS: Forty-two mature rats were used in the study. To induce hypermagnesemia, 12 rats received 270 mg/kg of magnesium sulfate intraperitoneally, followed every 20 minutes for 2 hours with 27 mg/kg magnesium sulfate. Ten control rats received an equal volume of saline. To induce hypomagnesemia, ten rats were placed on a magnesium-deficient diet for 4 (n = 5) or 8 (n = 5) days. Ten control rats were placed on basal diets of equal duration. Following treatment, rats were euthanized and serum and brain tissue were analyzed for ionized magnesium and calcium content. RESULTS: Hypermagnesemia produced a significant increase in serum ionized magnesium (P < .05) and calcium (P < .05). In addition, brain levels of ionized magnesium were significantly increased (P < .05), whereas calcium levels significantly decreased (P < .05) particularly in the hippocampus, parietal cortex, and cerebellum. Hypomagnesemia induced by 4 days on a magnesium-deficient diet led to decreased serum ionized magnesium (P < .01) and total magnesium (P < .05) but did not affect brain magnesium levels. Brain levels remained unaltered even after 8 days of hypomagnesemia. Serum and brain ionized calcium were not affected during peripheral magnesium deficiency. CONCLUSION: During peripheral magnesium deficiency, brain levels of ionized magnesium and ionized calcium are tightly regulated and appear unaffected. However, central levels of these electrolytes are altered under hypermagnesemic conditions. Thus, magnesium administration may change biologically active portions of magnesium and calcium in the brain.

Animals↗

Alterations of ionized Mg2+ in human blood after exercise.

Magnesium (Mg) is the second most abundant intracellular cation with modulating properties in a number of metabolic processes, e.g. in glycolysis, and intracellular signalling processes, e.g. regulation of ion channels and transporters. There are conflicting data available about the regulation of Mg in blood cells during exercise. Moreover, there are no data available about changes of the metabolic important fraction of ionized Mg(2+) both in blood and in blood cells during exercise. The present study investigated the changes of ionized Mg(2+) and total Mg concentration in different compartments after a stepwise treadmill ergometer test. Intracellular ionized Mg(2+) of thrombocytes and erythrocytes was determined by the magnesium sensitive fluorescent dyes mag-fura-2 and Mag-Green using fluorescence spectroscopy and flow cytometry, respectively. Ionized Mg(2+) in blood/serum was measured by an ion-sensitive microelectrode. Total cellular and serum Mg concentration were investigated using atomic absorbance spectroscopy and photometry, respectively. The present results shown that at the end of the ergometer test, ionized Mg(2+) in both blood and serum and total serum Mg decreased. In contrast, intracellular concentration of ionized Mg increased in both thrombocytes and erythrocytes. Total intracellular Mg was unchanged making a Mg(2+) shift between the intra- and extracellular compartment unlikely. The present study therefore demonstrated opposite changes of the ratio [ionized Mg(2+)]/[total Mg] in the intracellular and the extracellular compartment after anaerobic exercise. In in vitro experiments, similar changes of ionized Mg(2+) in both compartments could be mimicked by application of weak acids like propionic and lactic acid. It is concluded changes in the fraction of ionized Mg(2+) should be high enough to influence intracellular signalling and metabolic processes.

Adult↗

Glucose-induced alterations of intracellular ionized magnesium in human lymphocytes.

The intracellular ionic content of human erythrocytes may be altered by hyperglycaemia. Despite this, very little is known about the cellular mechanisms linking glucose and cellular magnesium homeostasis. We measured intracellular ionized magnesium in human lymphocytes, by means of a fluorimetric technique, total intracellular magnesium by means of atomic absorption spectrophotometry and intracellular ATP by means of HPLC. The incubation of lymphocytes with D-glucose in the absence of insulin was followed by a significant decrease in intracellular ionized magnesium; this effect did not occur when the cells were incubated with L-glucose. The effect of glucose on intracellular ionized magnesium was blocked by amphotericin B and the EC(50) of the effect of glucose on intracellular ionized magnesium was about 5 mmol/l of glucose. The increase of intracellular ionized magnesium in cells incubated in the absence of glucose was followed by a decrease in intracellular ATP. In a Na(+)-free medium the decrease of intracellular ionized magnesium in the presence of glucose was still present and the incubation of lymphocytes with glucose did not modify total intralymphocyte magnesium. By selective permeabilization of cell membranes, we established that glucose could not increase compartmentalized intracellular ionized magnesium. Our data supports the hypothesis that glucose per se induces a substantial decrease in intracellular ionized magnesium, which is probably due to an augmented binding of intracellular ionized magnesium to cellular ATP.

Acid Phosphatase↗

Ionized hypocalcemia during prolonged cardiac arrest and closed-chest CPR in a canine model.

STUDY BACKGROUND: Free or ionized calcium (Ca+2) is known to play a critical role in normal cardiovascular function, and Ca+2 administration in the setting of ionized hypocalcemia has been shown to improve indexes of cardiac function. The value of Ca+2 administration in the setting of cardiac arrest and resuscitation is unproven and controversial, in large part because ionized Ca+2 levels during cardiac arrest and resuscitation have not been adequately studied and exogenous calcium therapy may worsen ischemic cellular injury. STUDY PURPOSE: To measure free calcium during prolonged cardiac arrest and CPR in a canine model. METHODS AND MEASUREMENTS: Central arterial and venous catheters were positioned in nine dogs, and ventricular fibrillation (VF) was induced electrically. After seven and one-half minutes of VF, countershocks were administered, and CPR was initiated and performed in accordance with current recommendations for 20 minutes. At five-minute intervals during resuscitation efforts, arterial pH, ionized Ca+2, and lactate as well as aortic pressure were measured. RESULTS: During resuscitation, average systolic arterial pressure was 50 mm Hg. Within five minutes of instituting CPR, ionized Ca+2 significantly decreased from control values (5.1 +/- 0.1 at control to 4.0 +/- 0.1 mg/dL); after 20 minutes of attempted resuscitation, it averaged 3.2 +/- 0.2 mg/dL (P less than .05 vs control). There was no change in total Ca+2 during the arrest period (9.2 +/- 0.5 at control to 8.6 +/- 0.8 mg/dL at 27.5 minutes). Arterial lactate significantly increased throughout the arrest and resuscitation period (1.9 +/- 0.2 at control to 7.5 +/- 0.4 mM/L at 27.5 minutes). A significant correlation was demonstrated between ionized Ca+2 and lactate concentrations (r = -.72, P less than .001) but not between ionized calcium and pH (r = -.22, P greater than .20). CONCLUSION: Ionized hypocalcemia occurs during prolonged cardiac arrest and resuscitation, and ionized hypocalcemia during prolonged arrest and resuscitation may be due to binding by lactate, as has been demonstrated in vitro.

Animals↗

Determination of interactive thiol ionizations in bovine serum albumin, glutathione, and other thiols by potentiometric difference titration.

A potentiometric difference titration (PDT) method is used to study the ionization behavior of the thiol group in bovine serum albumin and in the following less complex compounds: glutathione, cysteine, 2-mercaptoethanol, 3-mercaptopropionic acid, 2-mercaptoethylamine, cis-2-mercaptocyclobutylamine, 2-aminothiophenol, and 5-mercapto-2-nitrobenzoic acid. In the PDT method the pH dependence of the amount of protons released in the reaction RSH + CH3SO2SCH3 leads to RSSCH3 + CH3SO2- + H+ is measured in order to obtain the pH dependence of the molar proton content of the thiol (hu) relative to the molar proton content of its methylthio derivative (hm). The pH dependence of hu--hm reflects the ionization behavior of the thiol group and of other groups whose ionization is thermodynamically linked to that of the thiol group. Data presented here indicate that the ionization behavior of the single thiol group in albumin is strikingly different in the native and the urea-denatured proteins. Three ionizable groups appear to affect ionization of the thiol in the native protein whereas only one group appears to affect ionization of the thiol in the urea-denatured protein. Furthermore, the measured PDT curves are consistent with an abnormally high acidity (pK less than 5) for the thiol in native albumin and a normal acidity for the thiol in the urea-denatured protein. Comparisons of microscopic ionization constants determined for cysteine by using the PDT method with those determined by other methods indicate that the PDT method should be useful in characterizing the ionization behavior of thiol groups in proteins and other polyprotic substances.

Animals↗

Importance of ionized magnesium measurement for monitoring of citrate-anticoagulated plateletpheresis.

BACKGROUND: The infusion of citrate during apheresis may affect the levels of ionized magnesium in the blood. Hypomagnesemia and concomitant hypocalcemia could influence the parathormone response and could be responsible for some of the symptoms observed during apheresis. STUDY DESIGN AND METHODS: The study reports measurement of ionized magnesium by the new ion-selective electrode technique in response to citrate infusion in 15 donors undergoing continuous flow high-yield plateletpheresis. The monitoring included measurement of ionized calcium and parathormone every 30 minutes during the 120-minute apheresis (plus the next 30 minutes to assess recovery). RESULTS: Ionized magnesium fell by 30 +/- 4 percent (mean +/- SD, p<0.01), which contrasts with minor changes in total concentrations. Comparison of variations in the levels of ionized and total magnesium found major formation of complexes during citrate infusion. Ionized calcium fell by 15 +/- 3 percent (p<0.01), while parathormone peaked at 356 +/- 114 percent (p<0.01) of initial value after 30 minutes. Ionized cations and parathormone recovered by more than 50 percent within 30 minutes of the end of apheresis. CONCLUSION: An acute and steep drop in ionized magnesium occurs during citrate administration. The measurement of ionized magnesium should be included in future prospective studies of donor safety and parathormone regulation during apheresis.

Anticoagulants↗

Pharmacokinetics of ionized versus total magnesium in subjects with preterm labor and preeclampsia.

OBJECTIVE: Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion. STUDY DESIGN: Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion. RESULTS: Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P <.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia. CONCLUSION: The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.

Adult↗

A comparison of serum ionized calcium concentrations and serum total calcium concentrations in dogs with lymphoma.

Serum ionized calcium and total calcium concentrations were measured in 16 dogs with lymphoma and 49 healthy control dogs. Blood samples for all determinations of ionized calcium were collected into tubes containing silicone separator gel and processed under a closed anaerobic system. An ionized calcium analyser with ion selective electrodes was used to determine pH, ionized calcium and ionized calcium adjusted to pH 7.4. Reference ranges for ionized calcium (iCa pH 7.4) of 1.30-1.46 mmol/l, and for total calcium of 2.37-2.82 mmol/l were established. A stronger correlation (r = 0.85) was found between measured ionized calcium and total calcium levels in dogs with lymphoma and hypercalcaemia than in those with lymphoma and normocalcaemia (r = 0.64). Measurement of serum ionized calcium was diagnostically concordant with the measurement of serum total calcium in the determination of calcium status in all dogs with lymphoma. Serum ionized calcium did not provide a diagnostic advantage over total calcium in the detection of hypercalcaemia of malignancy in these dogs.

Animals↗

A double-blind placebo-controlled crossover trial of intravenous magnesium sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients with AIDS and cytomegalovirus infection.

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO(4) at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO(4) reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO(4) was safe in this chronically ill population. Since parenteral MgSO(4) did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet.

AIDS-Related Opportunistic Infections↗

Formation and reactions of negative ions relevant to chemical ionization mass spectrometry. I. CL mass spectra of organic compounds produced by F- reactions.

A systematic study of the negative-ion chemical ionization mass spectra produced by the reaction of F(-) with a wide variety of organic compounds has been accomplished. A time-of-flight mass spectrometer fitted with a modified high pressure ion source was employed for these experiments. The F(-) reagent ion was generated from CF(3)H or NF(3), typically at an ion source pressure of 100 mum. In pure NF(3), F(-) is the major ion formed and constitutes more than 90% of the total ion intensity. While F(-) is also the major primary ion formed in pure CF(3)H, it undergoes rapid ion-molecule reactions at elevated source pressures, yielding (HF)(n)F(-) (n = 1-3) ions, which makes CF(3)H less suitable as a chemical ionization reagent gas. Among the organic compounds investigated were carboxylic acids, ketones, aldehydes, esters, alcohols, phenols, halides, nitriles, nitrobenzene, ethers, amines and hydrocarbons. An intense (M - 1)(-) ion was observed in the F(-) chemical ionization mass spectra of carboxylic acids, ketones, aldehydes and phenols. Alcohols yield only (M + F)(-) ions upon reaction with F(-). A weaker (M + F)(-) ion was also detected in the F(-) chemical ionization spectra of carboxylic acids, aldehydes, ketones and nitriles. The F(-) chemical ionization mass spectra of esters, halides, nitriles, nitrobenzene and ethers are characterized primarily by the ions, RCOO(-), X(-), CN(-), NO(2) (-), and OR(-), respectively. In addition, esters show a very weak (M - 1)(-) ion (except formates). In the F(-) chemical ionization spectra of some aliphatic alkanes and o-xylene, a very weak (M + F)(-) ion was observed. Amines and aliphatic alkenes exhibit only insignificant fragment ions under similar conditions, while aromatic hydrocarbons, such as benzene and toluene are not reactive at all with the F(-) ion. The mechanisms of the various reactions mentioned are discussed, and several experimental complications are noted. In still other studies, the effects of varying several experimental parameters, including source pressure, relative proportions of the reagent and analyte, and other ion source parameters, on the observed chemical ionization mass spectra were also investigated. In a mixture of NF(3) and n-butanol, for example, the ratio of the intensities of the ions characteristic of the alcohol to that of the (HF)(n)F(-) ion was found to decrease with increasing sample pressure, with increasing NF(3) pressure, and with increasing electron energy. No significant effects on the spectra were observed to result from variation of the source repeller field or the source temperature. The addition of argon to the source as a potential moderator did not alter the F(-) chemical ionization spectrum significantly, but the use of oxygen appears to inhibit formation of the (HF)(n)F(-) cluster ion. The advantages of using F(-) as a chemical ionization reagent are discussed, and comparisons are made with other reagent ions.

Anions↗