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Biomedical subjects

R J Elin

Publications and source records attributed to R J Elin.

At least 91 records · Page 5Linked to original sources

Magnesium metabolism in health and disease.

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.

Humans↗

Status of the determination of magnesium in mononuclear blood cells in humans.

The determination of magnesium in mononuclear blood cells (MBC) as an index of intracellular magnesium was proposed 10 years ago. Studies to date show relatively good agreement among investigators for the mean value of magnesium in MBC. The MBC magnesium value does not show a significant correlation with either serum or red blood cell magnesium concentrations in humans. However, there may be a correlation for magnesium between MBC and muscle and for magnesium and potassium in MBC. Studies suggest a clinical utility for the MBC magnesium in several disease entities.

Humans↗

Nutritional status of patients with acquired immunodeficiency syndrome.

Nutritional status may be an important factor in the prognosis of morbidity and mortality. We assessed the nutritional status of individuals seropositive for human immunodeficiency virus (HIV) (as confirmed by Western blot) and of patients with AIDS, by determining the concentration in serum of total protein, albumin, prealbumin (transthyretin), and retinol-binding protein. HIV-seropositive individuals showed no significant difference from normal volunteers in values for prealbumin, albumin, and retinol-binding protein. Patients with AIDS showed significantly smaller prealbumin and albumin concentrations than did normal and HIV-positive individuals. There was no significant difference in the concentration of retinol-binding protein among the three groups. The concentration of total serum protein was significantly greater in HIV-positive individuals and in patients with AIDS than in normal individuals. Thus, the nutritional status of patients with AIDS may be a factor for morbidity and mortality.

Acquired Immunodeficiency Syndrome↗

Analytical bias for cholesterol and the percent of the population deemed at risk for coronary heart disease.

The effect of methodological bias on the population at risk is dependent on the location of the reference value in the distribution of the population. We fitted the cumulative distribution for cholesterol to a rational function and calculated the apparent reference values for four biased methods: Technicon SMAC (2.6%), DuPont aca (4.0 to 4.8%), Kodak DT-60 (-2.0 to -5.5%), and BMD Reflotron (-7.4 to -7.8%). With the true and apparent reference values for cholesterol and the rational function, we determined the percentage increase or decrease in the population deemed at risk for coronary heart disease. The population at risk increased by as much as 48% for methods with positive bias, and decreased by as much as 54% for methods with negative bias. If we restrict the percentage of the population incorrectly diagnosed to 3% and use reference values (cut points) recommended by the National Cholesterol Education Program, the maximum allowable methodological bias would be 1.6% for positive bias and -1.55% for negative bias. Therefore, an absolute methodological bias of 3% (as recommended by the Laboratory Standardization Panel) may be too liberal.

Adult↗

A model for the effect of bias for cholesterol on the population at risk.

The location of the Reference Value for an analyte within the population distribution affects the magnitude of error due to methodological bias. Using the gaussian distribution, we evaluated the effects of systematic and proportional biases of the method (positive and negative), mean value, and standard deviation on the magnitude of error. We chose four Reference Values for cholesterol as a model. For a population with a mean of 2.0 and SD of 0.36 g of cholesterol per liter, a 3% positive proportional bias causes sixfold more error at the 50th percentile than at the 97.5th. In general, the error for a given bias (proportional or systematic) is greater for a Reference Value within the body than at the tails of the distribution. Further, the magnitude of the error varies as a function of the mean and standard deviation of the population.

Cholesterol↗

Enzyme abnormalities of patients with acquired immunodeficiency syndrome.

We determined the enzyme activities of glucose-6-phosphate isomerase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in serum from 23 normal controls, 27 anti-HIV seropositive individuals confirmed by Western blot, and 53 patients with acquired immunodeficiency syndrome (AIDS). There is a significant difference for all four enzyme activities among controls, HIV seropositive individuals, and patients with AIDS, the enzyme activities showing a progressive increase as the disease progresses. Evidently these enzyme measurements may be adjunctive biochemical markers for progression of AIDS.

Acquired Immunodeficiency Syndrome↗

Magnesium content and concentration of mononuclear and T lymphocyte blood cells.

The magnesium content of mononuclear blood cells (MBCs) may be a better indicator of intracellular or total body Mg status than either serum or red blood cell Mg. However, MBCs are a heterogeneous population composed primarily of lymphocytes and monocytes. A significant difference in the Mg concentration or content between lymphocytes and monocytes could alter the results for MBC Mg. We produced monocyte-poor MBCs (MPMBCs) by treating MBCs with carbonyl iron particles. We purified T lymphocytes from MPMBCs [antihuman F(ab)2 monolayer procedure]. The purity of T lymphocytes (T + NK cells) was 98% by flow-cytometric analysis. The mean (+/- SEM) Mg content and concentration of MPMBCs were 61.9 +/- 3.0 fg/cell and 10.6 +/- 0.4 mmol/l, respectively, and of T lymphocytes 60.8 +/- 2.7 fg/cell and 11.8 +/- 0.4 mmol/l, respectively. There was no significant difference in Mg content between MPMBCs and T lymphocytes. The Mg concentration of T lymphocytes was significantly higher (p less than 0.001) than MPMBCs. However, the difference is small and does not justify the increased complexity of the assay for T lymphocytes. We conclude that the cell composition of MBCs may affect the result for Mg concentration.

Flow Cytometry↗

Bias between enzymatic methods and the reference method for cholesterol.

Assaying 312 serum samples, we compared four enzymatic methods for serum cholesterol with the Reference Method (modified Abell-Kendall) of the Centers for Disease Control (CDC). The means for the aca, TDx, and SMAC methods (2.27, 2.27, and 2.24 g/L, respectively) were significantly higher (P less than 0.05) than those of the Reference Method and the RA-1000 method (2.19 and 2.18 g/L, respectively). The biased methods had positive proportional and (or) systematic biases. Results with these methods were 2.6% to 4.9% higher than with the Reference Method. The assigned concentrations of cholesterol in the calibration materials for the SMAC and aca agreed with those obtained by the Reference Method, but were lower for the TDx and higher for the RA-1000. These findings document positive biases for cholesterol with three enzymatic methods and suggest that misassignment of calibrators is not primarily responsible for the biases found with the aca and SMAC. It may, however, to be a significant factor for the TDx.

Autoanalysis↗

Density gradients for isolation of mononuclear blood cells for magnesium analysis by electron probe X-ray microanalysis.

We present a mononuclear blood cell (MBC) isolation method for magnesium analysis by electron probe X-ray microanalysis. We compare the inorganic elemental composition of individual MBC isolated by either arabinogalactan (Stractan) or conventional Ficoll-Hypaque density gradients. We find that the MBC isolated with Stractan have the expected cellular element composition, but MBC isolated with Ficoll-Hypaque are contaminated with iodine and sodium. We discuss the source and significance of iodine and sodium contamination of Ficoll-Hypaque isolated MBC and recommend the Stractan separation method for electron probe X-ray microanalysis.

Adult↗

Status of the mononuclear blood cell magnesium assay.

The tenth anniversary for the determination of magnesium in MBC shows progress, but fundamental questions are still unanswered. Uniformity of the methodology for the assay and the units for reporting the result is a key factor for the validity and comparability of results. There is relatively good agreement among investigators for the mean value of magnesium in MBC expressed with three different units. The MBC magnesium results do not correlate with serum or red blood cell magnesium concentrations in humans. There may be a correlation for magnesium between MBC and muscle and between magnesium and potassium in MBC. The correlation for magnesium between MBC and muscle or other body tissues, particularly bone, needs to be defined for the clinical utility of the assay. A number of studies to date suggest a possible clinical utility for the MBC magnesium assay in several disease entities. Thus, the MBC magnesium assay has come a long way in a relatively short time. The future for the assay is uncertain but does hold hope that this relatively simple test can provide useful information about intracellular or total body magnesium status.

Female↗

Dose-dependent changes in the antigenicity of bacterial endotoxin exposed to ionizing radiation.

The antigenic properties of the highly purified US reference standard endotoxin (RSE) exposed to varying doses of ionizing radiation were studied with double immunodiffusion, immunoelectrophoresis and immunoblotting. Rabbit RSE antisera identified 2 distinct major antigenic components for untreated RSE: one related to the O-polysaccharide side chain ("O-antigenic specificity"), the other to the R-core. Based on a serologic cross-reactivity of R-core of RSE (Escherichia coli 0113) with the R-core of the lipopolysaccharide from E. coli 0111, the core type of E. coli 0113 was identified as coli R3. Increasing exposure of RSE to ionizing radiation progressively destroyed all antigenic reactivities: at lower doses of radiation the rate of elimination differed for the 2 antigen classes. The O-polysaccharide was more sensitive to gamma-radiation than the R-core and the O-antigenicity was lost before that of the R-core. Endotoxin molecules containing incomplete R-core (radiation-induced or mutant) did not react with the RSE antiserum.

Animals↗

Assessment of magnesium status.

The adult human body contains approximately 24 g (1 mol) of magnesium--about half in bone and half in soft tissues. Only about 0.3% of the total body magnesium is present in serum, yet the majority of analytical data obtained is from this body fluid. Assessing the magnesium status of an individual is difficult, there being at present no simple, rapid, and accurate test to determine intracellular magnesium, but determination of total and free magnesium in tissues and physiological tests provide some information. Changes in magnesium status have been linked to cardiac arrhythmias, coronary heart disease, hypertension, and premenstrual syndrome. A better understanding of magnesium transport and of factors controlling magnesium metabolism is needed to elucidate the role of magnesium in disease processes.

Absorption↗

A model for assessing interference.

Most studies of analytical interference indicate the magnitude but not the type of interference. We developed a model for interference that assesses the magnitude of the following types of interference: independent of analyte concentration, dependent on analyte concentration, and a combination of the two. The experimental design for the model is an orthogonally arranged matrix with progressively increasing concentrations of analyte and interfering agent. Multiple regression with these independent variables (concentration of analyte, concentration of interfering agent, and the product of the two) is used to determine the magnitude, direction, and significance of each type of interference. Applying the model to study interference by hemoglobin with determinations of creatinine, direct bilirubin, and total bilirubin showed that hemoglobin interferes with determination of creatinine independent of the analyte concentration, interferes with total bilirubin dependent on the analyte concentration, and interferes with direct bilirubin by a combination of these two.

Bilirubin↗

Mechanism of interference with the Jaffé reaction for creatinine.

We investigated the mechanism of the Jaffé reaction for determination of creatinine by studying the spectrophotometric, kinetic, and equilibrium properties of the reaction of picrate with creatinine and with cyclic and aliphatic ketones. Absorbance spectra for the reaction products of picrate with all the ketones were superimposable with that of creatinine (Amax, 490 nm). Cyclic ketones not containing nitrogen had a molar absorptivity less than half that of creatinine and equilibrium constants approximately 0.01 that of creatinine. Aliphatic ketones, except for benzylacetone, had molar absorptivities similar to that of creatinine, but all of these compounds had equilibrium constants approximately a tenth or less that of creatinine. The common structure for all of the compounds reacting with picrate is the carbonyl group. The variable magnitude of interference for aliphatic and cyclic ketones is ascribable to the different rate constants, molar absorptivities, and equilibrium constants as compared with creatinine. Structures adjacent to the carbonyl group significantly affect the absorptivity and equilibrium constant, but steric hindrance is the major factor affecting the rate of reaction. We postulate that the carbonyl group is required for the Jaffé reaction, and we suggest a mechanism for the reaction.

Acetohexamide↗

Cefoxitin interferes with the "Clini-Skreen" column method for urinary 17-hydroxycorticosteroids.

Cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids. The apparent concentration of hormone is increased from three- to 10-fold in samples from patients receiving cefoxitin when the Amberlite XAD-2 "Clini-Skreen" column is used. To determine the mechanism of interference, we reacted aqueous solutions of cefoxitin, cortisol, cortisone, and 11-deoxycortisol with phenylhydrazine; recorded the adsorption spectra; and determined the molar absorptivities and the equilibrium and rate constants. Also, we recorded the absorption spectra of phenylhydrazine with eight other cepha antibiotics and benzylpenicillin. Cortisol, cortisone, 11-deoxycortisol, and cefoxitin react with phenylhydrazine and absorb light with superimposable spectra and absorption maxima of 410 nm. The other antibiotics react with phenylhydrazine but absorbance maxima of the products vary, none being at 410 nm. Cortisol, cortisone, and 11-deoxycortisol react with phenylhydrazine 35-fold faster, have equilibrium constants ninefold greater, and have molar absorptivities 1.6 times that of cefoxitin. Thus, cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids by forming a chromophore with the same absorbance maximum and with a molar absorptivity similar to cortisol, but much more slowly.

17-Hydroxycorticosteroids↗

Computer-assisted therapeutic drug monitoring.

The computer is a powerful technology that has been applied to many aspects of the practice of medicine. This report describes how the computer may enhance the process for therapeutic drug monitoring by coordination, control, and education of the medical care team.

Drug Therapy, Computer-Assisted↗