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Magnesium can be used to treat or prevent many cardiac arrhythmias and may improve post-MI outcome. It could also play a role in treating diabetes and hypertension and preventing atherogenesis. Second of two articles. [ABSTRACT FROM AUTHOR]

Clinicians are just beginning to appreciate the role magnesium plays in a vast array of acute and chronic diseases. This article, first of two, tells when to look for magnesium deficieny and how to respond. [ABSTRACT FROM AUTHOR]

Purpose: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization., Methods: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide., Results: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD., Conclusions: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: κ and λ free light chains (FLCs) are monitored to aid in the diagnosis of plasma cell disorders. Our goal was to validate the Diazyme Human κ and λ assays on Beckman Coulter UniCel DxC 800 Synchron and compare to Freelite κ and λ assays on Roche Cobas Integra., Methods: Linearity verification, within- and between-run precision, method comparison, and reference range (RR) verification were conducted using CLSI guidelines. Statistical analysis was performed using EP Evaluator ® . Mean, SD, CV, and bias were determined., Results: Diazyme κ FLC assay was linear within 0.00-191.00 mg/L. Diazyme λ FLC assay was linear within 0.00-205.30 mg/L. Diazyme κ FLC QC1 had a mean of 16.70 mg/L, CV of 7.0%. QC2 had a mean of 33.37 mg/L, CV of 2.6%. Diazyme λ FLC QC1 had a mean of 21.73 mg/L, CV of 2.3%. QC2 had a mean of 42.05 mg/L, CV of 1.5%. Bias of DxC-Diazyme FLCs compared to Integra-Freelite FLCs was -2.55 mg/L (κ FLC), and 4.54 mg/L (λ FLC). Qualitative comparison of κ FLC assays indicated 100% agreement for both normal and abnormal values. For λ FLC assay, agreement was 95% for normal values and 75% for abnormal values. For κ/λ ratio there was 50% agreement for normal values, and 100% for abnormal values. For RR verification, 1 sample was outside the Diazyme κ RR. For λ, all samples were within the manufacturer's RR., Conclusions: Diazyme assays for FLCs have excellent precision and accuracy and are comparable to Freelite assays., (© 2019 American Association for Clinical Chemistry.)

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health., Competing Interests: 4 Author disclosures: RB Costello, RJ Elin, A Rosanoff, TC Wallace, F Guerrero-Romero, A Hruby, PL Lutsey, FH Nielsen, M Rodriguez-Moran, Y Song, and LV Van Horn, no conflicts of interest., (© 2016 American Society for Nutrition.)

Background: Gestational diabetes mellitus (GDM) and low magnesium (Mg) intake and status are associated with an increased risk of type 2 diabetes. However, Mg homeostasis may be modified by GDM. We sought to determine if a history of GDM prospectively modifies associations between Mg and glycemic variables in mothers and their offspring., Methods: Plasma and dietary Mg, anthropometric, lifestyle and glycemic variables were assessed in mothers affected by GDM during 1989-1990, a comparative group of normoglycemic women, pregnant during the same time period, and the 15-year-old, nondiabetic daughters of affected and unaffected pregnancies (n = 332). Multivariate regression analyses evaluated the cross-sectional association between plasma and dietary Mg with glycemic variables in mothers and daughters., Results: Plasma Mg was lower in mothers with a history of GDM in comparison to control mothers after adjustment for current type 2 diabetes, race and body mass index (0.90 ± 0.01 versus 0.96 ± 0.01 mmol/L; p = 0.002). Plasma Mg was significantly associated with insulin sensitivity and was inversely associated with fasting insulin in GDM mothers only (p<0.05). Plasma and dietary Mg were significantly inversely associated with glycated hemoglobin and fasting glucose, respectively, in nondiabetic teenage daughters. For fasting glucose, plasma Mg was inversely associated in GDM-born daughters only., Conclusions: Associations between plasma Mg and some glycemic variables may be stronger in mothers and offspring with a history of GDM.

Background: Premature ventricular complexes (PVC) predict cardiovascular mortality among several adult populations. Increased arrhythmia prevalence has been reported during controlled magnesium (Mg) depletion studies in adults. We thus hypothesized that serum magnesium (sMg) concentrations are inversely associated with the prevalence of PVC in adults at high cardiovascular risk., Methods: Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate the associations between sMg and PVC., Results: PVC prevalence in adults with hypomagnesemia (sMg ≤ 0.70 mmol/L) was more than twice that of adults without hypomagnesemia (50% vs. 21%, p = 0.015); results were similar when adults with cardiovascular disease history were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM). Prevalence of PVC declined across the sMg concentration gradient in adults with T2DM only (p < 0.001 for linear trend). In multivariate logistic regressions adjusted for age, sex, community, body mass index, smoking, physical activity, alcohol consumption, kidney disease, antihypertensive and cholesterol lowering drug use, and blood docosahexaenoic acid concentrations, the odds ratio of PVC among T2DM subjects with sMg > 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98) p = 0.046 compared to those with sMg ≤ 0.70 mmol/L., Conclusions: sMg concentrations were inversely associated with the prevalence of PVC in patients with T2DM in a dose response manner, indicating that suboptimal sMg may be a contributor to arrhythmias among patients with T2DM.

Magnesium is an essential element needed for health. Even though only 1% of the total body magnesium is present in blood, the serum magnesium concentration (SMC) is the predominant test used by medicine to assess magnesium status in patients. The traditional method to establish a reference interval for the SMC is flawed by the large number of "normal" individuals who have a subtle chronic negative magnesium balance due to a significant decrease in magnesium intake over the past century. Evidence-based medicine should be used to establish the appropriate lower limit of the reference interval for health and I recommend 0.85 mmol/L based on current literature. The decrease in magnesium in the diet has led to chronic latent magnesium deficiency in a large number of people since their SMC is still within the reference interval due to primarily the bone magnesium supplementing the SMC. These individuals need adjustment of their diet or magnesium supplementation to achieve a normal magnesium status for health.

Ischemia modified albumin (IMA) is a relatively new marker for evaluating patients with cardiac ischemia. Data are emerging on its potential role in non-cardiac ischemic events. In this pilot study we evaluated the utility of IMA in diagnosing acute coronary syndromes (ACS), assessed its role in the diagnosis of non-cardiac ischemia, and correlated its efficacy with troponin T (TnT). Serum levels of IMA were measured in 89 sequential patients who presented to the emergency room with chest pain for which serum TnT was ordered. The patients were classified into 4 groups based on their IMA and TnT results and discharge diagnoses. The data were analyzed with Fischer's exact test. Multivariate logistic regression analysis relating acute coronary syndrome (ACS) to the combination of TnT and IMA was also performed. The results showed that IMA was a useful marker for the diagnosis of ACS. There was a significant relationship between TnT and IMA (p = 0.032), suggesting that both these biomarkers added significant information about the presence of ACS (p = 0.028) and may be useful for triage of patients who present to the emergency room with chest pain. Serum IMA was also increased in a small proportion of patients with symptoms of stroke, suggesting that it should be considered a marker of acute ischemic events and not specific for cardiac ischemia.

Background: Treatment of serum with ethanol at 100 ml/l eliminating fibrinogen from electrophoretic pattern produces an additional band at alpha2/beta junction. This study is to determine the source and the nature of this artifact., Methods: The supernatant after ethanol precipitation was used for electrophoresis. Protein concentrations of each fraction in ethanol- and saline-treated samples were compared, and immunofixation electrophoresis (IFE) to identify transferrin, C3, and LDL was performed. C3 IFE was also conducted for fresh sera and sera stored for 2 weeks., Results: The artificial band at alpha2/beta junction was identified in ethanol-treated sera but not in saline-treated sera. Protein concentration in the beta fraction was reduced after ethanol treatment as compared to saline-treated samples (n=10, p<0.01). The spurious band at alpha2/beta junction was recognized in C3 IFE. C3 IFE also showed a band at alpha2/beta junction in samples stored for 2 weeks., Conclusions: Ethanol treatment of serum creates an artificial band with C3 immunoreactivity at alpha2/beta junction. This could be due to the accelerated hydrolysis of C3 by ethanol treatment. Laboratories using ethanol to evaluate a possible fibrinogen band should be aware of this phenomenon, and the serum protein electrophoretic pattern after ethanol treatment should only be used to rule out fibrinogen.

Background: Conflicting data exist regarding the presence of magnesium (Mg) deficiency and the therapeutic efficacy of Mg in premenstrual syndrome or premenstrual dysphoric disorder (PMDD)., Methods: The % Mg retention was determined using 24-hour urinary Mg excretion and the total dose of Mg given intravenously. In women with (n = 17) and without (n = 14) prospectively diagnosed PMDD, several blood measures of Mg and mood were obtained before, immediately after, and the day following an intravenous Mg (.1 mmol/kg) loading dose. A positive mood response was seen under open conditions; as open Mg infusion improved mood, subsequent PMDD patients (n = 10) were randomized in a double-blind, placebo-controlled, crossover fashion., Results: Patients (31.5%) and control subjects (27.5%) retained comparable mean percentages of Mg. Neither group differed in measures of mean Mg before, immediately after, or the day following Mg infusion. Although there was a time effect for all mood measures in the patient group (p < .01 for all), there was neither a treatment nor time-by-treatment effect., Conclusions: Contrary to prior reports, we found no evidence of Mg deficiency in women with PMDD compared with control subjects. Furthermore, Mg was not superior to placebo in the mitigation of mood symptoms in women with PMDD.

Positive pregnancy test results occurred in a nongravid, premenopausal woman while she was receiving chemotherapy for multiple myeloma. We tested 2 hypotheses to account for this finding: (1) Heterophil antibodies caused positive interference in the immunoassays. (2) Genuine human chorionic gonadotropin (hCG) originated from a nonsyncytiotrophoblastic source. Paraprotein was eliminated as a source of positive interference because 3 different instruments with unique capture and signal antibodies gave similar results (83, 90, and 97 mIU/mL [83, 90, and 97 IU/L]). Human antimouse antibodies (HAMAs) were unlikely to cause positive interference because immunoreactivity was maintained after serum was treated to neutralize heterophil antibodies. Immunoassays performed after gel filtration of serum indicated that immunoreactivity was due to genuine hCG. The high-molecular-weight fraction (heterophil antibody) had 6 mIU/mL (6 IU/L) of hCG. The low-molecular-weight fraction (hCG) had 86 mIU/mL (86 IU/L) of hCG. Immunohistochemical stains revealed that myeloma cells expressed immunoreactive hCG. Hence, multiple myeloma caused positive pregnancy test results in a nongravid woman.

Reducing errors and improving quality are an integral part of Pathology and Laboratory Medicine. The rate of errors is reviewed for the pre-analytical, analytical, and post-analytical phases for a specimen. The quality systems in place in pathology today are identified and compared with benchmarks for quality. The types and frequency of errors and quality systems are reviewed for surgical pathology, cytopathology, clinical chemistry, hematology, microbiology, molecular biology, and transfusion medicine. Seven recommendations are made to reduce errors in future for Pathology and Laboratory Medicine.

Background: We determined the diagnostic value of the trypsin inhibitor, uristatin, that is commonly found in urine and plasma in patients with infections or inflammations of any kind., Methods: We collected urine specimens from patients with infections of the urinary or upper respiratory tract and from healthy controls. We also collected blood from patients with a likely upper respiratory tract infection and healthy controls. A bacterial count of >10(5) organisms/ml in urine was considered to represent infection rather than contamination., Results: The uristatin dipstick test in urine showed acceptable negative predictive values (NPV of up to 93%) for patients without infection or inflammation. Here, the dipsticks could eliminate some urine cultures. For those with infection or inflammation, the positive predictive values (PPV) of the dipsticks were lower (up to 57%). Including the leukocyte esterase and nitrite values increased the PPV of the dipsticks for those with disease., Conclusions: The uristatin strip was more accurate than the leukocyte and nitrite dipsticks for predicting upper respiratory infections (URI) and C-reactive protein for those with infection or inflammation. The uristatin dipstick was able to detect both the bikunin and uristatin inhibitors.

Although heart failure may be diagnosed readily in its advanced stages, it may be difficult to diagnose clinically in its early stages.Thus, there is a critical need for an inexpensive, simple, rapid,and objective test for heart failure. This article discusses the role and assessment of ventricular natriuretic peptides and related pep-tides in heart failure.

The interpretation of the total serum testosterone concentration is problematic because it is related directly to the serum SHBG concentration.Frequently, an estimate of the serum free testosterone concentration is obtained to better assess the clinical status of the patient. We reviewed five methods for the determination of free testosterone or a surrogate test/index and the problems with these methods. The calculated free testosterone or BAT (highly positively correlated) are recommended as the preferred tests to assess biologically-active testosterone, although interlaboratory values may differ because standards are not available. The controversies in evaluating gonadal function are illustrated by the andropause (elevated SHBG) and obese men (decreased SHBG).

Urinary trypsin inhibitor (uTi) is a product of elastase-mediated degradation of interleukin-alpha-inhibitor (I-alpha-I). Its activity increases in the urine of patients with a malignancy, inflammation, or infection, or in late pregnancy. The objective of this study was to compare the sensitivity of uTi in urine with that of serum quantitative C-reactive protein (CRP) for diagnosing infection, as indicated by white cell response and clinical assessment. Ninety controls and 171 patients with various systemic infections were enrolled. We measured uTi enzymatically on a Cobas Fara (Roche Diagnostics). Patients were separated into bacterial, probable bacterial, viral, or probable viral groups based on the results of a complete blood count with differential (CBC), urinalysis (UA), and clinical assessment. In the bacterial (n=70) and control (n=90) groups, the uTi values (mean+/-SE) were 25.3+/-3.1 mg/L and 2.8+/-0.8 mg/L, respectively. uTi (at 2.7 mg/L) had a diagnostic sensitivity of 91% and specificity of 82% (AUC=0.889), whereas CRP (at a cutoff of 10 mg/L) had a sensitivity and specificity of 82% and 96%, respectively (AUC=0.921). As a marker of infection (positive in both bacterial and viral groups), uTi had a sensitivity of 91% (AUC=0.884) vs. 89% (AUC=0.828) for CRP. Our data indicate that uTi has sufficient clinical sensitivity for screening systemic infections, and may have diagnostic value as a noninvasive test., ((c) 2004 Wiley-Liss, Inc.)

Background: Fibrinogen in serum specimens can be misinterpreted on protein electrophoresis as a monoclonal protein. We evaluated selective precipitation of fibrinogen with ethanol., Methods: Pooled human plasma was mixed with absolute ethanol or saline (final concentrations of 40, 80, 100, 120, and 160 mL/L) and incubated at 4 degrees C overnight or placed in an ice bath for 15 min. After centrifugation, the supernatants and resuspended pellets were used for protein electrophoresis and quantitative measurements of protein and fibrinogen., Results: The fibrinogen band was effectively eliminated from the electrophoretic pattern in the plasma samples treated with ethanol at 100 mL/L and incubated in an ice bath for 15 min without a significant change in immunoglobulin concentrations. The 100 mL/L ethanol did not noticeably change the electrophoretic pattern of monoclonal immunoglobulins. This approach allowed analysis of a sample collected from an arteriovenous shunt kept open with heparin., Conclusions: Ethanol, 100 mL/L, can selectively precipitate fibrinogen without significantly interfering with the immunoglobulins. The precipitation process can be completed in 15 min at 0-4 degrees C and can avoid the need to obtain another blood sample.

Objective: To assess whether, in children, oral magnesium oxide reduces migrainous headache frequency, severity, and associated features compared to placebo., Background: There is no single, safe, widely well-tolerated, and effective prophylactic treatment for all children and adolescents with frequent migrainous headache., Design: Randomized, double-blind, placebo-controlled, parallel-group trial., Methods: This study was conducted between June 1997 and January 2000 using 7 selected Northern California Kaiser Permanente sites. We recruited children of ages 3 to 17 years who reported a 4-week history of at least weekly, moderate-to-severe headache with a throbbing or pulsatile quality, associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with sleep, but no fever or evidence of infection. Subjects were randomly assigned to receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of headache days (days with at least one headache) during each of eight 2-week intervals was chosen to be the primary outcome variable., Results: Of those enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44 placebo); 74 of 192 eligible subjects declined to participate. Baseline information on demographic factors, health status, and headache history was similar comparing the 2 groups. By intention-to-treat analysis, we found a statistically significant decrease over time in headache frequency in the magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although the slopes of these 2 lines were not statistically significantly different from each other (P =.88). The group treated with magnesium oxide had significantly lower headache severity (P =.0029) relative to the placebo group., Conclusions: This study does not unequivocally determine whether oral magnesium oxide is or is not superior to placebo in preventing frequent migrainous headache in children, but treatment with the active agent did lead to a significant reduction in headache days. Larger trials involving this safe, appealing complementary therapy are needed.

The Magnesium and Neurologic Endpoints Trial (the so-called MagNET Trial) was a randomized clinical trial that was undertaken to establish whether the antenatal usage of magnesium sulphate could protect neonates from having adverse neurologic outcomes. Unfortunately, the trial was suspended after 15 months of enrolment because of excess total paediatric mortality among those exposed to magnesium sulphate. Following our original report and contrary to the original hypotheses, additional analyses of our data have actually shown a statistically significant increase in the risk of neonatal intraventricular hemorrhage, as well as total adverse paediatric outcomes, among those with higher levels of ionized magnesium at delivery. Nonetheless, it has been postulated, but not established, that anions of magnesium other than sulphate could have a more benign, or even beneficial, effect on health outcomes in the neonate.