Frequency of hypomagnesemia in hospitalized patients receiving digitalis.

We examined the frequency of hypokalemia and hypomagnesemia in patients receiving digitalis. Serum sodium, magnesium, and potassium levels were determined in 136 serum samples sent to the laboratory for digoxin assay. Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%), followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%, hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia (greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians are more attuned to avoiding hypokalemia than hypomagnesemia in patients receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to the toxic effects of digitalis, our observation suggests that hypomagnesemia may be a more frequent contributor than hypokalemia to induction of toxic reactions to digitalis. Routine serum magnesium determination in patients receiving digitalis, who often are also receiving potent diuretics, may assist in identifying additional patients at risk for the toxic effects of digitalis.

Relationship between arterial and venous bicarbonate values.

We determined the clinical efficacy of using the venous CO2 value, as obtained with routine "electrolytes", in acid-base management. Venipuncture samples for venous CO2 content and chloride concentrations were obtained in 336 patients with arterial blood pH, PaO2, PaCO2, and oxygen saturation determinations. The linear correlation between actual calculated arterial HCO3- and the measured venous CO2 was significant (P less than .001). Using venous CO2, chloride, and arterial pH values, we present various prediction equations for estimating arterial HCO3-. We determined the effects of time delay, exposure to air, and acute changes in arterial blood pH and PaCO2 on venous CO2 levels. Venous CO2 determinations should not be substituted for the arterial HCO3 value in the Henderson-Hasselbalch equation to calculate arterial blood pH or PaCO2. Clinically, the venous CO2 value has little direct use, but when venous CO2 content is abnormal, it should alert the clinician to the need for obtaining arterial blood gas and pH values.

Predictors of clinical hypomagnesemia. Hypokalemia, hypophosphatemia, hyponatremia, and hypocalcemia.

Four studies were conducted, each determining the frequency of hypomagnesemia in patients already found to have one abnormal electrolyte determination. Hypomagnesemia occurred in 42% of patients with hypokalemia, 29% of patients with hypophosphatemia, 27% of patients with hyponatremia, and 22% of patients with hypocalcemia. These observations suggest that detection of either hypokalemia, hypophosphatemia, hyponatremia, or hypocalcemia, all of which are routinely available determinations, should alert the clinician to order serum magnesium determinations because of the frequent association of hypomagnesemia with these electrolyte perturbations. Optimally, levels of serum Mg should be determined on a routine basis because of the frequency of the occurrence of hypomagnesemia in hospitalized patients.

Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumor: a prospective randomized study.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.

Lack of improved growth outcome related to nonnutritive sucking in very low birth weight premature infants fed a controlled nutrient intake: a randomized prospective study.

The effect of nonnutritive sucking during gavage feeding on nutritional outcome and gastrointestinal transit time was evaluated in 18 premature appropriate for gestational age infants whose birth weights were less than or equal to 1,400 g and gestational ages were less than or equal to 30 weeks. Infants were randomized to a treatment (nonnutritive sucking infants received a pacifier for 30 minutes with each feeding, 12 times per day until they reached a weight of 1,500 g, eight times per day thereafter) or control (no pacifier) group. The nine nonnutritive sucking (five girls, four boys) and nine control (five girls, four boys) infants were treated for 14 days. Infants were without medical complications and were fed a single premature formula by intermittent gastric gavage at exactly 120 kcal/kg/d throughout the study period. Weight gain, linear growth, subscapular and triceps skinfold, and arm circumference accretions were assessed weekly. Serum proteins (albumin, prealbumin, retinol-binding protein, and transferrin) were measured weekly. Gastrointestinal transit times were measured weekly using carmine red markers. In contrast to previous studies, these data indicate no apparent effect of nonnutritive sucking on growth outcome, serum proteins, or gastrointestinal transit time in growing, very low birth weight infants when nutrient intake was controlled. In a subgroup of eight boys (four nonnutritive sucking, four control), energy and fat excretions were determined from 72-hour fecal collections and energy expenditure was estimated from six-hour cumulative heart rate measurements. Neither excretion of fat and calories nor estimated energy expenditure was affected significantly by nonnutritive sucking in this subgroup of baby boys. Fat excretion correlated well (r = .987) with energy excretion.

Exercise-induced changes in common laboratory tests.

Examination of 19 serum biochemical and hematologic parameters in a group of white male runners, ranging in age from 23 to 47 years, just prior to and immediately after a 13-mile "mini-marathon," demonstrated a significant increase, by paired Student t-test, in mean values of: K+, BUN, creatinine, CK, LDH, AST (SGOT), alkaline phosphatase, bilirubin, uric acid and leukocyte counts. Prevailing environmental conditions were such as to produce no significant hemoconcentration. Using this group's statistics and this hospital laboratory's upper limits of normal, the percentage of values above two SDs are, for the resting state: K+ 7%, BUN 7%, creatinine 0%, CK 21%, LDH 21%, AST 0%, alkaline phosphatase 0%, bilirubin 7%, uric acid 7%, and leukocyte count 0%. Post-exertional values above normal limits are: K+ 7%, BUN 21%, creatinine 21%, CK 93%, LDH 86%, AST 0%, alkaline phosphatase 0%, bilirubin 14%, uric acid 36%, and leukocyte 71%. Consequently, abnormally high values for K+, BUN, creatinine, CK, LDH, bilirubin, uric acid, and leukocyte counts can often be expected in some patients who exercise heavily. The degree of the abnormality will depend on the level and length of exercise as well as the elapsed time between exercise and testing.

A radioassay for angiotensin converting enzyme.

Current methods for measuring angiotensin converting enzyme activity (EC 3.4.15.1, ACE) are somewhat cumbersome and have limited the general availability of the test. We describe here a simple four-step radioassay for ACE which uses the substrate 14C-Hippurate-L-Histidyl-L-Leucine and measures the product, 14C-Hippurate. We found that incubation at pH 7.0 (Hepes buffer) increased the sensitivity of the test by 50 percent when compared to results obtained with the pH 8.0 buffer normally used for ACE assays. A split sample comparison study between the radioassay and the spectrophotometric method showed good correlation (n = 47; mean, spectrophotometric, 26.0 U/mL; mean, radioassay, 26.1 U/mL; m = 0.86; b = 3.9; r = 0.868). We found that there was no significant difference between the spectrophotometric, kinetic and radioassay (Newman-Keuls multiple range test), but the liquid chromatographic method gave results significantly different from the other methods. The assay for ACE described here combines enhanced technical ease with the sensitivity of a radioassay.

Routine serum magnesium determination: a contemporary clinical imperative.

Identification of hypomagnesaemia or hypermagnesaemia is presently the most expeditious method of clinically identifying perturbations in Mg metabolism. Clinicians may overlook as much as 90% of clinical hypomagnesaemia and hypermagnesaemia when serum Mg is determined on order versus on a routine basis. Routine serum Mg determination will facilitate management of digitalis toxicity in patients who are not currently identified as being hypomagnesaemic as well as preventing the occurrence of refractory K repletion. In our opinion routine serum Mg determination represents a clinical need which has not been addressed to date.

Evaluation of a solid-phase enzyme immunoassay for human choriogonadotropin beta subunit.

We evaluated a quantitative solid-phase enzyme immunoassay for human choriogonadotropin beta subunit (beta-HCG) with anti-beta-HCG:horseradish peroxidase conjugate, recently marketed by Abbott Laboratories. We compared results on 56 patients' serum specimens, obtained mostly for followup of neoplastic disease, with those by a competitive radioimmunoassay kit. The correlation was good, the differences being of little clinical significance. Linear regression in the low and intermediate ranges gave a slope of 0.93, a y-intercept of 0.34, and a correlation coefficient of 0.97. Precision studies yielded an interassay CV of 6.4% in the intermediate range and 13% in the low range. Sensitivity was 0.69 int. unit/L. Cross reactivity was 1 to 2% with specimens fortified with lutropin or follitropin. The only substantial problem was with linearity in the upper part of the standard curve, especially in the interval, 100-200 int. units/L. This problem is obviated by adequate sample dilution.

Modified aca method for determination of iron chelated by deferoxamine and other chelators.

Iron in serum and urine specimens containing deferoxamine (a chelator used in treating acute iron intoxication) can be measured by the DuPont aca discrete-analyzer method for iron if 0.5 mL of a 100 mL/L solution of thioglycolic acid (mercaptoacetic acid) is added to the IRN-1 and IRN-2 test packs before their use. This reagent releases the unreactive chelated iron, allowing reliable colorimetry. Because about 50% of hemoglobin iron is measured by the modified method, hemolysed samples should not be used (or results should be corrected for hemoglobin iron). The modification allows emergency determination to total serum iron and assessment of urinary iron during chelation therapy, as well as measurement of plasma iron in samples treated with sodium citrate or oxalate plus fluoride (the unmodified aca iron method gives falsely low iron values in the presence of these chelators). About 60% of iron present as the dextran complex (Imferon) is measured by the modified aca method, as compared with <5% by the unmodified aca technique.

Comparison of the use of L-tyrosine apodecarboxylase and D-serine apodehydratase for plasma pyridoxal phosphate assay.

The enzymatic methods for plasma pyridoxal 5'-phosphate (PLP) assay using L-tyrosine apodecarboxylase (apo-LTD) and D-serine apodehydratase (apo-DSD) were compared with respect to their operating characteristics, accuracy and precision. With the apo-LTD assay, the recovery of authentic PLP added to irradiated plasma was 96-100% and the precision for within-run and run-to-run replicates was 4-5% (coefficient of variation). The recovery of authentic PLP with the apo-DSD assay tended to be lower (viz., 95%) and the within-run and run-to-run coefficients of variation tended to be higher (viz., 5-6%), but these differences were not statistically significant. When these two assay methods were directly compared in determining the plasma PLP levels of 67 hospitalized patients, the regression lines exhibited correlation coefficients of 0.89 and 0.92 and slopes of 0.77 and 0.78, respectively. When the plasma PLP values were less than 7.5 ng/ml, the values determined by the apo-DSD assay tended to be higher than those measured by the apo-LTD method and vice versa. The lack of better agreement between the two assay methods may be explained by the fact that an inhibitor exists in plasma extracts that impairs the binding of PLP to apo-DSD and that the correction for this interference may not be uniform from one plasma sample to another. However, if one is willing to tolerate the small discrepancies between the values obtained by the apo-DSD and apo-LTD assays, these assay methods can be used interchangeably. The apo-DSD assay has the advantage of being easily adapted to a modern automated spectrophotometric centrifugal analyzer.

An alternative method for assaying cerebrospinal fluid protein in the presence of methotrexate.

Therapeutic concentrations of methotrexate can cause significant positive interference in cerebrospinal fluid (CSF) protein values when assayed in the Du Pont aca. Conversely, our modified turbidimetric method, in which trichloroacetic acid (TCA) plus a sample blank containing dilute hydrochloric acid is used in place of TCA, exhibits little or no interference from methotrexate. This was verified by assaying solutions that contained a constant amount of protein (approximately 430 mg/L) and various amounts of methotrexate (0.0-2.3 x 10(-4) mol/L) by both the Du Pont aca and the manual turbidimetric method. As expected, the aca results showed increasing protein values with increasing methotrexate, whereas the manual method gave results approximating the expected protein value irrespective of the methotrexate concentration.

An enzyme immunoassay procedure for cancer antigen 125 evaluated.

The performance of a new enzyme immunoassay (EIA) procedure (Abbott Labs.) for cancer antigen 125 (CA 125) met or exceeded the manufacturer's claims for all analytical variables examined. Overall correlation with results obtained with a radioimmunoassay (RIA) were good. However, near the decision thresholds typically chosen to define a positive result for ovarian carcinoma, EIA results were 10 to 20 arbitrary units/mL less than the RIA results. At specific decision thresholds, therefore, the sensitivities and specificities of the EIA and RIA procedure differed. Adjusting the decision thresholds gave a similar optimum efficiency for each procedure: EIA, 82.9% (decision threshold, 35 units/mL); RIA, 83.4% (decision threshold, 54 units/mL). Receiver-operating characteristic curves showed that the two procedures' ability to distinguish patients with active ovarian carcinoma from those with disease in remission was the same.

Evaluation of liquid scintillation counting solutions for radioimmunoassay of hepatitis-associated antigen (HBsAg).

Liquid scintillation counting solutions for radioimmunoassay of hepatitis associated antigen (HBsAg) are evaluated and discussed. Data is also presented which indicates that liquid scintillation counting could be carried out by placing cut-off Ausria-125 test tubes in counting vials containing 10 ml of either Brays, Unogel, or Instagel solutions. The data suggest that Brays was the least effective and Unogel and Instagel were the most effective liquid scintillation counting solutions. This is a fundamental consideration if a laboratory is contemplating an initial investiment in counting equipment. The acquisition of a liquid scintillation counter provides additional capabilities for the clinical laboratory interested in radioisotope measurements. In addition, if a laboratory already has a liquid scintillation counter (Beta counter), the director of the clinical laboratory may elect not to purchase additional counting equipment (gamma counter) since he already has the added advantage of measuring iodine-125 with the Beta counter. The authors propose liquid scintillation (RIA) as an alternative counting system for HBsAg detection in hospital patients and donors.

High-pressure liquid chromatographic assay of chloramphenicol in biological fluids.

Chloramphenicol can be assayed by a sensitive and selective high-pressure liquid chromatographic assay technique. The method described is easily adapted to analysis of many other drugs.

Effect of diet on urinary excretion of VMA, HVA, metanephrine, and total free catecholamine in normal preschool children.

Quantitation of the urinary metabolites of catecholamines, including VMA, HVA, and metanephrines, from six normal preschool children was performed during a normal diet, a restricted diet, and a diet with increased amounts of vanilla, vanillin, and phenolic acids. Ingestion of these substances has been suspected of producing elevated values of urinary catecholamines and their metabolites. Urine was collected on the fourth day of each diet in two consecutive 12-hour aliquots, beginning at 8:00 AM. Statistically significant diurnal variation in excretion of all three metabolites and total free catecholamines (epinephrine, norepinephrine, and dopamine) was demonstrated. Diet did not alter exceretion of total free catecholamines or any of the three metabolites. This study suggests that a three-day restricted diet is not necessary prior to screening children for neuroblastoma when using quantitative assay methods and that all screening tests should be performed on a 24-hour urine sample.

Radioimmunoassay for arylsulfatase A in urine.

Purified arylsulfatase A (EC 3.1.6.1) from human urine was radioiodinated under conditions that caused no significant loss of antigenic activity. We used this labeled arylsulfatase A (specific radioactivity 4-7.5 Ci/g) together with nonlabeled enzyme and rabbit antiserum produced against homogeneous enzyme to develop a radioimmunoassay for arylsulfatase A in urine. A solid-phase, second-antibody technique (Immunobead Second Antibody; Bio-Rad Laboratories) was used to separate free enzyme from antigen-antibody complexes. The working range of the assay was 0.1-4.0 ng of enzyme; within- and between-assay CVs were around 10%, and the analytical recovery was 105.5% (SD 7.7%). The lower limit of detection was 0.08 ng of arysulfatase A per assay, substantially less than that of typical activity-based assays. Over a wide range of urinary arylsulfatase A activities, results by this method agreed well (r = 0.99) with those obtained by activity assays. We measured the enzyme in urines of 59 healthy volunteers and 92 patients with different diseases, including a group of colorectal cancer cases, to determine whether this could serve as a reliable marker for cancer of the colon; however, urinary excretion of arylsulfatase A by most patients with colon cancer was within normal limits.

An evaluation of four serum tests for pregnancy.

We evaluated four pregnancy tests (Biocept-G, Beta-CG, Preg/Stat, and HCG-Beta Screen), using sera from 59 nonpregnant subjects and 77 patients with serum human choriogonadotropin beta-subunit (beta-hCG) concentrations ranging from 4 to 100 000 int. units/L. The results obtained for each test were compared with the results predicted on the basis of the sample's beta-hCG concentration and the beta-hCG concentration the manufacturer claimed necessary for a positive result (the test's analytical sensitivity). Biocept-G had the best sensitivity (100%), specificity (98.9%), and accuracy (99.2%). Beta-CG had the poorest sensitivity (86.4%), Preg/Stat the poorest specificity (87.5%), and accuracy (92.6%). We confirmed the manufacturer's claimed analytical sensitivity (200 int. units/L) for the Biocept-G procedure, but our calculated analytical sensitivity for the other tests was significantly different from that claimed by their manufacturers. Best results were obtained with Biocept-G, but with its analytical sensitivity of 200 int. units/L, samples from early pregnancy will give negative results. None of the pregnancy tests evaluated here will establish the presence or absence of early pregnancy with certainty.

Five recent urinary tests for early pregnancy evaluated.

We evaluate five tests developed for the earlier detection of pregnancy, either in the clinical laboratory or by the patient in her home. These tests offer no advantage over other urinary pregnancy tests, and the results are distinctly inferior to those reported (Clin. Chem. 29: 561-563, 1983) for some serum tests for pregnancy.

PIP: 5 urinary tests developed for earlier detection of pregnancy were evaluated. 1 of these tests, Early-In-Home Pregnancy Test (e.p.t.), was developed for home pregnancy testing; the other 4 (Preg/Stat, Betacept, Sensi-Tex, and Sensi-Slide) are laboratory tests alleged by the manufacturers to have greater sensitivity than has been associated with such tests in the past. Urine samples were obtained from 59 control subjects known not to be pregnant and 29 patients with a wide range of gestational ages and serum human choriogonadotropin (hCG) concentrations who were being treated at a pregnancy termination clinic. The specificity and sensitivity of each test was determined. Betacept, Sensi-Tex, Sensi-Slide, and e.p.t. had specificity rates of 97-100%, which is consistent with the results reported for other pregnancy tests. For Preg/Stat, however, only 90% of the results were negative for nonpregnant subjects, yielding an unacceptabily high 10% false-positive rate. On the other hand, the Preg/Stat test was the most sensitive, providing a positive result for all urine specimens from patients whose beta-hCG concentrations exceeded 1000 IU/l of serum. Betacept was the next most sensitive, giving results equivalent to those reported for tube-type pregnancy tests. Betacept is not recommended for routine use because of the major technical problems associated with isotopic laboratory tests. The percentage of correct values for the remaining 3 tests was poorer than would be expected for most of the currently available tube-type pregnancy tests. It is concluded that the 5 tests evaluated in this study offer no advantage over other urinary tests, and the results are distinctly inferior to those reported for some serum tests of pregnancy.

Hyperammonemia after transurethral resection of the prostate: a report of 2 cases.

We report on 2 patients who became deeply comatose after transurethral resection of the prostate. Both patients were severely hyponatremic and hyperammonemic but the course of the comas followed serum ammonia concentrations more closely than serum sodium concentrations. The genitourinary irrigant used in both procedures was a 1.5 per cent glycine solution. Serum amino acid analyses in 1 patient suggested that the postoperative hyperammonemia was due to catabolism of glycine absorbed during surgery. The inadequate activation of normal pathways of ammonia metabolism in this patient may have been caused by a partial deficiency of the urea cycle enzyme argininosuccinate synthetase. We believe that hyperammonemia should be considered as a cause of encephalopathy after transurethral resection of the prostate. The 1.5 per cent glycine genitourinary irrigating solution may not be as nontoxic as generally believed.