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.

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.

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.

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.

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.

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.

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.

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.

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.

Inhibition of cholesterol oxidase in a patient with Cushing's syndrome.

Serum from a patient with Cushing's syndrome who was being treated with mitotane contained components that interfered with determination of cholesterol in the Du Pont aca. A measured concentration of cholesterol of 4.19 g/L in the undiluted serum increased to a calculated concentration of 9.50 g/L in diluted serum. Adding additional cholesterol oxidase (EC 1.1.3.6) overcame the reaction inhibition in the undiluted sample; adding additional cholesterol esterase (EC 3.1.1.13) had no effect. There is the potential for clinically significant underestimation of cholesterol with the aca in such patients, because the interference may remain undetected. On the other hand, the aca accurately quantified undiluted specimens containing as much as 10 g of cholesterol per liter when mitotane was not present.

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.

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.

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.

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.

Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.

The ventilatory response to intravenous and ventriculo-cisternal theophylline.

The stimulatory effect of theophylline on ventilation was studied in nine anesthetized dogs. Theophylline infused intravenously (10 mg/kg bolus, then 1.00 mg/kg/hr) for 210 minutes significantly increased the minute volume of ventilation (P less than 0.05 at 210 minutes). After a recovery period of seven to fourteen days, ventriculo-cisternal perfusion was performed with mock cerebrospinal fluid (CSF). Theophylline added to the mock CSF did not significantly change the minute ventilation. ventriculo-cisternal perfusion utilizing mock CSF not containing theophylline combined with intravenous theophylline infusion stimulated ventilation similarly to the previous intravenous theophylline infusion. Therefore, stimulation of ventilation by theophylline appears to relate to the serum theophylline concentration and not the ventricular CSF theophylline concentration.