A survey of wellness issues in emergency medicine (Part 3).
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Biomedical subjects
Publications and source records attributed to G Lum.
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The causes for low serum alkaline phosphatase (ALP) activity (reference range 30-115 U/L) in a large Veterans Medical Center were reviewed. Of 69,864 ALP determinations made over a 4-year period, 130 were low (< 30 U/L, 0.19%), representing 88 individual patients. Of these, 83 (primarily men, 96%) patients' charts were reviewed and classified into two groups, those with and those without conditions previously reported to be associated with decreased serum ALP activity: 47% had conditions associated with low ALP activity, the most frequent being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anemia (1.2%); 53% of patients did not have clinical conditions previously associated with low ALP activity. No case of clinically apparent hypophosphatasia, for which low ALP activity is the defining characteristic, was found in this population of veterans. A low serum ALP may be of significance in other patient populations such as children, where it is associated with achondroplasia and cretinism, or in postmenopausal women with osteoporosis taking estrogen replacement therapy. In the predominantly adult male population in this study, low ALP activity was rare; it was seen most frequently in cardiac surgery patients postoperatively, a clinical condition heretofore not commonly associated with low serum ALP activity.
OBJECTIVE: To assess the association between performance on graded chemistry surveys and evaluation of linearity and calibration in Linearity surveys. DESIGN: Data from Linearity Surveys (LN series) and from routine comprehensive College of American Pathologists chemistry surveys (all series) were used to evaluate the hypothesis that laboratories with nonlinear or univerified calibration would have a greater likelihood of unacceptable performance on comprehensive chemistry surveys. RESULTS: This study found that acceptable calibration verification evaluation is significantly related to acceptable rates for most analytes, including albumin, calcium, chloride, glucose, iron, magnesium, sodium, total bilirubin, uric acid, high-density lipoprotein cholesterol, triglycerides, alkaline phosphatase, alanine and aspartate aminotransferase, digoxin, gentamicin, phenobarbital, procainamide, and thyroxine. CONCLUSION: There is a consistent and strong relationship between calibration verification problems in the Linearity Surveys and failure rates in the College of American Pathologists chemistry surveys. Laboratories with poor calibration evaluations on Linearity Surveys have higher unacceptable rates on proficiency tests. Individual laboratories who were rated linear and whose calibration was verified by Linearity Surveys have lower unacceptable rates.
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The frequency and prevalence of hypomagnesemia (less than 0.72 mmol/L) in two divisions of a consolidated medical center with two distinct patient populations, acute and chronic, was studied. In the acute care patient population, the frequency and prevalence of hypomagnesemia was 41.4% (222 of 536 determinations) and 26.1% (92 of 353 patients) compared to a frequency of 12.5% (50 of 399 determinations) and prevalence of 3.5% (9 of 258 patients) in the chronic care population. Although the two divisions have similar numbers of hospital discharges, the acute care facility handles acute medical and all surgical cases, whereas the chronic care facility handles primarily psychiatric cases. In the acute care facility, the most common diagnoses associated with hypomagnesemia were coronary artery disease, malignancy, coronary artery bypass surgery, chronic obstructive pulmonary disease and alcoholism, whereas in the chronic care facility, alcoholism, liver disease, and carcinoma were the most frequent diagnoses associated with hypomagnesemia. The frequency and prevalence of hypomagnesemia in a patient population depends on the type of patient population studied and is significantly greater in the acute care compared to the chronic care patient population.
Plasma carnitine and the effect of oral carnitine supplementation on serum triglycerides was studied in 12 pediatric patients receiving continuous ambulatory peritoneal dialysis (CAPD). Baseline evaluation of all patients included plasma carnitine and serum triglyceride values. Following randomization into two groups, only group 2 patients received oral L-carnitine supplementation, 100 mg/kg/day, for 2 months. The initial laboratory evaluation was repeated at the conclusion of the study. Plasma carnitine values were also determined from a control population. Mean baseline plasma carnitine concentrations of group 1 (39.8 +/- 8.0 nmol/ml) and group 2 (45.2 +/- 10.3 nmol/ml) patients were not significantly different from each other or from the control population. Serum triglyceride values were elevated in both groups (group 1 - 206.5 +/- 100.0 mg/dl; group 2 - 279.3 +/- 74.5 mg/dl). After 2 months, the mean plasma carnitine concentration of group 2 patients increased to 147.7 +/- 84.1 nmol/ml, significantly greater than the value of group 1, 32.8 +/- 8.0 nmol/ml (p less than 0.004). However, no significant change in the serum triglyceride level was noted in either group. We conclude that the plasma carnitine status of pediatric patients receiving CAPD is normal and that oral carnitine supplementation does not lead to the resolution of hypertriglyceridemia.
The prevalence of low serum urea nitrogen concentrations (less than 50 mg/L) in our patient population was 1.2% (151 per 12,380 determinations), representing 95 individual cases. Of these, 81 of the patients' charts were located, reviewed, and classified into two groups, those with and those without hepatobiliary disease. Hepatobiliary disease was found in 36% of the 81 patients; 90% of these showed evidence of alcohol abuse, as did 19% of those without hepatobiliary disease. The remaining patients without hepatobiliary disease had various clinical conditions: psychiatric disorders (14.8%), overhydration (12.3%), endocrine disorders (7.4%), cardiovascular diseases (4.9%), prednisone administration (3.7%), and special diets (2.5%). Thus, in our patient population the most frequent cause of low serum urea nitrogen concentrations was alcohol abuse, found in about half of the cases.
Significant decreases in magnesium (Mg) concentration and alkaline phosphatase (ALP, EC 3.1.3.1) activity in serum were seen in patients after cardiac surgery with cardiopulmonary bypass (Group 1), as compared with non-cardiac-surgery patients after general anesthesia (Group 2) or only spinal anesthesia (Group 3). Mean changes for Mg and ALP by the first postoperative day, compared with pre-operative baseline values, were as follows: Group 1: Mg -7.5 mg/L (-38.3%), ALP -46U/L (-48.4%); Group 2: Mg -3.3 mg/L (-17.4%), ALP -17 U/L (-16.5%); and Group 3: Mg -1.9 mg/L (-10.0%), ALP -15 U/L (-14.0%). The decreases in Mg and ALP observed in post-cardiac-surgery patients appear to be a consequence of the cardiac surgery and the cardiopulmonary bypass pump. Measurement of Mg and ALP in a subgroup of 10 cardiac-surgery patients for 10 days postoperatively showed initial decreases, with gradual recovery to near-normal values by the 10th day. That the changes in Mg and ALP seen postoperatively were not attributable to hemodilution alone was confirmed by measuring total-protein concentrations before and after operation. ALP requires Mg ion in vitro for optimal activity, but addition of Mg in the appropriate amounts to sera with low ALP activity did not restore ALP activity. The low ALP activity seen in post-cardiac surgery patients in vivo may perhaps be related to factors other than Mg that were removed by the cardiopulmonary bypass pump.
Two divergent laboratory approaches to the determination of direct bilirubin were assessed. The first approach, assaying direct bilirubin (DB) on all total bilirubin (TB) requests regardless of TB values, resulted in a true negative rate (normal TB level less than 1.0 mg/dL [less than 17 mumol/L], and DB level, less than 0.4 mg/dL [less than 6.8 mumol/L]) of 98.7% (984/997 specimens) and a low false negative (normal TB level, abnormal DB level) rate of 1.3% (13 of 997). The second approach, assaying DB on physician request and only if the TB level was greater than or equal to 1.0 mg/dL (1.7 mumol/L), resulted in a true negative rate (normal TB level, no liver disease) of 87.7% (150%) of 171 patients) and a relatively low false negative rate (normal TB level, liver disease) of 12.3% (21 of 171) patients. Medical chart review revealed that, with either approach, none of the patients with false negative results with hepatobiliary disease would have been missed clinically, even if the DB assay had not been done. It is possible to screen DB requests using a TB of 1.0 mg/dL (17 mumol/L) as a means to determine whether DB should be assayed.
Two divergent laboratory approaches to the measurement of lactate dehydrogenase (LD) isoenzymes (LDIs) were evaluated. Abnormal values for total creatine kinase (CK), CK-MB, total LD, and LDIs were greater than 250 U/L, greater than or equal to 5% total CK, greater than 180 U/L, and LD1/LD2 ratio greater than 1.0, respectively. The first approach, measuring LDI on all requests regardless of total LD activity, showed the following results: 161 LDI specimens, 63 CK-MB + (LD1 greater than LD2, 6; LD1/LD2 normal, 57); 98 CK-MB - (LD1 greater than LD2, 5, LD1/LD2 normal, 93). Medical chart review of the 98 CK-MB negative specimens, representing 44 patients, showed that in seven patients with acute myocardial infarction (MI), none would have been missed clinically even if LDIs had not been done, and in only one case did LDIs play a confirmatory role in a patient who persistently had CK-MB-negative results but who had a strong clinical suspicion of MI. None of the 42 patient specimens with normal total LD activity had an LD1 greater than LD2. The second approach, measuring LDIs only if requested, only if total CK was abnormal, only if results for CK-MB were negative, and only if total LD was abnormal, showed the following results: 71 LDI specimens were not done (46 with normal total LD, 25 CK-MB + specimens). Medical chart review of the 71 LDIs not determined, representing 38 patients, showed that none of the 14 patients with the final diagnosis of MI would have been clinically missed, even if LDI had not been done, and in only one instance did LDIs confirm the clinical suspicion of MI in a patient with previously negative results for CK-MB. The LDI protocol represented by the second approach has been shown to be an effective means of identifying those occasional patients who require this confirmatory test, in whom the CK-MB results are negative but in whom there is a strong clinical suspicion of MI.
A weighted scoring system based on the selection of four measures of the performance characteristics of a laboratory test--sensitivity, specificity, and false positive and false negative rates--was devised to provide a rationale basis for ranking and evaluating dipstick urine screening tests as a criterion for elimination of routine urine microscopic examination. Equal weight was assigned to each performance characteristic, and an arbitrarily chosen scoring scale of 100 was selected for simplicity. When a summation procedure was applied to urine studies available in the medical literature, three categories of author acceptability were found: accept: score greater than 80; conditional accept: score 70-80; reject: score less than 70. Studies incorporating leukocyte esterase (LE) were found to have the highest scores and the highest author acceptability, whereas studies lacking LE had the lowest scores and lowest author acceptability. This easy-to-use, weighted scoring system is proposed as a guide for deciding whether dipstick screening tests are acceptable as a way of eliminating routine microscopic examination.
A 27-year-old man had an intracerebral hemorrhage and angiographic evidence of cerebral vasculitis after suicidal ingestion of 13 nasal decongestant tablets containing phenylpropanolamine (PPA). Toxicology screen and gas chromatography demonstrated PPA in the urine. Phenylpropanolamine is found in many over-the-counter preparations, but physicians should be aware of PPA's side effects and should be cautious about prescribing this potentially hazardous drug to suicidal patients.
One thousand consecutive urine specimens were studied to assess the sensitivity of a commercially available dipstick (Chemstrip 8, Boehringer Mannheim Corp., Indianapolis, IN) to predict the presence or absence of microscopic abnormalities. The Chemstrip 8 had a sensitivity of 78%, specificity of 54%, and a false negative rate of 38%. An additional 1,000 consecutive urine specimens were then studied using the Chemstrip 9, a reagent dipstick that includes the leukocyte esterase (LE) test. The Chemstrip 9 had a sensitivity of 82%, specificity of 42%, and a false negative rate of 36%. Chi-squared analysis revealed that the two dipsticks were not significantly different (chi 2 = 0.17, P greater than 0.5). Clinical review of patients with false negative results showed that approximately one-third to one-half of these patients had either spinal cord injury or genitourinary problems. Maximal potential savings in workload of approximately 10% were found if microscopic examinations were to be performed only on urine specimens with abnormal dipsticks. Our data suggest that in our patient population, we should not eliminate microscopic urine examination based on abnormal dipstick findings.
Paired serum and heparinized plasma samples were assayed simultaneously for lactate dehydrogenase (EC 1.1.1.27) isoenzyme 1 (LD1) activity by a commercially available immunochemical procedure. For all sera specimens tested, only LD1 activity was detected. For heparinized plasma, random discrepancies in LD1 activity were noted at normal (Group I), borderline (Group II), and increased (Group III) total LD activity. Incomplete precipitation of LD-M subunits was confirmed by electrophoresis and occurred in eight of 15, four of 13, and eight of 22 instances (total: 20/50, or 40%) with a mean difference of 13, 10.6, and 18.2 U/L (8.3, 4.0, and 4.4%) in Groups I, II, and III, respectively. We conclude that heparinized plasma is an unsuitable sample for the immunochemical determination of LD1.
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Over a five-month period, using data from patients in whom alkaline phosphatase (ALP) isoenzyme studies were requested routinely, we compared actual clinical diagnoses with the predicted diagnoses based on the results of electrophoretic separation of ALP isoenzymes on cellulose acetate before and after heat treatment and on elevated enzymatic activity of gamma glutamyl transferase (GGT) and alanine aminotransferase (ALT) activity. ALP isoenzymes were interpreted on a qualitative basis (presence or absence of liver, bone, or other isoenzyme) by individual clinical pathologists. Overall, the consistency of agreement in 61 patients was 66% for GGT, 51% for ALP isoenzymes, and 21% for ALT. In 44 patients with definite diagnoses, the sensitivity and specificity, respectively, of each laboratory test for patients with liver disease were 88 +/- 5.7% and 64 +/- 14.5% (ALP isoenzymes); 88 +/- 5.7% and 91 +/- 8.6% (GGT); and 6 +/- 4.1% and 91 +/- 8.6% (ALT). In patients with bone disease, the sensitivity and specificity of ALP isoenzymes was 75 +/- 10.8% and 86 +/- 6.6%, respectively. The results indicate that isoenzymes as currently performed need to be improved through standardization of the interpretation of ALP isoenzyme patterns to establish uniformity of comments.