Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B.

OBJECTIVES: We examined the diagnostic performance of serum myoglobin, creatine-kinase-MB (CK-MB) and cardiac troponin-I (cTnI) for predicting the infarct-related artery (IRA) patency in patients receiving TNK-tissue plasminogen activator (TNK-tPA) therapy for acute myocardial infarction (AMI) in the Thrombolysis in Myocardial Infarction (TIMI) 10B trial. BACKGROUND: A reliable noninvasive serum marker of IRA patency is desired to permit early identification of patients with a patent IRA after thrombolysis. METHODS: We measured myoglobin, CK-MB and cTnI concentrations in sera obtained just before thrombolysis (T0) and 60 min later (T60) in 442 patients given TNK-tPA and who underwent coronary angiography at 60 min. RESULTS: Angiography at 60 min showed a patent IRA (TIMI flow grade 2, 3) in 344 and occluded IRA (TIMI flow grade 0, 1) in 98 patients. The median serum T60 concentration, the ratio of the T60 and T0 serum concentration (60-min ratio) and the slope of increase over 60 min for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The area under the receiver-operating characteristic (ROC) curve for diagnosis of occlusion was 0.71, 0.70 and 0.71 for the 60-min ratio of myoglobin, cTnI and CKMB, respectively. The 60-min ratios of > or =4.0 for myoglobin, > or =3.3 for CK-MB and > or =2.0 for cTnI yielded a probability of patency of 90%, 88% and 87%, respectively. CONCLUSIONS: The diagnostic performance of serum myoglobin, CK-MB and cardiac troponin-I (cTnI) 60-min ratios was similar. The probability of a patent IRA was very high (90%) in patients with 60-min myoglobin ratio > or =4.0, and early invasive interventions to establish IRA patency may not be necessary in this group. Serum marker determinations at baseline and 60-min after thrombolysis may permit rapid triage of patients receiving thrombolytic therapy by ruling out IRA occlusion.

Evaluating the appropriateness of digoxin level monitoring.

BACKGROUND: Digoxin level determinations can be useful clinically in patients receiving digoxin therapy but are sometimes misused. METHODS: Explicit appropriateness criteria were adapted from previously published criteria and revised using local expert opinion. They were then used to evaluate the appropriateness of random samples of inpatient and outpatient serum digoxin levels. Overall agreement between reviewers regarding appropriateness was good (K = 0.65). Patients in the study included 162 inpatients in whom 224 digoxin levels were measured and 117 outpatients in whom 130 digoxin levels were measured during a 6-month period. The main outcome measure was the proportion of digoxin levels with an appropriate indication. RESULTS: Among inpatient levels, only 16% (95% confidence intervals [CI], 11%-20%) were appropriate. Of the 189 digoxin levels considered inappropriate, only 26 (14%) had a result of 2.3 nmol/L or more (> or =1.8 ng/ mL). None of these levels resulted in an important change in therapy, and no patient had a toxic reaction to the therapy. Among inappropriate levels, daily routine monitoring accounted for 78%. Of the 130 outpatient levels, 52% (95% CI, 44%-61%) were appropriate. Of 62 inappropriate levels, only 4 (6%) had a result of 2.3 nmol/L or more (> or =1.8 ng/mL). One result led to a change in therapy, but none of the patients were believed to experience a toxic reaction. Among the inappropriate levels, 87% of patients underwent early routine monitoring before a steady state was achieved. CONCLUSIONS: A high proportion of digoxin levels were inappropriate, particularly among inpatients. In both groups, the primary reason tests were judged inappropriate was early routine monitoring. Few inappropriate tests resulted in important data. Interventions to improve the use of digoxin levels could potentially save substantial resources without missing important clinical results.

Does the computerized display of charges affect inpatient ancillary test utilization?

BACKGROUND: The computerized display of charges for ancillary tests in outpatients has been found to affect physician-ordering behavior, but this issue has not been studied in inpatients. OBJECTIVE: To assess whether the computerized display of charges for clinical laboratory or radiological tests affected physician-ordering behavior. PATIENTS AND METHODS: Two prospective controlled trials, randomized by patient, were performed. Each trial included all medical and surgical inpatients at 1 large teaching hospital during 4 and 7 months: 3536 intervention and 3554 control inpatients in the group with clinical laboratory tests, and 8728 intervention and 8653 control inpatients in the group with radiological tests. The intervention consisted of the computerized display of charges for tests at the time of ordering. MAIN OUTCOME MEASURES: The number of clinical laboratory and radiological tests ordered per admission and the charges for these tests. RESULTS: For the clinical laboratory tests, during a 4-month study period, patients in the intervention group had 4.5% fewer tests ordered, and the total charges for these tests were 4.2% lower, although neither difference was statistically significant. Compared with historical controls from the same 4-month period a year before, the charges for the tests per admission had decreased 13.3%, but the decrease was temporally correlated with a restriction of future ordering of tests, and not with the introduction of the display of charges. For the radiological tests, during a 7-month period, the intervention group had almost identical numbers of tests ordered and charges for these tests. CONCLUSIONS: The computerized display of charges had no statistically significant effect on the number of clinical laboratory tests or radiological procedures ordered or performed, although small trends were present for clinical laboratory tests. More intensive interventions may be needed to affect physician test utilization.

What proportion of common diagnostic tests appear redundant?

PURPOSE: To identify ancillary tests for which there are criteria defining the earliest interval at which a repeat test might be indicated, to determine how often each test is repeated earlier than these intervals and, if repeated, provides useful information. SUBJECTS AND METHODS: We performed a retrospective cohort study of 6,007 adults discharged from a large teaching hospital during a 3-month period in 1991. We measured the proportion of commonly performed diagnostic tests that were redundant, and their associated charges. RESULTS: Of the 6,007 patients discharged, 5,289 (88%) had at least one of 12 target tests performed. Overall, 78,798 of the target tests were performed during the study period, of which 22,237 (28%) were repeated earlier than test-specific predefined intervals. This percentage varied substantially by test (range, 2% to 62%). To assess how many early repeats were justified, we performed chart reviews in a random sample stratified by test. For two tests, nearly all the initial results in the sample were abnormal, and all repeats were considered justified. Of early repeats following a normal initial result for the remaining 10 tests, chart review found no clinical indication for 92%, and a weighted mean of 40% appeared redundant. Overall, 8.6% of these 10 tests appeared redundant; if these were not performed, the annual charge reductions would be $930,000 at our hospital, although the impact on costs would be much smaller. CONCLUSIONS: For some tests, an important proportion are repeated too early to provide useful clinical information. Most such tests might be eliminated using computerized reminder systems.

How fast is fast enough for clinical laboratory turnaround time? Measurement of the interval between result entry and inquiries for reports.

We measured the time interval from result entry by the clinical laboratory to inquiry for reports by clinicians as a proxy for the actual turnaround time required to meet current patient care needs and to determine whether different patterns of report inquiry occur among clinical departments. The study included 4,004 complete blood cell (CBC) count reports that were sought by the clinical services using the hospital information system. The median time to report inquiry was 90 minutes for routine inpatient tests, 35 minutes for stat inpatient tests, and 30 minutes for the stat outpatient CBC counts. Most reports (range, 86%-94%) from these three subgroups were requested within 4 hours from entry of the results in the hospital information system. Of the routine outpatient test reports, 14%, 23%, and 31% were requested within the first 2 hours, 4 hours, and 8 hours, respectively. Although the interdepartmental variations in the median time for report inquiry were statistically significant for routine inpatient tests, stat inpatient tests, and stat outpatient tests, inquiries for the preponderance of reports for all three groups were within the first 1.5 to 3 hours from entry of the results in the hospital information system. We conclude that the majority of CBC counts and other tests with effects on immediate patient care management must be performed very rapidly on site and cannot be moved off site without compromising current standards of medical practice.

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

Prediction of fetal lung maturity in infants of diabetic mothers using the FLM S/A and disaturated phosphatidylcholine tests.

The authors evaluated the performance of the amniotic fluid surfactant to albumin ratio (FLM S/A), and disaturated phosphatidylcholine (DSPC) tests in assessing fetal lung maturity in infants of mothers with insulin-dependent diabetes mellitus antedating pregnancy. The distribution of the study population (n = 180) by class of diabetes was class B (27%); class C (28%); class D (29%); class F, FR and T (8%); and class R patients (8%). The diagnosis of respiratory distress syndrome (RDS) was the standard for evaluating the performance of FLM S/A and DSPC. The mean estimated gestational age was 37.4 weeks. Three infants (1.7%) were diagnosed with RDS. All three were delivered before 36 weeks. FLM S/A at the cut-off for "maturity" of > or = 70 mg/g, had a sensitivity of 66.6%, specificity of 94.9%, positive predictive value (PPV) of 18.2%, and negative predictive value (NPV) of 99.4%. DSPC at the cut-off for "maturity" of 1,000 micrograms/dL, had identical sensitivity and NPV, but lower specificity (89.2%) and PPV (9.5%) than FLM S/A. Both tests mispredicted maturity in the same case of RDS. The false "mature" rate of FLM S/A was 0.6% (95% confidence interval 0.0%-3.2%). The FLM S/A result of > or = 70 mg/g, obtained at or near-term, is a reliable predictor of the absence of RDS in infants of mothers with diabetes mellitus antedating pregnancy.

Comparison of disaturated phosphatidylcholine and fetal lung maturity surfactant/albumin ratio in diabetic and nondiabetic pregnancies.

We studied fetal lung maturity (FLM) by the amniotic fluid surfactant/albumin (FLM S/A) ratio and the disaturated phosphatidylcholine (DSPC) amniotic fluid levels at different gestational ages in diabetic (179 women with type 1 diabetes mellitus antedating pregnancy; infants delivered within 72 hours after amniotic fluid testing for DSPC level and FLM S/A ratio) and nondiabetic pregnancies (2 independent nondiabetic groups, 300 for FLM S/A ratio and 1,231 for DSPC level). The degree of maternal glycemia during gestation was estimated by serial measurements of hemoglobin A1. Multiple regression analyses, including gestational age (GAs) and diabetic status as independent variables and FLM S/A ratio and DSPC level as dependent variables, revealed significant effect from diabetic status and GA for FLM S/A ratio and a significant effect from GA but not from diabetic status for DSPC level. Glucose levels were controlled adequately throughout gestation as reflected by mean total glycated hemoglobin levels. Amniotic fluid levels of DSPC, the major surface tension-lowering component of pulmonary surfactant, are not significantly different between diabetic and nondiabetic pregnancies at different GAs.

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Improving response to critical laboratory results with automation: results of a randomized controlled trial.

OBJECTIVE: To evaluate the effect of an automatic alerting system on the time until treatment is ordered for patients with critical laboratory results. DESIGN: Prospective randomized controlled trial. INTERVENTION: A computer system to detect critical conditions and automatically notify the responsible physician via the hospital's paging system. PATIENTS: Medical and surgical inpatients at a large academic medical center. One two-month study period for each service. MAIN OUTCOMES: Interval from when a critical result was available for review until an appropriate treatment was ordered. Secondary outcomes were the time until the critical condition resolved and the frequency of adverse events. METHODS: The alerting system looked for 12 conditions involving laboratory results and medications. For intervention patients, the covering physician was automatically notified about the presence of the results. For control patients, no automatic notification was made. Chart review was performed to determine the outcomes. RESULTS: After exclusions, 192 alerting situations (94 interventions, 98 controls) were analyzed. The intervention group had a 38 percent shorter median time interval (1.0 hours vs. 1.6 hours, P = 0.003; mean, 4.1 vs. 4.6 hours, P = 0.003) until an appropriate treatment was ordered. The time until the alerting condition resolved was less in the intervention group (median, 8.4 hours vs. 8.9 hours, P = 0.11; mean, 14.4 hours vs. 20.2 hours, P = 0.11), although these results did not achieve statistical significance. The impact of the intervention was more pronounced for alerts that did not meet the laboratory's critical reporting criteria. There was no significant difference between the two groups in the number of adverse events. CONCLUSION: An automatic alerting system reduced the time until an appropriate treatment was ordered for patients who had critical laboratory results. Information technologies that facilitate the transmission of important patient data can potentially improve the quality of care.

How promptly are inpatients treated for critical laboratory results?

OBJECTIVE: The purpose of the study is to determine how frequently critical laboratory results (CLRs) occur and how rapidly they are acted upon. A CLR was defined as a result that met either the critical reporting criteria used by the laboratory at Brigham and Women's Hospital or other, more complex criteria. DESIGN: This is a retrospective cohort study in a large academic tertiary-care hospital. MEASUREMENTS: The proportion of chemistry and hematology results obtained in a 13-day period that met the hospital laboratory's critical reporting criteria were calculated. The charts of a stratified random sample of patients with CLRs due to sodium, potassium, and glucose were reviewed to determine the time interval until an appropriate treatment was ordered and the time interval until the critical condition was resolved. RESULTS: In 13 days, 1938 of 201,037 laboratory results (0.96%, or 0.44 per patient-day) met the hospital's critical reporting criteria. In the chart review, 222 CLRs were included in the stratified random sample, and 99 of these met the inclusion criteria. Among these 99 CLRs, the median time interval until an appropriate treatment was ordered was 2.5 hours. This interval was 1.8 hours when the CLR met the laboratory's criteria and a phone call was made, and 2.8 hours when the CLR met more complex criteria not requiring a phone call (p = 0.07). For 27 (27%) of the CLRs, an appropriate treatment was ordered only after five or more hours. The median time until the condition resolved was 14.3 hours: 12.0 hours for CLRs that met the hospital's criteria and 20.9 hours for the CLRs that met the more complex criteria (p = 0.006). CONCLUSION: Although CLRs meeting the hospital's criteria were reported promptly by the laboratory, treatment delays were still common. Results that did not meet the hospital's critical criteria but still represented serious clinical situations were more often associated with treatment delays. Difficulty communicating critical results directly to the responsible caregiver is the likely cause of some delays in treatment. New communications methods, including computer-based technologies, should be explored and tested for their potential to reduce treatment delays and improve clinical care.

Evolution beyond the shared services model of consolidated hospital clinical laboratories.

OBJECTIVE: To compare the operational and financial outcomes of the transition from shared laboratory services to a recentralized model, in a consolidated hospital system. SETTING: United Health Services Hospitals (Binghamton General, Wilson Memorial, and Ideal hospitals, New York State). INTERVENTION: Consolidation of hospital services and recentralization of laboratory testing to a single site (Wilson Memorial Hospital). MAIN OUTCOME MEASURES: Laboratory workload, testing efficiency, personnel and nonpersonnel expenses, analytic error rate, turnaround time, and proficiency-testing scores. RESULTS: The postintervention period (1988 to 1992) was characterized by a 51% and a 10% increase in the out- and inpatient workloads, respectively, with a concomitant 24% increase in testing efficiency. The salary expenses were 26% lower, while the total true cost savings ranged from $1,544,000 (11.6%) to $2,500,000 (21.9%) compared with the shared services model. The recentralization produced decreased analytic error rates and improved testing turnaround time. CONCLUSIONS: The total costs per test have been lowered in the recentralized model. Recentralization may provide further true cost savings over the shared services model while maintaining high-quality service.

The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable coronary artery disease.

In patients with chest pain at rest but no ST-segment elevation on the electrocardiogram, the diagnoses of unstable angina and non-Q-wave myocardial infarction (MI) are usually considered together because they cannot be differentiated clinically or angiographically. Since the extent of myocardial necrosis is an important determinant of the risk of death, it is important to identify serum markers with which to predict prognosis, in order to initiate appropriate medical treatment and/or invasive procedures in these patients. Cardiac troponin-I (cTnI), one of the subunits of the troponin regulatory complex, binds to actin and inhibits interactions between actin and myosin. The presence of elevated cTnI in serum is a significant prognostic indicator in patients with unstable angina and non-Q wave MI. Its independent prognostic potential persists even after adjustment for independent baseline variables known to be significantly associated with an increased risk of cardiac events. The use of cTnI in the triage of patients with unstable coronary disease may identify those at greater risk for adverse cardiac events.

The fiscal consequences of central vs distributed testing of glucose.

We have compared the operational, medical, and fiscal consequences of performing urgent glucose testing at the bedside vs in the central laboratory. The turnaround time (TAT) with bedside testing was only 1-2 min shorter than that from the central laboratory, to which specimens are sent by pneumatic tube and from which results are automatically broadcast by computer to the originating site. No significant adverse medical outcomes were associated with this difference in TAT. The cost of bedside testing is approximately twice that of central laboratory testing.

Total serum calcium reference intervals in postmenopausal outpatients.

The distribution of values of serum calcium has been studied in the following four outpatient populations: premenopausal (n = 411) and postmenopausal women (n = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361). Their respective average total serum calcium values (mg/dl) were 9.42, 9.56, 9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl) were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5 (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased total serum calcium levels were observed in the postmenopausal women as compared with both premenopausal women (p < 0.001) and with men over 55 years old (p < 0.003). Eight percent of the values obtained in postmenopausal women were above the current reference interval, as compared to 1.7% in premenopausal women, and 3.3% in men over 55 years old. In conclusion, the age-related increase in total serum calcium in postmenopausal female outpatients warrants a higher upper limit of the reference interval for this subpopulation.

Appropriateness of antiepileptic drug level monitoring.

OBJECTIVES: To develop explicit, reliable appropriateness criteria for antiepileptic drug level monitoring and to assess the appropriateness of monitoring in one tertiary care institution. DESIGN: Appropriateness criteria derived from the literature and through expert opinion were used to evaluate a stratified random sample of antiepileptic drug level determinations obtained from chart review. SETTING: Tertiary care center performing more than 10,000 antiepileptic drug level determinations per year. PATIENTS: A total of 330 inpatients in whom antiepileptic drug levels were measured a total of 855 times. METHODS: Drug levels were assessed at least 200 times for each of four antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, and valproic acid). MAIN OUTCOME MEASURES: The proportion of antiepileptic drug levels with an appropriate indication and, of those, the proportion sampled appropriately. RESULTS: Overall, 27% (95% confidence interval, 24% to 30%) of levels had an appropriate indication. Interrater agreement for appropriateness was substantial (kappa = 0.61). There was no significant difference in the appropriateness rate among the four drugs (range, 25% to 29%). Of the 624 antiepileptic drug level determinations considered inappropriate (73%), only four (0.6%) were more than 20% higher than the upper limit of normal, and none of the four patients had clinical signs of drug toxicity. A median of six levels (range, one through 69) was determined per patient, and the median interval between level determinations was 24 hours. Of the 27% of level determinations with an appropriate indication, 51% were sampled correctly, resulting in an overall appropriateness rate of 14%. CONCLUSIONS: Only 27% of antiepileptic drug level determinations had an appropriate indication, and half of these were not sampled correctly. Routine daily monitoring without pharmacological justification accounted for most of the inappropriate drug level determinations. Efforts to decrease inappropriate monitoring may result in substantial cost reductions without missing important clinical results.

Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy.

BACKGROUND: Significant analytic variability exists between the multiple assays for cardiac troponin I (cTnI) approved for clinical use. Until adequate cTnI standardization is possible, an evidence-based approach evaluating each assay at specific thresholds appears warranted. METHODS: We examined the efficacy of three cTnI assays for predicting death, myocardial infarction (MI), or the composite of death, MI, or urgent revascularization at 43 days among patients with non-ST-elevation acute coronary syndromes enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 11B study. RESULTS: Six hundred eighty-one patients with serum samples obtained at baseline and/or 12-24 h had cTnI determined using all three assays. Baseline cTnI was > or = 0.1 microg/L for 368, 395, and 418 patients with the Bayer Immuno 1(TM), ACS:180, and Dimension RxL assays, respectively. Correlation coefficients for the RxL with the ACS:180 and Bayer Immuno 1 results were 0.89 (P = 0.0001) and 0.87 (P = 0.0001), with a coefficient of 0.92 (P = 0.0001) for the ACS:180 and Bayer Immuno 1 assays. Patients with cTnI > or = 0.1 microg/L were at increased risk fo death or MI by 43 days (relative risk, 2.2-3.0; P <0.0006), regardless of the assay used. This prognostic capacity persisted among those with creatine kinase MB isoenzyme concentrations within the reference interval. Moreover, cTnI was the strongest multivariate predictor of death, MI, or urgent revascularization with adjusted odds ratios of 2.1-2.9 (P <0. 0006). CONCLUSION: This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.

Differences in TDx fetal lung maturity assay values between twin and singleton gestations.

OBJECTIVE: The purpose of this study was to quantify differences in indexes of pulmonary maturity between singleton and twin gestations by means of the TDx fetal lung maturity assay. STUDY DESIGN: We identified records of a total of 830 singleton and twin pregnancies not complicated by diabetes and delivered between 28 and 37 weeks' gestation from December 1994 through August 1995. Among these, 170 (20%) had TDx fetal lung maturity measurements performed within 72 hours of delivery. Linear regression was used to assess differences in TDx fetal lung maturity assay values between singleton gestations (n = 143 gestations) and twin gestations (n = 27 gestations) while controlling for potential confounding factors. RESULTS: Twin gestations were no more likely than singleton gestations to undergo TDx fetal lung maturity screening (odds ratio, 1.3; 95% confidence interval, 0.8-2.2). Pregnancy complications and corticosteroid treatment were similar in the two groups. After 31 weeks' gestation the twin gestations had significantly higher TDx fetal lung maturity values. Linear regression with controls for gestational age indicated that twin gestations on average had a TDx fetal lung maturity value that was 22.0 mg/g (95% confidence interval, 9.8-34.6 mg/g) higher than that of gestational age-matched singleton gestations. CONCLUSION: Beyond 31 weeks' gestation twin pregnancies appeared to have a TDx fetal lung maturity value that was 22 mg/g higher than that of singleton pregnancies. If the underlying incidences of respiratory distress syndrome are similar between twin and singleton gestations, then the potential exists for false-positive prediction of adequate lung maturity values among twin gestations.

Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase II.

IRS-1, a principal substrate of the insulin receptor, is phosphorylated on serine, threonine, and tyrosine residues in a variety of tissues during insulin stimulation. Casein kinase II, an insulin-sensitive serine/threonine kinase, catalyzed the in vitro incorporation of 1 to 2 mol of phosphate/mol of recombinant rat IRS-1. Two-dimensional phosphopeptide mapping of IRS-1 phosphorylated by casein kinase II in vitro and IRS-1 immunoprecipitated from intact Chinese hamster ovary cells demonstrated multiple common phosphopeptides, suggesting that overexpressed IRS-1 is a substrate for casein kinase II in these cells. Moreover, the common phosphopeptides that appeared to be insulin-sensitive in intact cells comprised 22% of casein kinase II-catalyzed 32P incorporation into IRS-1 in vitro. These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. By using phosphoamino acid analysis, strong cation exchange analysis, manual Edman degradation, and automated amino acid sequencing, Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1. Furthermore, Ser-99, an additional site labeled at low yield, appeared to be contained in an insulin-sensitive phosphopeptide. Thus, casein kinase II-catalyzed phosphorylation of IRS-1 may be a component of the intracellular insulin signalling cascade.

Racial differences in the predictive value of the TDx fetal lung maturity assay.

OBJECTIVE: Black newborns have lower rates of neonatal respiratory distress syndrome compared with nonblack newborns. This has been attributed to accelerated lung maturation. Previous studies have demonstrated a difference in the predictive value of the lecithin/sphingomyelin ratio, a test for lung maturity, between races. Our study examines the predictive value of the newer TDx Fetal Lung Maturity Surfactant-to-Albumin assay. STUDY DESIGN: We reviewed the records of 393 nonblack and 87 black infants delivered within 72 hours of the TDx FLM S/A assay testing. We compared the rates of neonatal respiratory distress syndrome by race, stratified by results. RESULTS: In our study population black newborns had less than one half the rate of respiratory distress syndrome compared with nonblack newborns (4.6% vs 10.4%). To adjust for possible differences in the timing of lung maturation, the results were stratified by the TDx FLM S/A assay result. Black race had a protective effect (Mantel-Haenszel weighted odds ratio 0.30, 95% confidence interval 0.06 to 0.93, p < 0.05). This significant racial difference remained when both TDx FLM S/A assay result and gestational age were controlled in a multiple logistic regression analysis. CONCLUSIONS: There are differences in the predictive value of the TDx FLM S/A assay among races. Black fetuses are less likely to have respiratory distress syndrome. The difference in rates of respiratory distress syndrome between races must be due to either a qualitative difference in the surfactant or to an anatomic difference in fetal lungs. Consideration should be given to a lower cutoff value for a mature test result in black women.