Abnormal serum lactate dehydrogenase isoenzyme in a case of laryngeal carcinoma and thyrotoxicosis.

An abnormal lactate dehydrogenase (LDH) isoenzyme was found in the serum of a patient with laryngeal carcinoma and hyperthyroidism. On electrophoresis it migrated as an additional band between LDH-1 and LDH-2. Follow-up studies suggested that this higher molecular weight, rather thermostable LDH isoenzyme, might have originated from the cancer tissue, though a possible relationship with the thyrotoxic state cannot be excluded.     

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.     

Patterns of lactate dehydrogenase isoenzymes 1 and 2 in serum of patients performing an exercise test

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity and LD isoenzymes were determined in serum from 56 patients and 40 healthy subjects before and 24, 48, and 72 h after they performed an exercise test. The mean (for all four times) total LD activity concentration and proportion of LD-2 were within the normal range for all 96 subjects. Mean LD-1 values for serum, although within the normal range in all subjects, were significantly higher in patients with positive exercise test results than in subjects with negative results: 75 (SD 12) U/L in 35 patients with ST depression greater than 2 mm; 63 (SD 14) U/L in 16 patients with ST depression of 1-2 mm; 43 (SD 11) U/L in subjects with negative test results, by 48 h after the test. The LD 1:2 ratio was also markedly higher in the group of patients with positive test exercise results, especially in those with ST depression greater than 2 mm (1.02, SD 0.06), compared with those subjects with negative results (0.60, SD 0.04). A similar trend was also found 24 and 72 h after the exercise test. We conclude that exercise-myocardial ischemia may lead to an increased LD 1:2 ratio in serum, and demonstrate a correlation between the degree of ischemia and the LD 1:2 ratio. Determination of the LD 1:2 ratio, even in the presence of normal total LD activity, may assist in the clinical evaluation of patients performing an exercise test.     

Abnormal lactate dehydrogenase isoenzyme in serum and tumor tissue of a patient with neuroblastoma

Serum and tumor tissue of a patient with neuroblastoma contained an abnormal isoenzyme of lactate dehydrogenase (LDH; EC 1.1.1.27), which, on agarose gel electrophoresis, migrated between LDH-2 and LDH-3 with a mobility the same as that of the extra LDH isoenzyme found in normal human erythrocytes. On surgical removal of the tumor, the high total LDH activity (775 U/L) in the serum of the patient rapidly decreased to normal (70-220 U/L), and the abnormal LDH isoenzyme was no longer detected. The total LDH activity of the abnormal LDH isoenzyme per gram of hemoglobin in the tumor tissue was 26 times that of erythrocytes, suggesting that the abnormal isoenzyme originated mainly from the tumor cells themselves rather than the erythrocytes contained in the tumor tissue. This first report on the appearance of the abnormal LDH isoenzyme in a patient with neuroblastoma suggests that this abnormal LDH isoenzyme may have some significance as a marker enzyme for neurogenic tumors.     

An evaluation of serum thyroxine binding globulin as a routine test of thyroid function.

Serum thyroxine binding globulin (TBG) values were correlated with other thyroid function test results and with the clinical condition in 680 patients. The estimation of serum TBG was helpful in the evaluation of thyroid status only in those patients who were either acutely ill, were taking the contraceptive pill, or were pregnant. Further, the derived index, thyroxine: TBG ratio, proved to be a better diagnostic index than the thyroxine:tri-iodothyronine uptake ratio and in many cases would have avoided the use of more expensive and time-consuming tests.     

Effect of isoenzyme composition on Kodak Ektachem test results for creatine kinase, lactate dehydrogenase, alkaline phosphatase, and amylase.

Seventy-four patients' sera containing macroenzymes or other uncommon enzyme forms were analyzed for total creatine kinase, lactate dehydrogenase, alkaline phosphatase, or amylase activity on an Ektachem 700XR analyzer. The Ektachem test results correlated well with activities obtained by means of liquid reagents on RA-1000. For each enzyme tested, linear-regression analysis yielded data comparable with those for sera containing exclusively the more common isoenzymes. Increased concentrations of intestinal ALP, however, resulted in higher activities of total ALP being reported for the Ektachem.     

Hospital efficiency measurement and evaluation. Empirical test of a new technique

A new technique for identifying inefficient hospitals, Data Envelopment Analysis (DEA), is field tested by application to a group of teaching hospitals. DEA is found to provide meaningful insights into the location and nature of hospital inefficiencies as judged by the opinion of a panel of hospital experts. DEA provides insights about hospital efficiency not available from the widely used efficiency evaluation techniques of ratio analysis and econometric-regression analysis. DEA is, therefore, suggested as a means to help identify and measure hospital inefficiency as a basis for directing management efforts toward increasing efficiency and reducing health care costs.     

Increased lactate dehydrogenase isoenzyme 1 in serum and tumor tissue of a patient with small-cell carcinoma

Histological examination of supraclavicular lymph node tissue obtained at biopsy from a 63-year-old man disclosed metastatic small-cell carcinoma. On admission and for four days subsequently, total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum was 6.5 times normal; studies of LD isoenzyme showed persistently increased LD-1, with LD-1 greater than LD-2. Isoenzyme electrophoresis of tissue homogenates prepared from the patient's tumor also showed the LD-1 greater than LD-2 pattern. Isoenzyme studies for supraclavicular lymph node tissue from five control subjects showed contrasting isoenzyme patterns as compared with the patients in whom LD-2, LD-3, and LD-4 predominated. Because these abnormalities were persistent, they differ from the temporal sequence for LD usually seen in myocardial infarction. This emphasizes the importance of repetitive sampling for clinical interpretation of data on this enzyme.     

Lactate dehydrogenase activity as a cause of metronidazole resistance in Bacteroides fragilis NCTC 11295.

Enzymes acting on pyruvate as a parameter of the ATP regeneration system were studied as a cause of metronidazole resistance in Bacteroides fragilis NCTC 11295. The resistant strain had higher lactate dehydrogenase activity and produced more lactate than susceptible strains, suggesting that the enzyme is more active in lactic acid fermentation. Furthermore, the reaction catalysed by lactate dehydrogenase occurred up to 48 mg/L metronidazole, whereas the reaction catalysed by pyruvate: ferredoxin oxidoreductase reaction stopped at 2 mg/L. The mechanism of metronidazole resistance in B. fragilis NCTC 11295 may be due to the high activity of lactate dehydrogenase which compensates for the decreased activity of pyruvate: ferredoxin oxidoreductase in the presence of metronidazole.     

Activity of lactate dehydrogenase isoenzymes LD1 and LD2 in serum as determined by using an inhibitor of the M-subunit

To measure activities of lactate dehydrogenase (EC 1.1.1.27) isoenzymes LD1 and LD2 in serum, we developed a method involving 1,6-hexanediol as specific inhibitor of the M-subunit. Addition of hexanediol, 0.6 mol/L, to five LD isoenzyme fractions purified from human liver and heart homogenates resulted in complete loss of activities of LD4 and LD5, and partial loss of LD2 and LD3. The activity of LD1, which is composed of the H-subunit only, was not affected. In studying what conditions would allow only the activities of LD1 or LD1 + LD2 to be expressed in serum, we found that the respective activities could be determined by treatment with hexanediol, 0.75 mol/L and 0.55 mol/L, respectively. Results of binding experiments and analytical-recovery tests supported the effectiveness of analyses with this inhibitor in determination of LD1 and LD1 + LD2 activities in serum. Results by this proposed inhibition method correlated well with those by the conventional electrophoretic method for determination of LD1 activity, but LD1 + LD2 activities by the inhibition method were a little less than those by the electrophoretic method, requiring some correction.     

Autoantibodies to lactate dehydrogenase in serum identified by use of immobilized protein G and immobilized jacalin, a jackfruit lectin

In this method for identifying autoantibodies to lactate dehydrogenase (anti-LDs) in serum, we used immobilized Protein G to bind IgG-complexed LD and immobilized jacalin to bind IgA-complexed LD, leaving non-complexed LD in solution. The non-complexed LD and total LD were kinetically measured. We report results as LD bound to immobilized Protein G and LD bound to immobilized jacalin. Using sera demonstrating IgG and IgA anti-LDs by immunoelectrophoresis (IEP), respectively, we optimized the method for incubation time and concentration of binding agents. We demonstrated concomitant binding of LD and greater than or equal to 98% of IgG and of LD and greater than or equal to 92% of IgA. For LD bound to immunobilized Protein G the detection limit was 10 U/L, within- and between-run CVs ranged from 2.9% to 9.1%, and values for normal sera were less than or equal to 3% of total LD. Results for LD bound to immobilized jacalin were similar. We tested 10 sera displaying aberrant LD electrophoretograms: In seven, LD bound to immobilized Protein G was increased (range: 26-99% of total LD), indicating IgG-complexed LD. This was confirmed by IEP, demonstrating IgG1,2, or IgG3 anti-LDs in these sera. In the other three sera, LD bound to immobilized jacalin was increased (range: 38-72% of total LD), indicating IgA-complexed LD. This was confirmed by IEP, demonstrating IgA anti-LDs in these sera. Evidently this method is an alternative to IEP for identifying anti-LDs in serum.     

An evaluation of several laboratory tests and test combinations in the detection of lupus anticoagulant.

The laboratory assessment of the lupus anticoagulant, a factor frequently associated with venous and arterial thrombosis, recurrent miscarriages and abortions, is not straightforward, as indicated by the variety of tests proposed and the different results obtained. On account of the marked variability and heterogeneity of lupus anticoagulant among patients, no single test or reagent will identify all patients with lupus anticoagulant, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to assess the minimum number of tests necessary for the satisfactory identification of the patient with lupus anticoagulant. Our study confirms that lupus anticoagulant may be present in a significant number of patients with normal routine activated partial thromboplastin time, a test which therefore cannot be used as the sole criterion for identifying patients suspected of having lupus anticoagulant. In contrast all patients who had positive results in at least one test could be detected (100% sensitivity) with two combinations of tests: (1) dilute activated partial thromboplastin time and Kaolin clotting time and (2) dilute activated partial thromboplastin time and tissue thromboplastin inhibition test. Since the latter inhibition test has been reported to give a high number of false-positive or negative results, we suggest the combination of dilute activated partial thromboplastin time and Kaolin clotting time as the standard pair of tests for the screening of suspected lupus anticoagulant patients.     

A rapid latex agglutination test for detection of elevated levels of myoglobin in serum and its value in the early diagnosis of acute myocardial infarction

A latex agglutination test for detection of elevated levels of myoglobin in serum has been studied, and its clinical value in diagnosis of acute myocardial infarction (AMI) has been evaluated on a retrospective material of fifty-five patients consecutively admitted to hospital on suspicion for AMI within 4 h after onset of symptoms. The analysis time was less than 10 min. There was no evidence of interference with other related proteins, as judged from analysis of sera with high content of aspartate and alanine aminotransferase, lactate dehydrogenase and creatine kinase, nor was the test sensitive to haemolysis. However, unspecific agglutination was seen with some sera containing a high concentration of rheumatoid factors. In sera with known concentrations of myoglobin, quantitated by a radioimmunoassay, the test was negative in all sera below 80 micrograms/l (n = 187), and positive in all sera above 140 micrograms/l (n = 209). In the range 80-140 micrograms/l the latex test could be either positive or negative (n = 105). The day-to-day reproducibility was high in the ranges below 80 micrograms/l and above 140 micrograms/l, but range 80-140 micrograms/l. In the diagnosis of AMI the predictive value of a positive result was 0.64, and the predictive value of a negative result was 1.0. The latex agglutination test is therefore clinically useful as an emergency test, and as a very early and sensitive indicator for AMI. Patients with a negative test result during the first 12 h after debut of symptoms can with great certainty be identified as not suffering from AMI, whereas patients with a positive test result should be monitored by further laboratory analyses.     

Immunological determination of muscle-type enolase in the serum as a diagnostic test for myocardial infarction.

An antiserum raised in the chicken against purified rat skeletal muscle enolase neutralized 86% of the enolase activity of human heart muscle and 8.7% +/- 4.8% (mean +/- S.D.) of the enolase activity in normal human serum. The fraction of enolase inhibited by the antiserum, designated as 'immunologically reacting muscle enolase', promptly rose after myocardial infarction in the serum of affected subjects, reaching peak values in excess of 40% in all but one of 23 subjects. Only one subject with ischaemic heart disease, but without infarction, and 2 with miscellaneous conditions, among 117 such patients tested, yielded comparable values. The test appears to be highly specific for myocardial infarction when muscle disease can be excluded and would not be difficult to introduce as a laboratory routine.     

Determination, by radioimmunoassay, of the mass of lactate dehydrogenase isoenzyme 1 in human serum and of its rate of removal from serum after a myocardial infarction

In this radioimmunoassay of lactate dehydrogenase-1 (LD-1; EC 1.1.1.27) in human serum we use a commercial LD-1-selective assay system and a goat antiserum. We have determined the fractional rate of disappearance from serum and the half-life of LD-1, in terms of both enzyme activity and enzyme mass, in 21 myocardial infarction patients. Our evidence suggests that this isoenzyme is inactivated in serum. Furthermore, our data suggest that the conventionally accepted half-life of about 110 h for serum LD-1 activity may grossly overestimate the actual LD-1 half-life in many post-myocardial infarction patients.     

Perinatal outcome in pregnancies with a positive serum screening for Down's syndrome due to elevated levels of free beta-human chorionic gonadotropin.

OBJECTIVE: To evaluate the potential clinical use of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and uterine artery Doppler investigation to screen for placenta-related adverse outcome in pregnancies at positive risk for Down's syndrome at 15-18 weeks. DESIGN: A cohort of 329 consecutive pregnant women with a singleton viable pregnancy and a positive risk for Down's syndrome was retrospectively investigated. This group was obtained from an unselected population of 3952 women attending the same hospital over a 2-year period. Using the results of this first analysis, we selected a group of 26 women with unexplained high levels of free beta-hCG and followed them prospectively with monthly ultrasound and uterine artery Doppler examinations. RESULTS: In the retrospective cohort, risk ratios stratified for maternal serum beta-hCG multiple of the median (MoM) values indicated that the highest incidence of adverse pregnancy outcome was in those women with values of > or = 5.0. In the prospective study, pregnancy outcome was complicated by uteroplacental disorders in eight cases. Analysis of the Doppler investigation indicated that, in women with a very high level of hCG, an abnormally high uterine artery pulsatility index (PI) had lower sensitivity and negative predictive value than early diastolic notch, whereas the specificity and positive predictive value were higher for a high uterine artery PI. CONCLUSIONS: These findings suggest an association between a high level of maternal serum beta-hCG at 15-18 weeks, the presence of an early diastolic notch in the uterine artery flow velocity waveform and adverse pregnancy outcome due to abnormal development of the uteroplacental circulation. Young women with an unexplained high beta-hCG level would benefit, apart from detailed sonography of the fetus and/or karyotyping, from uterine Doppler investigation and counselling about the follow-up and management of placenta-related pregnancy disorders.