Variation in plasma apolipoprotein A-1 and B concentrations following myocardial infarction.

Measurements of plasma apolipoprotein A-1 and B concentrations are increasingly used for the laboratory assessment of risk of coronary artery disease (CAD). This study of 22 patients investigated the response of plasma apolipoprotein A-1 and B levels for up to 20 days following a myocardial infarction. Seven of these patients participated in a clinical trial using the drug Tissue Plasminogen Activator (TPA). We established that, unlike many other plasma proteins, apolipoproteins do not display a classic acute phase response following myocardial infarction, although large variations in plasma apolipoprotein levels were observed in the patients investigated. Our studies also show that the measurement of plasma apolipoproteins A-1 and B to assess future CAD risk in myocardial infarction patients should be deferred for a minimum of at least 14 days post-infarction. No significant difference was observed in the pattern of apolipoprotein response between patients receiving TPA and those not given this drug.

A comparison of plasma magnesium values in patients with acute myocardial infarction and patients with chest pain due to other causes.

Plasma magnesium concentrations were monitored daily in 86 patients who were admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction. Twenty-six patients had suffered a myocardial infarction, while the remainder had angina or non-cardiac chest pain. Magnesium levels were also obtained daily for five consecutive days in five normal subjects, who served as the control group. Calculations of the 95% confidence intervals on the differences between Day 1, Day 2 and individual subjects' mean plasma magnesium concentrations for the group with acute myocardial infarctions versus the group that did not have an acute myocardial infarction, the group with acute myocardial infarctions versus the reference group, and the group that did not have an acute myocardial infarction versus the reference group, and analysis of variance for the data from the three subject groups revealed no significant difference between the plasma magnesium levels of patients with an acute myocardial infarction and those with chest pain due to other causes or the normal reference population.

Quantitative method for determining serum alkaline phosphatase isoenzyme activity II. Development and clinical application of method for measuring four serum alkaline phosphatase isoenzymes.

A method for quantitating the liver, bone, intestinal and placental alkaline phosphatase activity of serum, using an algorithm for converting selective inactivation by guanidine hydrochloride, L-phenylalanine, and heat into equivalent isoenzyme activity is described. The method can individually quantify mixtures of isoenzymes to within a margin of 3%; it has acceptable reproducibility and has been used to develop both age and sex related reference ranges. Analysis time is about 30 minutes. The clinical reliability of this method has been shown in a study of 101 patients, in 79% of whom isoenzyme results were compatible with the final clinical diagnosis; in 10% a clinical diagnosis resulted from isoenzyme analysis, and in a further 11% the source of the increased alkaline phosphatase activity was identified and supported by electrophoresis, with a definite clinical diagnosis yet to be made.

Routine plasma magnesium estimation: a useful test?

An investigation of 527 consecutive patients showed that 24 (4.5%) had hypomagnesaemia (plasma magnesium level, less than 0.70 mmol/L) and 26 (4.9%) had hypermagnesaemia (plasma magnesium level, greater than 1.00 mmol/L). The magnesium levels returned to normal values without specific treatment in 15 of the hypomagnesaemic patients. Magnesium levels of less than 0.60 mmol/L occurred only in patients with disorders that are known to cause magnesium deficiency. Seventeen of the hypermagnesaemic patients had plasma creatinine values in excess of 0.20 mmol/L; in the remainder, the plasma magnesium level was less than 1.10 mmol/L. Eighteen of the hypermagnesaemic patients received no specific treatment, in five the plasma magnesium values returned to normal levels within three days, while the high levels were maintained in the remaining 13 patients, but none was in excess of 1.15 mmol/L. These results suggest that many cases of hypomagnesaemia are transient and do not require treatment; severe hypomagnesaemia occurs only in patients with disorders that are known to cause magnesium deficiency; hypermagnesaemia is common in renal insufficiency; most cases of mild hypermagnesaemia (plasma magnesium level, less than 1.20 mmol/L) do not require specific treatment; and that screening all patients for hyper- or hypomagnesaemia is clinically unproductive and only those patients with disorders that are known to affect magnesium metabolism need to be investigated.

Normal "anion gap" (hyperchloremic) acidosis.

Hyperchloremic metabolic acidosis in which the anion gap is within normal limits is a common condition in the hospital population, and often presents a difficult diagnostic problem. We describe nine typical cases of this disorder and suggest a logical approach to its evaluation.

Mixed acid-base disorders.

Mixed acid-base disorders, the occurrence of two or more primary acid-base disturbances in the same patient, are common in the hospital population, but are usually misdiagnosed because of lack of knowledge of the consequences of the primary disturbances. This paper describes seven examples of these disorders recently seen in the authors' hospital, and provides a logical approach to their diagnosis.

Occult causes of hypokalemia.

Most causes of hypokalemia are obvious from the clinical picture and the values for plasma electrolytes. In cases with obscure etiology, a pretreatment estimation of urinary potassium and chloride often helps lead the clinician into new and fruitful avenues of clinical investigation. Here we present four cases of hypokalemia in which the pathogenesis was initially enigmatic but was clarified somewhat by the determination of the urinary electrolytes. These simple, inexpensive investigations were initiated by the clinical chemistry laboratory in each case. The results encouraged the physicians to consider further clinical investigations, which led to a definitive diagnosis, before invoking expensive hormonal analyses.

Hyperkalemia in the elderly.

Hyperkalemia is a common and potentially dangerous condition in elderly patients. These subjects are more likely to have a disease or be taking medications that may induce this disorder. We describe three such cases where the increased concentration of potassium in plasma resulted from decreased renal excretion of this ion, and suggest a simple approach to the etiological diagnosis of hyperkalemia.

Mechanism of platelet interference with measurement of lactate dehydrogenase activity in plasma.

Platelets reportedly inhibit lactate dehydrogenase activity in plasma under reaction conditions of low osmolality. We describe observations inconsistent with these reports, and we attribute this "inhibition" to optical interference by platelets during the course of a reaction. We conclude that when platelet lysis is prevented and the optical interference of platelets corrected, platelet-rich plasma, platelet-poor plasma, and serum show essentially the same lactate dehydrogenase activity. Furthermore, platelet contamination can cause unexpected problems when lactate dehydrogenase is assayed with centrifugal analyzers. Results can be high or low, depending on the volume of diluent pipetted with the sample, and extreme within-run variations in activity are possible. When plasma is used instead of serum for routine analyses, regular checks for platelet contamination should be performed as a quality-control procedure, especially by laboratories separating plasma with bench-top centrifuges. Platelets can also interfere optically with assay of other enzymes and metabolites.

Determination of inorganic sulfate in plasma with a centrifugal analyzer.

Turbidimetry of inorganic sulfate, after precipitation with barium sulfate, can be done simply in a Cobas Bio centrifugal analyzer. Polyethylene glycol is used as the precipitate-stabilizing agent. Reproducibility of precipitation is enhanced by the presence of BaSO4 particles, which function as seed nuclei. There is no interference by normal or above-normal concentrations of phosphate, heparin, bilirubin, hemoglobin, or erythrocyte contents, or by lipemia (triglyceride concentrations up to 6.5 mmol/L). Analytical recovery of added inorganic sulfate was found to be quantitative. Precision is similar to that for other methods for inorganic sulfate in plasma. This method is suitable for the rapid, routine analysis of plasma inorganic sulfate, and it is simple and less expensive to perform than alternative methods.

Plasma enzyme activities in primary hypothyroidism.

Results of clinical chemistry tests are often initially interpreted by relatively inexperienced junior medical staff, and therefore a major role of clinical chemists is to ensure that their laboratory tests are utilized and interpreted appropriately. The cases described below demonstrate the interaction of a diagnostic problem and clinical inexperience in an area where clinical chemists can, and should be, of professional assistance.

Hyponatremia: a diagnostic problem.

Hyponatremia, a common clinical problem, may result from a wide variety of causes. Treatment can vary from fluid restriction to rehydration, depending on the pathogenesis of the disorder. Essential to evaluation of hyponatremic patients is correct estimation of the status of the extracellular fluid volume, because this determines the type of therapy: a patient who is hypovolemic will not benefit from fluid restriction; a euvolemic patient should not be "rehydrated." To distinguish between these two conditions requires a searching history and clinical examination, including measurement of the blood pressure both while the subject is standing and lying. Not all patients with the classical biochemical features of the syndrome of inappropriate secretion of vasopressin (low plasma [Na+] and osmolality, high urinary [Na+] and osmolality) will have the disorder, because these same features may also be present in other hyponatremic disorders, including hypovolemic hyponatremia.

Clinical evaluation of immunoinhibition determination of creatine kinase B subunits in coronary care.

One hundred patients with chest pain of cardiac origin were evaluated on the basis of clinical findings, electrocardiograph results, and total creatine kinase (CK) and creatine kinase B-subunit (CK-B) activity (as determined by immunoinhibition with the Boehringer CK-MB kit) in serum. All patients diagnosed as having had an acute myocardial infarction had increased values for both CK-B and total CK. In no case was normal total CK activity associated with an increased CK-B, nor was normal CK-B associated with an increased total CK. During collection of data for reference ranges, we found 10 patients who had no evidence of cardiac disease but had various other diseases, who exhibited high values for CK-B in serum; four of these had normal values for total CK. We conclude that estimations of CK-B in serum by this method added no more diagnostic information than did data on total CK in the evaluation of chest pain.

Can the initial clinical assessment of thyroid function be improved?

The clinical reasons for requesting in-vitro thyroid-function tests were studied in 500 consecutive new patients with no known history of thyroid disease. 23 patients presented with five or more signs or symptoms of thyroid disease, and 18 of these required treatment for thyrometabolic dysfunction. Of 35 subjects with three or four thyroid-associated signs or symptoms, only 1 came to treatment. Of 442 subjects with one or two signs or symptoms, 2 were subsequently treated. These results suggest that there is little value in the biochemical investigation of patients who present with minimal clinical evidence of thyrometabolic disease.

Screening thyrometabolic disorders using total serum thyroxine level.

The results of in-vitro thyroid function tests and clinical details of 1,517 patients are reviewed, and the total serum thyroxine levels and the free thyroxine indices are compared in terms of their diagnostic value. Only 3-7% of the patients investigated had a total serum thyroxine level (T4) that did not correlate with the free thyroxine index. We believe that the evidence is strong enough to suggest that estimation of the T4 is an adequate screening test for thyrometabolic disease, and that performing the extra test (T3 resin uptake) in order to estimate the free thyroxine index (FTI) cannot be justified in terms of cost-benefit. We suggest that the FTI is indicated only in those cases in which the T4 is outside the 80% limit range. A simple scheme for the investigation of thyrometabolic disorders is presented.