Biomedical subjects
M M Lubran
Publications and source records attributed to M M Lubran.
Hyperglobulinemia may spuriously elevate measured serum inorganic phosphate levels.
Pseudohyperphosphatemia was noted in four patients with hyperglobulinemia when inorganic phosphate levels were measured on the Vickers M-300 discrete automated analyzer (Vickers, Raritan, NJ) used by our clinical laboratory. When the same samples were reanalyzed after protein removal by sulfosalicylic acid precipitation, ultrafiltration, or more extensive dilution, the measured serum inorganic phosphate levels were invariably normal. The addition of human globulin (but not albumin), to pooled normal sera, caused an increase in serum inorganic phosphate levels as measured by the discrete analyzer. The increase correlated with the amount of globulin added (r = 0.72, P less than 0.05), but measured levels did not reach those observed in the hyperphosphatemic, hyperglobulinemic patients. Identification of 13 additional hyperglobulinemia patients revealed that hyperglobulinemia was not invariably associated with hyperphosphatemia. These data suggest that (1) with discrete automated analyzer use, hyperglobulinemia but not hyperalbuminemia may falsely elevate serum inorganic phosphate levels; (2) increased measured serum inorganic phosphate levels appear to be determined by both the concentration and the physicochemical characteristics of the globulin; (3) physicians should avoid prescribing phosphate binders to hyperglobulinemia patients with "hyperphosphatemia" unless they have ascertained that the serum inorganic phosphate level has been measured in a specimen that is free of protein; and (4) the occurrence of "pseudohyperphosphatemia" should suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy.
Automation in the clinical laboratory.
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Serum and red cell magnesium levels in patients with premenstrual tension.
Magnesium deficiency has been implicated as a possible causative factor in premenstrual tension (PMT). We have assessed serum and red cell magnesium concentration in nine normal premenopausal women and 26 PMT patients, using atomic absorption spectrometry. The following means +/- SEM were obtained from serum and red cell magnesium, respectively, in mg/100 ml: normal subjects: 1.7 +/- 0.04 and 4.5 +/- 0.25 PMT patients: 1.8 +/- 0.05 and 3.1 +/- 0.24. Mean red cell magnesium level was significantly (p less than 0.01) lower in PMT patients. Red cell magnesium determinations should be included in the evaluation of PMT.
Effects of reagents on the measurement of hemoglobin using an automated cell counter.
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McArdle's disease: a review.
The clinical features of McArdle's disease (inherited deficiency of skeletal muscle phosphorylase) and the histological and biochemical changes are described. Their possible causes are discussed in the light of recent knowledge of the biochemistry of muscular contraction. Diagnostic tests are detailed. Attention is drawn to the possibility that the disease may be due to primary defect of motoneurons.
Hematologic side effects of drugs.
Bone marrow and peripheral blood cells may be adversely affected by drugs. Although the risk from most drugs is very small, many cases are reported because of the millions of doses of drugs taken each year by the population. Neutropenia, thrombocytopenia, hemolytic anemia, aplastic anemia, and macrocytic anemia are the commonest effects, in that order. Aplastic anemia is rare, but very serious when it does occur. Adverse effects may be produced by a direct toxic action of the drug or its metabolites on the bone marrow or, less often, on circulating cells. Antineoplastic drugs and chloramphenicol are examples. Most drugs produce their adverse effects through an immunological mechanism. The drug may act as a hapten or may affect the immune system leading to the production of antidrug antibodies and sometimes autoantibodies. Hemolytic anemia may result. Penicillins may behave in this manner. Some drugs act on erythrocytes with enzyme defects, e.g. glucose-6-phosphate dehydrogenase (G-6-PD) abnormalities, to produce hemolysis. In many cases, the mechanism underlying the adverse effect is unknown. The paper lists the drugs reported to have caused some hematological adverse effect and describes the mechanisms in those cases where they are known.
Measurement of enzymes in environmental intoxications.
The paper details the enzymes which have been shown to be affected by certain zenobiotics, principally industrial pollutants, toxic metals, toxic gases and food additives. The role of mixed function oxidases is discussed and methods of assessing their activity indicated.
Bacterial toxins.
Many bacterial toxins are proteins, encoded by the bacterial chromosomal genes, plasmids or phages. Lysogenic phages form part of the chromosome. The toxins are usually liberated from the organism by lysis, but some are shed with outer membrane proteins in outer membrane vesicles. An important non-protein toxin is lipopolysaccharide or endotoxin, which is a constituent of the cell wall of gram negative bacteria. Toxins may damage the eukaryotic cell membrane by combining with some structural component, or otherwise alter its function. Many toxins combine with specific receptors on the surface membrane, frequently glycoproteins or gangliosides, and penetrate the cell to reach their intracellular target. A common mechanism of entry is absorptive endocytosis. Many protein toxins have an A-B structure, B being a polypeptide which binds to the receptor and A being an enzyme. Many toxins are activated, either when produced by the bacterium or when bound to the membrane receptor, by proteases (nicking). An enzymatic process common to many toxins is adenosine diphosphate (ADP)-ribosylation of the adenylate cyclase regulatory proteins, leading to an increase in intracellular cyclic adenosine monophosphate (cAMP). This is the mechanism of action of cholera toxin. Diphtheria toxin catalyzes the transfer of ADP-ribose to elongation factor-2, inhibiting protein synthesis. Most toxins act on the target cells to which they bind, but tetanus toxin, and, to a lesser degree, botulinum toxin, ascend axons and affect more distant structures. Although many toxin effects caused by bacteria have been described, only a few toxins have been identified, characterized, and their mode of action determined at the molecular level. The best known of these are discussed.
Drug abuse in the workplace.
A program for drug-testing in the workplace requires careful planning. There should be a written policy, detailing for which drugs should there be testing, personnel to be tested, frequency and mode of testing, and sanctions if the tests are positive. Urine collection is best carried out under direct vision, but this may create problems because of invasion of privacy. A chain of custody for the urine specimen must be established and confidentiality of the employee's name maintained. The choice of drugs depends on the employer's objectives, but the illicit "street" drugs should be included. The drug testing laboratory should be carefully selected. Drug screening should be by an antibody method and all positive screening tests must be confirmed by gas chromatography or, even better, by gas chromatography/mass spectrometry. Concentrations of drugs constituting a positive test should be established. These values are usually set by the manufacturers of the reagent kits. Interpretation of positive results should be made by an expert and not by lay staff. Positive results for some drugs may result from prescription medication or food.
The measurement of total serum proteins by the Biuret method.
The biuret reaction for proteins provides a simple and precise method for measuring serum proteins; Beer's law is obeyed to at least 10 g per dl. Several stable biuret reagents are available. Hemoglobin is the only important cause of interference which cannot be minimized by use of a sample blank. The mechanism of the biuret reaction is described and attention is drawn to the heterogeneity of the serum proteins and to the use of a certified albumin standard.
The macrophage electrophoretic mobility test for malignancy.
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Estimation of plasma renin activity by radioimmunoassay of angiotensin I.
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Role of the lung in angiotensin metabolism.
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The meaning of pH.
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Accuracy and precision in clinical chemistry.
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A Pisgah view of clinical science. Sunderman award address.
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Radioisotopic assay of serum vitamin B 12 .
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