Search PubMed⌕ Search

Biomedical subjects

D T Forman

Publications and source records attributed to D T Forman.

At least 55 records · Page 3Linked to original sources

Laboratory analysis of cerebrospinal fluid.

OBJECTIVE: To review the physiology of cerebrospinal fluid (CSF), normal laboratory reference values, and key aspects of CSF sample collection, gross and microscopic examination, microbiologic testing, and chemical analysis. DATA SOURCES: Recent professional literature. STUDY SELECTION: Selected manually by the authors. DATA EXTRACTION: Articles manually by the authors. DATA SYNTHESIS: CSF is formed by a combined process of plasma ultrafiltration and active secretion. Mechanical and osmotic barriers exist between plasma and CSF and between CSF and brain. Lumbar puncture is the preferred technique for CSF sampling. Normal CSF should be clear, colorless, and free of clotted material. CSF can be examined for presence of microbes using stains. Additionally, the chemical composition of CSF can be examined; tests of interest include glucose, protein, lactate, enzymes, glutamine, specific amino acids, biogenic amines, and various drugs. CONCLUSION: Visual, microscopic, and chemical examination of CSF is essential to the clinical management of patients with CNS disease.

Cerebrospinal Fluid↗

Neonatal screening for biotinidase deficiency.

Children with juvenile-onset multiple carboxylase deficiency lack biotinidase activity (biotinamide amidohydrolase, EC 3.5.1.12) in the liver and other tissues. Hence, little free biotin is metabolically available, resulting in seizures, acidosis, and serious neurological damage. As the absence of hepatic biotinidase activity is reflected in serum, assessment of biotinidase status can easily be made from a blood sample. A convenient qualitative procedure for screening infants has been employed in order to estimate serum levels of biotinidase in as little as 10 microliters of sample. This colorimetric procedure detects the formation of free p-aminobenzoate cleaved from the substrate, N-biotinyl-p-aminobenzoate at pH 6.0. The assay is easily performed and has a low incidence of false positive results. A kinetic assay for serum biotinidase has also been developed using biotinyl-p-nitroanilide (BpNA) as substrate. When 50 microliters of biotinidase positive serum was incubated with 0.2 mM BpNA in phosphate buffer at pH 6.0, an increase in absorbance was observed at 405 nm. The rate of change in absorbance was followed kinetically on the Roche Cobas BIO analyzer at 37 degrees C. Monitoring the increase in absorbance of para-nitroanilide every 60 seconds over 30 minutes demonstrated linearity from 10 to 30 minutes. In comparing results from this kinetic assay on 48 randomly selected sera with those obtained using a colorimetric procedure, a correlation coefficient of 0.85 was obtained. Several false positive results were observed in clearly lipemic sera.

4-Aminobenzoic Acid↗

Ionized calcium: its significance and clinical usefulness.

Maintenance of normal blood levels of ionized calcium (Ca2+) plays an important role in the management of the critically ill patient. Therefore, Ca2+ should be collected properly and measured reliably. The sound analytical performance of today's Ca2+ analyzers using ion-selective electrode technology have made measurements accurate and precise. The introduction of this technology allows rapid and direct analysis in whole blood or serum, resulting in an enhanced reporting time. Since the amount of heparin in the syringe was shown to lower plasma ionized calcium concentration artifactually, samples for plasma Ca2+ determination should be anticoagulated with a measured quantity of heparin. Ancillary factors in Ca2+ determination include effects of changes in sample pH, and situations where abnormal concentrations of calcium ligands are present. Many clinical situations require Ca2+ rather than total calcium measurements. Liver transplantation, citrated blood transfusions, and neonatal hypocalcemia are examples of a few such circumstances where determination of Ca2+ may be more physiologically and clinically meaningful than total calcium.

Adult↗

Role of the laboratory in diagnosis of organic acidurias.

Clinical signs and symptoms of organic acidurias are usually subtle and non-specific. Laboratory evaluation, therefore, is usually the only conclusive way to reach a definitive diagnosis. Defects of amino acid catabolism generally caused by diminished activity or complete absence of specific enzymes usually occurs at the later stages of a pathway and results in organic aciduria. Most of these acids are effectively cleared from the blood by the kidneys, resulting in their concentration in urine to exceed greatly that in serum. Therefore, the detection of increased organic acids is greatly facilitated by a urine assay. The use of dual capillary column gas chromatography should allow the unambiguous determination of all known organic aciduria. Using this method provides a cost-effective alternative to gas chromatography-mass spectrometry.

Carboxylic Acids↗

Beta 2-microglobulin: its significance and clinical usefulness.

beta 2-Microglobulin (beta 2M), an interesting and underutilized metabolite, can be used in assessing renal function, particularly in kidney-transplant recipients and in patients suspected of having renal tubulointerstitial disease. It also can serve as a nonspecific but relatively sensitive marker of various neoplastic, inflammatory, and infectious conditions. Early hopes that it would be a useful serum test for malignancy have not been fulfilled, but it does have prognostic value for patients with lymphoproliferative disease, particularly multiple myeloma. More recent reports have suggested a role for beta 2M as a prognostic marker in human immunodeficiency virus (HIV) infection.

Acquired Immunodeficiency Syndrome↗

Erythrocyte uroporphyrinogen I synthase activity as an indicator of acute porphyria.

The pre-clinical diagnosis of acute intermittent porphyria (AIP) is important because acute attacks can be brought about by drugs, liver toxins, hormonal changes and diet. There also may be no obvious precipitating agent. The discovery that the activity of uroporphyrinogen I synthase (URO-S) activity in the red blood cells of patients with AIP is half that found in normal persons is of great value in diagnosing this disorder and also appears useful in detecting patients with the latent disease who have normal urinary delta-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. It must also be recognized that some red blood cells URO-S determinations will yield indeterminate results; therefore, repeat assays, including examination of kinship, will improve discrimination and confidence in the final diagnosis.

Ammonia-Lyases↗

Involvement of hormones in the swift increase in alcohol metabolism.

The purpose of this study was to determine the time course of changes in blood levels of various hormones in C57BL/6J mice during exposure to ethanol vapor. Groups of adult male mice were given 2.0 g per kg ethanol intraperitoneally or as continuous vapor for four hours and rates of ethanol elimination were measured. In parallel, blood samples were collected at timed intervals over 5.5 hours during and following exposure to ethanol. Blood levels of epinephrine, norepinephrine, corticosterone, and glucagon were elevated two- to four-fold during ethanol treatment and declined to basal values within one hour following termination of treatment. Elevated blood levels of epinephrine, norepinephrine and corticosterone were highly correlated with higher rates of ethanol elimination (r = 0.80, 0.78, and 0.72, respectively). In contrast, thyroxine and insulin levels were not affected by ethanol. These findings are consistent with the idea that acute administration of ethanol causes the release of glycogenolytic hormones which in turn increase rates of ethanol metabolism.

Animals↗

The effect of ethanol and its metabolites on carbohydrate, protein, and lipid metabolism.

The metabolic effects of ethanol are due to a direct action of ethanol or its metabolites, changes in the redox state occurring during its metabolism, and modifications of the effects of ethanol by several nutritional factors. Ethanol causes hyperglycemia or hypoglycemia depending whether or not glycogen stores are adequate, inhibits protein synthesis, and results in a fatty liver and elevations in serum triglyceride levels. Increases in serum lactate, results from the increased reduced nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide + (NADH/NAD+) ratio, and hyperuricemia probably occurs owing to the increased turnover of adenine nucleotides after ethanol ingestion. Ethanol decreases thiamine absorption and decreases the enterohepatic circulation of folate. Acetaldehyde, the major metabolite of ethanol, increases the degradation of pyridoxal 5'-phosphate by displacing it from its binding protein and making it susceptible to hydrolysis by membrane-bound alkaline phosphatase. Chronic ethanol administration also results in decreased vitamin A stores and reduced bone mass and blood levels of 25-hydroxyvitamin D. The mechanism whereby ethanol affects these vitamins and their associated enzymes is unknown.

Carbohydrate Metabolism↗

A qualitative assessment of biotinidase deficiency.

Screening programs for late-onset, biotin-responsive, multiple carboxylase deficiency (LMCD) detect colormetrically the presence of biotinidase activity in dried samples of whole-blood spotted on filter-papers as used in the neonatal screening of phenylketonuria. A sensitive and stable qualitative technique is described using 10 microliter of serum that avoids problems associated with poor sample collection, improper drying of blood-spots and transient color development. The modified assay is timely and suitable for the clinical laboratory not involved in mass screening programs.

4-Aminobenzoic Acid↗

Immunoassay of enzymes.

Antisera against purified human placental alkaline phosphatase (PAP) and crystallized creatine kinase (CK) isoenzyme from human skeletal muscle (MM) were raised in rabbits. The PAP antiserum was shown by radial immunodiffusion not to react with purified alkaline phosphatases from human liver and intestine, nor with the alkaline phosphatase in sera from patients with osteoblastic bone disease. CK antiserum also demonstrated no cross-reaction and was precipitated quantitatively by its homologous antisera. A "rocket" electroimmunoassay for PAP and CK is described. The method is simple, reproducible and uses small volumes of antiserum. The isoenzyme patterns were compared with those developed by several electrophoretic methods. These techniques share with other immunoassay the advantages of specificity for the antigen and enhance the quantitation of isoenzyme assays.

Alkaline Phosphatase↗

The significance of creatine kinase (CKBB) in metastatic cancer of the prostate.

Alterations of serum creatine kinase isoenzymes were observed in five cases of prostatic carcinoma. Creatine kinase isoenzyme BB was found in the serum of two of three cases with metastases. Its presence in serum does not seem to be related to acid phosphatase activity but seems associated with extension of the tumor to other tissues. Preliminary studies on effusions from patients with malignant and non-malignant prostates showed that CK-BB was detectable only in cytology positive effusions. This finding suggests that CK-BB may be a tumor product rather than a result of a host response. The observation of CK-BB in a significant percentage of patients (two of three) with metastatic carcinoma of the prostate is of interest and suggests that CK-BB isoenzymes may have some predictive value in following patients with malignant disease.

Acid Phosphatase↗

Beta-2 microglobulin--an immunogenetic marker of inflammatory and malignant origin.

Major contributions have been made in the last few years to the knowledge of the structure, fate and cellular origin of beta-2 microglobulin (B2M); but the question of its function still remains unclear. The concept of B2M being simply a marker of renal physiology seems less satisfactory when reference is made to its relationship to the immunogenetic system. Although assay of B2M cannot be considered as a specific diagnostic tool, it still may be regarded as a useful parameter in monitoring inflammatory, malignant, and auto-immune disease activity.

Beta-Globulins↗