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Biomedical subjects

P J Howanitz

Publications and source records attributed to P J Howanitz.

At least 73 records · Page 4Linked to original sources

The accuracy of frozen-section diagnoses in 34 hospitals.

We compared the diagnoses from intraoperative frozen-section consultation with the final diagnosis using permanent tissue sections from 34 hospitals throughout North America. Participating pathologists who provided data from their practices volunteered for a pilot study of Q-Probes, a modular quality assurance program of the College of American Pathologists, Skokie, III. During 4 weeks, 186 pathologists evaluated 1952 frozen-section cases and deferred diagnoses to the final permanent sections in 77 cases (3.9%). Concordance between frozen-section and the final histologic diagnoses was 96.5%; whereas the mean and median concordance rates for participating institutions were 96.8% and 97.4%, respectively. Of 67 discordant diagnoses, 29 occurred from sampling of nonrepresentative tissue specimens, and 29 from diagnostic misinterpretations. The pathologists indicated that the diagnostic discordance had little or no effect on patient care in 94% of cases. We conclude that the North American pathologists studied interpret frozen sections with exceedingly high accuracy, approximating that reported from teaching hospitals.

Frozen Sections↗

Use of proficiency test performance to determine clinical laboratory director qualifications.

Many activities and policies influence laboratory test quality. Proficiency test results are one measure of laboratory quality, and during the past 25 years, five studies have examined the relationship of laboratory director educational requirements to proficiency test results. Data from three studies support the association between director qualifications and quality as measured by proficiency test performance, whereas no relationship was found in the other two studies. Possible reasons for conflicting results include differences in database size and demographics; in addition, proficiency test results may be inappropriate, although widely used, as the sole measure of laboratory director performance.

Administrative Personnel↗

Immunoassay. Development and directions in antibody technology.

Improvements and new applications for the technique of immunoassay have been extensive, owing in part to improvements in specific binding reagents used. Early reports advocated application of naturally occurring antibodies, specific serum-binding proteins, and receptors as binding reagents in immunoassays. Each is still used today, although applications are limited because affinities are generally low. Polyclonal antibodies produced in laboratory animals in response to injection of specific antigens have been the cornerstone of immunoassay because of their high affinities and wide range of specificities. Recently, monoclonal antibodies have begun to replace polyclonal antibodies because of improved specificity, ease of use, production of an unlimited supply, and advantages of worldwide assay standardization. Although only 50 analytes are currently measured by Food and Drug Administration--approved reagents, widespread use in the future is predicted.

Antibodies, Monoclonal↗

Influence of specimen treatment on nonreactive HTLV-III sera.

We investigated effects of specimen treatment on HTLV-III antibody assay results. Freezing and thawing specimens 10 times did not increase specimen mean absorbance (A) values measured by the Abbott immunoenzymometric assay (IEMA). Heating blood donor serum specimens at 56 degrees C for at least 10 min inactivates virus, but converted 7.1% of nonreactive specimens to positive when measured by this IEMA. Also heating at 56 degrees C for 30 min increased A values of most specimens; however, the conversion to positive within assay ranged from 0 to 75%, with a mean of 17%. When 56 nonreactive patient specimens were heated, 55% became Abbott IEMA reactive, although ENI IEMA values did not increase and Western blot results remained nonreactive. Binding of immunoglobulins G and A to Abbott IEMA beads did not cause this conversion after heat treatment. We postulate that heating specimens causes alteration of some serum matrices and introduces nonspecific binding to assay bead antigen or antibody reagents. We recommend that for the Abbott IEMA, specimens may be stored frozen, and must not be heated to avoid altered reactivity.

Antibodies, Viral↗

Presence of HTLV-III antibodies in immune serum globulin preparations.

The authors tested 15 immune serum globulin pharmaceutical preparations for antibody reactivity to human T cell lymphotrophic virus type III (HTLV-III) by the Abbott immunoenzymometric assay (IEMA). Although no evidence of HTLV-III infectivity has appeared after injection of similar preparations into humans, the authors found all samples IEMA reactive. Upon dilution, the authors demonstrated parallel decreases of antibody reactivity among two samples of gamma globulin, the Abbott-positive control, and a markedly reactive patient specimen. Gamma globulin isolated from sera of six animal species was nonreactive in the Abbott assay. All samples were nonreactive with the H-9 cell line antigen. Antibody reactivity to HTLV-III was confirmed in 13 of 15 gamma globulin samples when tested by the Electro-Nucleonics IEMA, and 14 samples contained at least the p24 band on Western blot analysis. Although false positivity occurs in IEMA assays possibly because of elevated protein concentrations and nonspecific binding, the authors, results show that in most circumstances immune serum globulin preparations tested do contain true reactivity to HTLV-III.

Antibodies, Viral↗

Protein method influences on calculation of tissue receptor concentration.

Many protein methods are used for estimation of tissue receptor concentration. The authors compared performance, analytic variability, and accuracy of six protein methods used in these calculations. They found the Lowry protein procedure standardized with bovine serum albumin (BSA), usually considered the reference method, to be the most imprecise and most time consuming method. When the BSA standards from the Lowry procedure were assayed with the other methods, results ranged from 74 to 141% of expected. For three other protein standards, reactivity among the six methods varied almost twofold. Comparison of Lowry protein concentrations in cytosols from 46 tumors biopsies with other methods indicated best agreement was with an automated turbidometric (TCA) or a Coomassie dyebinding procedure. Use of protein standardization for the two direct spectrophotometric procedures decreased overestimation of receptor protein concentrations. Because receptor concentration is the quotient of receptor quantity and protein concentrations, tissue receptor results are dependent in part on standardization and choice of protein method.

Animals↗

Prevalence of antibodies to HTLV-III in quality-assurance sera.

We tested 146 clinical-laboratory quality-assurance sera for antibodies to human T-lymphotropic virus III (HTLV-III). Of 127 human-based samples, 39 (31%) were positive by an immunoenzymometric assay (IEMA). Samples of human origin that gave IEMA reactivity included four of 10 ethylene glycol-based (liquid) samples, two of six in-house pools of fresh sera, and 32 of 111 lyophilized samples. All 19 bovine-based samples were negative. Antibodies to HTLV-III in 16 samples were remeasured by a second IEMA and the Western blot technique. All assays detected antibody reactivity in four of the 16 samples; however, results of the second IEMA and the Western blot agreed best. We report large discrepancies between assay results when laboratory reagents are tested for HTLV-III antibodies, and find that many quality-assurance samples containing human sera have measurable IEMA reactivity for HTLV-III antibody. Reactivity in these assays indicates the presence of antibody, not viral infectivity.

Animals↗

Pituitary tumors.

The most frequent pituitary neoplasm is the adenoma, which can produce signs and symptoms owing to mass effects or secretion of pituitary hormones. The authors discuss these mass effects of pituitary tumors on the endocrine system and excess hormone secretion by pituitary adenomas.

Adenoma↗

Hypercortisolism.

The diagnostic evaluation of a patient with hypercortisolism should progress through screening and then confirmatory hormonal measurements. However, tests of the hypothalamic-pituitary-adrenal axis to predict the cause of hypercortisolism always should be viewed as providing supportive data, as exceptions that occur limit the usefulness of these tests. Familiarity with the diagnostic errors of the procedures is essential.

17-Hydroxycorticosteroids↗

Controversies in thyroid function testing.

Thyroid function tests can be abnormal in certain patients in the absence of thyroid dysfunction. All thyroid function tests can be affected in these patients, including the free thyroxine assays and free thyroxine index. Familiarity with the conditions affecting thyroid function tests is necessary to avoid incorrect diagnosis and unnecessary testing.

Female↗

Influences of specimen processing and storage conditions on results for plasma ammonia.

Ammonia concentrations in plasma may increase because of contamination and deterioration of blood components during specimen handling and storage. Using replicate specimens from healthy volunteers, we studied influences of specimen processing and storage procedures on ammonia measurements made with a self-contained reagent system. Under some conditions, ammonia concentrations more than doubled. The use of nonhemolyzed plasma specimens and prompt centrifugation, separation of plasma, and ammonia determination apparently were important in avoiding such increases, the duration of contact between plasma and cells being the most important factor. Lower temperatures had minimal effect on whole-blood storage and centrifugation, but retarded increases in ammonia in stored plasma. We conclude that procedures for collection and storage of specimens for ammonia determinations should be standardized and strictly observed.

Ammonia↗

Circulating human antibodies as a cause of falsely depressed ferritin values.

We have previously reported spuriously elevated values for serum thyrotropin (TSH) measured by immunoradiometric assay (IRMA). We tested those sera showing interference with the TSH assay in a ferritin IRMA which used 125I-rabbit antiferritin antibody and solid phase goat antiferritin antibody as reagents and spleen ferritin as standard. In this assay, we obtained falsely low ferritin values that were corrected by addition of 0.2% non-immune rabbit serum to the labelled antibody. Two other radioimmunoassays gave results with these sera that were not falsely lowered. The interference was shown to be due to human IgG reactive with rabbit serum, the specificity of the interfering antibody being similar in all affected sera. Human antibodies directed against immunoassay reagents may lead to spuriously increased or decreased immunoassay results depending on the specific reagents involved.

Animals↗

Bacterial interference with urine osmolality measurements.

We report bacterial interference with urine osmolality measurements using an instrument based on the principle of freezing point depression. Although the exact nature of the interfering activity has not been defined, the phenomenon is associated with a bacterium, identified as Pseudomonas putida, and is removed from the specimens by filtration at 0.45 micron. The bacteria led to osmometer dysfunction presumably by acting as a nidus for crystallization and preventing proper supercooling of specimens.

Freezing↗

Quality control for the clinical laboratory.

Quality control is a management discipline by which laboratories assure the validity of their results for bedside management of patients. The thrust of quality control has been the laboratory's efforts at improving analytic variability associated with the measurement process. Through increasing emphasis on automation and participation in laboratory improvement programs, laboratory imprecision and inaccuracy have decreased over the past 15 years. Recent advances in the practice of quality control include use of new types of quality control materials, changing concepts of what is out of control, and the introduction of microcomputer applications.

Clinical Laboratory Techniques↗

Analytical biases with liquid quality control material.

Biases were compared for eight analytes determined using common chemistry instruments. Data for three levels of liquid control sera were obtained from over 350 laboratories participating in a quality control program. These data were contrasted with comparable results for lyophilized material and reported in a CAP proficiency survey. In general, biases appeared to be proportional to analyte level. For some analytes, biases with liquid material were less than with lyophilized material, but for most analytes, biases were greater with liquid than lyophilized material. However, when liquid material is used for monitoring interlaboratory precision, the consequences of analytic biases are minimized because of large pool sizes.

Autoanalysis↗

Continuous propranolol infusion following abdominal surgery.

Thirteen patients given long-term propranolol hydrochloride therapy for heart disease required 15 abdominal surgical procedures. On each occasion, propranolol therapy was maintained postoperatively by continuous intravenous infusion. Duration of infusion ranged from one to nine days, and each infusion was monitored with frequent measurements of serum propranolol concentrations. In patients with normal hepatic and renal function, therapeutic serum propranolol levels were attained with a narrow dose range averaging 3.0 mg/hr, irrespective of body weight. All patients had postoperative courses free of complications attributable to beta-blockade. This form of therapy appears to protect against sympathetic stimulation during the perioperative period and to prevent the propranolol withdrawal syndrome in such patients. Continuous propranolol infusion might also be useful in other clinical situations, such as acute aortic dissection or severe thyrotoxicosis, where predictable therapeutic serum propranolol levels could be maintained when oral therapy was contraindicated.

Abdomen↗