Biomedical subjects

G G Klee

Publications and source records attributed to G G Klee.

At least 91 records · Page 5Linked to original sources

PubMed1990

Studies with purified human thyroid peroxidase and thyroid microsomal autoantibodies.

We have isolated highly purified thyroid peroxidase (TPO) from human thyroid tissue to study further the relationship between TPO and the thyroid microsomal antigen that elicits the production of microsomal autoantibodies in patients with autoimmune thyroid disease. Serum samples were obtained from 24 patients with suspected autoimmune thyroid disease, and from 7 normal subjects. Microsomal autoantibodies in the patient sera, as determined by the microsomal hemagglutination assay (MCHA), varied between 1:100 and 1:102,400. Antithyroglobulin antibodies, however, were very low (less than 1:100). Binding of serum autoantibodies to purified human TPO, as determined by enzyme-linked immunosorbent assay, correlated fairly well with MCHA titers (r = 0.72; P less than 0.001). An immunoblot procedure was developed to study the binding of serum antibodies to the major active fragment of TPO (93 kDa), after sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Binding under both conditions correlated very well with MCHA titers (r = 0.80-0.84; P less than 0.001). Studies were performed to determine the inhibitory effect of patient serum on the enzymatic activity of purified human TPO. A marked inhibitory effect on guaiacol activity was observed when TPO was preincubated with as little as 10 microL high titer serum. There was a significant correlation (r = 0.47; P less than 0.01) between MCHA titer and inhibitory effect. The addition of 2 micrograms purified human TPO completely or almost completely inhibited the binding of serum antibodies to thyroid microsomes (enzyme-linked immunosorbent assay) in 10 of 11 patient sera with high MCHA titers (1:25,600 or greater).

Antibody Formation↗

PubMed1990

Pituitary adenomas that produce adrenocorticotropic hormone and alpha-subunit: clinicopathological, immunohistochemical, ultrastructural, and immunoelectron microscopic studies in nine cases.

Eight surgical and one autopsy specimen of pituitary adenomas (six cases of Cushing's disease, two of Nelson's syndrome, and one of hypopituitarism) were studied by histochemical, immunohistocytological, and ultrastructural methods. Eight tumors showed the characteristic histochemical profile of corticotroph adenoma--amphophilic to basophilic, and periodic acid-Schiff-positive to some extent. In all tumors, immunohistochemical studies revealed adrenocorticotropic hormone (ACTH) and alpha-subunit in the cytoplasm of some adenoma cells. By electron microscopy, seven tumors were found to be monomorphous; six were typical corticotroph adenomas and one was a subtype II silent corticotroph adenoma. One unique lesion was bimorphous--i.e., composed of corticotrophs as well as cells resembling glycoprotein cells. Immunoelectron microscopy by the double-labeling immunogold technique, performed on one corticotroph adenoma, demonstrated the presence of ACTH and alpha-subunit not only within the same adenoma cells but also within the same secretory granules. The cytogenesis of ACTH alpha-subunit tumors, a rare form of plurihormonal adenoma, remains to be elucidated. The duration of disease associated with these tumors exceeded the duration in patients with ordinary corticotroph adenomas. Given the low frequency with which increases in serum alpha-subunit are detectable in patients with such tumors--13% in this series--hormone production is not recognized at preoperative evaluation.

Adenoma↗

PubMed1990

Anomalous serum thyroxin measurements with the Abbott TDx procedure.

We describe a patient whose serum gave consistently low results for thyroxin as measured with the Abbott TDx but normal results by radioimmunoassay. Further clinical and laboratory studies did not support the low TDx results. Anti-thyroxin antibodies did not explain the discordant results, and we found no evidence of heterophilic antibodies in the patient's serum. We were unable to identify the cause of the problem.

Adult↗

PubMed1990

The process of quality assurance. Quality indicators in clinical pathology.

The process of developing and using indicators of quality performance in laboratory medicine presents significant problems for clinical pathologists. Although there have been many proposed indicators, many fail to provide meaningful information. Four types of quality indicators (data reliability, laboratory management, clinical utilization, and pathologist credentialing) are proposed and examples of their use are given.

Credentialing↗

PubMed1990

Performance goals for internal quality control of multichannel haematology analysers.

Performance goals for analytic bias and analytic imprecision are presented for multichannel haematology analysers. These goals represent a compromise between limits that would cause minimal degradation in the information content for clinical decisions and limits that are achievable by current instruments. For midrange measurements the maximal limits for total analytic bias are +/- 14.6% for WBC, +/- 5.3% for RBC, +/- 4.5% for Hb concentration, +/- 4.2% for MCV, and +/- 22% for platelet counts. The limits include error inherent in calibrator value assignment, instrument calibration, instrument drift, and instrument non-linearity as well as the quality control systems necessary to monitor each of these processes. If analytic biases are held within the proposed limits, the clinical specificities of the assays will be decreased by less than 7% for all assays except that platelet counts will have a decrease in specificity of about 15%. Analytic imprecision has minimal direct effect on clinical decisions because the influence of within-person and across-person biological variation dominates. However, analytic imprecision is a major factor in the control of analytic bias and thereby remains an important quality control factor.

Blood Cell Count↗

PubMed1990

Power function graphs.

Explore the source record for details and available documents.

Data Interpretation, Statistical↗

PubMed1990

Colorectal cancer detection in the practice setting. Impact of fecal blood testing.

To assess the contribution of fecal blood testing to cancer detection in a clinical practice setting, we studied records from 160 patients with both a new tissue diagnosis of colorectal adenocarcinoma and a preceding stool blood test (HemoQuant, Mayo Medical Laboratories, Rochester, Minn) determination. In this group, 71% had suggestive colorectal symptoms (particularly stool changes, overt bleeding, and abdominal pain) or anemia at presentation, and 29% were asymptomatic. Fecal blood levels remained normal in more than 40% of both symptomatic and asymptomatic patients. In only 26 patients (16% overall) was an abnormal fecal blood level the sole heralding feature, but this subset of patients had a more favorable stage. Fecal blood levels were higher with advanced, larger, and more proximal tumors and with stools collected before purgation. We conclude that, in the practice setting, fecal blood level elevation alone is an uncommon but important manner of colorectal cancer presentation, most cancers present with symptoms, and fecal blood levels are often normal in both symptomatic and asymptomatic patients.

Abdominal Pain↗

PubMed1989

Serum bioactive parathyroid hormone in hemodialysis patients.

In 41 hemodialysis patients with bone disease (histological diagnosis with histomorphometric confirmation of PTH activity) results from a serum immunoreactive PTH (iPTH) assay correlated with results from a new serum bioactive PTH (bio-PTH) assay (r = 0.84; P less than 0.001). The serum bio-PTH values correlated well with osteoclast numbers (r = 0.70; P less than 0.001), resorption surfaces (r = 0.55; P less than 0.001), and presence of marrow fibrosis (P less than 0.02). The serum iPTH values also correlated with osteoclast numbers (r = 0.61; P less than 0.001), resorption surfaces (r = 0.47; P less than 0.003), and presence of marrow fibrosis (P less than 0.02). Serum bio-PTH and iPTH values were higher in patients with severe hyperparathyroidism than in other patients. The assays were equally useful in identifying dialysis patients with severe hyperparathyroidism. Patients with osteomalacia or low turnover bone disease had low serum bio-PTH and/or iPTH values. Low bio-PTH values (less than or equal to 3.6 pmol/L) had a sensitivity and a specificity of 93% for osteomalacia or low turnover bone disease. Low bio-PTH values also were useful in identifying those patients with positive aluminum staining in bone. The serum bio-PTH assay was useful in identifying patients with osteomalacia, low turnover bone disease, or aluminum accumulation.

Adult↗

PubMed1989

Thyroid peroxidase and thyroid microsomal autoantibodies.

The antithyroid microsomal antibodies found in the serum of patients with autoimmune thyroid disease are directed largely, if not entirely, against thyroid peroxidase (TPO). In this study we used a highly purified, well characterized, large tryptic fragment of porcine TPO (hereafter referred to as purified porcine TPO) to examine possible differences among microsomal antibodies in patients with autoimmune thyroid disease. Antibodies against this TPO preparation and also against a synthetic peptide corresponding to residues 780-793 of the deduced sequence of the native enzyme were compared with microsomal antibodies from patients in immunoblot experiments. The antiporcine TPO and antisynthetic peptide antibodies reacted with crude preparations of human TPO. Binding of serum microsomal antibodies to purified porcine TPO was also found. Purified porcine TPO shows two fragments after gel electrophoresis under reducing conditions: a 59K fragment corresponding to the amino end of the molecule, and two approximately 30K fragments corresponding to the carboxyl end. Using an immunoblot procedure with purified porcine TPO as the antigen, we found that at least two epitopes were involved in microsomal antibody production: one associated with the 59K fragment and the other with the approximately 30K fragment(s). The distribution of serum antibodies against these epitopes differed among the patients, indicating that these antibodies comprise a heterogeneous group. Serum from patients with autoimmune thyroid disease significantly inhibited human TPO activity, raising the possibility that microsomal antibodies may contribute to the impaired thyroid function that occurs in some patients with autoimmune thyroid disease.

Adolescent↗

PubMed1989

Effect of counting errors on immunoassay precision.

Using mathematical analysis and computer simulation, we studied the effect of gamma scintillation counting error on two radioimmunoassays (RIAs) and an immunoradiometric assay (IRMA). To analyze the propagation of the counting errors into the estimation of analyte concentration, we empirically derived parameters for logit-log data-reduction models for assays of digoxin and triiodothyronine (RIAs) and ferritin (IRMA). The component of the analytical error attributable to counting variability, when expressed as a CV of the analyte concentration, decreased approximately linearly with the inverse of the square root of the maximum counts bound. Larger counting-error CVs were found at lower concentrations for both RIAs and the IRMA. Substantially smaller CVs for overall assay were found when the maximum counts bound progressively increased from 500 to 10,000 counts, but further increases in maximum bound counts resulted in little decrease in overall assay CV except when very low concentrations of analyte were being measured. Therefore, RIA and IRMA systems based in duplicate determinations having at least 10,000 maximum counts bound should have adequate precision, except possibly at very low concentrations.

Computer Simulation↗

PubMed1988

Sensitive thyrotropin assays: analytic and clinical performance criteria.

Thyrotropin (TSH) measurements in serum traditionally have been used for the diagnosis and management of hypothyroidism; the availability of highly sensitive TSH assays has expanded the utility of these measurements to include detection of hyperthyroidism, monitoring of thyroxine replacement therapy, and front-line assessment of thyroid function. The analytic advancement that has expanded TSH utility is the noncompetitive "sandwich" immunoassay, which is faster and more sensitive than traditional radioimmunoassays. All such assays, however, are not equivalent; therefore, we have developed analytic and clinical performance criteria for evaluating sensitive TSH assays. These criteria are as follows: (1) the overlap between the assay detection limit and the lower limit of normal should be less than 1%, (2) basal TSH measurements should predict the TSH response to thyrotropin releasing hormone stimulation at least 95% of the time, and (3) basal TSH measurements should be 95% sensitive and 95% specific for detecting hyperthyroidism. Three allegedly sensitive TSH assays were evaluated: (1) the Hybritech two-step Tandem-R method (assay A), (2) the semiautomated Boots-Celltech Sucrosep method (assay B), and (3) a modified Ciba Corning Magic Lite method (assay C). Both assay B and assay C fulfilled out criteria for a sensitive assay; assay B had slightly better performance, and assay C was easier to perform.

Humans↗

PubMed1988

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities.

When infection of prosthetic orthopedic implants is suspected, optimal management requires accurate confirmation or exclusion of infection. The authors retrospectively studied 98 patients with possible infection who underwent scanning with indium-111-labeled white blood cells (WBCs) and subsequently underwent surgery within 14 days. At surgery, 50 patients had infections, as determined by means of culture or histologic results. The diagnostic accuracy of In-111 scanning was compared with that of plain radiography, arthrography, three-phase bone scanning, and various clinical and laboratory findings classically associated with infection. Positive findings on In-111 WBC scans and elevated erythrocyte sedimentation rates were found to be the most predictive variables in the diagnosis of septic prostheses (P less than or equal to .001 and P less than or equal to .002, respectively). Likelihood ratio analysis more clearly demonstrated the superiority of In-111 WBC scanning, with positive and negative scans yielding likelihood ratios of 5.0 and 0.16, respectively.

Adult↗

PubMed1988

Bioassay of parathyrin: analytical characteristics and clinical performance in patients with hypercalcemia.

This new bioassay for parathyrin (PTH) in plasma (bio-PTH) combines immunoextraction on affinity columns [goat anti-hPTH (1-44) conjugated to Sepharose 4B] and a receptor assay involving an osteosarcoma cell line. The mean extraction efficacy ranges from 87% (as determined with immunopurified 125I-labeled PTH) to 62% for hPTH bioactivity. The assay is standardized with synthetic hPTH (1-84) and can detect as little as 0.9 pmol/L of PTH in 2 mL of plasma. In 100 healthy adults, the 95% reference interval for bio-PTH was less than 0.9 to 6.1 pmol/L (median, 2.0 pmol/L). In 185 patients with surgically confirmed hyperparathyroidism, bio-PTH concentrations ranged from 1.0 to greater than 120 pmol/L (median, 12.9 pmol/L); 80% of values were greater than 6.1 pmol/L. In 50 patients with both preoperative and postoperative determinations, the mean (+/--SD) concentrations of calcium in serum were 113 +/- 10 and 89 +/- 6 mg/L, respectively; the median bio-PTH concentrations were 13.6 and 2.0 pmol/L, respectively. In 22 patients with nonparathyroid-mediated hypercalcemia, the concentration of bio-PTH ranged from less than 0.9 to 5.3 pmol/L (median, 1.8 pmol/L). This bio-PTH assay is slightly less sensitive than our GP235 immunoreactive PTH (iPTH) immunoassay for detecting hyperparathyroidism (Clin Chem 1982;28:69-74); however, the bioassay is more specific and detected some cases missed by the iPTH assay. Overall, 95% of the hyperparathyroid patients had an increased test result for either the bio-PTH or the iPTH assay.

Adult↗

PubMed1988

Primary aldosteronism. Diagnostic evaluation.

The regulation of mineralocorticoid secretion and the pathophysiology of primary aldosteronism are reviewed. For conceptual and practical purposes, the diagnostic evaluation of primary aldosteronism is discussed as two series of studies. The first series involves the studies necessary to confirm the diagnosis. The second series of studies guides the therapeutic approach by distinguishing unilateral from bilateral adrenal disease.

Humans↗

PubMed1988

Diagnostic evaluation of pheochromocytoma.

Progress in the diagnostic evaluation of pheochromocytoma has taken place in biochemical studies and localization techniques. Measurement of fractionated catecholamines and their metabolites has been subjected to sensitivity and specificity assessment. Magnetic resonance imaging and isotopic imaging have led to much better localization of extra-adrenal tumors. Flow cytometry of the DNA of the tumor cells very likely indicates the malignant nature of the tumor.

Adrenal Gland Neoplasms↗

PubMed1988

Thyroid dysfunction.

This article reviews currently available thyroid function tests and considers the utility of these tests in the investigation of suspected thyroid dysfunction. Potential thyroid screening tests as well as those secondary tests useful in establishing or excluding thyroid dysfunction are evaluated. Current controversies regarding free thyroid hormone and sensitive TSH assays are considered, and algorithms are provided for diagnosing both hypothyroidism and thyrotoxicosis.

Humans↗

PubMed1988

Hypercalcemia.

Hypercalcemia is a relatively common clinical finding; prevalence rates are 1.4 to 3.0 per cent in hospitalized and general clinical populations. Malignancy is the major cause of hypercalcemia in hospital patients, whereas primary hyperparathyroidism (HPT) is the major cause in ambulatory patients. In both hospitalized and ambulatory patients, however, there are many other causes of hypercalcemia, and numerous procedures have been proposed to aid in the differential diagnosis. Unfortunately, no single test is truly diagnostic. The work-up for hypercalcemia requires an integrated knowledge of the strengths and weaknesses of the various procedures as well as an understanding of the various clinical presentations associated with hypercalcemia.

Diagnosis, Differential↗

PubMed1988

A user's classification of problems identified by proficiency testing surveys.

Laboratory results judged as unacceptable in external proficiency surveys do not always signal laboratory testing problems. This is a report of the results of a user's investigation of the proficiency testing flags encountered in our laboratory from three survey programs over a two-year period. The survey programs were administered by the College of American Pathologists, the Centers for Disease Control, and the State of New York. The explanations for the abnormal survey results were classified into six categories: possible analytic measurement problem (28%), clerical error in transcription or completion of forms (16%), inappropriate survey criteria (17%), specimen problem (11%), agency amended report (5%), and no identifiable cause (23%).

Data Collection↗