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Biomedical subjects

C A Parvin

Publications and source records attributed to C A Parvin.

50 records · Page 3Linked to original sources

Influence of assay method differences on multiple of the median distributions: maternal serum alpha-fetoprotein as an example.

A straightforward statistical explanation is provided to show how differences between assay methods can affect the distribution of the multiples of the median (MoM). Evaluation of the impact of assay method differences reveals that the upper tails of the MoM distribution are not affected to the same degree as the lower tails of the distribution. The disparities in MoM distributions due to assay method differences result in various sensitivity/specificity combinations for different assays having the same fixed MoM cutoffs. Disparities do not exist if risks are calculated with use of the distributions for affected and unaffected populations that are based on a center's own assay method. Applying published risk tables, however, can affect the accuracy of the risk estimates. We used maternal serum alpha-fetoprotein as an example of an assay with an established history of reporting results in MoM values; however, the concepts presented apply equally well to any assay for which results are reported in MoMs.

Female↗

Estimating the performance characteristics of quality-control procedures when error persists until detection.

The concepts of the power function for a quality-control rule, the error detection rate, and the false rejection rate were major advances in evaluating the performance characteristics of quality-control procedures. Most early articles published in this area evaluated the performance characteristics of quality-control rules with the assumption that an intermittent error condition occurred only within the current run, as opposed to a persistent error that continued until detection. Difficulties occur when current simulation methods are applied to the persistent error case. Here, I examine these difficulties and propose an alternative method that handles persistent error conditions effectively when evaluating and quantifying the performance characteristics of a quality-control rule.

Chemistry, Clinical↗

Neuroaxonal dystrophy in aging human sympathetic ganglia.

Autonomic dysfunction is an increasingly recognized problem in aging animals and man. The pathologic changes that produce autonomic dysfunction in human aging are largely unknown; however, in experimental animal models specific pathologic changes have been found in selected sympathetic ganglia. To address whether similar neuropathologic changes occur in aging humans, the authors have examined paravertebral and prevertebral sympathetic ganglia from a series of 56 adult autopsied nondiabetic patients. They found significant, specific, age-related neuropathologic lesions in the prevertebral sympathetic superior mesenteric ganglia of autopsied patients. Markedly swollen dystrophic preterminal axons compressed or displaced the perikarya of principal sympathetic neurons. Ultrastructurally, these swollen presynaptic axons contained abundant disoriented neurofilaments surrounded by peripherally marginated dense core vesicles. Immunohistochemical studies demonstrated that dystrophic axons contained tyrosine hydroxylase and neuropeptide tyrosine (NPY)-like immunoreactivity but not other neuropeptides (VIP, substance P, gastrin-releasing peptide [GRP]/bombesin, met-enkephalin). Similar to the animal models of aging, lesions were much more frequent in the prevertebral superior mesenteric ganglia than in the paravertebral superior cervical ganglia. These studies demonstrate anatomic, peptidergic, and pathologic specificity in the aging human nervous system similar in many respects to that which the authors have described in experimental animal models. Neuroaxonal dystrophy in the sympathetic nervous system may underlie poorly understood alterations in clinical autonomic nervous system function that develop with age.

Adult↗

Interference in an automated radial partition fluorescent immunoassay of thyrotropin associated with liver-function abnormalities.

In a previous evaluation of a "sensitive" radial partition fluorescent immunoassay on the Stratus system, thyrotropin (TSH) values exhibited a positive bias in icteric samples when compared with results of a nonsensitive radioimmunoassay. In the present study, we evaluated 366 patients samples to assess whether any biochemical markers of liver function could identify samples for which TSH values would be falsely increased. gamma-Glutamyltransferase and total bilirubin concentrations were unrelated to discrepant TSH values. In contrast, alkaline phosphatase (ALP) was significantly positively correlated with differences in Stratus and RIA TSH concentrations (P less than 0.001). However, this correlation explained only 34% of the observed residual variability around the estimated regression line. On average, the higher ALP values were associated with larger discrepancies between Stratus and RIA TSH values, although several samples with increased ALP did not have falsely increased Stratus TSH values. TSH measurements performed with a Stratus should be interpreted with caution in patients with abnormal biochemical markers of liver function.

Autoanalysis↗

Aminophylline loading in asthmatic patients: a protocol trial.

We tested an aminophylline loading-dose protocol in which asthmatic patients presenting to an emergency department were given a half (3 mg/kg) IV loading dose based on total body weight (TBW) if they had taken a short-acting or sustained-release theophylline preparation within 12 or 24 hours, respectively, prior to arrival: otherwise, a full (6 mg/kg) loading dose was administered. Of the 28 patients given a full loading dose, 20 (71.4%) achieved a postload therapeutic level (10 to 20 micrograms/mL), and none developed a toxic level (greater than 20 micrograms/mL). Although 34 (60.7%) of 56 patients given a half loading dose attained a postload therapeutic level, 13 patients (23.2%) entered the toxic range. We were able to predict that loading doses of 7.6 mg/kg and 3.8 mg/kg based on ideal body weight (IBW) would have yielded very similar results. The mean change in theophylline level per mg/kg TBW of administered aminophylline was 2.01 micrograms/mL. When calculated on the basis of IBW, the mean change in theophylline level was 1.58 micrograms/mL. Evaluation of the change in theophylline level resulting from aminophylline loading doses based on either TBW or IBW revealed that each dosing method produced changes in blood level with similar variability that were not independent of obesity, indicating that neither dosing method is superior to the other. Thus, patients who report not having taken a theophylline preparation within the above time limits can be given a full aminophylline loading dose of either 6 mg/kg based on TBW or 7.6 mg/kg based on IBW. Other patients, however, require a preload blood level determination to optimize therapy and avoid toxic levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cephalic index: a gestational age-dependent biometric parameter.

Cephalic index was proposed originally as a means of recognizing altered head shape and confirming the validity of biparietal diameter (BPD) measurements. Two previous studies found cephalic index to be gestational age-independent. We tested this relationship by regression analysis in 777 well-dated pregnancies, evenly distributed between 14-40 weeks' gestation. Significant variation in cephalic index was found with advancing gestational age, with the highest and lowest values observed at 14 and 28 weeks, respectively. Based upon application in a separate test population of 1361 normal fetuses, a threshold of +/- 1 SD maximized identification of misleading BPDs due to altered head shape.

Cephalometry↗

Differential susceptibility of prevertebral and paravertebral sympathetic ganglia to experimental injury.

To investigate the response of selected sympathetic ganglia to experimental injury, neonatal rat pups were treated with either 6-hydroxydopamine (6-OHDA), guanethidine, or antiserum to nerve growth factor (anti-NGF). When examined at one month of age, each of the treatments resulted in a significantly greater loss of neurons and tyrosine hydroxylase activity in paravertebral (superior cervical and stellate) versus prevertebral (superior mesenteric and celiac) sympathetic ganglia. Guanethidine treatment produced the largest differential in neuron loss and tyrosine hydroxylase activity between pre- and paravertebral ganglia. Histologically, the acute phase of guanethidine-induced injury in the superior cervical, paravertebral, ganglia was characterized by a prominent mononuclear cell infiltrate and extensive neuronal degeneration. Minimal histopathologic changes were seen in the superior mesenteric, prevertebral, ganglia of the same animals. Immunolocalization of tyrosine hydroxylase and neuropeptide Y (NPY) in guanethidine-treated animals showed a preferential loss of sympathetic innervation of the extramural mesenteric vasculature with relative sparing of the noradrenergic innervation of Auerbach's myenteric plexus. Differences in the susceptibility of sympathetic ganglia to various insults may underlie the selective and heterogeneous involvement of sympathetic ganglia in clinical and experimental situations.

Animals↗

Semi-automated direct colorimetric measurement of creatine kinase isoenzyme MB activity after extraction from serum by use of a CK-MB-specific monoclonal antibody.

This semi-automated colorimetric assay for the MB isoenzyme of creatine kinase (EC 2.7.3.2) is based on a monoclonal antibody ("Conan-MB") specific for this isoenzyme and is a modification of a previously published method (Vaidya et al., Clin Chem 1986;32:657-63). A 0.64-cm bead coated with 2 to 3 micrograms of antibody is incubated with 100 microL of serum and 10 microL of 0.2 mol/L beta-mercaptoethanol for 1 h at room temperature, to extract CK-MB. The beads are washed with de-ionized water and incubated with CK substrate for 45 min at 37 degrees C. A solution containing trans-1,2-diaminocyclohexane-N,N,N', N'-tetraacetic acid, p-iodonitrotetrazolium violet, and diaphorase is added and the resulting colored product is measured at 492 nm. The standard curve is linear to 200 U of CK-MB per liter, and analytical recovery is 97-113%. Total assay CV for low (9.7 U/L) and high (50.7 U/L) quality-control materials was 14.1% (n = 1878) and 11.6% (n = 1842), respectively. CK-MB activity correlated well (r = 0.978, n = 226) with CK-MB measured by a two-site mass immunoassay, and 99.4% of samples with CK-MB greater than or equal to 12 U/L (n = 347) were verified by electrophoresis on agarose.

Adsorption↗

Extending the capabilities of a laboratory computer system through cooperative processing.

The concept of cooperative processing within the context of a hospital or laboratory computer systems environment is introduced. Two examples that produce graphical display of laboratory data are described to illustrate cooperative processing's ability to enhance a system's functionality without placing significant additional burden on system resources.

Clinical Laboratory Information Systems↗

Clinical predictors of theophylline blood levels in asthmatic patients.

To determine the usefulness of clinical information in predicting theophylline levels, 21 parameters were studied in 204 asthmatic patients. The best single parameter for predicting theophylline levels was the last outpatient level (r = 0.484), which was within +/- 5 micrograms/mL of the presenting theophylline level in 62.5% of cases. However, there was considerable variability in theophylline levels in the other 37.5% of cases. The best combination of predictors was the last outpatient level and time since the last dose in patients taking a short-acting preparation. Even with this combination, however, 20.8% of predicted levels fell outside a range of +/- 5 micrograms/mL of the presenting theophylline levels. The only patients in whom a theophylline level could be predicted reliably were those who reported taking a sustained-release or short-acting preparation more than 15 or 8 hours prior to evaluation, respectively. In these patients, all presenting theophylline levels were in the subtherapeutic range (ie, less than 10 micrograms/mL), with 92% of the levels less than 5 micrograms/mL. Except for these patients, readily available theophylline determinations are necessary in order to optimize theophylline therapy with minimal risk of toxicity.

Adolescent↗

A BASIC computer program for evaluating the effect of sample distribution on the least-squares regression slope estimate.

Least-squares regression analysis is widely used in analytical method comparison studies even though model assumptions are typically violated. The advantages favoring the use of the least-squares technique, when applicable, are that its theoretical characteristics are thoroughly developed and the calculations are straightforward and universally known. In order to aid an investigator in determining whether or not the least-squares technique can be acceptably applied in a given method comparison situation, a BASIC computer program is developed that evaluates the bias of the least-squares slope estimate as a function of the precision characteristics of the analytical methods and the proposed sampling distribution for the method comparison experiment.

Clinical Laboratory Techniques↗

Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans.

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.

Adult↗

A direct comparison of two slope-estimation techniques used in method-comparison studies.

Least-squares regression estimation of the slope and intercept in method-comparison studies is the most common method of data evaluation despite well known theoretical difficulties with this approach. An alternative estimation technique has been suggested, which avoids some of these theoretical difficulties. I developed an exact mathematical relationship between these two slope estimates in order to directly compare their characteristics. A simple approximate formula for the relative difference between the two slope estimates is also derived. Using these mathematical relationships, I compare the two estimation techniques, using data from published method-comparison studies. In most of the published method comparisons the differences between slope estimates were trivial, but in some the differences were large enough to have warranted use of the alternative slope estimate.

Mathematics↗

In vitro immunization to KLH. II. Limiting dilution analysis of antigen-reactive cells in primary and secondary culture.

Limiting dilution analysis was used to estimate the frequency of human peripheral blood T lymphocytes that proliferate in response to in vitro immunization with keyhole limpet hemocyanin (KLH). Antigen-reactive cells (ARC) were estimated 9 days after primary immunization with KLH. The ARC frequency of lymphocytes from 12 subjects ranged from 1:23,800 to 1:52,631. Lymphocytes from five of these subjects were also primed for 12 days with KLH, rechallenged in secondary culture with fresh adherent cells and KLH, and assayed 4 days later. The ARC frequency increased to 1:1,123 to 1:7,247, indicating that T cell clones responsive to KLH had expanded during primary culture. In addition, we observed that the proliferative response of lymphocytes from 5 of the 12 subjects were inhibited at high cell concentrations. Depletion of OKT8+ T cells before culturing with KLH however did not alter the inhibitory effect of high concentrations of T cells.

Cells, Cultured↗