Detection of glutamic acid decarboxylase autoantibodies with the varelisa ELISA.
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Adolescent↗
Biomedical subjects
C A Parvin
Publications and source records attributed to C A Parvin.
Singleton vs duplicate prostate-specific antigen measurements.
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Humans↗
The endogenous erythropoietin response and the erythropoietic response to blood loss anemia: the effects of age and gender.
The endogenous erythropoietin (EPO) response and the erythropoietic response to anemia in the elderly, as compared with that in younger subjects, is controversial. We therefore studied autologous blood donors undergoing aggressive phlebotomy to determine the effect of age and gender on the EPO response to blood loss anemia, along with the erythropoietic response to endogenous EPO and to exogenous recombinant human EPO therapy. Seventy-one patients underwent phlebotomy, up to 6 units over 3 weeks, and received either placebo (n = 18), EPO 150 U/kg (n = 16), EPO 300 U/kg (n = 18), or EPO 600 U/kg (n = 19) at each of the six visits. Linear regression analysis of the hemoglobin/log EPO relationship for 18 placebo patients revealed no differences in the endogenous EPO response to phlebotomy, as determined by the slopes and intercepts, for males versus females or as a function of age. We found no differences in endogenous EPO-stimulated red blood cell (RBC) volume expansion for males and females (7.06 +/- 2.4 and 7.22 +/- 2.2 ml/kg, respectively, p = 0.88) or as a function of age (estimated rate of change = -0.58 +/- 0.33 ml/kg for every 10 years of life, p = 0.10). Similarly, we found no differences in RBC response to EPO for males versus females (1.4 +/- 0.3 ml/kg vs 1.5 +/- 0.3 ml/kg per 1000 U/kg EPO, respectively, p = 0.80) or as a function of age (estimated rate of change = 0.051 +/- 0.15 ml/kg per 1000 U/kg EPO for every 10 years of life, p = 0.74).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy.
Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150 U/kg, n = 16, 300 U/kg, n = 18, or 600 U/kg, n = 19) or placebo (n = 18). Using data from the three preoperative study visits, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO-treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia.
Adult↗
Effect of diabetes and aging on human sympathetic autonomic ganglia.
Although autonomic dysfunction frequently complicates the clinical course of patients with diabetes, relatively little is known of its underlying neuropathology. Using experimental animal models as a guide, the prevertebral superior mesenteric (SMG) and paravertebral superior cervical (SCG) sympathetic ganglia have been examined in a series of adult autopsied diabetic and non-diabetic patients of various ages using histochemical, ultrastructural, morphometric, and immunohistochemical methods. Quantitative studies demonstrated that markedly swollen argyrophilic terminal axons (neuroaxonal dystrophy) containing large numbers of disorganized neurofilaments developed in the SMG but not SCG as a function of diabetes, increasing age, and gender (males were more severely affected than females). As in experimental animals, diabetic (types I and II) patients developed histologically identical lesions prematurely and in greater numbers than age-matched nondiabetic patients. Morphometric studies showed a small but statistically significant decrease in neuronal density in the SMG but not SCG of diabetic patients. The dimensions of individual sympathetic neurons were not significantly different in aging or diabetes. The pathological lesions identified in the SMG may contribute to the autonomic dysfunction so commonly observed in diabetic patients.
Adolescent↗
New insight into the comparative power of quality-control rules that use control observations within a single analytical run.
The error detection characteristics of quality-control (QC) rules that use control observations within a single analytical run are investigated. Unlike the evaluation of QC rules that span multiple analytical runs, most of the fundamental results regarding the performance of QC rules applied within a single analytical run can be obtained from statistical theory, without the need for simulation studies. The case of two control observations per run is investigated for ease of graphical display, but the conclusions can be extended to more than two control observations per run. Results are summarized in a graphical format that offers many interesting insights into the relations among the various QC rules. The graphs provide heuristic support to the theoretical conclusions that no QC rule is best under all error conditions, but the multirule that combines the mean rule and a within-run standard deviation rule offers an attractive compromise.
Chemistry, Clinical↗
Comparing the power of quality-control rules to detect persistent systematic error.
A simulation approach that allows direct estimation of the power of a quality-control rule to detect error that persists until detection is used to compare and evaluate the error detection capabilities of a group of quality-control rules. Two persistent error situations are considered: a constant shift and a linear trend in the quality-control mean. A recently proposed "moving slope" quality-control test for the detection of linear trends is shown to have poor error detection characteristics. A multimean quality-control rule is introduced to illustrate the strategy underlying multirule procedures, which is to increase power without sacrificing response rate. This strategy is shown to provide superior error detection capability when compared with other rules evaluated under both error situations.
Chemistry, Clinical↗
Comparing the power of quality-control rules to detect persistent increases in random error.
This paper continues an investigation into the merits of an alternative approach to the statistical evaluation of quality-control rules. In this report, computer simulation is used to evaluate and compare quality-control rules designed to detect increases in within-run or between-run imprecision. When out-of-control conditions are evaluated in terms of their impact on total analytical imprecision, the error detection ability of a rule depends on the relative magnitudes of the between-run and within-run error components under stable operating conditions. A recently proposed rule based on the F-test, designed to detect increases in between-run imprecision, is shown to have relatively poor performance characteristics. Additionally, several issues are examined that have been difficult to address with the traditional evaluation approach.
Chemistry, Clinical↗
Germinal center T cells are distinct helper-inducer T cells.
Germinal centers (GCs) contain a significant number of CD4+ T cells, but what role these T cells may play in the development of GC B cells has not been determined. To gain insight into their role, we studied the phenotype of GC T cells and the lymphokines secreted by GC T cells isolated from human tonsils obtained after tonsillectomies. In addition to confirming that a large fraction of GC T cells are Leu-7(CD57)+ and Leu-8-, we found that they have no binding sites for peanut agglutinin. Furthermore, we found that they are CD45RA- and CD45R0+, the phenotype of helper-inducer T cells. We also found that Leu-7(CD57)+ cells display CD69, a phenotypic marker of very early cell activation, but do not display three other markers of cell activation: CD25 [interleukin-2 (IL-2) receptor], CD71 (transferrin receptor), and DR. When isolated, Leu-7(CD57)+ cells were stimulated in vitro with a mitogen that can induce peripheral blood T cells with the helper-inducer phenotype to produce various cytokines, Leu-7(CD57)+ cells did not produce IL-2, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha) in significant amounts. Taken together, GC T cells from a distinct subpopulation of T cells with helper-inducer phenotype by their histologic location, by their surface phenotype, and by their ability to produce lymphokines. This finding is consistent with the possibility that GC T cells have been selectively recruited to actively help B cells develop in GCs.
Antigens, CD↗
Insulin and glucagon in prevention of hypoglycemia during exercise in humans.
To assess the roles of decrements in insulin and increments in glucagon in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal young men were studied during somatostatin infusions with insulin and glucagon infused to 1) hold insulin and glucagon levels constant, 2) decrease insulin, 3) increase glucagon, and 4) decrease insulin and increase glucagon during exercise. In contrast to a comparison study (saline infusion), when insulin and glucagon were held constant, glucose production did not increase and plasma glucose decreased from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.001) initially during exercise. Notably, plasma glucose then plateaued and was 3.3 +/- 0.2 mmol/l at the end of exercise. This decrease was at most only delayed when either insulin was decreased or glucagon was increased independently. However, when insulin was decreased and glucagon was increased simultaneously, there was an initial increase in glucose production, and the glucose level was 4.5 +/- 0.2 mmol/l at 60 min, a value not different from that in the comparison study. Thus we conclude that both decrements in insulin and increments in glucagon play important roles in the prevention of hypoglycemia during exercise and do so by signaling increments in glucose production. However, since hypoglycemia did not develop during exercise when changes in insulin and glucagon were prevented, an additional counterregulatory factor, such as epinephrine, must be involved in the prevention of hypoglycemia during exercise, at least when the primary factors, insulin and glucagon, are inoperative.
3-Hydroxybutyric Acid↗
Catecholamines in prevention of hypoglycemia during exercise in humans.
To assess the role of catecholamines in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal humans were studied with combined alpha- and beta-adrenergic blockade and with adrenergic blockade while changes in insulin and glucagon were prevented with the islet clamp technique (somatostatin infusion with insulin and glucagon infused at fixed rates). The results were compared with those from an islet clamp alone study. In contrast to a comparison study (saline infusion), adrenergic blockade resulted in a small initial decrease in plasma glucose during exercise, from 5.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l (P less than 0.01), but the level then plateaued. There was a substantial exercise-associated decrement in plasma glucose when insulin and glucagon were held constant, i.e., from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.0001), but the level again plateaued. However, when insulin and glucagon were held constant and catecholamine actions were blocked simultaneously, progressive hypoglycemia, to 2.6 +/- 0.6 mmol/l (P less than 0.001), developed during exercise. Hypoglycemia was the result of an absent increase in glucose production and an exaggerated initial increase in glucose utilization. Thus we conclude that sympathochromaffin activation plays a minor role when insulin and glucagon are operative, but a catecholamine, probably epinephrine, becomes critical to the prevention of hypoglycemia during exercise when changes in insulin and glucagon do not occur.
3-Hydroxybutyric Acid↗
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↗