Anti-beta-endorphin immunoglobulin G in humans.

Human IgG specific for beta-endorphin was identified by enzyme-linked immunoabsorbent assay and isolated by affinity chromatography. From a sample of 27 subjects, three individuals with major depression demonstrated plasma IgG highly reactive with human beta-endorphin, while four other subjects (two with depression and two randomly selected blood donors) had intermediate reactivity. The recognition site for beta-endorphin was retained by F(ab')2 fragments.     

CT-guided biopsy: prospective analysis of 1,000 procedures

The authors prospectively analyzed 1,000 biopsies guided with computed tomography (CT) and performed in 955 patients over a 30-month period. All patients were followed up from 3 months to 2 years. The biopsies were performed in an average of 22 minutes (range, 3-85 minutes) by 26 different radiologists; five radiologists performed 547 of the procedures. Of the 1,000 biopsies, 722 were performed in areas in the liver, retroperitoneum, pancreas, pelvis, and adrenal glands. Of 69 errors in diagnosis, 67 were falsely negative and two were falsely positive; 747 true-positive and 184 true-negative diagnoses were made. CT-directed biopsy for accurate diagnosis was 91.8% sensitive and 98.9% specific, with a positive predictive value of 99.7% and a negative predictive value of 73.3%. Of 11 patients with complications, seven had hematomas, three had pneumothorax, and one had hematuria. No deaths occurred, and only one patient required surgery.     

Antenatal treatment of fetal alloimmune cytopenias

Summary The antenatal use of intravenous immunoglobulin (IVG) was explored in 9 cases of alloimmune cytopenias affecting fetuses. In 7 cases of alloimmune thrombocytopenia, IVG at a dose of 1 gm/kg/week appeared to be uniformly effective in elevating the fetal platelet count and preventing a recurrence of antenatal intracranial hemorrhage (2 cases). In 2 cases of Rh disease the results were more equivocal. There did not appear to be any significant toxicity associated with its use. The mechanism of IVG effect in the successfully treated cases remains uncertain.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

Evaluating ELISPOT summary measures with criteria for obtaining reliable estimates

The ELISPOT assay is a commonly used technique for quantifying the occurrence of T lymphocyte cells secreting a cytokine after stimulation with an antigen or peptide. The assay endpoint, the number of spot-forming cells (SFC) at a specific concentration of effector cells, is typically estimated using either a simple arithmetic mean or the predicted value from a linear regression model. We compare statistical modeling approaches for summarizing these assays using data from the Pediatric AIDS Clinical Trial Group (PACTG) study 299. A simulation study was conducted to compare methods under controlled conditions. Assuming the optimal effector cell concentration is known, we demonstrate that the simple mean is appropriate if assays are conducted at the same concentration for all samples. Normalizing simple means to a summary concentration using results from a range of concentrations is not valid. A random effects or mixed model is superior to the simple mean when a large within-assay (subject) variance relative to between-subject variance exists. When assays are conducted over a range of effector cell concentrations for each individual, the theoretical linearity assumption of the regression model is often violated and can result in biased estimates. In this case, nonlinear models provide more accurate estimation. Collecting data over a range of concentrations allows reassessment of the optimal cell concentration after the data are generated.     

The role of radiotracer imaging in Parkinson disease

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I]beta-CIT SPECT, and [18F]fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.     

The health consciousness myth: implications of the near independence of major health behaviors in the North American population

Analysis of over 250,000 respondents from four of the largest epidemiological surveys in North America indicates that major health behaviors are largely unrelated to one another. On average, the percentage of shared variance among smoking, exercise, diet and alcohol consumption is approximately 1%. While many of these relationships are statistically significant, suggesting that the associations are nonzero in the population, they represent minute effect sizes. The weak associations among these behaviors are unlikely to be due to incorrect functional form of the relationship, measurement error, or biases in responding. The findings have implications for health behavior theories and interventions predicated on the notion that the health conscious individual attempts to improve his or her health by engaging in more than one of these behaviors at a time.