Uncertainty in Fitted Estimates of Apparent in Vivo Metabolic Constants for Chloroform

It has become common practice to rely on fitted estimates ofapparent in vivo metabolic constants (e.g., V_max and K_M) inparameterization of PBPK models. Yet, quantitative estimatesof precision in these fitted parameters are not routinely reported.Such information is needed to assess the reliability of modelpredictions. The purpose of this study was to assess the precisionin estimates of V_max and K_M for chloroform, accounting for boththe statistical uncertainties in parameter estimates from individualdata sets and any additional uncertainty due to differencesin the parameter estimates derived from various experiments.Joint confidence regions for V_max and K_M from each experiment,generated using maximum likelihood techniques, were used toevaluate these questions. Three previously published data setswere considered. Estimates of V_max and K_M obtained from thesedata sets differed more than could be explained as a consequenceof a limited number of observations, measurement error, or stochasticerror. Issues associated with the use of maximum likelihoodtechniques to estimate joint confidence regions, the estimationof metabolic constants from individual experiments within agas uptake study versus the full data set, the degree of overlapin the joint confidence regions for metabolic constants obtainedfrom separate data sets, and the implications for risk assessmentare discussed.     

Detection of undiagnosed coagulopathies using routine rapid heparin neutralization.

OBJECTIVE: To determine the most frequent clinical causes of a prolonged activated partial thromboplastin time (APTT) result, and to determine whether a new heparin-removal device (the Hepchek, Pall Biomedical, Glen Cove, NY 11542) is capable of efficiently detecting the causes of these values. DESIGN: A combination of chart review and laboratory testing comparing the criterion standard--the heparin chromogenic substrate assay--with the Hepchek. Laboratory investigations were blinded and controlled. SETTING: Inpatient, acute-care hospital. PATIENTS: A total of 1,000 hospital patients with a variety of hemostatic disorders. MAIN OUTCOME MEASURE: The extent to which the Hepchek accurately identified the etiology of a prolonged APTT result. RESULTS: The APTT was prolonged in 25.2% of samples. The presence of heparin in the sample was confirmed by chromogenic assay or by using the Hepchek heparin-removal filter. The presence of heparin was confirmed in 12.8% of all samples and in more than 50% of all abnormal samples. The cause of the abnormal APTT was often unappreciated by the clinician. Bayesian analysis of the Hepchek's ability to diagnose heparin correctly as the cause of the abnormal APTT showed a sensitivity of 100% and specificity of 99.9%. CONCLUSION: Use of the Hepchek in the routine clinical laboratory is an efficient and rapid method of detecting heparin as a cause of isolated prolonged APTT results, and should reduce demands for unwarranted coagulation analyses and inappropriate treatment with blood products.     

Bicycle helmet use by adults: the impact of companionship.

Most of the nearly 1,000 fatal bicycle-related injuries annually could be prevented if riders used safety helmets. Helmet use by adult bicyclists has received relatively little attention because educational campaigns to promote helmet use generally focus on children. Helmet use by adult and child bicyclists at 120 suburban and rural sites in three Maryland counties was observed on two Saturdays in 1990-91 during an evaluation of the impact of a mandatory helmet law. Concordance or discordance of helmet use within various groups of bicyclists--adults only, adults with children, and children only--was recorded. Helmet use among 2,068 adult bicyclists was 49 percent, 51 percent, and 74 percent in the three counties. In two counties combined, 52 percent (365 of 706) of solo adult bicyclists wore helmets compared with only 5 percent (5 of 94) of solo child bicyclists (P < .001). Helmet use or nonuse was concordant among 87 percent of 277 adult-adult pairs, 94 percent of 50 child-child pairs, and 91 percent of 32 adult-child pairs of bicyclists observed. Concordance rates of helmet use or nonuse were similarly high among pairs of adult bicyclists of the same or mixed sexes. These data are consistent with the concept that both adults and children tend to adopt the helmet-wearing behaviors of their companions. Public health efforts focused on adults should encourage helmet use by adult bicyclists both to prevent head injuries and to provide a role model for children.     

A multicentre assessment of the specificity of ten anti-HBc screening tests

SUMMARY. Samples from 1828 donations were screened for anti-HBc at seven sites in the UK using kits supplied by 10 manufacturers. Only 10 (0.55%) donations were considered to have true anti-HBc reactivity and these were detected by all 10 kits. Additional markers of HBV infection were found in nine of these 10 donations. Additional reactives were found by all kits, the number ranging from 1 to 43.
In the four more specific kits, the 10 true reactives were clearly distinguished from the 'false reactives' by the strength of the reaction. It is concluded that the reliance on a single ELISA test for anti-HBc diagnosis is unwise. The use of a second test known to be more specific than the screening ELISA is recommended.     

The HGAR1 familial hypercholesterolemia pedigree

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.     

Allografted keratinocytes used to accelerate the treatment of burn wounds are replaced by recipient cells

Cultured keratinocytes were used as allografts on burn wounds in two patients. In both patients successful covering of the wounds was obtained. DNA fingerprinting of the epidermis covering the wounds 21 days later showed that the cultured keratinocytes were replaced by the patients' cells.