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.     

Nutrition, Exercise, and Healthy Aging

Advancing age is associated with a remarkable number of changes in body composition, including reduction in lean body mass and increase in body fat, which have been well documented. Decreased lean body mass occurs primarily as a result of losses in skeletal muscle mass. This age-related loss in muscle mass has been termed “sarcopenia”. Loss in muscle mass accounts for the age-associated decreases in basal metabolic rate, muscle strength, and activity levels, which, in turn are the cause of the decreased energy requirements of the elderly. In sedentary persons, the main determinant of energy expenditure is fat-free mass, which declines by about 15% between the third and eighth decade of life. It also appears that declining energy needs are not matched by an appropriate decline in energy intake, with the ultimate result being increased body fat content. Increased body fatness and increased abdominal obesity are thought to be directly linked to the greatly increased incidence of non-insulin-dependent diabetes mellitus among the elderly. In this review we will discuss the extent to which regularly performed exercise can affect nutrition needs and functional capacity in the elderly. We will also discuss a variety of concerns when prescribing exercise in the elderly, such as planning for a wide variability in functional status, medical status, and training intensity and duration. Finally, we will attempt to provide some basic guidelines for beginning an exercise program for older men and women and establishing community-based programs.     

Evaluation of an Australian intervention to encourage breast feeding in primiparous women

Breast feeding has nutritional, immunologic and antiallergicadvantages for the infant. Although it has been widely recommendedthat infants be exclusively breast fed until 4–6 monthsof age, only about half of all Australian babies currently receiveextended breast feeding. The present study evaluated an intensiveprogramme designed to increase the proportion ofprimi-parousmothers who breast fed for 4 months or longer. Women who registeredwith the hospital at least 20 weeks before delivery and whointended to breastfeed were eligible for the study. Two hundredand thirty-five women were allocated to receive either usualcare or an intensive breast feeding programme when they registeredwith the hospital. The intensive programme consisted of writtenmaterials, and group and individual sessions with a lactationcounsellor. It also included a visit from a breastfeeding consultantwhile in hospital after the birth and contact on return home.Women were followed up 6 weeks and 4 months after delivery.There were no significant differences in breastfeeding ratesbetween the control and intervention groups at either follow-uppoint. Breast feeding until 4 months was more likely among womenwhose baby did not receive a bottle feed while still in hospitaland who did not smoke, use the combined oral contraceptive pillor introduce solid food before 4 months. Those mothers who enjoyedand felt satisfied with breastfeeding were more likely to continueto 4 months. It seems likely that programmes designed to increasebreastfeeding will need to address underlying factors such ashospital policy rather than simply providing more health education.     

Global Analysis of Antibody Repertoires. 1. An Immunoblot Method for the Quantitative Screening of a Large Number of Reactivities

This paper describes a procedure for analysing multiple antibody reactivities that explores a commercially available immunoblot system, and is based on a double staining of nitrocellulose membranes, revealing both antibody reactivities and the migration position of the blotted proteins in the membrane. Quantification of both stainings by densitometry allowed the accurate superposition of the immunoreactivity and total protein profiles of each Line. Moreover, the protein stainings ofthe different lanes could be adjusted with a simple-scale transformation algorithm, correcting for possible distortions during electrophoretic migration, and allowing for the precise comparison ofthe immunoreactivity profiles in different lanes. The procedure is discriminatory enough to identify unique reactivity patterns in random pools of 10⁴ activated B cells, and to define strain-specific natural antibody repertoires. The utilily of this immunoblot method as an assay for simultaneously scoring multiple reactivities to hundreds of antigens in complex mixtures of antibodies, and thus defining antibody repertoires in a global manner, is discussed.     

Erythema multiforme occurring in association with lupus erythematosus during therapy with doxycycline

A 62-year-old male with lupus erythematosus is described who presented with bullous erythema multiforme that had appeared during treatment with systemic doxycycline and topical tetracycline hydrochloride.     

Disproportional impact of the revised AIDS surveillance definition on the AIDS incidence among drug users compared to homosexual men

The impact of changes in 1993 of the old 1987 WHO/CDC AIDS casedefinition was studied in a cohort of 153 HIV-infected injectiondrug users (IDUs) and 502 HIV-infected homosexual men in Amsterdam.It appeared that the extension in Europe of the old AIDS definitionto also include recurrent pneumonia, pulmonary tuberculosisand invasive cervical neoplasia, strongly increases the numberof persons diagnosed with AIDS among IDUs, but will hardly influencethe AIDS incidence among homosexual men. As recurrent pneumoniaand pulmonary tuberculosis are present among drug users withhigh CD4 cell counts, the incidence of these diseases may partlybe determined by environmental factors. The extension of theold 1987 AIDS definition in the USA with CD4 count <200 cells/mm³In addition to the 3 above-mentioned diseases, will also havea larger impact on drug users than on homosexual men.