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.     

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.     

Outcome of surgery in patients with hematological malignancies: A 12-year retrospective analysis

Background: Surgical intervention in patients with malignant hematological disorders is a major undertaking due to the expected risks of bleeding, infection and poor wound healing. Methods and materials: A retrospective study of patients treated at the Riyadh Armed Forces Hospital, Saudi Arabia between January 1991 and December 2002 was conducted. The results of patients with acute leukemia and lymphoma who underwent surgical procedures (study group) were compared with those of a control group composed of patients with the same spectrum of disorders treated over the same period of time and given the same treatment protocols but never required any surgery. Results: No single death occurred intraoperatively or in the immediate postoperative period due to surgical therapy per se. However, follow up of both groups of patients revealed a shorter long‐term survival and higher rates of relapse and severe invasive infections in the surgical group compared to the control group of patients. The mean survival for the study group was 1871 ± 307 days versus 3094 ± 279 days for the control group of patients (P = 0.0027). Thirty (75%) study patients suffered relapses of their malignant hematological disorders versus 23 (37.1%) control patients. Forty‐five relapses were encountered in the study group of patients (1.5 relapses per relapsed patient) versus 26 relapses in the control group (1.13 relapses per relapsed patient). Various infections occurred in 37 (92.5%) study patients and 32 (51.6%) control patients. Recurrent infections developed in 30 (75%) study patients and 22 (35.5%) control patients (P = 0.00008). Infections causing tissue invasion were encountered in 29 (72.5%) study patients and 22 (35.5%) control patients. Conclusion: Even major surgical procedures can be performed in patients with leukemia or lymphoma provided enough preparatory measures are made to minimize bleeding and infectious complications. Surgery may, however, be associated with long‐term complications such as a high incidence of relapse of the primary malignant hematological disorder and an increased rate of severe and invasive infections.