A model of gallbladder motility.

Impaired gallbladder motility leads to some clinical manifestations associated with its muscle contraction and/or the rate of filling with bile. To gain a better understanding of the possible reasons for different filling/emptying patterns we developed a mathematical model of the gallbladder that takes into account the kinetics of its filling and emptying and changes in the concentration of the accumulated bile. The model is based on four parameters responsible for the maximum speed of bile evacuation (Mg), pulsation of contractions (ω), the kinetic filling rate (kg) and the maximum bile mass accumulated in the gallbladder (mtotal). The model results were fitted to different clinical results describing gallbladder motility depending on the meal composition, patient's age and health condition (obesity and gallstones). Compatibility of the model results with the experimental data allows us to draw physiological conclusions. We found that different gallbladder emptying patterns may result from differences in the amplitude of contraction of gallbladder muscles (e.g. for various meal composition), differences in the rate of bile inflow (e.g. for obese patients during filling), and differences in gallbladder muscle pulsations (e.g. for lean patients during early gallbladder emptying). The model of gallbladder motility can facilitate identification of causes of disorders, help to explore complicated physiological pathways, and can be applied in etiology analysis or studies of observable clinical indicators.

Is the water safe for my baby?

Children's behavior and physiology place them at unique risk from waterborne microbial and chemical contaminants. This article reveals children's susceptibility factors and the microbial and chemical contaminants of greatest importance to this age group. It also provides a primer on water treatment and alternatives to tap water. This article concludes with recommendations and resources to aid the practicing pediatrician in addressing patient concerns about drinking water.

Variations in concepts of "susceptibility" in risk assessment.

The Food Quality Protection Act and the 1996 amendments to the Safe Drinking Water Act are two of the most recent examples of legislation calling for protection of susceptible subpopulations. As regulatory deadlines draw nearer, controversies in scientific and policy arenas increase about incorporating susceptibility in risk assessment. The previously accepted working definition of "susceptibility" has already been called into question. Part of the controversy results from different disciplines conceiving of susceptibility in different ways. Understanding the conceptual differences embodied within definitions can provide a basis on which a revised working definition may be developed across disciplines. The purposes of this article are to describe the varying definitions of susceptibility, discuss the differing concepts incorporated in the definitions, and recommend ways in which susceptibility may be defined and framed to meet current risk assessment needs. The present analysis of definitions from the fields of ecology, biology, engineering, medicine, epidemiology, and toxicology revealed different emphases that relate to the underlying perspectives and methods of each field. It is likely that susceptibility will need to be formally defined for public policy purposes, but until that time, the use of more informal communication and decision-making processes is suggested to develop and utilize a new working consensus on the definition of susceptibility.

A definition for chronic sequelae applied to campylobacter and guillian-barre syndrome (Gbs).

PURPOSE: Chronic sequelae (CS) are increasingly important to drinking water risk assessment and management processes, but there has been relatively little scientific rigor in defining CS or reviewing the literature on water-related CS. Our purposes were to develop a scientific definition for CS and to evaluate the definition's practical merit.METHODS: We examined scientific publications for definitions of "chronic sequela." We developed a definition that is based on scientific concepts and that can be systematically applied to literature to assess whether pathogen-related health outcomes qualify as CS. As a case study, we conducted an extensive Medline search and tested our definition on the epidemiological and clinical literature linking Campylobacter and GBS.RESULTS: We defined "chronic sequela" as the secondary adverse health outcome that 1) occurs as a result of a previous infection by a microbial pathogen, and 2) is clearly distinguishable from the health events that initially result from the causative infection, and 3) lasts 3 months or more after recognition. The 12 Campylobacter and GBS studies (five epidemiological and seven clinical) revealed that current data reporting practices limit the evaluation of all three elements in our definition. Laboratory methods and criteria to characterize infection were not always adequately reported. Primary and secondary health events were always reported, but eight of the studies required obtaining additional articles to determine the GBS criteria used. Ten of the 12 articles contained duration data for the GBS symptoms.CONCLUSIONS: Much of the evidence needed to apply our definition was found in the studies reviewed, but changes in reporting practices would facilitate the scientific evaluation of pathogen-CS relationships and estimation of their public health magnitude.

Can varying concepts of susceptibility in risk assessment affect particulate matter standards?

The Clean Air Act mandates that sensitive subpopulations be considered in setting standards to protect the public's health. The purposes of this paper are to point out different conceptualizations of susceptibility, examine how it is approached in risk-related processes, and recommend ways it may be more explicitly framed for risk assessment and management purposes. We studied the traditional risk assessment paradigm, the U.S. Environmental Protection Agency (EPA) guidelines and revised PM standard, discussions from recent interdisciplinary meetings, and peer-reviewed literature. Areas of controversy include what factors intrinsic and extrinsic to the host should be incorporated in susceptibility, what health endpoints are of concern, whether susceptibility is deterministic or stochastic, and whether it should be defined on an individual or population scale. Recent discussions about susceptibility applied to PM indicate that it needs to be more clearly defined and evaluated for scientific and policy purposes. We conclude that varying concepts of susceptibility can affect risk-related processes such as PM standard setting. We recommend that susceptibility be clearly defined in the problem statement of risk assessments and be addressed in a specific subsection of risk characterization, integrating all susceptibility findings from the prior three steps in the risk assessment paradigm.

Occupational risk factors for pancreatic cancer: a case-control study based on death certificates from 24 U.S. states.

BACKGROUND: The relation between occupational exposure and pancreatic cancer is not well established. A population-based case-control study based on death certificates from 24 U.S. states was conducted to determine if occupations/industries or work-related exposures to solvents were associated with pancreatic cancer death. METHODS: The cases were 63,097 persons who died from pancreatic cancer occurring in the period 1984-1993. The controls were 252,386 persons who died from causes other than cancer in the same time period. RESULTS: Industries associated with significantly increased risk of pancreatic cancer included printing and paper manufacturing; chemical, petroleum, and related processing; transport, communication, and public service; wholesale and retail trades; and medical and other health-related services. Occupations associated with significantly increased risk included managerial, administrative, and other professional occupations; technical occupations; and sales, clerical, and other administrative support occupations. Potential exposures to formaldehyde and other solvents were assessed by using a job exposure matrix developed for this study. Occupational exposure to formaldehyde was associated with a moderately increased risk of pancreatic cancer, with ORs of 1.2, 1.2, 1.4 for subjects with low, medium, and high probabilities of exposure and 1.2, 1.2, and 1.1 for subjects with low, medium, and high intensity of exposure, respectively. CONCLUSIONS: The findings of this study did not suggest that industrial or occupational exposure is a major contributor to the etiology of pancreatic cancer. Further study may be needed to confirm the positive association between formaldehyde exposure and pancreatic cancer. Published 1999 Wiley-Liss, Inc.

Simple visual reaction time in organolead manufacturing workers: influence of the interstimulus interval.

The authors conducted this investigation to study the effects of interstimulus interval duration for a given simple visual reaction time trial on the relationship between lead exposure and reaction time. Organolead manufacturing workers (n=222) and nonexposed referents (n=62) were administered a neurobehavioral test battery that included simple visual reaction time. Simple visual reaction time was measured over 44 trials; interstimulus intervals ranged from 1 to 10 s in a randomly generated sequence that was identical for all study subjects. Mean reaction times for both lead-exposed and nonexposed subjects were longest for interstimulus intervals of 1 and 2 s. Mean reaction times in response to moderate (4-6 s) and long (7-10 s) interstimulus intervals were mainly associated with lead exposure; this association led the authors to suggest that interstimulus interval duration modifies the relationship between lead exposure and simple visual reaction time performance. In simple visual reaction time protocols, stronger associations between reaction time and lead exposure may be found if the analysis trials are separated with interstimulus intervals of less than 3 s duration.

Simple visual reaction time in organolead manufacturing workers: comparison of different methods of modeling lead exposure and reaction time.

In March 1990, 222 organolead manufacturing workers and 62 nonexposed referents were administered a neurobehavioral test battery that included simple visual reaction time (SVRT). SVRT was measured over 44 trials with interstimulus intervals ranging from 1 to 10 sec in a random but fixed order for all study subjects. Different measures of lead exposure and dose (e.g., recent and cumulative exposure based on personal sampling data, exposed/nonexposed status, recent blood lead and zinc protoporphyrin levels, and peak and cumulative urine lead levels) were examined as predictors of several different parameters of SVRT (e.g., mean, median, truncated mean, and standard deviation of SVRT over 44 trials). The association varied, depending on the measures used for SVRT and lead exposure and dose. In linear regression analyses, the strongest and most consistent associations of lead exposure and dose were observed with the standard deviation of SVRT. In assessing the different exposure measures, strong and consistent associations were observed with blood lead levels at the time of SVRT testing, but not with recent or cumulative exposure measures. That is, stronger associations were observed with measures of relatively recent internal dose (i.e., blood lead level) than with cumulative measures (i.e., cumulative exposure). Future studies using SVRT should consider parameters of SVRT that have not been commonly used to date, such as the standard deviation of the SVRT.

Global climate change and emerging infectious diseases.

Climatic factors influence the emergence and reemergence of infectious diseases, in addition to multiple human, biological, and ecological determinants. Climatologists have identified upward trends in global temperatures and now estimate an unprecedented rise of 2.0 degrees C by the year 2100. Of major concern is that these changes can affect the introduction and dissemination of many serious infectious diseases. The incidence of mosquito-borne diseases, including malaria, dengue, and viral encephalitides, are among those diseases most sensitive to climate. Climate change would directly affect disease transmission by shifting the vector's geographic range and increasing reproductive and biting rates and by shortening the pathogen incubation period. Climate-related increases in sea surface temperature and sea level can lead to higher incidence of water-borne infectious and toxin-related illnesses, such as cholera and shellfish poisoning. Human migration and damage to health infrastructures from the projected increase in climate variability could indirectly contribute to disease transmission. Human susceptibility to infections might be further compounded by malnutrition due to climate stress on agriculture and potential alterations in the human immune system caused by increased flux of ultraviolet radiation. Analyzing the role of climate in the emergence of human infectious diseases will require interdisciplinary cooperation among physicians, climatologists, biologists, and social scientists. Increased disease surveillance, integrated modeling, and use of geographically based data systems will afford more anticipatory measures by the medical community. Understanding the linkages between climatological and ecological change as determinants of disease emergence and redistribution will ultimately help optimize preventive strategies.