Clustering of post-diarrheal (Shiga toxin-mediated) hemolytic uremic syndrome in families.

AIMS: 1. To study the epidemiological and clinical features of Shiga toxin (Stx)-mediated (post-diarrheal) hemolytic uremic syndrome (HUS) occurring in more than 1 family member. 2. To compare familial with non-familial episodes, and concurrent familial with non-concurrent familial cases. 3. To determine the likelihood of Stx HUS occurring in a second family member. METHODS: A retrospective review from January 1970 through September 2001 of families in whom Stx HUS occurred in more than 1 family member was conducted using a computerized HUS registry. It contains information on 373 episodes that occurred in 356 families from Utah and neighboring states. Cases were categorized as being either concurrent (i.e., occurring within a month of one another) or non-concurrent, and the study was limited to those with typical (post-diarrheal) episodes. RESULTS: HUS occurred in 2 or more family members in 17 (4.8%) of the families in our registry. In 12 (3.4%) of these families episodes occurred with days to weeks of each other; in 5 families (1.4%) episodes were separated by intervals of several years. There were no statistically significant differences in demographic, seasonal, laboratory, clinical, or outcome variables between familial subsets (concurrent versus non-concurrent) or between familial and non-familial cases. CONCLUSIONS: When a child is diagnosed with D+ HUS, there is an increased risk that a second family member will also develop HUS; most often within days to weeks (i.e., within a month), but in some cases episodes may be separated by intervals of years. Non-concurrent cases suggest common environmental risk factors, or perhaps a genetic predisposition. Concurrent cases suggest a common source of infection or person-to-person transmission; a genetic predisposition cannot be excluded. These observations suggest that siblings of an index case who develop diarrhea should be kept under close surveillance.

Response to Shiga toxin-1, with and without lipopolysaccharide, in a primate model of hemolytic uremic syndrome.

Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate in the pathogenesis of post-diarrheal hemolytic uremic syndrome (HUS), yet little is known about the factors that modulate the host response to these toxins. We have previously shown that the baboon develops HUS if 100 ng/kg of purified Stx-1 is administered rapidly as a single bolus, but not if it is given as four 25-ng/kg doses every 12 h. We therefore used this baboon model to study the response to small intravenous doses of Stx-1, with and without the co-administration of LPS. The co-administration of two 1-mg/kg doses of LPS (given at 0 and 24 h) and four 25-ng/kg doses of Stx-1 (given at 0, 12, 24, and 36 h) resulted in HUS, but the administration of either toxin separately did not. The development of HUS was associated with a rise in urinary, but not plasma concentrations of TNF, and a rise in both urinary and plasma concentrations of IL-6 and IL-8. We speculate that LPS is not required for disease expression in the human, but that it can augment the response to otherwise subtoxic amounts of Stx and this augmentation may be mediated by LPS-induced cytokine release.

Seeds aren't anchors.

Exposure to a few task-relevant numerical facts (seed facts) often improves subsequent numerical estimates. We performed two experiments to investigate the mechanism that produces these seeding effects. In Experiment 1, participants estimated national populations; in Experiment 2, they estimated between-city distances. In both, items were selected so that the actual value of the seed facts (SA) was, on average, below participants' initial estimates for those items (S1) and above the initial estimates for the transfer items (T1). Given this configuration, the anchoring position predicts that the postseeding transfer estimates should be greater than the preseeding transfer estimates (T2 > T1), whereas the feedback/induction position predicts the opposite (T2 < T1). In both experiments, the latter pattern of results emerged, supporting the conclusion that seeds aren't anchors.

Buy low, sell high: the development of an informal theory of economics.

Two experiments were conducted to examine the development of economic understanding among 5-, 7-, and 9-year-olds (n = 31, 29, and 32, respectively). Most 5-year-olds exhibited understanding of the goal of acquiring desired goods but not of the goals of seeking profits, acquiring goods inexpensively, or competing successfully with other sellers. In contrast, most 7-year-olds and a large majority of 9-year-olds showed understanding of all of these concepts. The older children's understanding of these key concepts and the relations among them suggested that they had constructed an informal theory of economics, qualitatively different from the psychologically based understanding of the 5-year-olds. Increased information-processing skills appeared to be among the sources of this new understanding.

The rebirth of children's learning.

Learning is a central part of children's lives, but the study of learning is a rather peripheral part of the field of cognitive development. Fortunately, this situation is starting to change; recent theoretical and methodological advances have sparked renewed interest in children's learning. This renewed interest has already yielded a set of consistent and interesting findings regarding how children learn, as well as intriguing proposals regarding the mechanisms that underlie the learning. Increasing our focus on children's learning promises to yield practical benefits as well as a more exciting field of cognitive development.

Across the great divide: bridging the gap between understanding of toddlers' and older children's thinking.

Research on very young children's cognitive development differs greatly from research on cognitive development in older children. The differences include the questions that are asked, the methods that are used to address them, the measures that are employed to provide relevant evidence, and the level of detail at which children's knowledge is represented. The research approaches are so different that they create an impression that infants' and toddlers' thinking differs qualitatively from that of preschoolers and older children. This impression, however, may reflect differences in research approaches rather than differences in children's thinking. In the present study, we attempted to bridge this gap by applying to toddlers a type of process analysis that has proved fruitful in studies of older children. Overlapping waves theory, trial-by-trial strategy assessments, and microgenetic methods were used to analyze 1.5- and 2.5-year-olds' problem solving and learning. The results demonstrated that changes in toddlers' strategies could be assessed reliably on a trial-by-trial basis, that the changes followed the basic form predicted by the overlapping waves model, and that analyses of toddlers' strategies could tell us a great deal about both qualitative and quantitative aspects of their learning. A componential analysis of learning that previously had been applied to older children also proved useful for understanding toddlers' learning. The analysis specified that cognitive change frequently involves five components: acquisition of new strategies; strengthening of the strategies in their original context; improved mapping of strategies onto novel problems; increasingly refined choices among variants of the strategies; and increasingly skillful execution of the strategies. Independent measures of these components indicated that strategic development in toddlers involves improvements in all five components. Analyses of individual differences in learning showed that the effects of distal variables, such as age and sex, could be partially explained in terms of their influence on mastery of the components, but that the distal variables exercised additional direct effects as well. The process of learning in toddlers closely resembled that of older children in other ways as well. Like older children, toddlers use multiple strategies over the course of learning; their choices among strategies are quite adaptive from early on; their choices become progressively more adaptive as they gain experience with the task; they switch strategies not only from trial to trial but within a single trial; their transfer of learning from one problem to the next is primarily influenced by structural relations between problems but also is influenced by superficial features; they show utilization deficiencies early in learning that they gradually overcome; and they show individual differences in learning that fall into a few qualitatively distinct categories. Perhaps most striking, the 1.5- and 2.5-year-olds emerged as active learners, who continued to work out the lessons of previous instruction in the absence of further instruction. That is, they integrated the lessons of their own problem-solving efforts with the previous instruction in ways that magnified the initial effects of the instruction. Overall, the findings indicated that the gap can be bridged; that theories, methods, measures, and representations of knowledge typically used with older children can improve our understanding of toddlers' problem solving and learning as well.

Fatal poisoning from liquid dimethylmercury: a neuropathologic study.

Since ancient times, mercury has been recognized as a toxic substance. Dimethylmercury, a volatile liquid organic mercury compound, is used by a small number of chemistry laboratories as a reference material in nuclear magnetic resonance spectroscopy. To our knowledge, dimethylmercury has been reported in only three cases of human poisoning, each proving fatal. Very small amounts of this highly toxic chemical can result in devastating neurological damage and death. We report the neuropathologic findings in a fatal case of dimethylmercury intoxication occurring in a laboratory researcher that resulted from a small accidental spill. We compare these findings to those reported in one previously reported fatal case of dimethylmercury poisoning, and to earlier reports of monomethylmercury poisoning, and discuss the clinicopathologic correlation.

Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1.

The baboon response to intravenous infusion of Shiga toxin 1 (Stx-1) varied from acute renal failure, proteinuria, hyperkalemia, and melena with minimal perturbation of host inflammatory and hemostatic systems (high-dose group, 2.0 microg/kg; n = 5) to renal failure with hematuria, proteinuria, thrombocytopenia, schistocytosis, anemia, and melena (low-dose group, 0.05 to 0.2 microg/kg; n = 8). Both groups exhibited renal shutdown and died in 57 hours or less. Both groups produced urine that was positive for tumor necrosis factor and interleukin-6 although neither of these cytokines was detectable (

Explanation and generalization in young children's strategy learning.

Children often learn new problem-solving strategies by observing examples of other people's problem-solving. When children learn a new strategy through observation and also explain the new strategy to themselves, they generalize the strategy more widely than children who learn a new strategy but do not explain. We tested three hypothesized mechanisms through which explanations might facilitate strategy generalization: more accurate recall of the new strategy's procedures; increased selection of the new strategy over competing strategies; or more effective management of the new strategy's goal structure. Findings supported the third mechanism: Explanations facilitated generalization through the creation of novel goal structures that enabled children to persist in use of the new strategy despite potential interference from competing strategies. The facilitative effect of explanation did vary with children's age and did not vary between explanations children created by themselves versus explanations they learned from the experimenter.

Learning to spell: variability, choice, and change in children's strategy use.

We examined whether the overlapping waves model, originally developed to account for strategy choices in arithmetic, could also account for strategy choices in spelling. The contrast was of particular interest because arithmetic is an algorithmic domain (a domain that includes strategies that always yield correct answers if executed properly), whereas spelling is not. Thirty first-grade students spelled words under 2 conditions, and 23 of these students were retested in second grade. Trial-by-trial analysis of strategy use was used to identify which strategies first and second graders used, how adaptively they chose among them, how effective the strategies were, and what changes occurred from first to second grade along each dimension. The model proved useful for understanding the development of spelling, despite the fact that explicit use of backup strategies had a minimal impact on accuracy. Implications for understanding adaptive strategy choices in algorithmic and nonalgorithmic domains are discussed.

Conscious and unconscious strategy discoveries: a microgenetic analysis.

We examined second graders' strategy discoveries on a task that could be solved either by arithmetic computation or by a simple insight. Strategy use was assessed on each trial through both an implicit measure and an explicit one. The results provided unambiguous evidence that strategies can be discovered without conscious awareness. Almost 90% of children showed the insight at an implicit, unreportable level before they showed it at an explicit, reportable one. When children received the relevant problems on each trial, 80% reported the insight within 5 trials of when their solution times indicated that they first generated it. Implications for understanding the relation between unconscious and conscious discoveries and for the role of competing activations in strategy discovery are discussed.

Fatal heatstroke in a young woman with previously undiagnosed Hashimoto's thyroiditis.

Heatstroke represents the most severe form of the heat-related illnesses. Potentially fatal, heatstroke most often affects the elderly, obese, or chronically ill. Thyroid disease, which may interfere with the normal regulation of body temperature, has not previously been reported in cases of heatstroke. A fatal case is reported in a young woman discovered unconscious in a sauna who was found to have preexisting Hashimoto's thyroiditis on subsequent autopsy. The diagnosis of hypothyroidism in heatstroke rests on clinical information and morphologic observations. This case underscores the importance of evaluating the thyroid in unusual cases of heatstroke.

Developmental differences in rule learning: a microgenetic analysis.

Trial-by-trial strategy assessments and a microgenetic design were used to examine 4- and 5-year-olds' learning of rules for solving balance scale problems. The design allowed us to examine simultaneously the contribution to rule learning of distal variables (qualities and knowledge with which children enter the learning situation) and proximal variables (processes that they execute during learning). Developmental differences in learning arose through two distal variables that were correlated with age--initial rule use and initial encoding-helping older children to execute several proximal processes--noticing the potential explanatory role of a key variable, formulating a more advanced rule, and generalizing and maintaining the rule. Joint consideration of distal and proximal influences seems likely to be generally useful for understanding learning and development.

Fatal hypernatremic dehydration in exclusively breast-fed newborn infants due to maternal lactation failure.

Infants who die of hypernatremic dehydration usually demonstrate at autopsy an underlying condition or disease process that predisposes to increased water loss. In the absence of such findings, forensic concerns may focus sharply on parental or caretaker neglect as an underlying cause of death. In this case report, we describe unrecognized fatal hypernatremic dehydration in two exclusively breast-fed neonates due solely to failure of maternal lactation. We further describe epidemiologic and etiologic features of such deaths and discuss forensic difficulties encountered in their certification.

"Hey, would you like a nice cold cup of lemonade on this hot day?": children's understanding of economic causation.

Three experiments were performed to examine development of understanding of functional relations in economics by children between ages 4 and 10 years. Results of Experiment 1 indicated that preschoolers understood the effects of demand, and 2nd graders also understood the effects of supply, but even 4th graders often failed to demonstrate understanding of the effects of motivation and morality. In Experiment 2, 4th but not 2nd graders proved able to explain how motivation and morality might influence sales when told that these variables had an effect. In Experiment 3, 2nd and 4th graders' evaluations of the plausibility of other children's explanations of effects of motivation and morality showed evidence of understanding, though those of kindergartners did not. The data supported the 3 hypotheses that motivated the experiments: (a) direct links between causes and effects are understood before indirect ones, (b) positive correlations between causes and effects are understood before negative ones, and (c) variables that produce effects are understood before ones that do not.

Rethinking infant knowledge: toward an adaptive process account of successes and failures in object permanence tasks.

Infants seem sensitive to hidden objects in habituation tasks at 3.5 months but fail to retrieve hidden objects until 8 months. The authors first consider principle-based accounts of these successes and failures, in which early successes imply knowledge of principles and failures are attributed to ancillary deficits. One account is that infants younger than 8 months have the object permanence principle but lack means-ends abilities. To test this, 7-month-olds were trained on means-ends behaviors and were tested on retrieval of visible and occluded toys. Means-ends demands were the same, yet infants made more toy-guided retrievals in the visible case. The authors offer an adaptive process account in which knowledge is graded and embedded in specific behavioral processes. Simulation models that learn gradually to represent occluded objects show how this approach can account for success and failure in object permanence tasks without assuming principles and ancillary deficits.

Older and younger adults' strategy choices in multiplication: testing predictions of ASCM using the choice/no-choice method.

The choice/no-choice method provides a means of obtaining unbiased estimates of the performance characteristics of strategies. The three experiments in the study illustrate the method's usefulness for testing predictions of alternative models of strategy choice. The experiments focused on 20- and 70-year-olds' choices among mental calculation, use of a calculator, and use of pencil and paper as strategies for solving multidigit multiplication problems. As predicted by the Adaptive Strategy Choice Model (ASCM), (a) differences in the speed and accuracy yielded by the strategies were the strongest predictors of the frequency with which each strategy was chosen on a given problem; (b) features of problems exerted an additional independent influence; and (c) having a choice resulted in better performance than not having one. These results held true for both older and younger adults. Potential extensions of the choice/no-choice method and of ASCM are discussed.

Hemolytic-uremic syndrome in adolescents.

OBJECTIVE: To compare the epidemiological characteristics, clinical features, and outcome of adolescents with hemolytic-uremic syndrome (HUS) with those of children with HUS. DESIGN: A retrospective descriptive study using data stored in the computerized Utah HUS registry. SETTING: The HUS registry contains data on postdiarrheal and nondiarrheal HUS cases since 1970 in which the patients were younger than 18 years of age at the time of diagnosis and includes virtually all Utah cases as well as those referred from surrounding states. PATIENTS: Seventeen adolescents (age, 12-17 years) and 276 younger patients from September 30, 1970, through December 5, 1993, who met the diagnostic criteria for HUS. MAIN OUTCOME MEASURES: Age, sex, seasonality, prodromal features (eg, antecedent diarrhea), laboratory values, hospital course, outcome, and chronic sequelae. RESULTS: The 17 adolescent patients, who composed 5.8% of the study population, experienced a course of the disease that was similar to that of the younger patients. Diarrhea preceded HUS in approximately 90% of the patients in both groups. Laboratory values were similar in teenagers and younger patients. The hospital courses were also similar; seizures occurred in almost 20%, and hypertension and oligoanuric renal failure occurred in most. Two (12%) of the teenagers and 7 (2.4%) of the younger patients died during the acute phase of the syndrome (P = .09); almost 50% of both groups experienced 1 or more chronic renal sequelae. End-stage renal disease has occurred in 1 (5.8%) of the teenagers and 6 (2.2%) of the children. At follow-up, 1 or more years (median, 5 years) after the onset of HUS, hypertension was present in 22% of the teenagers and 6.7% of the preteens (P = .14). A below-normal glomerular filtration rate was seen in approximately 30% of both groups; proteinuria was noted in approximately 25% of both groups. Approximately 10% of both groups had a combination of proteinuria and a low glomerular filtration rate and are, therefore, at risk for eventual end-stage renal disease. CONCLUSIONS: In our region of the Intermountain West, HUS in adolescents closely resembles that seen in children and the outcome is more favorable than that experienced by adults.