Howard I. Kushner

Kawasaki Disease: A Brief History

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study. Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan before that time is currently under study. The most significant controversy in the 1960s in Japan was whether the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Childrens Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and infantile periarteritis nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier. What remains unknown is the reason for the simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases, such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century, but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factors responsible for KD were introduced into Japan after the World War II and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are ∼5000 to 6000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100 000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasakis original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years of age in the United States. The natural history of KD reveals that coronary artery aneurysms occur as a sequela of the vasculitis in 20% to 25% of untreated children. Echocardiography can be successfully used to detect coronary artery dilatation and aneurysms in virtually all patients. Patients with no acute phase coronary artery changes detected by echocardiogram are clinically asymptomatic at least 10 years later. The Japanese Ministry of Health has established a registry of 6500 children who will be followed longitundinally to determine the natural history of the illness. No similar registry of patients exists in the United States. Studies of KD pathogenesis show a progression of arterial lesions accompanying KD vasculitis and a number of immunoregulatory changes, including a deficiency of circulating CD8+ suppressor/cytotoxic T cells; an abundance of circulating B cells spontaneously producing immunoglobulins; and circulating, activated monocytes. Biochemical and immunologic evidence suggests endothelial cell activation and injury. Although the cause of KD remains unknown, clinical trials have established effective therapies, despite the absence of a proven cause. Intravenous immunoglobulin (IVIG) plus aspirin lowers the rate of coronary artery aneurysms from 20% to between 3% and 5%. In 1988, the Committee on Infectious Diseases of the American Academy of Pediatrics endorsed IVIG treatment as recommended therapy for KD. Questions remain regarding treatment of patients who fail to respond to an initial dose of IVIG. The role of steroids or other antiinflammatory agents in the treatment of KD is controversial. Areas for further research include: 1) a more sensitive case definition that includes laboratory and echocardiographic data, as well as clinical signs and symptoms; 2) development of a diagnostic test based on the biology of inflammation and acute endothelial cell damage that, in the absence of the causative agent, could be used to identify children with KD; 3) studies of index cases and their families to identify relevant genetic factors; and 4) long-term follow-up of patients into their third and fourth decades with monitoring for late cardiovascular sequelae.

The Limits of Social Capital: Durkheim, Suicide, and Social Cohesion

Recent applications of social capital theories to population health often draw on classic sociological theories for validation of the protective features of social cohesion and social integration. Durkheims work on suicide has been cited as evidence that modern life disrupts social cohesion and results in a greater risk of morbidity and mortality-including self-destructive behaviors and suicide. We argue that a close reading of Durkheims evidence supports the opposite conclusion and that the incidence of self-destructive behaviors such as suicide is often greatest among those with high levels of social integration. A reexamination of Durkheims data on female suicide and suicide in the military suggests that we should be skeptical about recent studies connecting improved population health to social capital.

Sports Participation and Problem Alcohol Use A Multi-Wave National Sample of Adolescents

BACKGROUND Sports participation, though offering numerous developmental benefits for youths, has been associated with adolescent alcohol use. Differences also exist between men/boys and women/girls in both sports participation and patterns of alcohol-related behaviors, but there are few longitudinal investigations of this relationship. PURPOSE This study investigated the relationship between school-based sports participation and alcohol-related behaviors using data from a multiwave national study of adolescent men/boys and women/girls. METHODS Nationally representative data from the National Longitudinal Study of Adolescent Health, collected between 1994 and 2001, were analyzed in 2009 (n=8271). Latent growth modeling, accommodating the complex sampling design, was applied to examine whether participation in school-based sports was associated with initial levels and change in problem alcohol use over three waves of data collection. RESULTS After taking into account time-invariant covariates including demographics and other predictors of alcohol use, greater involvement in sports during adolescence was associated with faster average acceleration in problem alcohol use over time among youths who took part in only sports. The findings suggest, however, that the relationship between sports participation and problem alcohol use depends on participation in sports in combination with other activities, but it does not differ between men/boys and women/girls. CONCLUSIONS Sports may represent an important and efficient context for selective interventions to prevent problem alcohol use and negative consequences of alcohol use among adolescents.

Suicide, social integration, and masculinity in the U.S. military

Reports indicate that suicide in the U.S. military has increased significantly in recent years. This increase has been attributed to a number of factors, including more frequent deployments, more relaxed screening of recruits, combat trauma, economic difficulty amongst soldiers, and the breakdown of interpersonal relationships. In this article, we add an element that we believe is crucial to an understanding of military suicide: the socio-cultural environment of the military itself. In particular, we examine the role that the masculine ideologies governing military life play in the internalization of individual frustrations and in suicidal behavior. Suicide investigators often have ignored the role of masculine ideologies in military suicide because of the assumption that suicide results from social disintegration. In contrast, we argue that military suicide is driven largely by excessive social integration. From this perspective, current explanations of military suicide are constrained by gender and etiological assumptions. Finally, this paper suggests the implications of these findings for designing more effective prevention programs for military suicide.

Autism, lateralisation, and handedness: A review of the literature and meta-analysis

A number of recent investigators have hypothesised a link between autism, left-handedness, and brain laterality. Their findings have varied widely, in part because these studies have relied on different methodologies and definitions. We conducted a systematic review and meta-analysis to assess the literature, with the hypothesis that there would be an association between autism and laterality that would be moderated by handedness, sex, age, brain region studied, and level of autism. From a broad search resulting in 259 papers, 54 were identified for inclusion in the literature review. This list was narrowed further to include only studies reporting results in the inferior frontal gyrus for meta-analysis, resulting in four papers. The meta-analysis found a moderate but non-significant effect size of group on lateralisation, suggesting a decrease in strength of lateralisation in the autistic group, a trend supported by the literature review. A subgroup analysis of sex and a meta-regression of handedness showed that these moderating variables did not have a significant effect on this relationship. Although the results are not conclusive, there appears to be a trend towards a relationship between autism and lateralisation. However, more rigorous studies with better controls and clearer reporting of definitions and results are needed.

Rethinking the Boundaries of Kawasaki Disease: Toward a Revised Case Definition

Abstract: This paper describes the historical evolution of the Kawasaki disease (KD) case definition and its limitations for identification and treatment of children at risk for coronary artery aneurysms (CAA). The dominant view of pathogenesis is that an unknown agent infects infants and children, who then develop the signs of KD. Some of the infected infants and children then develop CAA, and a few die from myocardial infarction. Because the etiologic agent remains unknown, diagnosis of KD relies on observation and recognition of the clinical signs that comprise the KD case definition criteria. This approach has been successful in identifying and treating many children at risk for CAA. Unfortunately, however, it has delayed the effective treatment of children who fail to meet the KD case definition criteria but who, nevertheless, develop CAA. The original case definition was developed before the general acceptance of CAA as sequelae of KD, the availability of the echocardiogram, and effective treatment with intravenous immunoglobulin. Despite an evolution in awareness, detection, and treatment of possible CAA sequela, the case definition has not been altered so as to incorporate this knowledge. Our investigation explores the transformation of the case definition from an epidemiological instrument to a diagnostic tool. We urge the construction of a more sensitive KD case definition that includes signs and laboratory findings associated with CAA.

The Two Emergences of Kawasaki Syndrome and the Implications for the Developing World

Kawasaki syndrome (KS) is the most common cause of acquired pediatric heart disease in the developed world. There have been 2 distinctive patterns for the emergence of KS that are likely related to several factors including exposure to the causative agent(s) and host genetics. In Europe and North America where we presume the genetic susceptibility seems to be low, KS has existed in the pediatric population for more than a century and is associated with relatively low incidence. In Japan where genetic susceptibility is presumed to be high, KS seems not to have existed before the early 1950s. This relatively recent exposure has resulted in 3 nationwide epidemics and a high current endemic rate of 200 per 100,000 in children less than 5 years. If our history of alternative patterns of the emergence of KS is valid, it may prove useful as a predictive tool for countries including India, where clusters of KS cases have been recently reported. This article examines the historical evidence in support of a 2-tiered emergence of KS in Euro-America and Japan and then returns briefly to discuss its implications for the pediatric populations of India and the health care delivery systems in the developing world.

Retraining left-handers and the aetiology of stuttering: The rise and fall of an intriguing theory

Many twentieth-century British and American educators, psychologists, and psychiatrists advocated forcing left-handed children to write with their right hands. These experts asserted that a childs decision to rely on his or her left hand was a reflection of a defiant personality that could best be corrected by forcible switching. The methods used to retrain left-handers were often tortuous, including restraining a resistant childs left hand. In contrast, those who saw left-handedness as inherited, but natural, not only disapproved of forced switching, but also often warned of its putative negative consequences, especially stuttering. These claims were given credence in the 1930s by influential University of Iowa researchers, including psychiatrist S. T. Orton, psychologist L. E. Travis, and their students. From the late 1920s until the 1950s, the Iowa researchers published articles and books connecting the etiology of stuttering to forcing natural left-handers to write and perform other tasks with their right hand. Based on their clinical studies these practitioners concluded that stutterers displayed weak laterality. The Iowa group also published detailed case studies of patients whose stuttering was putatively cured by the restoration of their left-handedness. By the late-1940s, the connection between stuttering and retraining evaporated, due in large part to the growing dominance of psychoanalytic psychiatry. Despite robust statistical and clinical evidence, the connection between forced hand switching and stuttering has largely been forgotten. Recent imaging studies of stutterers, however, have suggested that stuttering is tied to disturbed signal transmission between the hemispheres. Similar to the Iowa researchers of the 1930s, current investigators have found connections between stuttering and weak laterality.

Sports-specific factors, perceived peer drinking, and alcohol-related behaviors among adolescents participating in school-based sports in Southwest Georgia

This study investigated the relationships among sports-specific factors, perceived peer drinking, and alcohol-related behaviors among adolescents, examining sex differences in the relationship between perceived peer drinking and alcohol-related behaviors. A questionnaire assessing demographics, sports-specific factors, perceived peer drinking, and alcohol-related behaviors was administered among 378 adolescents who were mostly male (76.3%) and non-Hispanic black (70.0%). Varsity sports participants reported higher levels of perceived peer drinking compared to those who participated in sports at other levels (B 0.64, 95% CI 0.28, 0.99, p<0.001). Participants in both sports offering team- and individual-level competition reported greater perceived peer drinking (B 0.71, 95% CI 0.05, 1.38, p=0.04), compared to those who only participated in individual sports. Perceived peer drinking was associated with alcohol-related behaviors (B 0.39, 95% CI 0.31, 0.47, p<0.001) and there were no significant differences between males and females in this relationship. Suggestions for future research include examining factors contributing to the low prevalence of drinking behaviors, and investigating factors related to sports that impact perceived peer drinking and alcohol-related behaviors.

An integrated approach to addressing addiction and depression in college students.

The authors present an integrated, interdisciplinary approach to address the problem of increasing student mental health issues on college campuses. The model uses addiction and depression as lenses into the problem and links residence life and academic and community internship experiences. The project has a positive impact on student attitudes and actions and strengthens and broadens the campus network required to ensure optimal student mental health.